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 include non-Hodgkin lymphoma, chronic lymphocytic leukemia, Castleman tumor (angiofollicular lymph node hyperplasia), thymoma, spindle cell neoplasms, and Waldenström macroglobulinemia.
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.
L10.81 – Paraneoplastic pemphigus
402718003 – Pemphigus paraneoplastica
- 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
- Erythema multiforme – This condition may clinically appear virtually identical to PNP. Patients may have a history of previous episodes that resolved within 2-4 weeks. 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% showing cutaneous bullae. The relatively chronic, slow evolution of cicatricial pemphigoid would not be consistent with PNP either.
- Lichen planus – The erosive oral lesions of 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 smaller lesions (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 about 1-3 weeks after the inciting medication is started.
- Staphylococcal toxic shock syndrome – Look for sudden onset of exanthematous eruption.
- Streptococcal toxic shock syndrome – Patients are usually aged 20-50 years and have a deep soft-tissue infection.
- Acute graft-versus-host disease – Look for history of bone marrow transplant.
- 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
- Erythrodermic psoriasis
- Atopic dermatitis with erythroderma
- Contact dermatitis
- Pityriasis rubra pilaris
- Sézary syndrome
- Phototoxic reaction
- Photoallergic reaction