Paraneoplastic Pemphigus and Autoimmune Blistering Diseases Associated with Neoplasm: Characteristics, Diagnosis, Associated Neoplasms, Proposed Pathogenesis, Treatment

Abstract

Autoimmune paraneoplastic and neoplasm-associated skin syndromes are characterized by autoimmune-mediated cutaneous lesions in the presence of a neoplasm. The identification of these syndromes provides information about the underlying tumor, systemic symptoms, and debilitating complications. The recognition of these syndromes is particularly helpful in cases of skin lesions presenting as the first sign of the malignancy, and the underlying malignancy can be treated in a timely manner. Autoimmune paraneoplastic and neoplasm-associated bullous skin syndromes are characterized by blister formation due to an autoimmune response to components of the epidermis or basement membrane in the context of a neoplasm. The clinical manifestations, histopathology and immunopathology findings, target antigens, associated neoplasm, current diagnostic criteria, current understanding of pathogenesis, and treatment options for a selection of four diseases are reviewed. Paraneoplastic pemphigus manifests with clinically distinct painful mucosal erosions and polymorphic cutaneous lesions, and is often associated with lymphoproliferative neoplasm. In contrast, bullous pemphigoid associated with neoplasm presents with large tense subepidermal bullae of the skin, and mild mucosal involvement, but without unique clinical features. Mucous membrane pemphigoid associated with neoplasm is a disorder of chronic subepithelial blisters that evolve into erosions and ulcerations that heal with scarring, and involves stratified squamous mucosal surfaces. Linear IgA dermatosis associated with neoplasm is characterized by annularly grouped pruritic papules, vesicles, and bullae along the extensor surfaces of elbows, knees, and buttocks. Physicians should be aware that these autoimmune paraneoplastic and neoplasm-associated syndromes can manifest distinct or similar clinical features as compared with the non-neoplastic counterparts.

Pemphigus: Subtypes, Clinical Features, Diagnosis, and Treatment

“…The onset of the lesions usually presents with initially limited cheilitis and/or ulcerative stomatitis, which then progresses to severe, intractable, hemorrhagical stomatitis with persistent painful mucosal ulcerations in the oropharynx and esophagus [4,5,15,16,77]. Oral lesions usually extend to the vermillion border of the lips [15,77].…”

“…Oral lesions usually extend to the vermillion border of the lips [15,77]. Eye involvement especially includes conjunctival erosions and occurs in 70% of patients [79][80][81][82].…”

“…The palmar involvement is usually observed [4]. Lichen planus-like lesions localized on skin, nails and/or mucosa resemble lichen planus, target-like lesions resemble erythema multiforme, and bullous lesions and erosive lesions resemble PV and bullous pemphigoid [4,15,66,76,77,[83][84][85][86][87]. Cutaneous lesions mimicking graft versus host disease or Stevens-Johnson syndrome may also be observed [86,87].…”

“…As though most of the patients with PNP are associated with malignancies, the prognosis of PNP is severe with a high mortality rate [15,77,83,84,88,89]. Internal organ involvement including lungs (Bronchiolitis obliterans), thyroid, kidney and gastrointestinal system has been documented [15,88,89].…”

“…Internal organ involvement including lungs (Bronchiolitis obliterans), thyroid, kidney and gastrointestinal system has been documented [15,88,89]. Most authors have reported that the term "paraneoplastic pemphigus" is too restrictive to describe the developing multiorgan syndrome involvement and have suggested a new nomenclature named as paraneoplastic autoimmune multiorgan syndrome (PAMS) [15,88].…”