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Pemphigus Vulgaris

By

Daniel M. Peraza

, MD, Geisel School of Medicine at Dartmouth University

Last full review/revision Jun 2019| Content last modified Jun 2019
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Pemphigus vulgaris is an uncommon, potentially fatal, autoimmune disorder characterized by intraepidermal blisters and extensive erosions on apparently healthy skin and mucous membranes. Diagnosis is by skin biopsy with direct and indirect immunofluorescence and enzyme-linked immunosorbent assay (ELISA) testing. Treatment is with corticosteroids and sometimes other immunosuppressive therapies.

Bullae are elevated, fluid-filled blisters ≥ 10 mm in diameter.

Pemphigus vulgaris usually occurs in middle-aged patients, affecting men and women in equal numbers. Rarely, cases have been reported in children. One variant, paraneoplastic pemphigus, can occur in patients who have malignant or benign tumors, most commonly non-Hodgkin lymphoma.

Pemphigus vulgaris is characterized by IgG autoantibodies directed against the calcium-dependent cadherins desmoglein 3 and sometimes desmoglein 1 (1). These transmembrane glycoproteins affect cell-cell adhesion and signaling between epidermal cells. Acantholysis (loss of intercellular adhesion with consequent epidermal blister formation) results from either direct inhibition of desmoglein function by autoantibody binding or from autoantibody-induced cell signaling that results in down-regulation of cell-cell adhesion. The autoantibodies are present in both serum and skin during active disease. Any area of stratified squamous epithelium may be affected, including mucosal surfaces.

Pemphigus (vulgaris, foliaceus, or both) may coexist with certain central nervous system (CNS) disorders, especially dementia, epilepsy, and Parkinson disease. Desmoglein 1 is present in CNS neurons (and in all epithelial cells), and an immunologic cross-reaction between epithelial and CNS isoforms has been suggested.

General reference

  • 1. Russo I, De Siena FP, MD, Saponeri A, et al: Evaluation of anti-desmoglein-1 and anti-desmoglein-3 autoantibody titers in pemphigus patients at the time of the initial diagnosis and after clinical remission. Medicine (Baltimore) 96(46):e8801, 2017. doi: 10.1097/MD.0000000000008801.

Symptoms and Signs

Flaccid bullae, which are the primary lesions of pemphigus vulgaris, cause widespread and painful skin, oral, and other mucosal erosions. About half of patients have only oral erosions, which rupture and remain as chronic, painful lesions for variable periods. Often, oral lesions precede skin involvement. Dysphagia and poor oral intake are common because lesions also may occur in the upper esophagus. Cutaneous bullae typically arise in normal-appearing skin, rupture, and leave a raw area with crusting. Itching is usually absent. Erosions often become infected. If large portions of the body are affected, fluid and electrolyte loss may be significant.

Manifestations of Pemphigus Vulgaris

Diagnosis

  • Biopsy with immunofluorescence testing

Pemphigus vulgaris should be suspected in patients with unexplained chronic mucosal ulceration, particularly if they have bullous skin lesions. This disorder must be differentiated from other disorders that cause chronic oral ulcers and from other bullous dermatoses (eg, pemphigus foliaceus, bullous pemphigoid, mucous membrane pemphigoid, drug eruptions, toxic epidermal necrolysis, erythema multiforme, dermatitis herpetiformis, bullous contact dermatitis).

Two clinical findings, both reflecting lack of epidermal cohesion, that are somewhat specific for pemphigus vulgaris are the following:

  • Nikolsky sign: Upper layers of epidermis move laterally with slight pressure or rubbing of skin adjacent to a bulla.

  • Asboe-Hansen sign: Gentle pressure on intact bullae causes fluid to spread away from the site of pressure and beneath the adjacent skin.

The diagnosis of pemphigus vulgaris is confirmed by biopsy of lesional and surrounding (perilesional) normal skin. Immunofluorescence testing shows IgG autoantibodies against the keratinocyte's cell surface. Serum autoantibodies to desmoglein 1 and desmoglein 3 transmembrane glycoproteins can be identified via direct immunofluorescence, indirect immunofluorescence, and enzyme-linked immunosorbent assay (ELISA).

Prognosis

Without systemic corticosteroid treatment, pemphigus vulgaris is often fatal, usually within 5 years of disease onset. Systemic corticosteroid and immunosuppressive therapy has improved prognosis, but death may still result from complications of therapy.

Treatment

  • Corticosteroids, oral or IV

  • Sometimes immunosuppressants

  • Sometimes plasma exchange or IV immune globulin (IVIG)

Referral to a dermatologist with expertise in treating this disorder is recommended. Hospitalization is required initially for all but the most minor cases. Cleansing and dressing of open skin lesions is similar to that done to treat partial-thickness burns (eg, reverse isolation, hydrocolloid or silver sulfadiazine dressings).

Treatment of pemphigus vulgaris is aimed at decreasing production of pathogenic autoantibodies. The mainstay of treatment is systemic corticosteroids. Some patients with few lesions may respond to oral prednisone 20 to 30 mg once a day, but most require 1 mg/kg once a day as an initial dose. Some clinicians begin with even higher doses, which may slightly hasten initial response but do not appear to improve outcome. If new lesions continue to appear after 5 to 7 days, IV pulse therapy with methylprednisolone 1 g once a day can be tried.

Immunosuppressants such as rituximab (1), methotrexate, cyclophosphamide, azathioprine, gold, mycophenolate mofetil, or cyclosporine can reduce the need for corticosteroids and thus minimize the undesirable effects of long-term corticosteroid use. Plasma exchange and high-dose IV immune globulin to reduce antibody titers have also been effective.

Once no new lesions have appeared for 7 to 10 days, corticosteroid dose should be tapered monthly by about 10 mg/day (tapering continues more slowly once 20 mg/day is reached). A relapse requires a return to the starting dose. If the patient has been stable after a year, a trial without treatment can be attempted but must be closely monitored.

Treatment reference

  • 1. Craythorne EE, Mufti G, DuVivier AW: Rituximab used as a first-line single agent in the treatment of pemphigus vulgaris. J Am Acad Dermatol 65(5):1064–1065, 2011. doi: 10.1016/j.jaad.2010.06.033.

Key Points

  • About half of patients with pemphigus vulgaris have only oral lesions.

  • Use Nikolsky and Asboe-Hansen signs to help clinically differentiate pemphigus vulgaris from other bullous disorders.

  • Confirm the diagnosis by immunofluorescence testing of skin samples.

  • Treat with systemic corticosteroids, with or without other immunosuppressive therapies (drugs, IV immune globulin, or plasma exchange).

Drugs Mentioned In This Article

Drug Name Select Trade
SILVADENE
MEDROL
CYTOXAN (LYOPHILIZED)
Gammagard S/D
CELLCEPT
OTREXUP
IMURAN
NEORAL, SANDIMMUNE
RAYOS
RITUXAN
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NOTE: This is the Professional Version. CONSUMERS: Click here for the Consumer Version
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