American Journal of Clinical Dermatology

, Volume 20, Issue 2, pp 209–216 | Cite as

Rituximab and Omalizumab for the Treatment of Bullous Pemphigoid: A Systematic Review of the Literature

  • Noa KremerEmail author
  • Igor Snast
  • Efrat Solomon Cohen
  • Emmilia Hodak
  • Daniel Mimouni
  • Moshe Lapidoth
  • Sigal Mazor
  • Assi Levi
Systematic Review



Bullous pemphigoid (BP) is the most common autoimmune blistering skin disease worldwide. Systemic corticosteroids are considered the mainstay of therapy; however, they may cause significant adverse effects and treatment failures, so additional therapeutic modalities with better safety profiles are required. Rituximab and omalizumab are novel biologic agents administered in recent years for the treatment of BP, yet data regarding their use in the disease are limited.


Our objective was to systematically review the current literature regarding the use of rituximab and omalizumab for the treatment of BP to evaluate their safety and efficacy.


A systematic review of all publications evaluating patients with BP treated with rituximab or omalizumab was performed. The primary outcome was clinical response; secondary outcomes were adverse events and recurrence rate.


The systematic review included 35 publications (84 patients: 62 receiving rituximab and 22 receiving omalizumab). In total, 61 of 63 patients had not experienced disease control with systemic corticosteroids before receiving the biologic treatment. Complete response rates were 85% and 84% for rituximab and omalizumab, respectively. The recurrence rate was considerably lower with rituximab (29%) than with omalizumab (80%). Mean time to recurrence was 10.2 and 3.4 months, and adverse effects occurred in 24% and 20% of the patients, respectively.


Available data, although potentially limited because of publication bias, suggest that rituximab and omalizumab have similar safety profiles and provide clinical benefit for patients with BP. The reviewed data indicated that rituximab resulted in lower recurrence rates and a longer time until recurrence than omalizumab.



The authors acknowledge the help of Dr. Debby Mir in writing the manuscript.

Compliance with Ethical Standards


No sources of funding were used to conduct this study or prepare this manuscript.

Conflicts of interest

Noa Kremer, Igor Snast, Efrat Solomon Cohen, Emmilia Hodak, Daniel Mimouni, Moshe Lapidoth, Sigal Mazor and Assi Levi have no conflicts of interest that are directly relevant to the content of this article.

Supplementary material

40257_2018_401_MOESM1_ESM.pdf (460 kb)
Supplementary material 1 (PDF 460 kb)


  1. 1.
    Bilgiç Temel A, Bassorgun CI, Akman-Karakaş A, Alpsoy E, Uzun S. Successful treatment of a bullous pemphigoid patient with rituximab who was refractory to corticosteroid and omalizumab treatments. Case Rep Dermatol. 2017;9(1):38–44.CrossRefGoogle Scholar
  2. 2.
    Bolognia JL, Jorizzo JL, Rapini RP. Chapter 30 – Pemphigoid Group. In: Bolognia JL, Jorizzo JL, Rapini RP, editors. Dermatology. 3rd ed. Spain: Mosby Elsevier; 2012. p. 475–82.Google Scholar
  3. 3.
    Yu KK, Crew AB, Messingham KAN, Fairley JA, Woodley DT. Omalizumab therapy for bullous pemphigoid. J Am Acad Dermatol. 2014;71:468–74. Scholar
  4. 4.
    Schmidt E, Seitz CS, Benoit S, Bröcker EB, Goebeler M. Rituximab in autoimmune bullous diseases: mixed responses and adverse effects. Br J Dermatol. 2007;156:352–6. Scholar
  5. 5.
    Feliciani C, Joly P, Jonkman MF, Zambruno G, Zillikens D, Ioannides D, et al. Management of bullous pemphigoid: the European dermatology forum consensus in collaboration with the European academy of dermatology and venereology. Br J Dermatol. 2015;172:867–77. Scholar
  6. 6.
    Kirtschig G, Middleton P, Bennett C, Murrell DF, Wojnarowska F, Khumalo NP. Interventions for bullous pemphigoid. Cochrane Database Syst Rev. 2010. doi: 10.1002/14651858.CD002292.pub3Google Scholar
  7. 7.
    Venning VA, Taghipour K, Mohd Mustapa MF, Highet AS, Kirtschig G. British Association of Dermatologists’ guidelines for the management of bullous pemphigoid 2012. Br J Dermatol. 2012;167:1200–14. Scholar
  8. 8.
    Frew JW, Murrell DF. Corticosteroid use in autoimmune blistering diseases. Immunol Allergy Clin North Am. 2012;32:283–94.CrossRefGoogle Scholar
  9. 9.
    Iranzo P, Pigem R, Giavedoni P, Alsina-Gibert M. Remission time after rituximab treatment for autoimmune bullous disease: a proposed update definition. Skin Pharmacol Physiol. 2015;28:255–6.CrossRefGoogle Scholar
  10. 10.
    Cho YT, Chu CY, Wang LF. First-line combination therapy with rituximab and corticosteroids provides a high complete remission rate in moderate-to-severe bullous pemphigoid. Br J Dermatol. 2015;173:302–4. Scholar
  11. 11.
    Schmidt E, Hunzelmann N, Zillikens D, Brocker E-B, Goebeler M. Rituximab in refractory autoimmune bullous diseases. Clin Exp Dermatol. 2006;31:503–8. Scholar
  12. 12.
    Rituxmab FDA approval for pemphigus vulgaris. 2018. Accessed 15 May 2018
  13. 13.
    Metz M, Staubach P, Bauer A, Brehler R, Gericke J, Kangas M, et al. Clinical efficacy of omalizumab in chronic spontaneous urticaria is associated with a reduction of FcεRI-positive cells in the skin. Theranostics. 2017;7:1266–76.CrossRefGoogle Scholar
  14. 14.
    Saini SS, Bindslev-Jensen C, Maurer M, Grob J-J, Bülbül Baskan E, Bradley MS, et al. Efficacy and safety of omalizumab in patients with chronic idiopathic/spontaneous urticaria who remain symptomatic on H 1 antihistamines: a randomized placebo-controlled study. J Invest Dermatol. 2015;135:67–75.CrossRefGoogle Scholar
  15. 15.
    Van Beek N, Lüttmann N, Huebner F, Recke A, Karl I, Schulze FS, et al. Correlation of serum levels of ige autoantibodies against BP180 with bullous pemphigoid disease activity. JAMA Dermatol. 2017;153:30–8.CrossRefGoogle Scholar
  16. 16.
    Hashimoto T, Ohzono A, Teye K, Numata S, Hiroyasu S, Tsuruta D, et al. Detection of IgE autoantibodies to BP180 and BP230 and their relationship to clinical features in bullous pemphigoid. Br J Dermatol. 2017;177:141–51. Scholar
  17. 17.
    Moher D, Liberati A, Tetzlaff J, Altman DG, Group TP. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Phys Ther. 2009;6:873–80. Scholar
  18. 18.
    Shetty S, Ahmed AR. Treatment of bullous pemphigoid with rituximab: critical analysis of the current literature. J Drugs Dermatol. 2013;12:672–7. Accessed 15 May 2018
  19. 19.
    Murrell DF, Daniel BS, Joly P, Borradori L, Amagai M, Hashimoto T, et al. Definitions and outcome measures for bullous pemphigoid: recommendations by an international panel of experts. J Am Acad Dermatol. 2012;66:479–85.CrossRefGoogle Scholar
  20. 20.
    Kasperkiewicz M, Shimanovich I, Ludwig RJ, Rose C, Zillikens D, Schmidt E. Rituximab for treatment-refractory pemphigus and pemphigoid: a case series of 17 patients. J Am Acad Dermatol. 2011;65:552–8. Scholar
  21. 21.
    Maki N, Demitsu T, Umemoto N, Nagashima K, Nakamura T, Kakurai M, et al. Possible paraneoplastic syndrome case of bullous pemphigoid with immunoglobulin G anti-BP180 C-terminal domain antibodies associated with psoriasis and primary macroglobulinemia. J Dermatol. 2016;43:571–4. Scholar
  22. 22.
    Lourari S, Herve C, Doffoel-Hantz V, Meyer N, Bulai-Livideanu C, Viraben R, et al. Bullous and mucous membrane pemphigoid show a mixed response to rituximab: experience in seven patients. J Eur Acad Dermatol Venereol. 2011;25:1238–40. Scholar
  23. 23.
    Bernard P, Reguiai Z, Tancrède-Bohin E, Cordel N, Plantin P, Pauwels C, et al. Risk factors for relapse in patients with bullous pemphigoid in clinical remission: a multicenter, prospective, cohort study. Arch Dermatol. 2009;145:537–42.CrossRefGoogle Scholar
  24. 24.
    Chee R, Nagendran V, Bansal A, Casie Chetty SN, Harland C. B-cell targeted therapy alone may not be effective in bullous pemphigoid. Clin Exp Dermatol. 2007;32:111–2.Google Scholar
  25. 25.
    Kolesnik M, Becker E, Reinhold D, Ambach A, Heim MU, Gollnick H, et al. Treatment of severe autoimmune blistering skin diseases with combination of protein A immunoadsorption and rituximab: a protocol without initial high dose or pulse steroid medication. J Eur Acad Dermatology Venereol. 2014;28:771–80. Scholar
  26. 26.
    Hall RP, Streilein RD, Hannah DL, McNair PD, Fairley JA, Ronaghy A, et al. Association of serum B-cell activating factor level and proportion of memory and transitional b cells with clinical response after rituximab treatment of bullous pemphigoid patients. J Invest Dermatol. 2013;133:2786–8. Scholar
  27. 27.
    McGinness JL, Bivens M-MC, Greer KE, Patterson JW, Saulsbury FT. Immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) associated with pemphigoid nodularis: a case report and review of the literature. J Am Acad Dermatol. 2006;55:143–8.Google Scholar
  28. 28.
    Wang T, Tsai T. Remission of bullous pemphigoid after rituximab treatment in a psoriasis patient on regular low-dose methotrexate. Acta Dermatol Venereol. 2014;94:108–9.CrossRefGoogle Scholar
  29. 29.
    Khosravi H, Abdollahi M, Badakhsh M, Soori T, Jafari M, Bae G, et al. Rituximab induced neutropenia in a patient with bullous pemphigoid. Arch Med. 2017;09:8–9.CrossRefGoogle Scholar
  30. 30.
    Nguyen T, Ahmed AR. Positive clinical outcome in a patient with recalcitrant bullous pemphigoid treated with rituximab and intravenous immunoglobulin. Clin Exp Dermatol. 2017;42:516–9. Scholar
  31. 31.
    Cruz MJ, Santos P, Morais P, Barreto F, Azevedo F. Refractory bullous pemphigoid with fatal outcome in a young patient. Int J Dermatol. 2013;52:601–2. Scholar
  32. 32.
    Binet Q, Lambert C, Sacré L, Eeckhoudt S, Hermans C. Successful management of acquired hemophilia A associated with bullous pemphigoid: a case report and review of the literature. Case Rep Hematol. 2017;2017:1–7.CrossRefGoogle Scholar
  33. 33.
    Cianchini G, Masini C, Lupi F, Corona R, De Pità O, Puddu P. Severe persistent pemphigoid gestationis: long-term remission with rituximab. Br J Dermatol. 2007;157:388–9.CrossRefGoogle Scholar
  34. 34.
    Saouli Z, Papadopoulos A, Kaiafa G, Girtovitis F, Kontoninas Z. A new approach on bullous pemphigoid therapy. Ann Oncol. 2007;19:825–6.CrossRefGoogle Scholar
  35. 35.
    Sowerby L, Dewan AK, Granter S, Gandhi L, LeBoeuf NR. Rituximab treatment of nivolumab-induced bullous pemphigoid. JAMA Dermatol. 2017;153:603. Scholar
  36. 36.
    Tomsitz D, Stefaniak R, Worm M. Rituximab in patients with recalcitrant autoimmune blistering diseases: experience in a cohort of 22 patients. Br J Dermatol. 2015;172:829–31. Scholar
  37. 37.
    Schulze J, Bader P, Henke U, Rose MA, Zielen S. Severe bullous pemphigoid in an infant- successful treatment with rituximab. Pediatr Dermatol. 2008;25:462–5. Scholar
  38. 38.
    Saraceno R, Citarella L, Spallone G, Chimenti S. A biological approach in a patient with psoriasis and bullous pemphigoid associated with losartan therapy. Clin Exp Dermatol. 2008;33:154–5. Scholar
  39. 39.
    Fuertes I, Luelmo J, Leal L, Romaní J, Sánchez S, Mascaró JM. Refractory childhood pemphigoid successfully treated with rituximab. Pediatr Dermatol. 2013;30:e96–7. Scholar
  40. 40.
    Ahmed AR, Shetty S, Kaveri S, Spigelman ZS. Treatment of recalcitrant bullous pemphigoid (BP) with a novel protocol: a retrospective study with a 6-year follow-up. J Am Acad Dermatol. 2016;74(700–708):e3. Scholar
  41. 41.
    Batts AF, Jalalat SZ, Hunter-Ellul L, Wilkerson MG. Exacerbation of bullous pemphigoid after hand, foot, and mouth disease treated with rituximab. JAAD Case Rep. 2016;2:7–9. Scholar
  42. 42.
    AlJasser MI, Sladden C, Crawford RI, Au S. Bullous pemphigoid associated with acquired hemophilia A: a rare association of autoimmune disease. J Cutan Med Surg. 2014;18:123–6. Scholar
  43. 43.
    London VA, Kim GH, Fairley JA, Woodley DT. Successful treatment of bullous pemphigoid with omalizumab. Arch Dermatol. 2012;148:1241. Scholar
  44. 44.
    Menzinger S, Kaya G, Schmidt E, Fontao L, Laffitte E. Biological and clinical response to omalizumab in a patient with bullous pemphigoid. Acta Derm Venereol. 2018;98:284–6.CrossRefGoogle Scholar
  45. 45.
    Balakirski G, Alkhateeb A, Merk HF, Leverkus M, Megahed M. Successful treatment of bullous pemphigoid with omalizumab as corticosteroid-sparing agent: report of two cases and review of literature. J Eur Acad Dermatol Venereol. 2016;30:1778–82.CrossRefGoogle Scholar
  46. 46.
    Fairley JA, Baum CL, Brandt DS, Messingham KAN. Pathogenicity of IgE in autoimmunity: successful treatment of bullous pemphigoid with omalizumab. J Allergy Clin Immunol. 2009;123:704–5.CrossRefGoogle Scholar
  47. 47.
    Dufour C, Souillet AL, Chaneliere C, Jouen F, Bodemer C, Jullien D, et al. Successful management of severe infant bullous pemphigoid with omalizumab. Br J Dermatol. 2012;166:1140–2. Scholar
  48. 48.
    Yalcin A, Genc G, Celik B, Gumuslu S. Anti-IgE monoclonal antibody (omalizumab) is effective in treating bullous pemphigoid and its effects on soluble CD200. Clin Lab. 2014;60:523–4.Google Scholar
  49. 49.
    Gönül M, Keseroglu H, Ergin C, Özcan I, Erdem Ö. Bullous pemphigoid successfully treated with omalizumab. Indian J Dermatol Venereol Leprol. 2016;82:577.CrossRefGoogle Scholar
  50. 50.
    İncel Uysal P, Yalçın B, Öktem A. Our clinical experience with the use of omalizumab in the treatment of bullous pemphigoid. Turkderm. 2017;51:124–8.CrossRefGoogle Scholar
  51. 51.
    Snast I, Kremer N, Lapidoth M, Enk CD, Tal Y, Rosman Y, et al. Omalizumab for the treatment of solar urticaria: case series and systematic review of the literature. J Allergy Clin Immunol Pract. 2018;6(1198–1204):e3. Scholar
  52. 52.
    Türk M, Yılmaz İ, Bahçecioğlu SN. Treatment and retreatment with omalizumab in chronic spontaneous urticaria: real life experience with twenty-five patients. Allergol Int. 2018;67:85–9.CrossRefGoogle Scholar
  53. 53.
    Zhao Z-T, Ji C-M, Yu W-J, Meng L, Hawro T, Wei J-F, et al. Omalizumab for the treatment of chronic spontaneous urticaria: a meta-analysis of randomized clinical trials. J Allergy Clin Immunol. 2016;137(1742–1750):e4.Google Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Department of Dermatology, Beilinson HospitalRabin Medical CenterPetah-TikvaIsrael
  2. 2.Sackler School of MedicineTel Aviv UniversityTel AvivIsrael
  3. 3.Department of Community Dentistry, School of Dental MedicineHebrew University-Hadassah Medical CenterJerusalemIsrael

Personalised recommendations