Paraneoplastic Pemphigus

  • Diagnosis
  • Algorithms
  • Background
  • Lab Tests
  • References
  • Related Topics
  • Videos

Indications for Testing

  • Blistering disease
  • Suspected malignancy
    • Neoplasm usually precedes skin disease
    • Strong suspicion of paraneoplastic pemphigus in the absence of known cancer should trigger a diagnostic evaluation for malignancy

Laboratory Testing

  • Paraneoplastic pemphigus serum antibody screen
    • Positive screen – indicates serum antibodies to multiple epithelia (simple, columnar, transitional) and against desmoglein 1, 3; desmoplakin 1, 2; envoplakin; periplakin; BP230 and/or BP180
    • Positive antibody screen without known malignancy – perform aggressive evaluation for malignancy
    • Negative result – perform and/or correlate with perilesional skin biopsy; consider evaluation for other immunobullous diseases
  • Perilesional skin biopsy for cutaneous direct immunofluorescence submitted in Michel’s or Zeus medium
    • Staining is usually positive for IgG antibodies deposited on surface of epidermal and epithelial cells (cell surface antibodies)
    • IgG antibodies to basement membrane zone (BMZ) may also be present
    • Combination of cell surface and BMZ IgG antibody staining – indicates paraneoplastic pemphigus
    • IgA antibodies (cell surface and BMZ) – rarely identified

Differential Diagnosis

Paraneoplastic pemphigus (paraneoplastic autoimmune multiorgan syndrome) is a severely debilitating blistering disease affecting skin and mucous membranes in patients with malignancy, particularly hematologic malignancies.

Epidemiology

  • Incidence – very rare
  • Age – mean onset ≥60 years
  • Sex – M<F

Risk Factors

Pathophysiology

  • IgG antibodies to epithelial cell surface molecules with suprabasilar acantholysis and basal cell vacuolation; IgG antibodies to basement membrane zone may also be present
  • May have interface inflammatory changes, as in lichen planus
  • May have features of pemphigus vulgaris and erythema multiforme
  • Disease process may involve multiple organs (see Clinical Presentation)

Clinical Presentation

  • Skin lesions – polymorphous skin eruption
    • Flaccid bullae
    • Lichenoid lesions
    • Erythematous maculopapular lesions with dusky centers mimicking erythema multiforme
    • Erythroderma
  • Oral mucosal erosions – characteristically involves vermilion border of lips (may be first symptom)
  • Other organ systems involved
    • Gastrointestinal – esophagitis
    • Respiratory – bronchiolitis obliterans
    • Renal – nephrotic syndrome, glomerular nephritis
  • High mortality rate
Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

Paraneoplastic Pemphigus Antibody Screen 0092107
Method: Indirect Fluorescent Antibody

Cutaneous Direct Immunofluorescence, Biopsy 0092572
Method: Direct Immunofluorescence

Limitations 

Tissue must be submitted in Michel’s or Zeus medium; this test cannot be performed on formalin-fixed tissue

Epithelial Skin Antibody 0090299
Method: Indirect Immunofluorescence
(Indirect Fluorescent Antibody)

General References

AbreuVelez AM, Howard MS. Diagnosis and treatment of cutaneous paraneoplastic disorders. Dermatol Ther. 2010; 23(6): 662-75. PubMed

Frew JW, Murrell DF. Paraneoplastic pemphigus (paraneoplastic autoimmune multiorgan syndrome): clinical presentations and pathogenesis. Dermatol Clin. 2011; 29(3): 419-25, viii. PubMed

Parker SR, MacKelfresh J. Autoimmune blistering diseases in the elderly. Clin Dermatol. 2011; 29(1): 69-79. PubMed

Plager D, Leiferman K, Pittelkow M. Structural and Functional Cutaneous Immunology. In Adkinson NF et al. Middleton’s Allergy Principles and Practice, 6th ed. Philadelphia: Mosby, 2003.

Schmidt E, Zillikens D. Modern diagnosis of autoimmune blistering skin diseases. Autoimmun Rev. 2010; 10(2): 84-9. PubMed

Sehgal VN, Srivastava G. Paraneoplastic pemphigus/paraneoplastic autoimmune multiorgan syndrome. Int J Dermatol. 2009; 48(2): 162-9. PubMed

Zhu X, Zhang B. Paraneoplastic pemphigus. J Dermatol. 2007; 34(8): 503-11. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Taintor AR, Leiferman KM, Hashimoto T, Ishii N, Zone JJ, Hull CM. A novel case of IgA paraneoplastic pemphigus associated with chronic lymphocytic leukemia. J Am Acad Dermatol. 2007; 56(5 Suppl): S73-6. PubMed

Medical Reviewers

Last Update: October 2017