Connective Tissue Diseases Localized DLE

Mucinoses - Usually Iocalized above the neck: scalp, bridge of

Endocrine Diseases the nose, malar areas, lower lip and ears (concha
of the ear and external canal)
Connective Tissue Diseases - Some patients with periorbital edema and
erythema
- Lupus Erythematosus - Scalp: erythematous patches or plaques to white,
- Dermatomyositis often depressed, hairless patches
- Scleroderma - Lips: may be gray or red and hyperkeratotic; and
- Rheumatoid Arthritis are usually surrounded by a narrow, red
- Sjogren Syndrome inflammatory zone Signs of active disease:
- Eosinophilic Fasciitis Perifollicular erythema and easily extractable
- Relapsing Polychondritis anagen hairs

Lupus Erythematosus Generalized DLE

- LE is the designation of a spectrum of disease
patterns that are linked by distinct clinical findings
and distinct patterns of cellular and humoral
autoimmunity
- With skin-only disease at one end of the spectrum
and severe visceral involvement at the other
- Occurs commonly in women (9:1 female-male
ratio)
- LE ranges from life-threatening manifestations of
acute systemic LE (SLE) to the limited and exclusive
skin involvement in chronic cutaneous LE (CCLE)
Acute cutaneous lupus erythematosus (ACLE)
- is practically always associated with SLE
- almost always associated with underlying visceral
involvement
Subacute cutaneous lupus (SCLE)
- 50% meet the criteria of SLE
- Less common than localized DLE Predilection sites:
head, neck, thorax and upper extremities Scalp:
quite bald with striking patterns of
hyperpigmentation and depigmentation
- Diffuse scarring may involve the face and upper
extremities
- Laboratory abnormalities: elevated erythrocyte
sedimentation rate (ESR), elevated antinuclear
antibodies (ANAs), singlestranded (ss)DNA
antibodies, or leukopenia
CCLE: Hypertrophic
2. Hypertrophic LE
- Non-pruritic papulonodular lesions
- Predilection sites: arms, hands, scalp and lips
- Resembles keratoacanthoma or hypertrophic
lichen planus (LP) Seen in SLE while some have
only cutaneous involvement

Chronic cutaneous lupus (CCL) CCLE: LE-LP Overlap

- Discoid lupus erythematosus
- Lupus panniculitis
- Chilblain lupus
- Tumid lupus erythematosus
--Most often have skin-only or skin-predominant disease
Chronic Cutaneous LE: Discoid
1. Discoid Lupus Erythematosus
- F>M; young adults
- Most common form
- Characterized by dull red macules or indurated
plaques
- Presence of adherent scale atrophy, scarring, and
pigment changes
- Carpet tack-like spines under the scale
- In darker-skinned individualş: areas with
hyperpigmentation and depigmentation
- In lighter-skinned patients: gray or have little
pigment alteration
- Course of DLE is variable (95% of cases confined to
the skin at the outset will remain localized)
- Purely cutaneous DLE to SLE is uncommon. SLE
with discoid; lesions are common
- Fever and arthralgia are common in patients with
SLE and discoid lesions Do biopsy and DIF (75% of
cases positive)
3. LE-LP Overlap syndrome
- Lesions are large, atrophic, hypopigmented, red or
pink patches and plaques + fine telangiectasia and
scaling
- Predilection sites: extensor aspects of the
extremities and midline back
- Prominent palmoplantar involvement is
characteristic and most troublesome feature
- Nail dystrophy and anonychia
- Scarring alopecia and oral involvement
- Treatment: potent topical corticosteroids,
dapsone, thalidomide, isotretinoin,
mycophenolate, mofetil or azathioprine
- Response to treatment is poor
CCLE: Chilblain
4. Chilblain LE (Hutchinson)
- F>M
- Chronic and unremitting form of LE
- Predilection sites: fingertips, rims of ears, calves,
and heels
- It is usually preceded by DLE on the face
- Systemic involvement is sometimes seen
- Diffential Diagnosis: Sarcoidosis
 - Diagnostic: Cryoglobulins and antiphospholipid
antibody SCLE: Neonatal

CCLE: Tumid LE NEONATAL LE

F>M; born to mothers who carry
5. Tumid Lupus Erythematosus the Ro/SSA antibody
NO skin lesions at birth but
Rare but distinctive entity develop them during the first few
Present with edematous erythematous weeks of life.
plaques Annular erythematous macules
Predilection site: trunk and plaques
Resembles reticular erythematous Predilection site: head and
mucinosis extremities
Treatment: antimalarials Associated with periocular
involvement (raccoon eyes)
CCLE: Lupus Panniculitis
SCLE: Neonatal
6. Lupus Panniculitis (LE Profundus)
Kaposi Irgang Disease Associated with congenital heart block,
F>M; 20-45 years old thrombocytopenia and hepatic disease
Firm, sharply defined and nontender Strong association with Ro/SSA autoantibody
subcutaneous nodules Resolve spontaneously by 6 months of age and heal
Predilection site: proximal extremities without significant scarring +atrophy
May have DLE at other sites Dyspigmentation and persistent telangiectasias may
May heal with deep depressions from remain for months to years
loss of the panniculus.
DDx: Subcutaneous panniculitis-type SCLE: Complement Def Syndrome
lymphoma
Complement Deficiency Syndrome
Subacute Cutaneous LE
Deficiencies of the early components, especially C2 and
Clinically distinct subset of cases of LE C4
F>M; 15-40 years old; whites Presents as photosensitive annular sCLE lesions
Approximately 10-15% of the LE population Patients with C4 deficiency often have hyperkeratosis of
Presents as transient red to pink with faint violet polycyclic the palms and soles
annular lesions or psoriasiform plaques +Ro/SSA antibody formation
With thin easily detached scale and telangiectasia or Heterozygous deficiency of either complement
dyspigmentation component C4A or C4B has a frequency of approximately
Follicles are not involved; NO SCARRING 20% in white populations
Common in sun-exposed areas: face and neck, the V Homozygous deficiency of both is rare
portion of the chest and back; arms
Photosensitivity is prominent Acute Cutaneous LE
20% has concomitant DLE
Commonly affects the malar areas of the face
Associated with arthralgia or arthritis, autoimmune (Butterfly distribution)
thyroid disease Skin lesions are transient and heal with less
80% positive ANA test, 20% has leukopenia pigmentary change
Majority have antibodies to Ro/SSA antigen, and Well-demarcated patches of
most are positive for human leukocyte antigen erythema with fine overlying
(HLA)-DR3 scale on the dorsal aspect of
Drug-induced SCLE s related to hydrochlorothiazide, the hands, fingers, and
angiotensin-converting enzyme (ACE) inhibitors, periungual areas
calcium channel-blockers, interferons (IFNs), Characteristic sparing of the
anticonvulsants, griseofulvin, glyburide, piroxicam, knuckles (which are
penicillamine, spironolactone, terbinafine and statins. preferentially involved in DM)
Treatment: sun protection and antimalarial agent
Systemic Lupus Erythematosus
Annular polycylic erythenmatous plaques
on the V portion of the back Criteria for Clasification of SLE
- should fulfill 4 out of 11
Malar rash: fixed erythema, flat or raised, over the malar
Annular polyclic SCLE with central areas of eminences, tending the spare the nasolabial folds
hypopigmentation Discoid rash: erythematous raised patches with adherent
keratotic scaling and follicular plugging; atrophic scarring
Photosensitivity: skin rash as a result of unusual reaction to
sunlight, by patient history or physician observation
Oral ulcers: oral or nasopharyngeal ulceration, painless
Arthritis: Non-erosive arthritis involving two or more
periphery
joints, characterized by tenderness, swelling, or effusion
Immunologic findings in SLE
ANA test. This is positive in 95% of cases of SLE.
Lupus erythematosus cell test: specific but not very
sensitive
Double-stranded DNA. Anti-dsDNA: Specific but not very
sensitive; indicates high risk of renal disease
Anti-ssDNA antibody: sensitive but not specific. An igM
isotope
seen in DLE may identify a subset of patients at risk for
developing systemic synmptoms
Anti-Sm antibody: very high specificity but only 10%
sensitive
Antinuclear ribonucleic acid protein (anti-nRNP): Very high
titers
are present in mixed connective tissue disease, lower titers
may
be seen in SLE
Immunologic findings in SLE
Anti-La antibodies: common in SCLE and Sjögren syndrome,
and occasionally found in SLE
Anti-Ro antibodies: 25% of SLE and 40% of Sjögren cases.
They are more common in patients with SCLE (70%),
neonatal LE (95%), C2- and C4-deficient LE (50-75%), late-
onset LE (75%), and Asian patients with LE (50-60%).
Serum complement: Low levels indicate active disease and
often with renal involvement
Antiphospholipid antibodies: may occur in association with
lupus and other connective tissue disease
Childhood SLE
Onset of childhood occurs between the ages of 3 and 15
F>M: 4:1
Typical butterfly eruption on the face and photosensitivity
Involvement of the oral mucosa
May be associated with joint, renal, neurologic, and
gastrointestinal disease, weight loss, fatigue,
hepatosplenomegaly lymphadenopathy, and fever
SLE and Pregnancy
Women with LE may have successful pregnancies
Difficult in conceiving; greater frequency of miscarriages
Course of pregnancy may be entirely normal
(Remission of the LE or the symptoms of LE may
become worse)
Risk of fetal death is increased in women with a previous
history of fetal loss and anticardiolipin or anti-Ro
antibodies
A flare of SLE may occur during the postpartum period
Systemic Lupus Erythematosus
Local treatment
The single most effective local treatment is the
injection of corticosteroids into the lesions
Application potent or superpotent topical
corticosteroids
Topical calcineurin inhibitors (topical macrolactams)
may also be useful as second-line topical therapy
Photodynamic therapy has been reported as
effective
Systemic treatment
The safest class of systemic agent for LE is the antimalarials
Retinoids are second-line agents and are particularly
helpful in
treating hypertrophic LE
Systemic immunosuppressive agents are often required to
manage the systemic manifestations of LE and are third-line
systemic agents for cutaneous LE
Thalidomide can be effective but its use is limited by the
risk of
teratogenicity and neuropathy
Dapsone is the drug of choice for bullous systemic LE, and
may
be effective in some cases of SCLE and DLE
oral prednisone is generally reserved for acute flares of
disease
Dermatomyositis
FM; common in Blacks; relatively rare
Evolve through multiple sequential phases:
(1) a genetically determined susceptibility phase
(2) an induction phase triggered by an
environmental stimulus (e-g, ultraviolet light,
infection) involving loss of tolerance to self-
antigens in skin and skeletal muscle
(3) an autoimmune expansion phase
(4) an injury phase involving multiple immunologic
effector mechanisms.
Dermatomyositis
Characterized by inflammatory myositis and skin disease
Variant:
Amyopathic DM: subclinical or absent myopathy
Polymyositis PM: muscle involvement without skin
changes
Muscle involvement: weakness of proximal muscle
groups is characteristic
Dermatomyositis
Cutaneous Lesions:
Predilection sites: nape of the neck, upper chest (V)
pattern, and upper back, neck, and shoulder (shawl)
pattern
Edema and pink violet discoloration are often signs
of inflammation in the underlying striated orbicularis
Oculi muscle
Dermatomyositis involvement but some patients have typical skin findings
DIAGNOSTIC CRITERIA of DM but never develop clinically apparent muscle
*Dermatomyositis: Patients with the CUTANEOUS lesion +4 involvement.
remaining Muscle weakness is seen symmetrically involving the
*Polymyositis: Patients with NO CUTANEOUS lesion >4 shoulder girdle, pelvic region and hands
remaining Difficulty in lifting even the lightest objects, unable to
raise their arms to comb their hair and rising from a chair
Cutaneous lesions (erythema, scaling, and swelling) may be impossible without "pushing off" with the arms.
Heliotrope rash (pinkish violet edematous erythema on the Pain in the legs when standing barefoot or of being unable
upper to climb stairs.
palpebra
Gottron's papules or sign (pinkish violet flat-topped Dermatomyositis
papules,
atrophy, or erythema on the extensor surfaces and finger Muscle Involvement:
joints) Difficulty in swallowing, talking, and breathing
Some patients with severe diaphragmatic disease require
Dermatomyositis mechanical ventilation and cardiac failure may be present
in the terminal phase of the disease
DIAGNOSTIC CRITERIA Calcium deposits in the skin and muscle: 50% of children
Proximal muscle weakness (upper or lower extremity and with DM
trunk Calcification is related to duration of disease activity and
Muscle pain on grasping or spontaneous pain its severity
Myogenic changes on EMG Calcinosis of the dermis, subcutaneous tissue, and muscle
Elevated serum creatine kinase or aldolase level occur mostly on the upper half of the body around the
Positive anti-Jo-1 (histadyl tRNA Synthetase) antibody shoulder girdle, elbows, and hands
Nondestructive arthritis or arthralgias
Systemic inflammatory signs (fever, elevated serum CRP Dermatomyositis
levelor
accelerated ESR) DM may overlap with other connective tissue
Pathologic findings compatible with inflammatory myositis diseases
DM is associated with malignancy with highest
Dermatomyositis probability within 2 years of the diagnosis; 50-60s
years of age
Cutaneous Lesions: Factors associated with malignancy include age,
Telangiectatic vessels often become constitutional symptoms, rapid onset of DM, the
prominent in the proximal nailfolds lack of Raynaud phenomenon, and a grossly
Enlarged capillaries of the nailfold as elevated ESR or creatine kinase level
dilated, sausage-shaped loops with
adjacent avascular regions Dermatomyositis: Childhood

Dermatomyositis Two childhood variants

Mechanic's hands Brunsting type

Hyperkeratosis, scaling, fissuring,
hyperpigmentation over the
fingertips, sides of the thumb, and 4
fingers with occasional involvement
of the palms
Seen in 70% of patients with
antisynthetase antibodies
Dermatomyositis
Cutaneous Lesions:
Pruritic scaly pink patches are often seen in amyopathic DM
Pruritus may be severe in some cases and is much more
common in DM than in psoriasis or LE
Bullous DM may portend a poor prognosis (often with
severe inflammatory myopathy or lung disease)
more common, has a
slow course, progressive weakness,
calcinosis, and steroid responsiveness
Banker type
-characterized by a vasculitis
of the muscles and gastrointestinal tract,
rapid onset of severe weakness, steroid
unresponsiveness, and a high death rate
Internal malignancy is seldom seen in
children
Calcinosis cutis is more common in children
with severe disease
Dermatomyositis

Dermatomyositis Elevated serum levels of creatine kinase

Muscle Involvement: Other indicators of active muscle disease: aldolase, lactic
Skin involvement commonly precedes muscle dehydrogenase and transaminases
Laboratories: leukocytosis, anemia with low serum iron Thibierge-Weissenbach syndrome (commonly referred to
and an increased ESR as the CREST syndrome)
Positive ANA tests are seen in 60-80%;
35-40% have myositisspecific antibodies Scleroderma: Morphea
Cutaneous types
Dermatomyositis
Morphea:
Treatment: Self limited or chronically relapsing autoimmune disorder
Prednisone is the mainstay of acute treatment (doses targeting the skin with the following major features:
beginning with 1 mg/kg/day until the severity decreases Inflammatory, sclerotic, atrophic phases
and muscle enzymes are almost normal) Thickened sclerotic skin
Methotrexate and mycophenolate mofetil are used as Systemic disease including arthritis and neuro
steroid-sparing agents disorders
Daily use of sunscreens with high SPF
Antimalarials, such as hydroxychloroquine are useful in Scleroderma: Linear Morphea
abating the eruption of DM
1. Linear Morphea
Dermatomyositis F>M; children
Presents most often as macules or plaques a few
Prognosis: centimeters in diameter, but also may occur as bands
Major causes of death are cancer, ischemic heart disease, or in guttate lesions or nodules.
and lung disease Rose or violaceous smooth hard macules
Independent risk factors: depressed, yellowish-white or ivory lesions
failure to induce clinical remission Most common on the trunk> extremities
white blood cell count above 10 000/mm3
temperature greater than 38°C at diagnosis Linear indurated plaques
older age
shorter disease history Typical morphea plaque
dysphagia
Early aggressive therapy in juvenile cases is associated with Scleroderma: Morphea LSEA overlap
a lower incidence of disabling calcinosis cutis
2. Morphea-lichen sclerosus et atrophicus overlap
Connective Tissue Diseases Presents with both lesions of morphea and lichen sclerosus
et atrophicus (LSA).
Lupus Erythematosus FM
Dermatomyositis Widespread morphea who have typical LSA lesions either
Scleroderma separated from morphea or overlying morphea
Rheumatoid Arthritis
Sjogren Syndrome Sclerodernma: Generalized Morphea
Eosinophilic Fasciitis
Relapsing Polychondritis 3. Generalized Morphea
Mixed Connective Tissue Disease Widespread involvement by
indurated plaques with
Scleroderma pigmentary change
WITH Muscle atrophy
Scleroderma is characterized by NO visceral involvement
the appearance of Spontaneous involution is less
circumscribed or diffuse, hard, common
smooth, ivory-colored areas
that are immobile and give the Scleroderma: Pasini and Pierini
appearance of hidebound skin
It occurs in both localized and 4. Atrophoderma of Pasini and Pierini
systemic forms Consists of asymptomatic brownish-
gray, oval, round or irregular, smooth
Scleroderma atrophic lesions depressed below the
level of the skin with a well
Cutaneous types: demarcated, sharply siloping border
Morphea (localized, generalized, profunda, atrophic, and Atrophoderma occurs mainly on the
pansclerotic types) trunk of young individuals
Linear scleroderma predominately females

Systemic scleroderma Scleroderma: Linear

Progressive systemic sclerosis
5. Linear scleroderma
Begins during the first decade of life
Linear lesions may extend the length of the arm
or leg, and may follow lines of Blaschko
Lesions may also occur parasagittally on the
frontal scalp and extend part way down the
forehead (En Coup De Sabre)
The Parry-Romberg syndrome: a progressive
hemifacial atrophy, epilepsy, exophthalmos, and
alopecia
Physical therapy of the involved limb is of
paramount importance to prevent contractures
and frozen joints
Systemic Scleroderma
1. CREST Syndrome
This variant of systemic scleroderma has the most
favorable prognosis
Patients with the syndrome develop calcinosis cutis,
Raynaud phenomenon, esophageal dysmotility,
sclerodactyly, and telangiectasia
Present with sclerodactyly, severe heartburn, or
telangiectatic mats
Lacks serious renal or pulmonary involvement
Anticentromere antibodies are highly specific for the
CREST syndrome
Calcinosis in CREST syndrome
Systemic Scleroderma
2. Progressive systemic sclerosis
A generalized disorder of connective tissue
in which there is thickening of dermal
collagen bundles, and fibrosis and vascular
abnormalities in internal organs
Raynaud phenomenon is often the first
manifestation "woody edema" of the
hands
Systemic involvement: heart, lungs5,
gastrointestinal tract, kidney
F>M; 30-50 years of age
Systemic Scleroderma
Classic criteria include
either proximal sclerosis OR
two or all of the following
1. sclerodactyly
2. digital pitting scars of the
fingertips or loss of substance of the
distal finger pad
3. bilateral basilar pulmonary fibrosis
Systemic Scleroderma
Raynaud phenomenon
at least two-phase color change in fingers and often toes
consisting of pallor, cyanosis, and reactive hyperemia
Cutaneous findings:
The face appears drawn,
stretched, and taut, with loss of
lines of expression
Lips are thin, contracted, and
radially furrowed
The nose appears sharp and
pinched, and the chin may be
puckered
"Neck Sign" as a ridging and
tightening of the neck on
extension, which occurs in 90% of
patients with scleroderma
Internal Involvement:
Skeletal:
Polyarthritis may be the first symptom in systemic sclerosis
Tautness of skin > Limitation of motion- ankylosis and
severe contractual deformities
Hand joints are involved most frequently
Osteoporosis and sclerosis of the bones of the hands and
feet
of the vault of the skuil.
Gastrointestinal:
Esophageal involvement (>90% of patients); dysphagia and
reflux esophagitis
Small intestinal atonia >constipation, malabsorption, or
diarrhea.
Pulmonary: fibrosis with arterial hypoxia, dyspnea,
productive
cough
Most frequent pathologic change in the lungs: Progressive
nonspecific interstitial fibrosis, with bronchiectasis and cyst
formation
Ominous signs: Pulmonary hypertension and right-sided
heart failure
Prognosis
The course of PSS is variable
Pulmonary disease is the major cause of death
Patient's age at onset is a significant risk factor for
pulmonary arterial hypertension
Anticentromere antibodies correlate with CREST syndrome
and a good prognosis
Scl-70 and ANA correlate with a poorer prognosis
Malignancy may be associated with systemic sclerosis in up
to 10% of patients (lung and breast cancer as the most
frequent associated malignancies)
Systemic Scleroderma
Treatment
1. Raynaud Phenomenon
Vasodilating drugs (calcium-channel blockers, angiotensin I
receptor antagonists, topical nitrates, and prostanoids)
remain the mainstay of medical therapy for Raynaud
phenomenon.
Physical therapy emphasizing range of motion for all joints
and mouth
Avoidance of exposure to cold and smoking
Sildenafil (Viagra) and intravenous or inhaled iloprost for
both pulmonary hypertension and Raynaud phenomenon.
Systemic Scleroderma 59:501 1
Treatment
2. Cutaneous disease
Treatment of skin lesions remains unsatisfactory
Systemic corticosteroids, TNF blockade, Rituximab,
Cyclophosphamide, Methothrexate
Phototherapy and photochemotherapy, especialy with UVA
3. Antifibrotic for Systemic Sclerosis
D-penicillamine, Relaxin, Interferon, anti-TGF
Rheumatoid Arthritis
A systemic inflammatory autoimmune disease
Characterized by a debilitating chronic, symmetric
polyarthritis
Associated with significant extra-articular
manifestations: rheumatoid nodules, pyoderma
gangrenosum, granulomatous dermatitis,
rheumatoid vasculitis, and internal organ
involvement
Rheumatoid Arthritis
Rheumatoid nodule
Subcutaneous nodules are seen in
20-30%
Predilection sites: over the bony
prominences, especially on the
extensor surface of the forearm just
below the elbow and the dorsal
hands
Lesions are nontender, firm, skin- Rheumatoid nodule
colored, round nodules
Occur in 5-7% of patients with SLE
+Rheumatoid factor
Rheumatoid Arthritis
Rheumatoid nodule
nontender, firm, skin-
colored, round nodules
Differentitate with
Xanthoma (yellowish)
Heberden Nodes in OA
(tender, hard, bony exostoses,
DIPs)
Rheumatoid Arthritis
Rheumatoid Vasculitis
Peripheral vascular lesions appear as
typical features of RA
Small-to medium-sized vessels are
primarily affected
Associated with peripheral neuropathy
including motor), digital gangrene, nail
fold infarcts, and palpable purpura
Bywaters lesions are nail fold
telangiectasias with minute digital
ulcerations or petechiae and digital pulp
papules
Rheumatoid Arthritis
Rheumatoid Vasculitis
Rheumatoid papules are papular lesions
located primarily on the hands
+Rheumatoid factor
Treatment: Prednisone and cytotoxic
agents are commonly used
Rituximab has also been used
successfully
Juvenile Rheumatoid Arthritis
A group of disorders characterized by
arthritis and young age of onset
Most common type of Arthritis in
children
Still's disease accounts for only 20% of
the patients
Skin manifestations in 40% of young
patients ranging in age from 7 to 25
years.
Juvenile Rheumatoid Arthritis
Eruption consisting of evanescent,
non-pruritic, salmon-pink, macular,
or papular lesions on the trunk and
extremities onset of joint
manifestations by many months
Most remit permanently by
adulthood
Sjogren Syndome
One of the most common rheumatic autoimmune
diseases
FM (9:1); 50-60s
Chronic autoimmune disease characterized by chronic
inflammation involving the exocrine glands
Salivary and lacrimal glands are predominantly affected
leading to dry mouth (Xerostomia) and dry eyes
(Xerophthalmia)
One-third of patients present with extraglandular
manifestations such as vasculitis
Sjogren Syndome
Exocrine Gland Involvement:
Xerophthalmia or Keratoconjunctivitis sicca (dry eye):
burning and itching sensation exacerbated by smoke and
lack of tear production
xerostomia (dry mouth): decrease saliva secretion may
produce difficulty in speech and eating, increased tooth
decay, thrush, and decreased taste (hypogeusia)
Rhinitis sicca (dryness of the nasal mucous membranes)
may induce nasal crusting and decreased olfactory acuity
(hyposmia)
Vaginal dryness and dyspareunia may develop
Sjogren Syndome
Non-Exocrine Gland Involvement:
Cutaneous manifestations linear depressions occur within
1. Vascular lesions: the thickened skin follows the
Raynaud Phenomenon without telangiectasia course of underlying vessels
(unlike systemic sclerosis), Cutaneous vasculitis, Predilection sites: upper arms,
Annular erythema, Erythema multiforme, Erythema thighs, flanks
nodosum Sparing of the hands and face
2. Non-vascular Dry mucous membrane, atrophy of the Prodrome of strenuous muscular
tongue, candidiasis, angular cheilosis, eyelid dermatitis, activity-> weakness, fatigability,
alopecia, vitiligo pain, sweling of extremities

Sjogren Syndome Eosinophilic Fasciitis

Non-Exocrine Gland Involvement: Limitation of flexion and extension of the limbs

Non-Cutaneous manifestations Contractures may be present
1. Musculoskeletal: Associated systemic abnormalities: carpal tunnel
Symmetric nonerosive polyarthritis syndrome, peripheral neuropathy, seizures, optic
2. Visceral: neuropathy, pleuropericardial effusion, Sjögren
Tracheobronchitis Sicca (dryness of the tracheal syndrome, IgA nephropathy, anemia
mucosa) Peripheral blood eosinophilia of 10-40% is the rule
Genitourinary manifestations: interstitial cystitis, renal Treatment::systemic corticosteroids
tubular acidosis Response to treatment is generally excellent
3. Neurologic manifestations: peripheral polyneuropathy Complete recovery is usual within 1-3 years

Sjogren Syndome Relapsing Polychondritis

Salivary gland enlargement
Patients with systemic manifestations are at higher risk of
lymphoma, especially non Hodgkin B-cell lymphoma
Labial salivary gland biopsy from inside the lower lip is
regarded by many as the most definitive test for Sjögren
syndrome
Xerostomia is diagnosed by the Schirmer test and reflects
diminished glandular secretion from the lacrimal glands
Classically, the diagnosis is made when there is objective
evidence for two of the following three major criteria:
1. xerophthalmia
2. xerostomia
3. an associated autoimmune,rheumatic or
lymphoproliferative disorder
A rare multisystem autoimmune disease with
both autoantibodies and cellular immune
reactions to different cartilage proteins
Characterized by intermittent episodes of
inflammation of the articular and nonarticular
cartilage leading to progressive destruction of
cartilaginous structures
The course of the disease is chronic and
variable with episodic flares
F=M; 40-50s
saddle-nose deformity: destruction of the nasal septal
cartilage
Relapsing Polychondritis

Sjogren Syndrome Associated with conductive deafness, conjuntivitis,

Treatment: scleritis rhinitis, saddle-nose deformity, hoarseness,
SICCA-mainly symptomatic coughing and dyspnea.
Artificial lubricants are helpful for eye symptoms, as well Migratory arthralgia and atypical chest pain
as oral, nasal, and vaginal dryness. MAGIC syndrome is a combination of Behçet's disease
Topical lubricants for xerosis and relapsing.polychondritis (mouth and genital ulcers
Pharmacologic agents, such as pilocarpine and with inflamed cartilage)
cevimeline, are helpful to stimulate salivation Treatment: Dapsone, colchicine, leflunomide, or
hydroxychloroquine, azathioprine, methotrexate,
Sjogren Syndome mycophenolate mofetil, cyclophosphamide, IvIG
Treatment: Systemic corticosteroids should be used to treat acute
Extraglandular manifestations flares
Antimalarials
Corticosteroids Mixed Connective Tissue Disease
Immunosuppressive
A distinct disorder with a characteristic serologic marker
Eosinophilic Fasciitis Overlapping features of scleroderma, SLE, and DM, and
Presents as edematous and high U1RNP antibodies in the absence of anti-Sm
erythematous skin with a coarse antibodies
peau d'orange appearance Presents as severe arthralgia, swelling of the hands,
"Groove Sign" or "Dry Riverbed tapered fingers, Raynaud phenomenon, muscle pain
Sign" and weakness
Associated with abnormal esophageal motility,
pulmonary fibrosis Lichen Myxedematosus: Generalized

Mixed Connective Tissue Disease Generalized Lichen Myxedematosus

Pulmonary arterial hypertension is the major life-
threatening complication.
+ANA test demonstrates a particulate pattern in MCTD,
reflecting high titers of nuclear RNP antibodies (anti-
RNP antibodies)
DIF: particulate epidermal nuclear lgG deposition (a
distinctive finding in MCTD)
Mucinoses
Diverse group of disorders
Deposition of basophilic, finely
granular and stringy material
(MUCIN) in the
Connective tissues of the dermis
(DERMAL MUCINOSES)
Pilosebaceous follicles (FOLLICULAR
MUCINOSES)
Epidermis (EPITHELIAL MUCINOSES)|
Most important mucinoses are the
dermal ones
*Acid Mucopolysaccharides - dermal
volume and texture
AKA SCLEROMXYEDEMA
M=F; 30-80 y.o.
Chronic and progressive
Multiple, waxy, 2-4mm, dome shaped or flat topped
papules-> plaques
Arranged linearly Note
Predilection sites: dorsal hands, face, elbow,
extremities Text
No mucosal involvement
Lichen Myxedematosus: Generalized
Woody sclerosis: diffuse infiltration of the skin
Leonine facies: prominent furrowing of the forehead
and glabela
Doughnut sign: induration around a centrally
depressed area at the proximal interphalangeal joint
Reduced ROM: mouth, hands and extremities
Associated with: Cardiac, Hematologic, Neurologic,
GI diseases (dysphagia), Pulmonary (dyspnea),
Proximal muscle weakness, Carpal tunnel syndrome
(10%), Arthralgia/arthritis
Lichen Myxedematosus: Generalized

Mucinoses Inclusion criteria:

** mucin deposition
Four classes of Glycosaminoglycans (GAGs): Fibroblast proliferation and fibrosis
heparin/heparan, chondroitin/dermatan, keratan, Normal thyroid function tests
hyaluronic acid +monoclonal gammopathy
Chondroitin and heparan: primary dermal mucin
Methods for demonstrating mucin Treatment:
Alcian Blue Difficult multidiscplinary
Colloidal Iron Stain: blue green Immunosuppresive agents: Melphalan,Cyclophosphamide
Toluidine Blue Autologous stem cell transplantation + high dose
Melphalan
Mucinosis IVIG
Physical therapy
- Lichen Myxedematosus UVB and IFN a: exacerbates LM
- Scleredema Therapeutic challengepoor prognosis
- Reticular Erythema Mucinosis
- Follicular Mucinosis
- Cutaneous Focal Mucinosis
- Myxoid Cyst Lichen Myxedematosus: Localized

Lichen Myxedematosus Localized Lichen Myxedematosus

Benign but persistent
AKA as papular mucinosis No gammopathy, no visceral involvement, no
rare skin disorder characterised by deposits of thyroid disease
mucin in the skin Often no treatment needed
Shave exicision or C02 ablation for individual
TYPES: lesions
Generalized: systemic organ involvement and
+monoclonal gammopathy 1. Discrete papular LM
Localized: lack of a monoclonal antibody 2-5mm waxy, firm, flesh colored with erythematous
Discrete Papular LM, Acral Persistent Papular or yellowish hue papule on the linmbs or trunk
Mucinosis, Self healing Papular Mucinosis,
Papular mucinosis of infancy, Nodular LM Lichen Myxedematosus: Localized
Atypical/ Intermediate
2. Acral persistent papular mucinosis
F>M
2-5mm, flesh colored papules bilaterally symmetric
on hands and wrists (less common: knees, calves or
elbows) and SPARING of the face and trunk
Persistent; slowly progress
Lichen Myxedematosus: Localized
3. Self limiting papular mucinosis
Juvenile variant
rare; 5-15 yo
sudden onset of ivory white papules (head, neck,
trunk, periarticular regions)
deep nodules on the face and hard edema of the
periorbital area and face
Polyarthritis: knees, elbows, hand joints; acute
Adult variant
Papules WITHOUT arthritis
Spontaneous resolution without sequelae; excellent
prognosis
lvory white papules and deep nodules on the neck
Lichen Myxedematosus: Localized
4. Papular mucinosis of infancy
AKA Cutaneous mucinosis of infancy
Rare; occurs at birth or within few months
Translucent to skin colored, 2-8mm papules
Predilection sites: trunk, back of the hands
Gradual accumulation of new lesions with old
lesions remain static
5. Nodular LM
Multiple nodules
Predilection sites: trunk, extremities
Lichen Myxedematosus: Atypical
ATYPICAL Or Intermediate LM
Acral persistent papular mucinosis + paraprotein
Localized papular mucinosis+ igA nephropathy
Scleromyxedema with visceral involvement but NO
monoclonal gammopathy
Scleredema
Characterized by stiffening and hardening of the
subcutaneous tissues
2 Types:
Non diabetic type
Diabetes-associated disease
Non diabetic type
FM; Sudden onset following an strep infection and
drug eruption
Skin tightness and waxy/woody induration begins on the
neck and/or face, spreading symmetrically to involve the
arms, shoulders, back, and chest (SPARING the distal
extremities)
Masklike expression with difficulty opening the mouth/
eyes
Scleredema
Non diabetic type
Associated findings: dysphagia, cardiac arrhythmias,
pleural/pericardial effusion
Treatment: if with infection spontaneous resolution in
mos
Non infectious: prolonged course and no effective
treatment but patient may live with the disease for
many years
Diabetes-associated disease
More common type; affects M>F
Associated with late onset insulin-dependent
diabetes
Gradual onset and long lasting
Control of the diabetes does not affect the course of
the scleredema
Usually unresponsive to treatment (IV penicillin,
electron beam, narrow-band UVB and systemic
PUVA)
Diabetes-associated disease
Characterized as woody induration and thickening of
the skin with a sharp step-off from the affected area to
the normal skin
Pesistent erythema and folliculitis
Predilection sites: mid-upper back, neck and shoulders
Reticular Erythematous Mucinosis
F>M
30-40 years of age
Gradual evolution
Characterized as erythematous plaques or reticulated
pate
Predilection sites: most common in the midline of the
chest and back
Eruption frequently appears after intense sun
exposure (Photosensitivity is common)
Onset or exacerbation: Oral contraceptives, menses,
and pregnancy, UVB exposure
Erythematous plaque in the midline of the chest
Follicular Mucinosis
Alopecia Mucinosa
Characterized by hypopigmented/ erythematous/ flesh
colored, scaly/eczematous, follicular papules
Predilection sites: face, neck, and scalp
Types:
Primary follicular mucinosis: skin limited, benign;
lesions are solitary or few in number; cluster on the
head and neck; younger than 40 yo
Associated with Follicular Mycosis Fungoides: older
patient
Follicular Mucinosis
Histology: Mucin deposits on the outer root sheaths of
the hair follicles
Treatment: Hydroxychloroquine, Topical corticosteroids,
Dapsone, PUVA, Minocycline, Isotretinoin
Primary follicular mucinosis - spontaneous involution
(esp in children)
Follicular MF +mucin - refractory to treatment; worse
prognosis than classic CTCL
Erythematous follicular papules and plaques
Cutaneous Focal Mucinosis
Adulthood
Clinical appearance may be indistinctive with a cyst,
basal cell carcinoma or neurofibrama
Asymptor c ol ry nodule or papule
Predilection site: face, neck, trunk, extremities
Treatment: Surgical excision
Myxoid Cyst
Synovial mucous cysts, Digital mucous cysts
F>M
Solitary, 5-7mm, opalescent or skin colored cysts
Cyst contain a clear viscous sticky fluid covered in a
compacted fibrous wal
Osteoarthritis at the adjacent distal interphalangeal
joint
Predilection sites: dorsal hands, lateral terminal digits
of hands, toes
If multiple: associated with CTD (URA)
myxoid cyst under beneath the proximal nailfold forming a
characteristic groove in the nail plate by pressure of the
lesion on the
nail matrix
Myxoid Cyst
Treatment
Surgical excision - cure rate >90%
Proximal NF-puncture technique
Swelling- Intralesional injection of Sodium Tetradecyl
sulfate
Cryotherapy, CO2 ablation, curettage and fulguration
Endocrine Diseases
Endocrine Disease
Acromegaly
Hypersecretion of growth' hormone after the growth
plates are closed
GH facilitates growth of muscles, internal organs, and
bones, as well as stimulating secretion of its target
hormone insulin-like growth factor 1 (1GF-1)
Commonly caused by a benign pituitary adenoma;
rarely ectopic tumors
Mean age: 40s; insidious onset and slow progression
Changes in the soft tissues and bones form a
characteristic syndrome
Clinical features: thickening of the skin; frontal
bossing; thick lips and tongue; enlarged hands and
feet; enlarged fingers
Cutis verticis gyrata in approximately 30%
Skin tags, hypertrichosis, hyperpigmentation and
hyperhidrosis
Deepening of the voice
Enlarged visceral organs-> may develop a variety of
rheumatologic, cardiovascular, metabolic and
respiratory complications
Diagnostic test
measurement of serum insulin-like growth factor
and serum growth hormone after a glucose load
magnetic resonance imaging (MRI) of the pítuitary
Treatment
Excision of the tumor (trans sphenoidal
microsurgical)
Somastostain analogs/ Growth hormone inhibitors:
Octreotide and lanreotide are given as 1-2x a month
as intramuscular injections
Growth hormone receptor antagonist: Pegvisomant
Dopamine agonist: Bromocriptine as an adjuvant
therapy
Radiation is generally reserved for recaloitrant cases
Cushing Syndrome
Chronic excess of glucocorticoids of endogenous (increased
of ACTH) or exogenous source (systemic administration of
corticosteroids)
Age of onset: 20-30s
Clinical features
Central obesity (face, neck, trunk, and abdomen)
Buffalo hump (deposition of fat over the upper back)
Moon shaped face
Thin arms
Hypertrichosis
Abdominal striae
Skin fragility and atrophy with easy bruising and
cigarette paper type wrinkling (Liddle Sign)
Cushing Syndrome
Acne of recent onset without comedones
Susceptibility to superficial dermatophyte and Pityrosporon
infections
Symptoms of fatigue and muscle weakness, hypertension,
personality changes, amenorrhea females, polyuria, an
polydipsia
Associated with hypertension, arteriosclerosis,; progressive
weakness and pains in the back, limbs, and abdomen;
kyphosis of the dorsal spine and osteoporosis; loss of libido;
hyperglycemia, glycosuria, and diabetes mellitus
Plethoric moon facies with erythema and Abdominal Striae
telangiectases of cheeks and forehead
Diagnostic Test:
Determination of blood glucose, serum potassium and
free cortisol in 24-h urine (95-100% sensitive and
specific with a value of at least three times the upper
limit of normal)
Elevated ACTH (to determine if the source is the
adrenals, or a pituitary or ectopic tumor)
CT scan of the abdomen and the pituitary
Assessment of osteoporosis
Management consists of elimination of exogenous
glucocorticoids or the detection and correction of
underlying endogenous cause
Endogenous: surgical removal of the tumor; radiation and
chemotherapy as adjuvant therapy
Addison's Disease
A syndrome resulting from adrenocortical insufficiency
from
an autoantibody destruction of adrenocortical tissue
Onset is insidious
Characterized by progressive generalized brown
hyperpigmentation, slowly progressive weakness, fatigue,.
anorexia, nausea, and Gl symptoms (vomiting and diarrhea)
Hyperpigmentation is diffuse but most prominently
observed
in sun-exposed areas and sites exposed to recurrent trauma
or
pressure
Palmar crease darkening in patients of lighter skin type,
scar
hyperpigmentation, and darkening of nevi, mucous
membranes, hair, and nails
Decreased axillary and pubic hair is seen in women
Addison's Disease
Hyperpigmentation of hands and palmar crease
Addison's disease may be part of polyglandular
autoimmune
syndromes I and II
May occur with hypoparathyroidism, chronic candidiasis,
vitiligo or autoimmune thyroiditis and diabetes
Diagnosis is made by obtaininga serum cortisol, followed by
stimulation with cosyntropin. Failure to see an elevation
above
20 Hg/dL in 1h is diagnostic.
Plasma ACTH is elevated in primary insufficiency but normal
low in patients with secondary adrenal insufticiency
Computed tomography (CT) scan of the adrenal glands to
exclude infiltration or infection
Other laboratory test: serum sodium L, serum potassium H,
and elevationof the blood urea nitrogen
Treatment: replacement of the glucocorticoids and
mineralocorticoids
Hypothyroidism
Hypothyroidism is a deficiency of circulating thyroid
hormone and rarely peripheral resistance to hormonal
action
May be caused by iodine deficiency, late-stage Hashimoto
autoimmune thyroiditis, pituitary or hypothalamiç disease
causing central hypothyroidism, iatrogenic secondary to
Surgery, radioactive iodine treatment, drug therapy with
lithium, interferon, or bexarotene
Commonly affects middle aged women
Associated with Turner and Down syndrome
Hashimoto thyroiditis can be aşsociated with autoimmune
polyglandular syndrome types ll and lll, vitiligo, connective
tissue disease, and autoimmune urticaria
Cretinism
A form congenital hypothyroidism
Associated with mental retardation, growth retardation
and developmental delay
Characterized by cool, dry, pasty white to yellowish skin,
thick pale protuberant lips, enlarged tongue, delayed
dentition, wide set eyes, broad flat nose, periorbital
puffiness, patchy alopecia, acral swelling, coarse dry
brittle nails
Sweating is greatly diminished
Hypothermia with cutis marmorata are also seen
Hypothyroidism
Myxedema
results from insufficient production of thyroid hormones
and can
be caused by multiple disturbances
Early symptoms of myxedema: fatigue, lethargy, cold
intolerance,
constipation, stiffness and cramping of muscles, carpal
tunnel
syndrome, menorrhagia, slowing of intellectual and motor
activity,
decline in appetite, increase in weight, and deepening of
voice
Skin is waxy, coarse, rough and dry skin that may present
with
Ichthyosis in severe cases
Facial skin is puffy with chronic periorbital swelling
Large, smooth, red and clumsy tongue and a broad nose
are present
Dull and flat the expression
The hair is dry, coarse, and brittle; diffuse hair loss is
common with
alopecia of the lateral one third of the eyebrows
Brittle nails and onycholysis may occur
Hypothyroidism: Myxedema
Loss of outer third of the eyebrows
Chronic periorbital swelling
Hypothyroidism: Myxedema
Dry,pale skin;thinning of the lateral eyebrows; puffiness of
the face and
eyelids; increased number of skin creases; dull,
expressionless,
beardless facies
Hyperthyroidism
Excessive quantities of circulating thyroid
hormone
Possible causes:
Graves' thyroiditis (diffuse toxic goiter)/ Grave's
disease-55% of cases
Multinodular toxic goiter (Plummer's disease) or a single
toxic thyroid nodule
Early Hashimoto autoimmune thyroiditis
TSH-secreting pituitary adenoma
Pituitary resistance to thyroid hormone
Metastatic thyroid cancer
Excessive human chorionic gonadotropin
Hyperthyroidism: Graves
most common cause of noniatrogenic
hyperthyroidism
F>M ratio of 7:1
Peak age at onset: 20-30 yo
3 major manifestations: which often do not occu
together and run courses that are independent of each
other
hyperthyroidism with diffuse goiter
ophthalmopathy
dermopathy
Management:
Thyrotoxicosis: Antithyroid agents
Ablation of thyroid tissue: surgically or by radioactive iodine
hyperthyroidism: Graves
Dermopathy (pretibial myxedema)
Occurs in 4% of patients who have or have
had Graves disease
Early lesions: bilateral, asymmetric, firm,
nonpitting nodules and plaques that are
pink, skin-colored, or purple
Late lesions: confluence of early lesions
which symmetrically, involve the pretibial,
regions, smooth surface with orange pee-
like appearance, later becomes verrucous
Dermopathy may also occur after treatment of
hyperthyroidism
Improvement of plaques: intralesional injections
of triamcinolone acetonide and with high
potency topical steroids under occlusion
Stockings or complete decongestive
yonerdpy and a combination of manual
lymphatic drainage, bandaging and exercise are
useful and safe
Hyperthyroidism: Graves'
Ophthalmopathy
Spastic (stare, lid lag, lid retraction)
Mechanical (proptosis, conjunctivitis, periorbital swelling,
optic neuritis, optic atrophy.
Exophthalmic ophthalmoplegia: ocular muscle weakness
with
inward gaze, convergence, strabismus, and diplopia
Symptomatic treatment in mild cases.
Severe cases: prednisone 100-120 mg/d initialy, tapering to
5 mg/d, Orbital radiation, Orbital decompression
Hyperthyroidism: Graves
Acropachy is characterized by digital clubbing, soft-
tissue swelling of the hands and feet, and
diaphyseal proliferation of the periosteum in acral
and distal long bones (tibia, fibula, ulna, and radius)
Seen in approximately 0.1-1%
Usually occurs after treatment of hyperthyroidism
and is frequently associated with exophthalmos
and pretibial myxedema
Hypoparathyroidism
A condition wherein the body produces abnormally low
levels
of parathyroid hormones (PTH) which is key to regulation
and
maintaining a balance between calcium and phosphorus
Most common cause is injury to the parathyroid gland
Clinical features include:
faulty dentition
dry scaly skin
diffuse scanty hair; complete absence of axillary and pubic
hair
brittle and malformed nails; onycholysis may be present
Associated with the APECED (autoimmune
polyendocrinopathy, candidiasis, ectodermal dystrophy)
syndrome
Hypoparathyroidism with resultant hypocalcemia may
trigger
impetigo herpetiformis or pustular psoriasis
Hyperparathyroidism
A condition wherein one or more parathyroid glands
become overactive and secrete excessive PTH
Primary: enlargement of parathyroid gland/s such as seen
in multiple endocrine neoplasia (MEN) type
Secondary: disease that may cause low Ca levels in the
bodyovertime increases parathyroid hormones levels
Increase in calcium (> 65mg/dl) > Calcinosis Cutis (large
subcutaneous nodules common in joints)
Other findings: osteoporosis,kidney stones, excessive
urination, weakness, depression, bone and joint pains
Acanthosis Nigricans
Common in Native Americans, African
Americans and Hispanics
Insidious onset; Rapid in malignancy
Characterized by symmetrically distributed
hyperpigmentation and velvet textured
plaques
Affects the neck, axillae, external genitals,
groin, inner aspects of the thighs, flexor and
extensor surtace of the elbows and knees,
dorsal joints of the hands, umbilicus and anus
A cutaneous marker related to heredity,
obesity, endocrine disorderS (particularly
diabetes), drug administration, and
malignancy
Acanthosis Nigricans

Acrochordons are a frequently seen in the
axillae and groin
Thickening of the palmar skin with
exaggeration of the dermatoglyphics
Small, papillomatous, nonpigmented
lesions and pigmented macules may
occasionally be found in the mucous
membranes of the mouth, pharynx, and
vagina
Acanthosis Nigricans
Type I: Acanthosis nigricans associated with
malignancy
associated with adenocarcinoma: gastrointestinal tract
(60% stomach) > lungs, breast
begin after puberty or in adulthood
should be highly suspected if widespread lesions
develop ina nonobese male aged over 40
Tripe palms (acanthosis palmaris)
characterized by thickened, velvety palms with
pronounced dermatoglyphics
95% occur in patients with cancer and 77% are seen
with AN
tripe palms associated with AN: gastric cancer
Type ll: Familial acanthosis nigricans
rare type; autosomal dominant
present at birth or may develop during childhood;
accentuated at puberty
not associated with cancer
Type Ill: acanthosis nigricans asşociated with
insulin-resistant states and syndromes
most common type
Presents as grayish, velvety thickening of the skin of
the sides of the neck, axillae, and groíns
occurs in obese persons t endocrine disorders
Also occurs in acromegaly and eigantism, polycystic
ovary syndrome, cushíng syndrome, diabetes
mellitus, Addison's disease
Management of AN
Symptomatic
Treat associated disorder
Topical keratolytic and/or topical or systemic
retinoids may improve AN but all in all not very
effective
NUTRITIONAL DISORDERS
Hypovitaminosis A (phrynoderma)
- Phrynoderma, or "toadskin," - keratotic papules of
various sizes, distributed over the extremities and
shoulders, surrounding and arising from the
pilosebaceous follicles
- Diagnostic lesions: large 2-6 mm crateriform
papules filled with a central keratotic plug
- Eye findings are prominent and often
pathognomonic (night blindness, xerophthalmia,
xerosis corneae, and keratomalacia
o earliest finding is delayed adaptation to
the dark (nyctalopia)
o circumscribed areas of xerosis of the
conjunctiva lateral to the cornea,
Occasionally forming well-defined white
spots (Bitot spots)
Hypervitaminosis A
- Loss of hair and coarseness of the remaining hair,
loss of the eyebrows, exfoliative cheilitis,
generalized exfoliation and pigmentation of the
skin, and clubbing of the fingers
- Moderate widespread itching may occur
- Pseudotumor cerebri with papilledema
- In adults: early signs are dryness of the lips and
anorexia
Vitamin D deficiency
- Alopecia
- Patients with cutaneous lupus and other
photosensitive diseases who are counseled to
avoid the sun and use high sun protection factor
(SPF) sunscreens are at paticular risk
Vitamin B1 deficiency
- Vitamin B1 (thiamine) deficiency results in beriberi
- Skin manifestations: edema and red burning
tongue
- Peripheral neuropathy is common, and congestive
heart failure may develop
Vitamin B2 deficiency
- Vitamin B2 (riboflavin) deficiency -most often in
alcoholic patients
- Classic findings are the oral-ocular-genital
syndrome
- The lips are prominently affected with angular
chelitis (perlèche) and cheilosis
- The tongue is atrophic and magenta in colour
- A seborrheic-like dermatitis with follicular
keratosis around the nares primarily affects the
face
Vitamin B6
Pyridoxine deficiency
- may occur in cases of uremia and cirrhosis
- Skin changes include a seborrtheic dermatitis- like
eruption, atrophic glossitis with ulceration, angular
cheilitis, conjunctivitis, and intertrigo
Pyridoxine excess
- subepidermal vesicular dermatosis and sensory
peripheral neuropathy
Vitamin B12 deficiency
- Main dermatologic manifestations: glossitis,
hyperpigmentation, and canities
- Tongue is bright red, sore, and atrophic (linear
atrophic lesions may be an early sign)
- Hyperpigmentation is generalized
- Megaloblastic anemia is often present
Vitamin C deficiency (Scurvy)
- Elderly male alcoholics and psychiatric patients on
restrictive diets are most commonly affected.
- Dialysis patients are also at risk 4Hs characteristic
of scurvy: hemorrhagic signs, hyperkeratosis of
the hair follicles, hypochondriasis, and
hematologic abnormalities
- Characteristic finding: perifollicular petechiae
"corkscrew hairs": Hair shafts are curled in follicles
capped by keratotic plugs
- Hemorrhagic gingivitis occurs adjacent to teeth
and presents as swelling and bleeding of the gums
Niacin deficiency (pellagra)
- 3 Ds-diarrhea, dementia, and dermatitis
- Cutaneous finding: photosensitive eruption that
occurs symmetrically on the face, neck, and upper
chest (Casal necklace; extensor arms, and backs of
the hands
- After several phototoxic events, thickening,
scaling, and hyperpigmentation of the affected
skin occurs
- There is dull erythema of the bridge of the nose,
with fine, yellow, powdery scales over the
follicular orifices (sulfur flakes) Progressive and can
be fatal if untreated
Zinc deficiency
- Dermatitis found in all forms of zinc deficiency is
pustular and bullous, with an acral and periorificial
distribution
- On the face, in the groin, and in other flexors:
patchy, red, dry scaling with exudation and
crusting
- Angular cheilitis and stomatitis may be present
- Diarrhea is present in most cases
- Growth retardation, ophthalmic findings, impaired
wound healing and central nervous system
manifestations occur
- Dx of zinc deficiency should be suspected in at-risk
individuals with acral or periorificial dermatitis
Essential fatty acid deficiency
- There is a generalized xerosis
- Widespread erythema and an intertriginous
weeping eruption are seen
- The hair becomes lighter in color, and diffuse
alopecia is present
- Poor wound healing, growth failure, and increased
risk of infection may occur
Iron deficiency
- Mucocutaneous findings include koilonychia,
glossitis, angular cheilitis, pruritus, and telogen
effluvium diffuse hair loss
- Plummer-Vinson syndrome: microcytic anemia,
dysphagia, and glossitis, seen almost entirely in
middle-aged women
- The lips are thin and the opening of the mouth is
small and inelastic
- Smooth atrophy of the tongue is pronounced
- Koilonychia is present in 40-50% of patients, and
alopecia may be present
- An esophageal web in the postcricoid area may
occur, presenting as difficulty Swallowing, or the
feeling that food is stuck in the throat
Selenium deficiency
- Manifestations in children include
hypopigmentation of the skin and hair
(pseudoalbinism)
- Cardiomyopathy, muscle pain, and weakness with
elevated muscle enzymes are the major features
Protein-energy malnutrition
Marasmus
- represents prolonged deficiency of protein and
calories, and is diagnosed in children who are
below 60% of their ideal body weight without
edema or hypoproteinemia
Kwashiorkor
- occurs with protein deficiency but a relatively
adequate caloric intake. It is diagnosed in children
between 60% and 80% of their ideal body weight
with edema or hypoproteinemia
Marasmus
- the skin is dry, wrinkled, and loose because of
marked loss of subcutaneous fat "monkey facies,"
caused by loss of the buccal fat pad, is
characteristic
Kwashiorkor
- Produces hair and skin changes, edema, impaired
growth, and the characteristic potbelly Hair is
hypopigmented, varying in color from a reddish-
yellow to gray or even white.
- The hair is dry and lusterless; curly hair becomes
soft and straight; and marked scaling (crackled
hair) is seen.
- Especially striking is the flag sign, afecting long,
normally dark hair
- Skin lesions are hypopigmented on dark skin and
erythematous or purple on fair skin
ERRORS IN METABOLISM
Primary systemic amyloidosis
(AL amyloidosis)
- Involves the kidneys, liver, heart, gastrointestinal
tract or peripheral nerve, and skin
- Cutaneous eruption begins as shiny, smooth, firm,
flat-topped, or spherical papules of waxy color
(appear like translucent vesicles) that coalesce to
form nodules and plaques of various sizes
 - Commonly involves: regions about the eyes, nose,
mouth, and mucocutaneous junctions
- MC manifestation: purpuric lesions and
ecchymoses
- Purpura chiefly involves eyelids, limbs, and oral
cavity that typically Occurs after trauma (pinch
purpura)
- Glossitis, with macroglossia, occurs in at least 20%
of cases, may be an early symptom
Secondary systemic
amyloidosis (AA amyloidosis)
- Caused by chronic infectious or inflammatory
process
- Most cases are related to chronic inflammatory
conditions (rheumatoid arthritis, juvenile
idiopathic arthritis, ankylosing spondylitis, adult
Still's disease, inflammatory bowel disease, and
Behçet's disease)
- Common organs involved by AA amyloidosis are
the kidneys, adrenals, liver, and spleen
Dialysis-associated amyloidosis
(b2 microglobulin amyloidosis)
- Almost 100% of patients on dialysis for 15 years or
more will develop this form of amyloidosis
- Primarily affects the synovium, causing
musculoskeletal symptoms, often carpal tunnel
syndrome, and less commonly trigger finger, bone
cysts, and spondyloarthropathy
- Rarely, the skin may be involved, usually as a
subcutaneous tumor, often of the buttocks
overlying the sacrum
- Pedunculated sacral masses, lichenoid papules,
and localized hyperpigmentation can also be seen
Macular amyloidosis
- Moderately pruritic, brown, rippled macules
characteristically located in the interscapular
region of the back Pigmentation is typically not
uniform, giving the lesions a "salt and pepper or
rippled appearance
- Macular amyloidosis is a chronic condition
Lichen amyloidosis
- Characterized by the appearance of paroxysmally
itchy lichenoid papules, typically appearing
bilaterally on the shins
- Primary lesions are small, brown, discrete, slightly
scaly papules that group to form infiltrated large
plaques
Nodular amyloidosis
- Rare form of primary localized cutaneous
amyloidosis; single or, rarely, multiple nodules or
tumefactions preferentially involve the acral areas
- Lesions are asymptomatic, vary in size and may
grow slowly after their initial appearance
- The overlying epidermis may appear atrophic, and
lesions may resemble large bullae
Porphyria cutanea tarda
- Caused by a deficiency in the enzyme
uroporphyrinogen decarboxylase (UROD)
- Present most commonly in midlife
- Photosensitivity resulting in bullae, especially on
sun-exposed parts
- Dorsal hands and forearms, ears, and face are
primarily affected
- Bullae are noninflammatory, rupture easily to form
erosions or shallow ulcers that heals with scarring,
milia, and dyspigmentation
- There is hyperpigmentation of the skin, especially
of the face, neck, and hands
- Hypertrichosis of the face
- Liver disease is frequently present in patients with
PCT
Hepatoerythropoietic porphyria
- Caused by a homozygous or compound
heterozygous deficiency of UROD
- Dark urine is usually present from birth In infancy
vesicles occur in sun-exposed skin, followed by
sclerodermoid carring, hypertrichosis,
pigmentation, red fluorescence of the teeth under
Wood's light examination, and nail damage
Variegate porphyria
- Characterized by the combination of the skin
lesions of PCT and the acute gastrointestinal and
neurologic disease of acute intermittent porphyria
- Vesicles and bullae with erosions, especially on
sun-exposed areas
- Hypertrichosis is seen in the temporal area,
especially in women
- Facial scarring and thickening of the skin may give
the patient a prematurely aged appearance
Erythropoietic protoporphyria
- Presents early in childhood (3 months to 2 years
old), but presentation late in adulthood can occur
- Unique among the more common forms of
porphyria is an immediate burning of the skin on
sun exposure
- Erythema, plaque-like edema, and wheals such as
those seen in solar urticaria can be seen
- Shallow linear or elliptical scars, waxy thickening
and pebbling of the skin on the nose and cheeks
and over metacarpophalangeal joints, and atrophy
of the rims of the ears
- Perioral furrow-like scars are characteristic
- Urine porphyrin levels are normal
Congenital erythropoietic porphyria
- Defect of the enzyme uroporphyrinogen ll
synthase (UROS)
- Presents soon after birth with the appearance of
red urine
- Erythrodontia (coral-red fluorescence of the teeth
when exposed to a Wood's light) of both
deciduous and permanent teeth is characteristic
- Other features seen in CEP include growth
retardation, hemolytic anemia, thrombocytopenia,
porphyrin gallstones, osteopenia, and increased
fracturing of bones

Acute intermittent porphyria
- Caused by a deficiency in porphobilinogen
deaminase (PBGD)
- Characterized by periodic attacks of abdominal
pain, GI disturbances, pain and paresis, seizures
and mental symptoms including agitation,
hallucinations, and depression
- Skin lesions do not occur, since the elevated
porphyrin precursors are not photosensitizers
- Severe abdominal colic-most often the initial
symptom of AIP
- Attacks of AIP are triggered by certain medications
and other conditions
- Progesterone, anticonvulsants, rifampin,
sulfonamides are common triggers
Dystrophic calcinosis cutis
- Occurs in a pre-existing lesion or inflammatory
process
- Present as small deposits of chalky granular
material around the fingers and on the elbows,
spontaneously extrude from the skin
Metastatic calcinosis cutis
- Characterized by calcifications in the skin, elevated
serum calcium, and sometimes
hyperphosphatemia
- Often associated with bone loss or destruction, the
bone providing the source of the elevated serum
calcium
- Conditions associated with metastatic calcinosis:
parathyroid neoplasms, primary
hyperparathyroidism, chronic renal failure,
hypervitaminosis D, sarcoidosis, and excessive
intake of milk and alkali
- MC metabolic condition associated with
metastatic calcification is renal failure
Idiopathic scrotal calcinosis
- MC form of idiopathic calcinosis cutis
- Present in young to middle-aged adult men as
multiple, asymptomatic, firm, round, yellow
papules from several millimeters up to 1 cm in
diameter
Osteoma cutis
- Bone formation within the skin may be primary in
cases where there was no preceding lesion;
metastatic (associated with abnormalities of
parathyroid metabolism); or dystrophic (where
ossification occurs in a preexisting lesion or
inflammatory process)
- Multiple miliary osteomas of the face are clinically
the MC form of osteoma cutis
LIPID DISTURBANCES
Xanthoma tuberosum
- Flat or elevated and rounded, grouped, yellowish
or orange nodules located over the joints,
particularly on the elbows and knees
- Lesions are indurated and tend to coalesce
- Early lesions are usually bright yellow or
erythematous; older lesions tend to become
fibrotic and lose their color
Xanthoma tendinosum
- Papules or nodules 5-25 mm in diameter found in
the tendons, more especially in extensor tendons
on the backs of the hands and dorsa of the feet,
and in the Achilles tendons
- These predominate in conditions with elevated
LDL cholesterol
Eruptive xanthoma
- Small, yellowish-orange to reddish-brown papules
that appear in crops over the entire body
- Pruritis is variable
Xanthoma planum (plane xanthoma)
- Flat macules or slightly elevated plaques with a
yellowish-tan or orange coloration of the skin that
is spread diffusely over large areas
- Occur about the eyelids, neck, trunk, shoulders, or
axillae
- May not be associated with increased lipid
Palmar xanthomas
- Consist of nodules and irregular yellowish plaques
involving the palms and flexural surfaces of the
fingers
Xanthelasma palpebrarumn xanthelasma)
- MC type of xanthoma
- Occurs on the eyelids and is characterized by soft,
chamois-colored or yellowish-orange oblong
plaques, usually near the inner canthi
- Most cases are associated with dyslipidemia
Verruciform xanthoma
- Occurs as a reddish-orange or paler hyperkeratotic
plaque or papillomatous growth with a pebbly or
verrucous surface
- MC site is the oral mucosa
LYSOSOMAL STORAGE
DISEASE
Niemann-Pick disease
- Caused by mutations in the acid sphingomyelinase
gene (SMPD1)
- Type A disease is more severe, presents in infancy
with neurovisceral disease, and is often fatal
- Type B disease is purely visceral (non- neurologic)
and survival into adulthood is characteristic
- Skin lesions in type A and B patients include
xanthomas (skin- colored to tan papules) and
yellow-brown induration of the skin
Gaucher's disease
- Caused by insufficient activity of the lysosomal
enzyme acid-ß glucosidase (glucocerebrosidase,
GBA)
- Occurs at any age but three types are recognized:
 o type 1 (adult type), without neurologic
involvement;
o type 2, the infantile form, with acute early
neurologic manifestations, and
o type 3, the juvenile chronic neuropathic
type
- Hepatosplenomegaly,osteopenia/osteoporosis of
the long bones, pingueculae of the sclera, and a
distinctive bronze coloration of thee skin from
melanin characterize the adult type. A deeper
pigmentation may extend from the knees to the
feet
Lipoid proteinosis
- Caused by mutations in extracellular matrix
protein 1
- AKA as Urbach-Wiethe disease and hyalinosis cutis
et mucosae
- Usually presents in infancy with a hoarse cry or
voice
- Mucosal lesions include yellowish-white infiltrative
deposits on the inner surfaces of the lips,
undersurface of the tongue and uvula.
- Inability to protrude the "woody" tongue fully
- In childhood, beaded eyelid papules occur
- Waxy, yellow papules and nodules with
generalized skin thickening
- Minor trauma leads to bullae that heal with pock
like or acne-like scars, especially on the face
Angiokeratoma corporis diffusum (Fabry disease)
- Mutations in the alphagalactosidase A gene (GLA)
- Characteristic skin lesions are widespread
punctate telangiectatic vascular papules
- Lesions tend to occur in the "bathing trunk" area
- Other skin manifestations include lower limb
edema and lymphedema
- Visceral disease is common, especially of the
kidneys, cardiovascular system, and
gastrointestinal tract
- Neuropathic pain is the most common initial
presentation
Necrobiosis lipoidica/necrobiosis lipoidica diabeticorum
- Characterized by well-circumscribed, firm,
depressed, waxy, yellow brown plaques, usually of
the anterior shin
- Earliest changes are sharply bordered, elevated,
small red papules irregularly round or oval lesions
with well-defined borders and a smooth, glistening
(glazed) surface center becomes depressed and
sulfur-yellow a firm yellowish lesion forms,
surrounded by a broad violet-red or pink border.
- In the yellow portion, numerous telangiectases
and ectatic veins are evident
- Control of the diabetes does not influence the
course of the NL
Diabetic dermopathy (shin spots)
- Dull-red papules that progress to well-
circumscribed, small, round, atrophic,
hyperpigmented lesions on the shins
- Begin on the lower extremities as crops of four or
five dull red macules 0.5-1 cm in diameter. As the
lesions resolve, they become shallow, depressed,
and hyperpigmented scars
- Dull-red papules that progress to well-
circumscribed, small, round, atrophic,
hyperpigmented lesions on the shins
- Begin on the lower extremities as crops of four or
five dull red macules 0.5-1 cm in diameter. As the
lesions resolve, they become shallow, depressed,
and hyperpigmented scars
OTHER METABOLIC DISORDERS
Hartnup disease
- Inborn error of tryptophan excretion
- Characteristic findings are a pellagra-like
dermatitis following exposure to sunlight,
intermittent cerebellar ataxia, psychosis, and
constant aminoaciduria
Prolidase deficiency
- Most important cutaneous signs, which almost
always appear before the affected person is 12
years old, are skin fragility; ulceration and scarring
of the lower extremities; photosensitivity and
telangiectasia poliosis; scaly, erythematous,
maculopapular, and purpuric lesions; and
thickening of the skin with lymphedema of the legs
- Systemic signs and symptoms include mental
deficiency, splenomegaly, and recurrent infections
Phenylketonuria
- Deficiency in the enzyme phenylalanine
hydroxylase
- Characterized by mental deficiency; epileptic
seizures; pigmentary dilution of skin, hair, and
eyes; pseudoscleroderma; and dermatitis
- It is most common in white persons
- Affected children are blue-eyed, with blond hair
and fair skin.
- are usually extremely sensitive to light, and about
50% have an eczematous dermatitis (clinically
similar to AD)
Alkaptonuria and ochronosis
- Lack of renal and hepatic homogentisic acid
oxidase
- Urine is dark and becomes black on standing
- Early sign is the pigmentation of the sclera and the
cartilage of the ears; later the cartilage of the nose
and tendons, especially those on the hands,
becomes discolored
Exogenous ochronosis
- Produced by topically applied phenolic
intermediates, such as hydroquinone, carbolic acid
(phenol), picric acid, and resorcinol
- Typical findings are gray-brown or blue-black
macules, usually over the zygomatic regions.
Caviar-like hyperchromic pinpoint papules may
occur, which on dermoscopy can be seen
associated with follicular openings
 - Confetti-like depigmentation may be admixed with
the hyperpigmentation
Wilson's Disease (Hepatolenticular Degeneration)
- Due to a dysfunction of a copper-transporting
enzyme, P-type ATPase (ATP7B)
- Azure lunulae (sky-blue moons) of the nails occur
in 10% of patients, and the smoky, greenish-brown
Kayser-Fleischer rings develop at the edges of the
corneas
- Hyperpigmentation develops on the lower
extremities in most patients
- Vague greenish discoloration of the skin on the
face, neck, and genitalia may also be present
- There is progressive, fatal hepatic and central
nervous system degeneration
Tyrosinemia II (Richner-Hanhart syndrome)
- Deficiency of hepatic tyrosine aminotransferase
- Clinical features are mild to severe keratitis, and
hyperkeratotic and erosive lesions of palms and
soles, often with mild mental retardation
- Painful palmar and plantar hyperkeratosis may be
the only manifestation
- The fingertips, and hypothenar and thenar
eminences are primarily affected on the palms
- In any child presenting with palmoplantar
keratoderma, this diagnosis must be considered
- The rubbery subcutaneous nodules have a distinct
yellowish hue and are 1-2 cm in diameter. They
are usually located over the joints, lumbar spine,
scalp, and weight-bearing areas
Gout
- Classic gout presents as an acute monoarthritis,
usually of the great toe or knee, in a middle-aged
to elderly man with hyperuricemia
- Monosodium urate monohydrate may be
deposited in the subcutaneous tissues, forming
nodules called tophi; vary from pinhead to pea-
sized or, rarely, even baseball-sized
- Commonly found on the rims of the ears and over
the distal interphalangeal articulations
Lesch-Nyhan syndrome
- AKA juvenile gout
- Characterized by childhood hyperuricemia, gout,
tophi choreoathetosis, progressive mental
retardation, and self- mutilation
- Massive self-mutilation of lips with the teeth
occurs
- Fingers are also badly chewed
- Ears and nose are occasionally mutilated
- An early diagnostic clue is orange crystals in the
diaper

Hurler syndrome (mucopolysaccharidosis I)

- AKA gargoylism
- Deficiency of a-L-iduronidase
- Characterized by mental retardation,
hepatosplenomegaly, umbilical and inguinal
hernia, genital infantilism, corneal opacities, and
skin abnormalities
- Facial dysmorphism, with a broad saddle nose,
thick lips, and a large tongue; skin is thickened,
with ridges and grooves, especially on the upper
half of the body
- Fine lanugo hair is profusely distributed all over
the body
- Large, coarse hair is prominent, especially on the
extremities
Hunter syndrome
(mucopolysaccharidosis lI)
- Pebbly lesions of MPS Il in the skin of the upper
back, neck, chest, proximal arms, or thighs
represent the only diagnostic skin changes of the
mucopolysaccharidoses
- Lesions are firm, flesh-colored to white papules
and nodules, which coalesce into a cobblestone or
reticular pattern

Farber disease

AKA Farber lipogranulomatosis

- Characterized by periarticular swellings; a weak,
hoarse cry pulmonary failure; painful joint
deformities; and motor and mental retardation
- Onset is during the first months of life; death can
be expected before the age of 2