Paraneoplastic pemphigus

Abstract

Paraneoplastic pemphigus (PNP) is a distinct autoimmune blistering disease that can affect multiple organs other than the skin. It occurs in association with certain neoplasms, among which lymphoproliferative diseases are most commonly associated. The clinical presentation of PNP consists typically of painful, severe oral erosions that may be accompanied by a generalised cutaneous eruption and systemic involvement. The eruption may be of different morphology, consisting of lesions that resemble pemphigus, pemphigoid, erythema multiforme or graft versus host disease, as well as lesions resembling lichen planus. Similarly, the histological findings also show considerable variability. PNP is characterised by the presence of autoantibodies against various antigens: desmoplakin I (250 kd), bullous pemphigoid antigen I (230 kd), desmoplakin II (210 kd), envoplakin (210 kd), periplakin (190 kd), plectin (500 kd) and a 170-kd protein. This 170-kd protein has recently been identified as alpha-2-macroglobulin-like-1, a broad range protease inhibitor expressed in stratified epithelia and other tissue damaged in PNP. The prognosis of PNP is poor and the disease is often fatal. Immunosuppressive agents are often required to decrease blistering, and treating the underlying malignancy with chemotherapy may control autoantibody production. The prognosis is better when PNP is associated with benign tumours and these should be surgically excised when possible.

Desmosomes: Regulators of Cellular Signaling and Adhesion in Epidermal Health and Disease

“…The autoimmune skin disorders pemphigus and paraneoplastic pemphigus are associated with the presence of circulating autoantibodies attacking desmosomal components including Dsg1, Dsg3, Dsc3, and possibly Pkp3, bullous pemphigoid antigen 1, envoplakin, periplakin, and Perp (Koulu et al 1984;Amagai et al 1991;Nguyen et al 2009;Mao et al 2010;Yong and Tey 2012;Kalantari-Dehaghi et al 2013) and reviewed recently by several groups (Amagai and Stanley 2012;Grando 2012;Cirillo and Al-Jandan 2013). Although a potential role for antibodies directed against cytoplasmic components in disease pathogenesis has been suggested, the majority of data point to Dsg3 and Dsg1 as the primary targets in pemphigus vulgaris and foliaceus (see Fig.…”

Paraneoplastic pemphigus: A trait d’union between dermatology and oncology

“…Different kind of lesions may coexist and evolve from one type to another [3,40] . Cutaneous lesions could be similar to those seen in pemphigus, pemphigoid, erythema multiforme or graft versus host disease [11,38,40] . Pustular and psoriasis form presentation have also been described [3] .…”

“…Nearly 84% of all PNP are found in association with hematologic neoplasms or disorders [2,6] . Among these, non-Hodgkin's lymphoma accounts for 38.6%, chronic lymphocytic leukemia for 18.4%, Castleman's disease for 18.4%, thymoma for 5.5%, Waldenstrom's macroglobulinemia for 1.2%, Hodgkin's lymphoma for 0.6%, and monoclonal gammopathy for 0.6% [2,5,6,11] . In addition, carcinomas developed from epithelial cells (8.6%) [12][13][14] , sarcomas derived from mesenchymal lines (6.2%) [9,15,16] , and melanoma (0.6%) [17] also are reported in association with PNP.…”

“…Rituximab, the anti-CD20 monoclonal antibody, has improved the clinical picture in PNP patients with underlying B-cell lymphoma [11,68,69] . Alemtuzumab, a humanized monoclonal antibody which binds CD52, has induced a long-term remission in a patient with B-cell chronic lymphocytic leukemia [70] .…”

Paraneoplastic pemphigus and myasthenia gravis, associated with inflammatory pseudotumor‐like follicular dendritic cell sarcoma: response to rituximab

“…The pathogenesis is thought to be due to the production of antibodies against tumor‐derived antigens; the antibodies may attack components sharing the same or a similar epitope 8. Wang et al 9 reported that MG is a complication of PNP.…”