BSFCR DERMATOLOGY ANSWERS

Case 1:
A 46-year-old man comes to the physician because of a 4-day history of a burning,
painful skin rash on the right side of his chest associated with headache and a low-
grade fever. He has a 10-year history of type 2 diabetes mellitus. His past medical
history suggests that he had suffered from chickenpox when he was 10 years old. He
drinks alcohol in the weekends and has a 20-pack-year smoking history. Physical
examination shows a group of red papules in a continuous band on the upper right
chest. Right axillary lymph nodes are enlarged. Tzanck preparation and direct
fluorescence antibody (DFA) testing confirm herpes zoster infection in the patient.

Questions & learning objectives for discussion:

1. Compare herpes zoster and herpes simplex under the following heads:
pathogenetic agent, skin manifestations and other clinical features, diagnostic
laboratory tests.

Herpes Simplex:
Definition and Etiology- Herpes simplex virus (HSV) infection is a painful, self-limited,
often recurrent dermatitis, characterized by small grouped vesicles on an erythematous
base in the mucocutaneous regions. HSV type 1 is usually associated with orofacial
disease, and HSV type 2 is usually associated with genital infection.
Pathophysiology and Natural History: Disease follows implantation of the virus via direct
contact at mucosal surfaces or on sites of abraded skin. After primary infection, the
virus travels to the adjacent dorsal ganglia, where it remains dormant unless it is
reactivated by psychological or physical stress, illness, trauma, menses, or sunlight.
Signs and Symptoms: Primary infection manifests as vesicles and erosions on
erythematous skin or mucosa mainly on buccal mucosa, the palate, tongue, lips or
external genitalia. It is occasionally associated with fever, malaise, myalgia, and
regional lymphadenopathy. Prodromal symptoms of pain, burning, or itching can
precede herpes infections.
Diagnosis: Viral culture helps to confirm the diagnosis; direct fluorescent antibody (DFA)
is a helpful but less-specific test. Serology is helpful only for primary infection. The
Tzanck smear can be helpful in the rapid diagnosis of herpes virus infections, but it is
less sensitive than culture and DFA.

Herpes Zoster:
Definition and Etiology: Herpes zoster (shingles) is an acute, painful dermatomal
dermatitis that affects approximately 10% to 20% of adults, often in the presence of
immunosuppression.
Pathophysiology and Natural History: The patient must have had chicken pox (Varicella)
before. During this primary infection, the Varicella-zoster virus travels from the skin and
mucosal surfaces to the sensory ganglia, where it lies dormant for a patient's lifetime.
Reactivation often follows immunosuppression, emotional stress, trauma, and irradiation

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or surgical manipulation of the spine, producing secondary infection called herpes
zoster.
Signs and Symptoms: Herpes zoster is primarily a disease of adults and typically begins
with pain and paresthesia in a dermatomal or bandlike pattern followed by grouped
vesicles within the dermatome several days later. Occasionally, fever and malaise
occur. The thoracic area accounts for more than 50% of cases. It may also involve face
(cranial nerve V).
Diagnosis: Diagnosis is by clinical presentation, viral culture, or direct fluorescent
antibody.

2. Describe the normal histology of skin –include the listing of different strata of
the epidermis, organization of each stratum, special cells present and structures
in the dermis.

Layers of the skin are:

1. Epidermis – It is stratified squamous epithelium. Types of cells in epidermis are
keratinocytes, melanocytes, Langerhans cells and Merkel cells. The keratinocytes the
principal cells that become mature and differentiate and accumulate keratin as they
move outwards. They eventually fall off.
Layers of Epidermis (from outside to inside) are
 Stratum corneum (horny layer)
 Stratum granulosum (granular layer)
 Stratum spinosum (prickle layer)
 Stratum basale (basal layer)
Immediately below the Epidermis is the basement membrane. At certain places, there
are special epidermal adnexal structures (epidermal appendages) such as Hair, Nail,
Sweat glands and Sebaceous glands. Hair follicle is associated with sebaceous glands
and arrector pili smooth muscle.
2. Dermis - The dermis is the fibrous connective tissue layer of the skin. The collagen
and elastic fibers are bound together by ground substance, called mucopolysaccharide
gel. The dermis contains nerves and blood vessels. Dermis also has mast cells,
myoepithelial cells around sweat glands, Fibroblasts that produce and deposit collagen
and other elements of the dermis, Immune cells and other white cells.
Subcutaneous tissue (aka hypodermis/panniculus): It is a layer immediately below the
dermis that mainly consists of adipocytes, nerves and blood vessels.

3. Distinguish clinically the following skin lesions: Macule, Patch, Papule, Nodule,
Plaque, Vesicle, Bulla, Pustule, Scale, Excoriation and Lichenification.

LESION CHARACTERISTICS EXAMPLES

Primary Lesion: Nonpalpable
Macule < 1cm Freckles, mole
Patch > 1cm Congenital nevus, vitiligo,
café au lait spots
Primary Lesion: Palpable, solid mass
Papule < 1cm Mole (nevus), wart, acne

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Nodule Solid raised discrete raised discrete Erythema nodosum
lesion >1 cm in both diameter and
depth
Plaque Papule >1cm but surface area greater Psoriasis
than height
Primary Lesion: Palpable, fluid filled
Vesicle <1cm, filled with serous fluid Herpes simplex, shingles,
Chickenpox
Bullae >1cm, filled with serous fluid Pemphigus vulgaris
Pustule Vesicle filled with pus Pustular Psoriasis
Secondary Lesions
Scale Heaped up keratinized cells; Dandruff, psoriasis,
exfoliated epidermis. Appears above eczema
the skin plane
Excoriation A superficial linear, traumatized area, Abrasion, scratch mark
usually self-induced. Appears below
the skin plane
Lichenification Thick leathery skin usually a result of Eczema
constant scratching and rubbing

4. Describe the morphology, pathogenesis, location of lesion in the skin and

direct immunofluorescence in Pemphigus and bullous pemphigoid.

Pemphigus Bullous pemphigoid

Morphology Intraepidermal acantholysis, Generalized bullous form is the
Flaccid and fragile bullae and most common characterized by
erosions of the skin and/or tense bullae on any part of the
mucosa. Bullae had layering of skin surface, with a predilection
white fluid in its inferior portion. for the flexural areas of the skin.
Oral ulcerations common in Nikolsky sign negative.
pemphigus vulgaris.
Positive Nikolsky sign [the
ability to induce a blister by
applying lateral pressure on an
area of non-blistered skin on
non-eroded areas of skin].
2 major types of pemphigus
1. P. vulgaris [most common]
2. P. foliaceus [less severe]

Pathogenesis Type II hypersensitivity with IgG Type II hypersensitivity reaction,

autoantibodies target with the formation of IgG
desmosome proteins in the autoantibodies against
epidermis namely, desmoglein- hemidesmosomes present in the

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 1 protein [in case of P. dermoepidermal junction.
foliaceus] and desmoglein-3 [in IgG autoantibodies target Bullous
case of P. vulgaris]. Pemphigoid Antigen-1 and Bullous
Pemphigoid Antigen-2, which are
components of hemidesmosomes.

Location of lesion P. vulgaris: Suprabasal In the dermoepidermal junction

(between stratum basale and
stratum spinosum)
P. foliaceus: Subcorneal
(between stratum corneum and
stratum granulosum)
Direct P. vulgaris stains lower layers DIF tests demonstrates IgG in a
Immunofluoresce of epidermis, while P. foliaceus linear band at the dermal-
nce (DIF) stains only in the upper epidermal junction.
epidermis.

Case 2:
A 26-year-old Caucasian man comes to the physician because of erythematous skin
lesions on the extensor surfaces of his elbow, knee and scalp. He also has pain in his
distal interphalangeal joints. Physical examination shows irregular plaques containing
dry, thin, silvery-white micaceous scales on an erythematous base on the extensor
surface of his elbow, knee and scalp. Removing the scale reveals a smooth, red, glossy
membrane with tiny punctate bleeding point (Auspitz sign). Examination of his finger
nails shows pitting and onycholysis. His distal interphalangeal joints are red, warm and
tender.

Questions & learning objectives for discussion:

1. Describe the etiology, pathogenesis, morphology (macroscopic and
microscopic) and clinical features of Psoriasis.
Etiology: The cause of psoriasis is multifactorial.
i) Genetics – Associated with HLA-Cw6 (most definitively associated), HLA-B17 (earlier
onset and more severe disease) and HLA-B27 (associated with spondylitis).
ii) Lifestyle - Chronic infections, stress, scratching skin lesions, skin dryness, excessive
alcohol consumption, cigarette smoking, obesity and changes in season and climate.
iii) Medications - Drug-induced psoriasis may occur with beta blockers, lithium,
antimalarial medications, non-steroidal anti-inflammatory drugs, terbinafine, calcium
channel blockers, captopril, glyburide, granulocyte colony-stimulating factor,
interleukins, interferons, lipid-lowering drugs, and paradoxically TNF inhibitors such as
infliximab or adalimumab.
Pathogenesis: Psoriasis is characterized by an abnormally excessive and rapid growth
of the epidermal layer of the skin. These changes stem from the premature maturation
of keratinocytes induced by an inflammatory cascade in the dermis involving dendritic
cells, macrophages, and T cells. Immune cells move from the dermis to the epidermis
and secrete cytokines such as tumor necrosis factor-α, interleukin-1β, interleukin-6,

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interleukin-36 and interleukin-22. These secreted inflammatory signals are believed to
stimulate keratinocytes to proliferate. Dendritic cells bridge the innate immune system
and adaptive immune system. They are increased in psoriatic lesions and induce the
proliferation of T cells and type 1 helper T cells (Th1). Targeted immunotherapy as well
as psoralen and ultraviolet A (PUVA) therapy can reduce the number of dendritic cells
and favors a Th2 cell cytokine secretion pattern over a Th1/Th17 cell cytokine profile.
Signs and symptoms:
Plaque psoriasis typically appears as raised areas of inflamed skin covered with silvery-
white scaly skin. These areas are called plaques and are most commonly found on the
elbows, knees, scalp, and back.
Pustular psoriasis appears as raised bumps filled with noninfectious pus (pustules). The
skin under and surrounding the pustules is red and tender. Pustular psoriasis can be
localized, commonly to the hands and feet (palmoplantar pustules), or generalized with
widespread patches occurring randomly on any part of the body.
Psoriatic arthritis is a form of chronic inflammatory arthritis that is seen in about 30% of
psoriatic patients. It typically involves painful inflammation of the joints and surrounding
connective tissue and can occur in any joint, but most commonly affects the joints of the
fingers and toes. This can result in a sausage-shaped swelling of the fingers and toes
known as dactylitis. Psoriatic arthritis can also affect the hips, knees, spine (spondylitis),
and sacroiliac joint (sacroiliitis). Skin manifestations of psoriasis tend to occur before
arthritic manifestations.
Nail changes - Nail psoriasis occurs in large population with psoriasis. These changes
include pitting of the nails (pinhead-sized depressions), whitening of the nail, small
areas of bleeding from capillaries under the nail, yellow-reddish discoloration of the nails
known as the oil drop or salmon spot, thickening of the skin under the nail (subungual
hyperkeratosis), loosening and separation of the nail (onycholysis), and crumbling of the
nail. Nail changes are more common than joint involvement.

2. Explain the barrier, protection and regulatory functions of the skin. Indicate the
role of epidermal and dermal components in each function.

Functions of the skin - The most important functions of the skin are:
1. Regulates body temperature.
2. Prevents loss of essential body fluids, and penetration of toxic substances.
3. Protection of the body from harmful effects of the sun and radiation.
4. Mechanical support.
5. Immunological function mediated by Langerhans cells.
6. Sensory organ for touch, heat, cold, socio-sexual and emotional sensations.
7. Vitamin D synthesis from its precursors under the effect of sunlight and
introversion of steroids.

The epidermis is mainly a cellular structure without blood vessels or nerves. The layers
of the epidermis differentiate and gradually develop to a more rigid structure, which
provides a barrier to excessive loss of body fluids and the penetration of noxious
substances. The basal layer is the precursor of the different cells of the epidermis which
divide, pushed further upwards, loosing much of their metabolic function and enzymatic

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activity. The spinous layer is characterized by growth of keratin fibrils where these are
present also in the cells of the basal layer. Epidermal cells as they are pushed up away
from the basal layer, begin to dehydrate and become filled with cross-linked keratin,
which gives the cells a granular appearance. The intercellular lipids, the corneocytes,
amino acids, and other salts from sweat, sebaceous secretions, degradation products
from corneal proteins besides lipids and others all have an important barrier effect
preventing loss of water.
The dermis contains and supports blood vessels, lymph vessels, nerves, hair follicles,
glands and muscle elements. The collagen fibers, elastic fibers and ground substance
give the skin its toughness and elasticity. The dermis contains the specialized sensory
organs and the skin appendages. Below the dermis is a fatty layer known as the
subcutaneous tissue.
 
3. Explain the histological basis for first, second and third degree burns.

Characteristics

Classification Appearance Sensation Healing time Scarring

Superficial burn Dry and red; blanches with Painful Within a week None
(First degree) pressure
Invloves only
epidermis
Superficial Blisters; moist, red and Painful to air 1-3 weeks Unusual;
partial-thickness weeping; blanches with and pigmentary
burn pressure temperature changes
(Second
degree-
superficial)

Deep partial- Blisters (easily unroofed); Perceptive of >3 weeks Severe risk of
thickness burn wet or waxy dry; variable pressure only contracture
(Second color (patchy to cheesy
degree-deep) white to red); does not
blanch with pressure

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Full-thickness Waxy white to leathery Deep Never on its Very severe
burn gray to charred and black; pressure only own risk of
(Third degree) dry and inelastic; does not contracture
Extends through blanch with pressure
the entire
dermis and into
the underlying
subcutaneous
tissue.

CASE 3
A 36-year-old woman comes to the physician because of a changing mole on the
medial side of her left ankle. The mole has been increasing in size and changing its
color from brown to bluish black in the last 8 months. There is no history of itching or
pain. There is no history of skin cancer in the family. Her personal history is significant
for frequent sun baths. Physical examination shows an elevated bluish brown lesion of
12 mm diameter with irregular and asymmetric borders. The inguinal lymph nodes are
not palpable. Biopsy of the lesion shows an increased number of intraepithelial
melanocytes that are large, atypical, arranged haphazardly at the dermoepidermal
junction and show upward (pagetoid) migration.
Questions & learning objectives for discussion:

1. Describe the structure, nerve supply and functions of the hair follicles, sebaceous
glands, eccrine and apocrine sweat glands.

A hair follicle is an epidermal appendage that produces hair.

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The papilla is a large structure at the base of the hair follicle. The papilla is made up
mainly of connective tissue and a capillary loop. The substance around the papilla is the
hair matrix. The root sheath is composed of an external and internal root sheath.

Sebaceous glands are microscopic exocrine glands in the skin that secrete an oily or
waxy matter, called sebum, to lubricate and waterproof the skin and hair. In humans,
they occur in the greatest number on the face and scalp, but also on all parts of the skin
except the palms of the hands and soles of the feet. There are two types of sebaceous
gland – (i) some sebaceous glands are connected to hair follicles, in pilosebaceous
units, and are found in hair-covered areas. One or more glands may surround each hair
follicle, and the glands themselves are surrounded by arrector pili muscles. (ii) some
sebaceous glands exist independently. These glands are found mainly in hairless areas
such as the eyelids, nose, penis, labia minora, the inner mucosal membrane of the
cheek, and nipples. Androgens stimulate sebaceous secretion. Dihydrotestosterone
acts as the primary androgen.

Sweat glands: Two types namely, eccrine and apocrine.

Eccrine sweat glands: These are the major sweat glands found in all skin, with the
highest density in palms and soles. They are active in thermoregulation by providing
cooling from water evaporation of sweat secreted by the glands on the body surface
and emotional induced sweating (anxiety, fear, stress, and pain). Eccrine glands
function throughout life since birth. The secretion of eccrine glands is a sterile, dilute
electrolyte solution with primary components of bicarbonate, potassium, and sodium
chloride (NaCl). Eccrine glands are supplied by post ganglionic sympathetic
cholinergic fibers.
Apocrine sweat glands: This type of sweat gland is found only in certain locations of
the body, namely, in axillae, areola and nipples of the breast, ear canal, perianal region,
and the external genitalia. Being sensitive to adrenaline, apocrine sweat glands are

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involved in emotional sweating (induced by anxiety, stress, fear, sexual stimulation, and
pain) and in situations of generalized sympathetic stimulation. They are not involved in
the thermoregulation. Apocrine glands are supplied by post ganglionic sympathetic
adrenergic fibers.

2. Discuss the origin and role of melanocytes. Trace the development and fate of
the granule, melanin.

Origin and function: Melanocytes originate from the neural crest and migrate to the
specific locations within the skin and hair follicles, and to other sites in the body.
Melanocytes are thus found in the basal layer of the epidermis as well as in hair
follicles, the retina, uveal tract, and leptomeninges. Melanocytes primarily function to
produce a pigment, melanin, which absorbs radiant energy from the sun and protects
the skin from the harmful effects of UV radiation.
Production of Melanin: Three main chemical reactions occur in the synthesis of melanin,
all of which occur within the melanosome. Tyrosinase is an enzyme essential for
melanin synthesis that converts tyrosine to DOPA, and DOPA to Dopaquinone.
Dopaquinone in a final reaction is converted into one of the two types of melanin-
phaeomelanin (light melanin) or eumelanin (melanin).
Expression of melanin as skin pigments: Melanin is packaged and expressed on the
skin surface. Melanin accumulated within the melanosomes are incorporated into
dendrites anchoring the melanosome to the surrounding keratinocytes. Ultimately, the
melanosomes are transferred via phagocytosis to the adjacent keratinocytes in the
epidermis where they remain as granules.
The figure below shows the essential steps.

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3. Distinguish between thick and thin skin, including location and components
found in each type.

Thick skin refers to skin that contains all five of the major layers of the epidermis. It is
only found on the soles of the feet, the palms of the hand. There are no sebaceous
glands and hair follicles in the thick skin.
Thin skin is the one that has only 4 layers of epidermis. The stratum lucidum is absent.
Skin covering the whole body except palm and sole is made of thin skin.

4. Explain “A-B-C-D-E” of an existing nevus. Differentiate four major

clinicopathologic subtypes of cutaneous melanoma, namely superficial spreading
melanoma, Nodular melanoma, Lentigo maligna melanoma and Acral lentiginous
melanoma.

The earliest stage of melanoma starts when melanocytes begin out-of-control growth.
Melanocytes are found between the outer layer of the skin (the epidermis) and the next
layer (the dermis). This early stage of the disease is called the radial growth phase,
when the tumor is less than 1 mm thick. Because the cancer cells have not yet reached
the blood vessels deeper in the skin, it is very unlikely that this early-stage melanoma
will spread to other parts of the body. If the melanoma is detected at this stage, then it
can usually be completely removed with surgery. Tumor cells growing vertically up into
the epidermis and down into the papillary dermis is dangerous. The vertical tumor
thickness is an important factor in deciding the prognosis of melanoma.

Signs and symptoms:

Early signs of melanoma are changes to the shape or color of existing moles or, the
appearance of a new lump anywhere on the skin. At later stages, the mole may itch,
ulcerate or bleed. Early signs of melanoma are summarized by the mnemonic
"ABCDE":
 Asymmetry
 Borders (irregular)
 Color (variegated)
 Diameter (greater than 6 mm (0.24 in), about the size of a pencil eraser)
 Evolving over time.
Four major clinicopathologic subtypes of cutaneous melanoma are:
1) Superficial spreading melanoma
2) Nodular melanoma
3) Lentigo maligna melanoma
4) Acral lentiginous melanoma.

Superficial spreading melanoma:

 Most common in 30-50 years
 Most common subtype (70%)
 Most common on trunk in men and women and on the legs in women

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  Commonly displays the ABCD warning signs
 Flat or slightly elevated brown lesion with variegate pigmentation
 Histologically - pagetoid scatter of atypical melanocytes within the epidermis

Nodular melanoma:
 Commonly on the legs and trunk in both sexes
 Rapid growth occurs over weeks to months
 Dark brown-to-black papule or dome-shaped nodule
 May be amelanotic (not pigmented); thus, any rapidly growing flesh-colored
lesion
 Ulcerates or bleeds with minor trauma
 Tends to lack the typical ABCDE melanoma warning signs

Lentigo maligna melanoma:

• Elderly population (>65)
• Commonly on the head, neck, and arms (chronically sun-damaged skin)
• Grows slowly over 5-20 years
• The in-situ precursor lesion (termed lentigo maligna) is present for a minimum of
10-15 years, and demonstrates macular (flat) pigmentation
• Raised blue-black nodules within the in-situ lesion.
• Histologically, characterized by a predominantly junctional confluent proliferation
of melanocytes and extension along adnexal structures.

Acral lentiginous melanoma:

• Least common subtype of melanoma in white persons
• Most common subtype of melanoma in dark-skinned individuals (African
American, Asian, and Hispanic persons)
• Occurs on the palms, the soles, or beneath the nail plate (subungual variant)
• Hutchinson sign (pigments spreading to the proximal or lateral nail folds) is a
hallmark for subungual melanoma.

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