Pemphigus Vulgaris A Dermatological Condition

Introduction
Pemphigus is derived from the Greek word pemphix meaning bubble or blister.

The term pemphigus refers to a group of autoimmune blistering diseases of the skin and mucous membranes characterized histologically by intraepidermal blister and immunopathologically by the finding of in vivo bound and circulating immunoglobulin G (IgG) antibody directed against the cell surface of keratinocytes.

Pathophysiology
Pemphigus vulgaris is an autoimmune, intraepithelial, blistering disease affecting the skin and mucous membranes and is mediated by circulating autoantibodies directed against keratinocyte cell surfaces.

Blisters in pemphigus vulgaris are associated with the binding of IgG autoantibodies to keratinocyte cell surface molecules. These intercellular or pemphigus vulgaris antibodies bind to keratinocyte desmosomes and to desmosome-free areas of the keratinocyte cell membrane. The binding of autoantibodies results in a loss of cell-to-cell adhesion, a process termed acantholysis. The antibody alone is capable of causing blistering without complement or inflammatory cells.

Incidence
Pemphigus vulgaris has been reported to occur worldwide. Pemphigus vulgaris incidence varies from 0.5-3.2 cases per 100,000 population. Pemphigus vulgaris incidence is increased in patients of Ashkenazi Jewish descent and those of Mediterranean origin. Few familial cases have been reported.

The male-to-female ratio is approximately equal. In adolescence, girls are more likely to be affected than boys.

The mean age of onset is approximately 50-60 years.

Clinical Presentation
Pemphigus vulgaris presents with oral lesions in 50-70% of patients, and almost all patients have mucosal lesions at some point in the course of their disease. Mucosal lesions may be the sole sign for an average of 5 months before skin lesions develop, or they may be the sole manifestation of the disease. The diagnosis of pemphigus vulgaris shouldbe considered in any patient with persistent oral erosive lesions.

Most patients with pemphigus vulgaris develop cutaneous lesions. The primary lesion of pemphigus vulgaris is a flaccid blister, which usually arises on healthy-appearing skin but may be found on erythematous skin. New blisters usually are flaccid or become flaccid quickly. Affected skin often is painful but rarely pruritic.

Mucous membranes typically are affected first in pemphigus vulgaris. Mucosal lesions may precede cutaneous lesions by weeks or months.

Nikolsky sign: In patients with active blistering, firm sliding pressure with a finger separates normal-appearing epidermis, producing an erosion. This sign is not specific for pemphigus vulgaris and is found in other active blistering diseases.

Diagnosis
To establish a diagnosis of pemphigus vulgaris, perform the following tests:

• Histopathology from the edge of a blister
• Direct immunofluorescence (DIF) on normal-appearing perilesional skin
• Indirect immunofluorescence (IDIF) using the patient’s serum if DIF results are positive: The preferred substrate for IDIF is monkey esophagus or salt-split normal human skin substrate.

Management
The aim of treatment in pemphigus vulgaris is the same as in other autoimmune bullous diseases, which is to decrease blister formation, promote healing of blisters and erosions, and determine the minimal dose of medication necessary to control the disease process.  Therapy must be tailored for each patient, taking into account preexisting and coexisting conditions. Patients may continue to experience mild disease activity while under optimal treatment.

Corticosteroids have improved overall mortality.

Immunosuppressive drugs are steroid sparing and should be considered early in the course of the disease. 

Epidermal growth factor may speed healing of localized lesions.

Intravenous immunoglobulin therapy has been suggested as efficacious in pemphigus vulgaris treatment.

Management of patients with pemphigus vulgaris requires coordination of care between the dermatologist and the patient’s primary care physician.

An ophthalmologist should evaluate patients with suspected ocular involvement and those requiring prolonged high-dose steroids.

Patients with oral disease may require a dentist and/or an otolaryngologist for evaluation and care.

Patients on systemic steroids should maintain adequate vitamin D and calcium intake through diet and supplements. Patients with a history of renal calculi should not receive calcium carbonate.

Patients receiving long-term systemic corticosteroids should be evaluated by a rheumatologist within the first 30 days of treatment for osteoporosis risk assessment and consideration of a bisphosphonate for prophylaxis against osteoporosis.