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Treatment of Pemphigus Vulgaris and Pemphigus Foliaceus: A Systematic Review and Meta-Analysis

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Abstract

Background

No optimal therapeutic approach has been established for pemphigus.

Objective

Our objective was to evaluate the efficacy, steroid-sparing effect, and safety of available treatment modalities.

Methods

PubMed, LILACS (up to July 2014), the Cochrane Central Register of Controlled Trials (CENTRAL, issue 5 of 12, May 2014), and the ClinicalTrials.gov registry and reference lists were searched for randomized controlled trials of any treatment modality for pemphigus vulgaris and pemphigus foliaceus. Data were extracted independently by two authors using predefined appraisal criteria and data fields.

Results

A total of 20 studies (826 participants) were included. Most were small and open-labeled; all but seven were not concealed for allocation. Owing to the variability in intervention arms, five meta-analyses were performed, each pooling the data of two to three trials. Studies excluded from the meta-analyses were described quantitatively. Azathioprine had a steroid-sparing effect but did not increase remission rate. Mycophenolate mofetil induced sustained remission more quickly than did placebo and delayed time to relapse but did not have a steroid-sparing effect or favorable remission rate. Cyclophosphamide had a steroid-sparing effect, though less than azathioprine, but did not affect the remission rate or time-to-disease control. Intravenous immunoglobulin had more favorable short-term efficacy than did placebo. Topical epidermal growth factor hastened lesion healing.

Conclusions

Although some of the available therapeutic modalities for pemphigus are beneficial in terms of steroid-sparing, hastening response, or delaying relapse, none were found to increase the complete response rate compared with glucocorticoids alone, currently the mainstay of treatment. Multicenter randomized controlled trials and case control studies with uniform outcome measures are warranted.

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References

  1. Pemphigus Amagai M. In: Bolognia JL, Jorizzo JL, Schaffer JV, editors. Dermatology. 3rd ed. London: Mosby Elsevier; 2012. p. 461–74.

    Google Scholar 

  2. Bystryn JC, Steinman NM. The adjuvant therapy of pemphigus. An update. Arch Dermatol. 1996;132:203–12 (Review).

    Article  CAS  PubMed  Google Scholar 

  3. Martin LK, Murrell DF. Treatment of pemphigus: the need for more evidence. Arch Dermatol. 2008;144:100–1.

    CAS  PubMed  Google Scholar 

  4. Martin LK, Agero AL, Werth V, Villanueva E, Segall J, et al. Interventions for pemphigus vulgaris and pemphigus foliaceus. Cochrane Database Syst Rev. 2009;1:CD006263.

    PubMed  Google Scholar 

  5. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6:e1000097.

    Article  PubMed Central  PubMed  Google Scholar 

  6. Higgins JPT, Green S. Cochrane handbook for systematic reviews of interventions, Version 5.1.0 [updated March 2011]. The Cochrane Collaboration. 2011. http://www.cochrane-handbook.org. Accessed 20 Aug 2014.

  7. Murrell DF, Dick S, Ahmed AR, Amagai M, Barnadas MA, et al. Consensus statement on definitions of disease, end points, and therapeutic response for pemphigus. J Am Acad Dermatol. 2008;58:1043–6.

    Article  PubMed Central  PubMed  Google Scholar 

  8. Ratnam KV, Phay KL, Tan CK. Pemphigus therapy with oral prednisolone regimens. A 5-year study. Int J Dermatol. 1990;29:363–7.

    Article  CAS  PubMed  Google Scholar 

  9. Mentink LF, Mackenzie MW, Tóth GG, Laseur M, Lambert FP, et al. Randomized controlled trial of adjuvant oral dexamethasone pulse therapy in pemphigus vulgaris: PEMPULS trial. Arch Dermatol. 2006;142:570–6.

    Article  CAS  PubMed  Google Scholar 

  10. Chams-Davatchi C, Esmaili N, Daneshpazhooh M, Valikhani M, Balighi K, et al. Randomized controlled open-label trial of four treatment regimens for pemphigus vulgaris. J Am Acad Dermatol. 2007;57:622–8.

    Article  PubMed  Google Scholar 

  11. Chams-Davatchi C, Mortazavizadeh A, Daneshpazhooh M, Davatchi F, Balighi K, 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;27:1285–92.

    CAS  PubMed  Google Scholar 

  12. 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;26:855–60.

    Article  CAS  PubMed  Google Scholar 

  13. Beissert S, Mimouni D, Kanwar AJ, Solomons N, Kalia V, et al. Treating pemphigus vulgaris with prednisone and mycophenolatemofetil: a multicenter, randomized, placebo-controlled trial. J Invest Dermatol. 2010;130:2041–8.

    Article  CAS  PubMed  Google Scholar 

  14. Chrysomallis F, Ioannides D, Teknetzis A, Panagiotidou D, Minas A. Treatment of oral pemphigus vulgaris. Int J Dermatol. 1994;33:803–7.

    Article  CAS  PubMed  Google Scholar 

  15. Sharma VK, Khandpur S. Evaluation of cyclophosphamide pulse therapy as an adjuvant to oral corticosteroid in the management of pemphigus vulgaris. Clin Exp Dermatol. 2013;38:659–64.

    Article  CAS  PubMed  Google Scholar 

  16. Ioannides D, Chrysomallis F, Bystryn JC. Ineffectiveness of cyclosporine as an adjuvant to corticosteroids in the treatment of pemphigus. Arch Dermatol. 2000;136:868–72.

    CAS  PubMed  Google Scholar 

  17. Amagai M, Ikeda S, Shimizu H, Iizuka H, Hanada K, Pemphigus Study Group, et al. A randomized double-blind trial of intravenous immunoglobulin for pemphigus. J Am Acad Dermatol. 2009;60:595–603.

    Article  PubMed  Google Scholar 

  18. Guillaume JC, Roujeau JC, Morel P, Doutre MS, Guillot B, et al. Controlled study of plasma exchange in pemphigus. Arch Dermatol. 1988;124:1659–63.

    Article  CAS  PubMed  Google Scholar 

  19. Beissert S, Werfel T, Frieling U, Böhm M, Sticherling M, et al. A comparison of oral methylprednisolone plus azathioprine or mycophenolate mofetil for the treatment of pemphigus. Arch Dermatol. 2006;142:1447–54.

    Article  CAS  PubMed  Google Scholar 

  20. Dastgheib L, Sadati MS, Baghernejhad M. Assessment of the adjuvant effect of tacrolimus in the management of pemphigus vulgaris: a randomized controlled trial. J Dermatolog Treat. 2014 Feb 20. [Epub ahead of print].

  21. Rose E, Wever S, Zilliken D, Linse R, Haustein UF, et al. Intravenous dexamethasone-cyclophosphamide pulse therapy in comparison with oral methylprednisolone-azathioprine therapy in patients with pemphigus: results of a multicenter prospectively randomized study. J Dtsch Dermatol Ges. 2005;3:200–6.

    Article  PubMed  Google Scholar 

  22. Sethy PK, Khandpur S, Sharma VK. Randomized open comparative trial of dexamethasone-cyclophosphamide pulse and daily oral cyclophosphamide versus cyclophosphamide pulse and daily oral prednisolone in pemphigus vulgaris. Indian J Dermatol Venereol Leprol. 2009;75:476–82.

    Article  PubMed  Google Scholar 

  23. Parmar NV, Kanwar AJ, Minz RW, Parsad D, Vinay K, et al. Assessment of the therapeutic benefit of dexamethasone cyclophosphamide pulse versus only oral cyclophosphamide in phase II of the dexamethasone cyclophosphamide pulse therapy: a preliminary prospective randomized controlled study. Indian J Dermatol Venereol Leprol. 2013;79:70–6.

    Article  PubMed  Google Scholar 

  24. Werth VP, Fivenson D, Pandya AG, Chen D, Rico MJ, 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;144:25–32.

    Article  CAS  PubMed  Google Scholar 

  25. Kanwar AJ, Vinay K, Sawatkar GU, Dogra S, Minz RW, et al. Clinical and immunological outcomes of high and low dose rituximab treatments in pemphigus patients: a randomized comparative observer blinded study. Br J Dermatol. 2014;170:1341–9.

    Article  CAS  PubMed  Google Scholar 

  26. Iraji F, Faghihi G, Siadat AH. The efficacy of acyclovir in treatment of the pemphigus vulgaris. J Res Med Sci. 2013;18:976–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  27. Tabrizi MN, Chams-Davatchi C, Esmaeeli N, Noormohammadpoor P, Safar F, et al. Accelerating effects of epidermal growth factor on skin lesions of pemphigus vulgaris: a double-blind, randomized, controlled trial. J Eur Acad Dermatol Venereol. 2007;21:79–84.

    Article  CAS  PubMed  Google Scholar 

  28. Ahmed AR, Dahl MV. Consensus statement on the use of intravenous immunoglobulin therapy in the treatment of autoimmune mucocutaneous blistering diseases. Arch Dermatol. 2003;139:1051–9.

    Article  CAS  PubMed  Google Scholar 

  29. Salopek TG, Logsetty S, Tredget EE. Anti-CD20 chimeric monoclonal antibody (rituximab) for the treatment of recalcitrant, life-threatening pemphigus vulgaris with implications in the pathogenesis of the disorder. J Am Acad Dermatol. 2002;47:785–8.

    Article  PubMed  Google Scholar 

  30. Heelan K, Al-Mohammedi F, Smith MJ, Knowles S, Lansang P, et al. Durable remission of pemphigus with a fixed-dose rituximab protocol. JAMA Dermatol. 2014 Feb 5. doi:10.1001/jamadermatol.2013.6739. [Epub ahead of print].

  31. Leshem YA, Hodak E, David M, Anhalt GJ, Mimouni D. Successful treatment of pemphigus with biweekly 1-g infusions of rituximab: a retrospective study of 47 patients. J Am Acad Dermatol. 2013;68:404–11.

    Article  CAS  PubMed  Google Scholar 

  32. University Hospital, Rouen; Comparison between monoclonal antibody CD20 treatment (Rituximab (mabthéra))and general corticotherapy treatment in patients with pemphigus. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000. https://clinicaltrials.gov/show/NCT00784589. NLM Identifier: NCT00784589. Accessed 3 Aug 2014.

  33. Fernandes NC, Perez M. Treatment of pemphigus vulgaris and pemphigus foliaceus: experience with 71 patients over a 20 year period. Rev Inst Med Trop Sao Paulo. 2001;43:33–6.

    Article  CAS  PubMed  Google Scholar 

  34. 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;16:353–6.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

No sources of funding were used to conduct this study or prepare this manuscript. Lihi Atzmony, Emmilia Hodak, Michael Gdalevich, Omer Rosenbaum, and Daniel Mimouni have no conflicts of interest that are directly relevant to the content of this study.

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Authors and Affiliations

  1. Department of Dermatology, Rabin Medical Center, Beilinson Hospital, 39 Jabotinski St., 49100, Petach Tikva, Israel

    Lihi Atzmony, Emmilia Hodak, Omer Rosenbaum & Daniel Mimouni

  2. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Emmilia Hodak & Daniel Mimouni

  3. Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel

    Michael Gdalevich

  4. South District Health Office, Ministry of Health, Beer Sheva, Israel

    Michael Gdalevich

Authors
  1. Lihi Atzmony
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  2. Emmilia Hodak
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  5. Daniel Mimouni
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Corresponding author

Correspondence to Daniel Mimouni.

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Atzmony, L., Hodak, E., Gdalevich, M. et al. Treatment of Pemphigus Vulgaris and Pemphigus Foliaceus: A Systematic Review and Meta-Analysis. Am J Clin Dermatol 15, 503–515 (2014). https://doi.org/10.1007/s40257-014-0101-9

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  • DOI: https://doi.org/10.1007/s40257-014-0101-9

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