Pemphigus refers to a chronic, blistering, autoimmune disease of the skin and mucous membranes. There are four major subtypes: vulgaris, vegetans, foliaceus, and erythematosus. There are also drug-induced, paraneoplastic and endemic forms. Patients with myasthenia gravis and/or thymomas may display an increased tendency towards pemphigus lesions. Blister formation in pemphigus occurs secondary to loss of the cohesive junction between epidermal cells which results from intercellular edema and the disruption of intercellular bridges. The production of anti-desmogleins antibodies is pathogenic for this disease. Desmosomes are the cell adhesion junctions located in stratified squamous epithelium. Desmogleins are the transmembrane glycoproteins located at the core regions of desmosomes.
Pemphigus vulgaris (PV) is the most common form of this disease. Oral lesions, in conjunction with the cutaneous lesions, are common with this form of pemphigus. Lesions involving the mucous membranes (most commonly the oral mucosa) usually precede cutaneous involvement. Lesions start as small vesicles which generally progress to large bullae. Once the bullae rupture, they leave behind a painful ulceration which has a tendency to expand at its periphery. The ulcerations generally heal without residual scarring; however, they may leave a residual hyperpigmentation of the skin. Common sites of involvement include the oral mucosa, face, trunk, groin, axillae, and areas exposed to pressure. Less common areas of involvement include the conjunctiva, nasal mucosa, pharynx, larynx, esophagus, penis, labia, vagina and anus and may present as dysphagia, hoarseness, aphonia, dyspepsia, and chest pain. When lateral pressure is applied to the unaffected skin at the periphery of a lesion, this will result in shearing of the epidermis and is known as a positive Nikolsky sign. This is not diagnositic as a positive Nikolsky sign is also seen with pemphigus foliaceus, bullous pemphigoid, and erythema multiforme. Biopsy specimens demonstrate antikeratincyte IgG antibodies on indirect immunofluorescence testing. Monkey esophagus is the preferred substrate for autoantibody testing in pemphigus vulgaris. Light microscopy of biopsy specimens shows intraepithelial suprabasilar bullae with minimal inflammation. Middle aged patients of Jewish or Mediterranean descent are more commonly affected. There is an increased incidence of this disorder in patients with other autoimmune disorders such as systemic lupus erythematosus, rheumatoid arthritis, Hashimoto’s thyroiditis, pernicious anemia, bullous pemphigoid, thymoma, thymic hyperplasia, and myasthenia gravis. Medications to include penicillamine, captopril, phenylbutazone, and rifampin may cause a pemphiguslike syndrome. Patients of any age may be afflicted, but the average age of onset is between the fifth and sixth decade. If untreated, the mortality rate for PV is almost 100% at 5 years; whereas, the 5 year mortality rate for treated disease is approximately 10%. The major cause of morbidity and mortality is from infection secondary to therapy induced immunosuppression.
Pemphigus foliaceus is characterized by the formation of lesions of the trunk that demonstrate crusting and scaling. Oral lesions are uncommon with pemphigus foliaceus. Antikeratincyte IgG antibodies are demonstrated using direct and indirect immunofluorescence techniques on guinea pig esophagus substrate. Pemphigus vegetans is associated with involvement of the tongue (cerebriform tongue) and vegetating lesions of the intertriginous and flexuaral areas. The drugs most often implicated as causing drug-induced disease are penicillamine and captopril. Patients from South America may develop a condition called fogo selvagem which is similar to pemphigus foliaceus.
Therapy for pemphigus vulgaris and pemphigus vegetans includes topical or intralesional corticosteroids plus dapsone or tetracyline for mild disease, and for more diffuse disease, systemic steroids plus an immunosuppressant (azathiprine, cyclophosphamide, methotrexate, chlorambucil, cyclosporine, dapsone, gold, or mycophenolate mofetil) may be required. Refractory cases of pemphigus vulgaris may respond to plasmapheresis or intravenous immunoglobulin therapy. In cases of pemphigus foliaceus and pemphigus erythematosus topical steroids may be used initially. If this proves ineffective, dapsone, tetracyline or antimalarials should be employed. If this second line of therapy fails, low-dose steroids with or without immunosuppressants should be started. For drug-induced disease, removal of the offending medication is the first step. If needed, topical or systemic steroids will aid in recovery. Prior to initiating dapsone therapy, patients should undergo evaluation of their glucose-6-phosphate dehydrogenase level. If glucose-6-phosphate deficiency is present, dapsone should not be used.