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 immunofluorescence testing. Treatment is with corticosteroids and sometimes immunosuppressants.

Pemphigus vulgaris usually occurs in middle-aged or elderly patients and is rare in children. One variant, paraneoplastic pemphigus, occurs in older patients with cancer (primarily lymphoreticular); outcome is poor.

The disorder is characterized by the presence of autoantibodies directed against intercellular adhesion molecules desmoglein-1 and desmoglein-3 in the epidermis. They are Ca-dependent cadherins, involved in adhesion and cell signaling between epidermal cells. Acantholysis results from either direct inhibition of function of the desmogleins by autoantibody binding or from autoantibody-induced cell signaling that results in down-regulation of cell-cell adhesion and formation of blisters. These autoantibodies are present in both serum and skin during active disease. Any area of stratified squamous epithelium may be affected, including mucosal surfaces.

Symptoms and Signs

The primary lesions are flaccid bullae of various sizes, but often skin or mucosa just shears off, leaving painful erosions. Lesions typically occur first in the mouth, where they rupture and remain as chronic, often painful, erosions for variable periods before the skin is affected; dysphagia and poor oral intake are common. Lesions also may occur in the upper esophagus. Cutaneous bullae typically arise from normal-appearing skin, rupture, and leave a raw area and crusting. Itching is usually absent. Open skin lesions often become infected. If large portions of the body are affected, fluid and electrolyte loss may be significant.

Pemphigus Vulgaris (Flaccid Bullae)

Pemphigus Vulgaris (Shearing and Erosions)

Pemphigus Vulgaris (Oral)

Diagnosis

• Clinical evaluation
• Biopsy with direct immunofluorescence testing
• Sometimes titers of antibodies against desmoglein-3 or desmoglein-1

Pemphigus vulgaris should be suspected in patients with any bullous disorder or chronic mucosal ulceration. It must be differentiated from other 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 physical signs in pemphigus vulgaris are helpful:

• Lateral pressure on skin adjacent to a blister causes epidermal detachment (Nikolsky's sign).
• Pressure on a blister can cause the blister to extend to adjacent skin (Asboe-Hansen sign).

Biopsy of the edge of a fresh lesion and of a nearby area of normal skin is required; light microscopy and direct immunofluorescence testing are usually diagnostic. Serum antibodies (eg, to desmoglein-3) can be used for diagnosis and for differentiating from pemphigus foliaceus; serial titers can help follow disease activity.

Prognosis

Before systemic corticosteroids were used, pemphigus vulgaris was usually fatal; most patients died within 5 yr of disease onset. Even with treatment, pemphigus vulgaris is a serious disorder with an inconsistent and unpredictable response to treatment, a prolonged course, and virtually inevitable adverse drug effects.

Treatment

• Corticosteroids, oral or IV
• Sometimes immunosuppressants
• Sometimes plasmapheresis and 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 for partial-thickness burns (eg, reverse isolation, hydrocolloid or silver sulfadiazineSome Trade Names
SILVADENE
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dressings—see Burns: Initial wound care).

Drug treatment aims to decrease the production of autoantibodies and stop the eruption of new lesions. The mainstay is systemic corticosteroids. Some patients with few lesions may respond to oral prednisoneSome Trade Names
DELTASONE
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20 to 30 mg once/day, but most require 1.0 mg/kg once/day as an initial dose. Some clinicians begin with even higher doses, which may slightly hasten initial response but does not appear to improve outcome. If new lesions continue to appear after 5 to 7 days, IV pulse therapy with methylprednisoloneSome Trade Names
MEDROL
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1 g once/day can be tried.

Immunosuppressants such as methotrexateSome Trade Names
RHEUMATREX
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, cyclophosphamideSome Trade Names
CYTOXAN
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, azathioprineSome Trade Names
IMURAN
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, gold, mycophenolate mofetilSome Trade Names
CELLCEPT
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, cyclosporineSome Trade Names
NEORAL
SANDIMMUNE
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, or rituximabSome Trade Names
RITUXAN
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can reduce the need for corticosteroids and thus minimize the undesirable effects of long-term corticosteroid use. Plasmapheresis and high-dose IVIG 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.

Last full review/revision September 2008 by Julie E. Russak, MD

Content last modified February 2012