Digestive Diseases and Sciences

, Volume 52, Issue 6, pp 1481–1484

Pneumocystis jiroveci (carinii) Pneumonia After Infliximab Therapy: A Review of 84 Cases

Original Paper

Abstract

Anti-tumor necrosis factor-α therapy, infliximab, has become an established effective therapy for Crohn's disease and rheumatoid arthritis. However, infliximab has been associated with various opportunistic pathogens such as tuberculosis, histoplasmosis, listeriosis, aspergillosis, and Pneumocystis jiroveci (carinii) pneumonia. We reviewed the FDA Adverse Event Reporting System for cases of Pneumocystis associated with infliximab use from January 1998 through December 2003. The database revealed 84 cases of PCP following infliximab therapy. Concomitant immunosuppressive medications included methotrexate, prednisone, azathioprine, 6-mercaptopurine, and cyclosporine. Mean time between infliximab infusion and onset of symptoms of pneumonia, when reported, was 21 days (±18 days; n=40). Twenty-three of the 84 (27%) patients died. The use of infliximab is associated with PCP infection. Further, the mortality rate for Pneumocystis following the use of infliximab is significant. The potential for severe disease, mortality, and often subtle presentation of these infections warrant close follow-up and careful monitoring after therapy.

Keywords

Infliximab Remicade Pneumocystis Infection Pneumonia 

References

  1. 1.
    MacDonald TT, Hutchings P, Choy MY, et al. (1990) Tumor necrosis factor-alpha and interferon-gamma production measured at the single cell level in normal and inflamed human intestine. Clin Exp Immunol 81:301PubMedCrossRefGoogle Scholar
  2. 2.
    Murch SH, Lamkin VA, Savage MO, et al. (1991) Serum concentrations of tumour necrosis factor alpha in childhood chronic inflammatory bowel disease. Gut 32:913–917PubMedGoogle Scholar
  3. 3.
    Braegger CP, Nicholls S, Murch SH, et al. (1992) Tumour necrosis factor-alpha in stool as a marker of intestinal inflammation. Lancet 339:89–91PubMedCrossRefGoogle Scholar
  4. 4.
    Burrage PS, Mix KS, Brinckerhoff CE (2006) Matrix metalloproteinases: role in arthritis. Front Biosci 11:529–543PubMedCrossRefGoogle Scholar
  5. 5.
    Plevy AE, Landers CJ, Prehn J, et al. (1997) A role for TNF-a and mucosal T helper-1 cytokines in the pathogenesis of Crohn's disease. J Immunol 159:6276–6282PubMedGoogle Scholar
  6. 6.
    Paleolog EM, Hunt M, Elliott MJ, et al. (1996) Deactivation of vascular endothelium by monoclonal anti–tumor necrosis factor alpha antibody in rheumatoid arthritis. Arth Rheum 39:1082–1091CrossRefGoogle Scholar
  7. 7.
    Mauviel A (1993) Cytokine regulation of metalloproteinase gene expression. J Cell Biochem 53:288–295PubMedCrossRefGoogle Scholar
  8. 8.
    Tartaglia LA, Goeddel DV, Reynolds C, et al. (1993) Stimulation of human T cell proliferation by specific activation of the 75-kDa tumour necrosis factor receptor. J Immunol 151:4637–4641PubMedGoogle Scholar
  9. 9.
    Present DH, Rutgeerts P, Targan S, et al. (1999) Infliximab for the treatment of fistulas in patients with Crohn's Disease. N Engl J Med 340:1398–1405PubMedCrossRefGoogle Scholar
  10. 10.
    Parks M: Personal communication, Centocor Inc.Google Scholar
  11. 11.
    Serio RN (2003) Infliximab treatment of sarcoidosis. Ann Pharmacother 37:577–581PubMedCrossRefGoogle Scholar
  12. 12.
    Tobin AM, Kirby B (2005) TNF alpha inhibitors in the treatment of psoriasis and psoriatic arthritis. Biodrugs 19:47–57PubMedCrossRefGoogle Scholar
  13. 13.
    Wendling D, Toussirot E (2004) Anti-TNF-alpha therapy in ankylosing spondylitis. Expert Opin Pharmacother 5:1497–1507PubMedCrossRefGoogle Scholar
  14. 14.
    Lamprecht P, Voswinkel J, Lilienthal T, et al. (2003) Effectiveness of TNF–alpha blockade with infliximab in refractory Wegener's granulomatosis [Comment]. Rheumatology 42:1124–1125CrossRefGoogle Scholar
  15. 15.
    Brennan FM, Chantry D, Jackson A, et al. (1989) Inhibitory effect of TNF–a antibodies on synovial cell interleukin-1 production in rheumatoid arthritis. Lancet 2:244–247PubMedCrossRefGoogle Scholar
  16. 16.
    Keane J, Gershon S, Wise RP, et al. (2001) Tuberculosis associated with infliximab, a tumor necrosis factor α-neutralizing agent. N Engl J Med 345:1098–1104PubMedCrossRefGoogle Scholar
  17. 17.
    Warris A (2001) Invasive pulmonary aspergillosis associated with infliximab therapy. N Engl J Med 344:1099–1100PubMedCrossRefGoogle Scholar
  18. 18.
    Lee JH, Slifman NR, Gershon SK, et al. (2002) Life-threatening histoplasmosis complicating immunotherapy with tumor necrosis factor alpha antagonists infliximab and etanercept. Arth Rheum 46:2565–2670CrossRefGoogle Scholar
  19. 19.
    Helbling D, Breichtback TH, Kraus M (2002) Disseminated cytomegalovirus infection in Crohn's disease following anti-tumour necrosis factor therapy. Eur J Gastroenterol Hepatol 14:1393–1395PubMedCrossRefGoogle Scholar
  20. 20.
    Morelli J, Wilson FA (2000) Does infliximab therapy increase susceptibility to listeriosis? Am J Gastroenterol 95:841–842PubMedCrossRefGoogle Scholar
  21. 21.
    Shrestha RK, Stoller JK, Honari G, et al. (2004) Pneumonia due to Cryptococcus neoformans in a patient receiving infliximab: possible zoonotic transmission from a pet cockatiel. Respir Care 49:606–608PubMedGoogle Scholar
  22. 22.
    Katsarolis I, Tsiodras S, Panagopoulos P, et al. (2005) Septic arthritis due to Salmonella enteritidis associated with infliximab use. Scand J Infect Dis 37:304–305PubMedCrossRefGoogle Scholar
  23. 23.
    Vonkeman H, ten Napel C, Rasker H, et al. (2004) Disseminated primary varicella infection during infliximab treatment. J Rheumatol 31:2517–2518PubMedGoogle Scholar
  24. 24.
    Singh SM, Rau NV, Cohen LB, et al. (2004) Cutaneous nocardiosis complicating management of Crohn's disease with infliximab and prednisone. Can Med Assoc J 171:1063–1064CrossRefGoogle Scholar
  25. 25.
    Mohan N, Edwards ET, Cupps TR, et al. (2001) Demyelination occurring during anti-tumor necrosis factor alpha therapy for inflammatory arthritides. Arth Rheum 44:2862–2869CrossRefGoogle Scholar
  26. 26.
    Kaur N, Mahl TC (2004) Pneumocystis carinii pneumonia with oral candidiasis after infliximab therapy for Crohn's disease. Dig Dis Sci 49:1458–1460PubMedCrossRefGoogle Scholar
  27. 27.
    Tai TL, O'Rourke P, McWeeney M, et al. (2002) Pneumocystis carinii pneumonia following a second infusion of infliximab. Rheumatology 41:951–952PubMedCrossRefGoogle Scholar
  28. 28.
    Seddik M, Melliez H, Seguy D, et al. (2005) Pneumocystis jiroveci (carinii) pneumonia after initiation of infliximab and azathioprine therapy in a patient with Crohn's disease. Inflamm Bowel Dis 11:618–620PubMedCrossRefGoogle Scholar
  29. 29.
    Velayos FS, Sandborn WJ (2004) Pneumocystis carinii pneumonia during maintenance anti-tumor necrosis factor-alpha therapy with infliximab for Crohn's disease. Inflamm Bowel Dis 10:657–660PubMedCrossRefGoogle Scholar
  30. 30.
    Mansharamani NG, Garland R, Delaney D, Koziel H (2000) Management and outcome patterns for adult Pneumocystis carinii pneumonia, 1985–1995. Chest 118:704–711PubMedCrossRefGoogle Scholar
  31. 31.
    Brewer T, Colditz GA (1999) Postmarketing surveillance and adverse drug reactions: current perspectives and future needs. JAMA 281:824–829PubMedCrossRefGoogle Scholar
  32. 32.
    Marinosa M, Soler A, Nogues X, et al. (2004) Pulmonary coinfection by Pneumocystis carinii and Aspergillus fumigatus in a seronegative arthritis patient treated with low-dose methotrexate. Clin Rheumatol 23:555–556PubMedCrossRefGoogle Scholar
  33. 33.
    Oehling AG, Akdis CA, Schapowal A, et al. (1997) Suppression of the immune system by oral glucocorticoid therapy in bronchial asthma. Allergy 52:144–154PubMedCrossRefGoogle Scholar
  34. 34.
    Baert FJ, D'Haens GR, Peeters M, et al. (1999) Tumor necrosis factor alpha antibody (infliximab) therapy profoundly down-regulates the inflammation in Crohn's ileocolitis. Gastroenterology 116:22–28PubMedCrossRefGoogle Scholar
  35. 35.
    Van Den Brande JMH, Braat H, Van Den Brink GR, et al. (2003) Infliximab but not etanercept induces apoptosis in lamina propria T-lymphocytes from patients with Crohn's disease. Gastroenterology 124:1774–1785PubMedCrossRefGoogle Scholar
  36. 36.
    Favalli EG, Varenna M, Sinigaglia L (2005) Drug-induced agranulocytosis during treatment with infliximab in enteropathic spondyloarthropathy. Clin Exp Rheumatol 23:247–250PubMedGoogle Scholar
  37. 37.
    Sands BE, Anderson FH, Bernstein CN, et al. (2004) Infliximab maintenance therapy for fistulizing Crohn's disease. N Engl J Med 350:876–885PubMedCrossRefGoogle Scholar
  38. 38.
    Colombel JF, Loftus EV, Tremaine WJ, et al. (2004) The safety profile of infliximab in patients with Crohn's disease: The Mayo Clinic experience in 500 patients. Gastroenterology 126:19–31PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science + Business Media, Inc. 2006

Authors and Affiliations

  1. 1.Department of Internal MedicineUniversity of MichiganAnn ArborUSA
  2. 2.Division of GastroenterologyDepartment of Medicine, VA Upstate New York, State University of New York at Buffalo School of MedicineBuffaloUSA

Personalised recommendations