Pemphigus vulgaris

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Kiran Singh, M.D. [2]

Overview

Pemphigus vulgaris is a chronic blistering skin disease with skin lesions that are rarely pruritic, but which are often painful.

Pathophysiology

It is an autoimmune disease caused by antibodies directed against both desmoglein 1 and desmoglein 3 resulting in the loss of cohesion between keratinocytes in the epidermis, classified as a type II hypersensitivity reaction (in which antibodies bind to antigens on the body's own tissues). It is characterized by extensive flaccid blisters and mucocutaneous erosions. The severity of the disease, as well as the mucosal lesions, is believed to be directly proportional to the levels of desmoglein 3. Milder forms of pemphigus (like foliacious and erythematoses) are more desmoglein 1 heavy. It arises most often in middle-aged or older people, usually starting with a blister that ruptures easily. The lesions can become quite extensive. The pathogenesis of the disease involves autoantibodies against desmosome proteins, separating keratinocytes from the basal layer of the epidermis. On histology, the basal keratinocytes are usually still attached to the basement membrane leading to the appearance and thus the term, "tombstoning".

Transudative fluid accumulates in between the keratinocytes and basement membrane (suprabasal split), forming a blister and resulting in what is known as a positive Nikolsky's sign. This is a contrasting feature from bullous pemphigoid, where the detachment occurs between the epidermis and dermis (subepidermal bullae).

Diagnosis

On a physical exam, pemphigus vulgaris has flat bullae and a positive Nikolsky's sign. The gold standard for diagnosis is a punch biopsy from the area around the lesion that is examined by direct immunofluorescent staining, showing acantholytic cells. These can also be seen on a Tzanck smear. These cells are basically rounded, nucleated keratinocytes formed due to antibody mediated damage to cell adhesion protein: Desmoglein.

Pemphigus vulgaris is easy to confuse with impetigo and candidiasis. IgG4 is considered pathogenic. The diagnosis can be confirmed by testing for the infections that cause these other conditions, and by a lack of response to antibiotic treatment. Eosinophils tend to be found within the blisters and provide an important clue supporting bullous pemphigoid as the diagnosis.

Physical Examination

Skin

Oral cavity

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  Pemphigus vulgaris. With permission from Dermatology Atlas.

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  Pemphigus vulgaris. With permission from Dermatology Atlas.

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  Pemphigus vulgaris. With permission from Dermatology Atlas.

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  Pemphigus vulgaris. With permission from Dermatology Atlas.

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  Pemphigus vulgaris. With permission from Dermatology Atlas.

Axilla

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  Pemphigus vulgaris. With permission from Dermatology Atlas.

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  Pemphigus vulgaris. With permission from Dermatology Atlas.

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  Pemphigus vulgaris. With permission from Dermatology Atlas.

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  Pemphigus vulgaris. With permission from Dermatology Atlas.

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  Pemphigus vulgaris. With permission from Dermatology Atlas.

Treatment

Corticosteroids and other immunosuppressive drugs are the mainstay of treatment. Based on recent studies, corticosteroids can be used in Pulse Therapy/Supra-pharmacological doses once a month to decrease Hypothalamo-pituitary axis inhibition. IVIg, rituximab, mycophenolate mofetil, methotrexate, azathioprine, and cyclophosphamide have also been used with varying degrees of success. The development of new monoclonal antibodies holds promise for improved treatment of phemphigus in the future.

See also

• List of cutaneous conditions
• Pemphigus
• Pemphigoid
• Dermatitis herpetiformis
• List of conditions caused by problems with junctional proteins
• List of immunofluorescence findings for autoimmune bullous conditions