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Paraneoplastic Pemphigus at a Glance
  • Rare complication of malignancy, most commonly non-Hodgkin's lymphoma, chronic lymphocytic leukemia, or Castleman disease.
  • Painful, erosive stomatitis and polymorphous cutaneous lesions that may be blistering and erosive (resembling erythema multiforme), morbilliform, or lichenoid.
  • Serum autoantibodies directed against plakin proteins that are detected by indirect immunofluorescence against rodent bladder epithelium.
  • High mortality rate, with death due to sepsis, complications of treatment, or bronchiolitis obliterans.
  • No consistently effective therapy, but some success with the combined use of rituximab, systemic corticosteroids, and other immunosuppressive agents.

Paraneoplastic pemphigus (PNP) is an autoimmune disorder that is almost always linked to an underlying lymphoproliferative disorder. The following features define PNP:

  1. Painful stomatitis and a polymorphous cutaneous eruption with lesions that may be blistering, lichenoid, or resemble erythema multiforme.

  2. Histologic findings that reflect the variability of the cutaneous lesions, showing acantholysis, lichenoid, or interface change.

  3. Direct immunofluorescence findings of immunoglobulin G (IgG) and complement deposition in the epidermal intercellular spaces and, often, granular/linear complement deposition along the epidermal basement membrane zone.

  4. Serum autoantibodies that bind to the cell surface of skin and mucosae in a pattern typical of pemphigus, but in addition, bind to simple, columnar, and transitional epithelia.

  5. The serum autoantibodies identify desmogleins 1 and 3, in addition to members of the plakin family of epithelial proteins, such as desmoplakins, envoplakin, and periplakin.1

Non-Hodgkin's lymphoma (NHL), chronic lymphocytic leukemia (CLL), and Castleman disease are the neoplasms most commonly associated with PNP. There is no regularly effective treatment. Most patients die from complications of the disease, including pulmonary involvement with respiratory failure.

The incidence of PNP is unknown, although it is less common than pemphigus vulgaris or foliaceus (see Chapter 54). In an adverse events reporting analysis including 100,000 patients with known NHL and CLL, 12 were found to have PNP. Only three of them were identified by the reporting physician, and the remainder were identified only by retrospective data analysis, suggesting that the majority of cases of PNP are not being properly diagnosed. In this series, the most common misdiagnoses were erythema multiforme, Stevens–Johnson syndrome, toxic epidermal necrolysis (TEN), and drug reaction.

In almost all cases, PNP is associated with a limited number of lymphoproliferative neoplasms. On the basis of 140 cases of PNP confirmed by immunoprecipitation findings of the characteristic autoantibody profile, the estimated frequencies of specific neoplasms are 44% NHL, 19% CLL, 16% Castleman disease (giant follicular hyperplasia), 8% thymoma (malignant and benign), 7% sarcomas that are retroperitoneal and often poorly differentiated, 4% Waldenström's macroglobulinemia, and in 2% the neoplasms were too poorly differentiated to categorize (Fig. 55-1). The disproportionate representation of Castleman disease is notable, given its overall rarity. In children with PNP, Castleman disease is almost always the underlying neoplasm.2 Before the description of PNP, many cases of Castleman disease associated with atypical forms of pemphigus had been reported, and we suspect ...

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