Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Initial management of pemphigus vulgaris and pemphigus foliaceus

Michael Hertl, MD
Shamir Geller, MD
Section Editor
John J Zone, MD
Deputy Editor
Abena O Ofori, MD


The term pemphigus describes a group of autoimmune mucocutaneous blistering disorders characterized by acantholysis (loss of keratinocyte to keratinocyte adhesion) in the epithelium of mucous membranes or skin. Pemphigus vulgaris and pemphigus foliaceus are the two most common forms of pemphigus. Significant morbidity and mortality can occur as a result of complications of these diseases and their treatments.

Systemic glucocorticoids are the mainstay of therapy for pemphigus vulgaris and pemphigus foliaceus, and are usually highly effective for obtaining control of disease. Nonsteroidal immunomodulatory agents such as azathioprine, mycophenolate mofetil, and dapsone commonly are prescribed in conjunction with systemic glucocorticoids in an attempt to minimize the risk for adverse effects of long-term, high-dose glucocorticoid therapy. Emerging data suggest that rituximab, an agent traditionally reserved for refractory pemphigus, is also beneficial for the initial treatment of this disease. Other interventions, including intravenous immune globulin (IVIG), immunoadsorption, and cyclophosphamide, are typically reserved for patients with refractory disease. (See "Management of refractory pemphigus vulgaris and pemphigus foliaceus".)

The initial management of pemphigus vulgaris and pemphigus foliaceus will be reviewed here. The management of refractory pemphigus vulgaris and pemphigus foliaceus, the pathogenesis and diagnosis of pemphigus, and the diagnosis and management of paraneoplastic pemphigus are reviewed separately. (See "Management of refractory pemphigus vulgaris and pemphigus foliaceus" and "Pathogenesis, clinical manifestations, and diagnosis of pemphigus" and "Paraneoplastic pemphigus".)


Although pemphigus vulgaris typically presents as a more severe disorder than pemphigus foliaceus due to the common presence of both mucosal and cutaneous involvement (picture 1A-B), both disorders can lead to significant morbidity. Oral mucosal involvement, which occurs in almost all patients with pemphigus vulgaris, usually is accompanied by severe pain, and may lead to poor alimentation resulting in weight loss and malnutrition (picture 2A-C). In addition, the widespread loss of the epidermal barrier that occurs in pemphigus vulgaris and pemphigus foliaceus may lead to protein loss, fluid loss, electrolyte imbalances, dietary insufficiencies, increased catabolism, and increased risk for local and systemic infections (picture 3A-D). (See "Pathogenesis, clinical manifestations, and diagnosis of pemphigus", section on 'Clinical features'.)

The complications of pemphigus vulgaris can be life-threatening; it is estimated that prior to the use of systemic immunosuppressants, more than 70 percent to nearly 100 percent of patients died within one to five years [1-3]. Pemphigus foliaceus, which is characterized by shallow blisters and involvement limited to the skin, is considered to have a better prognosis than pemphigus vulgaris (picture 4A-C) [3]; however, progression of pemphigus foliaceus may lead to extensive involvement and similar complications.

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Dec 05, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Bystryn JC, Rudolph JL. Pemphigus. Lancet 2005; 366:61.
  2. Grando SA. Pemphigus autoimmunity: hypotheses and realities. Autoimmunity 2012; 45:7.
  3. LEVER WF. Pemphigus. Medicine (Baltimore) 1953; 32:1.
  4. Bystryn JC, Steinman NM. The adjuvant therapy of pemphigus. An update. Arch Dermatol 1996; 132:203.
  5. Beissert S, Werfel T, Frieling U, et al. A comparison of oral methylprednisolone plus azathioprine or mycophenolate mofetil for the treatment of pemphigus. Arch Dermatol 2006; 142:1447.
  6. Martin LK, Werth V, Villanueva E, et al. Interventions for pemphigus vulgaris and pemphigus foliaceus. Cochrane Database Syst Rev 2009; :CD006263.
  7. Cirillo N, Cozzani E, Carrozzo M, Grando SA. Urban legends: pemphigus vulgaris. Oral Dis 2012; 18:442.
  8. Leshem YA, Gdalevich M, Ziv M, et al. Opportunistic infections in patients with pemphigus. J Am Acad Dermatol 2014; 71:284.
  9. Chams-Davatchi C, Valikhani M, Daneshpazhooh M, et al. Pemphigus: analysis of 1209 cases. Int J Dermatol 2005; 44:470.
  10. Martin LK, Werth VP, Villaneuva EV, Murrell DF. A systematic review of randomized controlled trials for pemphigus vulgaris and pemphigus foliaceus. J Am Acad Dermatol 2011; 64:903.
  11. Murrell DF, Dick S, Ahmed AR, et al. Consensus statement on definitions of disease, end points, and therapeutic response for pemphigus. J Am Acad Dermatol 2008; 58:1043.
  12. Kasperkiewicz M, Schmidt E, Zillikens D. Current therapy of the pemphigus group. Clin Dermatol 2012; 30:84.
  13. Harman KE, Brown D, Exton LS, et al. British Association of Dermatologists' guidelines for the management of pemphigus vulgaris 2017. Br J Dermatol 2017; 177:1170.
  14. Kneisel A, Hertl M. Autoimmune bullous skin diseases. Part 2: diagnosis and therapy. J Dtsch Dermatol Ges 2011; 9:927.
  15. Aberer W, Wolff-Schreiner EC, Stingl G, Wolff K. Azathioprine in the treatment of pemphigus vulgaris. A long-term follow-up. J Am Acad Dermatol 1987; 16:527.
  16. Mimouni D, Nousari CH, Cummins DL, et al. Differences and similarities among expert opinions on the diagnosis and treatment of pemphigus vulgaris. J Am Acad Dermatol 2003; 49:1059.
  17. Chams-Davatchi C, Esmaili N, Daneshpazhooh M, et al. Randomized controlled open-label trial of four treatment regimens for pemphigus vulgaris. J Am Acad Dermatol 2007; 57:622.
  18. Almugairen N, Hospital V, Bedane C, et al. Assessment of the rate of long-term complete remission off therapy in patients with pemphigus treated with different regimens including medium- and high-dose corticosteroids. J Am Acad Dermatol 2013; 69:583.
  19. Carson PJ, Hameed A, Ahmed AR. Influence of treatment on the clinical course of pemphigus vulgaris. J Am Acad Dermatol 1996; 34:645.
  20. Chams-Davatchi C, Mortazavizadeh A, Daneshpazhooh M, et al. Randomized double blind trial of prednisolone and azathioprine, vs. prednisolone and placebo, in the treatment of pemphigus vulgaris. J Eur Acad Dermatol Venereol 2013; 27:1285.
  21. Beissert S, Mimouni D, Kanwar AJ, et al. Treating pemphigus vulgaris with prednisone and mycophenolate mofetil: a multicenter, randomized, placebo-controlled trial. J Invest Dermatol 2010; 130:2041.
  22. Ioannides D, Apalla Z, Lazaridou E, Rigopoulos D. Evaluation of mycophenolate mofetil as a steroid-sparing agent in pemphigus: a randomized, prospective study. J Eur Acad Dermatol Venereol 2012; 26:855.
  23. Ratnam KV, Phay KL, Tan CK. Pemphigus therapy with oral prednisolone regimens. A 5-year study. Int J Dermatol 1990; 29:363.
  24. Harman KE, Albert S, Black MM, British Association of Dermatologists. Guidelines for the management of pemphigus vulgaris. Br J Dermatol 2003; 149:926.
  25. Femiano F, Gombos F, Scully C. Pemphigus vulgaris with oral involvement: evaluation of two different systemic corticosteroid therapeutic protocols. J Eur Acad Dermatol Venereol 2002; 16:353.
  26. Werth VP. Treatment of pemphigus vulgaris with brief, high-dose intravenous glucocorticoids. Arch Dermatol 1996; 132:1435.
  27. Mentink LF, Mackenzie MW, Tóth GG, et al. Randomized controlled trial of adjuvant oral dexamethasone pulse therapy in pemphigus vulgaris: PEMPULS trial. Arch Dermatol 2006; 142:570.
  28. Joly P, Maho-Vaillant M, Prost-Squarcioni C, et al. First-line rituximab combined with short-term prednisone versus prednisone alone for the treatment of pemphigus (Ritux 3): a prospective, multicentre, parallel-group, open-label randomised trial. Lancet 2017; 389:2031.
  29. Craythorne EE, Mufti G, DuVivier AW. Rituximab used as a first-line single agent in the treatment of pemphigus vulgaris. J Am Acad Dermatol 2011; 65:1064.
  30. Colliou N, Picard D, Caillot F, et al. Long-term remissions of severe pemphigus after rituximab therapy are associated with prolonged failure of desmoglein B cell response. Sci Transl Med 2013; 5:175ra30.
  31. Cho YT, Lee FY, Chu CY, Wang LF. First-line combination therapy with rituximab and corticosteroids is effective and safe for pemphigus. Acta Derm Venereol 2014; 94:472.
  32. Ingen-Housz-Oro S, Valeyrie-Allanore L, Cosnes A, et al. First-line treatment of pemphigus vulgaris with a combination of rituximab and high-potency topical corticosteroids. JAMA Dermatol 2015; 151:200.
  33. Ahmed AR, Nguyen T, Kaveri S, Spigelman ZS. First line treatment of pemphigus vulgaris with a novel protocol in patients with contraindications to systemic corticosteroids and immunosuppressive agents: Preliminary retrospective study with a seven year follow-up. Int Immunopharmacol 2016; 34:25.
  34. Lunardon L, Tsai KJ, Propert KJ, et al. Adjuvant rituximab therapy of pemphigus: a single-center experience with 31 patients. Arch Dermatol 2012; 148:1031.
  35. Hertl M, Jedlickova H, Karpati S, et al. Pemphigus. S2 Guideline for diagnosis and treatment--guided by the European Dermatology Forum (EDF) in cooperation with the European Academy of Dermatology and Venereology (EADV). J Eur Acad Dermatol Venereol 2015; 29:405.
  36. Atzmony L, Hodak E, Leshem YA, et al. The role of adjuvant therapy in pemphigus: A systematic review and meta-analysis. J Am Acad Dermatol 2015; 73:264.
  37. Burton JL, Greaves MW, Marks J, Dawber RP. Azathioprine in pemphigus vulgaris. Br Med J 1970; 3:84.
  38. Mourellou O, Chaidemenos GC, Koussidou T, Kapetis E. The treatment of pemphigus vulgaris. Experience with 48 patients seen over an 11-year period. Br J Dermatol 1995; 133:83.
  39. Anstey AV, Wakelin S, Reynolds NJ, British Association of Dermatologists Therapy, Guidelines and Audit Subcommittee. Guidelines for prescribing azathioprine in dermatology. Br J Dermatol 2004; 151:1123.
  40. Jackson AP, Hall AG, McLelland J. Thiopurine methyltransferase levels should be measured before commencing patients on azathioprine. Br J Dermatol 1997; 136:133.
  41. Meggitt SJ, Anstey AV, Mohd Mustapa MF, et al. British Association of Dermatologists' guidelines for the safe and effective prescribing of azathioprine 2011. Br J Dermatol 2011; 165:711.
  42. Badalamenti SA, Kerdel FA. Azathioprine. In: Comprehensive Dermatologic Drug Therapy, 2nd ed, Wolverton SE (Ed), Elsevier, Philadelphia 2007. p.182.
  43. Enk AH, Knop J. Mycophenolate is effective in the treatment of pemphigus vulgaris. Arch Dermatol 1999; 135:54.
  44. Mimouni D, Anhalt GJ, Cummins DL, et al. Treatment of pemphigus vulgaris and pemphigus foliaceus with mycophenolate mofetil. Arch Dermatol 2003; 139:739.
  45. Powell AM, Albert S, Al Fares S, et al. An evaluation of the usefulness of mycophenolate mofetil in pemphigus. Br J Dermatol 2003; 149:138.
  46. Strowd LC, Taylor SL, Jorizzo JL, Namazi MR. Therapeutic ladder for pemphigus vulgaris: emphasis on achieving complete remission. J Am Acad Dermatol 2011; 64:490.
  47. De Simone C, Caldarola G, Perino F, et al. Enteric-coated mycophenolate sodium as a steroid-sparing agent in pemphigus treatment: a retrospective study. Dermatol Ther 2012; 25:219.
  48. Sollinger HW, Sundberg AK, Leverson G, et al. Mycophenolate mofetil versus enteric-coated mycophenolate sodium: a large, single-center comparison of dose adjustments and outcomes in kidney transplant recipients. Transplantation 2010; 89:446.
  49. Perlis C, Pan TD, McDonald CJ. Cytotoxic agents. In: Comprehensive Dermatologic Drug Therapy, 2nd ed, Wolverton SE (Ed), Elsevier Inc, Philadelphia 2007. p.197.
  50. Gürcan HM, Ahmed AR. Efficacy of dapsone in the treatment of pemphigus and pemphigoid: analysis of current data. Am J Clin Dermatol 2009; 10:383.
  51. Werth VP, Fivenson D, Pandya AG, et al. Multicenter randomized, double-blind, placebo-controlled, clinical trial of dapsone as a glucocorticoid-sparing agent in maintenance-phase pemphigus vulgaris. Arch Dermatol 2008; 144:25.
  52. Basset N, Guillot B, Michel B, et al. Dapsone as initial treatment in superficial pemphigus. Report of nine cases. Arch Dermatol 1987; 123:783.
  53. Chatterjee M, Meru S, Vasudevan B, et al. Pemphigus foliaceus masquerading as IgA pemphigus and responding to dapsone. Indian J Dermatol 2012; 57:495.
  54. Hirata Y, Abe R, Kikuchi K, et al. Intraepidermal neutrophilic IgA pemphigus successfully treated with dapsone. Eur J Dermatol 2012; 22:282.
  55. Suzuki M, Karube S, Kobori Y, et al. IgA pemphigus occurring in a 1-month-old infant. J Am Acad Dermatol 2003; 48:S22.
  56. Gniadecki R, Bygum A, Clemmensen O, et al. IgA pemphigus: the first two Scandinavian cases. Acta Derm Venereol 2002; 82:441.
  57. Baum S, Debby A, Gilboa S, et al. Efficacy of Dapsone in the Treatment of Pemphigus Vulgaris: A Single-Center Case Study. Dermatology 2016; 232:578.
  58. Gürcan HM, Ahmed AR. Analysis of current data on the use of methotrexate in the treatment of pemphigus and pemphigoid. Br J Dermatol 2009; 161:723.
  59. Baum S, Greenberger S, Samuelov L, et al. Methotrexate is an effective and safe adjuvant therapy for pemphigus vulgaris. Eur J Dermatol 2012; 22:83.
  60. Tran KD, Wolverton JE, Soter NA. Methotrexate in the treatment of pemphigus vulgaris: experience in 23 patients. Br J Dermatol 2013; 169:916.
  61. Smith TJ, Bystryn JC. Methotrexate as an adjuvant treatment for pemphigus vulgaris. Arch Dermatol 1999; 135:1275.
  62. Mobini N, Padilla T Jr, Ahmed AR. Long-term remission in selected patients with pemphigus vulgaris treated with cyclosporine. J Am Acad Dermatol 1997; 36:264.
  63. Vardy DA, Cohen AD. Cyclosporine therapy should be considered for maintenance of remission in patients with pemphigus. Arch Dermatol 2001; 137:505.
  64. Chrysomallis F, Ioannides D, Teknetzis A, et al. Treatment of oral pemphigus vulgaris. Int J Dermatol 1994; 33:803.
  65. Ioannides D, Chrysomallis F, Bystryn JC. Ineffectiveness of cyclosporine as an adjuvant to corticosteroids in the treatment of pemphigus. Arch Dermatol 2000; 136:868.
  66. McCarty M, Fivenson D. Two decades of using the combination of tetracycline derivatives and niacinamide as steroid-sparing agents in the management of pemphigus: defining a niche for these low toxicity agents. J Am Acad Dermatol 2014; 71:475.
  67. Chaffins ML, Collison D, Fivenson DP. Treatment of pemphigus and linear IgA dermatosis with nicotinamide and tetracycline: a review of 13 cases. J Am Acad Dermatol 1993; 28:998.
  68. Alpsoy E, Yilmaz E, Basaran E, et al. Is the combination of tetracycline and nicotinamide therapy alone effective in pemphigus? Arch Dermatol 1995; 131:1339.
  69. von Köckritz A, Ständer S, Zeidler C, et al. Successful monotherapy of pemphigus vegetans with minocycline and nicotinamide. J Eur Acad Dermatol Venereol 2017; 31:85.
  70. Amagai M, Komai A, Hashimoto T, et al. Usefulness of enzyme-linked immunosorbent assay using recombinant desmogleins 1 and 3 for serodiagnosis of pemphigus. Br J Dermatol 1999; 140:351.
  71. Cheng SW, Kobayashi M, Kinoshita-Kuroda K, et al. Monitoring disease activity in pemphigus with enzyme-linked immunosorbent assay using recombinant desmogleins 1 and 3. Br J Dermatol 2002; 147:261.
  72. Nagel A, Lang A, Engel D, et al. Clinical activity of pemphigus vulgaris relates to IgE autoantibodies against desmoglein 3. Clin Immunol 2010; 134:320.
  73. Ishii K, Amagai M, Hall RP, et al. Characterization of autoantibodies in pemphigus using antigen-specific enzyme-linked immunosorbent assays with baculovirus-expressed recombinant desmogleins. J Immunol 1997; 159:2010.
  74. Abasq C, Mouquet H, Gilbert D, et al. ELISA testing of anti-desmoglein 1 and 3 antibodies in the management of pemphigus. Arch Dermatol 2009; 145:529.
  75. Hertl M. Pemphigus vulgaris. CME Dermatol 2009; 4:94.
  76. Caldarola G, Kneisel A, Hertl M, Feliciani C. Herpes simplex virus infection in pemphigus vulgaris: clinical and immunological considerations. Eur J Dermatol 2008; 18:440.