Anhalt et al
first described paraneoplastic pemphigus in 1990. The authors reported five patients with underlying neoplasms who developed oral erosions and bullous skin eruptions. Skin biopsy samples showed both suprabasal acantholysis and interface dermatitis. Direct immunofluorescence (DIF) testing and indirect immunofluorescence (IDIF) testing revealed intraepidermal intercellular staining with immunoglobulin G (IgG); DIF testing also revealed deposition of complement at the dermoepidermal junction (see the image below). By immunoprecipitation, target antigens were identified from skin extracts with molecular weights of 250, 230, 210, and 190 kd. Since then, many patients with paraneoplastic pemphigus have been reported, and patients previously believed to have other diseases have been retrospectively diagnosed.
Direct immunofluorescence microscopy performed on epithelial biopsy specimen obtained from a patient with pemphigus vulgaris detects immunoglobulin G deposits at the epithelial cell surfaces.
A summary of the original criteria for the diagnosis of paraneoplastic pemphigus includes the following:
Painful mucosal erosions, sometimes with a skin eruption that eventually results in blisters and erosions, in the setting of confirmed or occult malignancy
Histopathologic changes of acantholysis, keratinocyte necrosis, and interface dermatitis
DIF observation of immunoreactants, typically IgG and complement (C3) within the epidermal intercellular spaces as well as at the epidermal basement membrane
IDIF observation of circulating antibodies specific for stratified squamous or transitional epithelia (transitional epithelium)
Immunoprecipitation of a complex of proteins with typical molecular weights, as described in Other Tests
Because not all patients demonstrate these original criteria, Anhalt
has proposed the following new, minimal criteria for the diagnosis of paraneoplastic pemphigus:
Painful, progressive stomatitis
Histopathologic changes of acantholysis or lichenoid/interface dermatitis
Demonstration of antiplakin antibodies
Demonstration of an underlying lymphoproliferative neoplasm
Paraneoplastic pemphigus is rare, and, while the exact incidence is unknown, it is likely underreported. In 2010, 450 cases were reported in the literature.
There is an association between paraneoplastic pemphigus and HLA class II DRB I*03 and HLA-Cw*14 (in Chinese patients).
Hematologic malignancies are most commonly associated with paraneoplastic pemphigus, although it can also be associated with carcinomas, sarcomas, and benign neoplasms.
Unlike other forms of pemphigus, paraneoplastic pemphigus affects organ systems other than the integument. Thus, the term “paraneoplastic autoimmune multiorgan syndrome”, or “PAMS”, has been suggested as a more appropriate name for the syndrome.