oro-pharyngeal pemphigus vulgaris

The term “Pemphigus” derives from the Greek Pemphix, which means bubble or blister. This represents a group of potentially life-threatening autoimmune mucocutaneous diseases characterized by epithelial blistering affecting cutaneous and/or mucosal surfaces. The worldwide epidemiology of pemphigus has shown that this disorder affects 0.1–0.5 patients per 100 000 population per year. Some authors reported its incidence as high as 3.2 cases per 100 000. The disease affects primarily middle-aged persons, and the mean age of onset is approximately 50–60 years of age. Male-to-female ratio is approximately equal, but in puberty, girls are more likely to be affected than boys. There are several variants of pemphigus described (Pemphigus vulgaris, pemphigus foliaceus, IgA pemphigus, paraneoplastic pemphigus, drug-induced pemphigus, pemphigus vegetans, Pemphigus erythematosus) with different autoantibody profiles and clinical manifestations. As far as pemphigus vulgaris (PV), there is a fairly strong genetic background; certain ethnic groups, such as Ashkenazian Jews and those of Mediterranean and South Asian origin seem to be particularly susceptible. PV has been found in association with HLA class II, HLA-DR4 (DRB1*0402), DRw14 (DRB1*1041) and DQB1*0503. The pathogenesis of PV is due to IgG antibodies directed against the extracellular domains particularly of Dsg3 located intercellulary, leading to the phenomenon of acantholysis. Since oral epithelium expresses largely Dsg3 (skin expresses Dsg1 as well as Dsg3), oral lesions appear at an early stage. There is, indeed, direct evidence that autoantibodies against Dsg3 are critical in the pathogenesis. The precise mechanism of the acantholysis after PV-IgG binding to Dsg3 on the cell surface is unknown but may involve proteinases. Possible etiological factors are : diet, drugs, viruses. Occasionally, PV may be associated with other autoimmune disorders such as rheumatoid arthritis, myasthenia gravis, lupus erythematosus, or pernicious anaemia. Diagnosis of PV is based on three independent groups of criteria: clinical features, histologic findings and immunological tests. Biopsy is mandatory to deduce the form of the disease. PV shows intaepithelial suprabasal cleft formation and acantholysis, whereas basal cells remain attached to the basement membrane. Immunologically, direct immunofluorescence usually shows the presence of IgG with or without complement deposites in the intercellular cementum substance (ICS) (net-like pattern), whereas indirect immunofluorescence assays of serum is able to detect circulating ICS autoantibodies by using different substrates, such as human skin, monkey oesophagus or guinea pig oesophagus. Systemic CS are the mainstay of treatment for pemphigus vulgaris (PV) and their use, together with the introduction of other immunosupressive drugs, has transformed what was almost invariably a fatal illness into one where mortality is now approximately between 5% and 10%. However, the high doses and prolonged administrations of corticosteroids that are often needed to control the disease can result in numerous adverse side effects, many of which are serious or even life-threatening. Accordingly it is widely accepted to discontinue these drugs whenever feasible. Adjuvant therapies for patients who do not respond to or who experience complications from corticosteroids include immunosuppressants such as cyclophosphamide, chlorambucil, azathioprine, cyclosporine, methotrexate, micophenolate mofetil, antimalarials, systemic antibiotics, dapsone and gold. Nevertheless, some patients do not respond to these agents or present serious adverse effects. In these unresponsive cases, alternative treatments such as plasmapheresis, extracorporeal photopheresis, immunoabsorption techniques and high dose intravenous immunoglobulins (IVIg) have been recommended.