CARTE DERMATO B5 Alb Negru PDF

Clinical Diagnosis
In
Dermatology
Laura Gheuc- Solovstru
Descrierea CIP a Bibliotecii Naionale a Romniei

SOLOVSTRU GHEUC, LAURA
Clinical diagnosis in dermatology / Solovstru Gheuc Laura . - Iai :
Editura Gr.T. Popa, 2014
Bibliogr.
ISBN 978-606-544-273-3
616.5
Refereni tiinifici:
Prof. univ. dr. Doina Azoici - U.M.F. Grigore T. Popa Iai

Conf. univ. dr. Mircea Beiu - U.M.F. Nicolae Testemianu Chiinu
Coperta: Marius Atanasiu
Editura Gr. T. Popa

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Clinical Diagnosis in Dermatology
Clinical Diagnosis
In Dermatology
Edited by
Laura Gheuc Solovstru
Contributors
Laura Gheuc Solovstru
Associate Professor
Dermatology Department
Faculty of Medicine
University of Medicine and Pharmacy Gr. T. Popa
Iasi, Romania
Elena Andrese
PhD student
Faculty of Medicine
Iasi, Romania
Dan V
Assistant Professor
Faculty of Medicine
Iasi, Romania
Laura Sttescu
Assistant Professor
Faculty of Medicine
Iasi, Romania
Alina Stncanu
M.D. dermatology
Dermatology Clinic
Emergency Clinical Hospital Sf. Spiridon
Iasi, Romania
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Table of Contents
SKIN STRUCTURE AND FUNCTIONS ....................................................... 7
GENERAL CONSIDERATIONS ................................................................. 37
Dermatological Examination ........................................................................ 37
Fundamentals Of Clinical Diagnosis ............................................................ 40
Lesions As A Result Of Color Alteration ................................................. 41
Raised Lesions .......................................................................................... 43
Fluid Filled Lesions .................................................................................. 46
Depressed Lesions..................................................................................... 47
Surface Change Lesions ............................................................................ 48
General Notions Of Dermatological Therapy ............................................... 50
INFECTIOUS DERMATOSES ..................................................................... 64

Bacterial skin infections ................................................................................ 64
Cutaneous Staphylococci .......................................................................... 65
Cutaneous streptococcal infections ........................................................... 75
Mixed streptococcal-staphylococcal infections ........................................ 79
Cutaneous infections with corynebacteria ................................................ 83
Cutaneous infections with gram-negative bacillus ................................... 86
Cutaneous infections caused by neisseria ................................................. 87
Cutaneous infections caused by mycobacteria.......................................... 88
Actinomycosis ......................................................................................... 104
Viral skin infections .................................................................................... 107
Herpesviruses .......................................................................................... 108
Epstein-Barr virus infection .................................................................... 117
Cytomegalovirus infection ...................................................................... 118
HPV infections ........................................................................................ 118
Poxviruses (degenerative and exudative epidermal viruses) .................. 123
Other mucocutaneous manifestations caused by viruses ........................ 125
Cutaneous syndromes related to viral infections .................................... 126
Dermatoses presumably of viral etiology ............................................... 127
Viral dermatoses related to eruptive fevers............................................. 128
Cutaneous fungal infections ........................................................................ 132
PARASITICAL DERMATOSES ................................................................ 160

Scabies ........................................................................................................ 160
Pediculosis .................................................................................................. 163
Cutaneous larva migrans ............................................................................. 166
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ALLERGIC DERMATOSES ...................................................................... 167

Urticaria (Hives) ......................................................................................... 167
Eczema ........................................................................................................ 172
Neurodermatitis ........................................................................................... 182
Prurigo ......................................................................................................... 183
Plurietiological Cutaneous Syndromes ....................................................... 185
ERYTHEMATO-SQUAMOUS DERMATOSES ...................................... 195

Psoriasis ...................................................................................................... 195
Parapsoriasis................................................................................................ 204
Pityriasis Rubra Pilaris ................................................................................ 205
Lichen Planus .............................................................................................. 209
BULLOUS (BLISTERING) DERMATOSES ............................................ 214

Pemphigus Vulgaris .................................................................................... 214
LeverS Bullous Pemphigoid ...................................................................... 227
Dermatitis Herpetiformis (Dhring-Brocq Disease) ................................... 231
Porphyria Cutanea Tarda ............................................................................ 233
MAJOR COLLAGENOSES ........................................................................ 235

Lupus Erythematosus (Le) .......................................................................... 235
Sclerodermas ............................................................................................... 245
Dermatomyositis ......................................................................................... 254
Sjgren Gougerots Syndrome ................................................................. 259
ACNE VULGARIS ....................................................................................... 261
BENIGN SKIN TUMORS............................................................................ 270
MALIGNANT SKIN TUMOURS ............................................................... 280

Skin Carcinomas ......................................................................................... 281
Cutaneous Sarcomas ................................................................................... 288
Malignant Melanoma .................................................................................. 291
SEXUALLY TRANSMITTED DISEASES ................................................ 295

Syphilis........................................................................................................ 295
Gonococcal Infection (Gonorrhea) ............................................................. 310
Chancroid (Soft Chancre, Soft Sore) .......................................................... 313
Trichonomas Vaginalis Infections .............................................................. 315
Lymphogranuloma Venereum (LGV)
(Nicolas-Favre Disease) .............................................................................. 316
Mucocutaneous manifestations in HIV disease .......................................... 318
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SKIN STRUCTURE AND FUNCTIONS
Our skin is the largest organ of the body (making up 16% of body
weight), with a total area of about 20 square feet. The skin together with its
annexes form the integumentary system performing outer layer of the
organism.
The skin consists of three layers that intertwine, having an irregular
shape:
the epidermis - the outermost layer of skin, provides a waterproof barrier
and creates our skin tone.
the dermis beneath the epidermis, contains tough connective tisssue, hair
follicles and sweat glands.
the hypodermis (subcutis) is a deeper skin layer that contains loose
connective tissue with abundant adipose lobules, which connects with the
subadjacent tissues, being thicker in colder regions of the body. It represents
a source of energy and insulation; it also contains a thin layer of striate
muscle panniculus carnosus.
Cross-section of the skin

(2009 WebMD, LLC. All rights reserved)
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The appendages of the skin are structures regarded as derivatives of

skin and include:
Sweat glands
Hair and hair follicles
Sebaceous glands
Nails.
The functions of the skin can be summarized as it follows:
it protects the body against physical, chemical, biological agents of the
environment, creating a mechanical barrier, a permeability barrier, an
UVscreen, protection from pathogens, or protection from electric
power;
it provides immunological information through antigen processing and
transfer of adequate effector cells from lymphoid tissues, being provided
with a proper immune system- SIS (Skin Immune System);
it has a role in homeostasis by regulating the body temperature (through
its thermoreceptors, cutaneous vascularization and sweat glands) and by
preventing dehydration;
it contains thermal, tactile, pain receptors, which transmit sensory
information to the CNS;
endocrine functions through the secretion of hormones, cytokines, growth
factors and the conversion of precursor molecules into hormonally active
molecule (vitamin D3);
elimination of certain substances through exocrine secretions;
the absorption of fat-soluble substances (the therapeutic administration of
medications such as ointments is based upon this function).
The skin varies in thickness, ranging from: 1 mm to 5 mm.
Therefore, skin can be classified according to the following criteria:
anatomically:
thick (4 mm): the upper-dorsal part of the body;
thin (1,5 mm): eyelids, scalp.
histologically:
thick: palms, plantar regions (Fig. no.1);
thin- the rest of the body (Fig. no.2).
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Fig. no. 1 Thick epidermis
Between the epidermis and dermis, there is a basement membrane, made up of

basal lamina and reticular lamina.
Horny
layer/Stratum
corneum
Spinous layer
Dermis
Fig. no. 2 Thin epidermis
Basal lamina is a 20-100nm extracellular structural support, conspicuous in

electron microscopy and optical microscopy using PAS (periodic acid-Schiff
reagent) and argentic staining. The basal lamina is made up of:
Type IV collagen, comprises three chains which keep their terminal
peptide, thus preventing their fiber-arrangement. It is rich in hydroxy-
lysine, 3-hydroxy-proline, laminin, linking one end to the specific
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receptors of the basement membrane and the other end to the collagen of
lamina densa. Laminin is a glycoprotein structure that binds the fibrils
to one another and the epithelial cells to the basal lamina; it forms a
cross-like structure (fig. no.3A).
Entactin, a small sulfated glycoprotein, localized in the basal lamina. It

adheres to laminin and binds type IV collagen from lamina densa to
laminin.
Fibronectin, is protein dimer located on the opposite side of the cells,
binding reticulin fibers to subadjacent stroma. Fibronectin is a
glycoprotein of the extracellular matrix. It consists of two chains linked
by disulfide bonds at one end (Fig. nr.3B). Along each chain, some
loops or domains are formed, with specific affinities, in order to bind
to:
fibrinogen
the plasma membrane
proteoglycans (mostly heparin sulfate)
integrins
heparin.
They function as adhesion molecules between cells or between cells and
the matrix. By anchoring the cells, the fibronectin allows them certain
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movement directions. acestora anumite orientri pentru deplasarea lor.

It does not bind to malignant cells, thus enabling their invasion and
metastasis.
Type VII collagen with the formula (1VII)3, is synthesized by keratinocytes
and it is commonly seen at the dermis-epidermis junction. It presents as
anchoring fibrils.
Basal lamina consists of two parts:
lamina lucida or rara, of 40-50 nm, rich in laminin
lamina densa, of 40-50 nm, consisting of a dense network of type
IV collagen, laminin, proteoglycans.
The anchoring fibrils are arranged in the shape of loops around other fibers of
collagen in the connective tissue, starting from the basement membrane and
ending in anchoring plaques, resembling lamina densa (made up of type IV
and VII collagen).
Basal lamina and lamina reticularis (made up of type III collagen)
make up the basement membrane, which can be seen in optical microscopy.
Type III collagen is synthesized by: fibroblast, smooth muscle cells,
reticular cells, Schwann cells. It can be pinpointed in the skin, arteries, uterus,
intestine, lymphoid organs, lung, granulation tissue, heart, liver and endonerve
of both fetus and adult individual. The role of reticulin is to provide structured
networks within expandable organs, in order to support and ensure flexibility to
the organ. These fibers are more numerous within the dermis.
The functions of the basement membrane are:
it sustains epithelia
it provides resistance to tensile strain and flexibility
substrate that guides the migration of newly formed cells at the edges of an
injury, to restore the damaged epithelium
molecular filter, with pores delineated by a network of type IV collagen.
The epidermis has ectodermic origin. It presents constant regeneration
(15-30 days) due to the mitotic activity of the basal layer of keratinocytes that
commonly divide by night. The epidermis is made up of stratified squamous
keratinized epithelium. It presents a series of protrudings - surface folds
/creases alternating with depressions corresponding to some projections to the
dermis epithelial crests, interrupted by projections of the dermis - dermal
papillae.
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The epithelial ridges corresponding to the palms, plantar regions and

epidermal ridges determine the fingerprints or dermatoglyphics, which have a
unique, genetically determined configuration.
The surface of the skin also presents a series of pores or infundibular
depressions.
The layers of the epidermis or keratinocytes are the following:
1. Basal or germinativum cell layer, the deepest, made up of cuboidal
and prismatic cells, less differentiated, basophils, active mitotically, containing
keratin filaments or tonofilament bundles (7-9 nm in size), diminished Golgi
apparatus, mitochondria, rough endoplasmic reticulum and numerous free
ribosomes. The cells are attached to the basement membrane by
hemidesmosomes.
Basal keratinocytes are interconnected by desmosomes (macula
adherens).
Some of the basal cells are rich in melanin, transferred from the
surrounding melanomocytic cells; the layer contains scattered melanocytes and
Merkel cells; as they divide, they give rise to new keratinocytes that move
upward to the next layer.
2. Spinous layer: consists of more than 20 layers within the thick
epidermis or averaging 5-6 layers within the thin epidermis, made up of
keratinocytes which are larger than the basal ones, cuboidal and polygonal, with
central rounded nuclei, progressively flattened in the upper layers, as a result of
a change in cell shape into squamous cells, flattened parallel to the skin surface.
The intercellular spaces contain a granulous material or extensions, intercellular
bridges or spines, representing broken desmosomes partially connected to
tonofibril bundles which confers resistance to friction and pressure. The
desmosomes (Fig. no. 6) delineate an intercellular space of 15-20 nm ,
representing a small adhesive site, disk-shaped, and can also be located outside
the junctional structures; they are made up of a dense plaque of proteins, 10-15
nm thick, consisting of desmosomal cadherins, among which were identified:
desmoglein I, 169 kDa, located in the intercellular space and dense plaque
desmocollin I, 130 kDa
desmocollin II, 115 kDa
desmoplakin I, 250 kDa, located mainly in the inner part of the dense plaque
desmoplakin II, 215 kDa, located mainly in the inner part of the dense plaque
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plakoglobin ,183 kDa, located mainly in dense plaque

basic polypeptide of 75 kDa, located particularly in the thick plaque
desmoyokin.
The innermost keratinocytes of this layer are mitotically active; along
with the basal layer, they form the Malpighian layer.
Superficial keratinocytes contain granules that are released into the
intercellular space, creating a lipid layer which does not allow water or other
foreign substances to penetrate.
The spinous layer (the prickle-cell layer) may contain Langerhans cells.
3. Granular layer (stratum granulosum): consists of flattened
polygonal or rhomboid cell, with the long axis parallel to the basement
membrane. The cells are averagely arranged either in four rows on the thick
epidermis or discontinuously on the thin epidermis. The cells have a membrane
coating which is electron-dense (10-12 nm thick) and an oval or pyknotic
nucleus.
The epidermal barrier also consists of a cell envelope or a marginal layer (15
nm thick protein layer, made up of insoluble protein located on the inner part of
the cell membrane). It contains small proteins rich in proline bound to large
structural proteins: cystatin, desmoplakin, elafin, envoplakin, filaggrin,
involucrin, 5 types of keratin chains and loricrin. Loricrin is the major structural
protein and accounts for approximately 80% of the total mass, has a molecular
weight of 26 kDa and contains the highest amount of glycine in the body.
The destruction of the epidermal barrier on extended areas, as in the
case of severe burns, may cause loss of body fluids, with fatal consequences.
4. The clear layer (stratum lucidum): clear, homogeneous, refractive
layer of flattened cells without nuclei or organelles; the cells contain eleidin,
which is a transformation product of keratohyalin; this layer is regarded as a
subdivision of the stratum corneum and it is not encountered in thin epidermis.
5 The horny layer (stratum corneum), superficial, with 15-20 layers
of anucleate, flattened cornified cells, rich in tonofilaments; it is as thick as all
the layers together within the epidermis and much thinner within the epidermis;
keratinocytes contain a filamentous protein - keratin (of 85% of the horny cell
structure); cells are not viable, they have a scaly appearance - horny cells or
scales; they contain hydrolytic enzymes responsible for the disappearance of
organelles; their actual shape is of a 14 side polygon; they undergo continuous
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peeling and therefore the layer is referred to as disjunctum layer, a process in

which the acid phosphatase appears to be involved by depositing itself in
keratinocytes ,starting from granular layer.
Keratinization represents a form of final differentiation among
keratinocytes, previously carried out in the form of columns along the
epidermal layers, involving the juxtaposition of two processes: degeneration of
the cell organelles and the synthesis of keratin.
Chemical characteristics of keratin include insolubility in diluted
aqueous buffers and solubility in diluted concentrated denaturants.
Factors that enable keratinization are estrogens, corticosteroids, thymic,
mechanical pressure forces and ultraviolet radiation. The inhibitors are vitamin
A, and thyroid hormones.
The final differentiation of keratinocytes is regarded as a specialized
form of apoptosis. As opposed to the normal apoptosis, in this form of
apoptosis the process of cell fragmentation is replaced by cytoplasmic fillings
of the keratin filaments, followed by desquamation of the cell.
Non-epidermal keratinocytes include:
Melanocytes
Langerhans cells
Merkel cells.
Melanocytes are scattered among the basal layer, being attached to the
basal lamina through hemidesmosomes; they are neural-crest-derived cells, that
enter the developing epidermis. Melanocytes establish specific associations,
known as epidermal melanin units, in which a melanocyte is associated with a
predetermined number of keratinocytes (an average of 36).
Melanocytes are dendritic cells whose rounded cell body, resides in the
basal keratinocytes and cytoplasmic extensions, inserts among the keratinocytes
of the superadjacent spinous layer, without establishing desmosomal
attachments with any type of keratinocyte. Melanocytes synthesize a brown
pigment (melanin) in oval organelles (melanosomes); melanosomes contain
tyrosinase, an enzyme sensitive to UV, directly involved in the synthesis of
melanin. The content, size, rate of transfer and the aggregation method of
melanosomes vary according to race, anatomical site or physiological status
(pregnancy). The ratio of melanocytes: basal cells range from 1: 4 to 1: 10 in
different parts of the body, being constant in all races. Melanocytes maintain
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their replication capacity during life at a slower rate than that of keratinocytes in
order to maintain the epidermal-melanin unit.
Melanin protects against tissue damage caused by UV radiation.
Melanin is a polymer composed of indoles and quinones.
Eumelanin is a dark brown pigment produced by melanocytes,
insoluble in all solvents.
Pheomelanin is the pigment of the red hair, cysteine-rich, poorly
soluble in alkaline solutions.
Melanogenesis
Four stages are distinguished during the synthesis, as the melanosomes migrate
from the perinuclear area to cytoplasmic processes:
stage I: spherical vesicles appear, delineated by membranes, called
premelanosomes.
stage II: the vesicle is called early melanosome, it is ovoid, contains
parallel filaments with a periodicity of around 10 nm , with transverse
striae due to tyrosinase molecules; the melanin starts to accumulate on
the protein matrix.
stage III: abundant formation of melanin into melanosomes, along
with the appearance of less conspicuous periodic structures.
stage IV mature melanin granules appear, visible in optical
microscopy - completely melanized melanosomes, the melanin
completely filling the ellipsoidal vesicles m of 1 length and m
diameter; the melanosomes become electronopaque m 0.4 granules,
arranged within the cell and at the bases of the cell processes .
Subsequently, the melanin granules are transferred to keratinocytes, by
pigment donation. This process, which involves the phagocytosis of the tips of
the melanocyte processes by keratinocytes, is a type of cytocrine secretion due
to the fact that a small amount of the surrounding cytoplasm is also
phagocytosed; the granules are deposited above the nucleus, protecting it
against the harmful effects of solar radiation. The extent of melanin transfer to
keratinocytes causes variable skin pigmentation. The melanin granules fuse
with lysosomes within the superficial epidermal layer, along with the
disappearance of melanin. The variety of the melanin-epidermal unit
contributes to the vast diversity in colour on various body areas.
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There are racial differences in terms of size, distribution, and

degradation of melanosomes as follows: the melanosomes of the dark skin, are
larger, individually scattered among keratinocytes, whereas those of the light
skin are dimensionally reduced and are clustered in groups of 2-3, within the
keratinocytes. Moreover, because of the lysosomal activity of the keratinocytes,
melanin is degraded more rapidly in individuals with light skin than in
individuals with dark skin.
Tanning requires UV radiation with wavelengths of 290-320 nm (UV-
A, of 320-400 nm wavelength and UV-B of 290-320 nm) and consists of two
phenomena:
physical-chemical reaction, in which the pre-existing melanin darkens
and releases keratinocytes rapidly; it occurs within minutes of exposure
to sunlight and fades within 6-8 hours; it is produced by UV A and
visible light
the increasing rate of melanin synthesis, along with an increased
proportion of melanocytes; it represents late tanning, which occurs
within 48-72 hours, being caused by UV-B and UV-A.
Other factors that enable pigmentation are: the estrogens, estrogen-
progestogens, prostaglandins E2 and D2, ACTH, psoralens, UV A, copper.
Skin color is the result of a combination of:
melanin
carotene
the number of vessels in the dermis
the colour of blood.
Langerhans cells are dendritic cells (their cytoplasmic processes are
long), they originate from common lymphoid progenitor cells in bone marrow
(stem cells CD34 +) and they constitute part of the mononuclear phagocytic
system. Langerhans cells are found in the spinous layer and they do not form
desmosomes with neighboring keratinocytes. The nucleus stains heavily with
hematoxylin and the cytoplasm is clear. With special techniques, such as gold
chloride impregnation or immunostaining with antibody against CD1a
molecules, Langerhanscells can be differentiated from keratinocytes.
Merkels cells possess antigenic markers of both epidermal and neural
type; they are rare, located in the basal layer, in the areas adjacent to connective
vessels and nerves and they are more numerous on the palms, fingers and
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nipple; they can be identified using special techniques such as argentic

impregnation; they present immunoreactivity to various neuropeptides;
Merkels cells are bound to adjoining keratinocytes by desmosomes and
contain keratin filaments, suggesting an epithelial origin and the cytoplasm is
somewhat denser than that of melanocytes and Langerhans cells; the cytoplasm
is characterized by the presence of 80 nm dense-core granules that resemble
those found in the adrenal medulla and carotid body; the granules contain
markers such as neuron-specific enolase, synaptophyisin and chromogranin A.
Merkels cells may contain some melanosomes in their cytoplasm. The nuclei
are unique, lobed.
The combination of the neuron and Merkel cell, called a Merkels
corpuscle, is a sensitive mechanoreceptor.
The dermis is located just below the epidermis and it has a mesodermal origin.
It is composed of connective tissue, abundant in:
glycosaminoglycans: dermatan sulfate; the amorphous matrix of the
connective tissue is an aqueous colloidal system containing a
disorganized amorphous substance, with glycosaminoglycans,
proteoglycans, and glycoproteins and a plasma-like tissual fluid.
Glycosaminoglycans are polysaccharide chains consisting of a
repeating disaccharide unit. Sulfated glycosaminoglycans have the
following functions:
- they regulate the molecular exchanges, preventing the diffusion of large
molecules
- they bind certain ions: sodium, tricalcium phosphate determine the
hardness of the ground substance
- they allow the motility of cells while maintaining their shape, the
migration taking place along their macromolecular unit
- they serve as a means of transport for the nutrients and other simple
molecules resulting from catabolism
- they provide the proper sites for the growth factors and other signal
molecules.
Dermatan-sulphate is composed of iduronic/glucuronic acid and galactosamine;
it binds collagen type I.
collagen type I; The collagen fiber is the most common fiber found in
connective tissue. It has a diameter of 0.5-10 m. In optical microscopy it
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appears as a meshwork of bundles, rarely isolated. The longitudinal section

reveals its straight or slightly wavy appearance, whereas the cross-section
reveals its round-oval appearance. The fibers do not have branches and are not
anastomotic but they form a network in which the fibers may move from one
cluster to another. They are birefringent in polarized light. Staining used to
highlight collagen fibers are:
HE (hematoxylin-eosin) - Pink
van Gieson, with Fuxin acid - crimson
Masson, Szekelly, green light - green
Mallory, aniline blue - blue
argentic impregnation, yellow-brown.
Each fibril consists of protofibrils (Fig. no. 4) with a diameter of 20-60
nm. They show clear bands alternating with bands of 67 nm called
microfibrillar subunits due to the periodicity of the tropocollagen molecule (64
nm).
lacunar region overlopping region
protofibril
fibril
fibril
cluster
lacunar region overlopping region
Fig. no. 4 Collagen fiber
This is composed of filaments with a diameter of 3 nm, made up of 1-3

polypeptide chains. The perifibrilar space is filled with interstitial fluid.
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Tropocollagen macromolecules form an ordered array, which provides

birefringence in polarized light Collagen type I consists of two 1I chains and a
2I (1I)2 2I chain . The 1I chain contains very little lysine whereas the 2I
(1I)2 2I chain is rich in hydrophobic amino acids. Collagen type I is the most
common and it has been isolated first. It is synthesized by many types of cells,
mainly by fibroblasts. Collagen type I is localized in adult skin in the deeper
dermis, arranged in thick fibers, grouped in bundles, providing support, tensile
strength, pressure and tension.
elastic fiber networks evident in specific stains: orcein: red-brown, reorcin-
Weigert fuxin- dark blue, Verhoeff: black; elastic fibers have a tensile capacity
of up to 150% of the length as they rest; depending on the arrangement of
microfibrils, there are two other types of fibers:
o oxytalan made up of ordered arrays of microfibrils and a small amount
of elastin, located in the dermis , perpendicular to the dermoepidermal
junction
o elaunein containing microfibrils and amorphous located under the
oxytalan fibers; the fibers are arranged parallel to the dermoepidermal
junction and around the sweat glands in the dermis.
vascular network,
arteriovenous anastomoses (small vessels that connect arteries to veins
directly, with thermoregulatory function in controlling the blood pressure)
glomus bodies (located in the fingertips, the nail bed, the ears): the artery
loses its internal elastic membrane , has a thick muscular wall and it continues
with the vein; the contraction of the arterial wall closes the vessel and therefore
the movement, thermoregulation and blood pressure are under control,
nerves.
The dermis is composed of two layers, without clear limits:
superficial papillary dermis, located in the dermal papillae, composed
of loose connective tissue, fine type I and type III collagen fibers in
loose arrangement, fine elastic fibers arranged in a network of irregular
fibroblasts, fibrocytes, mast cells, macrophages, leukocytes,
capillaries involved in thermoregulation and nutrition of the epidermis.
The fibroblast is an active cell with a diameter of 20 m, having a
spindle-shaped or stellate appearance, with fine cytoplasmic processes, a
round-oval nucleus with 1-2 nucleoli, a pair of centrioles and a small
19
Golgi complex, with basophilic cytoplasm due to the rough endoplasmic

reticulum. Mitochondria are more abundant around the nucleus. The
fibrocyte is the silent form of the fibroblast. It is smaller in size, it has a
spindle-shaped appearance, with fewer processes, with unique elongated
nuclei, without nucleoli, with an acidophil cytoplasm due to the
abundance of mitochondria. The fibrocyte can turn into a fibroblast in
wound repair processes. The myofibroblast is an intermediate form
between fibroblast and smooth muscle cells It plays an important role in
wound contractions, as a natural process that tends to close a wound
with the loss of tissue, it is abundant in the granulation tissues. The
superficial dermis contains sensory Meissner corpuscles which act as
tactile receptors, anchoring fibrils, free nerve endings, nerve
networks for hair follicles.
deeper reticular dermis, which is thicker, made up of dense connective
tissue, contains thick bundles of type I collagen fibers, parallel to the
skin surface, along the Langers lines; elastic fibers responsible for skin
elasticity, wich become thinner and thinner towards the superficial
dermis, where only the microfibrillar component remains, turning into
oxytalan. This tissue has limited flexibility but gives high resistance to
tensile forces, providing support, defense and nutrition roles.
With age, the collagen thickens, its synthesis is reduced, the elastic
fibers thicken and increase in numbers, then they reduce their numbers,
undergoing degeneration processes.
Reticular dermis may contain sensory Pacinian corpuscles
(presoreceptors) and Krauses bulboid receptors (presoreceptors and cold
thermal receptors) in the deeper portions.
NERVE SUPPLY
The skin is endowed with sensory receptors of various types, that are
peripheral terminations of sensory nerves. It is also supplied with motor nerve
endings to the blood vessels, arrector pili muscles and sweat glands.
Free nerve endings extend to the granular layer, they lack a connective
tissue or Schwann cell investment. These neuronal endings subserve numerous
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sensory modalities, including fine touch, heat and cold, without apparent
morphologic distinction.
Due to the fact that networks of free dermal endings surround most hair
follicles and attach to their outer root sheath, they are particularly sensitive to
hair movement and serve as mechanoreceptors.
Encapsulated nerve endings (enclosed in a connective tissue capsule)
include the following:
Pacinian or Vater-Pacini corpuscles (lamellar corpuscles) are ovoid
structures, measuring more than 1 mm along their long axis, found in
the deeper dermis and hypodermis, in connective tissue in general, and
in association with joints, periosteum and internal organs (Fig. No.5).
They are made up of a myelinated nerve ending surrounded by a
capsule structure.
arterioles
Pacinian
Corpuscle
nerve
Fig. No. 5 Pacinian Corpuscle
Meissners corpuscles are localized within the dermal papillae. They

serve as touch receptors that are responsive to low-frequency stimuli in
the papillary layer of hairless skin, particularly those of the fingers and
toes.
Ruffinis corpuscles are the simplest encapsulated mechano-
receptors.
Krauses corpuscles are rounded, irregular, endowed with a capsule
structure, highly branched. They are numerous on the tip of the lips,
21
tongue and in the papillary dermis. They detect pressure and function as
sensory cold receptors.
CUTANEOUS BLOOD VESSELS AND LYMPHATICS
The skin receives a rich blood supply from 2 arterial plexuses and 3
venous plexuses.
The arterial plexuses are:
An arterial plexus located between the superficial and deep dermis
An arterial plexus located between the dermis and hypodermis.
There is also a subcutaneous plexus, consisting of fine branches of
muscular arteries that penetrate the subcutaneous adipose tissue, each artery
being accompanied by two veins.
These plexuses give rise to branches that penetrate the dermal papillae,
forming a loop system that consists of an ascending arterial limb and a
descending venous limb.
The venous plexuses are:
2 venous plexuses that have the same site as the arterial ones
a plexus located in the middle of the dermis.
The dermis also contains an extensive lymphatic system, which is closely
associated with the vascular plexuses. Deep lymphatics are located between the
dermis and the subcutaneous tissue as well as in the septa of the latter.
The dermal microvascular unit consists of:
vessels
mastocytes
CD34 dendritic cells.
EPIDERMAL SKIN APPENDAGES
Skin appendages include:

-skin glands
-hair follicles
-nails.
22
Sweat glands include two major types:

Eccrine sweat glands, 2-4 million, are simple, coiled tubular
structures, that consist of a secretory segment (adenomer) and a duct
segment (Fig. no. 6); they are distributed over the entire body surface except
for vermilion lips and parts of external genitalia (the glans, the inner side of the
prepuce, labia minora); they are present in a large number on the palms, plantar
regions and armpits, and are innervated by cholinergic nerve endings.
Fig. no. 6 Eccrine sweat gland
The secretory segment (adenomer) is located deep in the dermis or in

the upper part of the hypodermis, measures about 0.4 mm diameter and contains
3 types of cells, in a pseudostratified layer:
-Dark cells, pyramidal, oriented towards the luminal surface; they
contain a large number of glycoproteic granules, abundant rough endoplasmic
reticulum, a relatively large Golgi apparatus; the secretory products of this type
of cells is eliminated towards the lumen of the tubule.
-Clear cells, subadjacent to dark cells, that serve as ion carriers, rich in
glycogen, smooth endoplasmic reticulum, relatively small Golgi apparatus,
extensive lateral, apical and basal folds; they are responsible for a watery
secretion, rich in electrolytes; their secretion is eliminated along the side edges,
in the intercellular canaliculi and therefore it reaches the lumen and mixes with
the proteinaceous secretion of the dark cells.
23
-Myoepithelial cells, scattered below the clear cells; they have stellate
or spindled cell morphology; they are engaged in long, radial processes and are
distributed in a spiral, parallel array along the long axis of the secretory tubule.
The myoepithelial cell are interconnected and connected to epithelial cells
through gap junctions and desmosomes. Contraction of the filaments enable the
rapid expression of sweat from the gland.
The duct is narrow, it takes a spiral course until it reaches the
epidermis, where it continues in a tighter spiral towards the surface. The duct is
made up of a stratified cuboidal epithelium, consisting of a basal cell layer
and a luminal cell layer. The duct has a smaller diameter than the secretory
portion. The cells of the duct are rich in keratin filaments, mitochondria,
ribosomes and a conspicuous nucleus that contains a prominent nucleolus. The
apical cytoplasm of the luminal cells appears hyalinized, as a result of the
aggregated tonofilaments in the apical cytoplasm.
As the secretion products pass along the duct, there is a partial
reabsorption of NaCl by duct cells, resulting in the delivery of a hypotonic fluid
to the skin surface, its pH ranging between 4 and 6.8. Inorganic compounds
include potassium, calcium, magnesium, phosphorus, iodine, carbon, iron,
zinc. The organic substances that are being secreted include: urea, lactate,
ammonia, uric acid, amino acids, glucose, pyruvate, histamine, bradykinin,
immunoglobulins, prostaglandins, vitamin C, B2, B6,K; various drugs can
also be eliminated; the composition is similar to that of an ultrafiltrated
plasmatic component and therefore the glands exhibit an excretory function.
Secretion of sweat provides a mechanism for thermoregulation via
evaporative heat loss.
Usually, the human body loses about 600 ml of water per day through
skin and lungs. If the ambient temperature increases, so does the sweating rate,
by cholinergic control, a process known as thermoregulated sweat. At first,
the process affects the forehead and the scalp, then the face, after that the entire
body and ultimately the palms and soles.
Exercising makes the entire skin surface sweat.
Emotional stress first causes sweating of the palms, soles and armpits -
emotional sweating. This process is under nervous adrenergic control.
Hyperhidrosis can lead to significant loss of elecrolytes: potassium,
magnesium and a great amount of water.
24
The composition of sweat can be modified either by nervous or

emotional factors, or by various disorders such as cystic fibrosis, in which high
concentrations of sodium are found in sweat gland secretion, uremia, in which
the level of urea is highly increasing; after the evaporation of the water,
cutaneous crystals may occur- ureic ice (uremic frost), affecting the upper lip
in particular.
Apocrine sweat glands are large coiled tubular glands, sometimes
branched, with a diameter ranging between 3 and 5mm, specialized, confined to
the axillae, areolae (Montgomery), perineum, external genitalia, inguinal
region, periumbilical region; two special examples of apocrine sweat glands are
the ceruminous glands in the external auditory meatus and the glands of
Moll of the margins of the eyelids. They become functionally active at puberty,
as they are sensitive to hormonal changes.
The secretory units are located in the deep dermis and subcutaneous
fat; they are large, coiled units, with a wider lumen, covered by scattered
myoepithelial cells; they dump their slimy secretion into the follicular canal;
they have a single layer of epithelial cells that forms a simple epithelium.
Apocrine gland secretion is found in the lumen. This sweat contains
proteins, carbohydrates, ammonia, lipids and some substances responsible for a
specific colour. Sweat is more abundant in the axillae and it has a slightly white
colour. Although apocrine sweat is initially odorless, bacteria on the skin
surface modify and degrade the secreted substances, resulting in typical rancid
body odor.
The ducts are coated with a double or triple layer of cuboidal
epithelium and have a straight course until the reach the hair follicle. The
glands become functionally active at puberty, under the influence of sex
hormones. In females, both axillary apocrine and areolar glands undergo
changes that synchronize with the menstrual cycle.
Apocrine sweat glands are considered to secrete two types of
pheromones:
- male pheromones: adrostenol and androstenone that have a
direct impact on women
- female pheromones: copulins that influence the male
perception of women and can induce hormonal changes in males.
25
Apocrine sweat glands are innervated by adrenergic nerve endings.

They respond to emotional stimuli (being stimulated by adrenaline and
noradrenaline and inhibited by drugs that block adrenergic neurons and
receptors), sensory and hormonal (sex hormones are responsible only for their
development).
Apoeccrine glands make up 50% of the total axillary glands on
individuals suffering from axillary hyperhidrosis.
The density of the sebaceous glands may vary from 100/cm2 to 400-
900/cm. They are unilobular or multilobular structures with multiple acini with
connective tissue separations. The contents is released into the upper portion of
the hair follicle (infundibulum), except for areas without hair follicles, which
open directly to the skin or epidermis. They arise from the external sheath of the
hair follicle, usually several glands for a follicle. The glands are surrounded by
dermis, the region of the palms and soles is totally devoid of sebaceous glands,
but they are more abundant on the face, forehead, scalp and chest.
They are holocrine glands (they exude lipids by disintegration of entire
cells).
Human sebum is an oily secretion that contains triglycerides,
phospholipids, waxes, squalene, cholesterol, cholesterol esters, fatty acids.
At the periphery, the gland has got cuboidal basal regenerative cells,
arranged in a single layer, intensely basophilic, rich in rough and smooth
endoplasmic reticulum, free ribosomes, mitochondria, particles of glycogen and
Golgi complex.
In the central part of the gland there are sebum producing cells, which
are polygonal or round, with a foamy-looking appearance in, usual staining,
linked by desmosomes. These cells contain lipid droplets that require a more
abundant smooth endoplasmic reticulum. Once the lipid accumulates within the
cells, they undergo apoptosis and move towards the upper part of the gland
where the cells no longer have organelles (nor nuclei), being filled with sebum.
(Fig. no.7). The sebum droplets remain separated by fine cytoplasmic bridges,
due to the attachment of the intermediate filaments to the cytoskeleton. This
process that starts with basal cell mitosis and continues up to the elimination of
sebum-laden cells, takes about 8 days.
26
Fig. no. 7 Sebaceous gland attached to a hair follicle.
From place to place, there are keratinized cells, arranged in fine bands,
which provide the supportive framework of the gland.
Around the glands, there is a smooth muscle-the arrector pili muscle,
which has the same role as myoepithelial cells. The contraction of this smooth
muscle elevates the hair and is responsible for formation of goose bumps.
The glands become functionally active at puberty, stimulated by
dihydrotestosterone and testosterone in men and ovarian and adrenal
androgens. Exogenous estrogens, fasting, exogenous retinoids are known to
diminish their secretion.
Damage to the epidermis appears to cause the sebaceous glands beneath
the wound to cease producing lipid.
Sebum is known to have bacteriostatic, antifungal, emollient, barrier
and pheromonal roles. At puberty, the amount of sebum increases
significantly in both sexes. Free fatty acids that come into being during the
breakdown of triglycerides by lipases secreted by bacteria, are present in sebum
and are thought to be irritants in the pathogenesis of acne vulgaris.
Histologically, acne is characterized by the retention of sebum in the
isthmus of the hair follicle, accompanied by variable amounts of infiltrating
lymphocytes. In severe cases, swollen hair follicles can cause dermal
abscesses. The sebaceous gland is a holocrine simple saccular
gland extending over the entire skin except for the palms and soles.
27
The secretory portion of the sebaceous gland lies in the dermis, and
the excretory duct opens into the neck of the hair follicle. Sebaceous glands
can be independent of the hairs and open directly on the surface of the skin of
the lips, the corner of the mouth, the glans penis, the labia minora, and the
mammary nipple.
The secretory portion of the sebaceous gland consists of groups of
alveoli connected to the excretory duct by a short ductule. Each alveolus is
lined by cells resembling multilocular adipocytes with numerous small lipid
droplets. The excretory duct is lined by stratified squamous epithelium
continuous with the external root sheath of the hair and the epidermis (the
malpighian layer). The oily secretion of the gland (sebum) is released on the
surface of the hair and the epidermis.
Hair follicles are invagination of the epidermis extending deep into
the dermis. The hairs are present almost all over the body surface, except on the
thick skin of the palms and soles, the lips, the sides of the fingers and toes, the
glans penis, the clitoris, labia minor and the nipple
Hair follicles develop as complex structures. Therefore, a cross section
of the hair shaft reveals three zones:
-infundibulum (has the form of a funnel)-the upper segment of the
pilosebaceous canal (where sebum is released); it extends from the upper
opening of the follicle up to the opening of the sebaceous gland
-isthmus extends from the base of the infundibulum up to the insertion
of the arrector pili muscle.
-the lower segment- the lower par, where the hair bulb (the terminal
expanded region of the hair follicle in which the hair is rooted); a vascularized
connective tissue core (dermal papilla) projects into the hair bulb.
The hair shaft is surrounded by (1) the external root sheath, a
downgrowth of the epidermis; and (2) the internal root sheath, generated by
the hair bulb (the hair matrix).The cells arranged in close proximity to the
dermal papilla represented the innermost layer,
The hair shaft is a long, thin filament, made up of three concentric zones
(fig.no. 8):
-the medulla consists of 3-4 layers of large, round cells, separated by air
bubbles; they are moderately keratinized.
28
-the cortex contains keratinized cuboidal cells, rich in melanin, compactly

arranged, responsible for hair colour; as it goes deeper, the cortex becomes
thicker
-the cuticle of the hair shaft consists of a row of flattened, prismatic cells;
the flattened cells of the cuticle of the inner sheath and the equally flattened
cells of the cuticle of the hair overlap one another like interlocking shingles,
thereby ensuring that the inner sheath and the hair ascend together at the same
pace; it continues with the root of the hair.
A cross-section through a hair follicle will reveal the following structures(
fig no.8):
-The internal root sheath lies deep to the entrance of the sebaceous gland and it
is composed of
- the cuticle
- the Huxley layer,
- the Henle layer
Fig no. 8. A cross-section through a hair follicle

(hairandscalpexpert.com.gif)
29
The external root sheath is a direct continuation of the stratum malpighii

of the epidermis (outer basal layer and inner spinous layer).
The glassy membrane is a noncellular layer, a thickening of the basement
membrane. It separates the hair follicle from the surrounding dermal sheath.
The dermal sheath is made up of thick collagen bundles coming from
the dermis that surrounds the hair follicle.
The arrector pili muscle attaches at an oblique angle to the dermal
sheath surrounding a hair follicle. It extends superficially to underlie sebaceous
glands, passing through the reticular layer of the dermis and inserting into the
papillary layer of the dermis.
The keratinization of the hair and internal root sheath occurs in a region
called the keratogenous zone, the transition zone between maturing epidermal
cells and hard keratin. As it grows, the hair becomes fully keratinized with
hard keratin.
The active growth phase of the hair is termed anagen, the involution
phase- catagen and the resting phase-telogen
Over 80% of all scalp hairs are in the anagen phase which lasts about 3-
5 years. Catagen phase lasts a few days. In telogen, the follicle can reach half its
length or even less.
At this stage, the hair may remain attached to the follicle for several
months (3-4 months).
These phases are influenced by genetic factors, androgens (stimulate
hair growth in the pubic region, axillae, chin and inhibit hair follicles on the
scalp in androgenetic alopecia), adrenal hormones, growth hormones, thyroid,
UV radiation, infrared radiation (stimulate hair growth) and bismuth, cytostatics
(inhibit hair growth).
Hair is different, morphologically and biologically, on different
anatomic sites.
-terminal hair- is long, thick, with a larger diameter ranging between 1cm to
1m or more ( mens scalp and beard). This type of hair is pigmented and
situated on the scalp, eyebrows, eyelashes, beard, armpits and pubic region.
Terminal hair originates in long large hair follicles. It can last for several years
in the anagen phase and only a few months in telogen.
30
-intermediate scalp hair is short, less than 1cm, fine, hypopigmented and it can
be seen in 11-16 year old individuals.
-vellus is fine, hypopigmented hair that covers most of the body in infants under
6 months (anterior surface of forearms and head) and the forehead of adult
individuals.
-lanugo -the soft, fine hair that covers the fetus.
Hair distribution is influenced by sex hormones. In both sexes, at
puberty, pubic and axillary hair appears as a secondary sex characteristic.
At puberty, males develop pigmented facial hair. In elderly males, the
insertion hair line of the scalp tends to move downwards and the surface
covered with hair diminishes.
In both sexes, with age, the scalp hair becomes thinner due to reduced
secretion of estrogens and similar hormones.
Every day about 100 scalp hairs are lost physiologically. The growth
rate varies from 0.35 mm to 0.37 mm / day.
The color of the hair depends on the amount and distribution of
melanin in the hair shaft.
Nails are located on the distal phalanx of each finger and toe.
They are hard keratinized plates that rest on the nail bed of the
epidermis. They consist of compacted, anucleate, keratin-filled squames in two
or three horizontal layers. Ultrastructurally, the squames contain closely packed
filaments which lie transversely to the direction of proximodistal growth, and
are embedded in a dense protein matrix. Unlike the general epidermis, squames
are not shed from the nail plate surface. The nail apparatus consists of five
structures: the nail plate, proximal and lateral nail folds, nail matrix, nail bed
and hyponychium (cuticle). The nail bed consists only of basal spinous layers
and is adherent to the base of the nail plate.
The proximal end-the root of the nail is covered by a fold of epidermis,
called the cuticle or eponychium (prone to breaking), which corresponds to the
stratum corneum. The cuticle overlies the crescent-shaped whitish lunula.
At the distal (free) edge, each nal is underlain by the hyponychium,
which is also composed of stratum corneum.
Nails grow as the result of mitoses of cells in the matrix of the nail root.
Most of the matrix underlies the proximal nail fold, but on some digits it
31
extends under the nail plate. The most proximal portion of the matrix forms the
top of the nail plate; the most distal portion forms the bottom of the nail plate.
Fig no. 9 (www.mynailsagain.com.gif)
The matrix contains a number of cell types, as follows: stem cells,

epithelial cells, melanocytes, Merkel, Langerhans. The stem cells divide,
migrate to the root of the nail, where they differentiate and produce keratin.
Keratin of the nail is tough, similar to the cortex of the hair and does not
undergo shedding. It consists of closely packed keratin filaments embedded in
an amorphous keratin matrix with a high content of sulfur, responsible for the
hardness of the nail.
Its production process does not involve the intermediate stage of
keratohyalin granules. Moreover, there is a cornified cell envelope that contains
proteins similar to those of the epidermis.
The nail plate is a hard, translucent structure composed of keratin.
Fingernails grow at a continuous rate of about 0.1 mm/day, whereas toenails
grow at about one third to one half that rate.
32
Transverse grooves in nails, known as Beaus lines, reflect temporary

malfunction of a nail matrix
Nails have several functions: they protect the terminal phalanges and
facilitate the tactile sensation of smoothness. Nails also are used as tools with
which to scratch the skin, grasp minute objects and, not least, they have an
aesthetic role.
HISTOGENESIS
Epidermis and cutaneous annexes develop from ectoderm. Dermis,

hypodermis, Langerhans cells, macrophages, mast cells, blood vessels,
lymphatic and arrrector pili muscles develop from the mesenchyme.
Melanocytes, cutaneous nerves and sensory receptors develop from neural crest.
Human embryonic epidermis consists of a single layer of flattened
glycogen-laden cells, by the third week of intrauterine life. In the fourth week,
it becomes a two-layered structure, with a basal layer, made up of cuboidal
cells, representing the generator layer and the superficial layer or the
periderm with flattened cells rich in glycogen and provided with microvilli
directed to the amniotic cavity. During the third month, the epidermis starts to
show a third intermediate layer (basal or germinative layer) composed of
polygonal cells, that increase in number and start to make intercellular
junctions. During the first term, basal lamina develops at the dermoepidermal
junction, and, at the end of the third month, keratinization.
The granular layer appears during the fifth month, whereas the clear layer
develops from the fifth month to the seventh month. The keratinization process
ends by the sixth month of intrauterine life. The cornified scales undergo
shedding, as vernix caseosa. Stratum corneum shows a marked thickening at
the end of the pregnancy.
Melanocytes migrate from the neural crest to the epidermis, a process
evident in the eighth week. Langerhans cells migrate from the bone marrow to
the epidermis in the fourteenth week of intrauterine life. Merkel cells in the
epidermis become conspicuous in the sixteenth w beek of embryonic
development.
By the end of the third month, starting with the inner surface of the phalanges,
palms and soles, certain irregularities appear on the lower part of the epidermis,
33
in the form of parallel crests, protruding in the dermis. These are the future
eccrine sweat glands.The lumens appear within the XXIVth week and the
process of glandular secretion begins. Epidermal and dermal ridges begin to
take shape, later becoming recognizable features of the surface landscape.
Dermis and hypodermis arise in the first 6 weeks from the mesenchyme,
with migrated cells. Starting with the second month, the fibrillar interstitial
substance arises, produced by the differentiated fibroblasts of the mesenchymal
cells. Collagen fibers appear in the third month, whereas elastic fibers appear in
the fourth month.
Later, the mesenchyme divides into a dense peripheral layer with a
compact arrangement of the constituents - the dermis and a deep loose layer,
the future hypodermis. The papillary layer differentiates within the dermis. The
vessels begin to arise from the mesenchyme at the end of the first trimester and
are fully developed by the end of the third trimester of pregnancy. The adipose
hypodermic tissue arises in the second trimester from the mesenchymal cells
that undergo intermediate stages of lipoblasts, when they start to accumulate
intracytoplasmic triglycerides. The nerves appear in the skin in the fifth,
subsequently continuing their further development.
In humans, the hair starts to develop at the end of the second month,
and this process is fully completed in the XVIIIth week Hair first covers the
eyebrows, the chin and the area above the upper lip.
The hairs follows a cephalocaudal gradient over the body, completely covering
the skin with lanugo, with the exception of glabrous skin areas. At first, a
group of prismatic cells arise in the deep layer of the epidermis. These cells
divide in order to increase the subadjacent connective tissue only to form an
epithelial cylinder that will gradually lengthen. This is the primary hair,
rounded and slightly flattened at the ends. At the end there is a deep reservoir of
condensed connective tissue that forms the hair papilla and protrudes into the
epithelial mass of the hair bulb. The epithelial cells on the surface of connective
papillae are known to become the future hair matrix. The connective tissue that
surrounds the bulb will later form the connective structures of the hair follicle.
Hair formation is recognizable for the first time at about the 12th week
of pregnancy as regularly spaced epidermal placodes associated with small
condensations of dermal cells so called dermal papillae. Under a continuing
influence of a dermal papilla, the placode forms an epidermal downgrowth,
34
which over the next few weeks forms an early hair peg. In succeeding weeks of
intrauterine life, the epidermal peg overgrows the dermal papilla, and this
process results in the shaping of an early hair follicle. At this stage, the hair
follicle still does not protrude beyond the outer surface of the epidermis, but in
the portion of the follicle that penetrates deeply into the dermis, two bulges
presage the formation of sebaceous glands, which secrete an oily skin lubricant
(sebum), and are the attachment site for the tiny arrector pili muscle. The
developing hair follicle induces the adjacent dermal mesoderm to form the
smooth muscle cells of this muscle. As the developing hair matures, a small
bulge below the sebaceous gland marks an aggregation of epidermal stem cells.
At the end of the third month, epidermal thickenings (primary nail
field) on the dorsal surfaces of the digits mark the beginnings of nail
development. Cells from the primary nail field expand proximally to undercut
the adjacent epidermis. Proliferation of cells in the proximal part of the nail
field results in the formation of a proximal matrix, which gives rise to the nail
plate that grows distally to cover the nail bed. The nail plate itself consists of
highly keratinized epidermal cells. A thin epidermal layer, the eponychium,
initially covers the entire nail plate, but it eventually degenerates, except for a
thin persisting rim along the proximal end of the nail. The thickened epidermis
underlying the distalmost part of the nail is called the hyponychium, and it
marks the border between dorsal and ventral skin.
Eccrine sweat gland development is independent of the hair. Early
structural units appear during the fifth month on the palms and soles, the lower
surface of the fingers. Starting with the seventh month, an irregular lumen is
formed in the lower part, which will become the adenomere. Across the future
duct, another lumen will develop and will later join the first one. The
epithelium that surrounds the lumen forms two layers that differentiate into an
external layer of myoepithelial elements and an internal layer of glandular
cells.
CUTANEOUS REPAIR
Healing of the damaged epidermis in case of incisions or dilacerations ,

takes place through the activity of basal cells in undamaged marginal areas or in
extensive cases, the epithelium of hair follicles or of the sweat glands. Mitotic
35
activity is highest in the first 24 hours after injury. The lesion is covered with a
crust and a large number of neutrophils are seen at the incision margin. Under
the crust, the basal cells migrate at a rate of 0.5 mm / day, starting with the first
8 to 18 hours after the appearance of the lesion and cover the entire surface.
After that, proliferation and differentiation into stratified epithelium are the next
steps, along with keratinization and shedding. The crust is removed from the
periphery towards the center.
In third degree burns or extensive abrasions, re-epithelization is almost
impossible, requiring skin grafts.
Dermal repair involves the removal of damaged collagen fibers by
macrophages and subsequently fibroblast proliferation, along with the
production of all the components of the extracellular matrix. Skin sutures
reduce the extension of the repair area by bringing in close proximity the edges
of the wound and therefore minimizing scarring. Surgical sections are made
along the cleavage lines, parallel to the collagen fibers and thereby reducing the
extension process for the production of collagen and thus reducing the size of
the scar. In pathological cases, excessive collagen production is known to
produce scars, termed keloids.
The regeneration capacity is influenced by growth factors (EGF,
epidermal growth factor, IGF-I, II - insulin-like growth factors, GH - Growth
hormone, somatomedins) and inhibitors of growth factors (chalone).
36
GENERAL CONSIDERATIONS
DERMATOLOGICAL EXAMINATION
It is structured by two important elements:
1. The morphology of the skin lesions- allows us to identify the skin

disease by taking into consideration the appearance of fundamental
lesions and their evolutive aspects
2. The etiology of skin disease
For a right diagnosis it is necessary to recognize many morphological and
clinical stages:
1) The history of skin eruption

a. The onset of lesion
b. The triggering factors
c. The presence/absence of previous episodes
2) The characteristics of the eruption

Identification of the main lesions by:
-direct examination
-scratching the skin with a scoop (for scaling lesions)
-vitropression-exertion of pressure with a slip of glass on a reddish-
purple lesion (for differentiation of erythema, redness due to vascular
dilatation, from purpura, redness due to extravasated erythrocytes)
Identification of main lesions can be difficult when:
- the lesions are grouped in plaques and patches (it is necessary to
examine closely the edge of the patch in order to distinguish the real
lesion)
- the lesions are modified by scratching, infection or local treatments
(escoriation, lichenification)
37
- the lesions have a transient nature ( urticarial papule or bullous lesions

that break open and leave polycyclic-shaped erosions)
3) The arrangement of multiple lesions is extremely evocative for the

right diagnosis:
ring shaped (granuloma annulare, erythema annulare
centrifugum)
circinate lesions for syphilides
linear/dermatomal/zosteriform- distribution on a single spinal
afferent nerve root is suggestive for herpes zoster
round/discoid/nummular (discoid lupus, nummular eczema)
clustered lesions (herpes simplex virus)
4) In many cases, the sites of lesions is important for diagnosis
elbows and knees involvement might suggest psoriasis
involvement of retroauricular regions might suggest a
streptococcal infection
intertriginous areas where the skin surfaces are in contact
(candidiasis)
5) Other characteristics of skin eruption important for diagnosis are:
the color of the lesion (violaceous papules suggest lichen
planus, a yellow color is suggestive for cutaneous
xanthomas)
the infiltration of lesions (more visible in dermal or
hypodermal lesions)
subjective signs (itch, pain, burn) are key elements in the
diagnosis of lichen planus or Dhring-Brocq disease.
6) General status of the patient
To appreciate his health status a complete examination is necessary.
Depending on the disorder, a thorough system examination is
recommended, which may indicate a possible connection between
cutaneous implication and disease of other organ systems. Many
dermatoses appear on a predisposed background:
atopic history (asthma) enables the development of eczema
38
psychological factors may be relevant for the development of

psoriasis, lichen planus, pelade.
Other dermatoses can reveal some systemic disorders.
Achantosis nigricans, Duhring-Broqc disease, shingles are disorders
that may accompany a deep neoplasm.
Additional clinical investigation (laboratory examination)
These tests involve additional laboratory processing of samples
1. Mycological examination
It is the basic technique for direct examination of skin, hair
and nail specimens. The material is examined with potassium
hydroxide (KOH) to dissolve the keratinocytes. Fungi can
occur in two basic growth stages: a filamentous or mould
form which is a vegetative growth of filaments-fungal
hyphae (branched filaments) making up a mycelium or
yeasts and a unicellular or yeast form. This allows us to give
adequate treatment with topical or systemic antifungals.
2. Bacteriological examination
It is efficient in bacterial dermatoses and indicates the
infectious agent involved. It is used in syphilis- primary or
secondary stage (for demonstration of spirochetes in lesional
exudates by dark- field microscopy), acute or chronic
bacterial urethritis, bullous or pustular disorders.
3. Parasitological examination
It is useful in tropical and parasitic dermatoses (scabies).
4. Viral examination
It is useful for the diagnosis of atypical forms of viral
diseases (herpes, shingles).
5. Cytodiagnosis
It allows the study of individual cells and their intrinsic
characteristics and functions. Its various methods are
aspiration cytology, exudates smear, imprint smear, skin
scraping or Tzanck smear. Cytodiagnosis is useful in
immunobullous diseases (pemphigus vulgaris, bullous
pephigoid), infective diseases (herpes simplex, varicella,
herpes zoster).
39
6. Skin biopsy
It is frequently performed in dermatology for histopathologic
and other analyses (immunofluorescence, electron
microsopy, special stains) to confirm a diagnosis or to
differentiate the clinical diagnosis. There are three main
types of skin biopsies:
shave biopsy- we use a tool similar to a razor to
remove small section of the top layer of skin (in
protruding skin lesions: seborrheic keratosis, warts,
actinic keratosis)
punch biopsy- we use a circular tool to remove a
small section of skin including deeper layers
(superficial inflammatory diseases, papulosquamous
disorders, connective-tissue disorders)
excisional biopsy-we use a small knife (scalpel) to
remove an entire area of abnormal skin, including a
portion of normal skin down to the fatty layer of skin
incisional biopsy we use a scalpel to take away the
entire lesion.
7. Immunological tests detect:

circulating antibodies (bullous dermatoses,
connective-tissue diseroders)
explore the delayed hypersensitivity (cutaneous tests
in allergic dermatoses-Prick test)
examine the cellular information (the lymphocyte
transformation test).
FUNDAMENTALS OF CLINICAL DIAGNOSIS

(PRIMARY SKIN LESIONS)
Primary skin lesions are morphopathological and clinical changes which

allow the systematization of the skin pathology.
40
Their presence is a response of external/ internal aggressions or the

expression of an organic disease, pathophysiologically linked to the skin.
Primary skin lesions are classified into: primary lesions (appear on
healthy-looking skin) or secondary lesions (appear following other
modifications).
Most authors prefer the morphological classification:
1. Lesions as a result of color alteration
2. Solid lesions
3. Fluid- filled lesions
4. Lesions by discontinuous loss of the skin
5. Surface changing lesions
6. Cutaneous sequelae
7. Special skin lesion
LESIONS AS A RESULT OF COLOR ALTERATION

The specific type of lesion is macule (patch)
- a circumscribed alteration in the color of the skin. It has the following
characteristics:
- It is visible at clinical examination
- non-palpable
- caused by dilatation of dermal blood vessels, extravasation of red blood
cells, destruction of melanocytes, deposits of other substances in the
skin layers
- can vary in size, forming plaques
Depending on the triggering mechanism they appear as:
Hemodymanic patches
changes in skin color due to dilatation of arteries and veins in the
papillary and reticular dermis
depending on the blood vessel involved, erythema can be active or
passive
Active erythema: it caused by capillaries and arterioles dilatation. It is
characterized by pink-red, warm skin.
Passive erythema (cyanotic): venules and veins dilatation. It is a purple
tinge macule with lowered local temperature.
41
Different clinical types of erythema: -localized erythema (solar erythema)

-difusse erythema (pudic erythema)
- generalized erythema (erythroderma)
- circumscrined erythema (erysipelas)
Vascular patches
Are produced by persistent vascular caliber changes (vascular ectasia) or by the
abnormal collection of blood vessels (hemangioma). Vascular patches are
congenital (hemangioma) or acquired (telangiectasia).
Purpuric patches (Lat. purpura meaning purple)
Are caused by damaged blood vessels or by an abnormality in blood clotting.
Depending on their size and shape, purpuric patches can have different clinical
manifestations:
petechia (pl. petechiae) is a punctate haemorrhagic spot, approximately
1-2 mm in diameter)
ecchymosis (are larger lesions, more than 2 mm in diameter)
vibices (linear purpuric lesions)
Diascopy is test used in dermatology for blanchability performed by applying
pressure with a finger or a glass slide on a reddish-purple lesion of the skin.
This simple method helps us to differentiate redness due to vascular dilatation
(erythema) from redness due to extravasated erythrocytes (purpura). If the
lesion does not disappear after the pressure, the lesion is a purpuric one.
Clinical characteristics of purpuric patches are:
- non-blanching on applying pressure
- the color of purpuric lesion changes from bluish-red to yellowish-brown
or green (decomposition of red blood cells)
- rapid onset
- last for 10-20 days
Macular lesions caused by changes in melanogenesis
hypomelanotic macule
hypermelanotic macule
Hyperpigmentation of the skin is produced as a result of an excess of melanin
and can be:
circumscribed hyperpigmented macules (melanocytic/ pigmented naevi)
diffuse hyperpigmented macules (melasma/chloasma faciei,
melanoderma)
42
hereditary congenital hyperpigmented macules (melanocytic naevi)

acquired hyperpigmentated macules (freckles/ephelides)
residual hyperpigmented macules (lichen planus)
Hypopigmented macules appear as a result of:
a decreasing number of melanocytes
a decrease of their capacity to retain melanin
Clinically they appear as hypopigmented (amelanotic) macules and depending
on the mode of transmission, they are classified into:
hereditary congenital hypopigmented macules (albinism)
acquired hypopigmented macules (vitiligo)
amelanotic primitive macules (vitiligo)
amelanotic secondary macules (tinea versicolor/pityriasis versiclor)
Macules determined by substances that are not normal constituents of the skin
This type of lesions appears in disorders with systemic involvement:
-metabolic disorders (carotenemia)
-infectious diseases (hepatitis)
-occupational diseases (lead poisoning with purple-blue lines within gingival
tissue)
A separate category is represented by the tattoos. Tattooing is the process by
which a pigment is permanently or temporary introduced into the skin for
cosmetic purpose.
RAISED LESIONS
These are circumscribed, well defined lesions which cause changes on the
surface and consistency of the skin. This group includes:
Papule- a circumscribed solid elevation of the skin, varying in size (1-

5mm) which protrudes from the surface
The appearance of the papules is pathognomic for a particular type of skin
disease.
Papules are round-oval (red-flat-topped papules in secondary syphilis),
polygonal (lichen planus), acuminate papules (in follicular keratotic
disorders such as keratosis pilaris), verrucous (wart).
43
A particular aspect is described for the urticarial plaque, also known as

wheal, hives or urticaria. Wheals may be papules (2-4 mm diameter) or
plaques (over than 10 cm in diameter). Wheals occur as a result of an
inflammatory process determined by the release of chemical mediators
(allergic or non-allergic mechanism). All these cause edema in superficial
dermis.
Clinical features:
- small flat elevated lesions, of different colors (pink to pale red), by
extension they can form plaques and patches.
- the main feature of wheal is its rapid onset and disappearance after a
short time (it lasts only a few hours).
epidermal papules characterized by hyperkeratosis, acanthosis (warts)
dermal papules due to the presence of cellular infiltrates in the
superficial dermis (papules from secondary syphilis)
dermo-epidermal papules formed by epidermal hyperplasia associated
with dermal infiltrate cell (papule from lichen planus)
Tubercle
is a deep lesion located in the dermis , circumscribed, that protrudes
slightly from the skin (becomes clearly visible at diascopy)
the tubercle can run a chronic course, may ulcerate leaving a
characteristic scar (tuberculosis luposa)
the morphological substrate of tubercle is represented by a deep dermal
cellular infiltrate
Nodule
is a solid mass located deep in the dermis and hypodermis, is less
prominent and well identified by palpation
it may run an acute (erythema nodosum), subacute (erythema
induratum/ Bazins disease) or chronic (sarcoidosis) course
A particular form of nodule is gumma whose evolution comprises several
stages:
-rawness( in which the nodule is firm, covered with large, shiny skin)
-weakening (as a result of a necrotic process)
-ulceration (elimination of necrotic tissue)
44
-healing (a slow process of tissue reparation)
Vegetation
is an outgrowth papillary excrescence with irregular surface,
cauliflower-like growths or cockscomb
has a hard consistency, can be found isolated (papilloma) or has the
tendency to form globular masses with pseudotumor -like
appearance (condyloma acuminatum)
Lichenification
It presents as a plaque with pseudopapules; it appears in pruritic
dermatoses as a result of prolonged scratching
Tumor
is a prominent and persistent lesion with a tendency towards expansion
, without inflammatory character
in terms of clinical and evolutionary features tumors are classified as:
- benign tumors (nevus, lipoma), are well defined, non-invasive,
do not metastasize
- malignant tumors (malignant melanoma, squamous- cell
carcinoma, basal-cell carcinoma, sarcoma) are invasive masses
with negative prediction , which lead to metastases
Comedo
It is a plug of keratin, sebum and lipids in a dilated pilosebaceous orifice.

An open comedo is the situation where the pilosebaceous unit is open to
the surface of the skin. When we see a blackhead it means that the sebaceous
content of the infundibulum is oxidized.
Lesions are found in large numbers on seborrheic areas and are specific
lesions for onset of acne.
Scar
45
It is produced by a complex process of repair where the fibrous tissue that

replace previously normal collagen after a wound breaches the reticular dermis.
Adnexal structures normally present in the dermis are destroyed.
A scar may be: atrophic, depressed
hypertrophic, elevated
keloid, elevated, that exceeds the area of initial wounding.
FLUID FILLED LESIONS
Vesicle
a vesicle is a fluid filled cavity or elevation equal or smaller than 0,5
cm, commonly located within the epidermis
the vesicle usually breaks open and forms erosions
in case of bacterial infection the content fluid becomes festering,
constituting itself a pustule
vesicles arise from the cleavage at various levels of the epidermis
(intraepidermal) or of the dermal-epidermal interface (sub-epidermal)
by the mechanism of organization, vesicles can be
- interstitial (due to the accumulation of fluid or acantholysis/ loss
of cohesion between keratinocytes)- vesicles from eczema
- parenchymal (is formed as a result of alteration in cellular
parenchyma of keratinocytes under the action of intracellular
pathogens such as viruses)- vesicles from shingles or herpes
simplex infection.
Bulla (blister)
is a fluid filled lesion, larger than 0,5 cm
it arises due to loss of cohesion at the intraepidermal level or at the
dermal-epidermal level
the original content is translucent, serous, hemorrhagic or pus filled
by the degree of filling, it can be flaccid (pemphigus vulgaris) or under
pressure (bullous pemphigoid)
after breaking open, only an erosion or white thin plaque may be noted
depending on the site involved, they are classified into:
- superficial bullae, below the corneous stratum (bullous impetigo)
46
- intra-Malpighian bullae (pemphigus vulgaris)

- subepidermal bullae (bullous pemphigoid)
Pustule
a circumscribed raised cavity containing pus
depending on the mechanism of evolution there are described:
- primitive pustules (the liquid is a purulent exudate from the
beginning)
- secondary pustules (the phenomenon occurs due to
superinfection of a vesicle)
- in relation to hair follicle, pustules can be follicular (superficial
folliculitis) or non-follicular (pustular psoriasis)
depending on the presence of microbial factor, the pustules can be
- pus-filled pustules (staphylococcal folliculitis)
- sterile pustules (pustular psoriasis)
DEPRESSED LESIONS
Erosion
An erosion is a loss of a portion of the viable epidermal epithelium. It does not
exceed the basement membrane and does not leave scar.
It may result from local trauma, rupture of vesicle or bullae.
Excoriation
An excoriation is a surface excavation of epidermis that is produced by
scratching.
Ulcer
An ulcer of the skin is a defect in which dermis and epidermis have been
removed, often with loss of the underlying tissue. The defect heals with
scarring. The base may be clean or necrotic. It appears as a chronic ulcer
(venous ulcers) or as an acute lesion (pyoderma gangrenosum).
47
Informative features for a right diagnosis are: the base, the borders and the
surrounding skin.
Atrophy
Is a loss of tissue involving epidermis, dermis or subcutaneous tissues. The skin
is atrophic, almost transparent and may not retain normal skin lines. If there is a
dermal atrophy, the area is normal in color with a circumscribed depression.
Atrophy may be physiological (older people) or pathological (scleroderma).
SURFACE CHANGE LESIONS
Scale
A scale is a group of coherent cornified cells, packed with filamentous proteins.
It is the result of a process of hyperkeratosis with accumulation of corneous
cells that descuamate in scales.
Their appearance is often diagnostically revelant.
In description it is useful to make the following clarifications:
size of scale- furfuraceous or pityriasiform are small, fine and loose
scales (pityriasis versicolor)
-lamellar scales have average size (psoriasis, lamellar ichthyosis)
-ichthyosiform scales, diameter of a few centimeters (ichthyosis
vulgaris)
color
- pearly white scales suggest a diagnosis of psoriasis

- yellow oily scales are found in seborrheic dermatitis
adherence of scales
- adherent scales as in lupus erythematosus
- less adherent scales - easily removed by the slightest
friction as in pityriasis simplex/ pityriasis alba.
48
Crust
A crust is a dry purulent exudate, serum or blood. The appearance of crust
depends on the nature of secretion: golden- yellow as in impetigo contagiosa
(meliceric/honey colored crust), reddish-black when formed from hemorrhagic
secretion (profound ulceration).
Lichenification
is presented as a plaque of thickening of the epidermis in response to
prolonged rubbing, with accentuated marking of the skin and
pseudopapules
it appears in pruritic dermatoses as a result of repeated rubbing
Eschar
an eschar is a tissue necrosis produced by ischemia
is a circumscribed, adherent black crust on the surface of the skin.
49
GENERAL NOTIONS OF DERMATOLOGICAL THERAPY
Dermatology benefits today, along with other branches, of complex and

effective methods of treatment. However, there is a wide range of dermatoses
whose pathophysiological mechanisms remain obscure, thus a rational
treatment that involves well- known pharmacodynamics is required.
In dermatology, the treatment involves two aspects related to its route of
administration:
1. topical treatment
2. general treatment.
Topical treatment uses:
- topical medications
- physical agents
- surgical methods.
Topical treatment depends on two important factors:
- permeability of the skin;
- capacity to absorb the active substance in the skin.
Skin permeability depends on a wide range of factors:
age (children's skin is more permeable than the adults);
sex;
the topographical area/ the site involved (high permeability was
noted in areas such as the face, the skin of the scalp and
moderate or low on the palms, soles of the feet);
the integrity of the hydrolipid film/ acid mantle;
the thickness and integrity of the stratum corneum (moist,
macerated surfaces are more permeable);
properties of the blood vessels within the dermis (vasodilation
processes increase the absorption of topical substances applied).
Absorption capacity:
the absorption of active substances occurs in different ways,
depending on their
50
physical and chemical properties;

the main mechanism, known passive diffusion, follows
transepidermal and transfollicular routes;
the transepidermal route enables the penetration of hydrophilic
and lipophilic substances (through absorption, capillarity or
chemical interaction);
the follicular passage allows the penetration of mainly soluble
substances, so it is necessary that:
a) the topical substance used to be conditioned in a galenic
form, adaptable to the skin type and its area of application;
b) to ensure an efficient resorption of the active substance;
c) the irritation and sensitivity potential should be low;
the qualities of the topical substance depend on its two
components: the vehicle (excipient) and active substance.
Excipients provide the transport of the active substance and allow its
interaction with the skin.
General characteristics of excipients
must be well tolerated;
to enable a uniform distribution of the active substance;
ensure an apprropriate absorption of the active substance;
should to modify the properties of the active substance;
should be easy to remove; should not stain the clothing items.
Excipients are classified into:
1. liquid excipients
2. powdery excipients
3. fatty excipients
Liquid excipients:
role of hydration of the stratum corneum , thus increasing its
permeability;
the following liquid excipients are used: water, distilled water,
serum, organic substances (alcohols, ether, acetone, glycerin);
liquid excipients are also used to prepare certain solutions used
as compresses, baths, sprinkling.
Powdery excipients:
51
are represented by inert powders ;

the most used are the mineral powders (talc, oxide zinc, titanium
dioxide, kaolin);
other powdery excipients include mineral powders (corn starch,
rice), organic powders (aluminum palmitate);
the powders are combined with liquids (mixtures), fat (pastes,
creams) or used as such (inert cosmetic powders).
Fatty excipients are represented by:
animal fats (lanolin, beeswax);
vegetable fats (flax oil, sunflower oil);
mixture of hydrocarbons;
polyethylene glycols - synthetic products of different
consistency (liquid or slimy), resulting from the condensation of
ethylene oxide and glycine;
silicones these are siloxane polymers with a variable degree of
viscosity;
emulsifying agents these are surfactants that hinder and
prevent particle aggregation and are used in the preparation of
water / oil or oil / water emulsions.
Active substances used in the topical treatment
The active substances are incorporated into topical excipients and have
antimicrobial, antifungal, antiinflammatory, keratolytic, reductive,
chemotherapeutic properties.
Topical antiseptic and antimicrobial substances used in dermatology
Antiseptics:
are used in the form of aqueous solutions, soaps or emulsions in
infectious processes;
the most used ones include: 0.1% zinc sulphate, iodine, crystal
violet solution, chlorhexidine 0.005 to 0.5%, hypochlorite
solution.
Antibiotics:
can be used alone or in combination with corticosteroids;
they are recommended in bacterial dermatoses and include
creams, ointments, pastes, powders, sprays, mixtures;
52
the most used antibiotics include: tetracycline, kanamycin,

neomycin, gentamicin in concentrations of 1-3%;
used in excess and without supervision, they might trigger
sensitivity reactions.
Topical antifungal drugs
They provide positive results in the treatment of superficial cutaneous
mycoses if:
the antifungal substance persists long enough in the skin layers;
do not trigger local sensitization or toxic secondary reactions
(systemic absorption);
do not interfere with epidermopoiesis
The most used antifungals include:
nystatin - polyenic antifungal recommended in cutaneous and
genital candidiasis;
ketoconazole- active imidazole in cutaneous dermatophytoses
and seborrhea;
1% terbinafine - useful in superficial mycoses;
econazole - antifungal of a wide spectrum;
amorolfine - recommended for onychomycosis only as a nail
varnish (5%);
natamycin - antibiotic macrolide with antifungal properties,
recommended in the treatment of candidiasis;
isoconazole - imidazole derivative with marked antifungal
properties.
Topical antiviral agents
This group includes: acyclovir, idoxuridine 5% gel, adenine -
arabinoside (vidarabine)
Topical antipruritic drugs
are used in pruritic dermatoses to reduce itching
for example: menthol 1%, phenol and camphor 1-2%,
anesthesine 2-10%
Topical anesthetics
have anesthetic effect; they are applied directly or as occlusive
dressings
53
mainly represented by a mixture of lidocaine, benzocaine

(anesthesine), pilocarpine and lidocaine (EMLA).
Topical anti-inflammatory medication
mainly represented by corticosteroids
strong anti-inflammatory effect
they are recommended in acute, allergic and chronic dermatitis
can be administered alone or in combination with keratolytic,
antifungal or antibacterial agents
topical corticosteroids effectiveness depends on their potency
and power of cutaneous penetration
depending on the intensity of the anti-inflammatory effect, the
glucocorticoids are classified into four classes:
- Class 1 - low anti-inflammatory effect; eg hydrocortisone
acetate 0.5-1%
- Class 2 - moderate effect:
- flumethasone pivalate 0.02%
- clobetasol nitrate 0.05%
- triamcinolone acetonide 0.1%, 0.25%
- Class 3 - strong anti-inflammatory effect:
- hydrocortisone butyrate 0.1%
- methylprednisolone aceponate
- mometasone furoate 0.1
- Class 4 super-high potency:
- Clobetasol propionate 0.05% .
Topical keratolytics
enable exfoliation (peeling), removal of residual skin parts
(scales, crusts)
this group includes: salicylic acid (3-6-10%) resorcinol (5-10%),
lactic acid (1-2%), urea (5-10%).
Reductive topical medication
these are substances that normalizes epidermopoiesis and reduce
redness
are used in the form of lotions, mixtures, creams or ointments
and may be associated with other substances
54
the most common are: tar (plant or mineral derived), anthranol

derivatives (cignolin).
Revulsive topical medication
aims to increase local blood flow by vasodilation
it is recommended for alopecia, frostbites
the following substances are used: ether, acetone, camphor,
alcohol.
Topical medication with cytostatic effect
the most used antifungal preparations include: 5-fluouracilul
(Efudix), podophyllin
Condylin 0.25% solution or gel Wartec (0.25%) and bleomycin
may be administered topically or as occlusive dressings in the
treatment of superficial basal cell carcinoma or actinic keratoses
Typical sunscreens
recommended as prophylactic measures for photosensitive
dermatoses (lupus erythematosus, cutaneous porphyria,
polymorphic eruption due to light)
para-aminobenzoic acid 10-15%, tannic acid or quinine
hydrobromide 5% are recommended
white substances that fully reflect solar radiation are less used.
Dermatological preparations may present as

1. Powders these are powdery excipients that dry the skin by
absorbing the fat and reducing the inflammatory process
2. Mixtures
- are powder suspensions in liquids, stabilized by emulsifiers
- are unstable and must be stirred before application
- talc and zinc oxide are the most used powders, whereas
liquids include distilled water, alcohol or glycerin
- are recommended in exudative dermatoses.
3. Lotions
- Are homogeneous mixtures of solid and liquid substances
- the following excipients may be used: alcohols, water,
chloroform, acetone
55
4. Varnishes
- Liquids which dry in direct contact with air to form a glossy
film
- they have protective or therapeutic effects.
5. Gels
- hydrogels use methylcellulose or carboxymethylcellulose as
a base
- have the ability to easily release the active substance and are
well tolerated
6. Pastes
- are equal mixtures of fat substances and powders
- have protective, soothing and siccative effects
- are recommended in dry acute dermatitis (such as subacute
eczema, intertrigo)
7. Creams
- these are are mixtures of fats and aqueous solutions, grease,
oils
- they act superficially, having emollient, soothing, refreshing
effects
8. Ointments
- a mixture of hydrophobic fats (grease) and inert powders
- can be combined with active substances such as antibiotics,
antifungals, keratolytics
- they have powerful occlusive effects and are recommended
in chronic lichenified dermatosis
9. Sprays
- mixtures containing solutions, emulsions and powders only
in the form of aerosols , which are applied by using a
pressurized inert gas (freon)
- give good results in wet acute inflammatory dermatitis
Topical treatment using physical agents
The topical treatment of various dermatoses uses therapeutic techniques
such as:
1. Radiotherapy (direct or indirect) - uses therapeutic radiation on
skin cancers or persistent inflammatory processes
56
2. Photochemotherapy and phototherapy

- use UV rays, with or without photoactive substances, orally
administered
- UV A and UV B treatment is recommended in: psoriasis
(PUVA), vitiligo, alopecia, lymphomas.
3. Electrotherapy
- uses electricity, electromagnetic waves and quantum energy
to cure diseases
- commonly used are: electrolysis (useful in the destruction of
hair follicles), electrocautery (used in the treatment of warts
and pyogenic granulomas), diadynamic currents
(recommended in circulatory disorders), ultrasound
(indicated in keloid treatment, the plastic induration of
corpus cavernosum).
4. Cryotherapy
- uses cryogenic substances in order to cure diseases
- it enables cell destruction
- the substances used include ethyl chloride, dry ice, liquid
nitrogen
- cryotherapy is recommended in the treatment of lupus
discoid, Keloids, angiomas, warts, actinic keratoses.
5. Laser therapy
- is an innovative method of treatment
- a monochromatic light beam, of certain wave length, enters
the tissues, causing several physical and chemical effects
(thermal, photochemical, electromagnetic, chromatic effects)
- surgical ( with CO2), vascular (argon laser YAG: Nd),
biostimulative (arrays of He-He) lasers are used in
dermatology
Surgical treatment in dermatology

It is a therapeutic method recommended in disorders such as: benign
tumors, cutaneous carcinomas, melanomas, injured or active naevi, sarcomas,
deep purulent collections, vicious or compressive scars.
General treatment in dermatology
57
A. Antibiotic therapy
it is recommended in dermatoses such as:
- primary skin infections (pyoderma)
- secondary skin infections (pyodermization of a pre-existing
lesion)
- sexually transmitted diseases
frequently involved pathogens are Staphylococcus aureus, beta
hemolytic streptococcus, gram-negative bacilli.
An appropriate antibiotic treatment must obey the following rules:
1. the antibiotic is chosen according to the antibiogram
2. the dosage is determined by taking into consideration the
characteristics of the antibiotic, clinical manifestations, body
weight, associated pathology
3. Keeping an effective plasma level that would control general
manifestations (fever, chills, pain).
The main antibiotics used include:
beta-lactams
- have bactericidal effect
- act on specific receptors on the cellular wall of bacteria
- the most used are: biosynthetic penicillins
anti-staphylococcal penicillins (oxacillin, cloxacillin,
dicloxacillin)
aminopenicillins (ampicillin, amoxicillin)
beta-lactamase inhibitors (clavulanic acid, sulbactam,
tazobactam)
cephalosporins (generation I: cephalothin, cefalozina, or
generation II: cefuroxime cefamadol; generation III: cefotaxime,
ceftriaxone, cefixime; generation IV: cefpiramide, cefepime)
aminoglycosides (streptomycin, gentamicin, tobramycin,
amikacin)
macrolides
- Natural (erythromycin, spiramycin, josamycin)
- Synthetic (azithromycin, clarithromycin)
synergistins- pristinamycin
58
lincosamides - lincomycin, clindamycin

glycopeptides - vancomycin
fusidic acid -
tetracyclines (tetracycline, doxycycline)
quinolones (nalidixic acid)
fluoroquinolones (norfloxacin, ciprofloxacin)
antibacterial sulfonamides (sulfamethoxazole)
chloramphenicols (chloramphenicol)
rifampicin
polymyxins and bacitracin (slightly used due to their high
toxicity)
B. Antifungal medication
The main antifungal agents used are:
griseofulvin - fungistatic antibiotic used in the treatment of
pilomycoses or dermatophytoses of the glabrous skin
imidazole derivatives: the most representative one is
ketoconazole, which damages the fungal cell membrane due to
ergosterol inhibition
triazole derivatives:
- itraconazole which acts better than ketoconazole. It is
recommended in all fungal diseases, especially in
onychomycoses, where it significantly reduces the duration
of treatment due to its "pulse therapy ".
- fluconazole is active in dermatophyte and Candida albicans
infections.
allylamines - group of antifungals that have fungicidal and
fungistatic roles
- the most representative of this class is terbinafine. This
interferes with fungal sterol biosynthesis by inhibiting the
squalene epoxidase from the fungal cell membrane.
- is recommended in dermatophytes and skin candidiasis
amphotericin B
- is a visceral candidiasis antifungal
59
- due to a reduced digestive resorption it is administered

intravenously
- stamicin, pimafucine, pimaricine do not actually resorb into
the digestive tract and do not achieve effective serum
concetrtions; often recommended in the treatment of
candidiasis of the digestive tract.
C. Antiviral Medication
General therapy uses the following:
antiviral chemotherapies - recommended for extended forms and
recurrent cutaneous herpes, shingles; the most commonly used
preparation is acyclovir - cyclic nucleotide that inhibits herpetic
DNA polymerase
the general route of administration requires only the use of
200mg capsules or tablets, having a wide range of labels:
Zovirax, Euvirox, Avyclor, Virolex
the pyrophosphate analogue foscarnet is recommended for
acyclovir-resistant forms of disease, as a therapy for herpes and
cytomegalovirus.
Other antiherpetic medications include:
- gamciclovir
- famciclovir
- valaciclovir
- brivudine
- vidarabine
- idoxuridine
- cytarabine
- moroxydine
D. Immunotherapy
Immunomodulatory therapy is recommended for chronic recurrent
dermatoses that sensitize the skin during microbial and viral infections, resistant
to conventional therapy and oncodermatology.
1. Immunotherapy
Immunisation comprises two alternatives:
an active immunization ( with vaccine and toxoid)
passive immunization (with antimicrobial sera).
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Once introduced into the body, the vaccines cause the appearance of
specific antibodies (which contain inactive germs).
Sera are preparations which contain specific antibodies.
2. Immunostimulant therapy
acts to stimulate transiently the bodys nonspecific immune
capacity and consists in the administration of biological or
medicinal preparations
commonly used immunostimulatory substances include:
- Corynebacterium parvum
- BCG
- interferons
- levamisole
- isoprinosine.
E. Hyposensitization therapy
comprises the gradual administration of a small amount of
sensitization allergen,
up to an optimal concentration
the major role is to improve symptoms (eg hypo-sensitization to
molds, pollen , microbial antigens)
F. Anticancer drugs and immunosuppressants
Anticancer drugs inhibit selectively the cell cycle or trigger metabolic
changes. Among these, the most important ones include:
- alkylating agents (cyclophosphamide, chlorambucil,
fotemustine)
- methyl agents (procarbazine)
- antibiotics (bleomycin)
- inhibitors of topoisomerases (amsacrine, etoposide)
- antimetabolites in combination with:
- antipurines(azathioprine, allopurinol)
- antipyrimidine (5-fluorouracil)
- antifolate (methotrexate)
- cyclosporine ( has immunosuppressive cell properties).
Immunosuppressive drugs act on the immune system, reducing the
ability to undergo multiplication, proliferation and blast transformation.
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Some substances may be used both as immunosuppressant and

antineoplasticagents.
Immunosuppressants are recommended in autoimmune diseases
(scleroderma, lupus erythematosus, periarteritis nodosa), in bullous dermatoses
(pemphigus, bullous pemphigoid), in systemic vasculitis.
Antiproliferative drugs (methotrexate, cyclophosphamide, cyclosporine,
Imuran) are used in psoriasis, cutaneous malignant melanoma.
G. Retinoid therapy
Retinoids are synthetic derivatives of the retinoic acid that regulate the
process of keratinogenesis, decrease the inflammatory process, reduce sebum
secretion, and control the immunity.
Their administration is subjected to numerous side effects
(hepatotoxicity, teratogenicity and embryotoxicity) and their transient effects
(several courses are required). The most used drugs are: isotretinoin
(Roaccutane), etetrinate (Tigason), acitetrin in conditions such as acne vulgaris,
psoriasis, pityriasis rubra pilaris.
H. Antihistamines
are commonly used in dermatology in the treatment of allergic
dermatoses (hives, eczema, prurigo, atopic dermatitis)
according to their mechanism of action, they are classified into:
- antihistamines that obstruct the H1 receptors
(chlorphenoxamine, cyproheptadine, hydroxyzine,
promethazinum, loratadine)
- antihistamine that obstruct the H2 receptors (cimetidine)
- inhibitors of histaminogenesis (hypostamine)
- inhibitors of mast cell degranulation (ketotifen, zaditen).
I. General Corticotherapy
Steroidal anti-inflammatory drugs are effective in many therapeutic
dermatological disorders, due to their anti-inflammatory, immunosuppressive
and antiproliferative properties. However, general corticosteroid therapy should
be recommended only in case of absolute necessity, because the doses that
exceed the physiological levels are responsible for: hypertension, osteoporosis,
psychosis, diabetes.
The duration of action of corticosteroids is estimated based on the
degree of inhibition of the hypothalamic-pituitary axis.
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Depending on the duration of action, corticosteroids are classified into:

short duration corticosteroids (24-36 hours): hydrocortisone,
prednisone, methylprednisolone, prednisolone
average duration corticosteroids (48 hours): triamcinolone
long duration corticosteroids (over 48 hours): betamethasone,
dexamethasone
General corticosteroid uses:
autoimmune diseases (pemphigus vulgaris, pemphigoid, lupus
erythematosus, scleroderma, dermatomyositis, systemic
vasculitis).
allergic skin manifestations (anaphylactic shock, acute urticaria,
Quinckes edema, Lyell's syndrome).
acute or chronic dermatoses that do not respond to conventional
therapy
(chronic eczema, lichen planus, alopecia).
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INFECTIOUS DERMATOSES
BACTERIAL SKIN INFECTIONS
Microbial dermatoses are skin diseases caused by infectious agents

which are capable of inducing an imbalance between the commensal flora and
the pathogenic one. When this imbalance is in favour of the pathogen, the
microbial infection sets in.
The surface of the tegument and hair follicles are colonized immediately
after their formation by an important number of commensal bacteria.
The density and composition of the commensal flora varies according to
region, age, sex, pathological skin changes, humidity, hygienic habits.
The flora of the skin can be classified as follows:
a) resident skin flora (it colonizes the skin permanently);
b) temporary resident skin flora (it colonizes the skin temporarily
and doesnt trigger pathological manifestations);
c) transient flora (responsible for pathological skin infections).
The cutaneous bacterial infectious manifestations are caused by:
the pathogenicity of the infectious agent;
the degree of contamination;
the host range.
Pathogenicity represents the ability of the infectious agent to produce
disease and depends on:
the degree of virulence of the strain involved;
the enzymatic and biochemical equipment that it holds;
the ability to achieve hypersensitivity reactions.
The degree of contamination - is the amount of bacteria existing at a
certain time on the skin and is related to the amount of time they stay on the
skin. The bacterial persistence in some areas is due to the bacterial adhesion
factors and to the surface of keratinocytes.
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There is a great variety of factors that control the persistence of

pathogenic micro-organisms on the skin.
The following are worth mentioning:
the integrity of the skin (barrier role);
the continuous peeling of the epidermis (it limits the number of
bacteria).
The host range
The local factors predisposing to the development of bacterial skin
infections are:
1. xerosis/xerotic skin;
2. hyperhidrosis and maceration;
3. excessive use of chemical scouring agents (washing powder,
bars of soap);
4. poor hygiene;
5. partial loss of a portion of healthy tissue.
A fundamental role in the anti-infective defense is represented by the
immunocompetent system, through the production of specific antibodies or
through the initiation of cell-mediated immunity. All these factors are closely
related to the overall condition/state of health of the organism and are
influenced by immunodeficiency, neoplastic or metabolic diseases.
Among the cutaneous inflammatory suppurative manifestations, the
most common are those triggered by pyogenic cocci (streptococci and
staphylococci) and are called pyoderma.
The clinical manifestations are directly related to the virulence,
microbiological particularities and course of action of the microbial agent.
Cutaneous Staphylococci
Cutaneous Staphylococci are pyoderma triggered by staphylococcal

infections: gram-positive and coagulasepositive.
In practice staphylococci are caused by pathogenic strains of
Staphylococcus aureus. They are capable of producing toxins which are
responsible for skin lesions:
65
exfoliative toxin (it produces toxic epidermal necrolysis, bullous

impetigo);
toxin TSST-1 (it causes the toxic shock syndrome).
Other factors that could cause pathogenic skin diseases include the
capsule, protein A, extracellular enzymes (coagulase, hemolysins).
Depending on the location, clinical appearance and structures involved,
the staphylococci can be classified as:
Glabrous skin staphylococci

Clinical manifestations:
1. Bullous staphylococci
Staphylococcus bullous impetigo
Etiology:
it is a contagious superficial pyoderma;
it is favored by poor hygiene, pre-existing skin disorders, partial loss
of a portion of healthy tissues, immunity;
the disease has an increased frequency in schoolchildren and in the
community.
Clinical features:
it is characterized by large, flaccid, superficial bullae with serocitrin
liquid that ruptures rapidly, leave erosive surfaces and cover
themselves with yellow meliceric crusts. They are sometimes
associated with lymphadenopathy.
an extended form of bullous impetigo is seen in newborns and it is
known as pemphigus neonatorum.
Sites: face, legs, forearms and torso; preferentially on the face (periorificial).
The lesions extend peripherally and heal centrally, having a coiled aspect.
Prognosis: healing occurs within 10-12 days.
Differential diagnosis is made with:
cutaneous herpes;
erythema multiforme;
syphilitic papulopustular erosion;
syphilitic pemphigus of the newborn.
Lyell Syndrome (staphylococcal toxic epidermal necrolysis)
66
Etiology:
the lesions are due to the action of the epidermolytic toxin produced
by type II Staphylococcus, 71 phage type;
the disorder occurs in children with immune deficient status;
the lesions are produced by shallow cleavage (granular stratum).
Clinically:
the skin is covered with large flaccid bubbles, located on an
erythematous base that breaks open quickly, the skin exfoliates into
flaps, leaving large bare areas. The appearance resembles that of a
scalded skin (Staphylococcal scalded Skin Syndrome). The general
condition is profoundly altered (fever, pain and skin burns).
Prognosis - reserved due to major hydro-electrolytic changes of the bare
surfaces.
Differential diagnosis:
Stevens Johnson Syndrome
bullous toxidermatosis as a reaction to drugs/ drug-induced bullous
toxidermatosis
2. Erythemato-squamous Staphylococci
Ritter von Rittersheim Exfoliative erythroderma
Etiology: the condition occurs in infants in the first month of life and is
determined by the specific exfoliative toxin, produced by Staphylococcus
aureus hemolytic 71 phage type.
Clinical features:
peribuccal initial erythema, accompanied by blisters and crusts on
the lips;
the erythema is expanding rapidly, with a tendency to generalize and
is accompanied by skin exfoliation;
a marked skin fragility (Nicolski positive sign).
Evolution and prognosis: the lesions usually epithelize withim 5-7 days, but
the process of exfoliation could last between 7 and 17 days.
Differential Diagnosis with
bullous impetigo,
Lyell syndrome.
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Staphylococcal scarlatiniform erythema

Etiology: it affects school children, carriers of a staphylococcal infection
Clinical features: acute onset of fever, anorexia, vomiting.
on the skin:
- erythematous punctiform rash without a clear delimitation , with
a tendency to generalize;
- linear purpuric lesions affecting the body folds (Grozovici -
Pastia lines);
- exfoliation into flaps.
the mucosas:
- are rarely involved;
- sometimes the lingual mucosa looks "raspberry-like" (aspect
frequently encountered in streptococcal scarlet fever).
Differential diagnosis with:
allergy to drugs
rubeola.
3. Exophytic Staphylococci
The Botryomycosis (pyogenic granuloma)
It is an inflammatory pseudotumoral mass, of unclear infectious origin .
Histologically, the appearance is of a vascular benign proliferation and a
granulomatous type reaction.
Clinical features:
it appears as a round red pseudotumoral mass, friable, with an
irregular scouring surface and covered with hematic crusts;
the base of the mass is delimited by an epidermal collar;
it normally develops on a partial loss of a portion of healthy tissue
occurring after a trauma;
Location: the mass can be located anywhere on the skin, with a predilection for
extremities (fingers), scalp and lips.
The differential diagnosis is made with other tumorous masses:
hemangiomas;
papilloma;
68
malignant melanoma;
Kaposi's sarcoma.
Pyoderma vegetans
Etiology: there were many antimicrobial agents involved in the etiology of this
disease: Staphylococcus aureus, group A Streptococcus. The disease develops
on a body with a poor immune status and was described in association with
immunodeficiency states or ulcerative colitis.
Clinical features:
it is characterized by an epithelial hyperplasia associated with
dermal granulomatous inflammatory changes;
the lesions are arranged in plaques or patches that evolve
eccentrically, exhibiting a raised, firm, papillomatous surface,
whereas the periphery is marked by small pustules.
Location: the localized forms are arranged around some infected wounds while
the generalized forms predominantly affect the inguinocrural folds, buttocks,
abdomen or thorax.
Differential diagnosis is made with tuberculosis vegetans, pemphigus vegetans.
4. Necrotic Staphylococci
Acute necrotizing cutaneous staphylococci
Epidemiology: it occurs in immunodepressed children in their first days of life.
Clinical features:
the teguments are intensely erythematous and infiltrative;
the lesions are evolving rapidly to intense necrosis of deep tissues ;
the general condition is profoundly damaged;
Sites: abdomen, lumbar-sacral region, thorax.
The prognosis is reserved.
Differential diagnosis includes other dermatitis caused by staphylococcus.
Staphylococci of the sweat glands

1. Multiple abscesses in infants
Etiology: it is a disorder of the eccrine sweat glands. It is frequently
encountered in infants with and a poor hygiene, and it is produced by
coagulase-positive Staphylococcus aureus. The source of infection is
69
represented by the carrier of the pathogen Staphylococcus, steming either from

his family or from the hospital.
Clinical features:
it is characterized by multiple erythematous dermal nodules,
resilient and painful;
usually it evolves by forming an abcess, discharging slimy pus;
healing leaves scarring.
Sites: The disorder typically affects the cephalic extremities (neck, scalp) and
the buttock region.
The prognosis: usually, the lesions tendency is towards epithelialization, but
the disorder has a relapsing nature
2. Hidroadenitis (hidradenitis suppurativa)

It is an inflammatory disorder of the apocrine sweat glands, running a
chronic course.
Etiology:
in etiology, other microbial germs such as anaerobic streptococci
were involved along with Staphylococcus aureus;
the inflammatory changes are due to both microbial factor and
glandular duct obstruction through local maceration;
heat, humidity, local use of antiperspirant products or deodorizers,
are factors that favour the lesions;
autoinoculations are frequent and promote the expansion and settling
of the lesions;
the disorder occurs predominantly in females, after puberty and its
evolution is influenced by hormonal changes.
Clinical features:
the lesions are firm, subcutaneous nodules, sensitive, slowly
evolving to fester;
a purulent discharge is being drained through the newly formed
fistulas;
the extension of the inflammatory process deeply into the
hypodermis, causes the formation of plaques or persistent endured
linear strips.
70
Sites: the cutaneous lesions are located in the same areas as the apocrine glands:
armpits, perineal region, buttocks, breast region.
Prognosis: the healing process is achieved with unsightly vicious scars and,
depending on the site, they may sometimes determine functional disabilities.
The differential diagnosis is made with:
furuncle
scrofuloderma
nail granuloma.
Pilosebaceous Staphylococci
1. Folliculitis (follicular staphylococci)
This is a disorder of the hair follicles, caused by a staphylococcus.
According to the depth and evolution of the inflammatory process folliculitises
are classified into:
Superficial Folliculitis
a) Superficial Pustular Folliculitis (Bockards impetigo)
b) chronic folliculitis of the legs
Deep Folliculitis
a) acute
- nasal folliculitis
- folliculitis of the eyelash (stye or hordeolum)
b) subacute
- staphylococcal sycosis
c) chronic
- lupoid sycosis
- folliculitis decalvans (Quinquad)
- keloidal folliculitis
Impetigo of Bockard
Etiopathogenesis: the causative agent is Staphylococcus aureus which enters
through the follicular ostium (the weakest point of the skin).
Clinical features: it develops through the appearance of small pustules
surrounded by an inflammatory halo, around the hair structure.
Location: it is located especially on the face after shaving, on the scalp,
buttocks or around some partial loss of a portion of healthy tissues (wounds,
ulcers).
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Prognosis: The evolution can be towards spontaneous healing or the lesions

may worsen, evolving towards deep folliculitis.
Chronic folliculitis of the legs
Etiopathogenesis:
this condition is favored by heat, moisture, repeated frictions due to
clothing, poor hygiene;
it usually affects young men.
Clinical features: multiple follicular pustules, extended and resistant to
treatment.
Location: thighs, legs and buttocks are the most preferred areas.
Staphylococcal Sycosis
Etiopathogenesis:
subacute folliculitis is caused by staphylococcus;
the infection goes beyond the follicular ostium and enters the depth
of the hair follicle, building up a follicular abscess as a "shirt
button".
Clinical features: the lesions are papular-nodular, pustular, surrounding the hair
and they are grouped into suppurative patches. A typical bilocular abscess is
formed in depth.
Sites: the beard and the mustache of adult males and rarely other areas (armpits,
pubic region).
Prognosis and evolution: subacute slightly inflammatory evolution. The hair is
shaved with difficulty.
The differential diagnosis is made with trichophytic sycosis.
The lupoid sycosis has got a chronic relapsing evolution.
Clinical features: the lesions have a tendency to a centrifugal active-evolving
extension, with papular pustules and they exhibit an atrophic cicatricial center.
The inflammatory changes are granulomatous, causing the destruction of the
hair follicles and leading to scarring.
Folliculitis decalvans is a deep form of disease with a chronic
development, affecting the hairy skin of the head, leading to cicatricial alopecia.
The inflammatory process consists in plaques that have a centrifugal evolution,
active at the periphery and covered with follicular pustules.
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Keloidal folliculitis (acne keloidalis)

Etiopathogenesis:
the pathological process affects the deep structures of the hair
follicles.
from the ostium and infundibulum, the process spreads towards the
root of the hair, followed by deep suppuration.
the condition is associated with obesity, seborrheic syndrome, it
affects only males and it is located on the nape of the neck.
Clinical features:
it starts with follicular pustules with a linear distribution on the outer
edges of the hairy region;
a fibriform dermo-hypodermic reaction is subsequently produced
with the appearance of a prominent sclerotic hypertrophic band;
isolated or clustered fibrous roots appear on these areas which
alternate with folliculitis areas.
Eyelid folliculitis (hordeolum/ stye)
It is an acute form of folliculitis.
Clinical features:
it is characterized by painful small inflammatory nodular structures,
arising from the eyelash follicle, affecting the eyelids;
after a few days, the infection softens and a purulent material
exudes;
the healing takes place without scarring.
Folliculitis nares perforans

this is a recurrent staphylococcus of the follicles pertaining to the
nasal vestibule (usually in chronic carriers of staphylococcus)
it usually occurs in adult males;
the lesions may be associated with episodes of cellulitis of the nose.
Clinical features: pustular lesions affecting the nasal vestibule, with chronic
evolution.
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2. Perifolliculitises
The boil (furuncle) is a deep acute staphylococcal infection which
affects the hair follicle, the sebaceous gland, the perifollicular connective tissue
and sometimes even the subcutaneous adipose tissue.
Etiopathogenesis:
Staphylococcus aureus is the etiologic agent, which spreads towards
the skin;
the predisposing factors are diabetes, malnutrition, immuno-
suppressive states, prolonged corticosteroid therapy.
Clinical features:
the initial lesion is a painful inflammatory hard lump, centered on a
follicular pustule;
the lesion develops within two to three days forming central
abscesses, enclosing a necrotic core (bourbillon);
the residual ulceration heals with scarring and local pigmentation.
The clinical symptoms are accompanied by changes of the overall
condition
fever
live pulsatile pain (when the location is in the vestibule of the nose
or upper lip)
significant edema (if the boils occur inside the nostrils, on the
eyelashes or between the eyebrows).
The recurrent prolonged evolution in different areas of the skin is called
furunculosis. This is explained by the increased virulence of Staphylococcus or
the existence of a significant immunosuppression.
The anthracoid furuncle (carbuncle)

It is a severe clinical form of staph that occurs in people with poor
health.
Clinical features:
it consists of a cluster of boils that form connecting sinuses;
fissures are formed among the boils and the necrosis is important;
the necrotic plugs are eliminated during the course of the disease,
exhibiting a sprinkling-like appearance;
74
the overall condition is profoundly damaged, with general septic

phenomena.
Sites: usually the neck region.
Evolution and prognosis: healing leaves scarring.
Nail and periungual staphylococci

These are conditions which affect the body of the nail and its proximal
folds and are produced by staphylococci.
1. Staphylococcal nail infection (staphylococcal paronychia)
Clinical features:
swelling, inflammation and pain around the lateral and posterior
periungual folds
when pressured, a drop of pus is released beneath the fold of the nail
the inflammation may extend to the nail matrix, producing changes
in the body of the nail
2. Staphylococcal Onyxis
Clinical features
it is characterized by the appearance of small yellow abscesses under
the body of the nail. The lesions are painful and the nail becomes
brittle with an uneven surface;
the lesion may occur alone or secondary to a perionyxis.
Cutaneous streptococcal infections
They are conditions caused by beta-hemolytic streptococci pathogens.

The manners of action in which the lesions occur are:
direct infection of the skin;
sensitivity to streptococcal endotoxins;
sensitivity to the streptococcal flora located on the skin surface.
Classification of streptococcal infections
75
Depending on the clinical and evolutionary aspect of the streptococci

are classified as:
a) erythematous streptococcal infection
- erysipelas
- acute Lymphadenitis
- streptococcal cellulitis
b) erythematous-squamous streptococcal infection
- pityriasis alba
- squamous streptococcal infection of the scalp
c) ulcerous streptococcal infection
- Streptococcal gangrene
d) bullous streptococcal infection
- contagious streptoccocal Impetigo
a) Erythematous streptococcal infection

Erysipelas
It is a dermo-hypodermitis caused by streptococcus.
Etiopathogenesis: the streptococcus penetrates the dermal lymphatic network
using a breach in the skin due to partial loss of a portion of healthy tissues
(insect bites, superficial wounds).
Clinical features:
sudden onset of fever, chills and sometimes vomiting and
convulsions;
the skin lesions are characteristic and are represented by a painful
erythematous-edematous plaque, disposed around the entrance area ;
the rims of the plaque are well differentiated by the surrounding skin
through a peripheral fold and the spreading of the lesion takes place
eccentrically in a "smear";
the skin lesions are accompanied by immunoblastic
lymphadenopathy.
Location: frequently on the limbs, face, outer ears.
Clinical forms:
1. bullous erysipelas - represents a severe form of the disease, is a
distinctive clinical form, characterized by bullous lesions containing
yellow serous liquid located on the surface of the crust.
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2. hemorrhagic erysipelas it is clinically characterized by bloody

blisters and purpuric spots on the surface of the crust. The lesions
occur as a result of dermal vessels involvement.
3. phlegmonous erysipelas -its clinical appearance is similar to a
phlegmon, forming abscesses.
4. recurrent erysipelas - is a distinctive clinical form manifested by the
apperance of the lesions for several times in the same skin areas.
After several relapses, a massive chronic lymphedema sets in,
sometimes having the classic appearance of elephantiasis.
Lymphadenitis is an acute inflammation of the superficial lymphatic

vessels, caused by streptococcus.
Clinical features: it appears as a painful erythematous-edematous strand,
located between the entrance area and the lymph node. The symptoms can be
accompanied by fever, chills or even headache.
Evolution and prognosis: in the absence of complications, the antibiotic therapy
seems to be working.
Streptococcal cellulitis
Etiology: The condition is caused by pyogenic cocci, and especially by group A
Streptococcus and less rarely by group B and C, to which other germs are
sometimes added . It has the appearance of an erythematous and oedematous
crust developed around the partial loss of a portion of healthy tissue and / or
due to a chronic venous insufficiency.
From an evolutionary perspective two clinical forms are described:
nonsuppurative cellulitis
cellulitis suppurativa (the crust is covered with bubbles which
open while the lesions lead to necrosis).
b) erythematous-squamous Streptococci
Pityriasis alba
Clinical features:
this condition is considered by some authors a form of atopy, with
atypical manifestations;
77
it is characterized by discrete small erythematous plaques covered

with fine scales which are more visible when scratched.
Sites: the lesions commonly appear on children's faces.
Squamous Streptococcal Infections

Clinical features: large white scaly lesions, which can easily rub off, layered
and easy to be restored, located on the scalp. After its detachment, the skin is
still erythematous and it is covered with meliceric crusts around the hairs. The
lesions may extend from the scalp to the retroauricular areas.
Special Clinical features:
tinea amiantacea (the lesions cover the scalp completely and the
scales are layered)
Alibert impetigo characterized by an abundance of thick squamous
crusts as a result of the exudative process.
Streptococcal gangrene (microbial necrotizing fasciitis)

Etiopathogenesis: It is caused either by group A streptococcus or associations
between aerobic and anaerobic bacteria. Their action is subject to the existence
of an entrance gate (partial loss of a portion of healthy tissue), elusive most of
the times.
Clinical features:
painful erythemato-edematous crust, progressing towards necrosis;
it appears in the deep areas of the skin, subcutaneous tissue and
muscle fascia.
Sites: usually areas exposed to trauma (legs, cephalic extremity).
Streptococcal impetigo contagiosa

Although its etiology is considered both streptococcal and staphylo-
coccal, the condition has been included in group A bullous streptococci.
Etiopathogenesis: the condition frequently occurs in schoolchildren and is
favoured by immunodeficiency lack of hygiene.
Impetigo affects the healthy skin of the children while for adults its
presence requires a dermatosis (scabies, pediculosis, eczema), having the
appearance of impetiginization. The contamination occurs from one person to
78
another by skin lesions and may take the form of an epidemic disease in
isolated communities.
Clinical features: the initial elementary lesions are bullous subcorneal
vesicules, of variable diameter (from a few millimeters to 3 cm), with a clear
content, located on an erythematous base. Their content is rapidly becoming
purulent, the lesions break open, leaving scourings and then they cover with
crusts. Clinical manifestation often includes a polymorphism due to lesions of
different types of coexisting elements (vesicles, bullae, pustulae, scourings and
crusts).
Sites: the lesions most commonly occur on the face, natural orifices (nose,
mouth), but they may appear on the extremities, scalp and trunk.
The presence of pruritus explains the extension of lesions through
autoinoculation.
Immunoblastic adenopathy is likely to occur. The overall condition is
generally unchanged.
Evolution and prognosis: if adequately treated, the evolution is favorable, the
lesions epithelialize within days without scarring. The lesions may rarely
relapse or become chronic due to an insufficient treatment, or due to the
existence of a favorable dermatosis.
The complications are rare:
locoregional infections (pyoderma vegetans, lymphangitis);
general infection (fever, septicemia);
acute poststreptococcal glomerulonephritis;
toxic syndrome (SSSS) - exceptional.
Mixed streptococcal-staphylococcal infections

1. Strepto-staphylococcal cheilitis
2. Intertrigo
3. Whitlow/Felon
4. Ecthyma
Strepto-staphylococcal Cheilitis
This disease occurs in children and has a low degree of infectiousness.
Clinical features: The lesions affect the mouth corners, through the appearance
of painful blisters covered with melicerous scabs; the inflammatory process
79
covers the submucosa of the lower lip, which appears rupturing and
erythemato-scaling.
Intertrigo
The condition affects mostly the body folds, its appearance being
favoured by heat, humidity, poor hygiene and other pre-existing conditions
(eczema, mycosis).
Clinical features: the erythematous and erosive plaque that occupies the folds
(retroauricular, groin), covered with melicerous scabs and accompanied by
cracks at the bottom of the fold. The affection is accompanied by dermatopathic
lymphadenopathy.
The Whitlow - is a streptococcal infection at the end of a finger or toe in

the area surrounding the nail.
Clinical features: it is characterized by a large purulent blister accompanied by
intense pain.
Ecthyma
This is a pyogenic infection that develops on a weak site, caused by
multiple factors such as:
chronic venous insufficiency;
superficial wounds;
metabolic deficiencies;
poor hygiene.
In etiology, germs such as Pseudomonas aeruginoasa, Escherichia coli
are sometimes involved along with Staphylococci and Streptococci.
Clinical features: it begins as a deep bullae located on an erythematous base,
which breaks open and is covered with haematic crusts, while maintaining a
perilesional inflammatory erythematous halo. Healing leaves pigmentation and
scarring.
A particular clinical form is gangrenous ecthyma that occurs on a
immune suppressed ground. The lesions are covered with brown, adherent
scabs, covering gangrenous ulcers and the necrotic tissue.
Sites: usually on the legs, but the lesions may extend on the thighs, buttocks,
and rarely on the arms.
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Treatment and prevention of cutaneous infections with pyogenic

germs
The treatment of infections caused by streptococcus and staphylococcus
is done locally and/or generally depending on the severity and extension of the
infection. The choice of antibacterial therapy should take into account many
factors:
1. the clinical form of the disease;
2. the pathogen involved (its virulence and antibiotic resistance);
3. the general status of the host (age, associated diseases,
pregnancy, atopy);
4. the antibiotic used (dose, method of administration, plasma and
tissue levels, cost).
Given these parameters, overall antibiotic therapy is recommended in
the following clinical forms of disease:
all staphylococci and streptococci that appear in the first year of
life;
staphylococci caused by group II type phage 71 staphylococcal;
furuncles and furunculosis;
nail and periungual staphylococci;
sycosis staphylococci;
hidradenitis;
impetigos;
cellulitis, erysipelas, necrotizing fasciitis;
felon;
General treatment:
The use of overall antibiotic therapy is recommended in all
immunodeficient patients regardless of the clinical form of the disease and
when the local treatment is not properly applied.
Advantages of overall antibiotic therapy:
1. it prevents complications;
2. it removes the outbreaks responsible for reinfection and
infectiousness;
3. it acts both on cutaneous and extracutaneous level;
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The most commonly antibiotics used for infections caused by

Staphylococcus are: Oxacillin, cloxacillin, erythromycin propionyl,
pristinamycin, Rifampicin.
For streptococcal infections, the following classes of antibiotics are
used: penicillins (penicillin G), macrolides, cephalosporins, aminoglycosides
and fluoroquinolones.
Topical treatment aims to:
suppress the amount of bacteria;
reduce the inflammatory phenomena;
sanitize the entrance area;
evacuate the collections or damaged tissues (necrosis);
prevent the expansion of lesions;
promote epithelialization.
Recommendations for the topical treatment may vary depending on the
clinical form of the disease, on the evolving moment or the spreading of the
bacterial process.
Therapeutic alternatives include:
1. hygienic measures;
2. local antibiotic therapy;
3. surgical treatment;
4. physiotherapeutic methods (physiotherapy).
Local hygienic measures
required in all clinical forms of the disease;
it is highly recommended the washing with soap and water and
the use of antiseptic solutions (such as baths, compresses),
clothing disinfection.
Local antibiotic therapy
from the antibiotics used locally, the most frequently used are :
neomycin, bacitracin, polymyxin, gentamicin, mupirocin and
fusidic acid
they are effective in single therapy only on the superficial forms
(impetigo, superficial folliculitis, angular cheilitis, etc.)
The surgical treatment consists of: incision, drainage or excision of the
necrotic tissue areas.
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Local physical therapy is used for the reduction of inflammatory

phenomena (inflammatory roentgen therapy, local infiltration with
corticosteroids).
The specific anti-infective therapy may be associated with methods of
immunotherapy (nonspecific immunotherapy, vaccinotherapy), diet therapy and
the correction of the favorable associated conditions.
The prevention of cutaneous infections with pyogenic germs

The most useful method of prevention is health education. To prevent
pyoderma both individual and general preventions measures are required, aimed
at communities or occupationally exposed individuals.
Individual prevention is closely related to overall status of the body and
includes:
1. rigorous hygiene;
2. clothing hygiene;
3. avoidance of predisposing factors (micro traumatisms, contact
with infected individuals);
4. detection and treatment of infectious outbreaks.
Overall prevention requires the following rules:

1. periodic check up of the communities at risk (nurseries,
kindergartens, schools);
2. temporary isolation and treatment of subjects with confirmed
bacterial outbreak;
3. immunotherapy for high-risk categories.
Cutaneous infections with corynebacteria
Erythrasma
Etiopathogenesis:
it is a bacterial intertrigo, caused by a gram positive bacteria -
Corynebacterium minutissimum and it mostly affects males;
the etiological agent is located in the corneum stratum and its
adhesion is favored by heat, humidity, poor hygiene
83
Clinical features: it is characterized by a round or oval plaque:

brownish;
covered with fine scales, uniformly distributed on the surface of
the plaque;
non-pruritic and non-vesicular;
fine flat edges;
large (3-6 cm).
Sites: usually affecting the folds (inguinonal-femoral, axillary and rarely
interdigitally).
Common clinical forms:
1. nail erythrasma - frequently appears on the nail of the big toe
and is characterized by a yellowish-orange coloration, cross-
striations and hyperkeratosis of the nail bed.
2. erythrasma between the toes the lesions are vesiculobullous,
located interdigitally and may be associated with nail
involvement.
Laboratory diagnosis:
in Wood light, the examination of the scales with the optic
microscope shows the presence of thin elements, grouped in
straight bundles, which have the appearance of some chained
bacilli. The lesion has a coral red fluorescence produced by
coproporphyrin III;
bacteriological examination and test probe allow the isolation of
C. minutissimum.
candidiasis intertrigo;
pityriasis versicolor;
inguinonal-femoral epidermolysis;
reversed psoriasis;
eczema of the folds.
Treatment:
1. topical: antibiotics (erythromycin 3%) or imidazole derivatives;
2. overall (for recurrent or disseminated forms): erythromycin is
recommended, 2g/day for 10 days.
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3. prevention: local hygiene, use of large linen, made of cotton

which does not favour oversweating.
Trichomycosis axillaris
Etiopathogenesis:
the disease is caused by C. tenuis, in combination with other
aerobic corynebacterias in axillary and pubic hair;
the bacterium has affinity for the hair shaft and causes changes
regarding the stregth of its filament.
Clinical features:
it is characterized by the presence of small corpuscles adherent
to the hair shaft, of different colours: yellow, red or black;
oversweating with odor that stains linen;
the disease is asymptomatic.
Differential diagnosis: pediculosis pubis, thinning of hair.
Treatment: local usage of antiperspirant or aqueous formaldehyde solution 1%.
Pitted keratolysis/ Keratolysis plantare sulcatum

Etiology: it is a superficial infection of the skin caused by Corynebacteria,
Streptomyces or both combinations.
Clinical features:
it manifests through pointy depressions in the corneum stratum
of the plantar area;
it is associated with skin maceration, oversweating and
unpleasant odor.
Differential diagnosis: is done with vesiculobullous erythrasma, tinea
pedis, hyperhidrosis.
Treatment: Local antibiotic therapy in combination with imidazole and rigorous
hygiene.
Cutaneous diphtheria
Etiology: Corynebacterium diphtheriae
Clinically, there are two forms:
1. primitive cutaneous diphtheria characterized by pustular lesions,
that ulcerate and become covered by a gray membrane;
85
2. overinfection of lesions with C. diphtheriae (pyoderma, wounds,

scabies).
In this form, the lesions change their classic appearance and are covered
with a gray membrane, becoming erythematous, edematous and painful.
Treatment:
- per os antibiotic therapy: erythromycin, clindamycin, penicillin
and rifampicin;
- specific antitoxin administration.
Cutaneous infections with gram-negative bacillus
Gram-negative folliculitis
Etiology: Bacillus Proteus is the microbial agent isolated from cutaneous
lesions.
Clinical features: small, multiple pustules, placed on a erythematous base,
accompanied by discrete itching; the lesions can sometimes take nodular or
cystic appearance.
Sites: the lesions are clustered on seborrheic facial areas, but they may also
appear on anterior and posterior thorax.
Differential diagnosis: is done with papulopustular acne, superficial and deep
staphylococcal folliculitis.
Treatment: lLocal antibiotic therapy.
Recurrent folliculitis associated with Pseudomonas aeruginosa
The disease occurs in young children, causing small outbreaks. The
lesions occur after a pool bath or a steam bath. Excessive humidity is a high risk
factor for the occurrence of lesions.
Clinical features: cutaneous rash is of papulopustular type, with follicular
arrangement, surrounded by an erythematous halo.
Sites: the lesions are commonly located on the trunk and buttocks, and rarely on
legs or face.
Differential diagnosis is done with: Staphylococcal folliculitis, Pytirosporum
folliculitis
Treatment:
- mild forms do not require treatment;
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- extended forms are in remission after topical application of

gentamicin ointment
Cutaneous infections caused by neisseria
Cutaneous gonococcal infection

Etiopathogenesis
The etiologic agent is Neisseria gonorrhoeae. Cutaneous outbreak
occurs due to:
direct contact with Neisseria gonorrhoeae through infected
secretions;
hematogenous dissemination from a conspicuous or
inconspicuous urogenital hotbed.
a) caused by direct inoculation of the germ:
- gonococcal Felon (ulcers and multiple erosions, round or
oval, well defined, situated in the perigenital area);
- perigenital Folliculitis (preceding ulcerative lesions).
b) caused by dissemination of infection through hematogenous
route:
- gonococcal cutaneous abscesses - having a hypodermic site,
namely the sheath of the penis or scrotum;
- Gonococcal dermatitis syndrome associating polymorphic
cutaneous lesions (papulovesicular type, pustular lesions,
purpura) with migratory arthralgia, fever and alteration of
overall state. The cutaneous lesions are located on the
extremeties of palms, base of the foot, fingers, periarthric.
Treatment: antibiotic therapy with high dose of penicillin.
Cutaneous meningococcal
Cutaneous contact is not rare in N. meningitides sepsis. Cutaneous
lesions may vary without special characteristics; erythematous rash; urticarial
lesions; papular or purpuric lesions located on the trunk, shoulders, arms.
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Cutaneous infections caused by mycobacteria
Cutaneous tuberculoses
They are skin conditions caused by Mycobacterium tuberculosis.
Koch bacillus (Mycobacterium tuberculosis) is an acid-alcohol resistant
bacillus, revealed through Ziehl -Nielsen staining and produced in Jensen and
Dubois selective environments (Lwenstein).
Inoculated on the skin level, the Koch bacillus produces a
granulomatous specific reaction, and the clinical manifestation is determined by
the amount of bacilli, its virulence and immunity of the body.
A variety of factors such as: malnutrition, lack of hygiene, infectious
diseases (HIV infection) creates optimal conditions for Koch bacillus
inoculation.
Mycobacterium tuberculosis reaches the skin either by exogenous
(tuberculous chancre, tuberculosis verrucosa), or endogenous inoculation
(lymphatic or hematogenous) from a severe tuberculosis epidemics.
The primary infection of tuberculosis is commonly inconspicuous, but
the penetration of Koch bacillus produces good overall immunization that can
be evidenced through skin tests (intrauctaneous reaction to tuberculin).
The diagnosis of cutaneous tuberculosis infection is made upon the
following criterias:
1. major criterias:
presence of Koch bacillus in the cutaneous lesions;
isolation of Koch bacillus from cutaneous lesions on
appropriate cultures;
reproduction of the tuberculous lesion in guinea pigs after
the inoculation of the pathological product.
2. minor criterias:
personal history of tuberculosis;
positive intraucutaneous tuberculin test;
histological structure of the tuberculid ;
Classification of cutaneous tuberculosis:
I. Typical cutaneous tuberculosis:
a) Primary inoculation tuberculosis
1) tuberculous chancre
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b) Secondary cutaneous tuberculosis

1) lupus vulgaris
2) scrofuloderma (tuberculosis colliquativa cutis)
3) tuberculosis verrucosa cutis/warty tuberculosis
4) tuberculosis vegetans
5) orificial tuberculosis (Tuberculosis cutis orificialis)
II Unusual forms of cutaneous tuberculosis (tuberculids)
1) micropapular epidermal tuberculids (lichen scrofulosorum)
2) papulonectrotic dermal tuberculids ( acnitis)
3) Pautrier's ulcerous dermal tuberculids/ Pautrier's microabscesses
4) nodular tuberculids (erythema induratum Bazin's disease)
The tubercular chancre (primary TB complex)

is a cutaneous manifestation caused by primary inoculation
tuberculosis on healthy individuals;
commonly occurs in children up to the age of 5
Clinical features:
in the early stages the lesion presents itself as a papulopustular mass
that quickly ulcerates;
the clinical appearance is that of an ulcerative lesion with irregular
edges and the base covered with sanguinolent secretions
(tuberculous chancre );
subsequently, the ulceration is covered with a sticky brown crust;
the tuberculous infectious chancre is constantly associated with
unilateral adenopathy forming the primary cutaneous complex.
Positive diagnosis is supported by:
1. its typical clinical appearance previously described;
2. presence of Koch bacilli within the lesion;
3. TST positive PPD;
4. typical histological structure of tuberculous granuloma (Kster
follicle).
Differential diagnosis is done with:
syphilitic canker;
soft canker;
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trivial pyococcus ulcers.
Lupus vulgaris
is the most common form of cutaneous tuberculosis and it occurs :
- through exogenous inoculation;
- through endogenous inoculation (lymphatic or hematogenous);
- contiguously (from a serious tuberculosis outbreak).
the disorder occurs in people with good overall resistance.
Clinical features:
the defining elementary lesion is lupus tubercle, located deep in the
dermis, of soft consistency, with a diameter of 3-4 mm, visible on
vitropressure;
the tubers coalesce to form well defined plaques, covered with fine
scales and having a slow rate of progress .
Sites: normally located on the face, the contamination occuring most frequently
on the endonasal mucosa.
Clinical forms:
a) plaque form:
is clinically characterized by small tubers, grouped in slightly
raised plaques, with infiltrated edges covered with scales;
vitropressure identifies the isolated tuber on the periphery of
plaques, that changes color to yellow-brownish , similar to an
apple marmalade;
the plaquess center evolves into cicatricial atrophy (through an
interstitial sclerosis process) and is marked by the appearence of
new relapsing tubers.
- chronic lupus erythematosus;
- pearl - shaped basal scar epitheliom.
b) lupus vulgaris profundus:
lupus myxomatous
lupus tumidus
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Lupus myxomatous /Tumor like-forms

It is located on ears concha, in the form of purple prominent plaques,
without being prone to ulceration.
Lupus tumidus
Affects the nasal pyramid, the appearance is characteristic, plaques
made of large non ulcerating lupomi/eruptions. Histopathological examination
reveals the presence of Kster follicle (Langhans cells, epithelioid and
lymphocytes) with inconsistent necrosis caseation.
c) Lupus tuberculosus ulcerated form
Clinical manifestations include an irregularly-shaped ulceration, having its base
covered with purulent secretions, located mainly on the face and the limbs.
Based on its clinical appearance, there are the following particular
forms:
ulcerative-crusty tuberculous lupus
gangrenous/vegetating form of lupus (the ulcerative process is
associated with a vegetating process)
tubercular lupus terebrant (vorax) characterized by large
eruptions , rapidly evolving to deep ulceration and scarring .
- terebrant basal squamous epithelioma of the face;
- centrofacial malignant granuloma;
- tertiary syphilis
Tubercular lupus runs a slow chronic course with typical scarring
(imperfect scars).
Scrofuloderma
is a clinical form of secondary cutaneous tuberculosis ;
the lesion occurs due to the localization of the Koch bacillus in
the skin , originated from a lymph node or bone infection.
the condition occurs in people with a defficient immunitary
system.
Clinical features: the characteristic lesion is represented by the gumma and it

develops in stages:
1. stage I - rawness stage (a painful firm swelling , located deeply in
the dermis).
91
2. stage II subsidence stage (the swelling becomes fluctuant and

adherent to the skin surface).
3. stage III canker stage (the appearance is that of a canker with deep
and irregular edges and the bottom is covered with purulent
discharge).
4. stage IV - scarring stage (healing is done with vicious adherent
scarring).
Sites:
The lesions predominantly affect the lateral- cervical region, but they may
occur in other areas as well: submaxillary, presternal region, armpits.
The positive diagnosis is supported by:
its clinical appearance;
the staging development;
location of lesions;
presence of bacillary outbreaks.
The differential diagnosis is done with other nodular lesions:
deep mycoses;
hidradenitis;
syphilis.
Tuberculosis verrucosa cutis
is a rare clinical form;
the lesions are produced by direct inoculation of the Koch bacillus
into the skin;
the lesions are located on the hands, fingers and lower limbs.
Clinical features:
presents as verrucous lesions, arranged in plaques, of different sizes
and irregular shapes;
within the same plates there are three distinctive areas:
1. a central hyperkeratotic area;
2. a solidified area, with cracks and pus (intermediate);
3. an inflammatory area, erythematous-violet (peripheral).
the skin lesions are accompanied by lymphadenopathy or
lymphangitic cords;
92
a distinctive clinical form is the anatomical tubercle a small nodule

with a keratinized surface, usually located on the hand (occupational
disease it occurs in people that come in direct contact with BK).
The differential diagnosis is done with:
pyoderma vegetans
Verrucous lichen.
Vegetating form of Tuberculosis

Clinical features:
it appears as a vegetative mass of pseudotumoral appearance;
the primary lesion consists of multiple nodules, rapidly evolving to
ulceration.
Ulcerous TB (periorificial tuberculosis)

the disorder occurs in people with an active outbreak of tuberculosis
as a result of autoinfection with pathological material;
the location of the tuberculous ulcer is directly related to the visceral
outbreak and the discharge of bacilli.
Pulmonary tuberculosis enables the location of TB ulcer on the mouth
(tongue, lips, gums). Intestinal tuberculosis induces lesions in the perianal
region.
Clinical features: it appears as an ulceration with loose edges, punctated with
small yellow granulations (caseation of tuberculids) with a soft base, not very
painful.
clinical appearance;
active TB outbreak;
abundance of Koch bacillus in the lesion;
characteristic histopathologic appearance.
Based on its usual sites, the diagnosis is done with:
epidermoid carcinoma of the lip;
syphilitic chancre.
93
Lichen scrofulosorum
Etiopathogenesis:
it is a rare condition affecting young BCG vaccinated or people with
deep tuberculosis outbreak (ganglionic or pulmonary) ;
lesions are produced by a reaction of sensitivity of the skin to
bacillary antigens ;
the structure of the lesions is tuberculous;
the condition manisfest itself after intercurrent febrile infection
(influenza, measles, scarlet fever).
Clinical features:
the lesions are small, yellowish or reddish papules, chronic,
acuminated, covered with scales or crust ;
the lesions prefer a perifollicular site, but they may be separated
from the pilosebaceous follicle;
the lesions may be isolated or they may coalesce into ill-defined
plaques;
they are not accompanied by subjective symptoms.
Sites: the lesions are commonly located on the trunk, rarely on the face and
extremities.
Progress: after a few weeks or months, the lesions heal spontaneously, however
relapses are also possible.
lichenoid syphilids;
follicular keratosis;
follicular microbial eczematides;
lichen planus;
pityriasis rubra pilaris.
Papulonecrotic Tuberculids
Etiopathogenesis:
skin lesions occur as a result of hematogenous dissemination of deep
tuberculous outbreaks;
an immunological hypersensitivity reaction to the tuberculous
bacillus occurs on a cutaneous level, causing a necrosis process;
94
the condition affects adolescents and adults with visceral

tuberculosis outbreaks.
Clinical manifestations include:
callous small dermal papules, pink-violet in colour, located in the
dermis, which necrose centrally and are covered with a brown crust;
the necrotic crusts detach themselves, leaving crater-shaped
ulcerations;
the lesions are symmetrical and they heal with final round scarring,
subsided, pathognomonic (varioliform appearance).
Depending on the site of the eruption, two clinical forms are described:
a) foliclis type:
purple papules around the pustule, which ulcerate and heal with
atrophic scars;
located on the extensor surface of the limbs and thorax.
b) acnitis type:
clinically they are papulopustular nodules which decrease and
discharge a yellow content, leave ulcers that heal with depressed
scars;
it affects the face, the seborrheic areas or trunk and resembles
like polymorphic acne.
Acne scrofulosorum
the lesions are similar to those of the foliclis type, but the lesions are
superficial;
located on the extensor surface of the upper limbs.
Acne cachecticorum
the lesions are papulo- crusted nodules and resemble acne vulgaris,
but the comedones are lacking ;
it commonly appears on the trunk and limbs.
Evolution: The eruption is seasonal (in autumn, spring) and can relapse.
polymorphic acne;
necrotic acne;
acneiform syphilides;
trivial folliculitis.
95
Miliary tuberculids (lupus miliaris)
Clinical features:
dusky- red small nodules of just a few millimeters in diameter, of
callous consistency
the lesions rarely ulcerate and the healing is done without scarring.
Sites: usually on the face.
Rosacea-like tuberculids
They represent a distinctive form of miliary tuberculids.
Clinical features: papulo-nodular lesions located on erythematous skin and
rosacea.
The differential diagnosis is done with rosacea and lupus vulgaris.
Ulcerous Tuberculids of Pautrier

Etiopathogenesis
it is a rare clinical form of tuberculosis;
it affects young females with old forms of pulmonary tuberculosis.
Clinical features:
ulcerous lesions with irregular borders (resembling ecthyma), which
heal with pigmentating scarring;
the lesions are arranged symmetrically on the legs.
ecthyma of the leg;
leg ulcer.
erythema induratum of Bazin.
Erythema induratum of Bazin

Etiopathogenesis:
it is a hypodermic nodular vasculitis with chronic evolution and
tuberculous etiology;
it occurs in women with a history of visceral tuberculosis, but in
most of the cases the tuberculous etiology is elusive;
96
the condition is stimulated by circulatory disorders (acrocyanosis)

prolonged standing, prolonged exposure to cold weather and
humidity.
Clinical features:
hypodermic firm nodules, with ill-defined edges, slightly painful,
scattered or in patches;
the nodules tend to reabsorb themselves leaving interstitial
depressed scars;
a distinctive clinical form is represented by Hutchinsons ulcerous
erythema, in which the nodules evolve to ulceration, having
irregular edges and being surrounded by a purple halo;
healing leaves unsightly atrophic scars.
The positive diagnosis is emphasized by:
the clinical appearance of the lesions;
the positivity of relative diagnostic criteria;
the histopathological exam which highlights:
- the atrophy of the fat cells with proliferation of the connective
tissue and lesions which infiltrate;
- nodular tuberculoids infiltrating through the hypodermis;
- endothelioid lesions, veinal and arterial thrombosis.

erythema nodosum;
syphilitic gumma;
tuberculous gumma;
varicose ulcer;
leg hypodermititis of other etiologies.
The treatment of cutaneous tuberculosis
I. The curative treatment:
is paramount, and uses chemotherapy and anti-tuberculosis
antibiotics;
as for cutaneous tuberculosis, the same priciples used in visceral
tuberculosis must be followed.
According to their use, the tuberculostatics have been categorized into:
97
a) main tuberculostatics (Rifampicin, Ethambutol, Isoniazid)

b) substitute tuberculostatics (streptomycin, pyrazinamide,
kanamycin)
The treatment regimes are continuous and associate specific
chemotherapy and antibiotics:
- Rifampicin 600 mg / day single dose;
- Isoniazid 5-10 mg / kg / day;
- Ethambutol 15-25 mg / kg / day.
The association of tuberculostatics and the duration of treatment should
be adapted to the type of skin lesion and the patient's immune status.
The most effective drug combination is: Rifampicin + Hydrazide +
Ethambutol.
The treatment is carried out in two stages:
1) aggression treatment it takes two months;
2) maintenance treatment 6- 9 months (just Hydrazide 5 mg / kg /
day).
In atypical cutaneous tuberculosis, corticosteroids and immunotherapy
are associated with classic tuberculostatics.
II) The adjuvant treatment recommends:
- anabolics;
- vitamin therapy;
- immunostimulants;
- specific medication related to disorders.
III) The hygienic-dietary treatment recommends:
- bed rest;
- diet rich in protein, vitamins and mineral salts;
IV) The Surgical treatment
In the most resistant forms of disease, excision can be carried out and
also electrocoagulation or curettage of lesions such as tuberculous gumma,
tuberculosis luposa, tuberculosis verrucosa.
V) The Preventive treatment:
primary aims at preventing the visceral tuberculoses and
especially the pulmonary one;
It is recommended:
98
1. to identify the source (through regular checks of risk

populations);
2. the isolation and treatment of the cases diagnosed with
visceral or cutaneous tuberculosis;
3. follow up of the patients until complete healing.
Leprosy
Leprosy or Hansen's disease is a chronic mycobacterial infection (with

Mycobacterium leprae or Hansen bacillus) with a low degree of infectiousness,
that affects primarily the peripheral nervous system and secondly the skin and
other tissues.
Epidemiology
It usually affects children and rarely young adults.
The average incubation period is 3-5 years, from a few months to 20
years.
It is assumed to be trasmitted through:
- the skin by direct inoculation (tattoos), existing abrasive injuries
or insect bites;
- the gastrointestinal tract;
- the respiratory tract through secretion droplets that reach the
atmosphere or through the dust during speaking, sneezing or
coughing.
The source of infection is represented by the undiagnosed patient who
oozes bacilli by nasal secretion, saliva, blood, urine, semen / vaginal secretion,
milk and skin wounds.
Favorable conditions are represented by: malnutrition, inadequate
hygiene, socio -economic limitations.
The disease, originating in Asia (VI century BC), is endemic in tropical
and subtropical countries but it is also encountered in temperate geographical
regions (the Mediterranean coast, the natives of Australia).
Etiology
Mycobacterium leprae is an acid-fast -alcohol resistant bacillus evidenced by a
modified Ziehl - Neelsen staining, the oldest human agent known, except for
Pseudomonas aeruginosa and Bacillus antracis (discovered by Hansen in 1873).
99
It has a particular affinity for the nervous tissue, the target cell being the
Schwann cell.
Clinical manifestations
After contamination, the type of clinical expression (otherwise varied)
depends on the individual resistance, especially on the cell mediated immunity.
The main clinical forms, grouped according to histopathological,
bacteriological and immunological criteria, are the following:
1. stable clinical forms (polar typical)
- lepromatous leprosy (LL)
- tuberculoid leprosy (LT)
2. unstable clinical forms (atypical)
- indeterminate leprosy (IL)
- borderline leprosy (BL)
Lepromatous leprosy
It is the most severe form of leprosy which can occur with:
symmetric skin lesions, bilateral, affecting the face, arms, legs, buttocks
(cutaneous areas with lower temperatures): small, relatively well delimited
erythematous or copper-colored macules; papules and nodules of regular
skin color or erythematous / copper-colored, stiff, in the thickness of the
skin, of varying sizes; facial skin and ears become thickened (infiltrated)
with deep folds, the nose becomes swollen and enlarged, eyebrows and
eyelashes are lost, becoming "leonine facies". A firm chronic swelling of
the legs, emphasized during the evening, is also present. A late cutaneous
sign is ichthyosis.
mucosal lesions: nasal obstruction and rhinorrhea, sometimes with blood,
can be the clinical sign of an onset. The nasal mucosa is infiltrated, folded
and subsequently ulcerated. In late evolutionary stages septum perforations,
destruction of the nasal cartilage or the collapse of the nasal pyramid may
occur. The condition can occur on other mucosas such as: oral mucosa
(papules, nodules on the labial mucosa, tongue, palate, evolving towards
ulceration), laryngeal mucosa (fibrous changes of the vocal cords with
hoarseness or painful ulcers and dysphonia), lining of the eye (iritis and
iridocyclitis, punctate keratitis).
100
nerve symptoms: abnormal sensitivity (sensory loss " in gloves and socks ,
involving limb extremities), which lead, due to the absence of pain and
thermal sensitivity, after repeated trauma, to trophic disorders : ulcers,
neuropathic ulcerations, distal digital amputations.
other systemic involvement:
- bones (hands, feet, skull): resorption, concentric bone atrophy as
a result of repeated trauma, abnormal vascularity and
innervation, osteoporosis, osteomyelitis secondary to chronic
mucositis;
- testicular (atrophy after repeated orchi-epididymitis), evolving to
impotence and gynecomastia;
- nefritic (amyloidosis, glomerulonephritis, interstitial nephritis,
pyelonephritis), reasons for an increased mortality.
the general condition is affected, patients suffer from fever and
fatigue, lose weight, develop poliadenomegaly.
Tuberculoid leprosy
It is a less severe clinical form, less contagious, which manifests itself
by:
various skin symptoms: macules or papules in single or multiple
plaques anywhere on the skin of cold regions (regions in the
proximity of hairy scalps, armpits, groin, perineum), erythematous /
copper-colored or hypopigmented, irregular, scaly, with raised
distinctive borders, alopecia and without tactile, thermal or pain
sensitivity;
nerve symptoms may be the only manifestations and consist in
sensory loss, muscle weakness or peripheral paralyses; they are
accompanied by thickening of a nerve that becomes palpable, in the
proximity of possible skin lesions.
Indeterminate Leprosy
It usually appears in childhood and it manifests as macular skin lesions,
usually single or multiple, with asymmetrical distribution, erythematous or
hyperpigmented, relatively well-defined on the face or limbs, accompanied by
slight sensory loss.
101
This clinical form may have a benign evolution, being self-contained, or

it may develop into a lepromatous leprosy or a borderline leprosy.
Borderline leprosy
It is a transitory clinical form ranging somewhere between lepromatous
leprosy and tuberculoid leprosy and it can go around these two poles. It differs
from the two poles by:
- immunological instability and hence the tendency to evolve
towards one of the two directions (if treated - towards
tuberculoid leprosy , in the absence of treatment - tuberculoid
lepromatous leprosy);
- treatment response and the time needed in order to eradicate the
infection;
- tendency to lepromatous reactions and deformities through nerve
damaging.
The clinical picture is dominated by asymmetric nerve damage and skin
lesions whose appearance is different, depending on the pole to which the
disease evolves: more numerous, less well defined if headed towards the
development of lepromatous leprosy and less numerous, sometimes outlining
defined borders- if headed towards the other pole of evolution.
Anesthesia and alopecia characterize borderline leprosy lesions but they
are more significant if headed towards tuberculoid leprosy. Bacilli are present
in the lesions, being absent or rare in the tuberculoid form and very numerous
in the lepromatous one.
The types of skin lesions in borderline leprosy are the following:
- erythematous and hyperpigmented macules;
- erythematous / copper-colored plaques;
- annular lesions, sometimes very large;
- bizarre injuries (geographical figurations);
- nodules.
During the treatment against leprosy there may occur sudden changes in
the immune reactivity with exacerbation of clinical signs that refer to two
aspects:
1. type I leprous reaction, characteristic to borderline leprosy
manifested by an exacerbation of skin and nerve lesions and
followed by either a favorable tendency towards healing (regarding
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the tuberculoid form) or to aggravation and development of

lepromatous leprosy;
2. type II lepromatous reaction, which occurs during the treatment of a
Borderline lepromatous leprosy and prone to lepromatous form, due
to the formation of circulating immune complexes.
The positive diagnosis
Is based on:
1. histopathological examination:
- in lepromatous leprosy the abounding presence of Hansen
bacillus within the lesions, densely infiltrated in the skin with
histiocytes invaded by Hansen bacilli, arranged in intra-and
extracellular globs, containing foamy Virchow cells
(macrophage vacuolated);
- in tuberculoid leprosy - the presence of tuberculoid dermal
granulomas (epithelioid cells, lymphocytes and giant cells)
around adnexal structures and nerve cells, the absence of
Vinchow cells and Hansen bacilli (or the presence of a small
number);
- in indeterminate leprosy - the presence of a perianexial and
perinervous non-specific infiltration, predominantly
lymphocytic, rare Hansen bacilli;
- In borderline leprosy - the presence of an infiltrate with
macrophages, epithelioid cells and bacillus Hansen among them;
in tuberculoid form there is a tendency to a granulomatous
infiltrate and a tendency towards the appearance of foam
Vivchow cells-in lepromatous form.
2. in skin lesions and nose secretions the bacteriological examination
highlights:
- in lepromatous leprosy - numerous Hansen bacilli;
- in tuberculoid leprosy a very rare number of Hansen bacilli;
- in indeterminate leprosy - no Hansen bacilli in nasal secretions
and the presence of a small number in cutaneous lesions;
- in borderline leprosy - a small number of Hansen bacilli in the
tuberculoid form and a great number in the lepromatous form.
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3. intradermal reaction to lepromin (Mitsuda reaction) is a reaction of

delayed hypersensitivity to Mycobacterium leprae or its antigens : it
is negative in borderline to lepromatous leprosy and lepromatous
leprosy, highly positive in tuberculoid leprosy and low positive in
indeterminate leprosy and tuberculoid borderline leprosy.
The differential diagnosis
Lepromatous leprosy and borderline leprosy must be distinguished
from:
- sarcoidosis;
- mycosis fungoides;
- cutaneous leukemic infiltrates.
Tuberculoid and indeterminate leprosy differentiate from:
- annular granuloma;
- lymphoma;
- vitiligo;
- localized scleroderma (morphoea).
Treatment
The elective treatment of leprosy is diaminodiphenylsulfone (Dapsone,
Disulone). Sulfonotherapy is currently associated with rifampicin and
clofazimine in lepromatous and borderline leprosy.
The responses (leprous reactions) require the interruption of
sulfonotherapy and the administration of corticosteroids or non-steroidal anti-
inflammatory drugs, antipaludic of synthesis.
Osteoarticular and motor sequelae require plastic and reconstructive
surgery, physiotherapy, orthopedic treatments.
Actinomycosis
It is a chronic suppurative disease characterized by subcutaneous

nodular lesions which suppurate discharging a specific grain-purulent secretion.
Etiopathogeny
Actinomycetes are filamentous bacteria that produce fungi-like
ramifications which is why cutaneous actinomycoses are classically considered
deep mycosis.
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Pathogenic actinomycetes are mostly saprophytic of the soil, those

pathogenic to humans are anaerobic and commonly colonize the oral cavity.
Most actinomycoses are therefore the result of endogenous infection.
The most common culprit is Actinomyces israelii which belongs to the
saprophytic flora of the oral cavity.
The main cause of tissue invasion by actinomycetes is trauma, which
creates breaches.
The disease may affect both sexes equally, all age types but is more
common in adults coming from rural areas, with poor oral hygiene.
Histopathology
The inflammatory process triggered by actinomycetes is of granulomatous type,
while the histologically detectable lesions are:
chronic neutrophilic and lymphocytic infiltrate around granular
colonies from which radiate filaments (some having a club-like
appearance);
lobulated masses of filaments that join and form " sulphur granules";
fistulas through which the "sulphur granules" are displayed on the
surface of the ulcerated skin.
Clinical features
Actinomycosis can affect any organ of the body. Depending on its spreading,
there are five types:
1. Cervicofacial actinomycosis - which presents as hard red lumps on
the cheek or on the submaxillary region, fistulas and scars on which
new nodular lesions occur, leading to suppurative plaques and
scarring nipples. The primary lesion is either in the mandible or
maxilla and arises as a direct extension, from a periodontal abscess
formed as a result of cavities, tooth extractions, or posttraumatically.
Maxillary lesions may extend to the orbit, bones of the skull and
encephalon. Another way of spreading the infection is from the
tonsillar crypts to mandible. Constantly, actinomycosis affects the
bones: periostitis, osteomyelitis. The granulomatous skin can lead to
well-defined fibrosis sequelae.
2. Thoracic actinomycosis - is clinically similar to an active
tuberculosis and subsequent to the aspiration of oral flora; the skin
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changes during this clinical form are secondary to the thoracic wall
involved.
3. Abdominal actinomycosis - it has appendicular and cecal
involvement, the source of infection being the oral cavity or the
tonsils.
4. Primary cutaneous actinomycosis - is a rare clinical form, which
occurs through inoculation (exogenous infection) resembling
mycetoma.
5. Pelvic actinomycosis - is associated with intrauterine contraception
devices and doesnt cause skin lesions.
The evolution of actinomycosis without treatment is serious, leaving marks;
cervicofacial and primary cutaneous actinomycosis remain localized
conditions for a long time.
The positive diagnosis is based on the appearance of the lesions, the presence of
sulphur granules (1-2 mm diameter, adherent to gauze dressings) which
histologically consist of narrow bacillary forms and elongate hyphae with
branching.
Histopathological examination is the one that confirms the clinical
diagnosis. The inoculators require enriched media and incubation at 37 C in
anaerobiosis. It develops in white shiny colonies, with irregular edges.
The differential diagnosis
For cutaneous lesions, the following are taken into consideration:
- scrofuloderma;
- accumulated syphilitic gummas;
- mycetoma;
- botryomycosis.
Treatment
The inflammatory cycle that follows the granulomatous reaction inhibits
the penetration of antibiotics. Therefore, the disease requires long periods of
treatment. Sulphonamide, streptomycin, penicillin in large doses i.v.,
chloramphenicol, tetracycline and imipenem are used.
The antibiotic treatment is sometimes associated with a surgical
treatment.
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VIRAL SKIN INFECTIONS
Mucocutaneous virus skin infections are conditions caused by viruses

with affinity for the skin and mucous membranes.
The viruses are microorganisms made of nucleic acid (DNA, RNA) and
a protein shell called capsid.
Their replication depends on the ribosomes of a host cell.
The types of viruses involved in cutaneous and mucosal pathology are:
Dezoxyriboviruses
1. herpes viruses (herpes simplex, varicella-zoster, cytomegalovirus,
Epstein-Barr virus, human herpesvirus 6, 7 and 8)
2. pox viruses (vaccinia virus, paravaccinia, smallpox, molluscum)
3. papovaviruses (human papillomavirus - HPV)
4. hepatoviruses(hepatitis A, B, and C)
5. parvoviruses (B 19)
6. adenoviruses
Riboviruses
1. retroviruses
2. paramyxoviruses
3. togaviruses
4. picornaviruses (ECHO virus)
5. rhabdoviruses (vesicular stomatitis virus)
Classification of viral dermatoses:
Specific viral skin infections
infections caused by herpes viruses (Epidermal herpes
infections)
HPV infections (Epidermal hyperplasia infections)
infection with poxviruses (degenerative and exudative epidermal
infections)
other mucocutaneous manifestations caused by the viruses
Cutaneous syndromes associated with viral infections:
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Gianotti-Crosti Syndrome (infantile papular acrodermatitis)

papular-purpuric gloves and socks syndrome
Dermatoses presumably of viral etiology

Pityriasis rosea Gibert
Kawasaki disease
Viral dermatoses of eruptive fevers:
infectious exanthema
- Varicella
- Rubella
- Measles
Herpesviruses
They are conditions produced by herpes viruses. This category includes:
1. Epidermal- neuro viral infections
herpes simplex
varicella zoster virus
2. Other types of herpes infections
infection with the Epstein-Barr virus (EBV)
cytomegalovirus Infection
human Herpesvirus 6
Epidermal-herpetic viruses
They are diseases caused by DNA viruses, which are part of the herpes
virus family, with intranuclear replication and persistence, remaining silent over
the years.
These viruses are reactivated in conditions of immune suppression and
prefer tissues of ectodermal origin (skin, nervous tissue).
The characteristic lesions are of erythematous vesicular type.
Herpes simplex
Etiology:
Herpes virus hominis (HSV) types 1 and 2 is the etiologic agent of
herpes simplex. HSV-1 is responsible for herpes infections located in the upper
half of the body while HSV-2 is associated with genital herpes infection, or the
lower half of the body.
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Primary infection with type 1 usually occurs in childhood and it rarely

manifests clinically.
Primary infection with antigenic type 2 occurs after puberty, it is usually
asymptomatic and it is sexually transmitted. After primary infection, the virus
persists in sensory nerve ganglia (where it remains latent) and can be detected
in genital secretions and saliva in apparently healthy subjects. Recurrences are
associated with temporary depression of the cell-mediated immunity.
In immunocompromised hosts, the primary HSV-1 infection is severe,
with large necrotic lesions, which tend to generalize and affect the viscera
(liver, meningoencephalitis).
Depending on the onset, the clinical manifestations of herpes are
classified into :
clinical manifestations of primary herpes infection
clinical manifestations of recurrent herpes infection
Clinical manifestations of primary herpes infection
Herpetic gingivostomatitis
It is induced by HSV1 and occurs in children between 1 and 5 years of
age with an immature immune system. The incubation period is about 5 - 6
days.
Clinical features: it is characterized by erythema, swelling and bleeding gums,
with diffuse vesicles, white plaques, erosions and ulcers covered with yellowish
pseudomembranes. The lesions are located predominantly on the tongue,
pharynx, palate but it may be affect the lips, perioral region and tonsils. In
severe cases the lesions are accompanied by general malaise, hypersalivation,
critical dysphagia and submandibular or cervical lymphadenopathy which
persists even after the healing of the eruption. The flare lasts about 20 days and
has a favorable prognosis.
Genital herpes/Herpes genitalis
It embodies the clinical manifestation of primary genital herpes
infection with HSV2. It normally occurs in the young females, in the form of
herpetic vulvo-vaginitis .
Clinic features: It is characterized by vesicles grouped on an erythematous and
edematous base, which break open quickly, forming polycyclic erosions, of an
aphtous appearance. Lesions may extend to the walls of the vagina, to cervical
and perianal region, they are painful, accompanied by lymphadenopathy,
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dysuria and fever. The evolution is favorable. The healing is occurs

spontaneously, in about 1-3 weeks.
In males, the primary genital herpes infection is less noisy, the lesions
are located on the glans, prepuce and shaft of the penis and it is frequently
confused with erosive balanitis.
Herpetic keratoconjunctivitis
Clinically, it can take two aspects:
a. superficial keratoconjunctivitis (dendritic)
b. deep keratoconjunctivitis (disciform)
The lesions translate into severe purulent conjunctival inflammation,
associated with significant edema of the eyelid and corneal ulcers which may
lead to corneal opacity.
Herpetic whitlow - posttraumatic herpes
It occurs due to direct inoculation of the herpes on normal or injured
skin.
Clinical features: the lesions are coalescing vesicles, located on an
erythematous and edematous base, painful, affecting the fingertips.
Occasionally they may associate with general moderate signs of
lymphadenopathy.
This is an occupational disease.
Eczema herpeticum
It is a severe form of primary herpes infection. It occurs in children with
atopic eczema and it is a manifestation of Kaposi Juliusberg varicelliform
pustulosis.
Clinical features: it manifests as an erythematous, generalized vesiculobullous
pustular rash, evolving towards erosions, ulcers and crusts. The lesions may
affect the buccal and conjunctival mucosa and are accompanied by fever and
general malaise. Mild forms resolve within 8 - 14 days, while severe forms
occur in immunocompromised children and may take a dramatic turn, with
visceral complications and even death.
Neonatal herpes
Primary infection with neonatal herpes is rare and can be produced by
HSV1 as well as by HVS2. The HVS1 infection may occur in the first day of
life, by direct contact with family members or medical staff.
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Primary infection with HVS2, typically occurs at the time of delivery,

the contamination occuring from maternal genital herpes.
Neonatal herpes infection clinically covers two forms:
1. cutaneous and septicemic form
2. meningo-encephalitis form
Clinical features:
It is characterized by an erythematous-vesicular disseminated
mucocutaneous rash, associated with severe malaise and signs of visceral
damage. Meningo-encephalitis describes a clinical picture of remarkable
severity, associating signs of meningitis, encephalitis and septicemia with
multifocal involvements.
Clinical manifestations of recurrent herpes infection
Recurrent herpes It commonly occurs in adults and can be caused by
HVS1 or HVS2. It has a high incidence due to a transitory decrease of cell
immunity. Genital herpes recurrences are more frequent (30 - 50%) than labial
herpes (8-10%) and prefer the same anatomical sites, where the primary
infection occured.
The occurrence of recurrent herpes is related to various triggering
factors: respiratory tract infections, local trauma, fever episodes, emotional
stress, digestive disorders, menstrual cycle, (catamenial herpes), UV radiation
exposure, dermatological treatments (dermabrasion), sexual intercourse.
Clinical features: it begins as a typical prodromal syndrome consisting
of itching and burning sensation at the site of the eruption. The lesions are
represented by closely grouped vesicles (clustered), located on a erythematous
and slightly edematous plaque. The vesicles have a distinct sero-citrine, are
small but they may join to form vesiculo- bullae which break open quite easily,
leading to erosions with polycyclic borders. After the erosion, the lesions are
covered with melicerous or sero-hematic crusts, adherent, that are removed
within a few days. Constantly the lesions are accompanied by painful
inflammatory lymphadenopathy. The duration of development ranges from 7 to
10 - 14 days, and healing doesnt leave any scars.
Clinical forms of recurrent herpes depending on the main sites:
1. Herpes labialis, located on the lips, accompanies the fever episodes.
2. Nasal Herpes - is less painful, usually located unilaterally, which
should be differentiated from nasal folliculitis.
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3. Recurrent genital herpes - is often profuse, it affects the

balanopreputial sulcus, the inner front of the foreskin and glans of
men whereas in women, it affects the vulva, the vagina and the
cervix. It raises therapeutic problems (disappointing treatment),
social problems (it occurs in sexually activepeople), but also
problems related to prognosis (possible oncogenic effect).
4. Recurrent ocular herpes (HSV1) has a low prognosis, due to
repeated corneal ulcerations, which can lead to blindness.
5. Herpetic stomatitis this rarely diagnosed clinical form can be
confused with aphthous stomatitis.
Positive diagnosis:
Ways of diagnosing the herpes:
1. Clinical examination (eloquent and sufficient for the classic forms)
2. Laboratory Tests
cytological examination - reveals the intranuclear inclusions
regarding the lesions
immunofluorescence - identifies the viral antigen using
monoclonal antibodies
serological examination-measures the titer of specific antibodies
from the patients serum
virus isolation by culture and typing.
histopathological examination: indicates the presence of
parenchymal intraepidermal vesicles, as a result of a distinctive
acantholysis, accompanied by reticular and bulging
degeneration.
The differential diagnosis of primary and recurrent herpes infection is
based on the clinical appearance and the sites involved:
for occurrence in the mouth:
- streptococcal angina
- herpangina
- oral thrush
- figurate ulcerative stomatitis
- oral Erythema multiforme
- pemphigus with classic onset
- secondary syphilides on the mouth
112
for occurrence on the genital mucosa:

- syphilitic canker
- circinate erosive balanitis
- genital thrush
for occurrence on the skin:
- impetigo vulgaris
- eczema
- shingles
The complications of herpes infection are:
1. systemic dissemination in neonates and immunocompromised
people
2. recurrent lymphocytic meningitis
3. encephalitis
4. erythema multiforme
5. radiculoneuropathies
The treatment of herpes infection

It aims to:
- limit the eruption
- reduce the inflammation and pain
- prevent the secondary infection
- fight relapses
- improve the prognosis
1. The general treatment is usually reserved for severe forms and
includes the administration of:
antiviral chemotherapeutic agents.
The most used antiherpetic drug is acyclovir, cyclic nucleoside, that
inhibit DNA herpetic polymerase after a prior phosphorylation.
It relieves the symptoms regarding the eruptive episode, but it
influences the recurrences in a lower degree.
Primary herpes infection and severe recurrences are the ones that
receive general antiviral therapy with acyclovir. Acyclovir can be administered
orally or intravenously and the dosages used will vary depending on the clinical
form. The dose of acyclovir administered per os is usually 2g/day for its
curative effect and 400-800mg/day to prevent recurrences.
113
In severe forms of herpes infection which occur in immunosuppressed

people or those resistant to acyclovir, another antiherpetic is recommended,
Forscarnet. Recently, other antiherpetics have been synthesized better than
acyclovir in terms of bioavailability, such as valacyclovir, ganciclovir,
brivudine, famciclovir.
anti-inflammatory and analgesics
They are recommended in extensive forms to improve subjective
symptoms.
immunomodulatory drugs
There are used specific immunomodulators: isoprinosine, interferon
gamma imunovir, antiherpetic vaccine.
The topical treatment consists in:
the administration of antivirals in the form of creams, ointments,
or solutions containing 5% acyclovir, foscarnet 20 %, 1%
penciclovir, idoxuridine 0.8 %
sprinkling with the zinc sulfate solutions, crystal violet1 %, 2%
eosin
Varicella zoster virus (shingles)
Etiology: It is a dermal neurovirosis caused by Varicella -zoster virus (VZV).

Varicella follows initial exposure to the virus, and after healing, the virus settles
itself in sensory nerve ganglia. Zoster results from reactivation of a latent virus
cumulated with a decrease of the hosts specific immunity.
Similarly to the recurrent herpes, varicella is facilitated by low
immunity.
Viral replication triggers an inflammatory reaction, with the infection of
sensory nerve fibers and lesions pertaining to the dermatomal area.
Consequently, ganglia necrosis phenomena may occur, which may cause
important neuralgia. The incidence increases with age and it is uncommon in
children. Factors such as trauma, neuro-surgical intervention, administration of
chemotherapy, metabolic disorders, are considered to favour or trigger shingles.
Clinical features: it is characterized by an erythematous-vesicular rash,
arranged in clusters, of unilateral metameric layout, accompanied by neuralgic
pain.
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The emergence of lesions follows a painful prodromal syndrome,

sometimes a severe one (fever, headache, asthenia), having the same
distribution as the following eruption.
The rash occurs after 1-4 days after the onset of pain. It has a band-like
distribution, along the midline and includes 1-2 neighboring dermatomes. The
vesicles turn into pustules, they dry after a few days and cover with crusts that
exfoliate, leaving residual, achromic or pigmented lesions. Regional lymph
nodes are enlarged and painful. During the progression of the disease, neuralgic
pain persists or exacerbates and they resolve along with yielding of the lesions.
The associated neurological syndrome (neuralgia) may not be present in
children, and it is often intense in elderly people and may persist long after the
healing of the lesions. The average duration of the eruption is 2-3 weeks.
The most common topographical clinical forms are:
- spinal region (intercostal, cervico-brachial, sacral, lombo-
abdominal regions )
- cephalic regions (ophthalmic, otic, oral-pharyngeal)
Depending on the clinical appearance, the following types of zoster are
described:
erythematous shingles- in which the vesicular eruption is absent
or insignificant
hemorrhagic shingles -characterized by vesicles with a
hemorrhagic content; it usually occurs in the elderly
necrotic shingles- in which the lesions appear necrotic, are
covered with brown crusts, have a slight tendency toward
epithelialization and leave scars. It occurs in
immunocompromised subjects, accompanied by visceral cancers
(paraneoplastic manifestation).
The complications associated with shingles include:
post herpetic neuralgia (post zoster pain) is the most common
complication which increases in incidence and severity with age;
secondary bacterial infections;
affections of the motor nerve (cranial clinical forms), such as :
facial paralysis, paresis of ocular muscles, monoplegias.
affections of the eyes (uveitis, keratitis, conjunctivitis, scleritis,
occlusion of retinal vessels, proptosis, ulcerations);
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rash generalization (generalized shingles);

bilateral positioning (bilateral shingles);
encephalitis, meningitis, segmental myelitis;
rarely: paroxysmal tachycardia, angina, vomiting, pseudo-
occlusion.
The positive diagnosis:
It is supported by:
the clinical appearance and characteristics of eruption
laboratory tests which should confirm the immune status of the
host, isolate the virus or measure the titer of viral antibodies
The differential diagnosis takes into consideration the cutaneous rash
and its accompanying pain and it is done with:
herpes simplex
herpetiformis Duhring-Brocq dermatitis
acute eczema with linear positioning
chickenpox
streptococcal impetigo
Treatment:
It aims at:
fighting against pain and inflammation
preventing of secondary infections
avoiding complications (postzoster pain)
General treatment:
It is recommended to be administered as early as possible after the
onset, and it includes:
antiviral medication
- acyclovir 2-3g/day
- valacyclovir (Valtrex) capsules 500mg; 3g/day
- brivudine (Helpin) 125mg; 500mg/ day
- rodilemid, 10ml vials, 1vial/ day
On average, the duration of treatment is 7-10 days.
anti-inflammatory drugs
- steroid-prednisone 30mg/day in short periods of time to prevent
post zoster pain.
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- non-steroidal drugs such as phenylbutazone, indomethacin,

diclofenac, administered orally or in the form of suppositories.
analgesics
- buffered aspirin, metanizole, acetaminophen are the most often
used and well tolerated.
antibiotics: used as a cure only in cases of superinfection or severely
immunocompromised patients, as a preventive measure.
adjunctive therapy (group B vitamin therapy, cimetidine, leukocyte
interferon)
CNS depressant medication
- neuroleptics (chlorpromazine, levomepromazine)
- anticonvulsants (carbamazepine)
- tricyclic antidepressants (amitriptyline, doxepin).
Local treatment:
It consists of topical applications:
- creams, ointments or solutions containing antivirals
aciclovir 5% (Zovirax, Euvirox, Avyclor)
foscarnet sodic 20%
moroxydine (Herpestop)
- sprinklings of sulfamidate talcum 20% or water paste
- use of dyes (gentian violet)
- Antibiotics and epithelizants
Regarding post zoster pain, the following are recommended:
subcutaneous infiltration with 2% lidocaine and triamcinolone
intradermal injections with distilled water, tracking the pain
topical application of capsaicin 0.025%
vibromassage
acupuncture
anti-inflammatory radiotherapy
Epstein-Barr virus infection (EBV)

Epstein-Barr virus belongs to herpes virus family, and has been
associated with Burkitt lymphoma, infectious mononucleosis, oral hairy
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leukoplakia in HIV positive patients, lymphomas and lymphoproliferative

diseases.
The virus usually infects B lymphocytes, some epithelial cells and the
common route of infection is kissing. The primary infection is asymptomatic or
includes manifestations such as fever, dysphagia, petechiae at the junction of
the hard palate with the soft palate, gingivitis, lymphadenopathy and sometimes
maculopapular exanthema. Other mucocutaneous manifestations caused by
Epstein-Barr virus include: Gianotti-Crosti syndrome, urticarial lesions, painful
genital ulcers (Lipschutz ulcers).
Cytomegalovirus infection
Primary CMV infection is commonly inapparent or it manifests as a
maculopapular morbilliform erythema and it is predominantly sexually
transmitted. The virus remains in the body without causing symptoms, while
recurrences are favored by a decreased cellular immunity. Possible clinical
manifestations include:
fever, lymphadenopathy, splenomegaly, purple maculopapular
rashes (in infectious mononucleosis)
severe mucosal ulcerations in immunocompromised patients
keratotic lesions in HIV positive patients
thrombocytopenic purpura
Human Herpesvirus 6 infection
Herpes virus 6 is the etiologic agent of roseola infantum (exanthema
subitum). Primary infection occurs in children up to 2 years old, it starts with a
fever, and it manifests clinically as a rose-coloured maculopapular rash,
affecting the trunk, accompanied by latero-cervical and occipital
lymphadenopathy. The rash persists for 1-2 days.
HPV infections
Hyperplastic epidermal viruses (proliferative disorders)
Etiopathogenesis:
They are caused by the viruses belonging to the papilloma group (HPV),
DNA viruses, and include more than 77 genotypes. These genotypes have
predilection for certain sites and have been grouped into three categories:
1. viruses with tropism for genital areas and mucosas (HPV 6, 11, 16,
18,31, 33)
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2. viruses with tropism for non-genital areas (HPV 1, 2, 3, 4, 10, 29,

57)
3. genotypes correlated to epidermodysplasia verruciformis (HPV 5
and 8).
After the primary infection, HPV persists in a latent form subsequently
undergoing reactivation processes.
The action of the virus consists in proliferation of the spinous cells of
the skin and mucosa, causing benign lesions. These papillomatous
proliferations may undergo dysplastic or neoplastic transformations.
HPV infection may cause the following types of lesions:
1. verrucas vulgaris (HPV2)
these are papular, horny, hard and rough, round-oval
protrudings, well circumscribed, having the colour of skin.
they commonly affect the back of the hands, fingers, areas
around the nails and rarely the elbows and knees, scalp
lesions may be isolated but they can be clustered, having a
mosaic-like appearance
they multiply by inoculation on a trauma site, simulating a
Kbner phenomenon
they are asymptomatic except for the subungual types
in 70% of cases they evolve spontaneously toward remission
differential diagnosis: flat warts/verruca plana, fibromas,
tuberculosis verrucosa, epidermodysplasia verruciformis.
2. plantar warts/ verruca plantaris (HPV1, 2,4,57)
are round, circumscribed, with a rough keratotic surface,
surrounded by a yellowish peripheral horny ring
yhey most commonly occur on the plantar pressure areas (heel,
head of the metatarsals)
they are solitary or arranged in plaques (mosaic warts)
they are very painful when pressured, due their deep
development and compression of nerve threads
differential diagnosis: clavi, papulosquamous syphilides,
congenital keratodermas featuring small elements, achromic
malignant melanoma
119
3. juvenile flat warts (HPV3,10)

they are described as papules with a flat, smooth, rounded
surface, of 3 - 4mm diameter, the colour of the normal skin or
yellowish brown coloured
Kbner sign is present and scratching favors self-inoculation
it commonly affects the face, the back of hands and the fingers
of children, teenagers and young women
the differential diagnosis includes: warts, lichen planus, planar
xanthoma, eruptive hidradenoamas.
4. papillomas (filiform or digitate warts) (HPV 2)
exophytic, pedunculated, filiform structures
verrucous nevus
they can take various clinical aspects: horny papillomas,
keratotic digitate papillomas or papilloma of the mouth
located on the sides of the neck, on the cleavage area, eyelids,
armpit (horny papillomas), on the scalp and beard (keratotic
digitate papillomas)
they arent accompanied by subjective symptoms but they are
unaesthetic
differential diagnosis: verrucous nevus, cellular naevi, verruca
vulgaris
5. anogenital verrucas (condyloma acuminatum) (HPV 6,11,16,18)
they are exophytic, pedunculated or "coxcomb"-like lesions,
soft, pink, usually multiple, they appear as cauliflower-like
masses
the sites are numerous: frenum, coronal part of the glans and
glans, the sheath of the penis, vulva, cervix, perianal region
the appearance of condylomas is favored by pregnancy,
immunosuppression and it is associated with other genital
infections
the evolution is chronic, there are great chances for relapses, but
they may also regress spontaneously
pain is present only in case of exuberant growth, when there is
suspicion of carcinomatous transformation
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differential diagnosis: papulo-hypertrophic syphilides,

spinocellular carcinoma
6. Bowenoid papulosis (HPV 16,18,33)
multicentric papular lesions with flat or keratotic pigmented
surface, purple or brown coloured, single or multiple
locate on the vulva and penis in young people
relapses are frequent and they are resistant to treatment
the disease has oncogenic potential (histologically similar to
Bowen's disease)
the differential diagnosis: condyloma acuminatum, condyloma
lata.
7. giant condylomata acuminata of Buschke and Lowenstein (HPV
6,11)
it starts as some common condylomas, expanding fast and taking
a tumor-like appearance
the lesions have keratotic surface, the base of implantation being
rough, infiltrated and may occur on the deep tissues (clinical
aspect of a vegetative spinocellular carcinoma)
the disease develops on hyporesponsive ground, it is recurrent,
resistant to treatment and prone to malignant transformation
the differential diagnosis is done with vegetative spinocellular
carcinoma, massive venereal vegetations
8. oral florid papillomatosis
it is characterized by protruding lesions of vegetative appearance
"in cockscomb", having the surface covered by whitish spots
they are rough, red coloured and develop on a normal or
leukokeratotic oral mucosa
they are characterized by local aggressiveness and oncogenic
potential
the differential diagnosis is done with gingival hypertrophy,
papillomas of the oral cavity, conjunctive benign tumors of the
oral cavity
9. epidermodysplasia verruciformis (HPV 3,5,8)
it is a generalized chronic infection with HPV
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it is an inherited disorder (probably in an autosomal recessive

manner)
it is clinically characterized by two types of lesions: keratotic
papules resembling verruca plana/ ordinary plane warts and
erythematous or hyperpigmented macules, resembling pityriasis
versicolor
there are multiple sites: trunk, face, forearms, dorsal hands
although malignant transformation is common, they have got an
exceptional ability to metastasize
the differential diagnosis is done with other types of verruca
plana, verruca vulgaris, verruca seborrheic, verrucous nevi
10. seborrheic keratoses (senile warts)
their viral etiology is disputed by some authors
they are circumscribed growths with hyperkeratotic surface, of
soft consistency, dark brown coloured
located on the trunk, arms, and seborrheic areas
the differential diagnosis is done with papillomas, nevus cells,
verruca vulgaris
Positive diagnosis:
The characteristic aspect of each clinical manifestation is usually
suggestive and adequate for the confirmation of a diagnosis.
Histopathological findings emphasize the cytopathogenic effect of HPV
whereas virological examinations allow detection of the genotype that needs to
be blamed.
Treatment:
The choice of treatment depends on the clinical form, the size and
location of the lesions. The therapeutic options are:
surgery: curettage, electrocautery, excision, therapy with carbon
dioxide laser, superficial and contact roentgen therapy
local treatment with cytotoxic substances: podophyllin, salicylic
acid, cantharidin, colchicine, 5-fluorouracil, bleomycin
cryotherapy: uses dry ice, liquid nitrogen
general treatment: with retinoids, methionine, Isoprinosine,
levamisole.
specific immunostimulation
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Poxviruses (degenerative and exudative epidermal viruses)

Molluscum contagiosum
Etiology and Epidemiology:
It is exclusively a disease of humans caused by a poxvirus (molluscum
contagiosum virus), with two strains that are clinically identical.
Viruses occur mainly in children and adults with a background of
systemic diseases (sarcoidosis, AIDS). Contamination is interpersonal or
through contaminated objects. The incubation varies from 14 days to 6 months.
Clinical features:
the characteristic lesion is a papule with an umbilicated center,
the colour of skin, painless, with a white grainy content
(moluscum grains, or Patterson corpuscles).
the lesions increase slowly, reaching the size of 5 - 10mm in 6 to
12 weeks.
located on the face, trunk, around the genitals, scalp (in infants).
Positive diagnosis:
is suggested by the clinical distinctive appearance of lesions
and confirmed by histopathological examination, which makes
the Patterson corpuscles visible
Differential diagnosis
It is done with: verruca plana, scabious nodules, lichen planus.
The treatment includes:
curettage of the lesions and their enucleation followed by topical
applications with iodinated alcohol and tetracycline ointment
superficial and central electrocoagulation
applications with podophyllin 20%
use of antibiotics and nonspecific immunomodulator drugs
Ecthyma contagiosum
(Contagious pustular dermatitis or Orf disease)
Etiology:
This is an exudative type of viral skin infection produced by a
parapoxvirus. The source of infection is represented by the goats and sheep
infected with pustular stomatitis. It can be transmitted by direct contact or
through fodder. The incubation period is 3-10 days.
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Clinical features: the lesions are firm purplish papules, which can turn
into vesiculo-bullous pustules or hemorrhagic bullae. After they break open, a
central crust is formed and it is surrounded by a distinctive purple or white
gray ring. The lesions are located on the fingers, hands and forearms, and may
be accompanied by lymphangitis and regional adenopathy.
Positive diagnosis is supported by their clinical appearance and the
epidemiological background.
Differential diagnosis is done with of milkers nodules, verruca
vulgaris.
Treatment
The condition heals spontaneously within 5-6 weeks and confers
sustainable immunity. To avoid a pyococcus superinfection, topical medication
with antibiotics and dermocorticoids may be applied.
Milkers nodules
This is an exudative occupational dermatitis.
Etiology:
The disease is caused by a parapoxvirus (paravaccinia poxvirus). The
source of infection is represented by sick animals and human disease is
contracted through direct contact with cattle affected by paravaccinia.
The incubation period is approximately 5-7 days.
Clinical features: they are firm nodules, brown-purple with an
erythematous margin and a slightly depressed center covered with a crust. The
lesions occur on the fingers, the dorsal part of hands and are accompanied by
lymphangitis and lymphadenopathy.
A positive diagnosis is supported by the distinctive clinical appearance
of the disease, anamnestic and epidemiological data and through microscopic
examination that outlines distinctive inclusion corpuscles within malpighian
cells.
The differential diagnosis is done with pyogenic granulomas, ecthyma
contagiosum, verruca vulgaris.
Treatment
The condition heals spontaneously within 4-6 weeks. Local applications
of dyes and antiseptic solutions such as gentian violet 1% or methylene blue are
recommended.
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Vaccinia
Etiology: poxvirus officinalis
It has the same antigenicity as Poxvirus variolae and it was used in
smallpox vaccination. The infection occured after vaccination and its possible
complications (generalized vaccinia) have disappeared with the eradication of
smallpox.
Other mucocutaneous manifestations caused by viruses
1. Herpangina
2. Hand, foot and mouth disease
3. Epidemic Erythema Infectiosum
Herpangina
Etiology: group A Coxsackie virus.
It usually manifests as short seasonal epidemics, affecting mainly
children up to the age of 3.
Clinical features: characterized by erosive vesiculobullous and
ulcerative lesions on an erythematous enanthema, developed on the palatal
mucosa, the pillars of the tonsils and pharynx. The lesions are accompanied by
fever, headache, vomiting and abdominal pain.
The evolution is favorable, the recovery occurs spontaneously within 5-
6 days, with healing of the lesions and remission of fever.
The positive diagnosis is suggested by the epidemiological features of
the disease, its clinical appearance and benign evolution.
Herpangina must be differentiated from aphthous stomatitis, herpetic
stomatitis and hand, foot and mouth disease.
The treatment consists of anti-pyretic drug administration and adequate
oral hygiene.
Hand-foot-and-mouth disease
Etiology Coxsackie A16, ECHO or enteroviruses.
The disease affects mostly children, it is contagious and the outbreaks
usually occur in the summer.
Clinical features: the eruption is characterized by painful lesions of
vesiculo-erosive stomatitis, affecting the oral mucosa, the palate, gums and
tongue, which hinders the nourishment.
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On the hands and feet the vesicles are elongated, surrounded by an

erythematous areola, and can be seen on the back sides of the hands and legs,
the cubital margin of the palms and around the nails.
The evolution is benign, the lesions resolve within 7-10 days.
The positive diagnosis is supported by its clinical signs and
epidemiological background.
The differential diagnosis brings up herpangina due to the lesions on the
oral mucosa, and dyshidrotic eczema, tinea dyshidrosiform due to the lesions on
the hands and feet.
Epidemic Erythema Infectiosum

Etiology: The disease is caused by human parvovirus B19.
It is transmitted through the air and the incubation period ranges from 4
to16 days. Small outbreaks occur in spring and autumn and affect mainly
schoolchildren.
Clinical features: maculopapular rash on the face and light pink macular
lesions on the shins.
Sometimes the rash spreads to the trunk, forming large plaques that
extend peripherally, while the central part gives rise to well-defined areas of
livedo. The lesions are exacerbated by heat, stress or UV exposure, and occur in
a relatively good overall status.
Cutaneous syndromes related to viral infections
Gianotti-Crosti syndrome (popular acrodermatitis of childhood)
It was described in 1958 by the Italian authors Gianotti and Crosti.
Etiology:
There is a variety of viral agents to be blamed: hepatitis B virus, Epstein
-Barr virus, Coxsackie A16, B4, B5, ECHO, hepatitis A, parvovirus B19. The
syndrome mainly affects schoolchildren and rarely teenagers or adults.
It is a syndrome characterized by
non-pruritic maculopapular eruption affecting the extremities
axillary and inguinal reactive micropolyadenopathy
mildly altered overall condition
discreete hepatosplenomegaly
The rash lasts for 4-8 weeks and resolves spontaneously, leaving
slightly local scaling, but the hepatomegaly may persist for several months.
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Papular acrodermatitis is a cutaneous symptom of epidemic hepatitis

and it is often considered a sign of this disease.
The positive diagnosis is supported by the morphology and distribution
of the lesions
Cutaneous lesions should be differentiated from: lichen planus,
lichenoid eruptions, the papular form of pityriasis rosea.
The treatment of cutaneous lesions is nonspecific and symptomatic.
Dermatoses presumably of viral etiology

Pityriasis rosea
It is a self-limiting disease that can occur at any age.
Etiology: the involvement of ECHO6 virus, herpetic virus 7, infections
with mycoplasmas and parainfluenza of types I, II and III are discussed.
A possible drug etiology was also suggested, idea supported by the
emergence of pityriasis as a pinkish rash following the administration of
captopril, metronidazole, ketotifen, barbiturates, clonidine.
Clinical features: the onset of the disease is achieved through a single
plaque of 1-5 cm diameter, erythematous, scaly, oval, with well defined
borders, slightly depressed, usually located on the chest, called primary
medallion.
After 4-5 days other erythematous lesions appear, with smooth scales, of
small dimensions (1cm) or plaques resembling the primary medallion, with a
diameter of 1-3cm.
The rash affects the trunk, the base of the neck and the base of the limbs.
The lesions are accompanied by moderate pruritus and the overall state is good.
The buccal mucosa is relatively common affected, the lesions are discreet
(bleeding marks, erythematous bleeding patches, small ulcerations), and may be
overlooked if the examination is superficial.
Clinical forms:
Pityriasis rosea circinata et marginata of Vidal
It is commonly seen in adults, the lesions are few, but arranged in large
patches, clustered in the axillar and inguinal areas. It is related to general
phenomena (headache, fever, arthralgia) and mouth involvement is frequent.
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Pityriasis rosea inverse (it is seen in in children and occurs on the

limbs)
Pityriasis rosea gigantea
Pityriasis rosea vesicular
pustular Pityriasis rosea
Pityriasis rosea urticata
The evolution is favorable, the lesions resolve spontaneously within 4-6
weeks.
The positive diagnosis:
The clinical appearance, anamnesis, onset and evolution of lesions
suggest this diagnosis.
Differential diagnosis includes tinea corporis, pityriasis versicolor,
secondary syphilide, parapsoriasis, guttate psoriasis, lichen planus.
Treatment
The treatment is not usually necessary. UV exposure is beneficial, and
in severe forms, antihistamines and local corticotherapy are indicated.
Regarding vesicular and pustular pityriasis, dapsone is recommended
for short periods.
Kawasaki disease
It is an immune condition characterized by mucocutaneous involvement,
high fever, that commonly affects children under 5 years of age. It is frequently
seen in Japan, and it is rare or even absent in other regions of the world.
Etiology: There are many causative agents (viruses, rickettsiae,
streptococci), and it has been established that the disease is a systemic
vasculitis.
Clinical features: it combines fever, glossitis, conjunctivitis,
lymphadenopathy and maculopapular erythema with progression to
desquamation in large flaps. The most severe complication of the disease is the
heart involvement, responsible for 1% mortality- reported for this disease.
Usually the condition resolves within 8-10 weeks.
Viral dermatoses related to eruptive fevers

Rubella
Etiology:
it is an infectious disease, caused by the rubella virus;
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it usually affects children and confers immunity;

the virus is transmitted directly by droplets from the nasopharynx.
Clinical features:
onset of mild fever, nasal and conjunctival catarrh, headache and
enanthema inside the mouth (red macules and petechiae located on
the soft palate);
on the skin:
pink patches, with a tendency to coalesce, forming a diffuse
erythema;
the lesions are seen on the trunk, limbs and face.
adenopathy associated with rubella is a constant sign of disease
(especially the occipital, retro, submastoidian or laterocervical
regions);
the ganglia are quite dense and sensitive to palpation and may
persist for several weeks.
The complications are rare, but possible:
- anginas;
- bacterial pneumonia;
- rubella-associated arthritis;
- encephalitis.
Evolution and prognosis: the evolution is usually benign, except for congenital
rubella, where there is a risk of fetal abnormality.
- secondary syphilis;
- infections with Coxsackie and Echo;
- drug exanthema.
The treatment is symptomatic (antipyretics, vitamin therapy).
Measles
Viral acute, contagious disease, occurring via the respiratory tract,
caused by measles virus. It is transmitted by droplets from the nasopharynx of
ill people.
Clinical features: onset with fever, conjunctival and respiratory catarrh,
headache.
During its course, the disease is characterized by:
skin lesions:
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- Macular rash and erythematous purplish papules that coalesce

into patches of healthy skin with irregular outline, located on the
face, trunk and limbs;
- the lesions are itchy and fade in about 10 days, leaving brownish
pigmentations followed by fine desquamation;
mucosal lesions:
- the buccal mucous membrane is congested with white
micropapules that spread on the cheek lining and the jugo-
maxillary crease (Kopliks spots);
- saburral tongue;
- bleeding spots of irregular shape located on the soft palate;
Other symptoms: digestive disorders (vomiting, abdominal pain),
nerve disorders, lymphadenopathy and fever up to 400 C
Complications:
- enteritis;
- bronchopneumonia;
- encephalitis.
Evolution and prognosis: the condition evolves spontaneously towards healing,
the prognosis is good and it is influenced by age, complications, nutrition or
morbid associations.
- clinical examination (typical appearance of the lesions);
- cytological examination of nasal secretion (which outlines giant
multinucleated cells);
- serological reactions that allow the identification of specific
antibodies;
- Indirect immunofluorescence (that detects the viral antigen).
- allergic drug eruptions;
- syphilitic Roseola;
- pityriasis rosea Gibert;
- rubella.
Treatment
The following are recommended:
- symptomatic medication (antipyretics, antihistamines);
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- antibiotics (only in case of bacterial complications);

- rest.
Varicella (Chickenpox)
Etiology:
- Varicella Zoster virus;
- the disease is caused by primary infection with varicella zoster virus,
after which the virus remains in a latent state in the nerve cells;
- it is transmitted by direct contact with skin or through airborne
droplets;
- the entrance gate is represented by the nasopharyngeal and
conjunctival mucosa;
- the condition produces long-lasting immunity.
Clinical features:
the classic eruption consists of numerous erythematous papular-
vesicular elements, of different ages, distributed on the skin (face,
trunk, limbs);
while evolving, the content of the vesicles becomes thick, centrally
umbilicated, it covers with a crust and it heals without scarring;
oral mucosa is frequently involved; the lesions are aphtoid, painful
and accompanied by profuse salivation;
malaise.
Evolution and prognosis:
- the evolution is favorable;
- except for some severe clinical forms (hemorrhagic varicella).
Complications
the most common is a superinfection with pioccoci. In that case, the
content of the vesicles becomes purulent, it covers with crusts
whereas healing leaves scars;
other complications (rarely encountered) include:
- encephalitis;
- glomerulonephritis;
- Lyell's syndrome
- thrombocytopenic purpura.
The treatment
- is symptomatic and prophylactic;
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- rest;
- adequate hygiene to prevent further bacterial complications.
CUTANEOUS FUNGAL INFECTIONS
Cutaneous mycoses
The etiology of mycoses:
Mycoses are conditions caused by the fungi. Fungi are eukaryotic
organisms that thrive in an aerobic, moist and neutral pH environment, which
feed themselves by absorption and reproduce by spores.
They have sufficient characteristics that place them apart from plants
and animals, and it is considered that they deserve their own world, called
regnum fungorum. Fungi can be unicellular (yeasts) or multicellular
(dermatophytes).
The talus (fungal head) consists of two structures: a vegetative apparatus
and a reproductive apparatus.
The vegetative apparatus is represented by hyphae, which are tubular
filaments that extract from the external environment the substances needed in
order to develop the talus and reproductive system. The reproduction apparatus
consists of a vegetative apparatus and its reproduction takes place either
asexually (by spores that come directly from the talus) or sexually (through the
development of sexual stages and fertilization).
Basically, from a medical point of view, we distinguish between the
following types of fungi with implications in the mucocutaneous pathology:
1. dermatophytes;
2. yeasts;
3. dimorphic fungi;
4. non-pathogenic fungi (but able to become pathogenic in certain
circumstances) - molds.
Classification of cutaneous mycoses
I. superficial cutaneous mycoses:
a) dermatophytes;
b) candidiasis;
c) pityriasis versicolor
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II. deep subcutaneous mycoses:

a) sporotrichosis;
b) mycetoma.
Dermatophytes are diseases caused by dermatophytes, multicellular
fungi, characterized by:
- increased pathogenicity for humans and animals
- good adaptability to environmental conditions
- affinity for keratin (keratophilic)
Classification of dermatophytes:
a) dermatophytes of the glabrous skin (non-follicular epidermal
mycoses);
b) epidermal follicular mycoses (mycoses related to hair);
c) onychomycoses;
d) otomycoses.
Laboratory diagnosis of cutaneous mycoses:
The clinical diagnosis of mucocutaneous mycoses imposes various
difficulties due to their variable polymorphic clinical presentation, and because
there is the possibility of association with other diseases (infectious or non -
infectious). The clinical features of mycosis are differentiated by taking into
consideration the clinical entities, grouped according to the structures involved,
the difficulties of giving a diagnosis and the manner in which the
epidemiological and laboratory findings are used.
Therefore, the clinical diagnosis of cutaneous mycoses must be
supported and supplemented by laboratory tests.
The laboratory techniques used aim at highlighting and isolating the
fungal agent found in the pathological material collected (scales, hair, nails,
secretion).
In order to have a correct diagnosis, a rigorous succession of various
techniques is required:
Techniques of sampling the pathogenic material
The sampling of the material that will further be examined requires
adequate instruments and needs to be taken from recent injuries, active areas of
the lesion, prior to the application of treatment.
The sampling of hairless skin scales is done by methodical scraping,
using the edges of a glass slide or curette.
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Regarding hair mycoses, the sampling of the hairs is done with a pair of
tweezers, choosing only hairs that have lost their colour, are torn or embedded
in scales. In suppurative forms, sampling is performed at the periphery of the
lesion.
Regarding onychomycoses, the sampling of the material is done with a
lancet in the distal part, from the subungual deposit.
Laboratory examination:
Direct microscopic examination - this examination is done methodically
and in most of the cases it is sufficient to diagnose a mycosis. The examination
is performed between the blade and the slide, on achromic items.
In order to see the filaments or spores of the pathological material
sampled, they are hydrolyzed into dissociated substances. In practice, in order
to see the dissociated material that will be later be examined, 40 % potassium
hydroxide is used to obtain clear images.
On direct microscopic examination of scales, fungal agents in the form
of myceloid filaments of different shapes and lengths can be seen.
On microscopic examination of the hairs, the hyphae are visualized as
arthrospores, while their parasitism could be endothrix, ectohtrix or mixed,
depending on the etiologic agent.
Over the years, various methods of dyeing the extemporaneous
preparations have been suggested, but none of the methods provided the same
clarity as achromous chemicals.
Mycological examination of cultures - this examination is used for the

identification of fungal agent species, isolated from the pathological product.
Thus, it is necessary to carry out inoculations in appropriate culture media. The
most common culture media are the following: Sabourand, Laugeran and
Raulin.
Macrocultures or microcultures can also be obtained, and in order to
give an accurate mycological diagnostic and to identify the species grown, the
following criteria need to be taken into consideration:
the appearance of the macroscopic colony (size, surface, colour,
consistency);
the time needed for the development of the culture (which is variable
from species to species);
134
the microscopic appearance - by examining a fragment of a mature

colony and by identifying the characteristic organs of fructification
(macroconidia, microconidia, nodular organs).
Fungal antibiogram - is used to determine the sensitivity of a fungal
agent to an antifungal product.
Wood's lamp examination - is a rapid method of diagnosis, an useful test
in the epidemiological surveillance of certain communities. If it is properly
carried out and interpreted, it has a high specificity for microspores, pityriasis
versicolor and erythrasma.
This method implies Wood's lamp, which uses ultraviolet light, filtered
through a barium silicate. In this light, the dermatophytes located on hairs or
scales give rise to the phenomenon of fluorescence.
Fluorescence is visible in a dark room, and this is due to the substances released
after hydrolysis of keratin, referred to as pteridine.
The fluorescence test diagnoses a mycosis, appreciates the extent of the
lesions according to the color of the fluorescence and provides guidelines on the
dermatophytic species involved.
A positive examination using Wood's lamp is conclusive, whereas a
negative test is not. It must be supplemented with other diagnostic methods.
Immunological tests
Intradermoreaction - is used to explore cellular immunity using isolated
antigens taken from dermatophytic cultures. Trichophytin is the standard
antigen used, the active principle extracted from zoophilic cultures of
tricophytons, which is common to dermatophytes.
The intradermoreaction regarding this extract is read within 48-72 hours
and it is intensely positive in patients with inflammatory mycoses.
Experimental inoculation on laboratory animals
This method is used to determine the pathogenicity of a species and
refers to the inoculation of antigens on the cutaneous surface of the limbs of
laboratory animals (guinea pigs or white mice). A positive result occurs within
5-7 days.
Histopathological examination
Histopathological examination is rarely used in the diagnosis of
superficial cutaneous mycosis.
135
Parts of the skin are collected and stabilized in 15% formalin while the
sections performed on paraffin are stained by the usual methods (PAS).
Without neglecting the utility of direct examination, the stabilization
and staining of the biopsies support the positive diagnosis in many superficial
mycoses and allow the isolation of some opportunistic fungi.
Ultramicroscopic examination
Using transmission electron microscopy (TEM), and scanning (SEM)
makes it possible to study the structural characteristics of a fungal agent,
elements that are different from one species to another.
Molecular tests
Given the large number of fungal species with a pathogenic potential,
the molecular tests are focusing on a single parameter, namely the detection of a
specific nucleotide sequence known as unique for certain species. Molecular
testing will become even more useful if they could identify the mutations that
turn normal fungal genes into antifungal-resistant genes.
Unfollicular epidermal mycoses (dermatophyte infections of the
glabrous skin)
These are superficial mycoses caused by dermatophytes pertaining to
the following genera: Microsporum, Trichophyton, Epidermophyton.
Depending on their usual habitat, a distinction has to be made between
anthropophilic, zoophilic and geophilic dermatophytes.
They are predominantly confined to the superficial keratin of the
corneum stratum and may present various clinical pictures.
All dermatophytes are generically known as tinea with the additional
Latin term for body sites.
Depending on the location and appearance of the lesions, the following
clinical forms can be distinguished:
1. tinea corporis (herpes circinatus);
2. tinea faciei;
3. tinea cruris (eczema marginatum of Hebra);
4. tinea pedis;
5. tinea manuum.
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Tinea corporis (herpes circinatus)

Etiology:
The most commonly involved dermatophytes are: M. canis,
Tr.mentographytes asteroides, Tr. rubrum, E. floccosum.
Pathogenesis
Dermatophytes may ignore local defensive factors, whereas spreading of
the mycotic infection towards the corneum stratum depends on the interaction
between arthroconidia and corneocytes.
From an ultrastructural point of view, a very close contact between
arthroconidia and corneocytes has been observed, the space between them being
filled with a fibrillar-floccular material. It has been shown that the germination
of arthroconidia and the penetration of the corneal layer of epidermis are
important factors related to the pathogenicity of dermatophytes.
Clinical features:
it is characterized by erythematous-squamous or erythematous
plaques, with a vesicular border, rounded and well defined;
the periphery of the lesions is circinate (ring-shaped), active,
with a tendency towards extension and with an apparently
resolved center;
when injuries are caused by zoophilic dermatophytes, the
ulcerated patch is raised, painful and covered with
papulopustular pustules and crusts. It associates with
lymphangitis and painful regional adenitis, thus the lesion is
called subinflammatory herpes circinatus.
direct mycological examination of the scales reveals the
presence of mycelial filaments of different lengths;
the culture on Saburoud medium identifies the species that
causes the lesion.
eczematides which are erythematous-squamous lesions but they
are not well defined and do not have peripheral vesiculation and
centrifugal evolution;
psoriasis;
nummular eczema;
137
seborrheic dermatitis;
pityriasis rosea.
Treatment:
Topical treatment with antifungal medication is often enough to achieve
healing of the lesions. As therapeutic alternatives the following may be used:
- local sprinkling with iodine alcohol, Castellani solution,
clotrimazole solution;
- application of creams, ointments with Miconazole, Bifonazole,
Tolnaftat, Ketoconazole or Naftifine - Hydrocloride with
complex antifungal, anti-inflammatory and antibacterial effects.
When the lesions are chronic and do not respond to topical treatment, an
oral treatment can be administered, with antifungals such as Ketoconazole or
Fluconazole, Itraconazole or Terbinafine.
Tinea faciei
It is a fungal infection that affects the glabrous skin of the face,
including the eyelids.
Etiology: any of the genera and species of dermatophytes can be
involved.
Clinical features: is a circinate herpes lesion that affects the face.
A certainty diagnosis is given by mycological examination and
anamnesis which often reveal the fact that it was acquired due to animal contact
- polymorphic light eruption;
- lupus erythematosus, discoid;
- rosacea.
Treatment:
- Imidazole derivatives can be used (clotrimazole, bifonazole,
miconazole, ketoconazole) in topical applications as solutions,
ointments or creams. Healing can take place within 3-6 weeks.
Tinea cruris (ringworm of the groin or eczema marginatum Hebra)
It is the mycosis of inguinal creases.
Etiology: anthropophilic and zoophilic dermatophytes such as T.rubrum,
E. floccosum and T. verrucosum are involved.
138
Pathogenesis: the contamination and the extention of the lesions are

favored by an individual predisposition as well as by local factors (sweating,
obesity etc.).
The condition commonly affects men, rarely women and extremely rare
children.
Clinical features:
the appearance is dominated by the presence of a round
erythematous plaque, slightly raised, with active edges covered
with vesicles and scales around the nail folds ;
the polycyclic limit of the patch is slightly raised, occasionally
marked by nodules and pustules, hence the name of eczema
marginatum ;
the lesions expand in time, sometimes overexceeding the usual
area and involving external genitals, buttocks, lumbosacral
region, abdomen etc. ;
itching constantly accompanies the lesions, it requires scratching
and favors cracks.
- mycological examination of scales;
- cultures on Sabouraud medium.
- bacterial intertrigo;
- candidal intertrigo;
- microbial eczema;
- inverse psoriasis.
Treatment:
- general - it uses antifungal drugs such as Ketoconazole,
Itraconazole, Griseofulvin;
- local - creams, ointments and solutions with antimycotic action;
Tinea pedis
It is the dermatomycosis of modern life.
Etiology: it is caused by Tr. rubrum, Tr. Mentographytes interdigitalis,
E. floccosum.
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Pathogenesis: arthroconidia distributed along the corneum stratum must

germinate quickly and penetrate the keratinized surface, otherwise they will be
removed as a result of a continuous peeling of the epithelium. Various
environmental factors can influence the sprouting process, such as the high
humidity that favors the penetration of colonized areas. Thus, it can be said that
an important role in the development of the disease is being held by the factors
(endogenous and exogenous) which enable hyperhidrosis, maceration and
prevent the evaporation of sweat.
Clinical features: three types are described:
1. intertriginous tinea pedis characterized by:
white macerated epidermis, slightly erythematous and fissuring
in the toe clefts;
the lesions are itchy and sometimes painful and they may extend
to the dorsal and plantar region of the foot, during hot seasons.
2. dyshidrotic tinea pedis is characterized by:
erythemato - vesicular lesions, arranged in plaques and patches
with eccentric evolution and polycyclic edges ;
the lesions are sometimes slightly represented by scalings and
fissures ;
sometimes they could become acutely inflamed with large
edema, resulting in the appearance of painful bullous lesions ;
the lesions are usually symmetrically distributed, affecting the
interdigital spaces, the sides or the plantar arch of both feet.
3. dry, scaly tinea pedis (hyperkeratosis):
it is a chronic form of mycosis;
it is clinically characterized by slightly erythematous plaques
covered with hyperkeratotic scales and cracks;
it commonly affects the heel and plantar arch.
Tinea pedis intertriginous differs from:
- intertrigo candidiasis;
- bacterial intertrigo;
- vesiculo-bullous erythrasma.
Dyshidrotic tinea pedis must be differentiated from:
- dyshidrosis microbial eczema;
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- contact dermatitis;
- vesiculo-bullous erythrasma.
Scaly or hyperkeratotic tinea differs from:
- plantar psoriasis;
- plantar keratoderma;
- hyperkeratotic eczema.
- the clinical examination;
- the mycological examination (which highlights the presence of
filaments and spores in the scales and crusts sampled from the
lesions).
Treatment:
1. the topical treatment consists in the application of keratolytics in
combination with antifungal substances (Dubreuilh pomade) or
creams / ointments with antifungal action.
2. oral treatment may be associated with topical treatment in resistant
forms of tinea pedis. Ketoconozole, Itraconazole, Griseofulvin can
be used.
3. a prophylactic treatment is vital to a successful therapy and consists
in:
- Disinfection of the stockings, shoes, toilet articles;
- Removal of predisposing factors (hyperhidrosis,
endocrinological imbalances, associated diseases).
Tinea manuum
It is the superficial mycosis of the hand.
Etiology: Tr. rubrum, E. floccosum, Tri. mentagrophytes interdigitalis.
Pathogenesis: the adhesion and germination of arthroconidia is favored
by partial loss of a portion of healthy tissues, skin maceration and deficient
peripheral circulation.
Clinical features- there are several forms:
a) dried form - with diffuse scaling;
b) exudative form-vesicular;
c) hyperkeratotic form - characterized by cracks and accentuating
flexural creases.
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The positive diagnosis is confirmed by:

clinical examination;
mycological examination (microscopic examination of scales);
culture on appropriate media;
skin biopsy.
- hyperkeratotic palmar eczema;
- contact eczema;
- palmar psoriasis;
- palmar-plantar keratoderma.
Local treatment - antifungal drugs in combination with topical
corticosteroids or keratolytics (in case of hyperkeratosis) are administered.
Pityriasis versicolor
It is a superficial keratomycosis that occurs in the corneum layer of
epidermis.
Etiology: the condition is caused by a lipophilic yeast - Malassezia
furfur.
Pathogenesis: fungi invade stratum corneum and they are found among
keratinocytes as well as inside them. The process of adherence is favored by
maceration and high humidity. Factors such as hypersecretion of the sweat
glands or hyperhidrosis determine the occurrence of lesions, by turning the
fungal agent from a skin saprophyte into a parasite. A hereditary predisposition
to this condition is also taken into consideration.
Clinically there are two forms:
- colored Pityriasis versicolor;
- achromatic Pityriasis versicolor.
On physical examination the following were noticed:
the presence of macules or plaques of varying sizes, well
marginated which tend to coalesce into shaped patches of
pigmentary alteration;
the lesions have different colours ranging from yellow, brown,
fawn or white, they present fine furfuraceous scales, visible after
methodical scratching (fingernail or shaving marks);
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the lesions are located on the trunk, along the cleavage line,
around the genitals but they can extend to the neck, face, upper
or lower limbs.
Laboratory diagnosis: several laboratory tests can be used in order to
establish a diagnosis:
a) Wood's lamp examination - which make the lesions visible due
to yellow-green fluorescence and allows the assessment of their
size;
b) direct mycological examination of the scales - showing many
thin elements, grouped in oval-to-round macules, fragmented,
distributed among round spores, clustered.
Differential diagnosis includes:
- eczematids;
- seborrheic dermatitis;
- herpes circinatus;
- pityriasis rosea.
Treatment: topical treatment is known to work well. Creams, ointments,
antifungal shampoos (Ketoconazole, Travocort, Clotrimazole) may be used. For
patients with extensive involvement or for those with recurrent infections, oral
drugs such as Itraconazole 200mg/day for 5-7 days, Fluconazole 50mg/day for
10 days may be indicated etc.
Follicular mycoses (follicular dermatophytosis)
They are dermatoses that mainly affect the hair. Depending on their
location, the major types include Tinea capitis which usually affects children
and Tinea barbae, seen in adults.
Dermatophyte infections of the scalp (tinea capitis)
Tinea capitis occurs in two different forms:
1. aplastic pilomycoses
microsporosis
trichophytosis
2. inflammatory pilomycoses
inflammatory trichophytosis
favus.
Microsporosis
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It is a contagious aplastic pilomycosis, which occurs most frequently in

children aged 5-15 years and has a self-limiting nature (it heals spontaneously
at puberty).
Etiology: The pathogen most commonly involved is Microsporum canis,
but there are also causative agents such as Microsporum species Audouin,
Microsporum ferugineum, Microsporum gypseum. The reservoir of parasites is
represented by infected children or pets (dogs, cats).
Pathogenesis: Microsporum initially invades the stratum corneum of the
epidermis and hence the hair follicle, penetrating the hair along its cuticle.
Inside the hair shaft there are numerous mycelia filaments slightly divided,
which explains their fragility. Outwards, the hairs are wrapped in a circle of
small arthrospores arranged as in a mosaic. Due to intense parasitic invasion,
the hair breaks off at 1-3 mm from its follicle.
Clinical features:
the lesions form large erythematous plaques (2-10 cm), round or
oval -shaped, well defined, located on the scalp. Their surface is
covered in branny powdery scales.
the hairs on the scalp break off at just 1-3 mm from the follicle,
they are straight, dull and firm (coarse hairs). The matted
appearance of the hairs is due to the spores surrounding the shaft
as a sleeve.
1. Wood's lamp examination shows green fluorescence of the
parasitized hairs;
2. direct examination of hairs highlights small spores arranged in a
mosaic pattern, on the exterior of the hair shaft. This parasitic
mode of infestation is called ectothrix.
3. Sabourauds culture reveals the Microsporum species involved.
- trichophytosis;
- tinea favosa;
- scalp psoriasis;
- common pityriasis of the scalp.
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Trichophytosis of the scalp

It is a dry but less contagious infection, with a chronic course. It
frequently occurs in childhood but more frequently is seen in adulthood, as a
chronic form.
Etiology: the dermatophytes involved are T. tonsurans, violaceum and
quinckeanum.
Pathogenesis: T. tonsurans and T. violaceum produce an endothrix
infection, with artrospores and the micelles inside the hair shaft, and hence its
high fragility that makes the hair break off above the surface.
Clinical features: the lesions are located on the scalp in the form of
small plaques, in a large number, with a slightly circular and irregular shape.
The plaques are covered with less adherent, furfuraceous scales. In this form, its
aplastic character is less obvious. The hairs are broken off at uneven distances,
some at the base, and others at 1-3 mm from the follicle.
The tonicity hairs is highly reduced, they are twisted and embedded in
scales, resembling some letters (S, V, Z).
Laboratory diagnosis: Microscopic examination of the hairs shows an
endothrix mode of infestation, the appearance is that of a bag filled with nuts.
Evolution: without treatment, dry scalp trichophytosis has a chronic
evolution and it heals at puberty. In some cases the disease continues to evolve
even after puberty, turning into the chronic trichophytosis of the adult.
scalp microsporosis;
tinea favosa;
scalp psoriasis;
pseudopelade.
Chronic Trichophytosis of the adult
It associates scalp lesions with lesions of glabrous skin. On the scalp,
the clinical elements of diagnosis are:
- infected hairs, broken from the base or
- small plaques with atrophic scarring.
On glabrous skin, the lesions are erythematous-violaceous macules,
arranged in plaques and patches, affecting the lateral and dorsal side of the legs,
buttocks or forearms.
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The expansion of mycosis implies the existence of a hyporesponsive site

with functional, endocrine disorders or hypovitaminosis.
The choice treatment consists in the oral administration of antifungal
medication for 4-6 weeks, the same therapeutic alternatives may be used as in
microsporosis.
Inflammatory Trichophytosis
It is defined as an inflammatory mycosis limited to the scalp in children
and to the beard and mustache in adults.
Etiology: Zoophilic species are involved (Tr. verrucosum, Tr
mentagrophytes), while the source of infection is represented by horses, cattle,
dogs and cats.
Epidemiology:
This condition occurs more frequently in rural areas. It is estimated that
the condition is more contagoius in the family, when sharing toiletries (however
without becoming as epidemic as microsporosis).
Clinical features:
From a clinical point of view, it is characterized by inflammatory
plaques of a pseudotumorous appearance, painful, round, well- delimited,
known as Kerion celsi.
Their surface is covered with multiple follicular pustules. The hairs on
the plaque could be easily shaved or they find themselves in an agglutinated
squamous crusty mass. When it manifests, drops of pus from the deep-seated
collection can be seen.
The lesions are often accompanied by painful lymphadenopathy.
In the course of evolution, hypersensitivity lesions may appear after a
while- tricophitydes - with different clinical aspects (lichen trichophytic,
erythema nodosum, etc).
In the beard and mustache, the lesions may have the same appearance as
the ones on the scalp of the children (kerion Celsi) or they may be scattered and
isolated (trichophytic sycosis). The disease tends to heal spontaneously.
Healing of the lesions is achieved with permanent cicatricial alopecia.
Direct examination of the hairs shows an endoectothrix infestation.
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- boil;
- carbuncle;
- sebaceous cyst;
- epidermoid carcinoma ;
- staphylococcal Sycosis;
- bacterial folliculitis of the beard
The treatment implies several stages:
1. topical treatment consists of:
- removing of the hair from the inflammatory plaque and 0.5 cm
additionally as a safety zone ;
- local compressions with Lugol solution until the deep purulent
collection resolves;
- application of the antimycotics in the form of solutions, creams
or ointments.
2. general treatment involves the administration of:
- antifungals (ketoconazole, itraconazole) for 10 -12 days;
- antibiotics (amoxicillin, oxacillin);
- anti-inflammatory medications(low-dose prednisone and short
treatment periods).
3. prophylactic treatment aims at:
- treating correctly the sick;
- sterilizing the toiletries;
- treating the sick animals.
Favus (tinea favosa)

-chronic inflammatory hair infection.
Epidemiology:
- it is less contagious;
- it is favored by poor hygiene, malnutrition;
- familial cases have been reported.
Etiology:
Anthropophilic dermatophyte Tr. schoenleinii or zoophilic agents such
as T. quinckeanum.
Clinical features- three forms are described:
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1. favus scutularis;
2. favus psoriasiformis (squamous);
3. favus impetigoides (crust-like).
Favus scutularis
It is characterized by inflammatory lesions with centrifugal evolution. It
is characterized by cup-shaped depressions developed on the thick horny layer,
consisting of dermatophytic colonies and yellow debris (similar to sulphur).
The lesions smell as unpleasantly as a mouses urine.
Although fragile, the hairs can keep their normal length, but they are
lacking luster (gray mat shade) and are compared with pig bristles (coarse
hairs).
The infection may affect the entire skin of the scalp, except the
peripheral hairy region. This area is not affected probably because it remains
uncovered or because of a natural immunity.
Favus psoriasiformis
It is characterized by scaly plaques on the scalp, which covers an
erythematous skin. The hairs are dull (without brightness) and fragile - typical
favic hair.
Favus impetigoides
It is characterized by yellowish brown squamous plaques, which are
sticky and dry, mimicking a ringworm. The hairs have a typical appearance.
Favus has no tendency to clear spontaneously at puberty and the three
clinical forms may lead to permanent cicatricial alopecia - some authors
described a fourth form of cicatricial favus.
direct microscopic examination of hairs shows a distinctive
endothrix infection, with mycelial tubes of different sizes,
unevenly segmented, forming rectangular arthrospores similar to
tarsus bones " favic tarsus "
Sabouraud culture medium helps visualize the fungal elements.
- other diseases that cause alopecia, associated with inflammatory
phenomena;
148
- impetigo;
- discoid lupus erythematosus;
- lichen planus.
General treatment is essential. It is recommended the use of oral
antifungals such as Ketoconazole, Itraconazole, Terbinafine for 4 weeks.
Onychomycoses (tinea unghium)

Etiology:
Onychomycosis are caused by Trichophyton dermatophytes: rubrum,
violaceum and interdigital mentagrophytes.
The lesions are produced by:
contact (scratching a mycotic outbreak);
indirect contact through toiletries (manicure kit) or soil.
Clinical features:
initially it begins at the distal or lateral edge of the nail ;
the onset lesion is a small triangular yellowish-white, matt,
spreading gradually;
the nail plate thickens, becomes dull and brittle;
a subungual layered deposit lifts the nail from the nail bed.
Clinical forms:
1. distal subungual onychomycosis ;
2. white superficial onychomycosis, characterized by white patches
on the nail plate;
3. proximal onychomycosis (a rare form, the onset is in the
proximal nail and occurs due to the expansion of a mycosis of
the glabrous skin towards the nail bed).
- direct mycological examination of the nail fragment in which the
mycelium filaments are visible;
- culture on Sabouraud medium.
Differential diagnosis includes other nail dystrophies such as:
- psoriasis;
- lichen planus;
- onyxis candidiasis.
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The treatment of onychomycosis is quite difficult and takes about 6

months for the fingernails to heal and 1 year for the toes.
Alternative treatment:
1. general treatment the following are recommended:
- itraconazole - pulse therapy (200 mg x 2/day, 7 days / month, 3
courses);
- ketoconazole - 200mg/day 4-6 months for fingernails and 8-18
months for the toes);
- fluconazole 150 mg / week, 6-8 months.
2. the topical treatment is associated with the general treatment to
increase its efficiency. The following may be used:
- amorolfine or ciclopiroxolamine nail polish;
- 50-60 % urea occlusive dressings that produce a chemical
avulsion of the nail.
Otomycoses
Etiology:
Infections of the external auditory canal, caused by dermatophytes, in
combination with molds and opportunistic fungi (Aspergillus Penicilium
migratum).
Clinical features:
They are characterized by scaling erythema, cracks and intense pruritus,
having an eczema-like appearance.
Positive diagnosis is supported by mycological examination that
highlights causative fungal agents.
Differential diagnosis includes external otitis, contact dermatites,
exogenous eczemas.
The treatment an antifungal local treatment is generally preferred, in
combination with antibacterial medication (naftifine, ciclopirox olamine).
Mucocutaneous candidiases
Etiology:
they are infections caused by yeasts of the genus Candida, albicans
species
150
yeasts are unicellular fungi that multiply by budding, forming

blastospores
Candida albicans is the main pathogen, but there are other species that
can cause infections: Candida tropicalis, krusei, glabrata
Candida albicans is a commensal of the mouth, gastrointestinal tract and
vagina, but it is not part of the normal resident skin flora
Pathogenesis:
infection with Candida albicans yeast starts by adhesion of the
commensal yeast to mucosal cells or to a keratinocyte
multiplication occurs after the adhesion and then the hyphae can
penetrate the tissue
the transition from a commensal to a parasitic stage takes place due to
predisposing factors such as :
- states of immunosuppression (AIDS, leukemia, lymphoma)
- use of antibiotics
- pregnancy, extreme ages
- endocrine diseases (diabetes, Cushing's syndrome, Addison's
disease)
or local factors as:
- decrease of the salivary flow
- pH changes
- tissue injuries
- high humidity
- skin maceration
Classification of mucocutaneous candidiasis
I. oral candidiasis
II. genital candidiasis
III. cutaneous candidiasis
IV. systemic candidiasis (pulmonary, gastrointestinal, urogenital)
I. Oral candidiasis:
a. acute pseudomembranous candidiasis (thrush)
erythematous plaques, edema, erosion and creamy deposits which
cannot be easily wiped away;
151
in the mouth it has the form of separate grains which can coalesce
and form pseudomembrane ;
it is associated with symptoms such as burning and pain.
b. acute atrophic (erythematous) candidiasis is characterized by:
depapillated area, leaving a smooth area on the tongue;
it occurs after antibiotic therapy;
clinical features: acute erythema on the mucosa, atrophic
appearance, areas of edema and secondary papilloma;
c. chronic atrophic candidiasis (denture-related stomatitis)
encountered mostly in denture wearers;
lesions are located on the palate;
little or no subjective symptoms.
d. chronic hyperplastic candidiasis (candidal leukoplakia)
white, slightly infiltrated patches on the mouth ;
differential diagnosis includes other leukoplakia (leukoplakia caused
by tobacco).
e. median rhomboid glossitis (candida is not the causative agent all the
time)
it is characterized clinically by a depapillated area on the dorsal side
of the tongue, having a rhomboid shape, located just anterior of the
circumvallate papillae, having a smooth or slightly raised surface;
the lesion is asymptomatic and has a self-limiting character.
f. black hairy tongue (candida is not the causative agent all the time)
it is characterized by hypertrophy of the lingual papillae which
become elongated as the hairs
keratinization on the tip of filiform papillae and oxidation by direct
contact with air causes mouth pigmentation
g. angular Stomatitis (perlche) lesions affect the angles of the mouth
Clinical features:
maceration of commissural submucosa
on the bottom of the fold there is fissure covered with crusts
the disease could be confused with streptococcal and
secondary syphilis lesions
h. angular cheilitis - inflammation of the lip caused by Candida
152
Clinical features:
erythema, swelling and erosion in the mucosal and submucosal areas
of the lips and sometimes white creamy deposits
Differential diagnosis of oral candidiasis includes:
a. for oral and lingual sites:
oral leukoplakia
mucous plaques of syphilis
leukoplakia caused by Epstein - Barr virus
oral lichen planus
b. for labial and commissural sites:
systemic lupus erythematosus
streptococcal perlche
leukoplakia cheilitis
papular erosive syphilide
actinic cheilitis
II. Candidiasis of the genital mucosa
a. vulvovaginal candidiasis this disease occurs frequently in sexually
active or pregnant women
Clinical features:
the vaginal mucosa is congested, edematous, with erosions and
creamy white deposits
thick, white, curdlike vaginal discharge
pruritus
there is also a special appearance with reduced secretion,
mucosal atrophy and reduced deposits
the lesions may extend to the vulva, resulting in erythema,
edema, erosion and deposits; they may extend to the fold
between the buttocks
chronic, relapsing development
Differential diagnosis of vulvovaginal candidiasis
bacterial vulvovaginatis
physiological leucorrhea
trichomoniasis
vulvar contact dermatitis
b. Candidal Balanitis or balanoposthitis
153
Clinical features:
erythematous, edematous mucosas, accompanied by small
pustules on the glans or foreskin, with erosion and creamy white
deposits
lesions extending to the folds erythemato-squamous
appearance
differential diagnosis:
- balanitis
- herpes simplex
- lichen planus
- erythroplasia
c. Inflammation of anal mucosa - perianal candidiasis
III. Cutaneous candidiasis
a. Candidal intertrigo is an inflammation of the folds caused by
Candida
clinical features: erythema, edema, having plaques with pustules
at the periphery, that either open and form erosions or they dry
and detach themselves, leaving a desquamation collar
skin is macerated at the bottom of the fold
it often occurs in the interdigital folds of the hand,
inframammary fold in women and rarely in the inguinal fold
Differential Diagnosis
epidermophytosis involving the folds
eczema involving the folds
erythrisma
Streptococcal intertrigo
b. Candidal perionyxis (paronychia)- inflammation of the tissue in the
periungual caused by Candida
Clinical features: edema and erythema, scaling cuticle. When
pressed, a small amount of creamy yellowish-white pus appears
from beneath the nail.
staphylococcal perionyxis
periungual psoriasis
154
c. Candidal Onyxis- the nail is attached to the base or to the side and
follows a perionyxis; nail slide shows changes in colour, striations, it
is friable, undergoing an onycholysis process
staphylococcal onyxis
dermatophytic onychomycosis
onychomycosis trigerred by general disorders
d. Candida folliculitis is characterized by pustules in the follicular
ostium, surrounded by discreet erythema
e. Otitis externa - inflammation of the outer ear canal
Clinical features:
Erythema and edema
desquamation, pruritus
IV. Chronic mucocutaneous candidiasis
it usually manifests in the first years of life
it is resistant to treatment
it affects the mucous membranes, skin and nails
Congenital chronic mucocutaneous candidiasis
it begins in the first days of life
it associates oral, ungual and severe skin lesions (autosomal
recessive form)
Diffuse chronic mucocutaneous candidiasis (granulomatous
candidiasis)
it is a chronic form of disease
it occurs in children
it affects the skin (face, scalp, glabrous skin)
the lesions are granulomatous-hyperkeratotic and papillomatous
it associates with severe immunosuppression
Mucocutaneous candidiasis with endocrinopathy
it begins in childhood
it is associated with hyperparathyroidism, ovarian insufficiency,
thymoma
155
Laboratory diagnosis
direct microscopic examination of pathological products
(secretions or nail fragments) highlights Candida filaments and
estimates the amount of fungal elements on the mucosas
Sabouraud agar culture identifies the species: Candida albicans
frequently present
serology tests are recommended for disseminated candidiasis
and they determine Ac specific, by highlighting flowing Ag
Treatment
Therapeutic principles:
in order to get good results in chronic forms, the treatment should be
aimed at:
- changing the favorable conditions (pH change, oral and
cutaneous hygiene and improvement of the immunosuppressed
factors)
- administration of effective antifungal medication
Treatment of oral candidiasis:
As a general treatment the following are recommended:
- antibiotics (polyenes, nystatin, natamycin)
- imidazoles (ketoconazole)
- triazoles (fluconazole, itraconazole)
Topical treatment: the administration of oral suspensions or gels
containing nystatin and amphotericin B.
Treatment of genital candidiasis: vaginal suppositories or tablets in
combination with antifungal medication administered orally (eg, fluconazole
150mg / in a single dose or itraconazole 600 mg / in a single dose).
Treatment of candidal balanitis consists in the administration of local
antifungals (nystatin, natamycin) in combination, or not necessarily, with oral
antifungal in a single dose.
Treatment of cutaneous candidiasis:
- azoles or polyenes in creams or ointments
- elimination of favorable conditions by applying compresses or
baths with antiseptic solutions
156
Treatment of Paronychia and onyxis Candidiasis

- antifungal medication in combination with corticosteroids,
administered locally and orally.
Mycetoma (Madura Foot)
It is a localized chronic infection, characterized by fistulae and deep
abscesses which results in a granulomatous inflammatory response.
Etiology:
fungi (eumycetoma) and actinomycetes (filamentous bacteria)-
Madurella mycetomatis, Madurella grisea, Actino-madura
madurae, Streptomyces somaliensis-are involved
the disorder has been described in tropical endemic regions
it affects the males that live in rural areas
Predisposing factors
trauma
poor hygiene
immune deficiencies
Clinical features:
- it usually affects the foot and the leg
- the lesions:
present as deep subcutaneous nodules, with a tendency to
coalesce, which break open by ulceration or fistulous sinuses
which discharge a thick pus containing grains of different colors-
pink, yellow, black
are accompanied by pain, functional impotence
spread of infection to deeper tissues causes periostitis,
osteomyelitis, arthritis and severe bone destructions
subjective symptoms (pain, functional impotence) are of minor
importance in comparison with the severity of the lesions.
The evolution has a slow, chronic course, with major deformations of
the affected segments.
other deep mycoses
TB osteoarthritis
staphylococcal osteomyelitis
Kaposis angiosarcoma
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Laboratory Diagnosis
direct microscopic examination reveals mycelial filaments
Sabouraud culture
histological examination
The treatment: is difficult, the chronic lesions are resistant to
antifungals.
systemic treatment
1. antibiotics (when the etiology is bacterial)
- penicillins
- sulfonamides
- tetracycline
- erythromycin
antifungals (when the etiology is fungal)
- itraconazole
- ketoconazole
surgery
- excision of lesion
- leg amputation when there is severe bone damage
Sporotrichosis - is a rare form of deep chronic mycosis.
Etiology The disease is caused by a dimorphic fungus (Sporothricum
schenckii) and is commonly found in temperate and tropical zones. The natural
habitat is represented by soil and plant debris.
Pathogenesis Fungus reaches the skin through a micro traumatism and
forms subcutaneous nodules that could progress along lymphatic channels.
Clinical features
The infection acquired through cutaneous inoculation is clinically
characterized by:
pustules or nodules that slowly progress to ulceration, becoming
chronic
a nodular formation that wears out appears at the site of inoculation ,
known as sporotrichotic canker
the surrounding lymph channels and ganglia are enlarged and
swollen
subsequently, similar nodules appear along the lymphatic channel
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lesions occur on the limbs (foot and leg), they are accompanied by
pain and functional impotence
a particular clinical form is verrucous sporotrichosis, affecting the
dorsal side of hands
Systemic form:
frequently the access path is pulmonary, following an inhalation of
spores, after which it can disseminate through blood ;
the disorder occurs in immunocompromised hosts
Clinical features:
The clinical manifestations are dominated by respiratory symptoms, but
articular or meningeal manifestations are also possible.
Mucocutaneous lesions are characteristic: nodules and ulcerations with a
chronic course.
1. direct examination of purulent secretion reveals mycelial filaments
2. culture on agar media shows colonies with folded surface, that
change their color from white to brown
3. histopathology - PAS staining reveals a mycotic granuloma (the
fungal element surrounded by an asteroid eosinophilic star-shaped
body).
mycetoma
tuberculosis
Kaposis angiosarcoma
Treatment
systemic - the following are indicated:
- systemic antifungals: itraconazole 200 mg / day, for 30 days;
Ketoconazole 200 mg / day for 1-2 months; amphotericin B,
terbinafine
- potassium iodide 30 droplets / day up to 1 ml / day,
depending on the patients tolerance
surgery: it is a rare alternative, that consists in the excision of the
nodules and in extreme situations - leg amputation.
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PARASITICAL DERMATOSES
SCABIES
Etiology: It is caused by Sarcoptes scabiae, variation hominis, belonging to the

arthropod class Arachnida, subclass Acari family Sarcoptidae.
Mode of transmission:
direct contact;
sexual contact;
through toiletries;
from animals.
Predisposing factors:
not being diagnosed in time;
incorrect treatment (use of corticosteroids );
disregarding measures of clothing disinfection;
highly contagious outbreaks, institutional buildings (nurseries,
schools, kindergartens). The incubation period ranges from 1 to 3
weeks.
Clinical features- diagnostic characteristics include:
a) specific injuries
- burrow
the most characteristic lesion, but is rarely seen in adults;
it presents as a linear sinuous lesion (filiform), ranging from
1-2 mm long, created by the female mite that carries eggs;
the preferred sites of infestation are the folds between the
fingers, palms and plantar regions.
- pearl-like vesicle- is a translucent bump, with or clear or
purulent liquid, which marks the end of the mite burrow.
b) nonspecific lesions:
- prurigo lesions
they are papular-vesicular lesions of varying sizes located on
an erythematous base;
their characteristic sites include the lower part of the
abdomen and navel, buttocks, thighs, elbows, knees, the top
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of the wrists, anterior wall of the axillae, genitalia,

perigenital region;
children may develop lesions that are common on the hands,
plantar regions, face and scalp.
- other nonspecific lesions include urticarial lesions, vesiculo-
bullous or scratching lesions.
Subjective manifestations:
itching is the main symptom, it is intense and it is characteristically
more severe at night;
are triggered by a hypersensitivity reaction to parasites, while the
nocturnal exacerbations are caused by direct irritation caused by
parasites on the move.
Clinical forms:
1. classic scabies (characterized by itchy specific lesions);
2. scabies incognito (undiagnosed form, treated with topical
corticosteroids);
3. clean mans scabies (it occurs in people with good hygiene, the skin
injuries are discreet but the itching is intense);
4. nodular scabies:
- characterized by pruritic persistent nodules, sometimes covered
with hematic crusts as a result of scratching;
- scabies nodules are produced by a granulomatous reaction to
arthropod fragments, and occurs in individuals with
hypersensitivity to parasitic antigens;
- this form hardly responds to treatment and the injuries can
persist for months;
- sites: the nodules are common seen on the buttocks, genitals,
thighs.
5. crusted scabies (Norwegian crusted scabies):
- it is a rare clinical form, it occurs in immunocompromised
people;
- clinically, it is characterized by squamous, scaly, thick lesions,
highly infested by parasites;
- sites: mostly seen on the scalp, palms, but the injuries may affect
other large skin areas;
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- the itching is moderate, but a generalized lymphadenopathy sets

in.
6. animal Scabies:
- source of infection: pets (cats, dogs, pigs)
- contamination: takes places by direct contact;
- most of the lesions are erythematous papular, and rarely papular-
vesicular and itchy;
- sites: commonly found on the uncovered parts of the hands,
arms, forearms.
7. scabies contracted from cereals: the lesions are papular-vesicular or
urticarial, having the appearance of a contact dermatitis on the
exposed areas.
Positive diagnosis is made on the following clinical criteria:
presence of nonspecific lesions;
the fact that the lesions (specific and nonspecific) prefer certain
areas;
itching with nocturnal exacerbation;
suggestive epidemiological context;
therapeutic trial.
Laboratory diagnosis: parasitological examination reveals the parasites or their
eggs.
Complications:
impetiginization (bacterial infection of the lesions);
eczematization;
lichenification (in chronic forms, as a result of prolonged
scratching).
Treatment: aims at destroying the mites on the skin, and disinfecting the linen
and clothing. The choice of treatment against scabies depends on the following
criteria:
age;
clinical form;
extent of the lesions;
presence / absence of complications.
The most common scabicidal substances include:
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- Lindane 1% (Lindanest) is used for the treatment of scabies in

adults ;
- precipitated sulfur 10% ointment for adults, and 3% for children,
or colloidal sulfur 8% ;
- Benzyl benzoate 25 % for adults and 12% for children;
- Permethrin 5% - effective in single applications ;
- Crotamiton 10% (for the treatment of scabies in children).
Distinctive Features:
The treatment of post scabies syndrome (characterized by persistent
nonspecific extended lesions and erythroderma) requires associations of
scabicidal substances with mixtures or ointments that have inflammatory and
antipruritic properties.
In nodular scabies, old and extended forms, local applications of topical
corticosteroids, dry ice or liquid nitrogen are recommended, or a short treatment
course (2 weeks) with 30 mg prednisone / day.
Regarding scabies contracted from animals or cereals: if the eruptions
are extensive, antihistamine and topical or systemic corticosteroids may be
administered in moderate doses.
PEDICULOSIS
It is a parasitic dermatosis caused by hematophagous parasites known as

lice.
Etiology: two species are capable of producing skin lesions in humans:
1. Pediculus humanus, with two subspecies, capitis and corporis.
2. Phthiriasis pubis (crab lice).
Pediculus humanus capitis - is responsible for pediculosis of the scalp.
Etiopathogenesis
The female is 3-4 mm long, lives for 40 days and lays 10 12 eggs / day.
The eggs are attached to the hair shaft, are gray and white and are called nits.
The disease is more common in children than in adults, causing outbreaks in the
community. Contamination takes place by direct contact or fomites and
clothing.
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Clinical features:
intense itching is the major clinical sign of disease in louse infested
areas.
Pruritus leads to prolonged scratching that results in excoriations
(ringworm crust) with tangling of the hair;
in old forms of the disease or when the lesions are intensely infested,
retromastoidian or laterocervical adenopathy may set in.
the nits are on the hairs, located a few mm from the emergence of the
hair (gray-white elongated formations), highly adherent.
Sites: the occipital region is the most common site for Pediculus capitis, but the
lesions may extend and the scalp is fully affected.
Treatment:
1. local hygiene (washing with soap and water and application of a 15-
20% acetic acid solution);
2. Application of substances against parasites:
- 1% lindane (smearing);
- pyrethrins;
- crotamiton;
- malathion 0.5-1 %
- topical antibiotics (for intense impetiginized forms).
The treatment is repeated after 8 10 days.
squamous streptococcal infection of the scalp;
neurodermatitis;
scalp eczema;
seborrheic dermatitis.
Clthing/Body lice(Pediculosis corporis)

are produced by Pediculus humanus corporis (body and clothing
louse);
the parasite clings on clothing and moves on the skin only to feed
itself.
the disease occurs in people with poor hygiene.
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Clinical features:
papular - vesicular lesions that occur from bites, accompanied by
intense itching.
other less characteristic lesions are hives, haemorrhagic lesions,
hematic crusts, linearly distributed scars, along the interscapular -
vertebral region ;
at the same time, a brown pigmentation of the skin also appears, due
to toxins found in the parasites saliva.
Treatment
- Lindane 2-3% of talc, topical sprinklings for 2-3 days.
- Crotamiton lotion 10%;
- Malathion lotion 0.5 %;
- Pipevonyl butoxide 3% in inert carriers;
- Disinfection of linen by sprinkling insecticides, washing, boiling and
ironing.
Differential diagnosis: scabies, chronic prurigo.
Phthiriasis pubic, Phthirus pubis(pubic lice, crab lice)
is produced by Phthiriasis pubis or crab and it affects
predominantly the genital area;
it is 1.5 mm long and has three pairs of feet, provided with strong
claws, with which it clings on the hairs;
they lay their eggs at the root of the hairs, after 7-8 days the nymphs
appear and every other week the adult crabs;
contamination takes place through direct contact (sexually
transmitted) or indirectly, through underwear.
Clinical features:
the specific lesions are small blue spots known as macules cerulea,
secondary to bites;
other possible lesions: papulovesicular lesions, hematic crusts,
excoriations, lichenification;
intense pruritus accompanies the lesions constantly;
the nits can be identified on the hairs as yellowish-gray grains.
Sites: lice can mostly be found in the genital region, but their involvement may
spread to the hair around the anus, thighs, armpits, beard, mustache, eyelashes
and eyebrows.
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Treatment:
- shaving of the hairs;
- lindane 1% spraying;
- yellow mercury precipitate 2% (for eyebrows and eyelashes);
- applications of fluorescein 20 % (instillations on the eyelid);
- linen disinfection.
Treatment should be repeated after 7-10 days. All sexual partners should
be treated.
- vulvar pruritus of other etiologies;
- contact dermatitis;
- inguinal Epidermophytosis
CUTANEOUS LARVA MIGRANS
Etiology:
parasites are nematodes that commonly infest animals: Ankylostoma
caninum, Strongyloides stercoides, A. duodenale;
the parasite normally lives in the intestine of animals, where eggs
pass into the feces;
filiform larvae develop from eggs and penetrate the skin;
the larva migrates along the skin, describing a cutaneous linear
lesion, advancing 1-2cm/day.
Clinical features:
initially a pruritic linear urticarial lesion appears on the skin, located
near the penetration site;
lesions subsequently migrate, creating linear paths and involving
large skin areas;
because of the scratching, secondary bacterial infection and
impetiginisation are common
linear dermographism;
acute urticaria;
centrifugal annular erythema.
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Treatment:
- general: administration of anti-helmintic drugs (thiobendazol 25 mg
/ day for 5 days)
- local - cryotherapy for the active extremity of the linear lesion
(where the larva is).
ALLERGIC DERMATOSES
URTICARIA (HIVES)
Definition
Urticaria refers to a group of allergic or nonallergic manifestations,
clinically characterized by a monomorphic cutaneous rash, erythematous-
edematous, migratory, transient and intensely pruriginous.
Classification
According to their evolution, urticarias may be categorized as acute,
when the eruption resolves within hours or days and occur in less than six
weeks, or chronic, when the eruption persists intermittently for several months /
years.
Regarding their occurrence, urticarias may be allergic - mediated by
immune reactions, especially type I (anaphylactic) and type II (with circulating
immune complexes and activation of the serum complement system) or non-
allergic, in which the mast cell activation is mediated directly by neuropeptides,
drugs, food.
Etiopathogenesis
The triggering or causative factors of allergic rashes are:
food and food additives: eggs (white), cocoa, milk and dairy
products, salami, fish, dyes, preservatives, sweeteners,
antioxidants;
medicines: antibiotics (penicillins, cephalosporins, tetracyclines,
sulfas), salicylates, non-steroidal anti-inflammatory drugs,
angiotensin-converting enzyme inhibitors;
allergens: pollens, molds, house dust, cigar smoke;
insect venom;
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implants: osteosynthetetic materials, metallic dentures, dental

amalgams ;
viral infections (hepatitis B, infections with Coxackie virus,
infectious mononucleosis), bacterial (dental, related to sinuses,
bladder, gallbladder, Helicobacter pylori), fungal (candidiasis);
protozoal infestations (lamblia), helminths, ankilostoma,
strongyloides, echinococcosis;
immune disorders related to collagen (lupus erythematosus,
dermatomyositis), autoimmune thyroiditis;
cancers- lymphomas, visceral neoplasms;
hormonal dysfunctions related to sensitivity to progesterone.
Non -allergic urticaria can be triggered by:
medicines- aspirin, non-steroidal anti-inflammatory drugs,
radiocontrast agents, macromolecular solutions (dextran),
anesthetics, drugs that release histamine such as morphine,
codeine, antibiotics such as polymyxins, ciprofloxacin, rifampin;
food - red wine (releasing histamine), cheese, fish, tomatoes,
avocado (rich in vasoactive substances), egg white ,
strawberries, herring (containing substances liberating
histamine);
food additives - tartrazine;
nonspecific, viral, bacterial infections.
A third of urticarias, especially those with a chronic evolution, occur
due to stress, depression and anxiety and 50 % of chronic urticarias remain
without an identifiable cause (idiopathic urticaria).
The pathophysiological process of allergic urticaria consists of
immunological activation of mast cell that release vasoactive mediators, which
lead to an increase in the dermal permeability of the capillaries and veins and to
edematous lesions.
Besides histamine, PGD2, LTC4, TNF are also involved, the
plasmatic mediators related to urticaria are bradykinin and C ' (serum
complement) while cellular mediators consist of a variety of cytokines with
proinflammatory properties that can enhance and perpetuate the swelling
response and which are released by basophils.
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Clinical features
Urticaria has got very suggestive features: circumscribed lesions that
have a monomorphic appearance, being edematous, erythematous or white
(depending on the importance of superficial dermal edema), migratory (from
one skin area to another), transient (resolving within minutes / hours), intensely
pruriginous (by stimulation of histamine H1 receptors), having different sizes
(either millimetric or forming plaques and patches) and shapes (round, oval,
figurate, ring-shaped).
Skin lesions are sometimes associated with digestive disorders
(vomiting, diarrhea, abdominal pain), arthralgia, dizziness, episodes of
faintness. Anaphylaxis can occur in severe forms, which could be lethal, IgE-
mediated, which associates urticarial eruption with: angioedema, hypotension,
cardiac arrhythmias, lacrimation, nasal obstruction, bronchospasm.
Positive diagnosis
The positive diagnosis is based on the appearance and progressive
features of the lesions. The etiologic diagnosis requires a detailed history of the
data that reveal the onset, duration of individual lesions and rash, associated
systemic signs, possible precipitating factors: heat, cold, pressure, friction, solar
radiation, recent infection, ingestion of food or medication, a family history of
atopy or angioedema and investigations such as:
the titre of specific IgE serum (RAST test) - in patients with
severe clinical forms;
prick - tests with the suspected allergen;
challenge tests involving food additives: during the periods of
remission of chronic food urticaria (eg sodium benzoate);
immunoelectrophoresis, measuring the serum complement.
Urticarial lesions should be differentiated from:
erythematous - edematous erythema multiforme;
dermatitis herpetiformis on its onset;
figurate rash (annular centrifugal erythema).
Treatment
The etiologic treatment aims at avoiding or removing the triggering
etiologic factors (food, medicines).
The pathogenic treatment refers to the administrations of:
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H1 antihistamines (classic antihistamines: hydroxyzine,

chlorpheniramine, cyproheptadine, advanced antihistamines:
cetirizine, loratadine, desloratadine, terfenadine, fexofenadine);
inhibitors of mast cell degranulation: Sodium cromoglycate,
ephedrine, glucocorticoids (in average doses and short courses),
epinephrine.
Specific or nonspecific immunotherapy (desensitizations, hypo-
sensitizations) may be useful.
Particular clinical forms of urticaria
1. Urticaria vasculitis
It presents with persistent edematous lesions (weals) that resolve with
discoloration or bruising, accompanied all the time by migratory arthralgia,
abdominal pain, nausea, vomiting and rarely ocular, pericardial or pleural
involvement.
2. Physical urticaria
Physical urticaria may take various clinical aspects and may be induced
by:
mechanical stimulation of the skin (rubbing, wiping, stroking or
scratching the skin), which causes capillary vasodilation and
edema with erythematous halo known as dermographism (skin
writing) or urticaria factitia;
pressure (wearing tight clothes or shoes, weights held in hands,
prolonged walking); edematous lesions occur accompanied by
itching or a painful sensation;
vibrations (handling the lawnmower); that cause localized
pruritic, erythematous, edematous lesions;
heat (by stimulating sweating due to an increased body
temperature); characterized by small erythematous papules
whose appearance is pathogenically related to acetylcholine
known as cholinergic urticaria;
cold (after exposure to cold, wind, cold rain, or after consuming
cold food or drinks);
water (skin contact with water); lesions that are similar to
cholinergic urticaria, known as aquagenic urticaria.
3. Contact urticaria
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It results from immunological or nonimunological mechanism of

reaction to the contact with irritating substances of vegetable origin (nettles),
secreted by jellyfish, caterpillars, insects that sting or chemicals (acetic acid),
rubber gloves.
ANGIO-OEDEMA (QUINCKES EDEMA)
It is a severe, life-threatening, allergic urticaria characterized by

significant swelling that affects the deeper dermal, subcutaneous or submucosal
tissue; it may accompany urticaria.
Etiopathogenesis
Similar to urticaria, acquired angioedema is also a pluricausal condition.
The hereditary angioedema is due to C1 esterase inhibitor deficiency and starts
in early childhood.
Other forms of ethiopatogenic angioedema include:
angioedema induced by angiotensin- converting enzyme
inhibitors;
angioedema by acquired deficiency of the natural inhibitor of the
first activated component of the complement, which may occur
associated with lymphoma or lupus erythematosus;
angioedema- urticaria - eosinophilia syndrome manifested by
recurrent episodes of angioedema, urticaria, fever, eosinophilia
and leukocytosis and dermal infiltrate with eosinophils.
Clinical Features
Angioedema usually affects the lips, eyelids, ear lobes, possibly limb
extremities and genital region. The clinical appearance is of a diffuse elastic
pale pink swelling, with local burning sensation and pain which installs
suddenly. It represents a medical emergency and requires prompt treatment,
especially when it affects the oral mucosa, tongue, pharynx, larynx causing
hoarseness, shortness of breath or sensation of suffocation and deep anxiety. It
commonly resolves within hours or 2-3 days.
Positive Diagnosis
It is supported by the way it sets in, its clinical appearance and history.
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Angioedema must be differentiated from:
- dermatomyositis;
- erysipelas;
- cellulite;
- acute contact dermatitis.
Treatment
It is similar to the treatment indicated for anaphylaxis:
- oxygen therapy;
- epinephrine (adrenaline) 0.1-1.5 ml sol. 1/1000 should be
administered i.m. / s.c. or inhaled;
- i.v. hydrocortisone hemisuccinate;
- antihistaminic i.m.
ECZEMA
It is an allergic skin disorder clinically manifested as a sequence of

lesions (erythema, edema, vesication, exudative erosions, crusts), accompanied
by itching and characterized histologically by spongiosis with varying degrees
of acanthosis and superficial perivascular lymphohistiocytic infiltrate.
Etiopathogenesis
Eczema is a very common allergic dermatitis, which can occur at any
age, the triggering factors may be environmental (external allergens), they may
reside within the organism or they may be associated with exogenous and
endogenous causes. A number of cases remain without any identifiable cause.
Therefore, from an etiopathogenic point of view, eczemas could be classified as
exogenous (dermatitis eczema), endogenous eczema and mixed eczema.
Exogenous allergens include:
- chemicals - cosmetics, detergents, cement, drugs;
- pathogens - bacteria or fungi found on the damaged skin.
The endogenous factors that may trigger and / or sustain eczematous
lesions are the following:
- products of metabolism and toxins from infectious agents resulting
from chronic sinuses, tonsilitis, dental problems, cholecystitis,
disorders of the urinary tract;
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- food or products resulting from an incomplete digestion in patients

with digestive distress;
- drugs.
There are other factors that may also occur, such as a genetic
predisposition, or local factors such as seborrhea, skin xerosis or hyperhidrosis,
trauma and environmental factors such as dry air, excessive heat, sunlight.
The pathogenic mechanism underlying the occurrence of eczema is
incompletely elucidated especially for the endogenous ones. Types I and II
immune reactions are also involved.
A very distinctive feature of this dermatosis is the tendency to spread far
from its origin, a few days or years after the onset.
Secondary eruption is often preceded by primary lesions that get worse,
it is characterized by erythematous macules, papules, papular vesicles of
symmetrical cutaneous distribution, that evolve progressively, sometimes
towards erythroderma if the primary eczematous outbreak maintains its
inflammatory acute character or resolves at the same time with the remission of
the primitive outbreak.
Classification according to its clinical course and histopathology
Depending on its clinical course, eczemas can be divided into acute,
subacute and chronic, each evolutionary stages having distinctive
histopathological features.
Acute eczema is characterized clinically by erythema, edema, vesication
and significant exudative erythema.
Histologically the epidermal intercellular edema and intraepidermal
vesicles (spongiosis) dominate as well as the increase of epidermal mitotic
activity (acanthosis).
The healing process of an acute eczema starts by drying of the exudative
secretions, the appearance of crusts, followed by scaling scar free erythema
before its complete resolution.
Subacute eczema is characterized clinically by moderate erythema,
discreet edema and squamous crusts. Histologically, there is a reduction of
spongiosis, significant acanthosis, parakeratosis.
Chronic eczema manifests clinically as lichenification: thickening of the
skin, raising of the normal border, scaling and pigmentation. Elongation and
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broadening of the interpapillary ridges (rete ridges) as well as hyperkeratosis

are noticeable histopathologically.
In all the developmental stages, vasodilation is also found in the
papillary dermis as well as the presence of a predominantly lympho -histiocytic
infiltrate, associating PMN and E in the acute stage and becoming dense,
mixed, pseudogranulomatos in the lichenification stage.
Exogenous eczema (eczematous dermatitis)

1. Microbial eczema
It is a dermatitis that results from increased sensitivity to antigens or
bacteria found in skin lesions such as pyoderma, burns or infected wounds,
chronic ulcers of the feet.
From a clinical point of view, microbial eczema is characterized by
plaques or patches with blurry and poorly demarcated borders, erythematous,
edematous, covered with vesicles, postvesiculous erosions, intensely exudative
or with squamous crusts. The lesions are intensely itchy and initially occur in
the proximity of the infectious outbreak.
Microbial dermatitis may complicate even an ectoparasitosis:
pediculosis, scabies.
2. Fungal eczema
Fungal eczema shows significant overlap with bacterial eczema,
appearing primarily around a fungal outbreak, mainly on the limbs: tinea pedis
or manum, interdigital intertrigo caused by yeast.
The clinical manifestations of fungal eczema are similar to those of
microbial eczema, the only distinctive feature being the tendency of
eczematous plaques / patches to a clearer delimitation.
3. Contact dermatitis
This disorder results from cutaneous contact with chemicals that may
irritate or induce sensitivity.
Regarding their etiopathogenesis, contact deermatitis may be
categorized into:
irritant, orthoergic or non-allergic, induced by substances that
can cause damage due to their nature, concentration or prolonged
contact with skin ;
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allergic or contact eczema which occurs after repeated skin

contact with a substance, on predisposed individuals (genetic,
metabolic or endocrinic disorder).
Irritant contact dermatitis may occur along with erythema, edema, bulla
formation or necrosis, or dry lesions (as a result of the cumulative effect of
washing with soaps and detergents in individuals with dry skin), infiltrated and
scaling skin (repeated exposure to sun, dust, sand, mechanical friction), diffuse
erythema with fissuring in the skin folds of obese people (simple intertrigo
caused by excessive local sweating or heat). They are confined to the area of
contact with an irritant substance.
Allergic contact eczema manifests clinically as an eczema that affects a
larger cutaneous area than its afferent sensitized skin. The agent that triggers
sensitivity is an allergen that forms antigenic complexes with the proteins of
the skin. After that, the agent is presented to T-lymphocytes by Langerhans
cells of the skin, then lymphocytic clones with Ag- specific memory appear in
the lymph nodes and are transported via lymphatic and blood circulation and
reach back into the skin.
A new contact with the allergen will cause the onset of eczematous
lesions and possibly their dissemination. Sometimes, the systemical placement
of a sensitizing agent that previously came into contact with skin, can trigger
generalized eczema with complications: fever, lymphadenopathy, digestive
disorders. Such eczemas can be caused by antibiotics, Ni, Cr.
Other possible contact allergens include:
- items of clothing (textile fabrics);
- clothing accessories, jewelry;
- washing powder;
- cement;
- topical drugs (lanolin, Peru balsam);
- plants (chrysanthemums, parsnip);
- cosmetic products.
Endogenous and mixed eczemas

They include clinical manifestations with a primitive disseminated and
symmetrical character, individual factors (digestive, endocrinical, neuro-
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psychical, immunological), with or without exogenous allergens being involved

in their etiopathogenesis.
Atopic dermatitis (constitutional eczema)

It is an endogenous eczema of unknown etiology, with chronic
progression, influenced by a wide array of factors.
Etiopathogenesis- atopic dermatitis is triggered by:
genetic factors (family predisposition to allergic manifestations
mediated by IgE) possibly with dominant autosomal transmission.
immunological factors (hyperproduction of IgE, functional
abnormalities of the lymphocytes, with a decrease in the cytotoxic
activity of natural killer cells and T- lymphocytes, an increased
production of interleukins by helper T lymphocytes).
environmental factors
- various allergens: airborne allergens (house dust, molds,
pollen from different types of grass and trees), tropho-
allergens (eggs, peanuts, milk from cows, mustard, fish, nuts,
soybeans, wheat, shellfish), contact allergens (metals - Ni,
Cr, Co, cosmetics - fragrances, Peru balsam; Topical
Medications - NSAIDs, chlorhexidine, neomycin, sometimes
corticosteroids);
- infectious agents: bacterial (staphylococcus aureus) flora that
colonizes the mucous membranes in the proximity of
eczematous skin lesions), fungal (Pityrosporum ovale,
Trichophyton rubrum), viral (HPV).
- climatic factors : a dry and warm environment or frequent
bathing induce the aggravation of cutaneous xerosis, the
appearance of cracks, increased pruritus and spreading of the
eczematous lesions, however heliotherapy has a beneficial
effect almost all the time;
- psychogenic and neurogenic factors: stress induces an
increasing number of cutaneous neuropeptides (substance P
and CGRP calcitonin gene-related peptide) with altered
thermoregulation and sweating, thus worsening the itching
and eczema from too much scratching.
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The cutaneous lesions are marked by age but they are constantly
accompanied by an incessant pruritus which enables their perpetuation. Thus,
their clinical manifestations are the following:
atopic dermatitis that starts in early infancy, characterized by
inflammatory erosive-exudative or dry lesions, fissuring of the
cheeks, with onset after the third month of life;
juvenile atopic dermatitis, manifested clinically by subacute eczema
affecting the flexural folds (elbows, popliteal, axillary folds), latero -
cervical regions, the back sides of hands and feet;
adult atopic dermatitis characterized by lichenified eczema
especially on the folds, around the orbit of the eye and mouth, the
dorsal side of hands.
The clinical cutaneous manifestations may be accompanied by relapsing
courses of asthma, seasonal rhinitis, kerato - conjunctivitis, kerato - conus,
subcapsular cataract.
Other suggestive signs of atopic skin include:
dry skin;
Derrnie - Morgan sign (extra fold of the lower eyelid);
Hertzoce sign (thinning of the hair on the lateral side of the
eyebrows) ;
follicular hyperkeratosis;
white dermographism (through predisposition to
vasoconstriction due to mechanical factors).
Positive Diagnosis:
According to the British Study Group regarding atopic dermatitis, the
major criterion in establishing a positive diagnosis is itching and the minor
criteria include a history of flexural, latero-cervical, perimalleolar lesions, a
history of one year of xerosis , present eczematous lesions on the folds or on the
cheek of children under 4 years, onset of cutaneous symptoms before the age of
two years.
Atypical cutaneous manifestations of atopic dermatitis include:
forefoot eczema in children between 3 and 14 years;
prurigo with small papular lesions distributed mainly on the
lower parts of the limbs;
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dry pulpitis accompanied by possible ungual dystrophies;

cheilitis sicca - dry, scaly and fissural cheilitis.
Eczema vulgaris
It is characterized by lesions arranged in plaques and patches, vaguely
delineated, located symmetrically on the dorsal side of hands and feet, calves,
forearms, arms, scalp, face, neck, groins, folds and rarely on the trunk. The
appearance of these lesions may be predominantly erythemato-edematous
(especially the facial and genital locations), keratosic and fissural (in palmar-
plantar location) or lichenified if the development is chronic.
Discoid or nummular eczema

It is an eczema characterized by round-to-oval erythematous
plaques(coin-shaped), clearly delineated by a monomorphic appearance, that
occurs especially in adulthood, correlated etiologically and pathogenetically to
local trauma, dry ambiental heat, alcohol abuse, stress or sensitivity to aloe,
golden salts or methyldopa.
These plaques are formed in the acute phase by vesicles grouped on an
erythematous base which subsequently become dry plaques, scaly and
peripherally extended. Episodic reactivation over one or more years is one of
their distinctive evolutionary feature.
The lesions can be seen:
- on the dorsal sides of hands or fingers ;
- on the limbs or most commonly
- on the limbs and trunk.
Papular - vesicular eczema

It is characterized by a papular - vesicular rash on the limbs and neck ,
prone to plaque formation. It is difficult to be distinguished from prurigo.
Seborrheic dermatitis
It is a dermatitis of unknown etiology linked on the one hand to
Malassezia ovale and sometimes to increased sebaceous secretion and a range
of anomalies and system diseases (myocardial ischemia, malabsorption,
obesity, alcohol abuse, ethanolic pancreatitis, Parkinson disease). On the other
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hand, seborrhoeic dermatitis may be a marker of HIV infection. It has an

increased incidence in the first months of life between 18-40 years and is more
common in males.
Clinical features
In children, the lesions are represented by erythematous plaques /
patches, with thick yellowish scales and their distribution follows the oily areas
of the scalp, axillary folds, anogenital region, forehead, cheeks and neck.
In adults, the affected skin areas are the scalp, the face, presternal and
interscapular region and axillary, inguinal, ano-genital, submammary folds, the
umbilical region.
The onset lesions follow the hair-bearing areas and are represented by
scales (dandruff) and perifollicular erythema; as they progress, erythematous
plaques with oily scales appear along the hairline of the scalp, affecting the
retroauricular regions, external auditory canal, eyebrows, the crease behind the
nose, the eyelids. The same kind of figurate-shaped plaques can occur in
presternal and and interscapular region.
If the creases are large, the lesions are accompanied with well defined
erythema, thick scales and eventually cracks.
All clinical forms of seborrheic dermatitis have a relapsing chronic
evolution.
Dyshidrosis (dyshidrotic eczema)

It is a skin condition that affects the palms and soles, which manifests
clinically as an itchy vesication.
The etiology is obscure but it is known that there is a genetic
predisposition, that it occurs frequently in those predisposed to allergies, and
can be triggered / aggravated by primary irritants (soluble oils or contact
allergens). Dyshidrosis may occur as a late secondary reaction induced by the
presence of a fungal outbreak.
Clinical features
The lesions are represented by clear vesicles located deeper in the
thickness of the epidermis that coalesce to form blisters (especially on the soles)
and are accompanied by burning, prickling and itching sensations. Remission is
accompanied by scaling, but it is temporary, relapses occur mainly in warmer
seasons.
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Positive diagnosis of eczema

It is based on the appearance and sites of the lesions, the stage character
of their onset, on anamnesis related to location, occupation. Laboratory
investigations can provide data about possible primitive bacterial or fungal
infections or secondary (smear, culture, antibiogram, mycological examination,
antifungigram); patch tests may be performed on almost all the types of eczema
after the remission of the acute phase. Immunoelectrophoresis, skin biopsy and
immunofluorescence are also useful in the etiological diagnosis of eczema.
Differential diagnosis of eczema:
- eczemas must be differentiated from:
- eczematid;
- herpes circinate;
- Dhring - Brocq disease;
- prurigo;
- scabies;
- neurodermatitis.
Complications of eczema:
- piodermization (bacterial superinfection);
- lichenification;
- Erythroderma.
Treatment of eczema:
It is individualized depending on the etiology, evolutionary stage (acute,
subacute, chronic), sites.
First-line treatment includes the removal of its causative agent (contact
allergen, bacterial or fungal infectious agent). Thus, in bacterial eczema,
antibiotics should be administered (topical and possibly systemic) whereas in
the fungal one- antifungals.
Second-line treatment aims at fighting the inflammation. In acute oozing
forms, wet compresses with mild antiseptic solutions are applied (boric acid
3%), dyes (blue methylene, gentian violet), dermocorticoids as sprays
(Oxycort).
In subacute forms, pasta with hydrocortisone, softening baths, oil,
potent dermocorticoids (elocom, flumethasone pivalate, Advantan, betaderm)
are prefered.
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In lichenified eczema, potent dermocorticoids are associated with

reducers (tars), possibly applications as occlusive dressing of some moderately
potent corticosteroids and keratolytics. Itching diminishes under pathogenic
treatment and under antihistanminics (loratadine, desloratadine, terfenadine,
cetirizine).
Severe extended forms of eczema require systemic corticosteroids
(prednisone) in short courses, a certain dietary compliance, avoidance of
contact with irritants and potentially sensitizing substances.
In atopic dermatitis, besides the topical treatment with moderately
potent and potent dermocorticoids (Locoid, elocom, betaderm) and selective
inhibitors of cytokines (pimecrolimus cream 1% and tacrolimus cream 1%), a
diet of exclusion (for food with allergy potential) and counselling are essential
in order to combat cutaneous xerosis with emollients.
Specific immunotherapy (hypo- and desensitization) can be made where
the allergen is known.
ECZEMATIDS
Etiopathogenesis
Eczematids are allergic dermatoses characterized by itchy erythemato-
squamous lesions, induced by reactions of sensitivity to internal allergens
(microbial food parasites) or from bacterial or fungal skin outbreaks. The
histological features are similar to eczema, but from a clinical point of view, the
lesions do not have a vesicular or an exudative stage.
Clinical features
Depending on lesion morphology, eczematids may have the following
appearances:
pityriasiform : round - oval plaques with ill-defined limits and
covered with branny powdery scales, located on the scalp
(simple pityriasis), on children 's faces, on the extensor sides of
the limbs, the sides of the thorax;
psoriasiform: scaly erythematous plaques covered with thick
scales that desquamate;
acromial: white round plaques with smooth scales (pityriasis
alba) that occur in children with ENT disorders or on atopic
place on the limbs.
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purpuric (purpuric eczematid): purpuric macules and erythemato

-squamous lesions that generally affect the lower limbs of males.
Positive diagnosis
It is based on the clinical appearance of the lesions, and sometimes on
the histopathological examination that highlights parakeratosis, small outbreaks
of epidermal spongiosis and discrete lymphocytic infiltrate in the superficial
dermis.
Eczematids must be differentiated from:
- pityriasis versicolor;
- pityriasis rosea Gibert;
- psoriasis;
- parapsoriasis;
- seborrheic syphilides.
Possible complications include:
- eczematization;
- pyodermization;
- lichenification.
Treatment
The etiologic treatment aims at fighting the infectious outbreak
(bacterial, fungal, parasitic).
The pathogenic treatment aims at fighting pruritus and local
inflammation using antihistamines: dermocorticoids associated with
keratolytics or reducers and antibiotics or antifungals (Diprogenta, Triderm,
Locacorten N.)
NEURODERMATITIS
It is a cutaneous manifestation dominated by marked pruritus and
characterized by a primary lichenification of the skin.
Etiopathogenesis
The disorder occurs in adulthood, especially in females. It affects
persons prone to scratching as a result of any pruritic stimulus. Emotional stress
causes paroxysmal episodes of scratching.
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The lesions are represented by solitary or multiple plaques that occur
more frequently on the nape of neck, the upper inner region of thighs, perineal
region, cubital edge of forearms, the dorsal and lateral side of feet. Initially,
these lesions are erythematous edematous plaques with raised borders and
subsequently their center is covered with scales, with infiltrated and pigmented
skin, whereas lichenoid papules, surrounded by an area of slightly pigmented
skin are formed at the periphery.
Positive diagnosis:
It is more obviously suggested by the clinical features of the lesions than
by the histopathological changes dominated by epidermal hyperplasia. Argentic
impregnation identifies the proliferation of Schwann cells.
The following should be excluded:
- secondary lichenification occurring in atopic dermatitis,
irritant contact dermatitis with chronic progression;
- lichen planus;
- psoriasis.
Treatment
Sedatives, anxiolytics and topical corticosteroids in occlusive dressing
and tars; 5% doxepin cream; solitary lesions should be treated with 10mg/ml
triamcinolone infiltrations.
PRURIGO
Prurigo refers to allergic manifestations clinically characterized by
papular and papular-vesicular lesions caused by scratching, that may develop
acutely or chronically.
Acute Prurigo
a) prurigo simplex acuta infantum or prurigo strophulus
It presents as an eruption of erythemato-edematous lesions surmounted
by intensely itchy vesicles, localized on the limbs and trunk. The lesions
occur in tandem and sometimes they are related to dental eruption,
consumption of a certain type of food and they may resolve
spontaneously, however they have the tendency to relapse. The
condition resolves around the age of 7.
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b) acute prurigo of adults

It is characterized clinically by pruritic papular-vesicular lesions
occurring in several episodes, as a result of consumption of food,
medicines or related to the existence of intestinal dismicrobism,
neuropsychiatric disorders.
Rarely, acute prurigo may occur in the summer months (prurigo
estivalis), with papular - vesicular lesions on the areas exposed to
sunlight or in the winter months (winter prurigo) where the most
common sites are on the limbs.
Pregnant women with atopic diathesis may develop prurigo of
pregnancy during the second trimester of gestation the pregnant resolves
after giving birth only to reoccur for the next pregnancies.
Chronic prurigo
a) Besnier prurigo
It coincides with the chronic manifestations of juvenile atopic dermatitis
with polymorphic lesions: lichenified hyperpigmented patches,
sometimes papular - vesicular and erosive and crusty. It affects the face,
the neck and the large folds. It attenuates after puberty or in adulthood;
b) chronic prurigo of adults
It is a condition characterized by sudden itching, followed by a papular
and papulo-vesicular eruption usually affecting the limbs.
Lichenification may occur as a result of intense itching. The evolution
can be long (it may take years).
Except predisposing biologic factors (digestive, endocrinical, metabolic,
neuropsychic), there are other ethiopatogenic circumstances such as
malignant neoplasms (eg Hodgkin's disease) that have a role in the
occurrence of chronic prurigo.
c) Hyde prurigo nodularis
It is characterized clinically by an eruption consisting in pruritic
nodules, with chronic progression and possibly areas of lichenification.
It is a condition of unknown etiology but 65-80 % of the patients are
atopic. It can occur at all ages but usually between 20-60 years in
equally both sexes.
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The lesions are globular, firm, raised nodules, with keratotic or eroded
surface, covered with hematic crusts and surrounded by a
hyperpigmentated ring. The most common sites are the extensor
surfaces of the limbs. They are accompanied by itching with
exacerbations and may resolve spontaneously leaving scars.
Positive diagnosis:
It is based on the appearance, site of lesions and lesion development. It
requires laboratory investigations and interdisciplinary consultations
regarding the biological factors.
Prurigo must be distinguished from:
- hives,
- papular - vesicular eczema;
- scabies;
- erythema multiforme;
- lichen planus;
- dermatitis herpetiformis;
- chickenpox.
Treatment:
It is adapted according to age, clinical context and severity of rash.
Besides the etiologic treatment antihistamines, sedatives, anxiolytics and topical
antipruritic medication (mixtures or lotions), dermocorticosteroids are also
administered.
Severe cases of chronic prurigo of adults, prurigo nodularis, benefit
from systemic corticosteroids, sulphonotherapy, nonspecific desensitization.
PLURIETIOLOGICAL CUTANEOUS SYNDROMES
ERYTHEMA MULTIFORME
Erythema multiforme is a dermatosis of plurietiological determinism,
commonly relapsing, with mucocutaneous involvement, usually affecting
young adults.
Etiopathogenesis
Erythema multiforme is linked to:
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genetic predisposition (demonstrated by a higher frequency of

HLAB15, HLA - B 35) ;
triggering agents such as:
- viral infections (herpes simplex, hepatitis, infectious
mononucleosis), bacterial infections (streptococcus,
colibacilloses), mycoplasma infections;
- drugs (Biseptol, barbiturates, anticonvulsants, contraceptives,
NSAIDs);
- food;
- tumor antigens (lymphomas, carcinomas);
The disorder can occur during the evolution of a collagenosis such as
lupus erythematosus, a systemic vasculitis such as Wegener granulomatosis but
it may remain in a number of cases, without etiopathogenic context.
Immunopathologically, erythema multiforme is triggered by type III and
IV immune reactions. Direct immunofluorescence shows IgM, C ' deposition
and fibrin around the superficial vessels of the dermis, which is why some
authors categorize erythema multiforme as superficial dermal vasculitis. Recent
data assert the presence of IgG autoantibodies directed against some
components pertaining to desmosomes plaque, detected in the patients serum
during the active phase of disease (anti-desmoplakin I and II antibody).
Clinical features
Nowadays it is believed that erythema multiforme presents three types
of clinical expression:
1. erythemato - papular erythema multiforme characterized by rounded
lesions, well delineated, erythematous - violaceous, slightly raised, with
a depressed center, cyanotic or purpuric, suggesting a cockade,
commonly affecting the extremities and rarely the face, neck, ears ; the
eruption resolves in 1-2 weeks and leaves a transient
hyperpigmentation; the oral mucosa is rarely affected. The cutaneous
lesions are moderately pruritic.
2. vesiculo-bullous erythema multiforme resembling the previous clinical
form in terms of localization but the appearance of a cockade or " target
" is given by the presence of bullae in the center of the lesions that
evolve either towards erosion and crusting or towards resorption. The
typical - " Herpes Iris " - cutaneous lesion is made up of a vesicular or
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bullous central area, surrounded by an erythemato-violaceous ring, also

surrounded by a crown of vesiculo-bullae, at the end of which there are
several concentric circles of different erythematous tints. Oral mucosa is
involved in about 50 % of the cases (buccal hydroa), the bullae open up
fast only to let red erosions or painful diphtheroids; The constitutional
signs that may accompany the mucocutaneous eruption include: fever,
arthralgia, myalgia.
3. pluri-orificial ectodermosis or Stevens- Johnson syndrome - a severe
form (medical emergency), of life-threatening generalized
vesiculobullous erythema multiforme ; the clinical picture is dominated
by malaise , high fever (39 - 40 C), asthenia, headache, dizziness and
constant lesions of the following mucosas:
oral and labial (in all cases, bullae and bleeding or crusting
covered by false membrane bleeding lesions occur, causing
dysphagia, difficulty in chewing and speech, salivation)
ocular (in 90 % of cases) catarrhal or purulent conjunctivitis,
corneal ulceration, anterior uveitis and even panoophtalmitis; the
lesions leave scarring and cause synechiae, corneal opacities,
blindness;
genital: bullae and erosions that are supra-infected bacterially
and are accompanied by dysuria, phimosis or urinary retention;
anorectal: abrasions causing tenesmus, diarrhea;
nasal: erosions and hemorrhagic crusts, nasal bleeding.
Over 50 % of the cases have respiratory symptoms: irritative cough and
subsequently muco - purulent and hemorrhagic expectoration. The pulmonary
involvement may be interstitial pneumonitis or bronchopneumonia.
Renal involvement translates into hematuria or tubular necrosis that
leads to renal failure.
Rarely (10% of cases) symptoms of CNS involvement occur:
meningism, brain hemorrhage, meningoencephalitis.
Some consider Stevens-Johnson syndrome a particular form of erythema
multiforme.
The evolution of Stevens-Johnson syndrome, occasionally recurrent, is
favorable except for pulmonary, renal or CNS complications, with resolution
within 3-6 weeks; systemic complications lead to death in 10-15% of cases.
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Clinical diagnosis
The "target" or cockade appearance as well as the herpes iris are
evocative for erythema multiforme.
Erythemato - papular clinical form must be differentiated from:
- papular syphilides;
- urticarial lesions;
- Gougerot - Ruiter vasculitis.
Vesiculobullous lesions of erythema multiforme must be differentiated
from:
- porphyria cutanea tarda;
- dermatitis herpetiformis;
- bullous pemphigoid.
Stevens-Johnson syndrome should be differentiated from autoimmune
bullous dermatitis and Lyell syndrome of adults (drug-induced toxic epidermal
necrolysis).
In adults, Lyell syndrome (toxic epidermal necrolysis) - life-threatening
condition in approximately 30 % of the cases, is considered to be the
consequence of a hypersensitivity reactions to drugs.
Clinically features: erythematous skin lesions with a tendency towards
spreading, followed by an epidermal flare up as a result of the flaccid bullae
that break open and may involve the entire skin surface. The mucosal lesions
are severe and affect the lips, oral cavity, pharynx, genital and connective
mucosa.
Malaise and high fever (38-39 C) occur whereas hyperacute or severe
forms are characterized by hydroelectrolytic imbalances along with visceral
lesions: renal (glomerulonephritis which may progress to acute renal failure),
hepatic, pulmonary, pancreatic.
Treatment
Minor and moderate clinical forms of erythemato-edematous and
vesiculobullous erythema multiforme can be self-limiting, requiring only the
suppressing of the cause and a symptomatic treatment: antihistamines, vitamin
C.
Extensive and severe clinical forms of vesiculobullous and Stevens-
Johnson syndrome of erythema multiforme require systemic corticosteroid
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therapy, prophylactic antibiotic therapy, restoration of the hydric and

electrolytic balance, parenteral diet. The topical treatment aims at preventing
superinfections by providing proper skin care: antiseptic compresses, dyes,
sprays with steroids and antibiotics; gargles with antiseptic solutions
(chlorhexidine, hydrogen peroxide1:4 dilution) dental paste containing
corticoids.
Recurrent postherpetic erythema multiforme may be treated with
acyclovir.
CUTANEOUS VASCULITIDES
Cutaneous vasculitis is thought to have many etiologic causes and
manifests as pleomorphic skin lesions (urticarial, purpuric, necrotic) resulting
or not in systemic involvement. Histopathologically it is characterized by
inflammation of the small and medium vessels in the dermis and hypodermis,
mediated immunologically.
Etiopathogenesis
It may affect both sexes and all age groups.
The triggering factors include:
bacterial infections (hemolitic streptococcus, sinus, dental,
urinary infections), viral infections (hepatitis B, C, herpes
simplex), parasitic infections ;
drugs (antibiotics, NSAIDs, aspirin, sulfonamides, purgatives);
food and food additives (colour additives);
environmental factors (cold, excessive heat);
anxiety,
pregnancy;
chronic conditions: diabetes mellitus, hematology (including
lymphomas), rheumatoid arthritis, liver disease, lupus
erythematosus;
gravitational eczemas.
The pathogenic mechanism is usually based on a hypersensitivity
reaction mediated by immune complexes that activate C ' and rarely on a cell
mediated immune reaction.
Histopathology
The typical morphological features include:
189
presence of a dense perivascular polymorphonuclear infiltrate;

vasodilation, endothelial swelling and possibly thrombosis;
erythrocytic extravasation and presence of nuclear debris (" Dust
")
fibrinoid degeneration.
Microscopy reveals disintegration of endothelial cells and PMN
presence in the vascular and perivascular walls.
Direct immunofluorescence reveals deposits of immunoglobulin and
complement on the vascular walls.
Clinical features
Skin lesions may evolve either acutely and chronically, or recurrently
and can involve various skin areas.
Clinical forms of acute injuries often present as purple hemorrhagic,
necrotic lesions, with vesicles and bullae filled with blood, usually located on
the legs, buttocks, thighs, arms.
In subacute clinical forms the lesions are purpuric, erythemato -
macular, edematous (urticaria -like), papular or nodular, whereas in chronic
forms, which may take months and years, they are associated with
erythematous patches, nodules, papules and purpuric or urticarial lesions.
Vasculitic skin rashes may be preceded and accompanied by fever,
aches, digestive disorders, headaches, malaise. This prodrome is moderate in
chronic clinical forms.
Cutaneous vasculitis should be differentiated from
erythema multiforme;
papulonecrotic tuberculids;
meningococcal septicemia;
subacute bacterial endocarditis.
Treatment considerations
The detection (anamnesis, paraclinical) of the triggering factors
requires:
specific treatment (for infectious factors);
avoidance of food allergens, medicines;
avoidance of exposure to cold, heat, or prolonged standing;
bed rest.
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The chronic recurrent cutaneous forms of vasculitis and cutaneous-

systemic vasculitis are treated with:
oral corticosteroids;
colchicine;
dapsone;
plasmapheresis.
Classification
According to A. Conu, cutaneous vasculitides have been categorized
depending on their anatomic and clinical criteria, into:
superficial dermal vasculitis;
deep, hypodermic cutaneous vasculitis;
mucocutaneous systemic vasculitis.
Superficial dermal vasculitis include:
leukocytoclastic vasculitis or Gougerot - Ruiter syndrome;
Henoch- Schnlein anaphylactoid purpura;
erythema elevatum et diutinum;
essential mixed cryoglobulinemia;
Mucha Haberman disease (pitiriazis lichenoides et
varioliformis acuta);
facial granuloma;
livedo reticularis and nodules;
eczematoid purpura.
Deep hypodermic cutaneous vasculitis include:
erythema nodosum ;
Bazins erythema induratum;
subacute nodular vasculitis.
Cutaneous- systemic vasculitis include:
periarteritis nodosa;
systemic lupus erythematosus;
Wegener 's granulomatosis,
allergic granulomatosis;
giant cell arteritis;
necrotizing angiitis;
malignant atrophic papulosis.
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Gougerot - Ruiter syndrome (allergic leukocytoclastic vasculitis)

It affects both sexes, can occur at any age and is manifested clinically
by:
skin lesions : erythematous - violaceous dermal nodules, which
are small, pruritic, invloving the feet, associated or not with
purpuric lesions, urticarial papules, erythema multiforme -like
lesions (Gougerot - Ruiter trisimptom or tetrasimptom);
fever, headache;
arthralgias, gastrointestinal symptoms, renal impairment (in 30-
60 % of cases).
The evolution can be acute, subacute or chronic.
Henoch- Schnlein anaphylactoid purpura

It is a superficial vasculitis with immune complexes, frequently seen in
young males, often after infections of the upper respiratory tract (streptococcal,
viral infections) or ingestion of medicine, food.
Clinical features include:
a febrile prodrome of headache, anorexia;
onset of arthralgia, abdominal pain accompanied by diarrhea
(sometimes with streaks of blood) and vomiting;
skin lesions that coalesce from the beginning or subsequently
and are made up of erythematous patches that later become
papules or petechiae.
The cutaneous lesions usually affect the lower limbs, the buttocks,
possibly the face and oral mucosa and, in children, they may be very soon
accompanied by periorbital edema of the scalp and extremities of the limbs.
Symptoms commonly resolve within 3-6 weeks, however recurrences
may occur.
A complication that influence the prognosis of the disease is the renal
impairment, which may progress towards a chronic nephritis or even renal
failure.
Laboratory investigations that confirm the diagnosis include high
serumal levels of IgA, whereas the histopathological findings attest
leukocytoclastic vasculitis with depositions of IgA immune complexes.
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ERYTHEMA NODOSUM
Erythema nodosum is a deep cutaneous vasculitis cuased by deposits of
immune complexes on the walls of the vessels in the deep dermis and
hypodermis.
Antigenic sources consist of bacteria (streptococcus, Mycobacterium
tuberculosis, Treponema pallidum, Salmonella), viruses (infectious
mononucleosis), fungi (dermatophytes, Histoplasma), chlamydia, drugs
(analgesics, antipyretics, gold salts, contraceptives). Erythema nodosum can
occur in hematologic, sarcoidosis, leukemia, lymphomas.
Clinical features include:
a febrile prodrome of malaise and possibly arthralgia;
a characteristic rash consisting in dermo- hypodermic lumps on
the anterior surface of the shins (rarely on the thighs or
forearms) having an inflammatory and fluctuant character (red,
warm, painful, discreetly raised);
during their evolutionary stages, the lumps become purple,
brown, yellow-green and may reabsorb without sequelae, within
approximately 2-3 weeks ; but they may recur.
Laboratory findings confirm an increased sedimentation rate,
leukocytosis, high levels of fibrinogen and 2 - globulins.
POLYARTERITIS NODOSA
It is a necrotizing vasculitis that can take two aspects:
1. benign periarteritis nodosa characterized clinically by cutaneous
lesions of livedo racemosa or nodular type, along the vascular
tracts of the limbs, face, posterior cervical region, evolving
towards ulceration or resorption, and histologically by a
leukocytoclastic vasculitis of the muscular arteries;
2. cutaneous-visceral polyarteritis nodosa, more frequent in males,
having clinical manifestations that may include skin lesions
(palpable purpura, ulcers, digital gangrenes) and visceral
involvement.
cardiovascular- myocardial arrhythmias, coronary artery
disease, myocardial infarction, hypertension;
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renal- microaneurysms or stenosis and thrombosis of the

renal vessels;
neuromuscular- motoneuritis multiplex, convulsive crisis,
paralysis, polymyositis syndrome;
digestive- paralytic ileus, intestinal perforations;
ocular- ocular hypertension, retinal detachment (optic
atrophy); histopathologically, the lesions affect medium
caliber arteries.
GRANULOMATOUS VASCULITIS
Wegener's granulomatosis
It is a rare systemic vasculitis caused by anti-neutrophil cytoplasmic
autoantibodies (ANCAs) that may be triggered by chronic infections such as
tuberculosis, syphilis. The presence of these autoantibodies causes damage to
tissues by blocking proteinase inhibitors.
Clinical manifestations include nodules on the face which ulcerate
unsteadily, papular and papulonecrotic lesions on the limbs, mouth ulcers.
Destructive granulomatous lesions affect the pharynx, larynx and
trachea.
Renal glomerulitis involvement may lead to uremia.
Churg-Strauss allergic granulomatosis
It is a systemic vasculitis that occurs in asthmatic patients, the clinical
manifestations include:
nodular skin lesions, palpable purpura, chronic ulcers located on
the limbs, trunk, scalp;
pulmonary infiltrates, carditis, arthralgia, neurological signs,
hematuria, bloody diarrhea.
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ERYTHEMATO-SQUAMOUS DERMATOSES
PSORIASIS
It is a dermatosis characterized by erythemato-squamous lesions, with
chronic evolution, genetically determined.
As the disorder progresses with flares, it has a negative impact on the
quality of life.
The treatment regimens target the lesions, maintaining its reactive
potential due to the fact that the disease is genetically determined.
Pathophysiology
Psoriasis is characterized by two types of anomalies:
1. abnormal epidermal hyperproliferation;
2. an immune disorder marked by an inflammatory dermal infiltrate
accompanied by exocytosis.
Etiopathogenesis
The main anomaly remains the disruption of keratinization, that
involves hyperproliferation of the keratinocytes in the superficial layer
(parakeratosis), thus shortening the epidermal cell turnover rate.
Keratinization disorders include:
inhibition of filagrin synthesis (protein involved in the final
process of keratinization);
early expression of involucrin and transglutaminase by
keratinocytes;
persistence of basal keratin (K5 and K14) on the superficial
layers of epidermis (granular and corneal);
presence of K6 and K16 abnormal keratins;
Absence of K1 and K10 keratins.
The keratinocytes pertaing to plaque lesions have revealed the following
changes responsible for cell division acceleration:
the ratio of cyclic nucleotides (cAMP /CGMP) changes in favor
of GMPC -factor favoring cell division;
195
the accumulation of prostaglandin E2 and leukotriene B4 with a

strong chemotactic effect - explains the accumulation of PMN
and formation of Munro Sabourouds micro abscesses;
chalonal activity and polyamine concentration are increased
(both substances having a promising effect);
calmodulin (specific membrane receptor for Ca + +), increases in
psoriatic lesions and normalizes after the treatment;
Changes in the activity of T helper lymphocytes (CD +),
hyperproliferation of cytokines and the induction of intercellular
adhesion molecule (ICAM) on the surface of keratinocytes.
Other factors involved in altering the balance between division and
differentiation include:
infectious diseases, fever or chronic conditions which aggravate
psoriasis;
stress - is responsible for the onset of the disease or it is
sometimes associated with its recurrences;
viral infection (HIV infection has a negative role in the evolution
of psoriasis);
Drugs ( -blockers aggravate the psoriatic lesions).
A prerequisite for this disease is that all these factors should act on a
"potentially psoriatic" environment.
Genetic predisposition is confirmed by the existence of psoriasis
cases that run in the family, which is consistent with an
autosomal recessive pattern of inheritance with incomplete
penetration.
Genetic studies confirmed a locus of impact, responsible for the genesis
of psoriasis on chromosome 17 and suggest the existence of two types psoriasis
in relation to HLA system:
Type I (a family trait) - associated with HLA- CW6, B13,
BW57;
Type II (sporadic) without any association with HLA.
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Clinical aspects
Psoriasis vulgaris
Psoriasis vulgaris is the most common type of psoriasis. Psoriasis is
typically characterized by plaques and patches of skin, which usually have very
well defined edges:
The lesions are represented by erythematous papules or plaques
covered with scales. The erythema is red violaceous and is largely
covered with thick, silvery, shiny, stratified and less adherent scales.
Brocq 's methodical scratching detaches the scales progressively,
highlighting typical signs of psoriasis :
- spermaceti droplets(fragmentation of the scale in small particles
and its bleaching when touched with a scoop)
- Auspitzs sign (punctate bleeding spots when the scales are fully
scraped off)
the lesions are not usually itchy
the sites of the lesions:
- are very suggestive for diagnosis
- preferentially affect the extensor surfaces, elbows and knee,
lumbar- sacral region, scalp
- other typical locations include : the palmar- plantar and genital
region and the flexural creases where the squamous appearance
is less visible but it is dominated by well-defined plaque
erythema
Classic lesions are frequently accompanied by ungual involvement
which becomes difficult to diagnose when it is isolated. Nail injuries
can be characterized by:
- small depressed dots, cupuliform depressions located on the nail
plate
- subungual hyperkeratosis and fragility
- distal onycholysis
Inverse psoriasis (flexural/ intertriginous psoriasis)
it occurs in the skin folds, having both a discreet squamous
appearance and an erythematous one, due to the nature of the area
(heat, moist)
197
it may simulate a mycotic intertrigo or erythrasma and requires a

direct mycological examination for diagnosis
In conclusion, the lesions can be located anywhere on the skin, but the
face is not usually affected.
Special clinical forms
Guttate Psoriasis - characterized by small scaly papular erythematous
lesions (from 1-2 mm to 1 cm), disseminated on the skin. It commonly appears
in children, has a sudden onset and is preceded by a viral or bacterial infection
(frequently streptococcal angina).
Rupioid, elephantine and ostraceous psoriasis - is characterized by a
significant hyperkeratosis with a pseudo warty appearance.
Generalized psoriasis - is a severe form of psoriasis, characterized by
plaques that extend and cover large portions of the skin. The lesions have the
same typical psoriatic appearance.
Erythrodermic psoriasis has a violent onset and it is characterized by
generalized erythema, which affects most of the skin. This type of psoriasis
loses its squamous appearance and it can be difficult to distinguish it from other
erythrodermas.
Pustular psoriasis - there are two clinical forms of psoriasis pustular,
differentiated according to their location, severity and evolution:
a) localized pustular psoriasis showing two different clinical aspects
1. Palmoplantar pustular psoriasis of the Barber type -
characterized by pustules and erythematous -squamous plaques,
symmetrically bilaterally disseminated on the palms
2. acrodermatitis continua of Hallopeau
- the lesions affect primarily the tips of the fingers and toes
and have a chronic development
- clinically characterized by pustules, onycholysis and peeling
of the digital extremities
b. generalized pustular psoriasis characterized by:
- violent onset and malaise (fever, chills)
- the skin lesions consist of red erythematous plaques and
patches and numerous pustules
- the clinical manifestation is represented by septicemia,
triggered by a cutaneous outbreak
198
- the diagnosis can be confirmed by bacteriological

examination (negative blood cultures and sterile pustules)
Psoriatic arthritis
is a clinical manifestation of psoriasis involving the joints
characterized clinically by cutaneous psoriatic lesions and
deforming, destructive and spondylitic arthropathies mostly
affecting the extremities (interphalangeal joints, knee joints)
can be accompanied by fever and malaise
Psoriasis in children
it commonly begins before puberty
Guttate psoriasis is the onset clinical form
in new-borns, the lesions are erythematous and squamous, well
defined, located in the diaper area and known as " Napkin psoriasis "
the scalp involvement is common, but it can mimick a tinea
amiantacea (round erythematous -squamous patches with thick
scales located at the root of the hair)
HIV-associated Psoriasis
HIV infection is responsible for the appearance of a form of psoriasis or
for the exacerbation of a pre-existing psoriasis. Therefore, serious and acute
forms of psoriasis require an HIV serology, especially for those at risk.
Positive diagnosis - is based on the clinical and histopathological
examination of lesions.
Criteria for a positive diagnosis:
presence of well-defined erythematous -squamous plaques
(spermaceti and Auspitz signs)
typical topography
absence of pruritus
chronic evolution
family history
negative mycological examination and negative culture for forms of
nail psoriasis and inversed psoriasis
The histopathological study of psoriatic erythematous squamous
lesions shows:
hyperkeratosis with parakeratosis
199
polymorphonuclear infiltrate (epidermal microabscesses)

finger glove elongation of dermal papillae
the presence of a polymorphous infiltrate in the dermis, associated
with vascular hyperplasia
Psoriasis vulgaris should be differentiated from:
- psoriasiform eczematids
- pityriasis rosea
- tinea corporis
- nummular eczema
- psoriasiform syphilides
- lichen planus psoriasiform
Pustular psoriasis should be differentiated from:
- papulopustular exanthema
- staphylococcal folliculitis
- impetiginized scabies
Treatment considerations in psoriasis
The management of psoriasis is chosen according to the following
criteria:
- clinical form of the disease
- extent of the lesions
- duration of evolution
- associated diseases
- age of the patient.
The local treatment regards only the stable forms of psoriasis, with
fewer lesions, within limited areas.
The main groups of drugs used are:
1. Keratinolitics - aimed at removing the scales and enabling the
penetration of subsequently applied substances. The most used
substances are salicylic acid (03/05/10 %), urea (10-15 %)
2. Dermatocorticoids
have anti-inflammatory and antimitotic effects
inhibit the immune reactions (the synthesis and release of
cytokines)
200
used as single medication or in combination with keratolytic

substances
produce significant improvement of the lesions, but their
effectiveness attenuates over time
if they are inappropriately used, there is an increased risk due to
their side effects:
- atrophy of the skin with stretch marks
- erythrosis and hyperpilosity
- vascular fragility
- risk of skin infection
- hypercortisolism
3. Vitamin D analogues
regulate the proliferation and differentiation of keratinocytes
inhibit the production of cytokines
decrease the number of T 4 lymphocytes in the epidermis and
dermal psoriasis
the most used analogues are calcitriol, calcipotriol. Calcitriol is
recommended to be used on its own, in mild to moderate
psoriasis or in combination with corticosteroids if the forms are
severe.
the side effects include:
- changes in bone and calcium metabolism
- The occurrence of hypercalcemia - renal calculus
4. Tars (vegetable or mineral origin)
they have anti-proliferative, anti-acanthotic, photosensitizing and
vasoconstrictive effects
mineral tar is used with the greatest efficiency
nowadays their clinical use is limited due to their unpleasant
odour and their capacity to stain the clothes, which reduces
patients compliance
5. Dithranol/cygnolin (anthralin)
has antimitotic effect
inhibits the granulocytic function
has immunosuppressive effects
201
it is used in low concentrations (0.1 to 2 %)

it may be associated with aromatic retinoids, with PUVA
therapy, with salicylic acid or tars
the side effects include :
- irritant contact dermatitis
- browning of the skin
6. Aromatic retinoids (derivatives of acidic vitamin A)
have a role in epidermal differentiation
reduce the epidermal turn over
have immunomodulatory effect
are used in facial psoriasis in the form of cream 0.1 % or 0.025
% gel
Side effects: redness, scaling, burning sensation.
7. Mercury salts - are rarely used on limited areas due to their toxicity
8. Local chemotherapy
mechlorethamine, methotrexate, 5- fluorouracil and caryolysine
are used
they are applied through local smearing on limited areas
the side effects can be serious:
- Nausea, vomiting
- Necrotic hemorrhagic cystitis
- Agranulocytosis
- Liver disorders
9. Compounds of zinc (zinc pyrithione 0.2 %)
antiproliferative, anti-inflammatory, antipruritic, antibacterial
effect
recommended for psoriasis vulgaris of glabrous skin or scalp
10. UVB phototherapy
artificial sources of UVB are used
the initial exposure is minimal (minimal dose erythema), but
after that the dose is gradually increased to get a mild
erythematous reaction
UVB may be associated with topical agents, corticosteroids,
cygnolin
202
the remission is controlled by cumulative total dose

Side effects :
- Redness, swelling or blisters
- Local hyperthermia or malaise
11. Photochemotherapy (PUVA)
PUVA is a combination treatment which consists of a
photosensitizing substance (psoralen) followed by skin exposure
to UVA
the psorelen molecules, activated by UVA, bind to nuclear DNA
reducing cell division and causing a normalization of
epidermopoiesis
PUVA may be associated with anthralin, UVB, cyclosporine or
aromatic retinoids (Re- PUVA)
side effects: severe phototoxic reactions, PUVA lentiginosis,
premature aging of the skin
The general treatment is recommended in severe forms of psoriasis with
extensive and serious lesions or in psoriasis vulgaris which is resistant to topical
treatment.
anticancer drugs : methotrexate, cyclosporine
aromatic retinoids
general corticosteroid therapy (in erythrodermic and pustular
psoriasis)
Adjuvant drugs in psoriasis include: antibiotics, vitamin therapy,
NSAIDs, sedatives, synthetic antimalarials (in actinic psoriasis and psoriatic
arthritis)
The last decade has brought major changes in the treatment of psoriasis.
The biological therapy it represents the use of agents that can target an immune
mediator from the pathophysiological process of the disease. These drugs are
made from organic human or animal proteins and are taken by injection or by
IV infusion.
This type of therapy is usually well tolerated and it represents the option
when the local treatment has failed or when the psoriasis is moderate to severe.
Examples:
tumor necrosis factor-alpha (TNF-) blockers such as etanercept
(Enbrel), adalimumab (Humira), infliximab (Remicade)
interleukin12/23 blokers ustekinumab (Stelara)
203
PARAPSORIASIS
Parapsoriasis is an erythemato - squamous dermatosis characterized by

scaly plaques, of underlying etiology and with a chronic course.
Parapsoriasis is classified according to the clinical appearance:
1. plaque parapsoriasis
2. drop-shaped/guttate parapsoriasis
Plaque parapsoriasis
Clinical features:
it manifests as erythematous plaques covered with a fine, adherent,
single-layered scale, having an atrophic quality;
the lesions are accompanied by moderate but persistent itching and
are located on the limbs, buttocks, abdomen, body folds.
From an evolutionary point of view there are two types of parapsoriasis:
1. a benign form, in which lesions have a digitate pattern, parallelly
distributed and located on the limbs;
2. a premalignant form, that combines large areas of reticular
pigmentation with telangiectasia. This form progresses towards T-
cell lymphoma.
Differential diagnosis includes: psoriasis vulgaris, pityriasis rosea.
From an evolutionary standpoint, the condition persists for a long time
and is resistant to treatment.
Drop-shaped parapsoriasis/Guttate parapsoriasis

Clinical features:
it manifests as small erythematous papules covered with a gray
scale, less adherent that scrapes off in chunks when scratched ;
preferential areas include the torso and limbs ;
the lesions are non-pruritic, persistent, they may wax and wane in
their clinical course whereas healing occurs with residual
pigmentation macules.
Clinical forms:
1. Mucha Habermann disease (Pityriazis lichenoides)
Clinically:
combines typical papules with purpuric elements;
204
the papular lesions present central necrosis and healing leaves

depressed varioliformis scars.
2. Lichenoid parapsoriasis
Clinically they are classic papulosquamous lesions evolving to a central
atrophy and a peripheral hyperpigmentation (reticular mottled appearance).
- Guttate psoriasis
- papulosquamous syphilides
- Pityriasis rosea
- prurigo
Treatment:
a) systemic treatment - vitamin D2, D3 and A are recommended
b) local treatment comprises a combination between corticosteroids
and keratolytics and emollients.
PITYRIASIS RUBRA PILARIS
Pityriasis rubra pilaris (PRP) is a rare erythemato - squamous

dermatosis, of unknown etiology, with an autosomal dominant inheritance
pattern.
This disorder was first described by Tarrant Alaudius in 1828. In 1857,
Devergie completed its description, and the name of PRP was given by Besnier
in 1889. In 1980, Griffiths proposed the classification of PRP into 5 clinical
types, after which a 6th type was currently added, namely the one associated
with HIV infection.
The classification proposed by Griffiths in 1980 brings up the following
clinical forms of PRP:
classic adult PRP (type I); is a common form of disease,
characterized clinically by erythematous lesions, palmoplantar
keratoderma and follicular hyperkeratosis ; this type of PRP has a
very good prognosis. Reportedly, about 80% of patients had
remission in an average of 3 years.
atypical adult PRP (type II); It is characterized by alopecia,
ichthyosiform lesions, and areas of chronic eczema. This form
accounts for 5% of patients.
205
PRP - Classic Juvenile PRP (Type III): this form accounts for 10 %
of all cases of PRP. The clinical picture is similar to type I and the
remissions occur more rapidly.
circumscribed juvenile PRP (Type IV) : this form accounts for 25 %
of all cases of PRP. It manifested clinically as corneous papules,
hyperkeratosis and erythema on elbows and knees. This form rarely
progresses.
atypical Juvenile PRP (Type V)-clinically manifested by follicular
hyperkeratosis, scleroderma -like lesions and erythematous lesions.
The frequency of this clinical form is about 5 %.
HIV -associated PRP (Type VI): In this form, the lesions are less
characteristic, aside from follicular papules, acneiform lesions may
also be encountered (pustules, papules, pustules and cystic nodules)
Clinical features
Cutaneous lesions
The basic typical lesion is the corneous follicular papule, element that
distinguishes PRP from other erythemato -squamous dematoses.
Other lesions include:
follicular hyperkeratosis
erythematous lesions
palmoplantar hyperkeratosis
pityriasis capitis lesions
subungual hyperkeratosis
the papular erythematous -squamous lesions are arranged in plaques
and large patches with sharp borders, with an orange hue, located on
the trunk, abdomen, limbs and feet
follicular keratotic papular lesions are commonly seen on forearms,
arms, thighs and buttocks.
erythematous lesions can be seen on the face, neck and ears
subjectively: pruritus
The emergence of the clinical signs generally follows a chronological
order.
206
The onset is at the cephalic extremity, with pityriasic lesions on the

scalp, which may extend to the face, the dorsal side of the ear and trunk in the
form of erythematous, papular, scaly plaques with an orange tint
familial forms of PRP are described, with an autosomal dominant
inheritance pattern, as well as acquired forms of disease that tend to
persist throughout life.
Localized forms of PRP are seen in the areas exposed to trauma
(equivalent of Kbner phenomenon).
Mucosal lesions
Mucosal lesions are leukoplakic plaques, erosions and sometimes mouth
ulcers.
Ocular lesions
The extensive forms of disease may be associated with ectropion.
In order to confirm a PRP diagnosis, the following parameters are
necessary to be assessed (M. Sanchez- Regan 1994).
age
craniocaudal progression
sites of the lesions
portions of uninvolved skin
histopathology
the course of the disesase
response to treatment
From an evolutionary point of view 2 types of PRP are described:
a chronic form, with slow evolution and spontaneous remission
an acute form, characterized by malaise, fever and clinically by
exfoliative erythroderma
clinical appearance
histopathological examination of the erythematous papulosquamous
lesions
Histopathologic diagnosis shows
irregular hyperkeratosis in the epidermis
bulky follicular keratotic plugs
207
Discreet spongiosis, exocytosis and a great amount of inflammatory

infiltrate around the adnexa (hair, sebaceous glands)
Possible associations
PRP may be associated with other conditions such as dermatomyositis,
myasthenia gravis, leukemia, hypothyroidism, HIV.
difficult to be confirmed from the beginning, sometimes repeated
histopathological exams are required
however, PRP must be distinguished from :
- follicular psoriasis
- erythroderma ichthyosiform
- follicular lichen planus
- palomoplantar keratodermas
- cutaneous lymphomas.
Evolution and prognosis
Usually, PRP acquired forms may resolve spontaneously within 1-3
years.
Treatment
The therapeutic alternatives recommended by the literature are as
follows:
For systemic treatment:
aromatic Retinoids - Borok (1990) suggests that etretinate is far
better than isotretinoin. The recommended dose is 1-1.5 mg / kg /
body weight / day
anticancer drugs with immunosuppressive effect (azathioprine,
methotrexate)
PUVA - therapy
vitamin therapy (Vit. A) in doses of 150000-500000IU/day
For topical treatment:
corticosteroids - with few long-term therapeutic effects
calcipotriol (vitamin D derivative) ;
softeners
encouraging results were obtained with topic isotretinoin 0.005 % in
combination with urea and Ichtyol.
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LICHEN PLANUS
Lichen planus is a dermatosis which affects the skin and / or mucosa
with chronic self-limiting evolution.
The condition is relatively common in both sexes and all races. The
prevalence is estimated at 1%.
The onset is usually in the 5th or 6th decade of life, it may be a familial
trait and it has a high incidence in patients with HLA A3, A5, B7 and DR1
antigens.
Lichen planus belongs to the group of lichenoid dermatoses and it is
characterized clinically by papular cutaneous lesions and histologically by
mononuclear cell infiltrate with linear distribution in the superficial dermis.
Etiopathogenesis
The etiopathogenetic mechanisms are not fully understood.
Many factors are incriminated:
1. viral infections (keratinocytes have revealed virus -like inclusions).
2. stress (the lesions are exacerbated by psychological trauma).
3. drugs (gold salts, antimalarials give rise to lichenoid eruptions.)
4. neurological diseases (lichen planus is associated with severe
neurological conditions, peripheral neuritis, syringomyelia).
Cutaneous lesions:
clinically, lichen planus is characterized by erythematous violaceous
papules. The lesions have 1-3 mm, they are shiny, polygonal, very
itchy and sometimes centrally depressed;
characteristic fine, white lines are often found on the papules
(Wickham stria);
the papules may be found separately or they may coalesce to form
plaques and patches;
the linear distribution of the papular lesions is typical for lichen
planus and it is known as the Kbner phenomenon or isomorphic
response;
healing leaves small persistent hyperpigmented spots.
Sites- the most affected areas are:
the anterior surface of the forearm and wrist;
the lumbar-sacral region;
the anterior surface of the feet;
209
the malleolar region.

Subjective symptoms: constant pruritus may be responsible for the Kbner
phenomenon (linear distribution of the papules along the scratching lines) and
lichenification lesions.
Mucosal lesions:
mucosal lesions may be associated or not with cutaneous lesions;
characterized clinically by white steady plaques, having reticular
appearance and a tendency towards atrophy or erosion;
notably, the lesions are located on the mucosa of the cheek, but the
tongue, the lips, the laryngeal, esophageal, genital, perianal mucosas
may also be affcted;
vulvar mucosal lesions have been described as having a
polymorphic appearance ranging from erythematous, erosive,
leukoplakic, to atrophic or scaly.
Nail lesions:
nail changes arent characteristic to lichen planus, but their presence
is necessary to confirm the diagnosis;
the most common changes are:
- nail striations;
- subungual hyperkeratosis;
- longitudinal melanonychia;
- ungual pterygium;
- onycholysis.
Hair damage: the presence of lichen planus on the scalp can lead to atrophic
cicatricial lesions.
Clinical forms:
1. Hypertrophic lichen planus (verrucous) is characterized by
hypertrophic patches covered by thick hyperkeratotic deposits
usually affecting the extensor surfaces of the lower extremities; it is
commonly associated with chronic venous insufficiency.
2. Follicular lichen planus
clinical features: red follicular papules with central keratotic
plug (hyperkeratosis acuminata);
210
the lesions are found on the flexor areas, upper chest, neck,
sacral region ;
on the scalp the lesions are characterized by follicular papules
associated with moderately adhesional scales which can lead to
atrophic cicatricial alopecia.
3. Annular lichen planus
clinical features: small round plaques with a depressed center
and lichenoid papules at the periphery;
the lesions can be found on the male genitalia.
4. Erosive oral lichen planus:
clinical features: erosive, ulcerative and persistent patches in the
mouth, sometimes associated with atrophic pigmented lesions
and desquamative gingivitis.
5. Vesicular and bullous lichen planus:
it associates lichenoid papular lesions with bullous lesions.
Positive diagnosis depends on:
1. clinical appearance;
2. subjective symptoms (pruritus);
3. histopathological examination.
Pathological diagnosis
Histopathological changes in lichen planus include:
hyperkeratosis accompanied by ortokeratosis
focal hypergranulosis
irregular acanthosis (" saw teeth " appearance)
hydropic degeneration of the basal layer
the upper dermis has a band-like infiltrate of lymphocytic and
histiocytic cells
presence of colloid bodies in the epidermis and upper dermis
4. direct immunofluorescence (DIF) reveals deposits of IgM, G, Aand
complement, in a band-like distribution along the basal membrane.
5. indirect immunofluorescence reveals antibodies of a specific lichen
planus antigen.
1. lichenoid eruptions;
211
2. papular-scaly syphilides;
3. chronic prurigo;
4. lichen amyloid;
5. verruca plana;
6. guttate psoriasis;
7. lichenified chronic prurigo;
8. papular - vesicular eczema.
Complications of lichen planus
- are rare and include:
1. candidal superinfections (for lesions in the mucosas);
2. lichenification;
3. persistent residual pigmentations;
4. atropho-cicatricial lesions;
5. synechiae in the genital region;
6. carcinomatous degenerations(in oral lesions).
This is a self-limited disease, it has a benign evolution, without any
signs of malaise. Skin lesions heal with persistent residual pigmentations.
The prognosis is usually good, the impact of the condition on the overall
state is controlled by the intensity of the subjective manifestations. Recurrences
are possible in about 20 % of patients.
Treatment
The effectiveness of the treatment is difficult to assess for this chronic
and benign condition. If the lesions are extensive and the pruritus is intense, the
following therapeutic options are available:
1. Abstinence therapy if:
the lesions are few in number and on limited areas;
the itching is intense;
the patient accepts.
2. Topical treatment:
topical corticosteroids applications with or without occlusive
dressing;
cyclosporine for oral mucosal lesions (topical applications) or
corticosteroids
retinoids (isotretinoin gel 0.1 %).
212
General treatment:
It is appropriate for acute extensive forms, involving a wide range of
areas, or for severe erosive forms.
Depending on the particularity of the case the following can be
administered:
corticosteroid therapy (prednisone 15-20 mg / day, 6-8 weeks)
systemic retinoids (etetrinate 75mg/day)
griseofulvin (500 mg / day)
cyclosporine (5 mg / kg c / d)
PUVA therapy
Other treatment methods
1. surgical excision of oral lesions of lichen planus;
2. cryosurgery;
3. laser therapy;
4. radiculomedullary radiotherapy.
213
BULLOUS (BLISTERING) DERMATOSES
Bullous dermatoses are disorders characterized by" blisters or bullae ",

due to a disturbance in the interkeratinocytic coherence of the dermis. This
segregation of epidermal structures is the result of an autoimmune process
(regarding the antibodies attachment to the structures involved) or it may arise
from an epidermal genetic abnormality as well.
Depending on the site of their cleavage, bullous dermatoses are
classified into:
intraepidermal autoimmune bullous dermatoses (in which the
loss of the interkeratinocytic cohesion occurs due to the
alteration of the desmosomal structures due to antibodies)
subepidermal autoimmune bullous dermatoses (due to
autoantibodies, the dermal and epidermal structures are affected
resulting in the loss of their cohesion)
INTRAEPIDERMAL AUTOIMMUNE BULLOUS DERMATOSES

Autoimmune pemphigus is a bullous dermatosis which affects the skin
and the mucous membranes and is characterized histologically by acantholysis.
Depending on the site of their cleavage, two groups of pemphigus can be
distinguished:
deep pemphigus (pemphigus vulgaris and vegetans)
superficial pemphigus (pemphigus foliaceus, erythematosus,
endemic)
PEMPHIGUS VULGARIS
It is a severe autoimmune disorder, usually seen in the adults with
genetic and ethnic predisposition. Groups HLA - B38, HLA - DR4, HLA - B55,
HLA - DPW4 are more commonly affected.
Etiopathogenesis
The pathogenic mechanism of the pemphigus is based on the process of
autoimmune acantholysis.
214
An important role in triggering acantholysis is played by IgG

autoantibodies, directed against some proteins pertaining to the structure of
desmosomes, known as desmogleins. (desmoglein III = pemphigus antigen).
Deposition of autoantibodies causes direct activation of intercellular
plasminogen, resulting in a plasmin - induced proteolysis and as a result, the
intercellular connections are broken. Therefore, the spiny cells are separated
from each other, and the gaps between them are filled with a fluid that contains
acantholytic cells. The serum samples taken from patients with pemphigus
vulgaris have revealed circulating autoantibodies with pathogenic role,
belonging to IgG1 and IgG4 subclasses. Immunological pathogenesis is
supported by the following aspects:
the presence of anti-intercellular cement substance antibodies
the titer of circulating antibody is linked to the disease morbid
course
the presence of IgG and complement deposits in the intercellular
malpighian spaces
the correlation between all forms of pemphigus and other
autoimmune diseases
The onset of the disease affects the mucosas in 50-70 % of cases. Buccal
mucosa is commonly affected and the lesions consist of bullae with very fragile
walls which may rupture, leaving round, oval, well-delimited erosions, covered
with whitish deposits. The mucous erosions are painful, indefinitely persisting,
they tend to expand along the digestive tract, disturbing digestion and
absorption processes. After a while, patients find it difficult to eat, experience
gradual weight loss, and physical deterioration occurs. In the oral cavity, lesions
are commonly seen on the inner surface of the cheeks, palate, pharyngeal
isthmus, but they may affect the entire mouth. Genital, conjunctival, urethral
and nasal mucosas can be affected as well.
The skin eruption has initially a monomorphic character, and consist of
small, flask blisters filled with clear fluid. Bullous lesions arise on a healthy-
appearing skin and are not preceded by subjective symptoms. Their rupturing
causes extensive painful erosions and sometimes gives rise to yellow- brown
crusting above the initial collarette. A relevant clinical sign is Nikolsky's sign,
which shows an increased skin fragility.
215
When pressed, the skin that covers a prominent bony surface exfoliates
and gives rise to erosions.
Bullous skin lesions exhibit a predilection for the scalp, face, inguinal
and axillary folds, chest, and for anatomical areas prone to pressure and trauma.
The onset of cutaneous lesions usually affects the oral mucosa, may appear
secondary to the skin rash or they may even be absent after the first flares.
The disease runs a chronic course, of increased severity, and as the
disease progresses, the general condition is deteriorating. Fever, electrolytic
disorders, severe superinfections of bare skin areas are major life-threatening
factors.
Positive diagnosis of pemphigus vulgaris rests upon its characteristic
clinical appearance and it is confirmed by laboratory tests.
Laboratory diagnosis
1. Tzanck cytodiagnosis reveals the process of acantholysis.
- the base of a blister is scraped, and a May- Grunwald Giemsa
staining is being performed
- the examination detects the presence of malpighian cells, either
scattered or clustered, with a distinctive morphology, known as
acantholytic cells (large nucleus, basophilic cytoplasm and a
reversed nucleo- cytoplasmic ratio)
2. Histopathological examination
Shows the presence of a blister located in the deeper malpighian
layer.
The base of the blister is made up of basal keratinocytes, whereas
acantholytic cells are found inside the blister
3. Direct immunofluorescence
- Shows a specific fluorescence of reticulated appearance caused
by deposition of IgG, M and fraction C3 of the complement
within the intercellular malpighian gaps (this method uses anti-
IgG antibodies, highlighted by fluorescein).
4. Indirect immunofluorescence
- reveals the presence and titer of circulating autoantibodies in the
patients serum
- demonstrates the presence of anti-intercellular cement substance
autoantibodies, pertaing to IgG class
216
- the titer of circulating autoantibodies is directly proportional to

the course of the disease
5. Immunoblotting and immunoprecipitation are techniques that
identify the target antigens
6. Nonspecific laboratory tests assess the general status and are
consistent with the disease. Without exhibiting a predilection for this
condition, the following changes can be found: hypochromic
anemia, increased sedimentation rate, electrolytic changes
(hyponatremia, hypocalcemia), hypoproteinemia, etc.
Pemphigus vulgaris is a serious disease with a reserved prognosis.
PEMPHIGUS VEGETANS
Pemphigus vegetans is a particular form of pemphigus, characterized by
papillomatous hypertrophic vegetating lesions, frequently involving large body
folds.
Etiopathogenesis:
The antigen of pemphigus vegetans is a 130KD molecule.
Two forms of pemphigus vegetans are described
1. Pemphigus vegetans of Neumann: this form is initially characterized
by flaccid bullae, with a clear fluid, that rupture, whereas the
erosions are covered with hypertrophic granulation tissue that
subsequently develops into plaques. Sometimes these vegetative
masses are covered with fetid secretions due to maceration and local
superinfection.
Sites: it usually appears on the axillary, inguinal, nasolabial folds, on
the corner of the lips, vulvar and anal region. Oral lesions may have
a vegetative appearance as well.
2. Pemphigus vegetans of Hallopeau: the onset lesions are pustules that
may develop into erosions that are quickly covered with
papillomatous proliferations forming plaques, with active edges and
a tendency to extend peripherally. The lesions are painful, have a
fetid smell, and have a predilection for intertriginous areas (groins,
axillary and perianal regions).
217
Laboratory diagnosis involves the same steps as pemphigus vegetans:

histopathological examination of the lesions: shows acantholytic
suprabasal bullae associated with acanthosis and papillomatosis. The
histological marker of pemphigus vegetans is represented by
intraepithelial eosinophilic microabscesses.
direct and indirect immunofluorescence reveal similar changes as in
pemphigus vulgaris
Differential Diagnosis includes:
- tuberculosis vegetans
- pyoderma vegetans
- syphilide vegetans (papulo-hypertrophic syphilide)
- acantozis nigricans.
Pemphigus vegetans runs a chronic course, but it can also evolve
towards pemphigus vulgaris.
PEMPHIGUS FOLIACEUS
Pemphigus foliaceus is a rare form of pemphigus and two varieties are
described, an endemic one and a sporadic one.
Etiopathogenesis:
This form of pemphigus is also characterized by antibodies which react
against intercellular adhesion molecules, belonging to the cadherin family. The
antibodies belong to IgG4 class and are directed against desmoglein 1, whereas
circulating antibodies are directed against desmoglein 1and 2.
The endemic variant (fogo selvagem) can be seen in Brazil and it is
caused by an insect bite (Simulium preunosum).
The onset lesions are flaccid vesiculo-bullae that rupture quickly and are
cover with multilayered squamous crusts. The characteristic appearance is of an
exfoliative erythematous - squamous crusty erythroderma. Nikolsky 's sign is
positive. The disease starts in the cephalic and thoracal extremities and from
here it may extend.
Mucous membranes are rarely affected, and the overall condition is
good.
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histopathological examination shows that acantholysis affects
superficial layers of the epidermis (spinosum and granular strata)
direct and indirect immunofluorescence show closely resemblances
to pemphigus vulgaris in all respects.
immunoelectron microscopy shows that the autoantibodies of
endemic pemphigus foliaceus bind diffusely not only to the
desmosomal region, but to the surface of keratinocytes as well.
Differential diagnosis include:
- seborrheic dermatitis
- impetigo
- Lyell Syndrome
PEMPHIGUS ERYTHEMATOSUS (SEBORRHEIC PEMPHIGUS -

SENEAR - USHER SYNDROME)
It was described by Senear and Usher, as a variety of pemphigus
clinically similar to lupus erythematosus.
Etiopathogenesis:
The condition is considered a combination between lupus erythematosus
and pemphigus foliaceus. Both antiepidermal and antinuclear antibodies have
been detected in the patientsserum.
The initial lesions are small bullae, which rupture, leading to the
formation of crusted erosions. They resemble seborrheic eczematids or the
exudative form of psoriasis. The eruption affects mainly the seborrheic areas
(sides of the nose, eyelashes, scalp, upper trunk) and it has a butterfly
distribution on the face. The lesions are photosensitive and some of the patients
experience a burning sensation. The mucous membranes are not affected, and
the overall condition is good.
histopathological examination highlights the acantholytic process,
in the upper malpighian layer
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direct Immunofluorescence testing (DIF) shows an intraepidermal

reticulated appearance and a band-like fluorescence on the basal
membrane
indirect immunofluorescence testing (IIF) highlights Ac- anti-
epidermal and anti-nuclear antibodies.
Evolution: The disease runs a chronic course, persisting for years, but it may be
associated with other autoimmune diseases (thymoma).
- chronic cutaneous lupus erythematosus
- seborrheic dermatitis
- eczema.
PARANEOPLASTIC PEMPHIGUS
It is a particular form of pemphigus found in patients with malignancies
(lymphoma, thymoma).
Etiopathogenesis:
Four target antigens are responsible for the initiation of the autoimmune
process, desmoplakina1 (250KD) desmoplakina2 (210KD), the major antigen
of pemphigoid B (230KD) and one molecule of 190KD. IgG antibodies are
anti-surface pemphigus -like cells that bind to the transitional epithelia.
The lesions are atypical, polymorphic and affect the mucous membranes
and the skin. Mucosal lesions are painful erosions and ulcerations, with necrotic
appearance. Oral mucosa and conjunctiva are often affected.
The skin rash is characterized by polymorphic bullae, erosions and
cockade lesions similar to those of erythema multiforme and subacute -like
lupus erythematosus.
Laboratory Studies
histopathological examination: shows suprabasal acantholysis,
keratinocyte necrosis and vacuolar degeneration of the basal layer.
direct Immunofluorescence testing (DIF) detects depositions of
immunoreactants IgG and C3 within the epidermal intercellular
spaces, or granular and linear depositions of C3 in the epidermal
basement membrane
220
indirect immunofluorescence testing (IIF) reveals circulating

antibodies directed against extracellular matrixes and sometimes
against basement membrane
Paraneoplastic pemphigus is usually associated with malignancy as well
as the prognosis. It is generally associated with severe forms of cancer, hence
the extremely reserved prognosis.
PEMPHIGUS HERPETIFORMIS
Pemphigus herpetiformis is a clinical variant of pemphigus, with distinct
clinical features.
The lesions are similar to those found in dermatitis herpetiformis: the
vesicles demonstrate aherpetiform pattern, being clustered on an
erythematous base and scattered along the trunk and limbs.
Histopathology shows characteristic changes: spongiosis accompanied
by eosinophils and acantholysis, intraepidermal edema and exocytosis of PMN.
DIF shows depositions of IgG, IgA and C3 on the surface of
keratinocytes without involving the desmosomes.
IIF highlights IgG circulating antibodies that recognize desmoglein 1
IATROGENIC PEMPHIGUS (DRUG-INDUCED PEMPHIGUS)

It is a clinical variant of pemphigus related to drug usage. The culprits
of drug-induced pemphigus are those that contain sulfhydryl reactive groups,
capable of reducing the disulfide bonds, and able to produce acantholysis
(captopril, penicillamine).
Other drugs capable of producing acantholysis are: enalapril,
cephalosporins, rifampin, interferon, piroxicam. The appearance of lesions in
pemphigus drug is similar to that of pemphigus erythematosus and foliaceous.
Drug-induced pemphigus resolves spontaneously after withdrawal of the
offending agent.
Treatment of pemphigus
Guidelines for the management of pemphigus
The choice of treatment will be based on:
the type of pemphigus
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extension of mucocutaneous lesions

response to treatment
the titer of circulating antibodies
drug-induced complications
associated diseases
general health status of the patient
General treatment:
It is usually carried out in 3 phases
1. control phase (brings the disorder under control)
2. consolidation phase (allows control of the flares until a significant
portion of lesions have healed)
3. maintenance phase (the dose of corticoid is reduced to a minimum
possible)
The control phase is aggressive, it uses corticosteroids and / or
chemotherapy, and is directed toward suppression of the mucocutaneous lesions
as soon as possible.
Corticosteroids
Prednisone (medium potency corticosteroid) is the one of the most used
drugs in the oral administration, with significant anti-inflammatory effect and
average action of 12-36 hours. The right dose in order to control the disorder is
1-2mg/kg/ /day, in 1-2 doses administered in combination with a
gastroprotector. If after 10-14 days the skin lesions do not resolve, the dose may
be increase up to 300mg/day. If high-doses do not seem to be working, the
corticoid needs to be changed, as well as the mode of administration. If control
of the disorder is achieved, the dose of medication should be gradually reduced
at 5mg within 8-10 days and then at 40-60mg/day, at which time an
immunosuppressive drug may be administered.
Other medications include:
- prednisolone
- dexamethasone
- betamethasone
Prolonged treatment with extremely high doses of corticosteroids may
induce an important number of side-effects:
- hypertension
- diabetes mellitus
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- osteoporosis
- gastrointestinal bleeding
- blood clotting
- iatrogenic Cushing syndrome
- resistance to corticoids.
Immunosuppressive drugs
Immunosuppressive drugs are recommended during the consolidation
and maintenance phase, either by means of a single drug (in cases of resistance
to corticosteroids or when there is contraindication to glucocorticosteroids) or
in combination with corticosteroids.
1. Azathioprine
is a nitroimidazole derivative of mercaptopurine, acting as an
intense and prolonged immunosuppressant;
it is recommended in serious forms of disease and in cases of
resistance to corticosteroids;
azathioprine is a safe drug when carefully administered;
its toxic effect can not be neglected (bone marrow and liver
involvement), nor its decreased resistance to infections and its
carcinogenic effect on the blood. Dermatologic doses (1.5 -
3mg/kg / day) are generally low and provide some protection in
this sense.
2. Cyclophosphamide
is a nitrogen mustard alkylating agent acting that interferes with
DNA structure and hinders its replication, transcription and
translation functions.
it has an important immunosuppressive effect, thus it is indicated
in autoimmune diseases.
is useful in the maintenance phase of treatment of severe forms
of pemphigus, single or in combination with corticosteroids.
The average dose is 1-3mg/kg/day, in 2-3 divided doses.
The side effects are common to all cytostatics and include acute (nausea,
vomiting, visual disturbances) or late reactions (myeloid toxicity, sterile
hemorrhagic cystitis, alopecia) and are determined by the frequency and
duration of administration.
223
Methotrexate
Methotrexate is an analogue of folic acid, that inhibits the formation
folic acid, by blocking the enzyme dihydrofolate reductase, necessary for DNA
and RNA synthesis. Its effect is cytostatic, antiproliferative, and strong
immunosuppressant.
Methotrexate is used in mild forms of disease, or as maintenance
treatment in severe forms, in combination with corticosteroids.
It is administered in doses ranging from 25-50mg/week in the control
stage of the treatment and 7.5 mg / week during the maintenance phase. The
dose is divided into 3-4 doses every 12 hours.
The side effects include:
high risk of liver toxicity and possibly cirrhosis
marked immunosuppression, increasing the risk of infections
worsening of oral lesions
Cyclosporine
Cyclosporine acts as an immunomodulatory drug. T-helper lymphocytes
are selectively inhibited. It is recommended in severe forms of pemphigus
vulgaris, but used alone, it has proved less effective. It is used in small doses of
3-5 mg / kg / day, in oral administration. Oral lesions of pemphigus vulgaris
respond well to topical therapy with cyclosporin (5 minutes gargle 3 times /
week, for 8 weeks), using 5 ml of the 100mg/ml Sandimmun solution. The
results are inconsistent with pemphigus foliaceous.
The side effects are numerous. Nephrotoxicity and hepatotoxicity
dependent on the dose, but they are present in 25-75 % of patients treated with
cyclosporine. Other frequent manifestations include gingival hyperplasia,
hypertension, hirsutism, neurological disorders.
Mycophenolate mofetil
This immunosuppressant has recently been used in the treatment of
pemphigus vulgaris, suppressing T and B lymphocyte proliferation by
inhibiting inosine monophosphate dehydrogenase, an enzyme essential for the
synthesis of guanine nucleotides. The inhibition of proliferation of B cells
suppresses the production of antibodies in pemphigus vulgaris. Mycophenolate
mofetil is recommended in cases of pemphigus vulgaris resistant to therapy.
The usual dose is 2g/day administered alone or in combination with
cyclosporine and prednisone.
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Higher doses are required in pemphigus foliaceus in order achieve

remission. (2.5 -3g / day).
Notable side effects include: gastrointestinal disorders, anemia,
lymphopenia, thrombocytopenia.
Gold salts
Sodium aurothiomalate
It is used in the treatment of pemphigus only as a backup medication for
individuals who do not respond to standard medication.
it acts as an inflammatory and stimulant of the
reticuloendothelial system.
it inhibits the cytolysis of leukocytes stimulated by antibodies
and diminishes the release of lysosomal enzymes.
it regulates some cellular and humoral immunobiological
parameters.
Gold salts remain in the body (liver, kidney, bone marrow, and the
monocyte -macrophage system), and are slowly eliminated through urine and
faeces.
Side effects are common and affect:
skin and mucous membranes (cutaneous rashes, exfoliative
dermatitis)
renal apparatus (albuminuria, hematuria)
digestive tract (gastroenteritis)
CNS (neuritis, encephalitis)
haematological (anemia, thrombocytopenia, eosinophilia)
Levamisole
Levamisole has immunostimulatory properties and it is used as an
anthelmintic. In pemphigus vulgaris it is used in a 50 mg dose / day, 3 days a
week for 2-8 weeks.
Plasmapheresis
It is recommended in severe forms of pemphigus, and is directed against
the reduction of antibody titer.
Immunoglobulins (IVIg)
Intravenous immunoglobulins represent a new therapeutic option for
autoimmune dermatoses. So far, favorable results have been obtained in the
treatment of bullous dermatoses such as pemphigus vulgaris, pemphigus
225
foliaceous, bullous pemphigoid. Although the exact Ig mechanisms are still not
fully understood, the main immunomodulatory mechanisms are described:
blocking of Fc receptor function
purification of circulating immune complexes
suppression of antibody production
reduction of complement-mediated damage
modulatory effects on the production and release of cytokines
regulation of cell-mediated immune response
The side effects of this therapy include:
anaphylactic reactions
renal failure
hemolysis
cardiovascular complications
Adjuvant therapy associates:
anabolic drugs
vitamins
sedatives
Topical treatment:
It is essential and consists of applying antiseptic, inflammatory
solutions, with a healing effect. The blisters must be cleaned up, then topical
antiseptics and siccatives must be applied. After drying of the lesions, topical
corticosteroids may be applied.
Epithelializing, antiseptic and anticandidal suspensions, are
recommended in mucosal lesions. Orabase corticoid preparations are known to
have beneficial effects.
Notably, lipo-soluble bases should be avoided in pemphigus vegetans
because they enhance the formation of vegetations.
Hygienic-dietary treatment
a diet rich in proteins, vitamins and minerals
a low sodium, hypoglucidic and hypolipidaemic diet
avoiding mucocutaneous trauma
an easy-going lifestyle
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AUTOIMMUNE SUBEPIDERMAL BULLOUS DERMATOSES
LEVERS BULLOUS PEMPHIGOID

Bullous pemphigoid is a subepidermal autoimmune bullous dermatosis,
which was later isolated as an autonomous entity by its separation from
Duhring Brocq dermatitis. This condition, primarily affects elderly individuals
over the age of 60, regardless of their sex or ethnicity. Children are rarely
affected.
Pathophysiology:
bullous lesions are due to an autoimmune mechanism
IgG autoantibodies are targeting the basement membrane, and
are directed against the collagen within lamina lucida structure
the target molecules of antibodies are found in the
hemidesmosomes, namely BPAG1 (major bullous pemphigoid
antigen - intercellular protein), and BPAG2 (minor antigen of
transmembrane bullous protein pemphigoid) and integrin alpha 6
beta -4
the binding of autoantibodies to target molecules activates
complement and inflammatory mediators, which leads to lysis of
the basement membrane and the formation of supra - basal
blisters
by producing proteolytic enzymes, the eosinophils may be
responsible for the disruption of adhesion molecules
pemphigoid antigen -specific T lymphocytes can be involved in
the chemotaxis and activation of eosinophils by Interleukin IL-4
and IL-5 production
The onset signs include:
generalized pruritus
common erythematous or urticarial lesions
erythemato - papular or eczematous plaques, localized or
generalized
The classic appearance after the onset is characterized by:
227
generalized pruritus tight bullae, with clear content, often large,

developing on a healthy-looking skin
polycyclic erythematous lesions and / or urticarial, covered with
variable sized blisters
erosion, crusting, pigmentation spots and milia (age-related
lesions)
the lesions are symmetrical, predominantly affecting the trunk
and flexural creases
mucosal lesions are rare and inconsistent, predominantly
affecting the buccal mucosa.
Laboratory studies
1. Tzanck cytodiagnosis
indicates the presence of eosinophils in the blister content
2. Skin biopsy
reveals a cleavage that gives rise to deep blisters, and
abundant eosinophilic inflammatory infiltrate
3. Direct immunofluorescence (DIF) studies
show IgG deposits in a band-like distribution along the
basement membrane
4. Indirect immunofluorescence (IIF) studies
detect the presence of IgG circulating autoantibodies in the
patient's serum that target the skin basement membrane
component, without being correlated with the course of the
disease
higher titers were revealed in patients with multiple mucosal
involvement
5. Immunoprecipitation and immunoblotting
demonstrate that the pemphigoid antigen is a 230kDa protein
that has homologous areas for desmoplakin I (protein
pertaining to hemidesmosomal plaques) in its structure
6. Chromosomal studies
have determined that the genes for the two antigens are
located on the short arm of chromosome 6 and on the long
arm of chromosome 10.
228
Associated diseases:
Bullous pemphigoid has often been associated with malignancy, being
considered a paraneoplastic disorder.
Differential diagnosis includes
pemphigus vulgaris
Duhring - Brocq dermatitis
erythema multiforme
bullous pemphigoid has a favorable evolution and a self-limited, but
prolonged course.
Treatment:
1. general corticosteroid therapy, alone or in combination with
cytostatic drugs such as (azathioprine, cyclophosphamide,
methotrexate);
2. sulfones (dapsone) in combination or not with systemic
corticosteroid therapy
3. antibiotic therapy (erythromycin);
4. the topical treatment includes corticosteroids.
Cicatricial pemphigoid
Cicatricial pemphigoid is a rare, chronic bullous dermatosis
characterized by blistering lesions on the mucous membranes, leading to the
residual scars.
Areas commonly involved are the ocular, nasal, buccal, genital mucosa
and occasionally the skin.
Etiopathogenesis
Cicatricial pemphigoid antigens are:
180 kDa and 230 kDa bullous pemphigoid antigens
160kda, 120kDa antigens and laminin 5
The clinical manifestations are dominated by mucosal involvement. Early
bullous eruptions become erosive, whereas healing leaves vicious scars.
Ocular mucosa
the initial sign is unilateral conjunctivitis, then the lesions
become bilateral.
229
clinically they are vesicles that turn into erosions that heal with
scarring
with persistent disease activity, a mucosal symblepharon affects
the conjunctiva, the eyelids become atrophic, and in the final
stages, the cornea becomes dry and opaque.
Oral mucosa
mucosal erosions affect the jugal (cheek) mucosa, the hard or
soft palate, having a persistent nature
desquamative gingivitis may be the only manifestation of the
disease (gum swelling and bleeding erosions)
healing takes place with adhesion between the oral mucosa and
alveolar processes.
Genital mucosa
vesicles and erosions on the labia heal with scarring or changes
of the vaginal opening or labia.
Pharyngeal and oesophageal mucosa
the lesions are responsible for dysphagia, dysphonia and
strictures.
Cutaneous lesions
are erythematous plaques covered with recurrent blisters, leaving
pigmented scars;
the rash can be generalized as in bullous pemphigoid or located
in the vicinity of the affected mucous membranes.
Laboratory findings
Histopathological examination- reveals the presence of an infiltrate in
the dermis made up of lymphocytes, plasmocytes, eosinophils and fibroblasts as
well as a deep subepidermal blister.
Direct immunofluorescence (DIF)
DIF studies demonstrate the presence of IgG or C3, rarely IgA or IgE
arranged linearly on the basement membrane zone.
Indirect immunofluorescence (IIF)
The presence of circulating anti-basement membrane autoantibodies is
very rarely seen.
230
Differential diagnosis is required to be made with pemphigus vulgaris

and erosive lichen planus.
Treatment
In cases of ocular involvement, ocular instillations or subconjunctival
injections with corticosteroid solutions are recommended and as systemic
treatment, Disulone in doses of 2 mg / kg / day or sulfapyridine 0.5-1 g / day
are recommended. General corticosteroid therapy improves only the cutaneous
lesions.
Mucous synechiae can be solved surgically.
DERMATITIS HERPETIFORMIS (DHRING-BROCQ DISEASE)

It is a chronic dermatosis, with periods of remission, characterized by
polymorphous, itchy and painful rashes, associated with the inability to digest
gluten (gluten intolerance).
Etiopathology:
the disease often affects young adults;
its etiology remains unknown, however, several factors are
suggested:
- genetic factors (familial cases have been described);
- association with HLA-B8, HLA-DR3 antigens (as in celiac
disease)
- gluten-sensitive enteropathy and marked atrophy of the villi of
jejunal mucosa through submucosal lymphoplasmacytic
infiltrates.
Gluten plays a significant role in the pathogenesis of the disease; one of
its components, gliadin, anchors into the dermis and produces lymphocytic
cytotoxicity, activation of the complement and the release of proteolytic
enzymes out of neutrophils.
the eruption has a polymorphic appearance;
the onset is marked by typical symptoms: itching, pain, burning
preceding the lesions by 24 -48 hours;
the lesions are papulovesicular eruptions (small blisters) always
affecting the preexisting lesions (urticarial or erythematous plaques),
grouped in herpetiform vesicles near the edge of the plaques ;
231
the polimorphic nature of lesions results from the sequence of

bullous flares and from the way each lesion progresses;
the vesiculobullous lesions break open, cover themselves with crusts
and heal leaving hyper and hypopigmentated macules.
Sites:
- the eruption occurs on the elbows, knees, trunk, buttocks and more
rarely on the face and scalp;
- in extremely rare cases the mucous membranes could be affected.
In 70-75 % of cases, the cutaneous lesions are associated with
gastrointestinal symptoms, such as enteropathy, which is similar to that of
celiac disease. A rich gluten diet or medicines containing halogens produce
exacerbations of cutaneous lesions.
Laboratory findings are essential and consists of:
1. Tzanck cytodiagnosis - reveals numerous eosinophils in the fluid of
the blister;
2. Histopathological studies show the following:
- subepidermal cleavage through degradation of collagen fibers;
- microabscesses with polynuclear eosinophils at the top of dermal
papilla, known as Pierard microabscesses.
3. Direct immunofluorescence studies - reveal granular IgA deposits
and fractions of the complement (C3) located at the top of dermal
papillae (situation encountered both in skin lesions and healthy-
looking skin);
4. Indirect immunofluorescence studies - demonstrate the presence of
circulating IgA autoantibodies, anti endomysial antibodies or IgG
antireticulin antibodies.
Differential diagnosis: is required because of the polymorphic nature of lesions.
Duhring - Brocq dermatitis should be distinguished from:
- linear IgA dermatitis;
- nummular eczema;
- bullous pemphigoid;
- pemphigus vulgaris;
- erythema multiforme.
Treatment: comprises the administration of:
232
1. sulfones (dapsone, disulon) at a dose of 100-200 mg / day or

sulfapyridine at a dose of 0.5-1.5 g / day ;
2. a gluten-free diet - significantly improves the cutaneous lesions and
those of the small intestine.
PORPHYRIA CUTANEA TARDA

It is an acquired photosensitive metabolic disorder (sporadic) or
inherited (familial), with an autosomal dominant mode of inheritance, caused
by deficient levels of uroporphyrinogen decarboxylase within the liver.
Etiopathogeny
The sporadic clinical form of porphyria cutanea tarda is more frequent
and the familial one seems to affect especially women.
Deficient levels of uroporphyrinogen decarboxylase within the liver can
be developed by alcohol abuse, by the estrogens found in oral contraceptives or
administered as replacements, or prostatic neoplasms, iron intake, halogenated
hydrocarbons or cholesterol lowering agents. Pregnancy can be both a
triggering and aggravating factor.
Other proven precipitating factors are HCV and HIV infections.
Histopathology
The histopathological changes include subepidermal blisters and dermal
inflammatory infiltrate, accompanied by deposition of PAS-positive material in
the vessel walls of the superficial dermis.
Main histopathological lesions include hepatic siderosis, hepatic
steatosis, inflammatory infiltrate, necrosis.
The onset of the sporadic acquired disease commonly occurs in the
third, fourth decade of life, whereas the familial form can occur at any age,
including childhood.
The cutaneous lesions are characterized by blisters (vesicles and bullae)
filled with a clear fluid, commonly seen on the sun-exposed areas (the back
sides of hands, forearms, face, nape). The remission of these lesions, often with
a sero- sanguinous content, leads to atrophic scarring or hyperpigmented
patches and small epidermal bumps (milia).
233
Other cutaneous changes include cutaneous sclerosis due to the

phototoxic effect of porphyrins, that give rise to indurated white or yellowish
plaques, difficult to be distinguished from the lesions of morphea, skin fragility
which fades in colour due to minor trauma, facial hypertrichosis (a more
prominent and exclusive clinical sign occuring in women) obvious on the
cheekbones and temporal regions, whereas sun-exposed areas induce a
senescent appearance (senescent) in patients.
Laboratory Findings
High plasma levels of iron is a characteristic of the disease.
Hyperglycemia is also common.
High plasmatic, urinary and fecal porphyrin levels are due to a
functional deficit in uroporphyrinogen decarboxylase and to a hepatic increase
in -aminolevulinic acid synthase (ALA synthase).
High levels of uroporphyrin and 7 - carboxylate porphyrin levels are
found in urine. Porphobilinogen and - aminolevulinic acid are normal.
Evolution:
Patients with porphyria cutanea tarda are prone to develop
hepatocellular carcinomas or lymphomas.
Porphyria-like cutaneous changes may be observed in other hepatic
disorders (liver tumors), in discoid lupus erythematosus and systemically, in
patients with hemodialysis for end-stage chronic renal failure.
Porphyria cutanea tarda must be distinguished from:
- epidermolysis bullosa acquisita;
- summer prurigo;
- photoinduced drug reactions;
- pemphigus vulgaris;
- cicatricial pemphigoid.
Treatment
The goals of therapy:
- exclusion of the precipitating factors (alcohol consumption,
estrogen medications or iron- containing preparations,
cholesterol lowering agents);
- topical photoprotection (creams with high protection factors) ;
234
- phlebotomy in order to bring serum iron values back to normal

(500ml blood every 2 weeks, until the hemoglobin level goes
below 12g/dl); synthetic antimalarial drugs (chloroquine or
hydroxychloroquine) can be used instead of venesection because
combined with porphyrin, they form soluble complexes which
are excreted through urine
- iron-chelating agents (Desferrioxamine) ;
- plasmapheresis.
MAJOR COLLAGENOSES
LUPUS ERYTHEMATOSUS (LE)
Lupus erythematosus is a major collagenosis, triggered by autoimmune

mechanisms which affect the skin and sometimes the internal organs.
The condition occurs in females (in 80 - 90 % of cases), suggesting the
fact that the estrogens play an important role in the pathogenesis of the disease.
Etiopathogenesis: like in most autoimmune diseases, there is favorable
genetic predisposition to develop lupus. Recent studies show an increased
incidence of LE in subjects of group HLA, class I (B8) and Class II (DRW3,
DRW2; various forms of disease have been described in monozygotic twins or
familial cases of LE.
The exact etiology remains unknown, whereas environmental and
immunological factors play a part in the pathophysiological mechanism.
Immunological factors:
LE is a complex syndrome of autoaggression, leading to
immunological reactions;
immunologically, suppressor T lymphocytes and T lymphocytes are
disturbed and produce an excess of antibodies and immune
complexes. Antibodies play a crucial role in the pathogenesis of this
disease by their direct action (cytotoxic effect) and by immune
complexes deposition in the skin, vessels and internal organs. They
are directed particularly against intracellular antigens :
- antinuclear autoantibodies (anti - double-stranded DNA,
anti-single-stranded DNA, antibodies against
235
desoxyribonucleoproteinic antigens or against RNP and

AGSM soluble nuclear antigens);
- antiplasmatic autoantibodies: anti Ro / SSA (anti acid
glycoproteins), anti La / SSB (anti RNP protein complex).
All these antibodies are responsible for the emergence and self-
maintenance of LE lesions.
The immune complexes are made up of antibodies of the IgG class, or
IgM and complement fractions (C1q, C3b or C3d).
Environmental factors
A variety of environmental factors trigger the onset of the disease. The
most important ones include: natural ultraviolet radiations, viral infections,
microbial infections, drugs (penicillin, contraceptives, streptomycin), trauma.
Classification of lupus erythematosus
Based on clinical, immunological, histological and evolutionary
considerations, LE can be divided into:
1. Chronic cutaneous LE;
2. Subacute LE;
3. Acute LE.
Chronic cutaneous lupus erythematosus

represents the most frequent clinical form and has a chronic
course ;
lesions are located on the sun-exposed areas : face, neck, scalp,
ears, the dorsal side of hands.
The classic presentation is a triad of erythema, scales, atrophic scarring.
The erythema - is arranged in raised, infiltrated plaques and patches,
well defined, of purpuric appearance.
The scale - is thick, very sticky, and when it detaches itself, some
hyperkeratotic extensions can be seen on the undersurface, penetrating the
epidermis through dilated follicular ostia (resulting a cats tongue
appearance).
The atrophia - occurs late, has a leucodermal or hyperpigmented
appearance, and it associates telangiectasia at the periphery.
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Subjective symptoms are discrete (itching) or absent.

Special clinical forms of chronic LE:
Depending on the topography and the appearance of the lesions, the
following clinical forms are described:
a) centrifugal LE (Bietti s erythema centrifugum)
- characterized by plaques and patches with symmetrical
distribution in the center of the face, namely across the bridge of
the nose and cheeks, appearance known as " Vespertilio "
(butterfly rash)
- lesions are predominantly erythematous, slightly infiltrated, with
less defined edges ;
- the scales are thin and adherent whereas the atrophy may be
absent.
b) discoid LE (fixed)
- made up of well-defined plaques and patches covered by scales,
they may lead to cicatricial atrophy;
- when the lesions are localized in close proximity to the cephalic
edge we talk about localized lupus, and when the lesions extend
to the thorax (cleavage area) and extremities, we talk about
disseminated LE.
Mucosal involvement occurs in 25-30% of subjects.
Oral mucosa - the lesions may be different:
- oral leukoplakic plaques;
- erosions;
- superficial ulcerations;
- erythematous plaques with a depressed center.
The tongue - presents:
- erythema;
- fissuring;
- papillary atrophy.
The lips
- are covered by fine scales, cracks and diffuse erythema;
Ocular lesions are rare and consist of:
- intense congestion of the conjunctiva;
- erythema at the eyelids margins.
237
Systemic involment are not common in chronic lupus erythematosus;

about 20 to 30 % of people developed subacute lupus erythematosus and just
1% of patients developed systemic lupus erythematosus.
Other clinical aspects of chronic LE include:
Hypertrophic verrucous LE:
it frequently affects the temporal regions, the nasal pyramid, the
ears, scalp;
it is characterized by warty hypertrophic lesions and
erythematous raised edges;
it occasionally associates with nail involvement such as:
onycholysis, cupuliform depressions or subungual hypertrophy.
LE tumidus
it usually occurs asymmetrically;
it is characterized by congestive erythematous infiltrated plaques
that heal without scarring ;
Lupus profundus Kaposi - Irgang (lupus panniculitis)
the most common affected areas are the cheeks and the deltoid
region;
clinically characterized by infiltrates and inflammation of the fat
underlying skin, resulting in nodules whose resorption cause
depressed scars.
Telangiectasic LE
the lesions are located on the face, neck, ears, the dorsal side of
the hands;
clinically characterized by persistent telangiectases;
healing leaves long-lasting atrophic scars.
Chilblain lupus
the lesions occur on the acral parts (fingers, knees, elbows,
ankles, nose, ears);
clinical features - infiltrative violaceous plaques resembling
frostbites are present on the skin, along with typical lupus
lesions.
Laboratory Studies
in chronic LE, most bioumoral markers are within normal limits;
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in disseminated LE, the following can be detected: anemia,

leukopenia, thrombocytopenia, hypergammaglobulinemia,
lupous cells, false-positive reactions for syphilis (Wassermann
reaction) and occasionally antinuclear antibodies (Ac anti single
-stranded DNA, anti double stranded DNA), suggesting the
evolution towards the systemic form of disease.
Histopathological examination reveals the following aspects:
hyperkeratosis and keratin plugs in the follicular ostia;
focal parakeratosis;
atrophy of the epidermis;
hydropic degeneration of the basal epidermal cells;
degenerative changes of the connective tissue (fibrinoid
degeneration in the superficial dermis and hyalinization);
inflammatory infiltrate of lymphocytes, histiocytes and
polynuclear that surrounds the skin appendages.
Immunohistopatology
IFD examination highlights the lupous band at the dermo - epidermal
junction, made up of IgG, MA and C1 and C3 complement fractions.
The cutaneous lesions should be differentiated from:
polymorphic light eruptions
rosacea
seborrheic eczema
tinea faciei.
The lesions of the oral mucosa should be distinguished from:
actinic cheilitis
oral candidiasis
lichen planus
leukoplakia.
Chronic LE is a predominantly relapsing condition. Recurrences are
induced by environmental factors (UV radiation, trauma) and stress.
The aesthetic prognosis is reserved as healing leaves atrophic scars.
Epidermoid carcinomas may occasionally arise from the skin lesions.
239
Treatment
The local treatment is often able to control the course of the disease and
is recommended for superficial forms of lupus, with just a few lesions. The
following preparations can be used:
- moderate topical corticosteroids (in the form of creams,
ointments or intralesional injections);
- cryotherapy or laser therapy for resistant forms of lupus;
- the use of sunscreens is recommended for highly
photosensitive people.
The general treatment consists of the administration of:
- synthetic antimalarials (chloroquine, hydroxychloroquine);
- low doses of systemic corticosteroids are recommended for
forms that respond to treatment with antimalarials;
- retinoids are recommended for hypertrophic forms or for
those that do not respond to conventional and local therapy;
- dapsone, clofamizine, beta - carotene, thalidomide are
considered backup variants.
Subacute cutaneous lupus erythematosus (SCLE)

Subacute cutaneous lupus erythematosus is a distinctive clinical form,
characterized by papulo-squamous lesions, annular or polycyclic, disseminated
on the trunk, face, neck and extensor arms.
Etiopathogenesis
the subacute form of lupus is often associated with HLAB8 -
and HLA- DR2 HLADR3 antigens.
the polycyclic /annular nature of the papular erythematous scaly
and erythemato -squamous lesions is the main clinical sign of
SCLE;
SCLE lesions have a multicentric ditribution and affect the face,
the neck, the upper third of the chest;
the evolution demonstrates no sign of atrophy, but they heal with
hypopigmentation and telangiectasis;
240
it sometimes associates with mucosal involvement (oral ulcers,

lip erythema), livedo reticularis, and periungual telangiectasis
noncicatricial alopecia.
Systemic invlovements are rare, but possible and consist of fever,
arthritis, nephropathies.
Laboratory findings
The immunological picture of subacute cutaneous lupus erythematosus
is characterized by the presence of the following types of antibodies:
antinuclear antibodies (50 % of cases)
anticytoplasmic antibodies (anti-Ro (SS-A) and antiLa (SS-B).
Histopathological findings:
Particular histopathological findings of subacute forms of lupus include:
- moderate hyperkeratosis;
- basal hydropic degeneration (without colloid bodies);
- inflammatory infiltrate superficially distributed.
Immunohistopathological tests
IFD tests highlight the lupus band at the dermoepidermal junction.
Evolution and prognosis subacute cutaneous lupus erythematosus runs a
chronic course, but the prognosis is generally favorable.
- LE chronic
- psoriasiform eczematids
- tinea capitis
- psoriasis.
Treatment the following are recommended:
- synthetic antimalarials (hydroxychloroquine 200-400 mg / day)
- corticosteroids per os
- sulfonate or retinoids
- sunscreens.
Systemic lupus erythematosus (SLE)
SLE is a multisystemic autoimmune disease that commonly affects
females.
241
Etiopathogenesis: is complex, whereas the development of cutaneous

and systemic lesions is linked to multiple factors, including genetic,
immunological and environmental factors.
Clinical manifestations the onset of the disease is marked by general
symptoms : fever, fatigue, weight loss, joint pain, myalgia.
The cutaneous lesions are classified into:
typical skin lesions are represented by diffuse erythematous infiltrated
plaques, covered with fine scales, distributed in the middle of the face
(butterfly/ malar rash) or on more or less sun-exposed areas.
atypical cutaneous lesions include:
- hive-like eruptions (hive-like vasculitis)
- purpuric lesions
- telangiectasic reticulated erythema, affecting the thenar and
hypothenar eminences
- livedo reticularis with or without superficial ulcerations
- vesiculobullous lesions (after prolonged exposure to UV
radiations)
- petechiae, erosions and ulcerations of the hard and soft palate
- nail dystrophy
- diffuse and noncicatricial alopecia.
Joint injuries include:
- arthralgia, morning stiffness in the joints of the hand, fist,
elbows, knees.
Cardiovascular lesions
- the most common manifestation is fibrinous pericarditis;
- other manifestations include: hypertension, arrhythmias,
atrioventricular conduction disorders and sometimes heart
attack.
Renal impairment
- in SLE, the renal impairment occurs early and has a significant
prognostic value correlated with the titer of antinuclear
antibodies ;
- the renal manifestations sometimes dominate the clinical picture
and can be exemplified by acute glomerulonephritis, lupus
nephritis, nephrotic syndrome or renal failure.
242
Pulmonary lesions include cough, hemoptysis or dyspnea.

Gastrointestinal injuries - Gastrointestinal manifestations consist
in vomiting, heartburn, diarrhea, ulcerative colitis,
hepatomegaly, chronic lupoid hepatitis.
Nervous system damage
- 50 % of patients with SLE present nervous system damage -
the lesions are vascular and are manifested by headaches,
seizures, chorea, sensory -motor neuropathy
- the psychiatric disorders consist of memory disorders,
depression, emotional lability
Ocular lesions are represented by conjunctival hemorrhages,
lacrimal hyposecretion, scleritis, episcleritis, uveitis, retinal
hemorrhage. Lupus retinopathy is a marker of poor prognosis for
survival.
Laboratory findings:
the diagnosis of SLE is based on thorough haematological,
biochemical, immunological and histopathological tests.
Blood tests reveal anemia, leucopenia, thrombocytopenia, high ESR
levels.
Biochemical tests show hyperglobulinemia with reversed serine /
globulin ratio, hypoalbuminemia, changes in the serum creatinine and its
clearance rate.
Immunological tests reveal the presence and titer of the autoantibodies
responsible for lesions of SLE.
1. antinuclear and anticitopalsmic antibodies (Ab)
- anti double stranded DNA antibodies of IgG or IgM classes
(typical for SLE with renal impairment)
- anti Sm antibodies, present only in SLE
- anti single-stranded DNA antibodies
- anti DNA / histone antibodies
- antiRo antibodies (distinctiveness for SLE up to 80 %).
2. other autoantibodies that play a significant role in the diagnosis and
prognosis of the disease are the following:
- antiphospholipid antibodies (IgG immunoglobulins)
- rheumatoid factor
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- anti-erythrocyte, antilymphocyte, anti - granulocyte, anti -

platelet, anticollagen VI antibodies.
Other significant changes include:
- the reduction of the total serum complement and of the C1 and
C3 fractions
- the increase of circulating immune complexes
Histopathological findings suggestive changes for the diagnosis of SLE
include:
- hyperkeratosis with orthokeratosis
- epidermal atrophy with vacuolization of the basal layer
- dermal lymphocytic infiltrate with edema and dilated capillaries
- degenerative alterations of dermal collagen fibers.
IFD reveals granular deposits of IgG and C, located at the dermo -
epidermal junction.
The positive diagnosis is based upon the clinical picture, the
immunological and histopathological changes, namely the presence of 4-5
criteria of the 11 set by ARA (American Rheumatism Association).
the cutaneous lesions of SLE could be confused with:
- polymorphic light eruption
- dermatomyositis
- rosacea
- erythema multiforme
- hives.
The treatment is adjusted according to the extent of the lesions and the
severity of the systemic involvement.
General treatment: The following are recommended:
1. corticosteroids (Prednisone 0.5-1.5 mg / kg / day)
2. synthetic antimalarials (in moderate systemic involvement)
3. cytostatics (in severe forms of vasculitis).
Other beneficial therapeutic options are: globulin, extracorporeal
photochemotherapy, interferon -2.
Topical treatment consists in the administration of:
- corticosteroid drugs in the form of creams, lotions
- sunscreens
244
- chemical peels (to remove residual pigmentation)

Symptomatic treatment consists in:
- correction of anemia
- diuretics with hypotensive efficacy
- maintenance of cardiac and renal functions
- controlling the side effects of prolonged corticosteroid therapy.
Prophylactic treatment:
- hygienic-dietary regimen correlated with standard medication
- photoprotection by wearing adequate clothing and avoidance of
exposure to solar radiation
- a balanced lifestyle.
SCLERODERMAS
Sclerodermas are connective tissue disorders, of unknown etiology, as a
result of some autoimmune mechanisms.
Clinicaly they are characterized by fibrosis of the dermis and atrophy of
the epidermis, with or without visceral involvement.
According to clinical, immunological and histopathological criteria,
sclerodermas are classified as follows:
1. Systemic scleroderma (generalized or progressive);
2. Circumscribed localized scleroderma (morphea).
Systemic scleroderma (generalized systemic scleroderma)
Systemic scleroderma is a multisystem disorder that results in sclerosis
and atrophy of the connective tissue, muscular abnormalities and
immunological alterations.
Etiopathogenesis: the etiology of this condition is obscure. However,
the fact is that the development of this condition is linked to a genetic factor.
Scleroderma associates with HLA-B8 and HLA9 groups frequently, and the
genotype susceptible to the disease is characterized by a dominant allele,
located on chromosome X.
On this highly "sclerodermiform" background, the lesions may develop
as a result of a microangiopathy, an immunological disorder or an imbalance
between the synthesis and degradation of collagen.
The primary lesions occur in the small blood vessels of skin, triggering
a chain of reactions targeting the endothelial cell.
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The factors able to produce vascular lesions include: microbial, viral

infections, toxic factors or trauma.
Thus, alterations may occur in the blood vessels: local ischemia,
vascular occlusion, vascular thrombosis and accumulation of cells belonging to
the immune system. Simultaneously, there is a secretion of clinical mediators
such as interleukins, the tumor necrosis factor (TNF- alpha), the platelet-
derived growth factor (PDGF), which are responsible for endothelial lesions.
Another theory that explains the etiopathogenic mechanisms of
scleroderma brings into focus the importance of the cellular oxidative stress.
The action of the free radicals on the vascular endothelium is proven by
a catalase reduction (substance that protects the endothelium from free radicals)
and an increase of the urinary excretion of arachidonic acid peroxidation
products (F2 - isoprostanes).
The excessive synthesis of collagen by fibroblasts will result in
sclerosis or fibrosis. The fact that the fibroblasts are hyperactive, combined with
a collagenase deficiency, causes an accumulation of fibrinogen, responsible for
tissue fibrosis.
Clinical manifestations three major clinical aspects of systemic
scleroderma are described:
a) acrosclerosis;
b) diffuse scleroderma;
c) CREST syndrome.
Acrosclerosis (the acral form)
This type of disease is slowly progressive, the lesions usually involve
the extremities, whereas visceral involvement occurs late in the disease.
Diffuse scleroderma
it progresses faster and the systemic involvement appears early ;
it often starts in the cephalic extremity, where it expands
centripetally.
CREST Syndrome (Calcinosis cutis, Raynaud phenomenom, Esophageal
dysmotility, Sclerodactyly, Telangiectasia). Raynaud's syndrome, cutaneous
calcinosis, esophageal dysmotility, sclerodactyly and telangiectasia are all
assigned to the same subjects.
All three clinical forms of scleroderma combine cutaneous and visceral
lesions.
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Cutaneous manifestations:
the onset is insidious in the upper extremities, with vasospastic
and skin colour changes, known as Raynaud's syndrome;
these vascular phenomena are accompanied by interphalangeal
and joint numbness and swelling of the fingers;
during the course of the disease, the fingers become thinner at
the distal extremity, the skin becomes shiny and tightly bound to
the underlying structures, the interphalangeal joints become
semiflexible and the nails undergo dystrophic changes
(sclerodactyly-like appearance);
at the base of the fingers there are necrotic ulcerative lesions that
heal leaving stellate scars;
other possible changes include:
- whitlow and paronychia which are resistant to treatment, due
to vascular disorders;
- thenar and hypothenar erythema;
- calcification of the fingers.
the lesions on the hand may advance to forearm and arm;
the lower extremities of the feet may also be affected, but the
lesions are less severe;
some changes in the cephalic extremity, especially on the face,
may occur at the same time with the lesions on the hands;
the typical appearance is that of a "Byzantine icon";
sclerosis and atrophy of the skin make the skin appear rough,
shiny, smooth and tightly bound to the underlying structures;
the wrinkles are erased, the nose becomes thinner, the lips retract
partially revealing the dental arch, microstomia with radial
furrowing, reduced facial expression;
the lower eyelids retract, enabling erosion and ulceration of the
cornea, whereas tear secretion is highly diminished.
Sometimes sclerosis extends to the entire skin, taking an armor-like
appearance, characterized by thickened dry skin, cardboad-like, because of the
sweat glands atrophy.
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Other skin changes:

cutaneous or subcutaneous calcinosis;
telangiectasia;
pigmentation disorders.
Systemic manifestations: systemic involvement only worsens the
prognosis.
Gastrointestinal lesions
Digestive involvement affects in varying degrees all the segments of the
digestive tract.
oropharyngeal lesions
- reduction of the salivary secretion;
- alveolar parodontosis involving the alveolar ligaments;
- dysarthria, dysphornia.
esophageal lesions
- occur in 50-80 % of cases;
- clinical manifestations:
- dysphagia;
- heartburn;
- burns
- gastroesophageal reflux (esophageal manometry shows a
decrease or even the disappearance of 2/3 of the lower
oesophageal pressure, corresponding to the smooth
muscle layers, with the disappearance of peristalsis and
hypotonia of the lower esophageal sphincter)
gastric lesions: the stomach is less affected during scleroderma (70-
75 % of cases);
the clinical signs are not specific and consist of:
- nausea, vomiting, epigastric pain or dyspepsia;
- rarely, gastrointestinal bleeding as a result of ulcers or vascular
ectasia.
lesions of the small intestine
- there are two clinical forms of small intestine enteropathy:
a) an occlusive form
b) a form associated with functional disorders (malabsorption
syndrome).
248
Clinical manifestations include abdominal cramps, bloating, constipation

alternating with diarrhea, fast weight loss and plurideficiency syndrome.
anorectal lesions
- the anorectal involvement is little known;
- clinical symptoms may refer to transit disorders, fecal
incontinence or rectal prolapse.
pleuro -pulmonary lesions
- clinical manifestations may include: exertional dyspnea and / or
dyspnea developed when resting, as a result of a ventilatory
dysfunction or pulmonary fibrosis (as demonstrated
radiologically by diffuse reticular pulmonary depiction);
- in time, chronic respiratory failure may set in.
cardiovascular damage include:
- scleroderma myocarditis
- mitral valve prolapse
- rhythm disorders (paroxysmal atrial tachycardia, fibrillation).
renal impairment: sclerodermal renal crisis is a serious complication,
affecting the prognosis in a negative way.
bone lesions:
- resorption of terminal phalanges of the fingers;
- temporomandibular arthropathy;
- osteolytic lesions of the long bones (radius, humerus).
Laboratory findings
Haematological, biochemical and immunological changes take place in
systemic scleroderma.
They include:
- anemia (forms of major gastrointestinal involvement);
- increased level of ESR ; - increased globulins levels; -
increased levels of CIC;
- presence of antinuclear antibodies revealing homogeneous or
fluorescence patterns of staining;
- anti-ribonucleoprotein antibody (RNP-Ab);
- anti-Scl -70 anti-topoisomerase 1- obvious in systemic
scleroderma with pulmonary involvement;
- anti-centromere-Ab (typical in CREST syndrome);
249
- anti-collagen Ab;
- anti- endothelial cell Ab;
- anti-histone Ab (found in scleroderma associated with
cardiovascular lesions);
Other useful investigations include:
- periungual capillaroscopy (shows a decreasing number of
capillary or megacapillary loops);
- digital plethysmography (absence of pulse waves);
- radiological studies in order to detect visceral involvement.
Histopathological findings
Skin biopsy reveals different aspects depending on the stage of the
lesions.
In the initial stages, the lesions are represented by:
edema and dermal and hypodermic perivascular infiltrates;
moderate collagen proliferation.
Older lesions are characterized by:
clusters of thick collagen bundles, oriented in different
directions;
a notably reduction of vascularity within the dermis;
the disappearance of the hair follicles, sebaceous and sweat
glands;
epidermal atrophy.
The positive diagnosis is confirmed by the following changes required
by ARA criteria:
1. cutaneous sclerosis involving the extremities (limbs, face, or throat)
and the trunk;
2. combination of two of the following changes
- sclerodactyly;
- stellate scars on the pulp of the fingers;
- bilateral basal pulmonary fibrosis.
Differential Diagnosis is done with other collagen or scleroderma -like
conditions as follows:
- morphea;
- dermatomyositis;
- scleromyxedema.
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Systemic treatment promotes the administration of:

- corticosteroids (prednisone 10-40mg/day)
- cytostatics (azathioprine, cyclophosphamide) for acute forms;
- anti-fibrotic drugs (D- penicillinamine, colchicine, piascledine,
vitamin E), progesterone;
- peripheral vasodilators (nifedipine, Xantinol nicotinate)
- antihypertensives (angiotensin-converting-enzyme inhibitors);
- antibiotic therapy.
Topical treatment may promote the use of drugs as follows: vasodilatory
drugs, anti-inflammatory corticosteroids (topical applications or intralesional
injections), physical therapy (ultrasonic therapy, hyaluronidase ionizations).
Morphea (localized sclerodermas)
Localized sclerodermas are usually benign skin conditions,
characterized by a localized sclerosis of the skin.
Etiopathogenesis:
the cause of morphea is unknown, although many factors have
been presumed to cause this disease;
a large number of clinical, histological and immunological
considerations suggest that both morphea and systemic
scleroderma have the same etiopathogenesis;
the following factors are considered important in triggering the
progression of the disease:
- trauma;
- viral and bacterial infections;
- BCG vaccination;
- radiotherapy;
- endocrine disorders;
- some drugs.
Depending on their clinical presentation, the following types of morphea
are described:
A. localized morphea:
circumscribed morphea with plaque-type lesions
linear " band -like" morphea
guttate morphea
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B. Generalized morphea
Circumscribed morphea with plaque-type lesions (morphea en

plaque/plaque morphea)
refers to the appearance of round - oval plaques and patches,
single or multiple, erythematous-edematous, which extend
peripherally ;
the skin near the plaque then becomes rough, infiltrative,
sclerosal, yellowish or waxy white, tightly bound to the
underlying structures, having only a purple peripheral halo
called " lilac ring".
Thus, the old plaques prove all three stages of evolution:
1. erythematous - edematous stage (manifested by the
erythematous ring at the periphery);
2. stage of sclerodermiform thickening (the middle area of white
waxy rough infiltrative skin);
3. Stage of atrophy (visible in the central area; the skin is thin,
transparent, hypo or hyperpigmentated, with calcification and
hypoesthesia)
the lesions are commonly located on the trunk and their size
ranges from 2 to 20 mm.
The lesions run a chronic course, towards spontaneous involution with
atrophy or hyperpigmentation. Plaque morphea rarely has a severe evolution,
with tendency to generalization, as in the systemic form.
Band-like or linear scleroderma
has the same clinical features as plaque scleroderma, but it has a
well defined band-like distribution and it is surrounded by a
purple border;
the linear bands of sclerotic skin usually affect the limbs
(regional scleroderma) or annular (ring-shaped scleroderma);
"en coup de sabre" (deep sabre wound) is a distinctive form of
scleroderma; it appears as an indented vertical line of skin on the
forehead.
The sclerotic band is atrophic and depressed, it affects the hemifacies
causing facial asymmetry and hemilateral lingual atrophy.
252
Retractile scars and facial hemiatrophy develop during the course of the
disease.
Guttate morphea (guttate / drop-shaped scleroderma)
The clinical features include a large number of lesions, which are small
(3-5 mm) round - oval, depressed, white, located on the torso.
The lesions tend to coalesce and become atrophic.
Laboratory findings
laboratory changes are less specific and inconsistent
can reveal antinuclear antibodies (anti - single-stranded DNA
Ab), anti - histone Ab and increased levels of procollagen type I
The antinuclear antibodies and eosinophils are markers of the disease
activity, whereas anti KV antibodies are markers of its progression.
1. polyarteritis nodosa;
2. panniculitis nodosa;
3. sclerodermiform hypodermitis;
4. plaque parapsoriasis;
5. keloidal scars.
Treatment:
a) general treatment promotes the administration of vasodilators,
anti-fibrotic drugs and corticosteroids
b) the following are recommended in the topical treatment:
- local vasoactive massages;
- physical therapy (ionization, ultrasound);
- infiltrations with cortisone preparations.
Generalized morphea
It is a rare disease, with an insidious onset, frequently affecting adult
females.
the lesions are represented by indurated ivory plaques and
patches, with a large purple halo, commonly affecting the
abdomen and the trunk ;
the plaques and patches coalesce, new lesions occur and the
entire skin may be affected;
253
extensive injuries can affect the face, neck, the scalp and the
extremities of the limbs;
may be associated with arthralgia, muscle contractures of the
limbs, or intercostal muscles, which impairs the movement of
thorax.
the evolution is chronic, it may last for years, sometimes
following a partially remitting course ;
in advanced stages the prognosis can be serious, leading to death
by respiratory failure.
Generalized morphea should be distinguished from:
1. Systemic scleroderma;
2. Sclerodermiform states;
3. eosinophilic fasciitis.
Treatment
There is no specific treatment, however for cutaneous symptom relief
the following can be administered:
- vasodilators;
- anti-fibrotic drugs;
- corticosteroids.
DERMATOMYOSITIS
Dermatomyositis is a major inflammatory muscle disease (such as

myositis) associated with cutaneous and visceral lesions. The disease is rare, it
affects children and adults and is associated with HLA - B8 histocompatibility
antigens.
Etiopathogenesis:
the etiology of this condition remains unknown;
dermatomyositis is an autoimmune disease, as demonstrated by
the presence of specific antibodies anti-myosin, anti-
myoglobin or antinuclear antibodies (antiPM 1 Ab; antiPA 1
Ab), which are linked to scleroderma and polymyositis.
254
involvement of cell-mediated immunity is demonstrated by the

presence of lymphocytic infiltration of T lymphocytes in the
fibers of the muscle;
the autoimmune process affects the blood vessels, the muscle
fibers, resulting in edema, dystrophy and degeneration of the
muscle fibers;
other factors involved in the onset of disease are infections,
drugs (penicillin, tamoxifen), sun exposure.
Classification
Two main clinical forms are described:
Wagner- Unvericht acute dermatomyositis
Petges - Clejat chronic dermatomyositis
Acute dermatomyositis
acute onset with fever, chills, muscle weakness, weight loss,
joint pain;
two major events dominate the course of the disease:
- muscle syndrome
- cutaneous Syndrome
The muscular syndrome is characterized by:
myalgia: affects the muscles of the shoulder girdle, of the pelvis
and calves ;
muscle weakness - marked fatigue;
muscle atrophy - occurs in the late stages of the disease, in
chronic forms and it manifests as myofibrosis and tendon
retraction. Other groups of muscles involved: the muscles of the
pharynx, of the diaphragm, the flexors of the neck and the
vertebral groove (their involvement triggers an unfavorable
prognosis)
Cutaneous Syndrome:
may be the first manifestation of the disease in 25 % of cases;
characteristic cutaneous lesions include:
255
- periorbital heliotrope erythema and edema, in a pair of

glasses distribution, with marked edema on the lower eyelid
known as the" swallow 's nest";
- purple maculo- papulosquamous rash, in a band-like
distribution on the limbs;
- (elbows, knees and the dorsal side of the hands) Gottrons
sign;
- erythema and telangiectasia on the proximal nail fold;
- exfoliative dermatitis on the palms and fingers;
- poikiloderma-like appearance (erythema, hyper- and
hypopigmentation, atrophy) on the abdomen and thorax.
other skin lesions include: livedo reticularis, bullae, lumps,
ulcerations, dermal calcinosis.
mucous membranes are affected in 20 % of cases, and they
manifest as erythemas, telangiectasia, thrush-like rashes,
leukoplasia.
Systemic manifestations
1. cardiovascular lesions such as acute myocarditis, arrhythmia or
heart failure ;
2. pulmonary lesions - manifested as aspiration pneumonia,
ventilatory dysfunctions and / or respiratory failure;
3. digestive lesions - caused by impairement of the muscles of the
digestive tract, mainly the esophagus muscles, manifested as
dysphagia and gastroesophageal reflux.
Chronic dermatomyositis
the predominant manifestations are those characteristic of the
cutaneous syndrome ;
polymorphic and poikiloderma-like lesions: erythema,
telangiectasia, hypo - and hyperpigmentation, atrophy, cutaneous
calcinosis (deep indurated plaques, located subcutaneously or
intramuscularly, versatile in their evolution towards ulceration);
the muscular syndrome is discreet, but after many years, the
occurrence of atrophy and significant muscle retractions is
inevitable.
256
Distinctive clinical forms

In terms of clinical course the following forms are described:
1. primary idiopathic dermatomyositis ;
2. paraneoplastic dermatomyositis or polymyositis;
3. pseudorheumatoid dermatomyositis;
4. primary idiopathic polymyositis;
5. dermatomyositis of the child (juvenile dermatomyositis);
6. drug-induced dermatomyositis.
Laboratory findings
Three elements have to be taken into consideration when performing
laboratory studies on dermatomyositis:
1. levels of certain muscle enzymes;
2. electromyography;
3. histopathological examination of the muscles involved.
The level of certain muscle enzymes shows a cytolysis of the muscles,
manifested through:
high levels of CK, LDH enzymes;
elevated levels of aldolases and TGO, TGP;
creatinuria over 1g/day;
myoglobinuria.
Electromyography (EMG) showed an inflammatory myopathy resulting
from a reduction of the amplitude waves, a diminished duration of the motor
unit potential and spontaneous fibrillations.
Histopathological examination
Skin biopsy shows the following changes:
a) in the acute phase
- atrophic epidermis ;
- focal basal hydropic degeneration;
- edema and inflammatory infiltrate in the superficial dermis.
b) in the late phase:
- fibrosis, sclerosis and calcium deposits in the subcutaneous
tissue ;
- degenerative lesions resulting in the disappearance of the cross
striations of the muscle fibers;
257
- sarcoplasmic degeneration (hyalinisation);

- pericellular lymphohistiocytic infiltrate.
Other useful laboratory tests for diagnosis include:
- identification of anti-nuclear, anti cytoplasmic, anti JO-1, anti
M, anti - K'v, anti - Sm, anti muscle, anti-myosin antibodies.
- increased level of IgG, M, A immunoglobulins;
- increased level of serum myoglobin;
- high ESR;
- leukocytosis.
Positive diagnosis
Diagnosis criteria according to Bohan and Peter:
1. progressive symmetrical muscle weakness of proximal type;
2. increased levels of muscle enzymes (CPK, LDH);
3. changes in EMG;
4. histopathological changes in muscle fiber;
5. typical skin lesions.
other collagenoses (lupus erythematosus, scleroderma,
periarteritis nodosa);
endocrine myopathies (hypothyroidism, Cushing's syndrome,
Addison disease);
neuromuscular disorders;
infectious myopathies.
The prognosis for dermatomyositis is usually reserved. The disorder
may have a fulminant course, leading to death or may have a chronic course,
with variable periods of calm. Systemic involvement indicates the fact that the
disease is severe.
Treatment
a) systemic
corticosteroids (prednisone 1-2mg/kg/day);
immunosuppressants (methotrexate and azathioprine);
immunoglobulins (intravenously);
synthetic antimalarials (200-400mg/day hydroxychloroquine);
258
unsaturated fatty acids (Piascledin);

anabolics.
b) local
low potency topical corticosteroids;
UVA and UVB sunscreen;
physical therapy, balneotherapy, medical gymnastics.
c) hygienic-dietary
bed rest;
a diet rich in proteins.
SJGREN GOUGEROTS SYNDROME

it is an autoimmune disease characterized by an inflammatory
immunological process that involves salivary and tear glands;
the disease occurs more frequently in female adults and is linked
to the histocompatibility HLA - B8D3DRW2 antigens.
Etiopathogenesis
the disease is triggered by various factors: genetic, hormonal,
immunological and infectious;
the hyperactivity of B and T lymphocytes has a determining role,
which on the one hand will lead to a lymphocytic infiltrate in the
salivary and tear gland, and on the other hand, to the appearance
of autoantibodies directed against nuclear and cytoplasmic
antigens.
dryness of the skin and mucous membranes is the main feature
of the disease;
the amount of salivary secretion is diminished, causing erosion
and fissuring of the tongue, oral mucosa and lips (xerostomia) ;
conjunctival mucosal involvement (xerophthalmia) results in tear
hyposecretion, photosensitivity, corneal erosions and
ulcerations;
other mucous membranes may be affected:
- vulvovaginal mucosa (erosions, pruritus and dyspareunia)
- nasal mucosa (xerorhinia).
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the cutaneous lesions are characterized by dry skin (xeroderma),

pruritus, furfuraceous desquamation, purpuric rashes and
eczematization.
Other parts involved: mucocutaneous lesions may also affect the joints,
the liver, the spleen or the lymph nodes.
Positive diagnosis is supported by
1. clinical manifestations (xerostomia, xerophthalmia, parotid
enlargement);
2. histological findings: the presence of a lymphoplasmacytic
infiltration of exocrine gland fibrosis, ductal cell proliferation,
decrease of the body fat ;
3. laboratory data reveal the presence of IgM paraproteins
antinuclear antibodies (anti -SSA and anti- SSB).
Sjgren's syndrome should be differentiated from:
- rheumatoid arthritis;
- malignant lymphomas.
The treatment is directed at improving mucosal xerosis:
1-2% pilocarpine ocular instillations;
artificial tears;
rigorous hygiene of natural cavities;
corticosteroids or synthetic antimalarials.
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ACNE VULGARIS
It is a chronic inflammatory dermatosis involving the pilosebaceous

segment, characterized clinically by polymorphic lesions.
Natural evolution
The disease commonly begins during adolescence and resolves within
the third decade of life. The disease sets in earlier in females and it seems to be
more frequent in males at puberty. The peak of incidence and severity is
between 14 to 17 years for girls and 16-19 for boys.
There may be a late onset (25 years) and the persistence of acne lesions
at the age of 30-40 years.
Etiopathogenesis
Etiopathogenic factors have been and continue to be studied, some of
them are still up for debate.
However, the following implications have been proven:
the genetic predisposing factor;
the hyperfunctional status of the sebaceous gland causing an
increase of sebum production (the activity of the sebaceous
gland is regulated as a result of the interaction between male sex
hormones and active androgen receptors found in the
secretionary cells within the epithelium of the sebaceous gland);
increased susceptibility of the peripheral receptors to androgens
(increased activity of 5 reductase or intracellular receptors);
increased plasma levels of androgens due to their serum globulin
transport deficit (SHB - G);
bacterial flora that colonizes the pilosebaceous duct;
Therefore, the four pathogenic factors that give rise to acne lesions are:
1. excess sebum production;
2. hypercornification of the pilosebaceous duct;
3. abnornalities of the bacterial flora of the pilosebaceous duct;
4. dermal inflammatory reaction.
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Hypercornification of the pilosebaceous duct causes primary lesions -

black comedones (open) and white comedones (closed) by retaining the
hyperproliferative keratinocytes.
The bacterial flora involved in inflammatory acne lesions and which
seems to slightly correlate with their severity is represented by:
Propionibacterium acnes, Staphylococcus epidermidis and Malassezia furfur.
Dermal inflammatory reaction is induced by:
proinflammatory mediators released from the walls of the
pilosebaceous duct;
enzymes released by Propionibacterium acnes (protease-lipase,
phosphatase, hyaluronate lyase);
interleukins (IL and IL) and TNF released by ductal
corneocytes
chemoattractants for polymorphonuclear and mononuclear
leukocytes found in the cell walls of Propionibacterium acnes;
It is exacerbated by foreign body inflammatory reaction triggered by the
pilosebaceous duct rupture.
Acne vulgaris lesions are represented by:
open and closed comedones;
superficial inflammatory lesions (papules, pustules) ;
deep inflammatory lesions (papulopustular lesions and nodules) ;
unsightly scarring (hypertrophic, atrophic) secondary to nodules
resolution.
In order of their frequency, the areas involved are the face and the
anterior- posterior and superior chest.
Other factors that may be involved in the development of acne include:
diet (which indirectly stimulates the sebaceous secretion);
premenstrual period (due to hydration changes within the
pilosebaceous epithelium);
sweating (a wet and warm environment aggravates acne due to
abnormalities regarding the ductal hydration);
UV- radiation (it can stimulate the comedogenicity of sebum);
262
chemical products: oils, halogenated hydrocarbons (chloracne),

residues from coal tar distillation give rise to acne.
Severe clinical forms include:
facial pyoderma;
acne conglobata;
acne fulminans;
Gram -negative folliculitis.
Clinical diagnosis easy to determine due to its clinical appearance,
simple background or its development related to a certain period of life.
Acne vulgaris must be differentiated from:
acneiform staphylococci;
acneiform tuberculides;
rosacea;
iatrogenic acne due to cortisone, tuberculostatic or psychotropic
drugs.
The treatment
It is complex, requires individualization and sometimes it involves
psychotherapy.
Systemic treatment includes:
broad-spectrum antibiotics: tetracyclines (minocycline,
doxycycline) propionyl erythromycin;
oral retinoids: isotretinoin (in severe forms of nodular acne, acne
conglobata);
oral contraceptives (in women, especially if they suffer from
polycystic ovarian diseases);
other medications: gluconate or zinc sulphate, spironolactone,
ketoconazole.
Topical treatment
It may be sufficient in mild cases and is based on the use of comedolytic
substances, antiseborrheic creams, antibiotics and anti-inflammatories.
retinoids- tretinoin, isotretinoin, adapalene, terazoten,
(comedolytic and anti-inflammatory drugs);
263
benzoyl peroxide (antimicrobial, anti-inflammatory);

antibiotics: erythromycin, clindamycin, metronidazole;
azelaic acid (antimicrobial and antikeratinising);
zinc salts.
Dermatocosmetic procedures and scar repair are performed along with
the morbistatic treatment presented above.
ACNE ROSACEA
Rosacea is a chronic dermatitis affecting predominantly females aged
35-50 years and it is rarely seen in adolescents or the elderly people. The
lesions predominantly affect the skin of the nose, surrounding the cheek area
and they are represented by papules and pustules, occurring on a background of
couperosis and evolve in successive stages. Despite its benign characters,
rosacea can be the source of an important aesthetic damage.
Etiopathogenesis
Many but unconfirmed factors have been involved in the etiology of this
disease, however the pathophysiological mechanism of rosacea remains
obscure. The role of digestive endocrinic, infectious, psycho- emotional and
vasomotor factors is frequently mentioned. The association of vascular lesions
with inflammatory lesions and the development in stages are universally
accepted.
Evolutionary stages of rosacea (Wilkin JK, Arch. Dermatol.)
I. pre - rosacea (flushing)
II. vascular rosacea (redness, telangiectasia)
III. inflammatory rosacea (papulopustular rosacea)
IV. hyperplasia of connective tissue (Rhinophyma)
Subjects who develop rosacea are believed to have a constitutional
predisposition. Primary vascular cephalic abnormalities, disturbed venous
drainage, physiological vascular reverse flow from the facial vein to its
collaterals, especially when cerebrovascular hyperthermia is involved, they all
lead to stasis accompanied by vascular dilatation. These vascular dilatations
have a paroxysmal nature"flushing" and are exacerbated by alcohol ingestion,
hot liquids, stress or sun exposure. Enkephalins, endorphins, bradikinins are
also responsible for flushing, due to the fact that their release is stimulated by
adrenaline.
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A high level of substance P with a vasodilator effect has been found in

patients with rosacea. Flushing is considered the first evolutionary stage of
rosacea, known as pre - rosacea.
In time, the vascular dilatations become permanent, telangiectases are
formed and the appearance becomes erythemato-cuperotic.
In spite of these conflicting results, more recent studies suspect a link
between rosacea and chronic gallbladder dysfunction and gastroenterological
pathology. The culprits seem to be the presence of Helicobacter pylori in the
stomach, the Gram negative bacillus associated with chronic gastritis, gastric
ulcer and stomach cancer. Arguments in favor of this theory include a large
percentage of patients with rosacea which have also been diagnosed with
Helicobacter pilory, as a result of histological examination of antral mucosal
biopsy, serological detection of anti-Helicobacter Pilory antibodies (IgG, IgM,
IgA), and the simultaneous therapeutic efficacy of generally administered
metronidazole on rosacea and Helicobacter Pilory.
During the papulopustular eruption phase, the pathogenic mechanisms
are little known. The infectious factors do not seem to be essential to rosacea.
The role of a commensal follicle mite, Demodex folliculorum, which would
enhance an inflammatory reaction by mechanical obstruction of follicles, has
long been discussed. Currently, its etiologic role is disregarded, despite the fact
that it was confirmed by parasitological testing on a large number of subjects
diagnosed with rosacea. The involvement of an immune inflammatory reaction
is still often discussed and proven by immunoglobulins and complement at the
dermoepidermal junction with a lupous band distribution highlighted by direct
immunofluorescence. Inflammatory infiltrates resulted from lesions in
advanced stages of the eruption have a granulomatous appearance, entailed by
epithelial debris. Anti-collagen and antinuclear antibodies have been found in
the serum of patients with rosacea.
Clinical diagnosis
Indisputable clinical signs for the diagnosis of rosacea include:
erythema, telangiectasia, papules, pustules, scales. The pattern of progression is
suggestive and consists of rhythmicity restricted by eating habits, sudden
outbursts and even short improvements. Another important element for
diagnosis is the dynamic eruption. The onset is of a transient congestive
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dermatosis (paroxysmal flushing) followed by a remarkable stability of the

lesions (rosacea and papulopustular lesions).
Papulo-pustular lesions may become nodular in severe forms of rosacea,
having a lupous infiltrate appearance at vitropression. Integumentary edema can
be associated with eruptive papulopustular flares and it can persist beside them.
The eruption usually affects symmetrically the central area of the face,
forehead, cheeks, nose, chin, and rarely the cervical area, the alopecic areas of
the scalp, forearms or legs. In stage IV of tissual hyperplasia, the skin has an
edematous inflammatory appearance, with wide open pores, in relation to the
dermal connective tissue hypertrophy and sebaceous hyperplasia, which give an
irregular aspect to facies. The affected areas are the cheeks and nose.
Clinical forms
Ocular Rosacea (Rosacea of the eye)
The incidence of this clinical form is differently assessed by some
authors, ranging from 3% to 50 %. The ocular manifestations are inflammatory
and an etiopathogenical link to the cutaneous rash has not been established yet.
Minor involvement may appear (conjunctivitis, iritis, blepharitis,
episcleritis) as well as major complications (iridocyclitis, keratitis, corneal ulcer
and corneal opacity). Eye involvement may occur before the cutaneous signs,
therefore ophthalmological supervision is mandatory for all patients with
rosacea.
Rosacea Hyperplasia
It is considered a progressive clinical form of disease, as described in a
small number of patients who develop progressively prominent inflammatory
nodules, sebaceous and tissual hyperplasia, predominantly affecting the nose
(rhinophyma), the chin (gnatophyma) and the ears (otophyma). The skin is
violaceous, it presents venous inflammations and dilated follicular openings
through which sebum and cellular debris are eliminated. The disease commonly
occurs in males and it has been associated with chronic alcoholism.
Granulomatous or lupoid rosacea
It is characterized by a large number of purplish- brown papules or
small nodules on an erythematous and edematous base, having a chronic
evolution. The condition commonly affects the lower eyelids, the cheeks or the
hairy skin of the scalp. The clinical diagnosis is often difficult because it has to
rule out of a sarcoidosis with small nodules, a contact eczema or a perioral
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dermatitis. This clinical form is associated with ulcero-hemorrhagic rectocolitis

in a significant number of patients.
Rosacea conglobata
It is a severe form of rosacea, which mimics acne conglobata,
characterized by indurated plaques, nodules, cysts and abscesses, highly
hemorrhagic and purulent. A history of rosacea and its restricted topography
leads to this diagnosis.
Corticosteroid-induced rosacea
This clinical form combines papulopustular lesions, multiple
telangiectasias and atrophy. It sets in as a result of using topical corticosteroids
in excess, exacerbating a pre-existing rosacea.
Lymphoedematous rosacea
It is characterized by massive rough, diffuse edema of the skin,
associated with a chronic cutaneous inflammation which affects the forehead,
the nose and the cheeks. It is a rare form of rosacea.
Rosacea fulminans
It is a controversial entity, rarely affecting young women. The lesions
are nodular, confluent, forming abscesses on a rosacea base.
Guidelines for the clinical diagnosis of rosacea

(National Rosacea Society Expert Committee on the Classification and
Staging of Rosacea - J. Am. Acad Dermatol).
1. Identification of one or more primary elementary typical lesions
a. flushing
b. fixed erythema
c. papules and pustules
d. telangiectasia
2. Identification and inclusion of one or more of secondary factors
a. pruritus, stinging, burning
b. patches
c. scales
d. edema
e. ocular manifestations
f. cephalic distribution
g. deep-seated nodules / evolution to phyma
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Treatment
The treatment needs to be adapted according to the disease progression.
Treatment of vascular hyperreactivity (flushing)
At this stage the therapeutic goal is to reduce the discomfort caused by
paroxysmal flushing, by reducing its intensity and duration. Patients must be
advised to have a proper lifestyle and diet and they must understand that this is
the key to a successful long-term treatment. Avoidance of alcohol, spicy foods,
highly emotional states, changes of temperature and exposure to sunlight are
some of the ordinary rules that must be followed by the patient with rosacea.
The control of the vascular component can be done by using topical
vasoconstrictors or by systemic administration of substances that could control
the circulatory anomaly. Clonidine 1-2mg/day has satisfactory vasoconstrictor
effects, but its use is limited by its general secondary effects (vertigo,
constipation).
Treatment of rosacea
The therapeutic alternatives for erythematotelangiectatic rosacea
include:
cryotherapy
linear scarification
dermabrasion
electrocautery
micro-injections with sclerosing substances
laser therapy
Treatment of papulopustular rosacea
The use of general and local antibiotic therapy represents the first choice
of treatment for this stage.
General treatment
Second-generation cyclines (minocycline, doxycycline) are well
tolerated when administered for several weeks as they prevent eye involvement.
In case of intolerance or ineffectiveness, medium dose macrolides may be
prescribed (erythromycin, clarithromycin), in repeated courses.
Metronidazole is effective but poorly tolerated on a long-term basis,
therefore, its topical administration is preferred. For subjects diagnosed with
Helicobacter pylori, the use of metronidazole is beneficial in doses of 250 mg
twice a day, for a month, and then 250mg/day in the second month, followed by
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125mg/day for 2-4 months. Topic 1 % metronidazole is an effective molecule

and can be used during the control treatment and as a single dose in the
maintenance treatment.
Isotretinoin has been suggested for severe forms (granulomatous
rosacea, rosacea conglobata or rosacea fulminans), administered in small doses
2.5 mg / day for about 6 months but with the monitoring of its adverse effects
(ocular disorders, angiogenesis stimulation, changes in serum transaminases).
For lupoid infiltrates, isoniazid 300mg/day can be used for a few weeks, and for
rosacea conglobata, isotretinoin and corticosteroids are reccomended in short
courses.
Topical treatment
1% topical metronidazole is an efficient molecule and may be used
during the attack treatment and as a single-dose, as maintenance treatment.
Resorcinol alcoholic lotions 3-5%, 0.3 % vitamin A acetate or erythromycin
cream 2% can also be used.
Rhinophyma
The treatment of rhinophyma usually involves surgery or cryosurgery
and it is indicated in case of significant tumor hyperplasia where a remodeling
of the nasal pyramid is required. When the lesions are not very severe,
cryotherapy may be used in combination with electrocoagulation or excision
and vaporization with Argon laser. Before surgery, patients may benefit from a
systemic therapy with retinoids at a dose of 0.5 mg / kg / day, in order to
decrease sebaceous hyperplasia.
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BENIGN SKIN TUMORS
Skin tumors are benign proliferative masses of tissue, prone to growth

and persistence, which replicate the structure of the original tissue. They may
be hereditary or acquired.
General clinical features of benign skin tumors:
1. they are well defined growths
2. they develop slowly
3. they do not metastasize
4. they are confined to the topographic area where they arose
Histologically, the benign skin tumors are characterized by:
1. a neat structure
2. absence of atypical cells and nuclear atypia
3. absence of atypical mitoses
Classification of benign skin tumors
Depending on the tissue of origin, benign skin tumors are classified as
follows:
I. Benign epithelial tumors
seborrheic verrucas
verrucous epidermal nevi
keratoacanthoma
II. Skin adnexal benign tumors:
benign tumors involving the sebaceous glands
- symmetrical sebaceous adenomas
- Fordyces Adenomas
- nevus sebaceous of Jadahsson
benign tumors of sweat glands:
- eruptive hidradenoamas (eruptive syringomas)
- eccrine poromas, of Pinkus type
- cylindroma.
III. Benign hair follicle tumors:
trichofolliculoma
pilomatricoma
trichoepithelioma
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IV. Benign tumors by retention:

epidermoid cyst
sebaceous cyst
corneous cyst (milium)
dermoid cyst
pilonidal cyst
mucous cyst
V. Benign connective tissue tumors:
cutaneous fibroma
disseminated dermatofibrosis
moluscum pendulum (soft fibroma)
keloid
xanthoma
VI. Benign tumors of the muscle tissue
leiomyoma
VII. Benign tumors of nervous system
neuroma
schwannoma
VIII. Benign tumors of adipose tissue
lipoma
IX. Benign tumors of vascular tissue
angiomas
lymphangiomas
X. Benign tumors of melanocytic system
Pigmented nevi
Benign epithelial tumors

Seborrheic verrucas (seborrheic keratosis)
blackish brown prominent pigmented growth, with irregular
surface, covered with well demarcated thick scales, of variable
diameter (0.2 - 4cm);
they are seen on seborrheic areas, face, hands, upper chest;
the sudden onset of numerous seborrheic verrucas is known as
the Lesser - Trelat syndrome.
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Histopathologically it is characterized by:

hyperkeratosis
hyperacanthosis
papillomatosis
Progress - usually benign
actinic keratoses
pigmented nevi
pigmented basal cell epithelioma.
Treatment: electrocoagulation, curettage, cryotherapy, laser therapy or
surgical excision.
Verrucous epidermal nevi
verrucous papillomatous growths that occur in childhood
they may be located unilaterally, along a dermatome
(systematized nevus) or anywhere on the skin (trunk, limbs,
scalp).
Histopathology : their structure exhibits papillomatosis, acanthosis and
sometimes dyskeratosis
Differential diagnosis is done with inflammatory linear verrucous
epidermal nevus (Nevil) characterized by erythematous -squamous lesions,
pruritic and persistent.
Treatment:
superficial electrocoagulation
cryotherapy
dermabrasion
laser therapy
topical keratolytics.
Keratoacanthoma
benign tumor of the skin which develops within the
infundibulum of the
hair follicle
the tumor is more common in adults and is located in sun-
exposed areas (cephalic extremity, the dorsal surface of the
hands);
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a large number of factors have been are considered responsible

for this condition:
- viral infections (papilloma viruses)
- trauma
- exposure to UV
- carcinogenic substances (resins, tars)
- genetic factors.
Clinical features
firm, rounded, flesh-coloured nodule, well demarcated by raised
margins ;
the center contains a keratotic plug that leaves a crateriform
ulcer after its detachment
Clinical forms
solitary keratoacanthoma
giant keratoacanthoma
multiple keratoacanthoma
generalized eruptive keratoacanthoma
familial keratoacanthoma (which are transmitted in an autosomal
dominant manner).
Histopathological examination shows
pseudoepitheliomatous hyperplasia
epidermal cells with atypia
dyskeratotic epidermal cells
corneous globules with complete keratinization.
Evolution and prognosis : keratoacanthoma evolves in stages
1. rapid growth rate
2. stationary stage
3. stage of slow spontaneous involution
4. in 15-20% of cases keratoacanthoma evolves into a squamous
cell carcinoma.
Keratoacanthoma must be differentiated from:
basal cell epithelioma
squamous cell epithelioma
273
cutaneous horn
botryomycome.
Treatment:
surgical excision
electrocautery
curettage
radiotherapy.
Benign tumors of the skin appendages

1. benign tumors involving the sebaceous glands
a. symmetrical sebaceous adenomas:
They are rigid growths, yellowish white coloured, asymptomatic,
commonly seen on the face. They usually appear as multiple tumors varying in
size (0.2-2 cm).
Histologically they are characterized by a hyperplasia of the sebaceous
glands.
Treatment: cauterization or surgical excision of the lesions.
b. Fordyces Adenomas
Clinically manifested as yellowish-white granules with spot-like
appearance, affecting the cheek mucosa and the semimucoasa of the upper lip.
The condition is considered an ectopy of the sebaceous glands.
c. nevus sebaceus of Jadahsson
Clinical features: flat hairless patch, brownish-yellow, circumscribed, of
2-5 cm in size.
it occurs at birth or in childhood and after puberty the
appearance becomes nodular and rough;
it affects the scalp and the face;
congenital dysembrioplasia that usually has a benign course, but
which can also turn into a basal epithelioma;
The treatment consists of surgical excision followed by graft or
electrocoagulation
2. benign tumors involving the sweat glands
a. eruptive hidradenoamas (eruptive syringomas)
they are benign tumors of epidermal eccrine ducts;
274
they are especially common in females, after puberty;

Clinical features:
small yellowish- brown nodular lesions, of firm texture, having
a diameter of 1-3 mm;
Site
lower eyelids, anterior chest, abdomen, armpits and vulva
Treatment: electrocautery, dermabrasion, laser therapy.
b. eccrine poroma (of Pinkus type)
tumorous growth, having a bosselated pink-red surface and firm
consistency;
it commonly affects the palms and the plantar regions, as well as
other regions;
histologically it is characterized by pseudoepitheliomatous
proliferation of cells, having a basophil nucleus
treatment: surgical excision, diatermocoagulation or cryotherapy
c. cylindroma
genetically determined tumor, occurring in childhood,
characterized by prominent nodules having a diameter of 0.5 3
cm, firm, situated on the scalp;
the nodules may coalesce and create a turban-like patch ;
Treatment consists of surgical excision followed by suture and
graft.
Benign tumors of the hair
they are rare tumors that develop in the matrix and sheaths of the
hair, clinically they manifest as unique or multiple nodular
growths affecting particularly the face, the scalp, the occipital
region and the trunk.
This group includes: trichofolliculoma, trichoepithelioma,
trichilemmoma, pilomatricoma.
Benign tumors by retention
They are cystic cavities that emerge from keratinized or glandular
epithelium.
a. epidermoid cyst
275
round circumscribed growth, smooth, yellowish to white in

colour, of firm or elastic consistency, with a small central pore
it frequently affects the scalp, the scrotum.
Histopathology the cystic cavity is lined with pluristratified squamous
epithelium and contains a large amount of keratin.
Treatment surgical excision.
b. sebaceous cyst
round tumor growth of varying sizes, firm, painless,
nonadherent;
it affects the femalesscalp;
histopathological findings: the wall of the cyst resembles the
structure of external sheath of the hair, whereas and its content is
made up of keratin and its degradation products;
The treatment requires either surgical excision or incision and
evacuation.
c. corneous cysts (milia)
small white pearly cystic growths, 1-2 mm in diameter, covered
by thin skin;
they can develop as a result of pilosebaceous follicles
obliteration or they may derive from embryons
they are commonly seen on the face (cheeks, forehead), genitalia
or on scars;
histopathological examination reveals a cavitary structure filled
with orthokeratotic keratin, arranged in concentric blades and
delimited by a stratified squamous epithelium
Treatment of milia- surgical excision.
d. dermoid cyst
tumour of elastic consistency, affecting the midline of the body,
consisting of adnexal and epidermal embryonic residues.
e. pilonidal cyst - is a variety of dysembryoplastic cyst, affecting the
sacrococcygeal region
f. mucous cyst - is formed by the obstruction of the excretory duct of
the salivary gland.
Treatment: surgical excision.
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Benign tumours of the connective tissue/soft-tissue tumours

They develop as a result of hyperplasia of the connective tissue (adult or
embryonic) and tissular elements derived from the mesoderm.
a. cutaneous fibromas- firm dermal tumours, pink to yellow in colour,
painless
Clinical varieties:
fibrous histiocytoma (dermatofibroma) is a lentil-shaped growth,
slightly pigmented (brown), slightly pruritic;
- it frequently affects the limbs
- it occurs spontaneously and does not degenerate
- treatment: surgical excision.
disseminated dermatofibromatosis associates an increasing
number of fibromas with bone lesions, as it is a hereditary
condition;
fibroma molluscum (soft fibroma or molluscum pendulum) is a
benign pediculated tumor of soft consistency, flaccid, flesh-
coloured, affecting the armpit region, the groins or the neck.
- treatment: surgical excision and electrocoagulation of the
base
b. keloid is a fibrous well-defined hypertrophic growth, of irregular
shape, red in colour, exhibiting digitate peripheral expansions. Skin
coverage is thin and smooth. It normally occurs after a skin injury
but spontaneous occurrences have also been described.
Site: it commonly occurs on the trunk, neck, limb extremities.
Treatment: -the following are recommended: intralesional
corticosteroids injections, cryotherapy, local radiotherapy.
c. xanthomas - are yellow benign tumours, as a result of a disorder
regarding the lipid metabolism.
According to their clinical appearance, the following are described:
1. tuberous xanthomata are arranged symmetrically on the elbows,
knees and buttocks.
Clinical features: tumors of varying sizes, yellowish, firm, painless,
sliding on the underlying structures.
2. planar xanthomata (small yellow plaques affecting the eyelids);
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3. eruptive xanthomas (they are small yellowish papules that appear

suddenly, clustered on the buttocks, extensor aspects of the limbs).
Benign tumors of the muscle tissue

Leiomyoma - a rare benign tumor, developed from the erector muscles
of the hair or from the muscular wall of cutaneous vessels
clinically described as a small brown growth, slightly raised,
firm, deep, spontaneously painful or when it is subjected to
pressure;
the lesions may be single or multiple and can occur at any age;
treatment - surgical excision.
Benign tumors of the nervous system
a. neuroma - derived from the nerve threads
clinical features: it presents as a small growth, firm, painful,
located in the deeper dermis.
b. schwannoma is a bulky benign tumor, elastic in consistency, located
on the face or limbs, which arises from Schwann 's sheath.
Benign tumors of fat cells
Lipoma is a benign tumor, single or multiple, well defined, covered with
healthy-looking skin. It is composed of mature adipocytes and has multiple sites
(trunk, limbs).
Benign tumours of the vascular tissue
Angiomas are tumors derived from circumscribed vascular hyperplasias.
they are relatively common, have multiple clinical aspects, are
unsightly and may evolve unpredictably to necroses, hemorrhage.
Clinical aspects:
planar angioma
Clinical features: flat intensely colored plaques (red to violaceous), with
clearly defined edges and a wide range of shapes.
cavernous angioma
Clinical features: prominent tumor, located deeper within the dermo-
hypodermic layer, irregularly shaped, red violet in colour. It consists of
multiple dilated vessels and sometimes it has a pulsatile nature.
Venous angioma
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Clinical features: it is characterized by small thin dilated veins, under

healthy-looking skin.
stellate/spider angioma (telangiectatic)
Clinical features: small nodular erythematous -violet tumour, centrally
located, spreading fine telangiectasias.
Treatment of angiomas:
some of mucocutaneous angioamas do not require treatment because
they can regress spontaneously during childhood
therapeutic indications are usually adapted to their clinical form and
site
therapeutic alternatives include:
- cryotherapy (with liquid nitrogen)
- sclerotherapy with sodium morrhuate
- radiation therapy(radioactive strontium)
- electrocoagulation
- laser therapy.
Benign tumors of the melanocytic system
Pigmented naevi / Lentigo
these are dermal dysplasias as a result of naevus cell proliferation;
Clinical features: circumscribed pigmentary lesions that occur in the
first days of life or much later in life;
their histological appearance is typical and consists of important
naevus cell proliferation arranged in crops and sheaths;
according to their histopathology, naevi are classified into :
- junctional naevi (of highly malignant potential)
- intradermal naevi
- mixed naevi.
According to their clinical appearance (shape, size, color) the following
types of naevi are distinguished
1. naevus planus
2. papillomatous naevi
3. hairy congenital naevi
4. dome-shaped naevi
5. giant pigmented naevi
6. Suttons naevus
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7. blue naevi.
Naevus planus it presents as a round - oval pigmented spot, slightly
raised.
Papillomatous naevus dark brown protruding structure, irregularly
shaped, of blackberry-like appearance.
Hairy congenital naevi - brown protruding structures, of irregular
surface and covered with hairs.
Dome-shaped naevi - firm pigmentary lesion, dome-shaped, of smooth
surface.
Giant pigmented naevus denotes a very large infiltrated pigmented
patch , of irregular surface, covered with hairs. It is a dystrophy, usually
systematic, visible even from birth.
Suttons naevus - small prominent pigmented structure, surrounded by
an achromatic halo.
Blue naevi - small dark blue growth, which does not degenerate.
Treatment:
usually pigmentary naevi need close supervision
their number, size, and color are being monitored;
any sign of activity (increase in size or surface, color variations,
ulceration, bleeding) is considered a dermatological emergency
and requires immediate excision.
MALIGNANT SKIN TUMOURS

These are neoplasms that develop on the skin, frequently on
precancerous lesions, and their appearance is caused by the interference of
complex intrinsic (genetic, immunologic, metabolic), or extrinsic (UV
radiation, repeated traumas) factors.
Malignant skin tumours account for approximately 20-25% of all
cancers and have the following features:
1. they develop on precancerous lesions
2. they are well defined clinically and histopathologically;
3. their site is superficial;
4. they have a marked clinical polymorphism which makes the
histological examination indispensable.
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Genetic factors
Recent studies have highlighted the role of three major types of genes
involved in the process of carcinogenesis: oncogenes (Bcl -2- Beel leukalmia
lymphoma), antioncogenes (RB gene, located on chromosome 13q14) and
metastogenes (NM23 gene - metastasis suppressor gene). All these genetic
mutations damage the cell division rate and increase the ability of invasion and
metastasis of neoplastic cells.
Immunological factors
Immunosuppression is a condition that enables the development of
cutaneous malignancies (HIV infections, metabolic disorders, viral diseases -
HPV which is highly oncogenic).
Extrinsic factors along with individual phenotypical predisposition, play
a major role in the appearance of skin cancers.
Ultraviolet radiation (photocarcinogenesis)
has a carcinogenic action, having a cumulative effect, due to
excessive exposure to sun or artificial light;
Phenotype I people and those who live in sunny geographical
areas are prone to develop skin tumors.
Depending on their histogenesis, malignant skin tumors are classified
into:
cutaneous carcinomas (of epithelial origin);
malignant melanomas (malignancies of the pigmentary system);
cutaneous sarcomas (malignant tumours of mesenchymal
origin).
SKIN CARCINOMAS
Skin carcinomas account for 90 % of all skin cancers. Histologically
they are classified into:
1. basal cell carcinomas
2. squamous cell carcinomas
Basal cell carcinomas
General features
1. they are tumorous masses which develop slowly on unharmed skin
or other pre-existing lesions;
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2. their malignancy is "in situ" - manifested by its invading and

relapsing nature;
3. they do not metastasize;
4. they are not accompanied by subjective symptoms;
5. they do not have spontaneous tendency towards healing.
Clinical aspects
A. endophytic basal cell carcinomas:
a) pearly basal cell carcinoma
Clinical features:
small pearly white nodule, translucent, covered by
telangiectasias ;
subsequently other pearly nodules appear, having a arciform
or annular distribution.
b) pearly ulcerated basal cell carcinoma
Clinical features it is a progressive form of pearly carcinoma that
extends peripherally through a crease of pearly nodules, whereas the
center undergoes ulceration;
c) pearly cicatricial basal-cell carcinoma
Clinical features
it presents as an ulcer that extends peripherally, whereas an
atrophic scar develeops in the center;
the edges are delimited by an arciform pearl-like border;
d) ulcerating basal cell carcinoma (ulcus rodens/rodent ulcer):
Clinical features - deep ulceration with straight margins, slightly
infiltrated, often accompanied by a pearly border;
e) terebrant basal cell carcinoma - clinical form of predominantly
endophytic development and clinically manifested as a deep
anfractuous ulceration that affects the soft tissues and even the
bone structures.
B. exophytic basal cell carcinomas:
a) globose basal cell carcinoma clinical features
globular tumorous mass, renitent, slightly pigmentary, of
smooth surface;
during its development it can ulcerate and eliminate a
yellowish philanthe liquid.
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b) nodular basal cell carcinoma - clinical features: round

prominent nodule, red in colour, rough prone to ulceration;
c) vegetative or burgeoning carcinoma - clinical features:
prominent tumorous mass, of irregular surface, covered with
crusts, having the periphery marked by a translucent border.
C. superficial basal cell carcinomas
pagetoid basal cell carcinoma - clinical features:
erythematous or erythemato - squamous plaque, covered
with thin atrophic skin, irregularly shaped, limited by a thin
border consisting of epitheliomatous pearls.
D. sclerodermiform basal cell carcinoma (morpheiform) - Clinical
features:
firm yellowish-white waxy plaque, ill-delimited;
its diameter varies between 1-3 cm, it evolves slowly and
may ulcerate.
E. pigmented basal cell carcinoma:
this is not a well-defined clinical form;
the presence of pigmentation is a clinical sign that can be
added up to any clinical forms, and is primarily due to an
individual predisposition.
Sites of basal cell carcinomas
Carcinomas commonly affect two thirds of the upper face, particularly
the following areas: suborbital region, nose, inner corner of the eye, forehead,
temporal region, but they can occur anywhere on the skin.
The pre-existing lesions on which they may develop include: actinic
keratoses, seborrheic warts, microtraumatisms.
Histological findings:
cytologically they are characterized by a unitary structure;
The tumorous cells are arranged in a palisade at the periphery of
the tumor, have a large intensely basophilic oval nucleus, with
abundant cytoplasm;
nulear and cellular atypia are rare.
The positive diagnosis of basal cell carcinoma is based on the following:
1. well defined tumor, of frequently ulcerated surface, with a firm
base;
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2. the fact that the tumour affects two thirds of the upper face (or
other sun-exposed areas);
3. slow rate of progression;
4. it does not metastasize;
5. it develops on a pre-epitheliomatous lesion (solar keratosis);
6. absence of subjective symptoms.
Basal cell carcinoma runs a chronic course, slowly increases in size, and
evolves spontaneously to ulceration.
Treatment
The choice of the therapeutic method depends on:
clinical form;
tumor size;
site;
age of the patient.
1. surgical excision;
2. electrosurgery;
3. curettage (recommended for superficial forms);
4. cryosurgery;
5. CO2 Laser Therapy.
6. radiotherapy (for severe extended forms, which can not be
addressed surgically);
7. topical cytotoxics (5- fluouracil, podophyllin);
8. interferon gamma - administered systemically or intralesionally.
Spindle cell squamous cell carcinoma (Spindle cell SCC)

Spindle cell SCC is a malignant skin tumor, derived from keratinocytes,
characterized by rapid development and considerable metastatic capacity.
This neoplasia develops mainly on pre-epitheliomatous lesions (actinic
keratoses, actinic cheilitis, leukoplakia).
Spindle cell SCC can occur in any region of the skin and mucous
membranes, but the most common site is at the mucocutaneous junction (lower
lip).
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General features
these are invasive tumours, with a high potential of becoming
malignant;
they metastasize lymphatically;
clinical polymorphism is lower than that of basal cell
carcinomas;
they occur frequently on precancerous lesions ;
they are evolving faster (compared to basal cell carcinomas).
Clinical aspects regarding the onset of spindle cell carcinoma SCC
Spindle cell carcinoma SCC may begin as following:
a) persistent fissure without being prone to epithelialization;
b) papillomatous or verrucous tumour;
c) small keratotic plaque progressing to cutaneous horn;
d) ulcerated and indurated base.
During its development, spindle cell carcinoma may present the
following clinical forms:
Spindle cell carcinoma SCC of the skin
1. vegetative squamous cell carcinoma is the typical clinical form
of squamous cell carcinoma and it presents as a vegetative and
ulcerated mass, covered with fetid discharge, of indurated base
and infiltrating adjacent structures;
2. nodular squamous cell carcinoma presents as a nodular mass of
hematic crusts;
3. keratotic squamous cell carcinoma: clinically, it appears as a
small node (1-2 cm in diameter) with gray verrucous
hyperkeratotic surface. It frequently affects the lips;
4. gigant cauliflower-like vegetative squamous cell carcinoma:
clinically, it is an irregularly shaped vegetative tumorous mass,
mammillated surface, covered with fetid discharge;
5. ulcerous-endophytic squamous cell carcinoma, is an irregularly
shaped ulceration, of hardened infiltrated base, usually affecting
the mucosas.
6. superficially infiltrating/ invasive squamous cell carcinoma:
- it presents as a red -violet infiltrated plaque, ill delimited and
extensive; it may ulcerate during its course of development;
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- it affects the naso - genian fold, the sides of the nose, the
subnarinar region.
7. actinomycotic squamous cell carcinoma - this is a rare clinical
form and is characterized by ulcerative lesions, necrotic
tumorous masses and polymorphic microbial flora, affecting the
face.
Spindle cell carcinoma of the mucosas
Clinical features: it presents as a persistent ulceration which bleeds
easily, having an infiltrated base and a surface covered by hematic crusts.
Sites: it affects semi-mucosas and mucosas (oral or genital).
Anatomical and clinical distinctive features of spindle cell carcinoma in
relation to location of Squamous cell carcinoma of the lip:
is the most common clinical form of squamous cell carcinoma;
it occurs frequently in males, smokers, those with poor hygiene
of the mouth, and those who are chronically exposed to solar
radiation;
it develops on preexisting lesions such as: chronic or actinic
cheilitis, leukoplakia, trauma;
it occurs with predilection for the lower lip mucosa and semi
mucosa;
the clinical form is ulcerous vegetative
rapid rate of progression;
it metastasizes lymphatically in regional lymph nodes.
Squamous cell carcinoma of the genitalia:
the usual clinical form is ulcerous -vegetative or keratotic;
it develops on a scleroatrophic balanitis in males or on a
leukoplasic plaque in females; it arises from
Squamous cell carcinoma of the oral cavity:
common clinical forms are vegetative or ulcerous -vegetative;
it commonly affects the tongue, the gums, the palate, the floor of
the mouth;
predisposing factors include : smoking, microtraumas produced
by the accumulation of miscellaneous particles at the root of the
teeth, poor oral hygiene.
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Histopathological diagnosis of squamous cell carcinoma:

histopathological examination shows tumor proliferations made
up of spindle epitheliomatous cells arranged into lobes and with
different levels of differentiation;
the numerous keratinized tumorous cells are organized into
corneous globes (thick lamellar eosinophilic structures);
the degree of differentiation has been linked to malignancy (low
grade of differentiation = poor prognosis).
Positive diagnosis of squamous cell carcinoma is supported by:
1. tumorous mass, with indurated, infiltrated base and ulcerated
surface;
2. the fact that it affects one third of the lower face (on the skin or
mucosas);
3. rapid rate of progression;
4. it metastasizes lymphatically in regional lymph nodes and rarely
goes farther;
5. the mass is painless and does not undergo spontaneous
remission;
6. the usual clinical form is the ulcerous vegetative one.
Squamous cell carcinoma of the lower lip must be differentiated from:
syphilitic chanker;
TB ulcer;
botryomycoma;
ulcerated papilloma.
For other sites, the differential diagnosis is done with:
basal cell carcinoma;
keratoacanthoma;
pyoderma vegetans.
Squamous cell carcinoma has a rapid rate of progression and
metastasizes early, lymphatically.
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Treatment:
usually, the surgical excision is the first line of treatment, within
oncological limits, followed by contact radiation therapy or
transcutaneous penetrating radiation;
intralesional chemotherapy using bleomycin or methotrexate is
recommended in extensive form of disease.
CUTANEOUS SARCOMAS
Sarcomas are malignant skin tumors of the connective tissue.
Clinical forms:
Fibrosarcoma
Clinical features:
it presents as an erythematous -violet nodular mass, unique,
indurated, ranging in size from 5 to 10 cm.
it most commonly affects the knee, the thighs and upper
extremities of the arms and is rarely seen on the trunk
the development of fibrosarcoma is infiltrating, destructive, the
prognosis is poor due to its increased ability to metastasize
Histological findings:
it is characterized by proliferation of atypical spindle cells
arranged in bundles
the tumorous cells have an ill-developed cytoplasm and nuclei of
uniform appearance
a large number of mitoses takes place.
Treatment: wide surgical excision, followed by radiation therapy, or
chemotherapy.
Recurrent dermatofibrosarcoma (Darier - Ferand)
Clinical features: at first, it appears as a patch made up of firm, dermal
nodules, flesh-coloured, which have coalesced. During its course, the tumorous
mass has a plurinodular appearance and the superjacent skin is subjected to
pressure.
Sites: it especially affects the young and the male adults and it occurs on
the scalp, anterior thorax or abdomen.
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the tumorous cells resemble the fibroblasts and they are arranged
in short bundles like arranged in a particular pattern (storiform or
"wagon wheel")
nuclear pleomorphism is discreet and the mitotic activity is
moderate
tumorous stroma has a myxoid appearance.
The treatment consists of surgical excision and radiotherapy.
Kaposi's sarcoma - is a tumor developed as a result of a conjunctive-
vascular proliferation.
Etiology:
Viral infections account for one of the most important etiological factors
that cause Kaposi's sarcoma.
Possible viruses involved include: cytomegalovirus (CMV), hepatitis B
virus, herpes - virus, papilloma virus type (HPV), HIV.
Besides viral factors, Kaposi's sarcoma is thought to be derived from
genetic lineage or from immunological factors.
Investigation of HLA antigens in Kaposi's sarcoma has revealed a
significant link between HLA - DK5 and this sarcoma.
Clinical forms
Four clinical etiological forms of Kaposi's sarcoma are described:
1. Classic Kaposi's sarcoma (European)
2. Endemic (African)
3. Epidemic Kaposi's sarcoma (HIV -related)
4. Drug-induced (Immunocompromised) Kaposi's sarcoma (due to
immunosuppression ; posttransplant).
The four types differ in terms of etiology. They have similar clinical
aspects, but their clinical course is different.
Classic Kaposi's sarcoma
Clinically characterized by specific skin lesions: infiltrated plaques and
nodulo -tumorous lesions.
The infiltrated plaques are protruding purplish- red masses, well
enclosed by the surrounding tissues, oval or irregularly shaped. The surface of
the plaques is usually flat, but it can also be scaly or keretotic.
Nodulo -tumorous lesions are deep dermal nodules or large
angiomatous tumours, progressing to central ulceration.
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Sites: initially the lesions are grouped on the extremities of the lower
and upper limbs and on the cephalic extremity.
Other clinical cutaneous manifestations include: telangiectasia, purpura,
bruising, hematomas (inconsistent elements without any influence on
diagnosis).
Extracutaneous sites:
isolated nodules may occur on the internal organs, having a slow
evolution, without subjective symptoms
the lesions usually affects the skeletal system, the digestive tract,
the respiratory apparatus, the heart and the pericardium
Although the clinical expression of these systemic lesions is
secondary, in 20 % of cases they are causing death.
Endemic Kaposi syndrome
It is characterized clinically by marked polymorphism, the lesions have
a gradual progression, from the nodes to ulcerative lesions located at the end of
the limbs.
A distinctive form of endemic sarcoma, namely lymphadenopathy, is
seen in young people and it is characterized by general impairement of mucosas
and nodes, with reduced or absent skin involvement. Visceral involments are
multiple, while the progression is unpredictable and often fatal.
Epidemic Kaposi sarcoma
This form occurs in individuals infected with HIV.
Clinically, the lesions are similar to those of Kaposi's classic sarcoma,
but they can occur anywhere in the body and and have a rapid rate of
progression. They are accompanied by general symptoms (fever, fatigue,
weight loss).
Iatrogenic Kaposi's Syndrome
It occurs in subjects with liver lung and heart transplants, approximately
16 months after having started the immunosuppressive therapy.
Clinically, the lesions are similar to those described in the classic form
disease, whereas their progression is linked to the degree of immune deficiency.
Reducing the immunosuppressive therapy and improving the immune status
have as effect the regression up to the disappearance of the lesions.
Histopathological examination:
The structure of Kaposi's sarcoma is made up of three types of cells:
290
1. endothelial cells
2. Spindle cells
3. cells of the inflammatory infiltrate (plasma cells or
macrophages).
In general, there is a balance between vascular proliferation and cell
proliferation within the lesions of Kaposi's sarcoma.
In some cases there is a predominance of vascular proliferation, known
as angiomatous or fibroblastic (sarcomatous) aspect, when cell proliferation
prevails.
Treatment
Treatment of Kaposi's sarcoma is varied.
radiotherapy
cytostatics
interferon
retinoids
antibiotic therapy.
The topical treatment is reserved for forms of single or less damaged
lesions, small in size, for which general therapy is not indicated due to its side
effects.
The most important methods of topical therapy include:
surgical excision
laser therapy
cryotherapy
sclerotherapy.
MALIGNANT MELANOMA
Malignant melanoma is a tumour arising primarily from melanocytes, or
secondarily due to naevi.
It is one of the most aggressive malignancies. It has a rapid rate of
progression and metastasizes lymphatically and hematogenously. Among the
risk factors in the occurrence of melanoma, we can mention genetic factors, sun
exposure, pigmentary damage.
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Some authors have attempted classifications of malignant melanoma

using clinical, histological or predictive criteria.
Using purely morphological criteria, Clark classifies malignant
melanoma into three types:
1. superficially spreading malignant melanoma (superficially
extensive)
2. malignant melanoma arising from Dubreuilhs melanosis
3. nodular malignant melanoma.
Superficially spreading malignant melanoma
Clinical features
it is characterized by an inhomogeneously pigmented macule,
slightly raised, infiltrated, irregularly shaped that extends slowly
through the periphery;
it may develop on a healthy-looking skin or a flat junctional
naevus;
on the surface of the pigmentary plaque raised nodules may
occur, which develop vertically, invading deeper the dermis.
This type of melanoma is frequently seen on middle-aged people
and affects the legs, the fingers and genitalia.
Malignant melanoma is made up of typical melanocytes that invade all
layers of the epidermis.
clusters of atypical melanocytes are found in the epidermal
growth phase
the monomorphic appearance is the distinctive feature of
intradermal atypical melanocytes
edema, fibrosis and a large number of melanophages account for
the inflammatory changes within the dermis.
Malignant melanoma arising from Dubreuilhs melanosis
It begins as a slowly extending pigmentary plaque, tan or dark brown in
colour, showing a polychrome inhomogeneous nature.
Papules or brown lumps appear on the plaque during its vertical growth
phase.
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Histopathological findings
the histological structure is dominated by atypical melanocytes
arranged singly or in clusters;
the atypical cells are arranged at the dermo - epidermal junction
and around the adnexal areas;
the dermis is abundant in inflammatory infiltrate;
the tumorous cells are spindly and a variable amount of melanin
is found in the cytoplasm.
Nodular malignant melanoma
Clinical features: round nodular mass, polylobulated, with a narrow
implantation base, unevenly colored (red, tan or brown).
The evolution of the tumour is towards ulceration, whereas satellite
lesions appear around the primary tumor (small blue nodules or patches with
intense pigmentation); elements that are considered micrometastases. They
commonly appear on the scalp, neck or trunk.
Clinical forms and particular sites of malignant melanoma:
1. primary malignant melanoma of the mucosas- is a rare form and
may affect the buccal, conjunctival mucosa, the nasal cavities,
the vaginal and anorectal mucosa. The clinical picture varies
from pigmented plaque to sessile pedunculated nodule.
2. subungual malignant melanoma -the clinical aspect is of a higly
pigmented macule, brown, evenly coloured, or it may occur in
longitudinal striations. It affects the matrix region of the nail and
has a slow rate of progression.
3. achromic malignant melanoma - clinical features: nodular, pink
or flesh-like mass, that develops on healthy-looking skin. The
palms and the genitals are possible sites for this form of
melanoma.
4. multiple malignant melanoma - this form is frequently common
in people who have dysplastic naevi and consists of: successive
appearance of two or more primary melanomas.
The classification of malignant melanoma clinically and evolutionarily:
stage I - localized malignant melanoma, without metastases
(primary tumor);
293
stage II malignant melanoma with cutaneous metastases or

regional lymph nodes ;
stage III - multiple visceral metastatic melanoma.
Evolution and prognosis of cutaneous malignant melanoma rest upon its
size, sites, presence of metastases and the tumors degree of invasion.
Metastases are mainly focused on vital organs: liver, lungs, brain and
bone structures. Clark mentions five levels of invasion:
level I melanoma " in situ" (the tumorous cells do not affect the
basement membrane) ;
level II the tumorous cells extend to the basement membrane,
until they reach the papillary dermis;
level III - the tumorous cells are present at the boundary between
the papillary and reticular layer of the dermis;
level IV - the presence of tumorous cells disseminated through
the collagen bands of the dermis;
level V - hypodermis is invaded by tumorous cells.
Positive diagnosis:
The clinical diagnosis does not usually pose difficulty regarding the
typical pigmented forms.
Laboratory methods of investigation are numerous and are valuable in
different ways. Among them we are mentioning: cytodiagnosis, pathological
examination, histoenzimological and immunohistochemical methods,
detrmination of melanuria DNA (D1) index, homovanillic acid and detection of
cistenil 5 - Dopa.
Malignant melanoma should be differentiated from:
1. botryomycoma;
2. hemangioma;
3. pigmentary naevus;
4. subungual hematoma.
Treatment
The treatment should be applied as soon as possible. The therapeutic
alternatives are adapted to their clinical forms and evolutionary stage:
surgical excision within oncological limits is recommended in
stage I (primary tumour);
294
in stage II (lymph node skin and metastases) melphalan

chemotherapy, hyperthermia and lymph node dissection are
recommended;
stage III requires multi-agent chemotherapy (vinblastine), DTIC
(dimetiltriazenoimidazol carboxamide), fotemustine
(Muphoran).
Adjuvant therapeutic alternatives:
immunotherapy using double strength bacillary endotoxin
Corynebacterium parvum, or interferon alfa-2b;
radiotherapy - recommended for the primary tumor and in case
of liver and bone metastases.
SEXUALLY TRANSMITTED DISEASES

SYPHILIS
Syphilis is a an infectious, sexually-transmitted disease.
Etiology
Syphilis is causes by Treponema pallidum, a spirochete microorganism,
Treponemetaceae family, genus Treponema, subspecies pallidum.
Treponemes have different degrees of pathogenicity. Pathogenic species
are responsible for diseases such as syphilis (Treponema pallidum), pinta
(produced by Treponema carateum), Treponema endemicum or bejel (the
etiologic agent of nonvenerian endemic syphilis).
Nonpathogenic species are saprophytes of the genital tract (Treponema
genitalis), oral cavity (Treponema microdentium) or digestive tract (Treponema
perfringens).
Morphology of Treponema pallidum
it is spirochaete of variable length, ranging from 7 to13 , of
helical shape (corkscrew) (6-14 coils) and tapered ends ;
the outer membrane is made up of lipids and proteins, giving rise
to a wide range of antigens from its surface, very useful in
establishing the laboratory diagnosis of syphilis;
a glycoprotein known as peptidoglycan is found in the structure
of the inner membrane, which plays a role in cell division ;
the cell body consists of cytoplasm and nucleus;
295
the musculoskeletal apparatus consists of two filaments that are

twisted on the spirochete from end to the other.
Epidemiology
The source of infection is the patient with syphilis.
The routes of infection caused by Treponema pallidum are:
1. sexually-transmitted (98 % of cases)
2. extra sexual contamination is rare and can be :
a) direct, through contaminated medical instruments, blood
transfusions;
b) indirect through toiletries or tableware (extremely rare).
3. transplacental transmission from mother to fetus.
The incidence of syphilis in the general population is affected by many
factors, of which the most important are:
- educational background;
- the financial situation of an individual;
- change in the sexual behavior;
- extention of behavioral manifestations of social pathology.
The pathology of syphilis
Treponeme inoculation is achieved through a breach in the skin or the
mucous membranes. Thus, with the help of molecules that adhere to its surface
(fibronectin, transferrin, lactoferrin), the treponeme easily penetrates the
epithelial cells and stimulates the immune mechanisms of the host.
The primary lesions occur at the skin breach and the main cells involved
are:
1. the neutrophils - the accumulation of neutrophils will determine
a phagocytose and only a partial destruction of treponemes,
probably due to a natural resistance to the action of lysosomal
enzymes. From the breach, the stongest treponemes are being
transported lymphatically, reaching the ganglia;
2. the lymphocytes - treponemes of the regional lymph nodes are
surrounded by B and T lymphocytes and cause a cellular
immune and a nonspecific humoral response.
3. the macrophages phagocytize the treponemes and heal the
syphilis.
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The persistence of syphiloma and lymphadenopathy coincides with a

positive serological reaction (42-45 days after the contamination).
After spontaneous healing of the chancre, there follows a period of
asymptomatic clinical disease known as the second incubation, which lasts for
about two weeks. When treponemes spread beyond ganglia, a true sepsis of
spirochaetes occurs and marks the beginning of the secondary syphilis.
The secondary stage lasts between 2-5 years and is characterized by
eruptive outbursts interlaced with periods of latency.
Both latency periods and eruptive flares are characterized by strongly
positive serological reactions. The presence of clinical lesions is characteristic
to florid secondary syphilis, and their absence characterizes latent secondary
syphilis.
After the end of the second stage of disease, there follows a period of
apparent
clinical healing which lasts for about 10-20 years, in which the expressed
clinical lesions are minimal and the serological reactions are fading away (late
latent syphilis).
Cutaneous, mucous and visceral lesions may occur late during the
latency period.
The final stage of the disease is represented by tertiary syphilis
characterized by lesions of distinctive morphoclinical aspect (nodules and
gumma). At this stage the lesions are small, however they have a highly
destructive potential.
Classification of syphilis
Clinically and evolutionally, syphilis is classified as follows:
1. early syphilis - with a time frame of less than 2 years, clinically
marked by primary or secondary syphilis
2. latent syphilis - without mucocutaneous lesions, marked only by
positive serology
3. late syphilis - with a time frame of over 2 years, clinically marked
by tertiary syphilis
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Primary syphilis
the average incubation period is 21-25 days and may vary depending
on the number and aggressiveness of treponeme inoculation, but also
on the way the body reacts to this aggression;
the lesions are always located on the skin breach and they are
represented by: a syphilitic chancre and regional lymphadenopathy.
The syphilitic chancre appears on average after 3 weeks of exposure to
infection.
Clinical features
it begins as a small erythematous spot, which erodes and
gradually extends (micro chancre);
it reaches maturation within 8-10 days and achieves its classic
appearance
the classic chancre is a round erosion, measuring 0.5-2 cm in
diameter, well defined, red-copper in colour, of smooth surface,
covered by a clear serosity which gives it a shiny appearance;
the erosion edges are slightly blurred and they easily get lost into
the healthy-looking skin;
the base of the chancre is rough, cardboard-like, painless,
persistent even if the chancre has healed, thereby enabling a
retrospective diagnosis of the disease;
the chancre heals spontaneously (without treatment) in 30-40
days and leaves a pigmented mark.
Sites
It usually affects the genital region. Depending on their sites, the
chancres are classified into:
1. genital chancres (on the glans penis, near the frenum or on the
underside of the prepuce, labia, cervix)
2. perigenital chancres (perianal, rectal, anal)
3. genital chancres (lip, tonsillar, lingual, gingival chancre )
Clinically, a distinction has to be made between:
small chancre it is small and has nodular appearance, affecting
the perianal and vulvovaginal folds;
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ulcerous chancre - ulceration that has its base covered by tissular

debris, enclosed by an erythematous-edematous area, commonly
affecting the teguments;
crusty chancre - the surface of the lesion is covered with crust;
hypertrophic chancre it is large, it has an infiltrated base and it
commonly affects the lower lip, tonsils, the narinar region.
Complications of primary chancre
The most common complications include:
a) marked proliferation of microbial bacteria such as Neisseria
gonorrhoeae, chlamydia or common germs; the presence of the
superinfection enables the development of atypical cankers;
b) phimosis (the foreskin is prevented from being drawn back to
uncover the glans penis) due to an inflammation of the foreskin,
accompanied by a purulent discharge;
c) joint/intermingled chanker rarely seen due to the association
between Treponeme pallidum and Ducrey bacillus.
The positive diagnosis of the syphilitic chancre is supported by:
1. the classic appearance of lesions (canker and lymphadenopathy)
2. presence of a previous infectious contact (as proved by
anamnesis and / or epidemiological investigations);
3. the presence of treponemes within the chancre highlighted on
ultramicroscopic examination;
4. Positive serology - after the third week of development.
Laboratory diagnosis of primary syphilis
In order to confirm syphilis, the following investigation methods are
used:
1. methods to single out the treponemes
a) microscopy singles out the treponemes on a dark
microscopic field, by examining the secretions sampled from
primary lesions;
b) immunofluorescence - singles out the spirochaetes on a
smear sampled from lesional secretions. It is more valuable
than dark-field microscopy, but it can not differentiate
pathogenic treponemes from the saprophytic ones;
299
c) staining methods - are little used and single out treponemes

using Giemsa staining, Congo red or silver impregnation.
2. serological reactions for syphilis
- the first serological reaction which turns positive FTA-ABS
(a few days after the appearance of the syphilitic chancre);
- after 10-15-20 days FTA and RCFC turn positive;
- after 21 days TPHA and VDRL turn positive.
The differential diagnosis of primary chancre is done with:
soft canker;
scab-like canker;
genital herpes;
genital thrush;
Nicolas-Favre disease.
Secondary syphilis
it begins 63-65 days of exposure to infection or 42-45 days after
onset of the chancre
the second period corresponds to the generalization of infection
and the mucocutaneous syphilitic lesions are known as
syphilides
the lesions are multiple, symmetrical, asymptomatic, superficial,
they may resolve spontaneously and have a predilection for three
areas: orofacial, anogenital and palmar-plantar.
lesions of secondary syphilis may be preceded by general
phenomena: fever, headache, osteocopic or neuralgic pain,
diffuse muscle pain
mucocutaneous lesions are accompanied by generalized uniform
noninflammatory and resolutive polyadenopaty.
Morphologically, the secondary syphilides are polymorphic and can
mimic many skin disorders.
The following types of syphilides are described:
1. erythematous syphilides (syphilitic roseola/roseolar rash)
- it is the first manifestation of secondary syphilis
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- clinical features: it appears as erythematous, pale pink, round

and oval spots, with a diameter of 0.5 cm, with diffuse,
noncoalescent edges
- non-prurutic eruption that resolves spontaneously within 35-
45 days
- the condition usually affects the thorax (the anterolateral
sides) but the eruption may become generalized
2. papular syphilides
- they usually appear 2-4 months after the onset of the disease
or they may associate with roseola
- several clinical forms of papular syphilides have been
described:
papulo-pustular syphilides these are firm papular
lenticular lesions, coppery red, with a diameter of 3-10
mm, of smooth surface covered by a white scale, more
adherent to the periphery of the papule, in the shape of a
collar (Bietti's collar)
papulo- seborrheic syphilides the lesions manifest as
infiltrated plaques, covered with a thick layer of
yellowish scales, affecting the seborrheic areas (forehead,
nasogenian fold)
psoriasiform syphilides their clinical appearance
resembles guttate psoriasis. They are erythematous
papules, covered with multilayered thick scale, with a
tendency to coalesce and form figurate plaques and
patches
papular palmoplantar syphilides they may have varied
clinical aspects:
- papulo- erythematous
- papulo-keratotic
- papulosquamous.
papulo -erosive syphilides -these are papular structures
having an eroded surface, affecting the flexural regions
subjected to maceration; sometimes they may undergo
hypertrophic or vegetative changes
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follicular syphilides - they manifest as keratotic

protuberances, having a follicular distribution; they occur
in the final phase of the secondary lesions
ulcerative syphilides these are ulcers covered with
hematic adherent scabs, of trimmed margins, commonly
affecting the limbs. Sparse ulcerative syphilides can
coexist with typical papular syphilides, and appear in the
late stages of secondary syphilis
mucous syphilides they may or may not accompany
cutaneous syphilides and affect the oral, genital, anal,
pharyngeal, laryngeal mucosas and are called "mucous
plaques." The clinical aspects include:
a) erythematous syphilides - round erythematous
painless patches, scattered on the pharyngeal mucosa
(anginous/ pharyngeal syphilides) or having a
laryngeal site (Syphilitic laryngitis)
b) erosive syphilides - round oval lesions,superficial,
covered with a pseudomembranous deposit. Erosive
syphilides may affect the tongue, the cheek mucosa,
the tonsils and may display special aspects-
ragadiform/fissured syphilides or depapillated
plaques resembling a " mowed orchard "
c) papulo-erosive syphilides these are papular lesions
with an erosive surface, covered by a grayish-white
adherent deposit
d) papulo-hypertrophic syphilides they usually affect
the vaginal mucosa and the tongue
e) ulcerative syphilides linear or round - oval ulcers,
surrounded by a leukoplakic halo, affecting the
tongue or the tonsils
pigmentary syphilides (venereal necklace/corona veneris)
- clinically they are round or oval pigmented spots,
noncoalescent, symmetrically distributed on the sides of
the neck
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ulcerative syphilides - these lesions characterize the late

stage of secondary syphilis. Clinical features: they are
round ulcerations, having an infiltrated base, covered
with hematic crusts. They commonly affect the trunk and
the limbs.
Appendage involvement:
The most common manifestation is syphilitic alopecia; it can take a
diffuse or insular form, resembling "a clearing".
It usually affects temporo-parietal region and forms plaques with a
diameter of 1-3 cm.
This is a noncicatricial the type of alopecia which is always reversible.
Syphilitic nail involvement is rare and it is the result of Treponemes
location in the capillaries of the nail matrix.
Clinical manifestations include onixis and syphilitic perionixis.
Visceral manifestations
These are rare and they clinically manifest by kidney damage
(proteinuria) liver involvement (hepatitis syphilitic), nervous system (meningeal
reactions) digestive disorders.
Early malignant syphilis
It is a particular form of syphilis, characterized by multiple, large,
polymorphic lesions. This expression implies the existence of a marked
immunosuppression (e.g. HIV).
Tertiary syphilis
cutaneous manifestations of tertiary syphilis occur after a
fluctuant period between 2 and 10 years
tertiary lesions generally occur in small numbers, they are
isolated, destructive, they always leave scars and affect the skin,
the mucous membranes, the viscera and the musculoskeletal
apparatus.
A. cutaneous lesions
A. nodular or tubercular syphilides
these are firm, coppery red nodules, well defined,
appearing in patches, with a tendency to a circinate
arrangement, leaving central scarring;
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the way the nodules associate, give rise to specific

clinical aspects (annular, serpiginous, arciform
syphilides)
syphilitic nodule development is either towards
resolution or towards ulceration, leaving depressed
atrophic scarring
the nodules progress in flares and are being disintegrated
in successive stages (mosaic-like scarring)
tertiary tubercular syphilides are not accompanied by
subjective manifestations
cases where nodules relapse on syphilitic scars are rare
the lesions affect the extensor surfaces of the of the arms,
the back and the face
B. gumma
it is a firm, round-oval nodule, of various sizes, non-
inflammatory, painless and slides on the underlying
structures
This stage corresponds to the stage of rawness
In its progression, the nodule adheres to the superficial surface of the
skin, it wears out centrally (decrepit state), it breaks open and ulcerates, oozing
a slimy fluid and the core of the gumma (ulcerative stage). Healing leaves deep
depigmented scarring (scarring stage). Lesions are found mainly on the scalp,
forehead, presternal, pretibial regions.
B. mucous membrane lesions
they frequently affect the palate, the tongue, the nasal
cavities
ulcerative lesions lead to the perforation of the hard palate, or
to significant deformations regarding the cartilages and
bones of the nose ("saddle" nose)
Visceral tertiary syphilis
it predominantly affects the cardiovascular system and the
liver (myocarditis, syphilitic aortitis and syphilitic hepatitis)
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Neurosyphilis
the lesions affect the brain and spinal masses, namely the
meninges and the brain matter
Clinical manifestations include: headache, vertigo,
paresthesia, paralysis, sensory disturbance
Osteo-myo-articular tertiary syphilis
the lesions of the osteoarticular system are the result of a
highly hyperplastic or destructive process
the following are described: plastic osteoperiostitis,
gummatous osteomyelitis, sclerosing osteitis
The most commonly affected are the tibia, the clavicle, the
humerus
articular manifestations include: arthritis, synovitis and pain
Congenital syphilis
Congenital syphilis is an infectious disease that is transmitted from a
mother with syphilis to her fetus. The evolution and clinical manifestations of
congenital syphilis are caused by:
the elapsed time of the disease (prior to or during pregnancy)
the treatment given.
Maternal syphilis (recently untreated pregnant women with syphilis) can
cause: premature births, stillbirths or death of the neonates. Mothers with late
untreated syphilis can bore apparently healthy children, children with positive
serology and rarely children with florid syphilis.
Clinically and evolutionally, congenital syphilis is classified into early
congenital syphilis and late congenital syphilis.
Early congenital syphilis
syphilis becomes symptomatic at birth or within the first two
years of life
clinical manifestations overlap with those of secondary florid
syphilis, with the difference that the fragility of the skin and
mucous membranes of the toddler are the ones that determine the
special features of this disease.
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Cutaneous manifestations
The cutaneous manifestations are represented by bullous (palmar-
plantar), infiltrative (perioral), papular, psoriasiform, papulo- hypertrophic and
ulcerative syphilides.
Mucous manifestations
These can clinically be expressed by:
syphilitic laryngitis of early onset, characteristic to the child with
congenital syphilis
syphilitic coryza, occurring in the first weeks of life and
manifested as a purulent or bloody nasal discharge, which
obstructs the newborns nostrils.
Osteo-articular manifestations
they are typical and suggestive, affecting both the long and the
wide bones of the skull
the most important lesions are:
- diaphyseal-epiphyseal osteochondritis which leads to Parots
pseudoparalysis (painful and unable to function limbs)
- syphilitic osteochondritis which affects the tibia, visible on
X-ray, which leads to a typical anterior curving resembling a
"scimitar blade"
- syphilitic osteomyelitis, confirmed on X-ray by geodes and
bone condensation.
Late congenital syphilis
Late congenital syphilis includes the events occurring after the first two
years of life, and clinically they are categorized into:
- active lesions
- stigmata
- dystrophies.
Active lesions - are similar to those of tertiary syphilis and affect:
the skin and mucous membranes (tubercular syphilides and
gummas)
the osteo-articular system (arthritis, osteomyelitis,
osteoperiostitis)
the nervous system (meningitis, encephalitis, tabes)
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auditory apparatus (suppurative otitis media, acoustic neuritis,

deafness)
the eyes (optic neuritis).
Stigmata
Stigmatas are sequelae of the former active lesions: skin scarring,
deformities of the nasal pyramid, perforation of the palate.
Dystrophies
Dystrophies are significant for late congenital syphilis and they are
clinically characterized by:
adiposogenital syndrome
gigantism
dental dystrophies - which include structural abnormalities
(cuspal deformations, coronary erosions), volume abnormalities
(micro or macrodontia), shape abnormalities (teeth with extra
cusps).
The most characteristic feature is the Hutchinson triad and consists of
dental abnormalities, parenchymal keratitis and deafness.
Serological diagnosis of syphilis
Serological tests are crucial because they are linked to the natural
evolution of the disease.
They emphasize the antibodies from the patient's serum, synthesized
against different antigenic fractions of Treponema pallidum.
For serological diagnosis of syphilis the following types of tests are
used :
A. Cardiolipin antigen tests (non-treponemal antigens)
B. Treponemal antigen tests.
A. Cardiolipin antigen tests
1. Flocculation reactions
VDRL slide test (Venereal Disease Research Laboratories)
- it has increased sensitivity, but is less specific
- it becomes positive 10-20 days after the emergence of the
chancre
- it allows the assessment of the condition as it progresses
and the therapeutic efficacy
RPR (rapid plasma reagin Test)
307
- the sensitivity and specificity are similar to VDRL

- it allows qualitative and quantitative assessment
- it is useful for screening.
The downside of flocculation reactions is that they can give false-
positive biological reactions in situations such as hemolytic anemia, leucosis,
autoimmune disorders, or in chronic antihypertensive treatment.
2. complement fixation reactions
- Bordet-Wassermann and Kolmer reaction
- have low sensitivity and are little used
B. Treponemal antigen tests.
- have high specificity and sensitivity
1. Treponema pallidum hemagglutination tests (TPHA)
- the reaction becomes positive 4 weeks after the infection
- they allow the determination of antibody titers
- they become negative 3-4 months after the treatment of early
syphilis and remain as a serological stigma in late syphilis
2. immunofluorescence tests (FTA-abs)
- they become positive 2 weeks after the infection
- they are highly sensitive and specific, especially in primary
syphilis, when the flocculation reactions are negative
- they allow the differentiation of IgM and IgG antibodies /
FTA-absIgM, FTA-absIgG) and potentiate a correct
diagnosis of congenital syphilis (IgM does not cross the
placenta)
3. T. pallidum immobilization test (TPI)
- it is highly specificic to treponematosis in general (does not
allow a clinical diagnosis)
- it becomes positive late, at the beginning of the secondary
stage
- it is used as reference test to distinguish a false-positive
reaction from a negative one
4. complement fixation test with protein antigen from the Reiter
strain of Treponema pallidum
- it is rarely used because it has low specificity
5. Treponemal enzyme immunoassay (EIA) tests
308
- they have an increased sensitivity in primary infections

- among these, ELISA ( enzyme-linked immunosorbent assay)
and PTA (peroxidase treponemal antibody test) tests are used
6. Westernn-Blot test
- it is a rather new method of diagnosis
- it uses treponemas isolated by electrophoresis
- it has very high specificity
7. polymerase chain reaction (PCR)
- it highlights the treponemal DNA by gene amplification
In conclusion, in case of inconsistent results regarding the serological
diagnosis, FTA-abs, EIA or immunoblotting tests are recommended.
To assess the therapeutic efficacy, VDRL or EIA-IgM tests are
recommended.
Management of syphilis
Penicillin remains the drug of choice in the treatment of syphilis.
The therapeutic dose must be steady for a certain period of time,
characteristic for each form of syphilis.
In syphilis, the effective therapeutic principle is dose / time, as the
penicillin works against treponemes only when they undergo the process of
division.
Penicillin is used in the form of crystalline penicillin G and benzathine-
penicillin.
Treatment regimens vary from one country to another and are adapted to
each clinical form.
The most used regimens are:
Seronegative primary syphilis treatment can optionally include:
crystalline penicillin G 1,600,000 IU / day intramuscularly,
administered in 2 doses, for 10 days
benzathine- penicillin (Moldamin) - 2 inoculations 2,400,000 IU
intramuscularly , in 5 days
Treatment of recent syphilis (primary seropositive, secondary florid)
crystalline penicillin G - 1.600.000 UI / day, intramuscularly, for
14 days
benzathine penicillin - 2,400,000 IU every 4-5 days, 5 injections
Treatment of late syphilis
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benzathine- penicillin - 2.400.000UI/dose, 5 injections at 5 day

interval (in forms without neurological involvement)
crystalline penicillin G - IU 2-400000 administered from 4 to 4
hours, intravenously, for 14 days (neurosyphilis)
Treatment of congenital syphilis
In children, the doses are adjusted according to their age and weight, the
average being 50,000 IU / kg body weight / day.
Those allergic to penicillin may be given tetracycline 2g/day or
erythromycin 2g/day for 15 days. After the treatment, the patients are clinically
and biologically monitored on a daily basis, according to the clinical form of
disease.
GONOCOCCAL INFECTION (GONORRHEA)
gonorrhea is an infectious sexually transmitted disease, caused
by Neisseria gonorrhoeae
it is the most common sexually transmitted disease and affects
especially young males.
Etiology
the etiologic agent is a gram negative diplococcus, arranged in
pairs, resembling the shape of coffee beans
ultrastructurally, it presents capsular layers and filamentous
structures (pili) with adhesive properties
the pathogenic mechanisms are determined by adhesive factors,
the strength of the capsule, the outer membrane of the pili and
the intracellular multiplication capacity
the incubation period varies between 2 and 7 days
the gonococcus affects the urethral epithelium, the ducts of
periurethral glands, the epithelium of the cervix and manifests
differently, dependent on the gender
Gonococcal infection in men
It manifests as an acute or chronic urethritis.
Acute gonococcal urethritis
it occurs within days of exposure to an infected partner and its
manifestations include urethral meatus congestion, itching,
310
burning sensation in the navicular fossa, yellow purulent urethral

discharge
the urethral discharge is abundant and it is accompanied by
pollakiuria, dysuria and painful erections
after 10-12 days of development, the infection affects the
posterior urethra, the secretion diminishes in intensity but
dysuria and pollakiuria still persist, along with a terminal
hematuria
all these manifestations can be accompanied by malaise: fever,
headache, tachycardia, fatigue and inflammatory
lymphadenopathy.
Subacute urethritis
Its manifestations include:
urethral discharge in the morning
urethral pruritus affecting the urethral ducts
limy urine
perineal discomfort.
Chronic urethritis
this phase of the gonoccocal infection affects components such
as : urethral glands, paraurethral ducts
permanent purulent secretion, little abundant (open chronic
urethritis)
intermittent purulent discharge alternating with periods of lull
(closed chronic urethritis) due to the release of gonococcal
contents.
Complications of gonococcal infection:
1. local complications:
- balanitis
- phimosis
- paraphimosis
- cystitis
- littritis
- periurethritis.
311
2. Locoregional complications:
- prostatitis
- epididymitis
- orchitis.
Gonococcal infection in women
it presents as an acute urethro-cervicitis characterized by
urinary frequency, dysuria, yellow-green purulent vaginal
discharge
complications include salpingitis, metritis, bartholinitis,
skenitis, which may increase the risk of infertility.
Gonococcal infection in girls
Infant gonorrhea occurs due to contact with contaminated toiletries
(linen, towels).
It manifests as an acute, purulent vulvovaginitis accompanied by
significant inflammatory phenomena.
Extragenital Gonococcal infections
1. rectal gonococcal infection (rectitis)
- manifested by pus, tenesmus and bleeding
- it is common in gay people.
2. Gonococcal oropharyngitis
- clinical manifestations include erythema, swelling, erosion,
purulent deposits and dysphagia
- it occurs as a result of oral-genital sexual practices
3. Gonococcal conjunctivitis
- clinical manifestations include erythema and eyelid edema,
accompanied by purulent secretion
- it occurs in infants who are infected by their mothers during
childbirth, or in adults by self-inoculation of a primary
gonorrheal infection
A hematogenous dissemination can enable remote events such as
gonococcal arthritis, gonococcal carditis or gonococcal septicemia.
Laboratory findings
1. microscopic examination of heavy secretions evidences intracellular
paired gonococci
2. culture on selective media (useful in chronic forms of the disease)
312
Treatment
targets both the source of infection and the sexual partner
uncomplicated forms of disease may require instant treatment
antibiotics belonging to the group of cephalosporins, quinolones
or aminoglycosides are also recommended
chronic , complicated forms of disease require higher doses and
longer courses of antibiotics (7-15 days).
The regimens proposed in the treatment of gonococcal infections must
comply with the following requirements:
they have to be administered in low doses
to achieve up to 100% rate of curing
the side effects should be minimal
that the treatment would not conceal a syphilitic infection
they should not favor the development of other pathogens
they should have a broad spectrum in order to be effective in
cases of miscellaneous infections.
CHANCROID (SOFT CHANCRE, SOFT SORE)

It is a contagious disease caused by Haemophylus Ducrey bacillus,
transmitted through sexual intercourse.
Epidemiology
The source of infection is the patient diagnosed with soft canker and the
only mode of transmission is sexually. Self inoculations may occur
occasionally.
The disease is highly infectious.
Chancroid is frequently found in Africa, South America, whereas in
Europe it has been reported as an eradicated disease.
Etiology
The etiologic agent is a gram negative bacillus, namely Haemophylus
Ducrey, arranged in small groups or pairs. It barely disseminates on special
media due to its strains that release beta-lactamase, providing it resistance to
sulfonamides.
The incubation period ranges from 7 to 30 days.
313
Cutaneous lesions
the lesion of chancroid begins as an erythematous-papular lesion
that ulcerates rapidly
as the disease progresses, the typical lesion presents as a rounded
or oval ulcer, of 0.5-2 cm diameter embedded in the dermis and
surrounded by a double collarette (Petges double collarette)
the base of the ulcer is soft and the bottom is covered with pus
and cellular debris
the edges of the ulcer are straight
the lesion is spontaneously painful or if it is pressed.
Sites
Typically, the ulcers are located in the genital area (fourchette,
balanopreputial fold, prepuce, the sheath of the penis, labia, clitoris, cervix,
perineal region) and rarely extra- genitally. The presence of multiple ulcers is
usually the result of autoinoculation with Ducrey bacillus of the surrounding
areas. Cutaneous lesions are accompanied by lymphangitis and
lymphadenopathy.
Adenopathy
it occurs after approximately 2 weeks after initial infection
iniatially a single lymph node is affected but as the disease
progresses, many more are affected
this adenopathy is inflammatory, painful, leading to a localized
collection of fistulas of oozing pus.
Distinctive clinical forms
a) follicular canker affecting the pilosebaceous follicles
b) phagedenic canker - characterized by significant ulcer, resulting
in erosion of the surrounding tissues
c) papular canker its clinical appearance is of a papule with
slightly protruding edges, resembling papulo-hypertrophic
syphilides.
Evolution - soft chancre heals spontaneously within a few weeks.
Laboratory investigations of diagnostic value include:
1. direct bacteriological examination:
- it uses secretion or pus extracted from the ulcer lymph nodes
314
- special specific staining (Gram, Ziehl, blue toluidine) emphasize

Ducrey bacilli.
2. bacterial growth on selective media:
- Ducrey bacillus requires special culture media, it barely develops
colonies and requires supplementary inoculation
3. ITO Intradermal reaction - the positive reactions at the site of
inoculation give rise to an erythematous papule
4. histopathological examination - reveals an ulcer with necrotic
debris, edematous capillaries, newly generated vessels and vascular
thrombosis.
Differential Diagnosis
Soft canker must be differentiated from:
syphilitic canker
scabby canker
papulo-erosive syphilides
genital thrush
erosive balanitis.
Complications
they are usually the result of the association between Ducrey
bacillus and other anaerobes
clinical manifestations include: phimosis, paraphimosis, fistulas,
extended ulcers.
Treatment
The following types of antibiotics are recommended:
- tetracycline 2g/day for 7-10 days
- erythromycin 2g/day, for 10 days
- ceftriaxone 250mg as a single dose, intramuscularly
- ciprofloxacin 1g/day, for 3 days.
TRICHONOMAS VAGINALIS INFECTIONS

(UROGENITAL TRICHOMONIASIS)
Trichomonas vaginalis is a flagellated protozoan which causes
urogenital infections and it is sexually transmitted. The average incubation
period is about 7 days.
315
The disease is enabled by a number of local factors such as vaginal pH

(alkalinity), estrogen excess, oral contraceptive administration.
Clinical features
women develop a vulvovaginitis characterized by foamy yellow-
green secretion, erythema and erosion of the vaginal mucosa,
accompanied by persistent vulvar itching
in men, the main symptom of infection with Trichomonas
vaginalis is subacute urethritis characterized by minimum
secretion (the morning drop), dysuria, urethral itching and
burning sensations after intercourse
Complications of trichomoniasis
the most common complications are trichomonal prostatitis,
epididymitis and orchiepididymitis, littritis and cowperitis
in women, the complications are rare, however skenitis,
bartholinitis, salpingitis may also occur.
Laboratory findings
the protozoan found in genital secretions is identified through
direct microscopy
the inoculation of the parasite is performed on specific selective
media (Magara medium)
serological diagnosis has not been required in practice.
Treatment
consists in the administration of 2 g metronidazole or fasigin
taken orally, in a single dose
in women, the general treatment is associated with local
treatment: vaginal washes with solutions containing acidic pH
are recommended along with the administration of
metronidazole vaginal tablets.
LYMPHOGRANULOMA VENEREUM (LGV) (NICOLAS-FAVRE

DISEASE)
It is a sexually transmitted disease caused by Chlamydia trachomatis.
The disease is found in tropical and subtropical regions.
316
Etiology
LGV is caused by serovars L1, L2, L3 of Chlamydia trachomatis.
Clinical features
the incubation period is 10-12 days
the initial lesion may be a small shallow ulcer, that heals
spontaneously within a few days, known as
lymphogranulomatous canker (stage I of the disease)
it commonly affects the glans, the foreskin, large and small
labia, the rectal region (in homosexuals)
after a period of 2-4 weeks after the onset, an inguinal
lymphadenopathy occurs, which is unilateral, inflammatory,
forming enlarged lymph nodes (stage II)
during the course of the disease, adenitis fistulizes in many
places, having a typical appearance (of a sprinkler)
usually, the crural and inguinal lymph nodes are affected
untreated, the course of the diesease is higly ulcerative and
destructive, causing ano-rectal strictures, vulvar elephantiasis or
important external genital ulcers (stage III). These lesions may
be accompanied by systemic manifestations: fever, generalized
lymphadenopathy, myalgias.
Positive diagnosis
Chlamydia trachomatis is identified in purulent secretions, which
confirms the diagnosis
detection of chlamydial antigens
the detection of antibodies in the serum and local secretions.
Treatment
general: consists of taking one of the following antibiotics:
- doxycycline 200mg/day, for 21 days
- erythromycin 2g/day, for 21 days
local: it is directed only against important destructive
processes or against long-lasting recto-vaginal fistulas.
317
MUCOCUTANEOUS MANIFESTATIONS IN HIV DISEASE

Various and frequent skin disorders are commonly encountered in HIV-
infected patients. These are described in all stages of the disease, from the
primary infection to the full manifestation of AIDS.
The presence of various lesions in the mouth, is a certainty factor for
AIDS and the presence of other lesions is considered an evolutional marker to
AIDS. It is estimated that up to 10% of the HIV-infected patients develop
lesions of the oral mucosa, and this figure illustrates the importance of knowing
these lesions in medical practice. The HIV subjects frequently develop
opportunistic infections due a low number of T-helper lymphocytes.
Mucocutaneous pathology in HIV is very varied and include events caused by
viruses, fungi, bacteria, protozoa, parasites and may suggest the following: the
onset of an HIV infection, the prognosis of an already known HIV infection, the
worsening of immunosuppression or the onset of therapy.
VIRAL INFECTIONS
Oral hairy leukoplakia
It was described in 1984 in homosexuals, and it accounts for 25% of the
HIV + patients. This manifestation was considered a pathognomonic marker of
HIV infection, but later it has also been reported in other immunocompromised
individuals.
Nowadays it is common knowledge that these lesions are manifestations
of Epstein Barr virus. The presence of oral hairy leukoplakia in HIV + patients
marks the progression of AIDS. Oral hairy leukoplakia manifests as ill
delimited white striae, mucosal adherent, of verrucous surface, commonly
affecting the two posterior thirds and the sides of the tongue. The following
changes are relevant for the diagnosis:
the whiteness of the lesions
the fact that the lesions are present on the sides of the tongue
the stiffness of the lesions
the hairy tongue appearance
the fluctuant nature of the lesions
the fact they do not respond to antifungals.
In most cases the lesions are asymptomatic and the clinical diagnosis
can be confirmed by skin biopsy and by evidencing the Epstein Barr virus in
318
electron microscopy. In practice, oral hairy leukoplakia must be differentiated

from oral candidiasis, but they are intertwined most of the time. A similar
clinical and histological picture, but characterized by the absence of the Epstein
Barr virus, has been identified in HIV + subjects, and it is known as the pseudo
oral hairy leukoplakia.
Herpes simplex (Herpes infection with HSV1 or HPV2)

HIV + subjects are carriers of herpes virus in a proportion of 15%.
Herpes infection singles out due to:
the appearance and severity of its lesions
the extension of its lesions
its recurrent nature.
Clinical manifestations include diffuse erosions, necrotic or
hemorrhagic ulcerations accompanied by fever, located on the dorsal side of the
tongue, cheek mucosa, palate and gums. A particular clinical aspect of HIV +
subjects, is represented by central, longitudinal or transverse linear fissures,
located under the tongue. A clinical diagnosis should be confirmed in all
atypical cases by identifying HSV1 in special cultures.
Common sites for the herpetic lesions include genital, perigenital, anal
or perianal regions, characterized by long-lasting, extensive ulcerations and
recurrent nature.
Shingles (Herpes Zoster)

It is generally regarded as a dermatosis that occurs early in the course of
HIV infection and exhibits the following features
the erythemato-vesicular eruption involves several dermatomes
the lesions are hemorrhagic or necrotic and are accompanied by
severe algia
varicelliform cutaneous disseminations occur frequently
the usual site is cranial or cervical
there may be complications such as encephalitis, pneumonia,
hepatitis.
319
Moluscum contagiosum
as AIDS runs its course, moluscum lesions are large and
numerous, affecting especially the genital and perigenital
regions, as well as the face.
these are typical papulo-nodular lesions with a tendency to
cluster together
they have got a recurrent nature and they barely respond to
treatment.
HPV infections
clinically manifested as common warts (verruca vulgaris), flat
warts (verruca plana) condylomata acuminata or
epidermodysplasia verruciformis.
the lesions are large, numerous, recurrent and present a high risk
of malignancy
they affect the face, the oral or genital mucosa
infections resulted.
BACTERIAL INFECTIONS
Cutaneous manifestations of Staphylococci
Staphylococcus aureus is the pathogen frequently singled out in
patients with AIDS
it is responsible for different clinical forms of the disease:
staphylococcal impetigo, recurrent and treatment-resistant
folliculitis.
Mycobacterial skin infections

commonly involved mycobacteria include the opportunistic
species Mycobacterium avium intracellular, M. fortuitum, which
are responsible for cutaneous or visceral disseminated infections.
Periodontal diseases
The prevalence of periodontitis in HIV + individuals is differently
assessed, and varies from 3% to 69%. Three severe clinical forms are described:
320
comon gingivitis, characterized by painful erythematous

macules, that bleed when in contact with food
necrotic ulcerative gingivitis, in which painful ulcers covered
with false membranes develop on the gums .Their spontaneous
evolution is towards extention, commonly affecting the
interdental papillae. The lesions may be accompanied by fever.
periodontitis is a severe clinical form but commonly seen in HIV
+ patients. The infectious lesions affect not only the buccal
mucosa, but also the bone structures causing acute periodontal
lysis. Abscess and facial cellulitis are common and can be
complicated by septicemia. The diagnosis of periodontitis is a
clinical one. In HIV + subjects, the microbiological examination
reveals varied anaerobic bacteria, gram negative streptococci,
enterococci, staphylococci and yeasts. Gum diseases can occur
early during HIV infection and is linked to a poor prognosis.
Syphilitic infection
The association of HIV infection with Treponema palidum determines
evolutionary changes in each condition. HIV + patients who develop a
syphilitic infection exhibit the following features:
extremely severe clinical manifestations (painful giant canker ,
extensive mucous plaques, fetid ulcerative lesions)
early development of meningovascular syphilis/lues
emergence of malignant lesions of syphilis
limited or no humoral immune response, resulting in reagin and
false- negative treponemal tests.
Bacillary angiomatosis
it is a rare opportunistic ricketsiasis
it manifests clinically as papular-nodular skin lesions of
angiomatous appearance
it usually occurs in advanced stages of disease.
321
FUNGAL INFECTIONS
Oral candidiases are common problems encountered during HIV
infection. Different sequencing or coexisting clinical forms have been described
during the development of the disease.
Muguet is considered a marker of evolutivity and it manifests as
white deposits that rub off easily, located on the back side of the
tongue or in the mouth. This clinical form is usually
asymptomatic but it sometimes may be accompanied by a
stinging sensation that occurs spontaneously or when in contact
with food.
Erythematous candidiasis can take the appearance of
erythematous plaque-like stomatitis commonly affecting the
tongue.Oral candidiasis may rarely take a hyperplastic aspect,
but when this happens, biopsy and pathological examination are
mandatory in order to rule out epidermoid carcinoma.
Perleche or angular cheilitis usually accompany other forms of
candidiasis. Candida species are usually singularised, include
Candida albicans, krusei and tropicalis. Oral candidiasis may
complicate other manifestations in the oral mucosa, and HIV +
patients are subjected to a new evolutionary spurt.
Dermatophytoses
clinical manifestations include: tinea faciei, corporis, cruris,
capitis, pedis and onychomycoses.
the species of fungi involved are: Trichopyton rubrum,
Trichopyton interdigitale and Epidermophyton floccosum
the lesions are extensive, atypical and require prolonged
treatment
Systemic/ Deep mycoses
Cryptococcosis
it is caused by Cryptococcus neoformans
it manifests as chronic ulcerations of the oral mucosa, exhibiting
infiltrated edges, nodules or pseudo-carcinomatous vegetative
structures.
322
the skin lesions are represented by umbilicated papules and

painless erythematous nodules or papulopustular lesions, bullae,
tumorous masses, ulcerations
sites: face, scalp, neck.
Histoplasmosis
it is produced by Histoplama capsulatum
cutaneous lesions include papules, nodules, or ulcers and are
associated with general symptoms such as fever, chills,
hepatosplenomegaly.
Coccidioidomycosis
it is caused by a dimorphic fungus, Coccidoides immitis
clinically manifestations include papules, plaques or
hemorrhagic nodules.
PARASITICAL DERMATOSES
Scabies
widespread parasitic dermatosis, with normal benign
development
in HIV - infected individuals, the lesions are extensive, covered
with scales and crusts filled with parasites (Norwegian scabies).
Rosacea-like eruptions
they are caused by Demodex Folliculorum, a mite that colonizes
the pilosebaceous follicle
these are common lesions in patients with AIDS.
TUMOROUS SKIN LESIONS
KAPOSI'S DISEASE/ KAPOSI'S SARCOMA

The fact that sarcoma lesions affect the mouth of young homosexual
men along with other opportunistic infections, has been linked to AIDS. Even
the presence of a single kaposiform lesion marks the beginning of the disease,
and is relatively independent of the immune status.
Common sites include the hard palate, gums and tongue. Clinical
manifestations include purplish red, slightly infiltrated plaques which
323
subsequently exhibit a tumorous aspect. They are usually multiple lesions,

clustered at the cephalic extremity, showing both a vascular and fibroblastic
proliferation as revealed by skin biopsy.
LYMPHOMAS
Lymphomas occur as a result of a severe immune deficiency. The most
common histological type is large cell immunoblastic lymphoma, accompanied
by lesions in the mouth that include swelling of of the palate, exhibiting an
ecchymotic appearance. Lymphomas usually mark the beginning of the disease
and have a poor prognosis.
ULCERS AND THRUSH (MOUTH SORES)

Ulcerative lesions can be seen on the oral mucosa, since the early stages
of HIV infection. Common clinical characteristics of thrush (regularity,
shallowness) are replaced by the distinctive appearance of the lesions (irregular
borders, base of the ulcerations covered with fetid deposits, and chronic
evolution). These ulcers have a multiple etiology: bacterial, viral, fungal or
iatrogenic.
IATROGENIC LESIONS
Many mouth ulcers can be caused by toxic or immuno-allergic
neutropenia due to sulfonamides, antibiotics or betalactams administration.
Ulcerative lesions may be accompanied by petechial or haemorrhagic bullae, as
a result of an idiopathic thrombocytopenia, frequent and early manifestation of
HIV infection.
Other nonspecific skin manifestations, relevant to HIV infection
include:
Pytirosporum infections (cause an increased prevalence of seborrheic
dermatitis, pityriasis versicolor or pytirosporum folliculitis), prurigo
(manifested as a pruritic erythematous-vesicular eruption, that affects the
extensor surfaces of the limbs), psoriasis vulgaris (during HIV infection, the
lesions are extensive, and their evolution is to erythroderma), lymphomatoid
granulomatosis (characterized by aphtous lesions that affect the oral or
esophageal mucosa), skin xerosis, bullous eruptions (toxic dermal type),
changes in the hair follicle (alopecia) and so on.
324
Rigorous examination of the mouth can suggest:

the onset of HIV infection
the prognosis of an already known HIV infection
worsening of the immunosuppression
the onset of therapy.
325
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Clinical Diagnosis

Descrierea CIP a Bibliotecii Naionale a Romniei

Prof. univ. dr. Doina Azoici - U.M.F. Grigore T. Popa Iai

Coperta: Marius Atanasiu

Editura Gr. T. Popa

Editura Gr. T. Popaeste acreditat de CNCSIS - Consiliul Naional al Cercetrii

Tiparul executat la Tipografia Universitii de Medicin i Farmacie "Gr. T. Popa" Iai

INFECTIOUS DERMATOSES ..................................................................... 64

PARASITICAL DERMATOSES ................................................................ 160

ALLERGIC DERMATOSES ...................................................................... 167

ERYTHEMATO-SQUAMOUS DERMATOSES ...................................... 195

BULLOUS (BLISTERING) DERMATOSES ............................................ 214

MAJOR COLLAGENOSES ........................................................................ 235

ACNE VULGARIS ....................................................................................... 261

BENIGN SKIN TUMORS............................................................................ 270

MALIGNANT SKIN TUMOURS ............................................................... 280

SEXUALLY TRANSMITTED DISEASES ................................................ 295

SKIN STRUCTURE AND FUNCTIONS

Cross-section of the skin

The appendages of the skin are structures regarded as derivatives of

Fig. no. 1 Thick epidermis

Between the epidermis and dermis, there is a basement membrane, made up of

Fig. no. 2 Thin epidermis

Basal lamina is a 20-100nm extracellular structural support, conspicuous in

Entactin, a small sulfated glycoprotein, localized in the basal lamina. It

movement directions. acestora anumite orientri pentru deplasarea lor.

The epithelial ridges corresponding to the palms, plantar regions and

plakoglobin ,183 kDa, located mainly in dense plaque

peeling and therefore the layer is referred to as disjunctum layer, a process in

There are racial differences in terms of size, distribution, and

nipple; they can be identified using special techniques such as argentic

appears as a meshwork of bundles, rarely isolated. The longitudinal section

lacunar region overlopping region

Fig. no. 4 Collagen fiber

This is composed of filaments with a diameter of 3 nm, made up of 1-3

Tropocollagen macromolecules form an ordered array, which provides

Golgi complex, with basophilic cytoplasm due to the rough endoplasmic

Fig. No. 5 Pacinian Corpuscle

Meissners corpuscles are localized within the dermal papillae. They

CUTANEOUS BLOOD VESSELS AND LYMPHATICS

EPIDERMAL SKIN APPENDAGES

Skin appendages include:

Sweat glands include two major types:

Fig. no. 6 Eccrine sweat gland

The secretory segment (adenomer) is located deep in the dermis or in

The composition of sweat can be modified either by nervous or

Apocrine sweat glands are innervated by adrenergic nerve endings.

Fig. no. 7 Sebaceous gland attached to a hair follicle.

-the cortex contains keratinized cuboidal cells, rich in melanin, compactly

Fig no. 8. A cross-section through a hair follicle

The external root sheath is a direct continuation of the stratum malpighii

Fig no. 9 (www.mynailsagain.com.gif)

The matrix contains a number of cell types, as follows: stem cells,

Transverse grooves in nails, known as Beaus lines, reflect temporary

Epidermis and cutaneous annexes develop from ectoderm. Dermis,

Healing of the damaged epidermis in case of incisions or dilacerations ,

1. The morphology of the skin lesions- allows us to identify the skin

1) The history of skin eruption

2) The characteristics of the eruption

- the lesions have a transient nature ( urticarial papule or bullous lesions

3) The arrangement of multiple lesions is extremely evocative for the

psychological factors may be relevant for the development of

7. Immunological tests detect: