Chronic Blistering Dermatoses Part 2 and Nutritional Diseases

1. Chronic Blistering Dermatoses Part 2 and Nutritional Diseases Adam Wray, D.O. May 9, 2006

2. Pregnancy- Related Dermatoses • Intrahepatic Cholestasis of Pregnancy • Polymorphic Eruption of Pregnancy • Herpes (pemphigoid) gestationis • Pruritic Urticarial Papules and Plaques of Pregnancy (PUPPP) • Papular Dermatitis of Pregnancy • Pruritic Folliculitis of Pregnancy

4. Intrahepatic Cholestasis of Pregnancy • Generalized pruritus and jaundice • No primary skin lesions, secondary excoriations • Caused by cholestasis, occurs late in pregnancy, resolves after delivery • Increased incidence of fetal comp. • 0.5% of pregnancies • Tx: ursodeoxycholic acid more effective than S-adenosyl-L-methionine

5. 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

8. PUPPP • 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 • More common in those carrying twins/triplets

10. PUPPP • Histology: perivascular infiltrate in upper and mid dermis, epidermis normal • DIF negative • Tx: topical or oral steroids

11. Papular Dermatitis of Pregnancy • Controversial entity • Pruritic generalized eruption of 3-5 mm erythematous papules surmounted by a small, firm, central crust • May erupt at any time during pregnancy and resolve with delivery • Marked elevation of 24 hr urine HCG • Tx: oral steroids, may recur in subsequent pregnancies

12. Prurigo Gestationis (Besnier) • Pruritic, 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

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

15. 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

16. 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 • Ocular complications: bilateral, flaccid vesicles on conjuntivia, xerosis, symblepharon, and blindness may result. • Generally confined to head and neck

18. 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

19. Cicatricial Pemphigoid • 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

21. Cicatricial Pemphigoid • Little tendency to remission (unlike bullous pemphigoid) • Subtypes include types that target basement membrane zone antigens (laminin, glycoproteins,) • Intracellular C-terminal domain of BP-180 • Laminin 5 (antiepiligrin cicatricial pemphigoid) • Beta4 subunit of alpha6beta4 integrin

24. Cicatricial Pemphigoid • 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, cyclosporine, TCN

25. Epidermolysis Bullosa Acquisita • Antibodies to Type VII collagen • Skin fragility, healing with scars • Bullous eruption, scaring, milia • Histo: epidermal necrosis, subepidermal blister, dermal necrosis, lack of inflammation until lesions become older. • IgG deposition on dermal side of salt-split • Associations: myeloma, granulomatous colitis, diabetes, lymphoma, leukemia, amyloidosis, and carcinoma

26. EBA IgG on floor of blister, in contrast to pemphigoid.

27. EBA criteria proposed in 1971 by Roenigk • 1) clinical lesions of EBA • 2) adult onset • 3) lack of a family hx of EB • 4) exclusion of all other bullous dz • 5) IgG at BMZ by DIF • 6) blister beneath basal lamina • 7) deposition of IgG beneath basal lamina

29. Epidermolysis Bullosa Acquisita • Tx; unsatisfactory, steroids, dapsone, colchicine, IV Immunoglobulin, Cyclosporin

32. Dermatitis Herpetiformis • Chronic, relapsing, severely pruritic dz • Grouped symmetrical, polymorphous, erythematous-based lesions • May be papular, papulovesicular, vesiculobullous, bullous, or urticarial • Linear petechial lesions on palms, fingers • Pigmented spots over lumbosacral region • Itching and burning are intense • Spontaneous remissions lasting a week

34. Dermatitis Herpetiformis • Laryngeal lesions  hoarseness • Premenstrual flares may occur • Oral iodides may flare dz

36. 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

38. Dermatitis Herpetiformis • Associated with; Thyroid disorders, small bowel lymphoma, non-Hodgkins lymphoma • 70-100% of pts have abnormalities of the jejunal mucosa • Gluten-free diet decreases Dapsone dose requirements after 3-4 months

39. Dermatitis Herpetiformis • 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

42. Dermatitis Herpetiformis • 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

43. Dermatitis Herpetiformis • 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

44. 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

47. 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

48. 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, carbamazapine, captopril, PCN, PUVA, lasix, dilantin, oxaprozin, statins, tea tree oil, and others

50. Linear IgA Bullous Dermatosis Adult Form • 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 • On salt-split, deposition of IgA may be on the roof, base, or a combination of both. • Tx: Dapsone, topical steroids