Pemphigus - Bullous disorders

Bullous disorders

Pemphigus

Definition

Pemphigus is a group of severe, chronic, autoimmune, superficial blistering diseases of the mucous membranes and skin. The commonest form is pemphigus vulgaris. Two other forms have been described: pemphigus foliaceus and paraneoplastic pemphigus.

Incidence

Uncommon

Age

Peaks in the middle-aged and elderly.

Sex

M = F

Geography

Increased incidence in Ashkenazi Jews.

Aetiology/pathophysiology

Patients have IgG autoantibodies against desmoglein (dsg), which are adhesion molecules that hold epidermal cells together. The absence of epidermal adhesion results in intraepidermal blisters. The genetic predisposition to develop these autoantibodies may be HLA related. Paraneoplastic pemphigus is associated with lymphoreticular malignancies such as non-Hodgkin’s lymphoma, chronic lymphocytic leukaemia and Waldenstrom’s¨ macroglobulinaemia. Drugs such as penicillamine, penicillin or captopril may induce pemphigus or unmask latent disease.

Clinical features

Pemphigus vulgaris presents with flaccid painful blisters and erosions often initially in the oropharynx and then the scalp, face, groin and chest. The blisters rupture easily, so often only erosions are seen. Sliding pressure easily dislodges the epidermis at the edge of blister (Nikolsky sign).

Pemphigus foliaceus causes a more superficial epidermal weakness causing erosions rather than blisters. Patients present with erythema, and crusting on the face and scalp, chest and back without involvement of the mucous membrane.

Paraneoplastic pemphigus causes severe disease involving both the skin and mucosal membranes.

Complications

There may be extensive fluid and protein loss and secondary infection particularly due to the immunosup-pressive nature of medications.

Investigations

Diagnosed by biopsy of an early, small blister or the edge of new erosion. Light microscopy and direct immunofluorescence for IgG deposition at epidermal cell junctions. Identification of anti-dsg autoantibodies may be useful.

Management

High-dose systemic corticosteroids tailored dependent on clinical response. If control cannot be maintained on low-dose steroids, immunosuppressive agents are used as steroid sparing agents including azathioprine, cyclophosphamide and methotrexate. Plasmapheresis and intravenous immunoglobulin have been used in refractory cases.

Prognosis

Without treatment pemphigus carries a high risk of mortality. With combination therapy the mortality rate is around 5%, mainly due to sepsis and other drug complications. Most patients require long-term immunosup-pressive treatment with maintenance therapy to remain in remission.