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Therapy of Immunobullous Disorders

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Clinical and Basic Immunodermatology

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Abstract

Immunobullous disorders are chronic-relapsing diseases of the skin and mucous membranes with high morbidity and mortality which are linked to IgG autoantibodies that target adhesion molecules of the skin. In most instances, therapeutic approaches comprise the application of general immunosuppressive drugs. Treatment with high-dose systemic glucocorticoids and adjuvant immunosuppressive drugs is effective, but also bears the risk of considerable side-effects. In light of recent advances in the pathogenic understanding of immunobullous disorders, additional therapeutic targets including pro-inflammatory cytokines (TNF- α) and peripheral B cells have been identified. Herein we review the role of biologic inhibitors of these two processes.

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References

  1. Kneisel A, Hertl M. Autoimmune bullous skin diseases. Part 1: clinical manifestations. J Dtsch Dermatol Ges. 2011;9:844–56; quiz 857.

    PubMed  Google Scholar 

  2. Kneisel A, Hertl M. Autoimmune bullous skin diseases. Part 2: diagnosis and therapy. J Dtsch Dermatol Ges. 2011;9:927–47.

    PubMed  Google Scholar 

  3. Hertl MJH, Karpati S, Marinovic B, Uzun S, Yayli S, Mimouni D, Borradori L, Feliciani C, Ioannides D, Joly P, Kowalewski C, Zambruno G, Zillikens D, Jonkman MF. Pemphigus – S2 guidelines – 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(3):405–14.

    Article  CAS  PubMed  Google Scholar 

  4. Feliciani CJP, Jonkman MF, Zambruno G, Zillikens D, Ioannides D, Kowalewski C, Jedlickova H, Karpati S, Marinovic B, Mimouni D, Uzun S, Yayli S, Hertl M, Borradori L. Management of bullous pemphigoid – European S2 guideline on behalf of the European Dermatology Forum in collaboration with the European Academy of Dermatology and Venereology. Br J Dermatol. 2015;172(4):867–77.

    Article  CAS  PubMed  Google Scholar 

  5. 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;64:903–8.

    Article  PubMed  Google Scholar 

  6. Kirtschig G, Middleton P, Bennett C, Murrell DF, Wojnarowska F, Khumalo NP. Interventions for bullous pemphigoid. Cochrane Database Syst Rev. 2010;(10):CD002292.

    Google Scholar 

  7. 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;57:622–8.

    Article  PubMed  Google Scholar 

  8. Pasricha JS, Khaitan BK, Raman RS, Chandra M. Dexamethasone-cyclophosphamide pulse therapy for pemphigus. Int J Dermatol. 1995;34:875–82.

    Article  CAS  PubMed  Google Scholar 

  9. Nousari CH, Brodsky R, Anhalt GJ. Evaluating the role of immunoablative high-dose cyclophosphamide therapy in pemphigus vulgaris. J Am Acad Dermatol. 2003;49:148–50.

    Article  PubMed  Google Scholar 

  10. Zillikens D, Derfler K, Eming R, et al. Recommendations for the use of immunoapheresis in the treatment of autoimmune bullous diseases. J Dtsch Dermatol Ges. 2007;5:881–7.

    Article  PubMed  Google Scholar 

  11. Eming R, Hertl M. Immunoadsorption in pemphigus. Autoimmunity. 2006;39:609–16.

    Article  CAS  PubMed  Google Scholar 

  12. Pfutze M, Eming R, Kneisel A, Kuhlmann U, Hoyer J, Hertl M. Clinical and immunological follow-up of pemphigus patients on adjuvant treatment with immunoadsorption or rituximab. Dermatology. 2009;218:237–45.

    Article  PubMed  Google Scholar 

  13. Ahmed AR, Spigelman Z, Cavacini LA, Posner MR. Treatment of pemphigus vulgaris with rituximab and intravenous immune globulin. N Engl J Med. 2006;355:1772–9.

    Article  CAS  PubMed  Google Scholar 

  14. Joly P, Mouquet H, Roujeau JC, et al. A single cycle of rituximab for the treatment of severe pemphigus. N Engl J Med. 2007;357:545–52.

    Article  CAS  PubMed  Google Scholar 

  15. Behzad M, Mobs C, Kneisel A, et al. Combined treatment with immunoadsorption and rituximab leads to fast and prolonged clinical remission in difficult-to-treat pemphigus vulgaris. Br J Dermatol. 2012;166:844–52.

    Article  CAS  PubMed  Google Scholar 

  16. Kodama S, Davis M, Faustman DL. The therapeutic potential of tumor necrosis factor for autoimmune disease: a mechanistically based hypothesis. Cell Mol Life Sci. 2005;62:1850–62.

    Article  CAS  PubMed  Google Scholar 

  17. D'Auria L, Mussi A, Bonifati C, Mastroianni A, Giacalone B, Ameglio F. Increased serum IL-6, TNF-alpha and IL-10 levels in patients with bullous pemphigoid: relationships with disease activity. J Eur Acad Dermatol Venereol. 1999;12:11–5.

    Article  PubMed  Google Scholar 

  18. Saw VP, Dart RJ, Galatowicz G, Daniels JT, Dart JK, Calder VL. Tumor necrosis factor-alpha in ocular mucous membrane pemphigoid and its effect on conjunctival fibroblasts. Invest Ophthalmol Vis Sci. 2009;50:5310–7.

    Article  PubMed  Google Scholar 

  19. D'Auria L, Bonifati C, Mussi A, et al. Cytokines in the sera of patients with pemphigus vulgaris: interleukin-6 and tumour necrosis factor-alpha levels are significantly increased as compared to healthy subjects and correlate with disease activity. Eur Cytokine Netw. 1997;8:383–7.

    PubMed  Google Scholar 

  20. Ameglio F, D'Auria L, Cordiali-Fei P, et al. Anti-intercellular substance antibody log titres are correlated with serum concentrations of interleukin-6, interleukin-15 and tumor necrosis factor-alpha in patients with Pemphigus vulgaris relationships with peripheral blood neutrophil counts, disease severity and duration and patients’ age. J Biol Regul Homeost Agents. 1999;13:220–4.

    CAS  PubMed  Google Scholar 

  21. Ameglio F, D'Auria L, Cordiali-Fei P, et al. Bullous pemphigoid and pemphigus vulgaris: correlated behaviour of serum VEGF, sE-selectin and TNF-alpha levels. J Biol Regul Homeost Agents. 1997;11:148–53.

    CAS  PubMed  Google Scholar 

  22. Ameglio F, D'Auria L, Bonifati C, Ferraro C, Mastroianni A, Giacalone B. Cytokine pattern in blister fluid and serum of patients with bullous pemphigoid: relationships with disease intensity. Br J Dermatol. 1998;138:611–4.

    Article  CAS  PubMed  Google Scholar 

  23. Giacalone B, D'Auria L, Bonifati C, et al. Decreased interleukin-7 and transforming growth factor-beta1 levels in blister fluids as compared to the respective serum levels in patients with bullous pemphigoid. Opposite behavior of TNF-alpha, interleukin-4 and interleukin-10. Exp Dermatol. 1998;7:157–61.

    Article  CAS  PubMed  Google Scholar 

  24. Alecu M, Alecu S, Coman G, Galatescu E, Ursaciuc C. ICAM-1, ELAM-1, TNF-alpha and IL-6 in serum and blister liquid of pemphigus vulgaris patients. Roum Arch Microbiol Immunol. 1999;58:121–30.

    CAS  PubMed  Google Scholar 

  25. Feliciani C, Toto P, Amerio P. In vitro C3 mRNA expression in Pemphigus vulgaris: complement activation is increased by IL-1alpha and TNF-alpha. J Cutan Med Surg. 1999;3:140–4.

    CAS  PubMed  Google Scholar 

  26. Feliciani C, Toto P, Amerio P, et al. In vitro and in vivo expression of interleukin-1alpha and tumor necrosis factor-alpha mRNA in pemphigus vulgaris: interleukin-1alpha and tumor necrosis factor-alpha are involved in acantholysis. J Invest Dermatol. 2000;114:71–7.

    Article  CAS  PubMed  Google Scholar 

  27. Pardo J, Mercader P, Mahiques L, Sanchez-Carazo JL, Oliver V, Fortea JM. Infliximab in the management of severe pemphigus vulgaris. Br J Dermatol. 2005;153:222–3.

    Article  CAS  PubMed  Google Scholar 

  28. Jacobi A, Shuler G, Hertl M. Rapid control of therapy-refractory pemphigus vulgaris by treatment with the tumour necrosis factor-alpha inhibitor infliximab. Br J Dermatol. 2005;153:448–9.

    Article  CAS  PubMed  Google Scholar 

  29. Heffernan MP, Bentley DD. Successful treatment of mucous membrane pemphigoid with infliximab. Arch Dermatol. 2006;142:1268–70.

    Article  PubMed  Google Scholar 

  30. Vojackova N, Fialova J, Vanousova D, Hercogova J. Pemphigus vulgaris treated with adalimumab: case study. Dermatol Ther. 2012;25:95–7.

    Article  PubMed  Google Scholar 

  31. Berookhim B, Fischer HD, Weinberg JM. Treatment of recalcitrant pemphigus vulgaris with the tumor necrosis factor alpha antagonist etanercept. Cutis. 2004;74:245–7.

    PubMed  Google Scholar 

  32. Canizares MJ, Smith DI, Conners MS, Maverick KJ, Heffernan MP. Successful treatment of mucous membrane pemphigoid with etanercept in 3 patients. Arch Dermatol. 2006;142:1457–61.

    Article  CAS  PubMed  Google Scholar 

  33. Sacher C, Rubbert A, Konig C, Scharffetter-Kochanek K, Krieg T, Hunzelmann N. Treatment of recalcitrant cicatricial pemphigoid with the tumor necrosis factor alpha antagonist etanercept. J Am Acad Dermatol. 2002;46:113–5.

    Article  PubMed  Google Scholar 

  34. Gubinelli E, Bergamo F, Didona B, Annessi G, Atzori F, Raskovic D. Pemphigus foliaceus treated with etanercept. J Am Acad Dermatol. 2006;55:1107–8.

    Article  PubMed  Google Scholar 

  35. Schulz S, Deuster D, Schmidt E, Bonsmann G, Beissert S. Therapeutic effect of etanercept in anti-laminin 5 (laminin 332) mucous membrane pemphigoid. Int J Dermatol. 2011;50:1129–31.

    Article  PubMed  Google Scholar 

  36. John H, Whallett A, Quinlan M. Successful biologic treatment of ocular mucous membrane pemphigoid with anti-TNF-alpha. Eye (Lond). 2007;21:1434–5.

    Article  CAS  Google Scholar 

  37. Fiorentino DF, Garcia MS, Rehmus W, Kimball AB. A pilot study of etanercept treatment for pemphigus vulgaris. Arch Dermatol. 2011;147:117–8.

    Article  PubMed  Google Scholar 

  38. Hall RP, Fairley J, Woodley D, et al. A multi-centered randomized trial of the treatment of pemphigus vulgaris patients with infliximab and prednisone compared to prednisone alone. Br J Dermatol. 2015;172(3):760–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. el-Darouti M, Marzouk S, Abdel Hay R, et al. The use of sulfasalazine and pentoxifylline (low-cost antitumour necrosis factor drugs) as adjuvant therapy for the treatment of pemphigus vulgaris: a comparative study. Br J Dermatol. 2009;161:313–9.

    Article  CAS  PubMed  Google Scholar 

  40. El Darouti MA, Fakhry Khattab MA, Hegazy RA, Hafez DA, Gawdat HI. Pentoxifylline (anti-tumor necrosis factor drug): effective adjuvant therapy in the control of ocular cicatricial pemphigoid. Eur J Ophthalmol. 2011;21:529–37.

    Article  PubMed  Google Scholar 

  41. Boussemart L, Jacobelli S, Batteux F, et al. Autoimmune bullous skin diseases occurring under anti-tumor necrosis factor therapy: two case reports. Dermatology. 2010;221:201–5.

    Article  CAS  PubMed  Google Scholar 

  42. Stausbol-Gron B, Deleuran M, Sommer Hansen E, Kragballe K. Development of bullous pemphigoid during treatment of psoriasis with adalimumab. Clin Exp Dermatol. 2009;34:e285–6.

    Article  CAS  PubMed  Google Scholar 

  43. Bordignon M, Belloni-Fortina A, Pigozzi B, Tarantello M, Alaibac M. Bullous pemphigoid during long-term TNF-alpha blocker therapy. Dermatology. 2009;219:357–8.

    Article  PubMed  Google Scholar 

  44. Daulat S, Detweiler JG, Pandya AG. Development of pemphigus vulgaris in a patient with psoriasis treated with etanercept. J Eur Acad Dermatol Venereol. 2009;23:483–4.

    Article  CAS  PubMed  Google Scholar 

  45. Wendling D, Prati C. Paradoxical effects of anti-TNF-alpha agents in inflammatory diseases. Expert Rev Clin Immunol. 2014;10:159–69.

    Article  CAS  PubMed  Google Scholar 

  46. Narbutt J, Lukamowicz J, Bogaczewicz J, Sysa-Jedrzejowska A, Torzecka JD, Lesiak A. Serum concentration of interleukin-6 is increased both in active and remission stages of pemphigus vulgaris. Mediators Inflamm. 2008;2008:875394.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Cambridge G, Leandro MJ, Edwards JC, et al. Serologic changes following B lymphocyte depletion therapy for rheumatoid arthritis. Arthritis Rheum. 2003;48:2146–54.

    Article  PubMed  Google Scholar 

  48. Cambridge G, Isenberg DA, Edwards JC, et al. B cell depletion therapy in systemic lupus erythematosus: relationships among serum B lymphocyte stimulator levels, autoantibody profile and clinical response. Ann Rheum Dis. 2008;67:1011–6.

    Article  CAS  PubMed  Google Scholar 

  49. Teng YK, Wheater G, Hogan VE, et al. Induction of long-term B-cell depletion in refractory rheumatoid arthritis patients preferentially affects autoreactive more than protective humoral immunity. Arthritis Res Ther. 2012;14:R57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Ferraro AJ, Drayson MT, Savage CO, MacLennan IC. Levels of autoantibodies, unlike antibodies to all extrinsic antigen groups, fall following B cell depletion with Rituximab. Eur J Immunol. 2008;38:292–8.

    Article  CAS  PubMed  Google Scholar 

  51. Amber KT, Staropoli P, Shiman MI, Elgart GW, Hertl M. Autoreactive T cells in the immune pathogenesis of pemphigus vulgaris. Exp Dermatol. 2013;22:699–704.

    Article  CAS  PubMed  Google Scholar 

  52. Eming R, Nagel A, Wolff-Franke S, Podstawa E, Debus D, Hertl M. Rituximab exerts a dual effect in pemphigus vulgaris. J Invest Dermatol. 2008;128:2850–8.

    Article  CAS  PubMed  Google Scholar 

  53. Rouziere AS, Kneitz C, Palanichamy A, Dorner T, Tony HP. Regeneration of the immunoglobulin heavy-chain repertoire after transient B-cell depletion with an anti-CD20 antibody. Arthritis Res Ther. 2005;7:R714–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Leandro MJ, Cambridge G, Ehrenstein MR, Edwards JC. Reconstitution of peripheral blood B cells after depletion with rituximab in patients with rheumatoid arthritis. Arthritis Rheum. 2006;54:613–20.

    Article  CAS  PubMed  Google Scholar 

  55. Reguiai Z, Tabary T, Maizieres M, Bernard P. Rituximab treatment of severe pemphigus: long-term results including immunologic follow-up. J Am Acad Dermatol. 2012;67:623–9.

    Article  CAS  PubMed  Google Scholar 

  56. 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 

  57. Balighi K, Daneshpazhooh M, Khezri S, Mahdavi-nia M, Hajiseyed-javadi M, Chams-Davatchi C. Adjuvant rituximab in the treatment of pemphigus vulgaris: a phase II clinical trial. Int J Dermatol. 2013;52:862–7.

    Article  PubMed  Google Scholar 

  58. Lunardon L, Tsai KJ, Propert KJ, et al. Adjuvant rituximab therapy of pemphigus: a single-center experience with 31 patients. Arch Dermatol. 2012;148:1031–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Cianchini G, Lupi F, Masini C, Corona R, Puddu P, De Pita O. Therapy with rituximab for autoimmune pemphigus: results from a single-center observational study on 42 cases with long-term follow-up. J Am Acad Dermatol. 2012;67:617–22.

    Article  CAS  PubMed  Google Scholar 

  60. Heelan K, Al-Mohammedi F, Smith MJ, et al. Durable remission of pemphigus with a fixed-dose rituximab protocol. JAMA Dermatol. 2014;150(7):703–8.

    Article  CAS  PubMed  Google Scholar 

  61. Feldman RJ, Ahmed AR. Relevance of rituximab therapy in pemphigus vulgaris: analysis of current data and the immunologic basis for its observed responses. Expert Rev Clin Immunol. 2011;7:529–41.

    Article  CAS  PubMed  Google Scholar 

  62. Zakka LR, Shetty SS, Ahmed AR. Rituximab in the treatment of pemphigus vulgaris. Dermatol Ther (Heidelb). 2012;2:17.

    Article  Google Scholar 

  63. Kasperkiewicz M, Eming R, Behzad M, et al. Efficacy and safety of rituximab in pemphigus: experience of the German registry of autoimmune diseases. J Dtsch Dermatol Ges. 2012;10:727–32.

    PubMed  Google Scholar 

  64. Le Roux-Villet C, Prost-Squarcioni C, Alexandre M, et al. Rituximab for patients with refractory mucous membrane pemphigoid. Arch Dermatol. 2011;147:843–9.

    Article  PubMed  Google Scholar 

  65. Heelan K, Walsh S, Shear NH. Treatment of mucous membrane pemphigoid with rituximab. J Am Acad Dermatol. 2013;69:310–1.

    Article  PubMed  Google Scholar 

  66. Shetty S, Ahmed AR. Treatment of bullous pemphigoid with rituximab: critical analysis of the current literature. J Drugs Dermatol. 2013;12:672–7.

    CAS  PubMed  Google Scholar 

  67. Niedermeier A, Eming R, Pfutze M, et al. Clinical response of severe mechanobullous epidermolysis bullosa acquisita to combined treatment with immunoadsorption and rituximab (anti-CD20 monoclonal antibodies). Arch Dermatol. 2007;143:192–8.

    Article  CAS  PubMed  Google Scholar 

  68. McKinley SK, Huang JT, Tan J, Kroshinsky D, Gellis S. A case of recalcitrant epidermolysis bullosa acquisita responsive to rituximab therapy. Pediatr Dermatol. 2014;31(2):241–4.

    Article  PubMed  Google Scholar 

  69. Cavailhes A, Balme B, Gilbert D, Skowron F. Successful use of combined corticosteroids and rituximab in the treatment of recalcitrant epidermolysis bullosa acquisita. Ann Dermatol Venereol. 2009;136:795–9.

    Article  CAS  PubMed  Google Scholar 

  70. Schmidt E, Benoit S, Brocker EB, Zillikens D, Goebeler M. Successful adjuvant treatment of recalcitrant epidermolysis bullosa acquisita with anti-CD20 antibody rituximab. Arch Dermatol. 2006;142:147–50.

    Article  PubMed  Google Scholar 

  71. Kim JH, Lee SE, Kim SC. Successful treatment of epidermolysis bullosa acquisita with rituximab therapy. J Dermatol. 2012;39:477–9.

    Article  CAS  PubMed  Google Scholar 

  72. Kubisch I, Diessenbacher P, Schmidt E, Gollnick H, Leverkus M. Premonitory epidermolysis bullosa acquisita mimicking eyelid dermatitis: successful treatment with rituximab and protein A immunoapheresis. Am J Clin Dermatol. 2010;11:289–93.

    PubMed  Google Scholar 

  73. Saha M, Cutler T, Bhogal B, Black MM, Groves RW. Refractory epidermolysis bullosa acquisita: successful treatment with rituximab. Clin Exp Dermatol. 2009;34:e979–80.

    Article  CAS  PubMed  Google Scholar 

  74. Sadler E, Schafleitner B, Lanschuetzer C, et al. Treatment-resistant classical epidermolysis bullosa acquisita responding to rituximab. Br J Dermatol. 2007;157:417–9.

    Article  CAS  PubMed  Google Scholar 

  75. Crichlow SM, Mortimer NJ, Harman KE. A successful therapeutic trial of rituximab in the treatment of a patient with recalcitrant, high-titre epidermolysis bullosa acquisita. Br J Dermatol. 2007;156:194–6.

    Article  CAS  PubMed  Google Scholar 

  76. Ludwig RJ. Clinical presentation, pathogenesis, diagnosis, and treatment of epidermolysis bullosa acquisita. ISRN Dermatol. 2013;2013:812029.

    PubMed  PubMed Central  Google Scholar 

  77. Vezzoli P, Berti E, Marzano AV. Rationale and efficacy for the use of rituximab in paraneoplastic pemphigus. Expert Rev Clin Immunol. 2008;4:351–63.

    Article  CAS  PubMed  Google Scholar 

  78. Schadlow MB, Anhalt GJ, Sinha AA. Using rituximab (anti-CD20 antibody) in a patient with paraneoplastic pemphigus. J Drugs Dermatol. 2003;2:564–7.

    PubMed  Google Scholar 

  79. Amber KT, Hertl M. An assessment of treatment history and its association with clinical outcomes and relapse in 155 pemphigus patients with response to a single cycle of rituximab. J Eur Acad Dermatol Venereol. 2015;29(4):777–82.

    Article  CAS  PubMed  Google Scholar 

  80. Kanwar AJ, Vinay K, Sawatkar GU, 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(6):1341–9.

    Article  CAS  PubMed  Google Scholar 

  81. Mimouni D, Nousari CH, Cummins DL, Kouba DJ, David M, Anhalt GJ. Differences and similarities among expert opinions on the diagnosis and treatment of pemphigus vulgaris. J Am Acad Dermatol. 2003;49:1059–62.

    Article  PubMed  Google Scholar 

  82. Hainsworth JD. Safety of rituximab in the treatment of B cell malignancies: implications for rheumatoid arthritis. Arthritis Res Ther. 2003:5 Suppl 4:S12–6.

    Google Scholar 

  83. Cobo-Ibanez T, Loza-Santamaria E, Pego-Reigosa JM, et al. Efficacy and safety of rituximab in the treatment of non-renal systemic lupus erythematosus: a systematic review. Semin Arthritis Rheum. 2014;44(2):175–85.

    Article  CAS  PubMed  Google Scholar 

  84. Shetty S, Ahmed AR. Preliminary analysis of mortality associated with rituximab use in autoimmune diseases. Autoimmunity. 2013;46:487–96.

    Article  CAS  PubMed  Google Scholar 

  85. Hadjinicolaou AV, Nisar MK, Parfrey H, Chilvers ER, Ostor AJ. Non-infectious pulmonary toxicity of rituximab: a systematic review. Rheumatology (Oxford). 2012;51:653–62.

    Article  CAS  Google Scholar 

  86. Merrill JT, Neuwelt CM, Wallace DJ, et al. Efficacy and safety of rituximab in moderately-to-severely active systemic lupus erythematosus: the randomized, double-blind, phase II/III systemic lupus erythematosus evaluation of rituximab trial. Arthritis Rheum. 2010;62:222–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Tony HP, Burmester G, Schulze-Koops H, et al. Safety and clinical outcomes of rituximab therapy in patients with different autoimmune diseases: experience from a national registry (GRAID). Arthritis Res Ther. 2011;13:R75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Beissert S, Mimouni D, Kanwar AJ, Solomons N, Kalia V, Anhalt GJ. Treating pemphigus vulgaris with prednisone and mycophenolate mofetil: a multicenter, randomized, placebo-controlled trial. J Invest Dermatol. 2010;130:2041–8.

    Article  CAS  PubMed  Google Scholar 

  89. Riedell P, Carson KR. A drug safety evaluation of rituximab and risk of hepatitis B. Expert Opin Drug Saf. 2014;13:977–87.

    Article  CAS  PubMed  Google Scholar 

  90. Kim TW, Kim MN, Kwon JW, et al. Risk of hepatitis B virus reactivation in patients with asthma or chronic obstructive pulmonary disease treated with corticosteroids. Respirology. 2010;15:1092–7.

    Article  PubMed  Google Scholar 

  91. Foster CS, Chang PY, Ahmed AR. Combination of rituximab and intravenous immunoglobulin for recalcitrant ocular cicatricial pemphigoid: a preliminary report. Ophthalmology. 2010;117:861–9.

    Article  PubMed  Google Scholar 

  92. Ventura F, Rocha J, Fernandes JC, Machado A, Brito C. Recalcitrant pemphigus vulgaris: aseptic meningitis associated with intravenous immunoglobulin therapy and successful treatment with rituximab. Int J Dermatol. 2013;52:501–2.

    Article  PubMed  Google Scholar 

  93. Lunardon L, Payne AS. Inhibitory human antichimeric antibodies to rituximab in a patient with pemphigus. J Allergy Clin Immunol. 2012;130:800–3.

    Article  PubMed  PubMed Central  Google Scholar 

  94. Schmidt E, Hennig K, Mengede C, Zillikens D, Kromminga A. Immunogenicity of rituximab in patients with severe pemphigus. Clin Immunol. 2009;132:334–41.

    Article  CAS  PubMed  Google Scholar 

  95. Weng WK, Levy R. Two immunoglobulin G fragment C receptor polymorphisms independently predict response to rituximab in patients with follicular lymphoma. J Clin Oncol. 2003;21:3940–7.

    Article  CAS  PubMed  Google Scholar 

  96. Gamonet C, Ferrand C, Colliou N, et al. Lack of expression of an alternative CD20 transcript variant in circulating B cells from patients with pemphigus. Exp Dermatol. 2014;23:66–7.

    Article  CAS  PubMed  Google Scholar 

  97. Rehnberg M, Amu S, Tarkowski A, Bokarewa MI, Brisslert M. Short- and long-term effects of anti-CD20 treatment on B cell ontogeny in bone marrow of patients with rheumatoid arthritis. Arthritis Res Ther. 2009;11:R123.

    Article  PubMed  PubMed Central  Google Scholar 

  98. Shetty S, Ahmed AR. Critical analysis of the use of rituximab in mucous membrane pemphigoid: a review of the literature. J Am Acad Dermatol. 2013;68:499–506.

    Article  CAS  PubMed  Google Scholar 

  99. Hammers CM, Chen J, Lin C, et al. Persistence of anti-desmoglein 3 IgG B-cell clones in pemphigus patients over years. J Invest Dermatol. 2015;135(3):742–9.

    Article  CAS  PubMed  Google Scholar 

  100. Cho MJ, Lo AS, Mao X, et al. Shared VH1-46 gene usage by pemphigus vulgaris autoantibodies indicates common humoral immune responses among patients. Nat Commun. 2014;5:4167.

    CAS  PubMed  PubMed Central  Google Scholar 

  101. Gregoriou S, Giatrakou S, Theodoropoulos K, et al. Pilot study of 19 patients with severe pemphigus: prophylactic treatment with rituximab does not appear to be beneficial. Dermatology. 2014;228:158–65.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Dermatology, UC Irvine Health, Irvine, CA, USA

    Kyle Amber MD

  2. Department of Dermatology, Philipps University Marburg, Marburg, D-35043, Germany

    Michael Hertl MD

Authors
  1. Kyle Amber MD
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  2. Michael Hertl MD
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Correspondence to Michael Hertl MD .

Editor information

Editors and Affiliations

  1. School of Medicine, University of Maryland Baltimore, Baltimore, Maryland, USA

    Anthony A. Gaspari

  2. Department of Dermatology, University of Texas Health Science Center, Houston, Texas, USA

    Stephen K. Tyring

  3. Department of Dermatology and Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

    Daniel H. Kaplan

Questions

Questions

  1. 1.

    What is the most common adverse reaction occurring with rituximab administration?

    1. A.

      Mild transfusion reactions

  2. 2.

    Does rituximab directly deplete plasma cells?

    1. A.

      No. It destroys pre-B-cells and mature B cells which eventually develop into plasma cells, but it has no direct effect on plasma cells or stem cells

  3. 3.

    What are the two most common dosing protocols for rituximab in the treatment of immunobullous disease?

    1. A.

      The lymphoma protocol (375 mg/m2 × 4 weeks) and the rheumatology protocol (1000 mg weekly × 2 weeks)

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Amber, K., Hertl, M. (2017). Therapy of Immunobullous Disorders. In: Gaspari, A., Tyring, S., Kaplan, D. (eds) Clinical and Basic Immunodermatology. Springer, Cham. https://doi.org/10.1007/978-3-319-29785-9_44

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  • DOI: https://doi.org/10.1007/978-3-319-29785-9_44

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  • Online ISBN: 978-3-319-29785-9

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