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Paraneoplastic pemphigus - Oral Mucosal Lesion
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Paraneoplastic pemphigus - Oral Mucosal Lesion

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Contributors: Connie Zhong, Sook-Bin Woo MS, DMD, MMSc, Carl Allen DDS, MSD, Susan Burgin MD
Other Resources UpToDate PubMed

Synopsis

Paraneoplastic pemphigus (PNP), also referred to as paraneoplastic autoimmune multiorgan syndrome (PAMS; some prefer this designation), is a variable multiorgan autoimmune syndrome with severe mucocutaneous disease that typically develops in the setting of current or past history of a lymphoreticular neoplasm, mainly B-cell or thymoma-like neoplasms. It is a rare disease, accounting for 3%-5% of all pemphigus cases.

Most patients (approximately two-thirds) who develop PNP have a preceding history of the neoplasm. In the remaining patients, the onset of PNP will be the first clue that a lymphoreticular neoplasm is present. Specific neoplasms associated with PNP are Hodgkin disease (42%), chronic lymphocytic leukemia (29%), Castleman tumor (angiofollicular lymph node hyperplasia) (10%), thymoma (6%), spindle cell neoplasms (6%), and Waldenström macroglobulinemia (6%).

The disease is thought to be due to the neoplastic process inducing both a humoral and cell-mediated humoral response. In particular, antibodies against tumor antigens cross-react with epithelial antigens, which is thought to cause the skin lesions. Immunoglobulin G (IgG) antibodies develop against multiple antigens, such as members of the plakin and desmoglein families.

The disease is most commonly identified in an adult population aged 45-70 years, as this is the demographic group most likely to develop lymphoma. Patients with Castleman tumor tend to be younger, in the second or third decade of life. There is no association with sex, ethnicity, or geographic region, although there may be an association with DRB1*03 and HLA-Cw*14 alleles.

Symptoms and signs include painful cutaneous and oral lesions secondary to the vesicles and bullae that form and subsequently rupture. Severe eye irritation may also be seen with conjunctival involvement, and esophageal, nasopharyngeal, vaginal, and penile mucosal lesions may also be seen. Pulmonary involvement, which is frequent, takes the form of bronchiolitis obliterans leading to dyspnea.

Prognosis depends on the associated malignancy. Removal of some tumors (thymoma or Castleman disease) may induce disease remission. However, patients with other malignancies may deteriorate, with death due to sepsis, gastrointestinal bleeding, or organ failure. Decreased survival has also been noted in patients with a bullous pemphigoid-like and a toxic epidermal necrolysis (TEN)-like picture as well as the presence of bronchiolitis obliterans.

Codes

ICD10CM:
L10.81 – Paraneoplastic pemphigus

SNOMEDCT:
402718003 – Pemphigus paraneoplastica

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Diagnostic Pearls

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Differential Diagnosis & Pitfalls

  • Pemphigus vulgaris – Oral erosions and ulcerations are usually the dominant feature for weeks to months before cutaneous vesicles and bullae begin to appear. Skin lesions in PNP are more pleomorphic than in pemphigus vulgaris.
  • Pemphigus foliaceus does not usually show oral involvement.
  • Erythema multiforme – Patients may have a history of previous episodes that resolved within 2-4 weeks, which is usually not seen in PNP. Patients may have a history of preceding herpetic infection. If classic "target" lesions of the skin are present, this would be more consistent with erythema multiforme.
  • Bullous pemphigoid – Cutaneous vesicles and bullae are the predominant feature of this condition, with only 20% of patients having oral involvement. Hemorrhagic crusting of the lips would be unusual.
  • Mucous membrane pemphigoid – This condition mostly affects the mucosa at various sites, with only 20% of patients showing cutaneous bullae. The relatively chronic, slow evolution of cicatricial pemphigoid would not be consistent with PNP.
  • Lichen planus – The erosive and ulcerative lesions of oral lichen planus are usually surrounded by radiating keratotic striae, a feature that is typically not evident in the oral lesions of PNP.
  • Herpetic stomatitis – The oral ulcerations may be diffuse but are comprised of crops of small ulcers (1-2 mm) that coalesce. Unlike PNP, significant cutaneous involvement in herpetic stomatitis would be unusual.
  • Stevens-Johnson syndrome / TEN – Drug-induced high fevers, skin tenderness, mucosal erosions, and skin detachment (necrolysis) develop 1-3 weeks after the inciting medication is started.
  • Drug hypersensitivity syndrome (drug reaction with eosinophilia and systemic symptoms [DRESS]) – Look for facial edema (hallmark of DRESS), eosinophilia, hepatitis, and other visceral involvement.
  • Drug-induced erythroderma

Best Tests

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Therapy

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References

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Last Reviewed: 06/21/2019
Last Updated: 06/24/2019
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Paraneoplastic pemphigus - Oral Mucosal Lesion
See also in: Overview
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Paraneoplastic pemphigus : Bullae, Oral erosions, Painful oral ulcers, Dyspnea
Clinical image of Paraneoplastic pemphigus
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