Skip to main content

Advertisement

SpringerLink
Log in

Pneumocystis jirovecii pneumonia in mycophenolate mofetil-treated patients with connective tissue disease: analysis of 17 cases

  • Original Article
  • Published:
Rheumatology International Aims and scope Submit manuscript

Abstract

The association of Pneumocystis jirovecii pneumonia (PJP) with connective tissue disease (CTD) and mycophenolate mofetil’s (MMF) potent activity against PJP have been separately reported. Until now, there have been no papers describing the occurrence of PJP following MMF treatment in CTD patients. The objective of this study was to describe the clinical features, risk factors, outcomes of PJP in patients with CTD and investigates the effects of MMF on the occurrence of PJP in China. In this retrospective cohort study, we performed a chart review, analyzing clinical features, treatment, and outcomes of PJP in patients with CTD in a single hospital. A total of 17 cases met the inclusion criteria of having PJP and a CTD diagnosis: systemic lupus erythematosus; polymyositis; dermatomyositis; rheumatoid arthritis; Wegener’s granulomatosis; and microscopic polyangiitis. Sixteen patients were treated with glucocorticoids (GCs) plus immunosuppressive drugs. Only one patient had GCs without immunosuppressive drugs. Ten subjects (62.5 %) received MMF (1–1.5 g/day), and all ten had lymphopenia. The mortality rates of MMF and non-MMF patients were 50 and 14 %, respectively. This study is the first report of PJP following MMF plus GC treatment in patients with CTD. CTD itself may be a risk factor for PJP. When CTD patients receiving MMF therapy have low lymphocyte counts and/or CD4 lymphocyte counts <250/µL, we should be care of occurrence of PJP.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Ward MM, Donald F (1999) Pneumocystis carinii pneumonia in patients with connective tissue diseases: the role of hospital experience in diagnosis and mortality. Arthritis Rheum 42(4):780–789. doi:10.1002/1529-0131(199904)42:4<780:AID-ANR23>3.0.CO;2-M

    Article  CAS  PubMed  Google Scholar 

  2. Li J, Huang XM, Fang WG, Zeng XJ (2006) Pneumocystis carinii pneumonia in patients with connective tissue disease. J Clin Rheumatol 12(3):114–117. doi:10.1097/01.rhu.0000221794.24431.36

    Article  PubMed  Google Scholar 

  3. Azevedo LS, Castro MC, Paula FJ, Ianhez LE, David-Neto E (2005) Mycophenolate mofetil may protect against Pneumocystis carinii pneumonia in renal transplanted patients. Rev Inst Med Trop Sao Paulo 47(3):143–145

    Article  PubMed  Google Scholar 

  4. Hochberg MC (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40(9):1725

    Article  CAS  PubMed  Google Scholar 

  5. Bohan A, Peter JB (1975) Polymyositis and dermatomyositis (first of two parts). N Engl J Med 292(7):344–347

    Article  CAS  PubMed  Google Scholar 

  6. Bohan A, Peter JB (1975) Polymyositis and dermatomyositis (second of two parts). N Engl J Med 292(7):403–407

    Article  CAS  PubMed  Google Scholar 

  7. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31(3):315–324

    Article  CAS  PubMed  Google Scholar 

  8. Leavitt RY, Fauci AS, Bloch DA, Michel BA, Hunder GG, Arend WP, Calabrese LH, Fries JF, Lie JT, Lightfoot RW Jr et al (1990) The American College of Rheumatology 1990 criteria for the classification of Wegener’s granulomatosis. Arthritis Rheum 33(8):1101–1107

    Article  CAS  PubMed  Google Scholar 

  9. Jennette JC, Falk RJ, Andrassy K, Bacon PA, Churg J, Gross WL, Hagen EC, Hoffman GS, Hunder GG, Kallenberg CG et al (1994) Nomenclature of systemic vasculitides. Proposal of an international consensus conference. Arthritis Rheum 37(2):187–192

    Article  CAS  PubMed  Google Scholar 

  10. Godeau B, Coutant-Perronne V, Le Thi Huong D, Guillevin L, Magadur G, De Bandt M, Dellion S, Rossert J, Rostoker G, Piette JC et al (1994) Pneumocystis carinii pneumonia in the course of connective tissue disease: report of 34 cases. J Rheumatol 21(2):246–251

    CAS  PubMed  Google Scholar 

  11. Aoki Y, Iwamoto M, Kamata Y, Nagashima T, Yoshio T, Okazaki H, Minota S (2009) Prognostic indicators related to death in patients with Pneumocystis pneumonia associated with collagen vascular diseases. Rheumatol Int 29(11):1327–1330. doi:10.1007/s00296-009-0857-z

    Article  PubMed  Google Scholar 

  12. Falagas ME, Manta KG, Betsi GI, Pappas G (2007) Infection-related morbidity and mortality in patients with connective tissue diseases: a systematic review. Clin Rheumatol 26(5):663–670. doi:10.1007/s10067-006-0441-9

    Article  PubMed  Google Scholar 

  13. Iikuni N, Kitahama M, Ohta S, Okamoto H, Kamatani N, Nishinarita M (2006) Evaluation of Pneumocystis pneumonia infection risk factors in patients with connective tissue disease. Mod Rheumatol 16(5):282–288. doi:10.1007/s10165-006-0502-6

    Article  PubMed  Google Scholar 

  14. Mori S, Sugimoto M (2012) Pneumocystis jirovecii infection: an emerging threat to patients with rheumatoid arthritis. Rheumatology 51(12):2120–2130. doi:10.1093/rheumatology/kes244

    Article  PubMed Central  PubMed  Google Scholar 

  15. Kameda H, Tokuda H, Sakai F, Johkoh T, Mori S, Yoshida Y, Takayanagi N, Taki H, Hasegawa Y, Hatta K, Yamanaka H, Dohi M, Hashimoto S, Yamada H, Kawai S, Takeuchi T, Tateda K, Goto H (2011) Clinical and radiological features of acute-onset diffuse interstitial lung diseases in patients with rheumatoid arthritis receiving treatment with biological agents: importance of Pneumocystis pneumonia in Japan revealed by a multicenter study. Intern Med 50(4):305–313

    Article  CAS  PubMed  Google Scholar 

  16. Lertnawapan R, Totemchokchyakarn K, Nantiruj K, Janwityanujit S (2009) Risk factors of Pneumocystis jeroveci pneumonia in patients with systemic lupus erythematosus. Rheumatol Int 29(5):491–496. doi:10.1007/s00296-008-0721-6

    Article  PubMed  Google Scholar 

  17. Weng CT, Liu MF, Weng MY, Lee NY, Wang MC, Lin WC, Ou CY, Lai WW, Hsu SC, Chao SC, Chung TJ, Lee CT, Shieh CC, Wang JY, Wang CR (2013) Pneumocystis jirovecii pneumonia in systemic lupus erythematosus from southern Taiwan. J Clin Rheumatol 19(5):252–258. doi:10.1097/RHU.0b013e31829d5017

    Article  PubMed  Google Scholar 

  18. Husain S, Singh N (2002) The impact of novel immunosuppressive agents on infections in organ transplant recipients and the interactions of these agents with antimicrobials. Clin Infect Dis 35(1):53–61. doi:10.1086/340867

    Article  CAS  PubMed  Google Scholar 

  19. Oz HS, Hughes WT (1997) Novel anti-Pneumocystis carinii effects of the immunosuppressant mycophenolate mofetil in contrast to provocative effects of tacrolimus, sirolimus, and dexamethasone. J Infect Dis 175(4):901–904

    Article  CAS  PubMed  Google Scholar 

  20. Arichi N, Kishikawa H, Mitsui Y, Kato T, Nishimura K, Tachikawa R, Tomii K, Shiina H, Igawa M, Ichikawa Y (2009) Cluster outbreak of Pneumocystis pneumonia among kidney transplant patients within a single center. Transpl Proc 41(1):170–172. doi:10.1016/j.transproceed.2008.10.027

    Article  CAS  Google Scholar 

  21. Lv J, Zhang H, Cui Z, Su T, Zhang Y, Wang H (2008) Delayed severe pneumonia in mycophenolate mofetil-treated patients with IgA nephropathy. Nephrol Dial Transplant 23(9):2868–2872. doi:10.1093/ndt/gfn161

    Article  CAS  PubMed  Google Scholar 

  22. Fritzsche C, Riebold D, Munk-Hartig A, Klammt S, Neeck G, Reisinger E (2012) High prevalence of Pneumocystis jirovecii colonization among patients with autoimmune inflammatory diseases and corticosteroid therapy. Scand J Rheumatol 41(3):208–213. doi:10.3109/03009742.2011.630328

    Article  CAS  PubMed  Google Scholar 

  23. Zaman MK, White DA (1988) Serum lactate dehydrogenase levels and Pneumocystis carinii pneumonia. Diagnostic and prognostic significance. Am Rev Respir Dis 137(4):796–800. doi:10.1164/ajrccm/137.4.796

    Article  CAS  PubMed  Google Scholar 

  24. Tasaka S, Tokuda H (2012) Pneumocystis jirovecii pneumonia in non-HIV-infected patients in the era of novel immunosuppressive therapies. J Infect Chemother 18(6):793–806. doi:10.1007/s10156-012-0453-0

    Article  CAS  PubMed  Google Scholar 

  25. Saito K, Nakayamada S, Nakano K, Tokunaga M, Tsujimura S, Nakatsuka K, Adachi T, Tanaka Y (2004) Detection of Pneumocystis carinii by DNA amplification in patients with connective tissue diseases: re-evaluation of clinical features of P. carinii pneumonia in rheumatic diseases. Rheumatology 43(4):479–485. doi:10.1093/rheumatology/keh071

    Article  CAS  PubMed  Google Scholar 

  26. Sato T, Inokuma S, Maezawa R, Nakayama H, Hamasaki K, Miwa Y, Okazaki Y, Yamashita M, Tanaka Y, Kono H (2005) Clinical characteristics of Pneumocystis carinii pneumonia in patients with connective tissue diseases. Mod Rheumatol 15(3):191–197. doi:10.1007/s10165-005-0395-9

    Article  PubMed  Google Scholar 

  27. Gupta D, Zachariah A, Roppelt H, Patel AM, Gruber BL (2008) Prophylactic antibiotic usage for Pneumocystis jirovecii pneumonia in patients with systemic lupus erythematosus on cyclophosphamide: a survey of US rheumatologists and the review of literature. J Clin Rheumatol 14(5):267–272. doi:10.1097/RHU.0b013e31817a7e30

    Article  PubMed  Google Scholar 

  28. Stamp LK, Hurst M (2010) Is there a role for consensus guidelines for P. jiroveci pneumonia prophylaxis in immunosuppressed patients with rheumatic diseases? J Rheumatol 37(4):686–688. doi:10.3899/jrheum.091426

    Article  PubMed  Google Scholar 

  29. Vananuvat P, Suwannalai P, Sungkanuparph S, Limsuwan T, Ngamjanyaporn P, Janwityanujit S (2011) Primary prophylaxis for Pneumocystis jirovecii pneumonia in patients with connective tissue diseases. Semin Arthritis Rheum 41(3):497–502. doi:10.1016/j.semarthrit.2011.05.004

    Article  PubMed  Google Scholar 

Download references

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Rheumatology and Immunology, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, 100020, China

    Yongfeng Zhang & Yi Zheng

Authors
  1. Yongfeng Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yi Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yi Zheng.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, Y., Zheng, Y. Pneumocystis jirovecii pneumonia in mycophenolate mofetil-treated patients with connective tissue disease: analysis of 17 cases. Rheumatol Int 34, 1765–1771 (2014). https://doi.org/10.1007/s00296-014-3073-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00296-014-3073-4

Keywords

Search

Navigation