Rituximab and its Use in Autoimmune Bullous Disorders (original) (raw)

Abstract

Rituximab is a chimeric murine-human monoclonal antibody against the CD20 antigen of B lymphocytes 1,2 (anti-CD20 mAb). It is used in multiple medical conditions and its therapeutic role in dermatology has been increasing in the last decade. Initially used in the treatment of non-Hodgkin B-cell lymphoma, the scope of rituximab has been expanded to include autoimmune diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and chronic immune thrombocytopenic purpura syndrome. 3,4 Because the B cells produce immunoglobulins, which in turn have a pathogenic role in autoimmune diseases, their depletion is surmised to result in improved symptoms and disease control. Depleting B cells inevitably decreases the activation of antigen-presenting cells and the transmission of signaling pathways to other key mediators, such as T cells. MECHANISM OF ACTION The B-cell antigen CD20 is a transmembrane glycoprotein expressed on nearly all B cells and most B-cell lymphomas. 5,6 However, it is not found on early pre-B cells or stem cells. 5 B cells, originally arising from the bone marrow, mature by migrating through peripheral blood, lymph nodes, and spleen. In bone marrow (BM) they are known as plasma cells. CD20, specific for B cells, is expressed on B cells between the pre-B cell and pre-plasma stages. 7,8 Because rituximab targets CD20, plasma cells in the BM responsible for antibody production 6 are spared. Once rituximab binds A version of this article was previously published in Dermatologic Clinics 29:4.

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References (34)

  1. Carr DR, Heffernan MP. Innovative uses of rituximab in dermatology. Dermatol Clin 2010;28(3):547-57.
  2. 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(6):545-52.
  3. Looney RJ. B cells as a therapeutic target in autoimmune diseases other than rheumatoid arthritis. Rheumatology (Oxford) 2005;44(Suppl 2):ii13-7.
  4. Sanz I. Indications of rituximab in autoimmune diseases. Drug Discov Today Ther Strateg 2009;6(1):13-9.
  5. Maloney DG, Liles TM, Czerwinski DK, et al. Phase I clinical trial using escalating single-dose infusion of chimeric anti-CD20 monoclonal antibody (IDEC-C2B8) in patients with recurrent B cell lymphoma. Blood 1994;84(8):2457-66.
  6. Zambruno G, Borradori L. Rituximab immunotherapy in pemphigus: therapeutic effects beyond B cell depletion. J Invest Dermatol 2008;128(12):2745-7.
  7. Edwards JC, Cambridge G. B cell targeting in rheumatoid arthritis and other autoimmune diseases. Nat Rev Immunol 2006;6(5):394-403.
  8. Schmidt E, Hunzelmann N, Zillikens D, et al. Rituximab in refractory autoimmune bullous diseases. Clin Exp Dermatol 2006;31(4):503-8.
  9. McDonald V, Leandro M. Rituximab in non-haematological disorders of adults and its mode of action. Br J Haematol 2009;146(3):233-46. Rituximab in Autoimmune Bullous Disorders
  10. Onrust SV, Lamb HM, Balfour JA. Rituximab. Drugs 1999;58(1):79-88 [discus- sion: 89-90].
  11. Eming R, Nagel A, Wolff-Franke S, et al. Rituximab exerts a dual effect in pemphigus vulgaris. J Invest Dermatol 2008;128(12):2850-8.
  12. Mouquet H, Musette P, Gougeon ML, et al. B cell depletion immunotherapy in pemphigus: effects on cellular and humoral immune responses. J Invest Derma- tol 2008;128(12):2859-69.
  13. Muller R, Hunzelmann N, Baur V, et al. Targeted immunotherapy with rituximab leads to a transient alteration of the IgG autoantibody profile in pemphigus vulga- ris. Dermatol Res Pract 2010;2010:321950.
  14. 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.
  15. Sadler E, Schafleitner B, Lanschuetzer C, et al. Treatment-resistant classical epi- dermolysis bullosa acquisita responding to rituximab. Br J Dermatol 2007;157(2): 417-9.
  16. Daniel BS, Murrell DF. The actual management of pemphigus. G Ital Dermatol Ve- nereol 2010;145(5):689-702.
  17. Martin LK, Werth V, Villanueva E, et al. Interventions for pemphigus vulgaris and pemphigus foliaceus. Cochrane Database Syst Rev 2009;1:CD006263.
  18. Fernando SL, O'Connor KS. Treatment of severe pemphigus foliaceus with ritux- imab. Med J Aust 2008;189(5):289-90.
  19. Virgolini L, Marzocchi V. Anti-CD20 monoclonal antibody (rituximab) in the treat- ment of autoimmune diseases. Successful result in refractory pemphigus vulga- ris: report of a case. Haematologica 2003;88(7):ELT24.
  20. Ahmed AR, Spigelman Z, Cavacini LA, et al. Treatment of pemphigus vulgaris with rituximab and intravenous immune globulin. N Engl J Med 2006;355(17): 1772-9.
  21. Faurschou A, Gniadecki R. Two courses of rituximab (anti-CD20 monoclonal anti- body) for recalcitrant pemphigus vulgaris. Int J Dermatol 2008;47(3):292-4.
  22. Schmidt E, Seitz CS, Benoit S, et al. Rituximab in autoimmune bullous diseases: mixed responses and adverse effects. Br J Dermatol 2007;156(2):352-6.
  23. Kirtschig G, Murrell D, Wojnarowska F, et al. Interventions for mucous membrane pemphigoid/cicatricial pemphigoid and epidermolysis bullosa acquisita: a systematic literature review. Arch Dermatol 2002;138(3):380-4.
  24. Chan LS, Ahmed AR, Anhalt GJ, et al. The first international consensus on mucous membrane pemphigoid: definition, diagnostic criteria, pathogenic factors, medical treatment, and prognostic indicators. Arch Dermatol 2002;138(3):370-9.
  25. Zillikens D, Wever S, Roth A, et al. Incidence of autoimmune subepidermal blis- tering dermatoses in a region of central Germany. Arch Dermatol 1995;131(8): 957-8.
  26. Bernard P, Vaillant L, Labeille B, et al. Incidence and distribution of subepidermal autoimmune bullous skin diseases in three French regions. Bullous Diseases French Study Group. Arch Dermatol 1995;131(1):48-52.
  27. Niedermeier A, Eming R, Pfu ¨tze M, et al. Clinical response of severe mechanobul- lous epidermolysis bullosa acquisita to combined treatment with immunoadsorp- tion and rituximab (anti-CD20 monoclonal antibodies). Arch Dermatol 2007; 143(2):192-8.
  28. Crichlow SM, Mortimer NJ, Harman KE. A successful therapeutic trial of rituximab in the treatment of a patient with recalcitrant, high-titer epidermolysis bullosa ac- quisita. Br J Dermatol 2007;156(1):194-6.
  29. Foster CS, Chang PY, Ahmed AR. Combination of rituximab and intravenous immunoglobulin for recalcitrant ocular cicatricial pemphigoid: a preliminary report. Ophthalmology 2010;117(5):861-9.
  30. Joly P, Roujeau JC, Benichou J, et al, Bullous Diseases French Study Group. A comparison of oral and topical corticosteroids in patients with bullous pemphi- goid. N Engl J Med 2002;346(5):321-7.
  31. Langan SM, Smeeth L, Hubbard R, et al. Bullous pemphigoid and pemphigus vulgaris-incidence and mortality in the UK: population based cohort study. BMJ 2008;337:a180.
  32. Saouli Z, Papadopoulos A, Kaiafa G, et al. A new approach on bullous pemphi- goid therapy. Ann Oncol 2008;19(4):825-6.
  33. Schulze J, Bader P, Henke U, et al. Severe bullous pemphigoid in an infant- successful treatment with rituximab. Pediatr Dermatol 2008;25(4):462-5.
  34. Lourari S, Herve C, Doffoel-Hantz V, et al. Bullous and mucous membrane pem- phigoid show a mixed response to rituximab: experience in seven patients. J Eur Acad Dermatol Venereol 2010. [Epub ahead of print].