Paraneoplastic pemphigus: a short review

Abstract

Paraneoplastic pemphigus (PNP) is a fatal autoimmune blistering disease associated with an underlying malignancy. It is a newly recognized blistering disease, which was first recognized in 1990 by Dr Anhalt who described an atypical pemphigus with associated neoplasia. In 2001, Nguyen proposed the term paraneoplastic autoimmune multiorgan syndrome because of the recognition that the condition affects multiple organ systems. PNP presents most frequently between 45 and 70 years old, but it also occurs in children and adolescents. A wide variety of lesions (florid oral mucosal lesions, a generalized polymorphous cutaneous eruption, and pulmonary involvement) may occur in patients with PNP. The earliest and most consistent finding is severe stomatitis. There is a spectrum of at least five clinical variants with different morphology. Similarly, the histological findings are very variable. Investigations to diagnose PNP should include checking for systemic complications (to identify tumor), skin biopsies (for histopathological and immunofluorescence studies), and serum immunological studies. PNP is characterized by the presence of autoantibodies against antigens such as desmoplakin I (250 kD), bullous pemphigoid aniygen I (230 kD), desmoplakin II (210 kD), envoplakin (210 kD), periplakin (190 kD), plectin (500 kD), and a 170 kD protein. Unlike other forms of pemphigus, PNP can affect other types of epithelia, such as gastrointestinal and respiratory tract. Treatment of PNP is difficult, and the best outcomes have been reported with benign neoplasms that have been surgically excised. The first-line treatment is high-dose corticosteroids with the addition of steroid-sparing agents. Treatment failures are often managed with rituximab with or without concomitant intravenous immunoglobulin. In general, the prognosis is poor, not only because of eventual progression of malignant tumors but also because treatment with aggressive immunosuppression therapy often results in infectious complications, which is unfortunately at this time the most common cause of death in PNP.

Diagnosis of Autoimmune Blistering Diseases

“…First, PNP mainly affects the oral mucosa with other mucous membranes less frequently involved ( 95 – 97 ). Cutaneous lesions may arise on any part of the skin and may include: (i) pemphigus-like lesions with flaccid blisters, erosions, erythema and crusts; (ii) BP-like lesions such as urticarial lesions and tense blisters ( 96 ); (iii) erythema multiforme-like lesions and (iv) lichen planus-like lesions presenting as flat scaly papules and intense mucous membrane involvement ( 95 ). Furthermore, pulmonary destruction leading to bronchiolitis obliterans was noticed in many PNP-patients ( 98 ).…”

Skin Barrier and Autoimmunity—Mechanisms and Novel Therapeutic Approaches for Autoimmune Blistering Diseases of the Skin

“…These autoantibodies have shown cross reactivity to proteins present in sand fly saliva (45), which may represent epitope spreading from foreign proteins to similar autoantigens. Epitope spreading is also thought to be involved in paraneoplastic (PNP) pemphigus (46) where tumor-associated antigens may become targeted in an effort to destroy the tumor, however similar antigens may also be shared by keratinocytes (47). PNP pemphigus is most commonly associated with lymphatic malignancies, including non-Hodgkin's lymphoma and chronic lymphocytic leukemia.…”

Current Therapy in Autoimmune Bullous Diseases

“…Perioperative intravenous immunoglobulins administration in an obvious dose (2 g/kg/cycle) is recommended to block autoantibody release from the tumor during surgery [79]. In the case of benign neoplasm, surgical removal ameliorates the condition and may induce remission of paraneoplastic pemphigus with contemporary decrease of autoantibodies within 6-8 weeks [80]. In malignant neoplasm, the prognosis is poor and depends on the behavior of malignant tumor and development of severe respiratory failure.…”

“…In malignant neoplasm, the prognosis is poor and depends on the behavior of malignant tumor and development of severe respiratory failure. The mortality rate is high and ranges from 75 to 90% [80]. The disease may progress despite surgery and chemotherapy.…”