Top

Clinical Reviews in Allergy & Immunology

Published in:

01-02-2008

Rituximab in Treatment-Resistant Autoimmune Blistering Skin Disorders

Authors: Enno Schmidt, Eva-Bettina Bröcker, Matthias Goebeler

Published in: Clinical Reviews in Allergy & Immunology | Issue 1/2008

Abstract

Autoimmune blistering diseases are associated with autoantibodies to desmosomal (pemphigus group) or hemidesmosomal proteins (autoimmune subepidermal blistering disorders) that are essential for the structural integrity of the epidermis and dermoepidermal junction. Treatment is usually based on systemic glucocorticosteroids, which are often combined with additional immunosuppressants such as azathioprine and mycophenolate mofetil or immunomodulators including dapsone, antibiotics, and intravenous immunoglobulins. These interventions are sometimes not sufficient to induce remission and/or may be associated with intolerable adverse events. In such situations, the anti-CD20 antibody rituximab has been successfully applied in recent years. Rituximab transitorily depletes CD20-positive B lymphocytes from the circulation. It has been employed in more than 1 million patients with CD20-positive non-Hodgkin’s lymphoma and severe side effects were only rarely observed. Subsequently, the B cell-modulating effect of rituximab has encouraged its use in a variety of autoimmune diseases, including more than 40 patients with pemphigus. In addition, a few patients with bullous pemphigoid, mucous membrane pemphigoid, and epidermolysis bullosa acquisita have received rituximab. In the majority of these patients, clinical remission was induced; however, serious adverse events were considerable higher compared to both patients with non-Hodgkin’s lymphoma or nonbullous autoimmune disorders like lupus erythematosus, dermatomyositis, and rheumatoid arthritis.

Schmidt E, Zillikens D (2000) Autoimmune and inherited subepidermal blistering diseases: advances in the clinic and the laboratory. Adv Dermatol 16:113–157PubMed

Stanley JR, Amagai M (2006) Pemphigus, bullous impetigo, and the staphylococcal scalded-skin syndrome. N Engl J Med 355:1800–1810PubMedCrossRef

Harman KE, Albert S, Black MM (2003) Guidelines for the management of pemphigus vulgaris. Br J Dermatol 149:926–937PubMedCrossRef

Goebeler M, Sitaru C, Zillikens D (2004) Bullous autoimmune disorders: therapy. J Dtsch Dermatol Ges 2:774–793PubMedCrossRef

Goebeler M, Zillikens D (2006) Bullous pemphigoid: diagnosis and management. Expert Review of Dermatology 1:401–411CrossRef

Cohen Y, Solal-Celigny P, Polliack A (2003) Rituximab therapy for follicular lymphoma: a comprehensive review of its efficacy as primary treatment, treatment for relapsed disease, re-treatment and maintenance. Haematologica 88:811–823PubMed

George JN, el-Harake MA, Raskob GE (1994) Chronic idiopathic thrombocytopenic purpura. N Engl J Med 331:1207–1211PubMedCrossRef

Isenberg DA (2006) B cell targeted therapies in autoimmune diseases. J Rheumatol Suppl 77:24–28PubMed

Edwards JC, Szczepanski L, Szechinski J, Filipowicz-Sosnowska A, Emery P, Close DR, Stevens RM, Shaw T (2004) Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med 350:2572–2581PubMedCrossRef

10.

Browning JL (2006) B cells move to centre stage: novel opportunities for autoimmune disease treatment. Nat Rev Drug Discov 5:564–576PubMedCrossRef

11.

Anolik JH, Barnard J, Cappione A, Pugh-Bernard AE, Felgar RE, Looney RJ, Sanz I (2004) Rituximab improves peripheral B cell abnormalities in human systemic lupus erythematosus. Arthritis Rheum 50:3580–3590PubMedCrossRef

12.

Leandro MJ, Cambridge G, Ehrenstein MR, Edwards JC (2006) Reconstitution of peripheral blood B cells after depletion with rituximab in patients with rheumatoid arthritis. Arthritis Rheum 54:613–620PubMedCrossRef

13.

Vugmeyster Y, Howell K (2005) Rituximab-mediated depletion of cynomolgus monkey B cells in vitro in different matrices: possible inhibitory effect of IgG. Int Immunopharmacol 4:1117–1124CrossRef

14.

Anolik JH, Campbell D, Felgar RE, Young F, Sanz I, Rosenblatt J, Looney RJ (2003) The relationship of FcgammaRIIIa genotype to degree of B cell depletion by rituximab in the treatment of systemic lupus erythematosus. Arthritis Rheum 48:455–459PubMedCrossRef

15.

Janas E, Priest R, Wilde JI, White JH, Malhotra R (2005) Rituxan (anti-CD20 antibody)-induced translocation of CD20 into lipid rafts is crucial for calcium influx and apoptosis. Clin Exp Immunol 139:439–446PubMedCrossRef

16.

Schmidt E, Obe K, Bröcker EB, Zillikens D (2000) Serum levels of autoantibodies to BP180 correlate with disease activity in patients with bullous pemphigoid. Arch Dermatol 136:174–178PubMedCrossRef

17.

Sitaru C, Mihai S, Otto C, Chiriac MT, Hausser I, Dotterweich B, Saito H, Rose C, Ishiko A, Zillikens D (2005) Induction of dermal–epidermal separation in mice by passive transfer of antibodies specific to type VII collagen. J Clin Invest 115:870–878PubMedCrossRef

18.

Leandro MJ, Edwards JC, Cambridge G (2002) Clinical outcome in 22 patients with rheumatoid arthritis treated with B lymphocyte depletion. Ann Rheum Dis 61:883–888PubMedCrossRef

19.

Schmidt E, Hunzelmann N, Zillikens D, Broecker EB, Goebeler M (2006) Rituximab in refractory autoimmune bullous diseases. Clin Exp Dermatol 31:503–508PubMedCrossRef

20.

Schmidt E, Seitz CS, Benoit S, Bröecker EB, Goebeler M (2007) Rituximab in autoimmune bullous diseases: mixed responses and adverse effects. Br J Dermatol 156:352–356PubMedCrossRef

21.

Belgi AS, Azeez M, Hoyle C, Williams RE (2006) Response of pemphigus vulgaris to anti-CD20 antibody therapy (rituximab) may be delayed. Clin Exp Dermatol 31:143PubMedCrossRef

22.

Kong HH, Prose NS, Ware RE, Hall RP 3rd (2005) Successful treatment of refractory childhood pemphigus vulgaris with anti-CD20 monoclonal antibody (rituximab). Pediatr Dermatol 22:461–464PubMedCrossRef

23.

Ahmed AR, Spigelman Z, Cavacini LA, Posner MR (2006) Treatment of pemphigus vulgaris with rituximab and intravenous immune globulin. N Engl J Med 355:1772–1779PubMedCrossRef

24.

Borradori L, Lombardi T, Samson J, Girardet C, Saurat JH, Hugli A (2001) Anti-CD20 monoclonal antibody (rituximab) for refractory erosive stomatitis secondary to CD20(+) follicular lymphoma-associated paraneoplastic pemphigus. Arch Dermatol 137:269–272PubMed

25.

Barnadas M, Roe E, Brunet S, Garcia P, Bergua P, Pimentel L, Puig L, Francia A, Garcia R, Gelpi C, Sierra J, Coll P, Alomar A (2006) Therapy of paraneoplastic pemphigus with rituximab: a case report and review of literature. J Eur Acad Dermatol Venereol 20:69–74PubMedCrossRef

26.

Esposito M, Capriotti E, Giunta A, Bianchi L, Chimenti S (2006) Long-lasting remission of pemphigus vulgaris treated with rituximab. Acta Derm Venereol 86:87–89PubMed

27.

Borel C, Launay F, Garrouste C, Astudillo L, Bazex J, Arlet P, Paul C, Viraben R, Sailler L (2006) Rituximab induced remission of pemphigus vulgaris: 2 cases. Rev Med Interne 28:266–268PubMedCrossRef

28.

Niedermeier A, Worl P, Barth S, Schuler G, Hertl M (2006) Delayed response of oral pemphigus vulgaris to rituximab treatment. Eur J Dermatol 16:266–270PubMed

29.

McGinness JL, Bivens MM, Greer KE, Patterson JW, Saulsbury FT (2006) Immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) associated with pemphigoid nodularis: a case report and review of the literature. J Am Acad Dermatol 55:143–148PubMedCrossRef

30.

Sadler E, Schafleitner B, Lanschuetzer C, Laimer M, Pohla-Gubo G, Hametner R, Hintner H, Bauer JW (2007) Treatment-resistant classical epidermolysis bullosa acquisita responding to rituximab. Br J Dermatol 157:417–419PubMedCrossRef

31.

Goebeler M, Herzog S, Bröcker EB, Zillikens D (2003) Rapid response of treatment-resistant pemphigus foliaceus to the anti-CD20 antibody rituximab. Br J Dermatol 149:899–901PubMedCrossRef

32.

Arin MP, Engert A, Krieg T, Hunzelmann N (2005) Anti-CD20 monoclonal antibody (rituximab) in the treatment of pemphigus. Br J Dermatol 153:620–625PubMedCrossRef

33.

Szabolcs P, Reese M, Yancey KB, Hall RP, Kurtzberg J (2002) Combination treatment of bullous pemphigoid with anti-CD20 and anti-CD25 antibodies in a patient with chronic graft-versus-host disease. Bone Marrow Transplant 30:327–329PubMedCrossRef

34.

Schmidt E, Benoit S, Bröcker EB, Zillikens D, Goebeler M (2006) Successful adjuvant treatment of recalcitrant epidermolysis bullosa acquisita with anti-CD20 antibody rituximab. Arch Dermatol 142:147–150PubMedCrossRef

35.

Cambridge G, Leandro MJ, Teodorescu M, Manson J, Rahman A, Isenberg DA, Edwards JC (2006) B cell depletion therapy in systemic lupus erythematosus: effect on autoantibody and antimicrobial antibody profiles. Arthritis Rheum 54:3612–3622PubMedCrossRef

36.

Dupuy A, Viguier M, Bedane C, Cordoliani F, Blaise S, Aucouturier F, Bonnetblanc JM, Morel P, Dubertret L, Bachelez H (2004) Treatment of refractory pemphigus vulgaris with rituximab (anti-CD20 monoclonal antibody). Arch Dermatol 140:91–96PubMedCrossRef

37.

Schmidt E, Herzog S, Bröcker EB, Zillikens D, Goebeler M (2005) Long-standing remission of recalcitrant juvenile pemphigus vulgaris after adjuvant therapy with rituximab. Br J Dermatol 153:449–451PubMedCrossRef

38.

Radbruch A, Muehlinghaus G, Luger EO, Inamine A, Smith KG, Dorner T, Hiepe F (2006) Competence and competition: the challenge of becoming a long-lived plasma cell. Nat Rev Immunol 6:741–750PubMedCrossRef

39.

Looney RJ, Anolik JH, Campbell D, Felgar RE, Young F, Arend LJ, Sloand JA, Rosenblatt J, Sanz I (2004) B cell depletion as a novel treatment for systemic lupus erythematosus: a phase I/II dose-escalation trial of rituximab. Arthritis Rheum 50:2580–2589PubMedCrossRef

40.

Levine TD (2005) Rituximab in the treatment of dermatomyositis: an open-label pilot study. Arthritis Rheum 52:601–607PubMedCrossRef

41.

Willems M, Haddad E, Niaudet P, Kone-Paut I, Bensman A, Cochat P, Deschenes G, Fakhouri F, Leblanc T, Llanas B, Loirat C, Pillet P, Ranchin B, Salomon R, Ulinski T, Bader-Meunier B (2006) Rituximab therapy for childhood-onset systemic lupus erythematosus. J Pediatr 148:623–627PubMedCrossRef

42.

Quartier P, Brethon B, Philippet P, Landman-Parker J, Le Deist F, Fischer A (2001) Treatment of childhood autoimmune haemolytic anaemia with rituximab. Lancet 358:1511–1513PubMedCrossRef

43.

Zecca M, Nobili B, Ramenghi U, Perrotta S, Amendola G, Rosito P, Jankovic M, Pierani P, De Stefano P, Bonora MR, Locatelli F (2003) Rituximab for the treatment of refractory autoimmune hemolytic anemia in children. Blood 101:3857–3861PubMedCrossRef

44.

Bennett CM, Rogers ZR, Kinnamon DD, Bussel JB, Mahoney DH, Abshire TC, Sawaf H, Moore TB, Loh ML, Glader BE, McCarthy MC, Mueller BU, Olson TA, Lorenzana AN, Mentzer WC, Buchanan GR, Feldman HA, Neufeld EJ (2006) Prospective phase 1/2 study of rituximab in childhood and adolescent chronic immune thrombocytopenic purpura. Blood 107:2639–2642PubMedCrossRef

Title: Rituximab in Treatment-Resistant Autoimmune Blistering Skin Disorders
Authors: Enno Schmidt
Eva-Bettina Bröcker
Matthias Goebeler
Publication date: 01-02-2008
Publisher: Humana Press Inc
Published in: Clinical Reviews in Allergy & Immunology / Issue 1/2008
Print ISSN: 1080-0549
Electronic ISSN: 1559-0267
DOI: https://doi.org/10.1007/s12016-007-8021-6

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2008

Hepatitis B Virus (HBV) and Autoimmune Disease

Comparison of Three Anti-CCP Antibody Tests and Rheumatoid Factor in RA and Control Patients

Should Rituximab be Considered as the First-Choice Treatment for Severe Autoimmune Rheumatic Diseases?

Rituximab as a Therapeutic Tool in Severe Mixed Cryoglobulinemia

B-Cell Depletion and Repopulation in Autoimmune Diseases

Antibodies to Citrullinated Vimentin are a Specific and Sensitive Marker for the Diagnosis of Rheumatoid Arthritis

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials