Chronic Blistering Dermatoses

Chronic Blistering Dermatoses Part 2
By:David M. Bracciano, D.O.

Pregnancy- Related Dermatoses
* Intrahepatic Cholestasis of Pregnancy
* Polymorphic Eruption of Pregnancy
* Herpes (pemphigoid) gestationis
* purity Urticarial Papules and Plaques of Pregnancy (PUPPP)
* Papular Dermatitis of Pregnancy
* purity Folliculitis of Pregnancy

Intrahepatic Cholestasis of Pregnancy
* Generalized purities and jaundice
* No primary skin lesions, secondary excoriations
* Caused by cholestasis, occurs late in pregnancy, resolves after delivery
* 0.5% of pregnancies
* Tx; oral steroids

Polymorphic Eruption of Pregnancy
* Classification of all purity inflammatory dermatoses of pregnancy:
* Toxemic rash of pregnancy
* Pruigo annularis
* EM gestationis
* PUPPP
* purity Folliculitis of Pregnancy

Polymorphic Eruption of Pregnancy
* Pruritic inflammatory dermatoses of pregnancy occur in 1 of every 120 to 240
* Treatment and prognosis is similar in subtypes

Pruritic Urticarial Papules and Plaques of Pregnancy (PUPP)
* First reported in 1979
* Erythematous papules and plaques that begin as 1-2 mm lesions within the abdominal striae
* Spread over the course of a few days to involve the abdomen, buttocks, thighs
* Upper chest, face, and mucous membranes spared

PUPPP
* Lesions coalesce to form urticarial plaques
* Intense pruritis is characteristic
* Primigravidas 75% of the time, usually does not recur with subsequent pregnancies
* Begins late in third trimester and resolves with delivery
* May be associated with increase weight gain
* Histology: perivascular infiltrate in upper and mid dermis, epidermis normal
* Tx: topical or oral steroids

Papular Dermatitis of Pregnancy
* Pruritic generalized eruption of 3-5 mm erythematous papule surmounted by a small, firm, central crust
* May erupt at any time during pregnancy and resolve with delivery
* Marked elevation of urine HCG
* Tx; oral steroids, may recur in subsequent pregnancies

Prurigo Gestationis (Besnier)
* purity, excoriated papules of the proximal limbs and upper trunk
* Onset is 20-34 weeks gestation
* Clears in postpartum period and does not recur
* Tx: topical steroids

Pruritic Folliculitis of Pregnancy
* 2nd or 3rd trimester
* Small follicular pustules scattered widely over the trunk
* May be a type of hormonally induced acne

Impetigo Herpetiformis
* Form of severe pustular psoriasis occurring in pregnancy
* Acute, usually febrile onset of grouped pustules on an erythematous base
* Begins in the groin, axillae, and neck
* Increased WBC, hypocalcemia
* Recurs with pregnancy, fetal death due to placental insufficiency
* Tx; prednisone 1mg/kg

Cicatricial Pemphigoid (Benign Mucosal Pemphigoid)
* Vesicles which quickly rupture, leaving erosions and ulcers with scarring
* Primarily occur on mucous membranes, conjunctiva (66%) and oral mucosa (90%)
* Oral mucosa may be the only affected site for years; desquamative gingivitis of buccal mucosa
Cicatricial Pemphigoid
* Tends to affect middle-aged to elderly women 2:1 female/male
* Ddx; oral lichen planus (biopsy and IF)
* Chronic disease that may lead to slowly progressive shrinkage of the ocular mucous membranes and blindness
* Also occurs in pharynx, esophagus, larynx, nose, penis, vagina, anal mucosa, deafness
* Cutaneous lesions in 25%; tense bullae
* Bullae heal with or without scarring, occur on the face, scalp, neck, and inguinal region and extremities
* Some pts may have antibodies targeted against classic bullous pemphigoid antigens and should be classified as “mucosal predominate bullous pemphigoid”
* Chronic course, pts health not usually affected
* IgA antibodies may explain mucosal scarring tendency
* Little tendency to remission (unlike bullous pemphigoid)
* Subtypes include types that target basement membrane zone antigens (laminin, glycoproteins, )
* Direct IF testing C3 and IgG at the lamina lucida in 80-95%
* Tx: mild cases topical steroids (Temovate/Orabase), intralesional triamcinolone every 2-4 weeks
* Tx: Dapsone, prednisone, Azathioprine or cyclophosphamide

Epidermolysis Bullosa Acquisita
* Antibodies to Type VII collagen
* Skin fragility, healing with scars
* Bullous eruption, scaring, milia
* Need to exclude all other bullous diseases: porphyria cutanea tarda, pemphigoid, pemphigus, dermatitis herpetiformis, and bullous drug eruption

Epidermolysis Bullosa Acquisita
* Tx; unsatisfactory, steroids, dapsone, colchicine, IV Immunoglobulin, Cyclosporin

Dermatitis Herpetiformis
* Chronic, relapsing, severely purity disease
* Grouped symmetrical, polymorphous, erythematous-based lesions
* May be papular, papulovesicular, vesiculobullous, bullous, or urticarial
* Itching and burning are intense
* Spontaneous remissions lasting a week

Dermatitis Herpetiformis
* Eruption usually symmetrical
* Scalp, nuchal area, posterior axillary folds, sacral region, buttocks, knees, forearms
* Pruriginous papules are a common feature
* Vesicles are more common than bullae; however all types of these lesions may be present in one patient
* Course of the disease is generally lifelong, with prolonged remissions being rare

Dermatitis Herpetiformis
* Very few patients with DH ever have diarrhea although DH is associated with Gluten-sensitive-enteropathy (GSE)
* 87% of pts with DH and IgA deposits in the skin are HLA-B8 positive (like GSE)
* Gluten is a protein found in cereals except for rice, oats, and corn
* IgA antibodies are formed in the jejunum, may deposit in the skin
* Associated with; Thyroid disorders, small bowel lymphoma, non-Hodgkins lymphoma
* 70% of pts have abnormalities of the jejunal mucosa
* Gluten-free diet decreases Dapsone dose requirements after 3-4 months
* Ddx: pemphigoid, EM, scabies, contact dermatitis, atopic dermatitis, eczema, insect bites, pruigo nodularis
* IgA in a granular pattern in the dermal papillae in normal skin is specific and pathognomonic for DH
* IgA deposits may be focal, so multiple biopsies may be needed.
* Deposits of the antibody are more often seen in previously involved skin or normal appearing skin adjacent to involved skin
* Equal male:female
* Onset between 20 to 40 years
* Tx: Dapsone 50-300mg daily (hemolytic anemia, methemoglobinemia, check G6PD prior to tx) monitor Hct,WBCs, LFTs
* Tx: Sulfapyridine 0.5g QID to 2-4g/day
* Gluten-free diet will decrease need for meds or allow pt to go off them Celiac Society

Linear IgA Bullous Dermatosis
* Subepidermal blisters, a neutrophillic infiltrate, circulating IGA antibasement membrane zone antibody
* Deposition of IgA antibody at the dermoepidermal junction by direct IF

Linear IgA Bullous Dermatosis Adult Form
* Acquired autoimmune blistering disease
* Clinical pattern similar to dermatitis herpetiformis, or with vesicles and bullae in a bullous pemphigoid-like appearance
* 50% mucous membrane involvement
* Oral and conjunctival lesions may be scarring
* No association with enteropathy or with HLA-B8
* Tends to remit over several years

Linear IgA Bullous Dermatosis Adult Form
* Linear IgA dermatosis can occur as a drug-induced disease:
* Self-limited, less mucosal involvement, usually does not have circulating autoantibody
* IgA is usually deposited in the subbasal lamina area
* Vanco, Lithium, amiodarone, captopril, PCN, lasix, dilantin, and others
* Histo: papillary dermal microabscess with neutrophils, subepidermal bullae may be seen with neutrophils and eosinophils
* Direct IF: homogeneous linear deposition of IgA is present at the BMZ
* Indirect IF: few will have circulating IgA autoantibody with anti-BMZ specificity
* Tx: Dapsone, topical steroids

Linear IgA Bullous Dermatosis Childhood Form
* Chronic Bullous Disease of Childhood: acquired, self-limited bullous disease
* Onset by 2 or 3, remits by age 13
* Bullae develop on erythematous or normal appearing skin
* Trunk, buttocks, genitalia, and thighs
* Perioral and scalp lesions are common, oral lesions not uncommon
* Bullae arranged in a rosette or annular array “cluster of jewels”
* Histo: subepidermal bullae filled with neutrophils, eosinophils may predominate
* Direct IF: linear deposition of IgA at the BMZ
* Indirect IF: positive for circulating IgA antibodies in 50%
* Tx: Sulfapyridine or dapsone, topical steroids

Transient Acantholytic Dermatosis
* Over age 50, fragile vesicles, limited extent, sparse, limited duration
* Rapid crusting, keratotic erosion <1cm
* Usually chest, shoulder
* Direct IF is negative
* Tx: topical steroids, isotretinoin

Nutritional Diseases
* Caused by insufficiency or excess of dietary essentials
* Common in underdeveloped countries, infants and children
* Often pts have features of several disorders if diet is generally restricted
* Alcoholism is the main cause in developed countries
* Postoperative pts, psychiatric pts (anorexia nervosa, bulimia), surgical or inflammatory bowel dysfunction, Crohn’s

Hypovitaminosis A (Phrynoderma)
* Vitamin A: fat soluble found in milk, fish oil, liver, eggs, and as carotenoids in plants
* Common in children in developing world
* Developed countries found in diseases of fat malabsorption; Crohn’s, celiac, cystic fibrosis, cholestatic liver disease
* Vitamin A required for keratinization of mucosal surfaces
* Abnormal keratinization leads to increased mortality from inflammatory disease of the gut and lung ie; diarrhea and pneumonia
* Phrynoderma or “toadskin” resembles keratosis pilaris.
* Keratotic papules over extremities and shoulders arising from pilosebaceous follicles
* Eruption begins on thighs or upper arms. Spreads to shoulders, abdomen, back, and buttocks, face and neck
* Skin displays dryness and scaling

Hypovitaminosis A Ocular Findings
* Major cause of blindness in children in the developing world!
* Earliest finding is delayed adaptation to the dark (nyctalopia)
* Night blindness, xeropthalmia, xerosis corneae, keratomalacia
* Bitot’s Spots; circumscribed areas of xerosis of the conjuctiva lateral to the cornea

Hypovitaminosis A
* Diagnosis: based on eye findings, serum Vitamin A level.
* Tx: 300,000 IU Vitamin A

* Skin findings similar to side effects of Retinoid therapy. Children are at greater risk.
* Loss of hair and coarseness, loss of eyebrows, exfoliation and pigmentation of skin, clubbing, hepatosplenomegaly, anemia, increased LFTs, pseudotumor cerebri with papilledema

Hypervitaminosis A Adults
* Early signs are dryness of the lips and anorexia. Followed by bone and joint pains, follicular hyperkeratosis, branny desquamation of the skin, loss of scalp hair and eyebrows, dystrophy of the nails.
* Fatigue, myalgia, depression, anorexia, liver disease
* Birth defects with excess Vit A in pregnancy

Vitamin D
* Deficiency of Vitamin D causes alopecia, osteomalacia
* Vitamin D overdose can cause hypercalcemia and calcinosis.

Vitamin E Deficiency
* Most common in infants of low birth weight
* Peripheral edema, progressive neuromyopathy, and ophthalmoplegia

Vitamin K Deficiency
* Dietary deficiency of vitamin K, a fat soluble vitamin, does not occur in adults because it is synthesized by bacteria in the large intestine
* Liver disease causes deficiency
* Drugs: coumadin, salicylates, cholestyramine
* Decrease in the vitamin K-dependent clotting factor II, VII, IX, and X.
* Purpura, hemorrhage, and ecchymosis.
* Tx: 5 to 10 mg/day IM Vit K for 2-3 days

Vitamin B1 Deficiency
* Thiamine deficiency results in Beriberi
* Edema, and peripheral neuropathy

Vitamin B2 Deficiency
* Riboflavin deficiency is seen most often in alcoholics.
* Phototherapy for neonatal icterus, boric acid ingestion, hypothyroidism, chlorpromazine
* Oral-ocular-genital Syndrome: angular chelitis, atrophic tongue, photophobia, blepharitis, confluent dermatitis of scrotum
* Tx: 5mg Riboflavin qd

Vitamin B6- Pyridoxine
* Deficiency: occurs in uremia and cirrhosis
* Seborrheic dermatitis, glossitis, chelitis, conjunctivitis, confusion, neuropathy
* Excess: subepidermal vesicular dermatosis, peripheral sensory neuropathy

Vitamin B12 Deficiency Cyanocobalamin
* Absorbed through the distal ileum after binding to gastric intrinsic factor in an acid ph.
* Deficiency caused by: decreased intrinsic factor, achlorhydria, malabsorption syndromes (pancreatic, sprue)
* Because of large body stores in adults, deficiency occurs 3 to 6 years after onset of GI disease!
* Glossitis, hyperpigmentation accentuated in exposed areas resembling Addison’s disease
* Megaloblastic anemia, weakness, paresthesias, ataxia
* Tx: IM B12, neuro defects may not improve

Folic Acid Deficiency
* Diffuse hyperpigmentation, glossitis, chelitis, and megaloblastic anemia

Scurvy Vitamin C Deficiency
* Most common vitamin deficiency dxd by dermalologists
* Elderly alcoholics and psychiatric pts

Scurvy “The Four H’s”
* Hemorrhagic signs
* Hyperkeratosis of the hair follicles
* Hypochondriasis
* Hematologic abnormalities
* Perifollicular petechiae and ecchymoses, subungual, subconjunctival, intramuscular, and intraarticular hemorrhage
* “Corkscrew hairs”; hairshafts are curled in follicles capped by keratotic plugs
* Hemorrhagic gingivitis; bleeding gums, epistaxsis, anemia
* Dx: serum ascorbic acid level
* Tx: ascorbic acid 800-1000mg qd x 1 week

Niacin Deficiency Pellagra
* Nicotinic acid, vitamin B3, niacin or its precursor tryptophan is associated with a diet entirely composed of corn, millet or sorghum
* Other vitamin defficiencies or malnutrition coexist
* Most cases are alcoholics in developed countries

Pellegra Causes
* Carcinoid tumors, which divert tryptophan to serotonin
* Intestinal parasites esp; hookworm
* GI diseases ie; Chron’s
* IV alimentation
* Anorexia nervosa
* Meds; Isoniazid, azathioprine, 5-FU, Hydantoins

Pelegra
* Chronic disease affecting GI tract, CNS, skin
* “3 D’s”; diarrhea, dementia, dermatitis
* Dermatitis: photosensative eruption, perineal lesions, thickening and pigmentation over boney prominences, seborrheic dermatitis-like eruption on face

* Photosensitive eruption on face, neck, chest
* (Casal’s necklace), eruption may be vesicular or bullous (wet pellegra)
* After several phototoxic events the skin shows hyperpigmentation, scaling, a copper hue
* Scrotal and perineal erosions, fissures, angular chelitis
* CNS and GI symptoms may occur without skin changes; apathy, muscle weakness, parasthesias, dizziness, psychosis
* Disease is progressive, majority of pts die in 4-5 years if untreated

Pellegra Diagnosis and Treatment
* Diet: Animal protiens, eggs, milk, vegetables
* 100mg nicotinamide qid
* Skin lesions begin to resolve within 24 hours of tx

Biotin Deficiency
* Biotin is universally available and is produced by intestinal bacteria
* Deficiency is rare, can occur in short gut or malabsorption
* Dermatitis is perioral; pathcy, red, eroded lesions on the face and groin
* Candida overgrowth of lesions occurs
* Alopecia including loss of eyebrows and eyelashes
* Neuro: depression, lethargy, parasthesias
* Infants: hypotonia, lethagry seizures, developmental delays
* Inherited form: detecting organic aminoaciduria with 3-hydroxyisovaleric acid
* Tx: 10mg Biotin qd Skin lesions resolve rapidly, but neuro damage may be permenant

Zinc Deficiency
* Inherited or Aquired
* Inherited: Acrodermatitis enteropathica
* Premies at risk due to inadequate body zinc stores
* Weaning from breast from breast milk precipitates clinical zinc deficiency
* Parental nutrition without adequate zinc content may contribute

Zinc
* Acquired: alcoholics, bowel disease, anorexia, AIDS
* Zinc requirements increase with metabolic stress
* Diets containing mainly cereal grains are high in phytate, which binds zinc, Middle East, North Africa

Zinc Dermatitis
* Pustular and bullous, acral and perioral
* Patchy, red, dry, scaling with exudation and crusts. Angular chelitis and stomatitis
* Nail dystrophy, alopecia
* Diarrhea, growth retardation, CNS
* Histo: vacuolation of the keratinocytes of the upper stratum malpighii

Zinc Deficiency Diagnosis and Treatment
* Characteristic skin findings, acral or perioral dermatitis
* Chronic diaper rash with diarrhea in an infant should lead to evaluation for zinc deficiency
* Diagnosis: low serum zinc, alkaline phosphatase
* Tx: zinc sulfate 1-2 mg/kg/day
* Tx: acrodermatitis enteropathica is lifelong

Essential Fatty Acid Defficiency
* Lbw infants, bowel disease, alimentation
* Dermatitis similar to zinc def : xerosis, EFA’s constitute 25% of the fatty acids of the stratum corneum
* Widespread erythema, intertriginous weeping eruption, infection, alopecia
* Decrease in linoleic acid and an increase in palmitoleic and oleic acids
* Ratio of eicosatrienoic acid to arachidonic acid of >0.4 is diagnostic
* Tx: Intralipid 10% IV

Iron Deficiency
* Common in menstration
* Mucocutaneous; glossitis, angular chelitis, pruitus, telogen effluvium
* Plummer-Vinson syndrome: microcytic anemia, dysphagia, glossitis (middle aged women) thin lips, narrow mouth, koilonchia in 50%
* Post-cricoid esophageal web
* Diagnosis: serum iron (Fe+)
* Tx: iron sulfate 325 mg tid

Selenium Deficiency
* IV alimentation, poor soil selenium content, lbw infants
* Children: hypopigmentation of skin and hair (psuedoalbinism), leukonychia
* Cardiomyopathy, muscle pain, elevated muscle enzymes (cpk)
* Tx: 3 ug/kg/day selenium

Protein-energy Malnutrition
* Spectrum of diseases: marasmus, kwashiorkor, and marasmic kwashiorkor
* Endemic in developing world
* Marasmus; def of protein and calories, children < 60% of IBW without edema
* Kwashiorkor; protein def, 60-80% of IBW with edema or hypoproteinemia

Marasmus/ Kwashiorkor
* Cystic fibrosis, dietary restrictions
* Marasmus: skin is dry, wrinkled, loose
* “Monkey facies”; due to lose of buccal fat pad, no edema
* Kwashiorkor; edema, potbelly, hair and areas of skin are hypopigmented, hair is red, gray to white
* Africans call them “Red Children”
* “Flag Sign”; alternating bands of pale and dark hair along a single strand correspond to periods of good and poor nutrition
* “Mosaic skin”; areas of hyper/hypopigmentation resemble peeling paint

Carotenemia and Lycopenemia

* Excessive ingestion of : carots, oranges, squash, spinach, turnips, corn, beans, butter, eggs, pumpkins, sweet potatoes, papaya (seen in Kirksville)
* Yellowish discoloration of skin, palms, soles, central face
* Carotenemia occurs in vegitarians
* Lyconpenemia; red foods, beets, tomatoes, chili beans (flatulence), berries leads to reddish discoloration of skin aka “K.C. Chiefs’ syndrome


Chronic Blistering Dermatoses.ppt