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Paraneoplastic Pemphigus Treatment & Management

  • Author: Lynne J Goldberg, MD; Chief Editor: Dirk M Elston, MD  more...
Updated: Mar 04, 2016

Medical Care

Response to treatment paraneoplastic pemphigus is generally poor, especially for mucosal lesions. Initial care is aimed at treating superinfection, if present. Warm compresses, nonadherent wound dressings, and topical antibiotic ointment are helpful. Potent immunosuppressive agents are required to decrease blistering, but they are often ineffective. High-dose corticosteroids are first-line therapy for paraneoplastic pemphigus,[11] followed by steroid-sparing agents such as azathioprine, cyclosporine, and mycophenolate mofetil. In general, the skin lesions of paraneoplastic pemphigus are more responsive to therapy than mucosal lesions.[39]

Other therapeutic options for paraneoplastic pemphigus include plasmapheresis, immunophoresis, intravenous gammaglobulin,[27] and stem cell ablation therapy with high-dose cyclophosphamide[10] without stem cell rescue. Rituximab has been tried in several patients with mixed results.[40, 41] Alemtuzumab, an agent that targets CD52, has also been used with success.[42] Treating the underlying malignancy may control autoantibody production, and intravenous gammaglobulin (IVIG) at the time of surgery may help prevent the development of bronchiolitis obliterans. However, once this develops, it is typically not reversible.[6]


Surgical Care

For solid neoplasms, curative resection should be attempted when appropriate, but this does not halt disease progression, especially when malignant. If surgery results in decreased autoantibody production, the paraneoplastic pemphigus may improve. IVIG before, during, and after the surgery may block autoantibody released from the tumor. Respiratory symptoms are persistent.



Respiratory therapy may be beneficial when pulmonary involvement from paraneoplastic pemphigus causes respiratory insufficiency. Consultations from a pulmonary medicine specialist, an ophthalmologist, a gastroenterologist, and an otolaryngologist should be obtained when appropriate.

Contributor Information and Disclosures

Lynne J Goldberg, MD Professor, Departments of Dermatology and Pathology, Boston University School of Medicine

Lynne J Goldberg, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Society of Dermatopathology, International Society of Dermatopathology, Massachusetts Academy of Dermatology, New England Dermatological Society, North American Hair Research Society, Phi Beta Kappa, Women's Dermatologic Society

Disclosure: Nothing to disclose.


Nauman Nisar, MD Dermatopathologist, Mercy Medical Center, Sioux City, IA

Nauman Nisar, MD is a member of the following medical societies: College of American Pathologists

Disclosure: Nothing to disclose.

Specialty Editor Board

Richard P Vinson, MD Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Texas Medical Association, Association of Military Dermatologists, Texas Dermatological Society

Disclosure: Nothing to disclose.

Jeffrey P Callen, MD Professor of Medicine (Dermatology), Chief, Division of Dermatology, University of Louisville School of Medicine

Jeffrey P Callen, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, American College of Rheumatology

Disclosure: Received income in an amount equal to or greater than $250 from: XOMA; Biogen/IDEC; Novartis; Janssen Biotech, Abbvie, CSL pharma<br/>Received honoraria from UpToDate for author/editor; Received honoraria from JAMA Dermatology for associate editor and intermittent author; Received royalty from Elsevier for book author/editor; Received dividends from trust accounts, but I do not control these accounts, and have directed our managers to divest pharmaceutical stocks as is fiscally prudent from Stock holdings in various trust accounts include some pharmaceutical companies and device makers for i inherited these trust accounts; for: Celgene; Pfizer; 3M; Johnson and Johnson; Merck; Abbott Laboratories; AbbVie; Procter and Gamble; Amgen.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Ponciano D Cruz, Jr, MD Professor and Vice-Chair, Paul R Bergstresser Chair, Department of Dermatology, University of Texas Southwestern Medical Center

Ponciano D Cruz, Jr, MD is a member of the following medical societies: Texas Medical Association

Disclosure: Received consulting fee from RCTS for independent contractor; Received honoraria from Mary Kay Cosmetics for consulting; Received grant/research funds from Galderma for principal investigator.

  1. Anhalt GJ, Kim SC, Stanley JR, et al. Paraneoplastic pemphigus. An autoimmune mucocutaneous disease associated with neoplasia. N Engl J Med. 1990 Dec 20. 323(25):1729-35. [Medline].

  2. Anhalt GJ. Paraneoplastic pemphigus. J Investig Dermatol Symp Proc. 2004 Jan. 9(1):29-33. [Medline].

  3. Zimmermann J, Bahmer F, Rose C, Zillikens D, Schmidt E. Clinical and immunopathological spectrum of paraneoplastic pemphigus. J Dtsch Dermatol Ges. 2010 Aug. 8 (8):598-606. [Medline].

  4. Martel P, Loiseau P, Joly P, Busson M, Lepage V, Mouquet H, et al. Paraneoplastic pemphigus is associated with the DRB1*03 allele. J Autoimmun. 2003 Feb. 20 (1):91-5. [Medline].

  5. Liu Q, Bu DF, Li D, Zhu XJ. Genotyping of HLA-I and HLA-II alleles in Chinese patients with paraneoplastic pemphigus. Br J Dermatol. 2008 Mar. 158 (3):587-91. [Medline].

  6. Czernik A, Camilleri M, Pittelkow MR, Grando SA. Paraneoplastic autoimmune multiorgan syndrome: 20 years after. Int J Dermatol. 2011 Aug. 50 (8):905-14. [Medline].

  7. Qian SX, Li JY, Hong M, Xu W, Qiu HX. Nonhematological autoimmunity (glomerulosclerosis, paraneoplastic pemphigus and paraneoplastic neurological syndrome) in a patient with chronic lymphocytic leukemia: Diagnosis, prognosis and management. Leuk Res. 2009 Mar. 33 (3):500-5. [Medline].

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

  9. Yong AA, Tey HL. Paraneoplastic pemphigus. Australas J Dermatol. 2013 Nov. 54(4):241-50. [Medline].

  10. Hertzberg MS, Schifter M, Sullivan J, Stapleton K. Paraneoplastic pemphigus in two patients with B-cell non-Hodgkin's lymphoma: significant responses to cyclophosphamide and prednisolone. Am J Hematol. 2000 Feb. 63(2):105-6. [Medline].

  11. Martinez De Pablo MI, Iranzo P, Mascaro JM, Llambrich A, Baradad M, Herrero C. Paraneoplastic pemphigus associated with non-Hodgkin B-cell lymphoma and good response to prednisone. Acta Derm Venereol. 2005. 85(3):233-5. [Medline].

  12. Tilakaratne W, Dissanayake M. Paraneoplastic pemphigus: a case report and review of literature. Oral Dis. 2005 Sep. 11(5):326-9. [Medline].

  13. Hung IJ, Lin JJ, Yang CP, Hsueh C. Paraneoplastic syndrome and intrathoracic Castleman disease. Pediatr Blood Cancer. 2006 Oct 15. 47(5):616-20. [Medline].

  14. Marzano AV, Vezzoli P, Mariotti F, Boneschi V, Caputo R, Berti E. Paraneoplastic pemphigus associated with follicular dendritic cell sarcoma and Castleman disease. Br J Dermatol. 2005 Jul. 153(1):214-5. [Medline].

  15. Wang J, Zhu X, Li R, et al. Paraneoplastic pemphigus associated with Castleman tumor: a commonly reported subtype of paraneoplastic pemphigus in China. Arch Dermatol. 2005 Oct. 141(10):1285-93. [Medline].

  16. Koch LH, Layton CJ, Pilichowska M, Stadecker MJ, Barak O. Paraneoplastic Pemphigus and Castleman's Disease in the Setting of Herpes Simplex Virus Infection. Pediatr Dermatol. 2011 Oct 20. [Medline].

  17. Perera GK, Devereux S, Mufti G, Salisbury J, Creamer D. PNP with Waldenström's macroglobulinaemia. Clin Exp Dermatol. 2005 Jan. 30(1):27-9. [Medline].

  18. Wang J, Bu DF, Li T, et al. Autoantibody production from a thymoma and a follicular dendritic cell sarcoma associated with paraneoplastic pemphigus. Br J Dermatol. 2005 Sep. 153(3):558-64. [Medline].

  19. Tull T, Papineni P, Cook C, Mee J, Bower M, Morar N. Paraneoplastic pemphigus in patient infected with the human immunodeficiency virus. Clin Exp Dermatol. 2014 Jan. 39(1):83-5. [Medline].

  20. Eccersley LR, Hoffbrand AV, Rustin MH, McNamara CJ. Paraneoplastic pemphigus associated with systemic mastocytosis. Am J Hematol. 2009 May 27. [Medline].

  21. Kennedy NA, Dawe S. Atypical paraneoplastic pemphigus secondary to endometrial carcinoma with no mucosal involvement. Clin Exp Dermatol. 2009 Jul. 34(5):e130-3. [Medline].

  22. Kakurai M, Demitsu T, Iida E, et al. Coexistence of paraneoplastic pemphigus and bullous pemphigoid. J Eur Acad Dermatol Venereol. 2009 Aug. 23(8):962-4. [Medline].

  23. Ishii N, Hashimoto T. A case of paraneoplastic pemphigus who shifted to pemphigus vulgaris. J Eur Acad Dermatol Venereol. 2008 Mar. 22(3):374-5. [Medline].

  24. Cummins DL, Mimouni D, Tzu J, Owens N, Anhalt GJ, Meyerle JH. Lichenoid paraneoplastic pemphigus in the absence of detectable antibodies. J Am Acad Dermatol. 2007 Jan. 56(1):153-9. [Medline].

  25. Coelho S, Reis JP, Tellechea O, Figueiredo A, Black M. Paraneoplastic pemphigus with clinical features of lichen planus associated with low-grade B cell lymphoma. Int J Dermatol. 2005 May. 44(5):366-71. [Medline].

  26. Leger S, Picard D, Ingen-Housz-Oro S, Arnault JP, Aubin F, Carsuzaa F. Prognostic factors of paraneoplastic pemphigus. Arch Dermatol. 2012 Oct. 148(10):1165-72. [Medline].

  27. Zhu X, Zhang B. Paraneoplastic pemphigus. J Dermatol. 2007 Aug. 34(8):503-11. [Medline].

  28. Laforest C, Huilgol SC, Casson R, Selva D, Leibovitch I. Autoimmune bullous diseases: ocular manifestations and management. Drugs. 2005. 65(13):1767-79. [Medline].

  29. Camisa C, Helm TN. Paraneoplastic pemphigus is a distinct neoplasia-induced autoimmune disease. Arch Dermatol. 1993 Jul. 129(7):883-6. [Medline].

  30. Proby C, Fujii Y, Owaribe K, Nishikawa T, Amagai M. Human autoantibodies against HD1/plectin in paraneoplastic pemphigus. J Invest Dermatol. 1999 Feb. 112(2):153-6. [Medline].

  31. Poot AM, Diercks GF, Kramer D, Schepens I, Klunder G, Hashimoto T. Laboratory diagnosis of paraneoplastic pemphigus. Br J Dermatol. 2013 Nov. 169(5):1016-24. [Medline].

  32. Helou J, Allbritton J, Anhalt GJ. Accuracy of indirect immunofluorescence testing in the diagnosis of paraneoplastic pemphigus. J Am Acad Dermatol. 1995 Mar. 32(3):441-7. [Medline].

  33. Bennett DD, Busick TL. Delayed detection of autoantibodies in paraneoplastic pemphigus. J Am Acad Dermatol. 2007 Dec. 57(6):1094-5. [Medline].

  34. Huang Y, Li J, Zhu X. Detection of anti-envoplakin and anti-periplakin autoantibodies by ELISA in patients with paraneoplastic pemphigus. Arch Dermatol Res. 2009 Nov. 301(10):703-9. [Medline].

  35. Mouquet H, Drenovska K, Lartigue A, et al. Detection and characterization of anti-envoplakin linker autoantibodies in paraneoplastic pemphigus using specific bead-based assay. Clin Immunol. 2008 Nov. 129(2):304-12. [Medline].

  36. Probst C, Schlumberger W, Stocker W, et al. Development of ELISA for the specific determination of autoantibodies against envoplakin and periplakin in paraneoplastic pemphigus. Clin Chim Acta. 2009 Sep 6. [Medline].

  37. Barnadas MA, Curell R, Alomar A, Gelpi C. Paraneoplastic pemphigus with negative direct immunofluorescence in epidermis or mucosa but positive findings in adnexal structures. J Cutan Pathol. 2009 Jan. 36(1):34-8. [Medline].

  38. Khudhur AS, Di Zenzo G, Carrozzo M. Oral lichenoid tissue reactions: diagnosis and classification. Expert Rev Mol Diagn. 2014 Mar. 14 (2):169-84. [Medline].

  39. Frew JW, Murrell DF. Current management strategies in paraneoplastic pemphigus (paraneoplastic autoimmune multiorgan syndrome). Dermatol Clin. 2011 Oct. 29(4):607-12. [Medline].

  40. Barnadas M, Roe E, Brunet S, et al. Therapy of paraneoplastic pemphigus with Rituximab: a case report and review of literature. J Eur Acad Dermatol Venereol. 2006 Jan. 20(1):69-74. [Medline].

  41. Peterson JD, Chan LS. Effectiveness and side effects of anti-CD20 therapy for autoantibody-mediated blistering skin diseases: A comprehensive survey of 71 consecutive patients from the Initial use to 2007. Ther Clin Risk Manag. 2009 Feb. 5(1):1-7. [Medline]. [Full Text].

  42. Hohwy T, Bang K, Steiniche T, Peterslund NA, d'Amore F. Alemtuzumab-induced remission of both severe paraneoplastic pemphigus and leukaemic bone marrow infiltration in a case of treatment-resistant B-cell chronic lymphocytic leukaemia. Eur J Haematol. 2004 Sep. 73 (3):206-9. [Medline].

Direct immunofluorescence microscopy performed on epithelial biopsy specimen obtained from a patient with pemphigus vulgaris detects immunoglobulin G deposits at the epithelial cell surfaces.
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