Chronic Blistering Disease Part I

1. Chronic Blistering Disease Part I Rick Lin, DO MPH SECOND year resident

12. Pemphigus Vulgaris • Easily rupture bullae • Bulla is clear at first but may become hemorrhagic or even seropurulent then form erosion • Appear first in the mouth and them commonly in the groin, scalp, face, neck, axillae, or genitals • Nikolsky sign is present

13. Nikolsky sign vs. Asboe-Hansen • Nikolsky sign: absence of cohesion in the epidermis, upper layers are easily made to slip laterally by slight pression or rubbing. • Asboe-Hansen sign: direct pression on intact bulla leading to bulla-spread phenomenon

14. Pemphigus Vulgaris • Mouth lesion first appear in 60% of the case • Mucosa with painful erosion • Mouth odor is offensive and penetratingly unpleasant • Esophagus may be involved and sloughing of entire lining to form a cast (esophagitis dissecans superficialis)

15. Pemphigus Vulgaris • Epidemiology: M=F, usually 5th and 6th decades, rare in young person • Etiology: autoimmune blistering disease mediated by intercellular antibodies • IgG throughout epidermis, C3 reliably found • Desmoglein-3 antibody detected

16. Pemphigus Vulgaris • Drugs which induces pemphigus • Penicillamine for treatment of RA, most often for foliaceous type • Captopril, penicillin, thiopronine, interleukin-2, rifampin

21. The hallmark of pemphigus is the finding of IgG autoantibodies directed against the cell surface of keratinocytes. A Pemphigusvulgaris sera containing anti-desmoglein 3 IgG alone stain the cell surfaces in the lower epidermis. B Pemphigusvulgaris sera containing both anti-desmoglein 3 IgG and anti-desmoglein 1 IgG stain the cell surfaces throughout the epidermis. C Pemphigus foliaceus sera, which contain only anti-desmoglein 1 IgG, stain the cell surfaces throughout the epidermis, but more intensely in the superficial layers.

24. Pemphigus Vulgaris • Treatment: • Topical: Silvadene, Maalox for mouth • Systemic: Prednisone 60mg to 100mg daily • Systemic: Azathioprine (Imuran), cyclophasphamide (Cytoxin), Mexotrexate maybe used in combination • Repeat pemphigus antibody titer in 4-8 weeks after treatment. If not improving, increase prednisone up to 150mg/day • Solu-medrol IV pulse therapy at 1g/day over 2-3 hour period, repeat for 5 days if patient is not responding orally.

25. Pemphigus Vulgaris • Use of an immunosuppresant is helpful in diminishing the need for corticosteroids. • Imuran is one of the best • Risk of death in pemphigus from side effect of oral prednisone is greater than the risk of death from the disease itself

27. Pemphigus Vegetans • A variant of pemphigus vulgaris • Characterized by flaccid bullae that become erosions and form fungoid vegetation or papillomatous proliferations, especially in body folds • Histology finding are identicla with those of pemphigus vulgaris, but there is an increased papillary proliferations and marked epidermal hyperplasia.

31. Pemphigus Foliaceus • Mild, chronic variety of pemphigus characterized by flaccid bullae and generalized or localized exfoliation. • Nikolsky sign present. Oral lesions rarely seen. • Desmoglein-1 antibody. • Patient with Pemphigus Foliaceus are not severely ill.

36. Fogo Selvagem • AKA Brazilian Pemphigus • Endemic form of pemphigus foliaceus found in tropical regions • Histologically and immunohistologically identical to pemphigus foliaceus

37. Pemphigus Erythematosus • Senear-Usher Syndrome • Resemble lupus erythematosus • Positive for lupus band in 80% of patients • Histologically resemble Pemphigus foliaceus • Dosage of prednisone required for control usually is much lower than that of Pemphigus Foliaceus

39. Paraneoplastic Pemphigus • Mucosal lesions may present as lichenoid with Stevens-Johnson-like presentation • Skin lesions may appear as erythematous macules, lichenoid lesions, erythema multiforme-like lesion, flaccid bullae, and erosion. • Immunohistopathologic reveals IgG and C3.

40. The characteristic clinical feature is severe intractable stomatitis that extends onto the vermilion lip.

42. Intraepidermal Neutrophilic IgA Dermatosis • Generalized flaccid bullae, which may rapidly ruptured and crusted • Histological finding shows neutrophilic exocytosis and in some areas neutrophils arranged in a linear fashion at the dermal-epidermal junction. • Direct IF showed an intrercellular deposition of IgA with in epidermis with minimal staining of basal layer.

43. Intraepidermal Neutrophilic IgA Dermatosis • Second subset of patients develop disease that more closely simulates subcorneal pustular dermatosis • Present much more like Sneddon-Wilkinson patient with serpiginous and annular pustules • Treatment with Dapsone is often effective at as low as 25mg per day.

46. Bullous Pemphigoid • Large bullae • When rupture, shows large denuded area and do not materially increase in size. • Denuded areas show a tendency to heal spontaneously • Begins at a localized site, frequently the shin • Young girls maybe initially seen with localized vulvar erosion and ulcers that resemble signs of child abuse.

47. Bullous Pemphigoid • Occurs most frequently in the elderly. • Age of average onset is 65 to 75 years • Etiology: circulating basement membrane zone antibodies of the IgG class present 70%. • Site of IgG binding has been localized to the lamina lucida, with accentuation near hemidesmosome • Bullous pemphigoid antigen 1 (BPAg1) and 2 (BPAg2) identified in 90% of patients