Paraneoplastic pemphigus (ORPHA:63455)
A rare form of autoimmune bullous skin disease characterized by polyformative skin lesions, typically beginning on the oral mucus membranes, and generally associated with lymphoma or chronic lymphoid leukemia.
Epidemiology
The prevalence of this form of pemphigus is unknown. About 500 cases of paraneoplastic pemphigus have been reported worldwide in the literature. This form accounts for 3-5% of all pemphigus cases.
Clinical description
Paraneoplastic pemphigus occurs in a background of suspected or proven neoplasia. The associated cancers are mostly lymphomas, chronic lymphoid leukaemia and in some cases, Kaposi sarcoma, Castelman's disease, thymomas, carcinomas, and poorly differentiated sarcomas. The disease almost always begins with severe diffuse blisters in the mouth, on the lips and on the oesophagus. Eyes are frequently involved. Skin lesions vary and can be misleading, presenting as bullous lichenoid lesions, evocative of urticaria or polymorphous erythema. Lungs can also be involved (in 30% to 40% of cases), as well as the gastrointestinal tract.
Etiology
The etiology and pathogenesis of paraneoplastic pemphigus are poorly understood.
Diagnostic methods
Histopathological analysis shows intra-epidermal acantholysis with the presence of necrotic keratinocyte cells, vacuolisation of the basal layer and dermic lichenoid inflammatory infiltrate. Direct immunofluorescence test usually shows granular-linear IgG and/or C3 deposits in the epidermal intercellular spaces, and/or at the dermo-epidermal junction (basement membrane zone). IgA and IgM can also be detected. Anti-plakine antibodies can be present (desmoplakin, periplakin, envoplakin), as well as anti-plectin, anti-desmoglein 1 and 3 antibodies, anti-BP180, and anti-BP230 antibodies.
Differential diagnosis
Differential diagnosis includes some forms of bullous pemphigoid, pemphigus vulgaris, drug-induced rash (toxic epidermal necrolysis, Stevens-Johnson syndrom), erythema multiforme, Graft Versus Host Disease (GVHD), lichen planus, or major aphthous stomatitis.
Management and treatment
The progression of paraneoplastic pemphigus rarely parallels neoplastic progression. The most commonly used treatment is systemic corticosteroids, but immunosuppressant drugs are often required. Some patients have been treated with intravenous immunoglobulin, plasmapheresis, and monoclonal antibodies. However, the efficacy of treatment varies depending on the underlying malignancy.
Prognosis
Paraneoplastic pemphigus is often fatal (in 90% of cases), however, the prognosis depends on the nature of the underlying malignancy and is improved when the associated tumor is benign. The high mortality rate is explained by the occurrence of severe infections (sometimes due to immunosuppressive drugs), the evolution of the underlying malignancy, or bronchiolitis obliterans which is related to the autoimmune response in paraneoplastic pemphigus.

                            Last update: 
                            May 2020


                            - Expert reviewer(s): 
                            Dr Marion CASTEL | ERN-Skin* - Pr Pascal JOLY | ERN-Skin*


                                * European Reference Network