Occurence of autoimmune diseases following the biological treatment

Authors: K. Pavelka;  K. Jarošová
Authors‘ workplace: Revmatologický ústav a Klinika revmatologie 1. LF UK Praha
Published in: Čes. Revmatol., 19, 2011, No. 1, p. 4-10.
Category: Reviews


Biological therapy of chronic inflammatory, rheumatic, gastroenterological and dermatological diseases has revolutionized the treatment of these conditions. The number of patients treated with biologicals as well as the range of indications for this therapy is still growing. Although this treatment is relatively safe, adverse events may occur including development of autoimmune disorders. These autoimmune diseases may be divided into autoimmune systemic diseases and organ specific autoimmune diseases. Systemic lupus erythematosus (SLE) and vasculitides are among the most frequently induced systemic autoimmune diseases, whereas demyelinating diseases of the central nervous system (CNS) and peripheral neuropathy, interstitial lung disease and autoimmune hepatitis represent the organ specific group. Autoimmune diseases are most frequently induced by anti-TNF agents. Drug induced lupus usually manifests with consitutional symptoms, skin and joint involvement, haematological abnormalities and serositis. Nephritis and CNS involvement are less common. Anti-TNF induced SLE patients are ANA positive in 100% and anti dsDNA positive in 90%, whereas in classical drug induced SLE and idiopathic SLE, anti dsDNA positivity occurs less frequently. Antinuclear antibodies (ANA) are typical for classical drug induced SLE (occurs in 95%), less frequent in TNF induced SLE (57%) and least frequent in idiopathic SLE (25–40%). The treatment of drug induced SLE consists of discontinuation of TNF therapy in mild cases and mandatory use of corticosteroids and immunosuppressive therapy in more severe cases. The prognosis is good; the portion of patients with persistent disease is approximately 13%. In this review article, the author included two case reports describing patients with drug induced lupus from the Institute of Rheumatology in Prague including their treatment. Patients with skin vasculitis dominated the group of vasculitis patients with 88%, whereas renal involvement and peripheral neuropathy were rare. Conclusion: It is necessary to consider the possibility of drug induced autoimmune disease following a biological therapy when forming a differential diagnosis, and to take adequate therapeutic actions. In most cases, discontinuation of anti-TNF therapy is sufficient, whereas in more severe cases, introduction of immunosuppressive treatment is mandatory.

Key words:
autoimmune disease, anti-TNF therapy, drug induced systemic lupus erythematosus


1. Smolen J, Aletaha D, Koller M, et al. New therapies for treatment for rheumatoid arthritis. Lancet 2007; 370: 1861-74.

2. Aletaha D, Furovits J, Breedveld JC, et al. Rheumatoid arthritis joint progression in sustained remission is determined by disease activity levels preceding the period of radiographic assessment. Arthritis Rheum 2009; 60: 1242-52.

3. Saag K, GuTeng GC, Patkar NM, et al. American College of Rheumatology 2008 Recommendations for the use of nonbiologic and biologic disease modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum 2008;59: 762-784.

4. Baeclund E, Iliadou A, Askling J, et al. Association of chronic inflammation, not its treatment with increased lymphoma risk in rheumatoid arthritis. Arthritis Rheum 2006; 54: 692-701.

5. Zink A, Askling J, Dixon WG, et al. European biologicals registry: methodology, selected results and perspectives. Ann Rheum Dis 2009; 68: 1240-1246.

6. Charles PJ, Smeenk RJ, De Jong J, et al. Assessment of antibodies to double – stranded DNA in rheumatoid arthritis patients following treatment with infliximab, a monoclonal antibody tu tumor necrosis factor alpha. findings in open label randomized placebo controlled trials. Arthritis Rheum 2000; 43: 2383-90.

7. Ramos Casals M, Brito-Zeron P, Muňoz S, et al. BIOGEAS study Group. A systematic review of the off label use of biological therapies in systematic autoimmune diseases. Medicine (Baltimore) 2008; 87: 345-364.

8. Ramos Casals M, Brito-Zeron P, Soto MJ, et al. Autoimmune diseases induced by TNF targeted therapies. Best Pract Res Clin Rheumatol 2008; 22: 847-861.

9. Gonnet Gracia C, Barnatehe T, Richez J, et al. Antinuclear antibodies, anti ds DNA and C4 complement evolution in rheumatoid arthritis and ankylosing spondylitis treated with TNF blockers. Clin Exp Rheumatol 2008; 26: 401-407.

10. Erikkson C, Engstrand S, Sudquist KG, et al. Autoantibody formation in patients rheumatoid arthritis treated with anti TNF. Ann Rheum Dis 2005; 64: 403-407.

11. Zheng L, Fisher G, Miller R, et al. Induction of apoptosis in mature T cells by tumor necrosis factor. Nature 1995; 377: 348-51.

12. Sarzi Putini P, Atzeni F, Capsoni F, et al. Drug induced lupus erythematodes. Autoimmunity 2005; 38: 507-518.

13. Benucci M, Saviola G, Balardi P, et al. Anti-nucleosome antibodies as prediction factor of development of autoantibodies during therapy with three different TNF alpha blocking agents in rheumatoid arthritis. Clin Rheumatol 2008; 27: 91-95.

14. Hoffman BJ. Sensitivity to sulfadiazine resembling acute disseminated lupus erythematosus. Arch Dermatol Syph 1945; 51: 190-192.

15. Tan EM, Cohen AS, Fries JF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982; 25: 1271-7.

16. Vasoo S. Drug induced lupus: an update. Lupus 2006; 15: 757-61.

17. De Bandt M, Sibilia J, Loet X, et al. Rheumatismes et inflammation. Systemic lupus erytematosus induced by anti tumour necrosis factor alpha therapy: a French national survey. Arthritis Res Ther 2005;7:45-51.

18. Ramos Casals MR, Perez Alvarez R, Diaz –Lagares C, et al. Autoimmune diseases induced by biological agents. A double-edged sword? Autoimmunity reviews 2010; 9: 188-193.

19. Williams EL, Gadola S, Edwards CH. Anti TNF induced lupus. Rheumatology 2009; 48: 716-720.

20. Costa MF, Said NR, Zimmermann B. Drug induced lupus due to anti-tumor necrosis factor alfa agents. Semin Arthritis Rheum 2008;37:381-387.

21. Ramos Casal MF, Brito-Zeron P, Muňoz S et al. Autoimmune diseases induced by TNF-targeted therapies. Analysis of 233 cases. Medicine 2007; 86: 242-251.

22. Ramos Casals M, Brito- Zeron P, Cuadrado MJ et al. Vasculitis induced by tumor necrosis factor-targeted therapies. Curr Rheumatol Rep 2008; 10: 442-448.

23. Jonsdotirr T, Forslid J, van Vollenhoven A, et al. Treatment with tumor necrosis factor alpha antagonist in patients with rheumatoid arthritis induces cardiolipin antibodies. Ann Rheum Dis 2004; 63: 1075-1078.

24. van Oosten BW, Barkhof F, Truyen L, et al. Increased MRI activity and immune activation in two multiple sclerosis patients treated with the monoclonal anti-tumor necrosis factor antibody cA2. Neurology 1996; 47: 1531-4.

25. TNF neutralization in MS: results of a randomized, placebo controlled multicenter study. The Lenercept Multiple Sclerosis Study group and The University of British Columbia MS/MRI Analysis Group. Neurology 1999; 53: 57-65.

26. Stübgen JP. Tumor necrosis factor-alpha antagonists and neuropathy. Muscle Nerve 2008; 37: 281-292.

27. Ledingham J, Deighton C, British Society of Rheumatology Standards.Guidelines and Audit Working Group. (SGAWG). Update on the British Society of Rheumatology guidelines for prescribing TNF blockade in adults with rheumatoid artrhritis. Rheumatology 2005; 44: 157-163.

Dermatology & STDs Paediatric rheumatology Rheumatology
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