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Development of sarcoidosis following etanercept treatment: a report of three cases

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Abstract

After over 10 years of use of tumor necrosis factor-alpha (TNF-α) inhibitors, their side effects and complications are reasonably well documented. Recently, however, granulomatous reactions and cases of complete sarcoidosis have been reported, especially in patients treated with the TNF-α receptor protein, etanercept. This is intriguing because the TNF-α antibody drugs infliximab and adalimumab are reportedly used to treat sarcoidosis. We present three patients who developed sarcoidosis while on etanercept treatment, and discuss if possible differences in cytokine profiles and T regulatory cell function in patients taking different TNF-α inhibitors may explain this paradox.

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References

  1. Massara A, Cavazzini L, La Corte R, Trotta F (2009) Sarcoidosis appearing during anti-tumor necrosis factor alpha therapy: a new “class effect” paradoxical phenomenon. Two case reports and literature review. Semin Arthritis Rheum 2009 14 Jan [Epub ahead of print]

  2. Daïen CI, Monnier A, Claudepierre P et al (2009) Sarcoid-like granulomatosis in patients treated with tumor necrosis factor blockers: 10 cases. Rheumatology (Oxford) 48(8):865–866

    Article  Google Scholar 

  3. Josse S, Klemmer N, Moreno-Swirc S, Goëb V, Lequerré T, Vittecoq O (2009) Infliximab induced skin and pulmonary sarcoidosis in a rheumatoid arthritis patient. Jt Bone Spine 76(6):718–719

    Article  Google Scholar 

  4. Metyas SK, Tadros RM, Arkfeld DG (2009) Adalimumab-induced noncaseating granuloma in the bone marrow of a patient being treated for rheumatoid arthritis. Rheumatol Int 29:437–439

    Article  PubMed  CAS  Google Scholar 

  5. Toussirot E, Pertuiset E, Kantelip B, Wendling D (2008) Sarcoidosis occurring during anti-TNF-alpha treatment for inflammatory rheumatic diseases: report of two cases. Clin Exp Rheumatol 26:471–475

    PubMed  CAS  Google Scholar 

  6. González-López MA, Blanco R, González-Vela MC, Fernández-Llaca H, Rodríguez-Valverde V (2006) Development of sarcoidosis during etanercept therapy. Arthritis Rheum 55:817–820

    Article  PubMed  Google Scholar 

  7. Ishiguro T, Takayanagi N, Kurashima K et al (2008) Development of sarcoidosis during etanercept therapy. Intern Med 47:1021–1025

    Article  PubMed  Google Scholar 

  8. Farah RE, Shay MD (2007) Pulmonary sarcoidosis associated with etanercept therapy. Pharmacotherapy 27:1446–1448

    Article  PubMed  CAS  Google Scholar 

  9. Almodóvar R, Izquierdo M, Zarco P, Javier Quirós F, Mazzucchelli R, Steen B (2007) Pulmonary sarcoidosis in a patient with ankylosing spondylitis treated with infliximab. Clin Exp Rheumatol 25:99–101

    PubMed  Google Scholar 

  10. Kudrin A, Chilvers ER, Ginawi A et al (2007) Sarcoid-like granulomatous disease following etanercept treatment for RA. J Rheumatol 34:648–649

    PubMed  Google Scholar 

  11. Verschueren K, Van Essche E, Verschueren P, Taelman V, Westhovens R (2007) Development of sarcoidosis in etanercept-treated rheumatoid arthritis patients. Clin Rheumatol 26:1969–1971

    Article  PubMed  Google Scholar 

  12. O’Shea FD, Marras TK, Inman RD (2006) Pulmonary sarcoidosis developing during infliximab therapy. Arthritis Rheum 55:978–981

    Article  PubMed  Google Scholar 

  13. Hashkes PJ, Shajrawi I (2003) Sarcoid-related uveitis occurring during etanercept therapy. Clin Exp Rheumatol 21:645–646

    PubMed  CAS  Google Scholar 

  14. Phillips K, Weinblatt M (2005) Granulomatous lung disease occurring during etanercept treatment. Arthritis Rheum 53:618–620

    Article  PubMed  Google Scholar 

  15. Vavricka SR, Wettstein T, Speich R, Gaspert A, Bachli EB (2003) Pulmonary granulomas after tumour necrosis factor alpha antagonist therapy. Thorax 58:278–279

    Article  PubMed  CAS  Google Scholar 

  16. Peno-Green L, Lluberas G, Kingsley T, Brantley S (2002) Lung injury linked to etanercept therapy. Chest 122:1858–1860

    Article  PubMed  Google Scholar 

  17. Sturfelt G, Christensson B, Bynke G, Saxne T (2007) Neurosarcoidosis in a patient with rheumatoid arthritis during treatment with infliximab. J Rheumatol 34:2313–2314

    PubMed  Google Scholar 

  18. Louie GH, Chitkara P, Ward MM (2008) Relapse of sarcoidosis upon treatment with etanercept. Ann Rheum Dis 67:896–898

    Article  PubMed  CAS  Google Scholar 

  19. Roach DR, Bean AG, Demangel C, France MP, Briscoe H, Britton WJ (2002) TNF regulates chemokine induction essential for cell recruitment, granuloma formation, and clearance of mycobacterial infection. J Immunol 168:4620–4627

    PubMed  CAS  Google Scholar 

  20. Baughman RP, Drent M, Kavuru M, Sarcoidosis Investigators et al (2006) Infliximab therapy in patients with chronic sarcoidosis and pulmonary involvement. Am J Respir Crit Care Med 174:795–802

    Article  PubMed  CAS  Google Scholar 

  21. Rossman MD, Newman LS, Baughman RP et al (2006) A double-blinded, randomized, placebo-controlled trial of infliximab in subjects with active pulmonary sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 23:201–208

    PubMed  Google Scholar 

  22. Utz JP, Limper AH, Kalra S et al (2003) Etanercept for the treatment of stage II and III progressive pulmonary sarcoidosis. Chest 124:177–185

    Article  PubMed  CAS  Google Scholar 

  23. Baughman RP, Lower EE, Bradley DA, Raymond LA, Kaufman A (2005) Etanercept for refractory ocular sarcoidosis: results of a double-blind randomized trial. Chest 128:47–1062

    Article  Google Scholar 

  24. Sandborn WJ, Hanauer SB, Katz S et al (2001) Etanercept for active Crohn’s disease: a randomized, double-blind, placebo-controlled trial. Gastroenterology 121:1088–1094

    Article  PubMed  CAS  Google Scholar 

  25. Brown SJ, Abreu MT (2005) Antibodies to tumor necrosis factor-alpha in the treatment of Crohn’s disease. Curr Opin Drug Discov Dev 8:160–168

    CAS  Google Scholar 

  26. Sands BE, Anderson FH, Bernstein CN et al (2004) Infliximab maintenance therapy for fistulizing Crohn’s disease. N Engl J Med 350:876–885

    Article  PubMed  CAS  Google Scholar 

  27. Sandborn WJ, Hanauer S, Loftus EV Jr et al (2004) An open-label study of the human anti-TNF monoclonal antibody adalimumab in subjects with prior loss of response or intolerance to infliximab for Crohn’s disease. Am J Gastroenterol 99:1984–1989

    Article  PubMed  CAS  Google Scholar 

  28. Keane J, Gershon S, Wise RP et al (2001) Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med 345:1098–1104

    Article  PubMed  CAS  Google Scholar 

  29. Wallis RS, Broder MS, Wong JY, Hanson ME, Beenhouwer DO (2004) Granulomatous infectious diseases associated with tumor necrosis factor antagonists. Clin Infect Dis 38:1261–1265

    Article  PubMed  CAS  Google Scholar 

  30. Furst DE, Wallis R, Broder M, Beenhouwer DO (2006) Tumor necrosis factor antagonists: different kinetics and/or mechanisms of action may explain differences in the risk for developing granulomatous infection. Semin Arthritis Rheum 36:159–167

    Article  PubMed  CAS  Google Scholar 

  31. Wallis RS, Ehlers S (2005) Tumor necrosis factor and granuloma biology: explaining the differential infection risk of etanercept and infliximab. Semin Arthritis Rheum 34:34–38

    Article  PubMed  CAS  Google Scholar 

  32. Iannuzzi MC, Rybicki BA, Teirstein AS (2007) Sarcoidosis. N Engl J Med 357:2153–2165

    Article  PubMed  CAS  Google Scholar 

  33. Ziegenhagen MW, Müller-Quernheim J (2003) The cytokine network in sarcoidosis and its clinical relevance. J Intern Med 253:18–30

    Article  PubMed  CAS  Google Scholar 

  34. Valencia X, Stephens G, Goldbach-Mansky R, Wilson M, Shevach EM, Lipsky PE (2006) TNF downmodulates the function of human CD4+ CD25hi T-regulatory cells. Blood 108:253–261

    Article  PubMed  CAS  Google Scholar 

  35. Ehrenstein MR, Evans JG, Singh A, Moore S, Warnes G, Isenberg DA, Mauri C (2004) Compromised function of regulatory T cells in rheumatoid arthritis and reversal by anti-TNFalpha therapy. J Exp Med 200:277–285

    Article  PubMed  CAS  Google Scholar 

  36. Idali F, Wahlström J, Müller-Suur C, Eklund A, Grunewald J (2008) Analysis of regulatory T cell associated forkhead box P3 expression in the lungs of patients with sarcoidosis. Clin Exp Immunol 152:127–137

    Article  PubMed  CAS  Google Scholar 

  37. Saliu OY, Sofer C, Stein DS, Schwander SK, Wallis RS (2006) Tumor-necrosis-factor blockers: differential effects on mycobacterial immunity. J Infect Dis 194:486–492

    Article  PubMed  CAS  Google Scholar 

  38. Ioannou Y, Isenberg DA (2000) Current evidence for the induction of autoimmune rheumatic manifestations by cytokine therapy. Arthritis Rheum 43:1431–1442

    Article  PubMed  CAS  Google Scholar 

  39. Doyle MK, Berggren R, Magnus JH (2006) Interferon-induced sarcoidosis. J Clin Rheumatol 12:241–248

    Article  PubMed  Google Scholar 

  40. Flynn JL, Chan J, Triebold KJ, Dalton DK, Stewart TA, Bloom BR (1993) An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection. J Exp Med 178:2249–2254

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Clinical Immunology Unit, Department of Internal Medicine, Stavanger University Hospital, POB 8100, 4068, Stavanger, Norway

    Inger Marie Skoie, Klaus Wildhagen & Roald Omdal

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  1. Inger Marie Skoie
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  2. Klaus Wildhagen
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  3. Roald Omdal
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Correspondence to Inger Marie Skoie.

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Skoie, I.M., Wildhagen, K. & Omdal, R. Development of sarcoidosis following etanercept treatment: a report of three cases. Rheumatol Int 32, 1049–1053 (2012). https://doi.org/10.1007/s00296-009-1349-x

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  • DOI: https://doi.org/10.1007/s00296-009-1349-x

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