Clinical Rheumatology

, Volume 37, Issue 8, pp 2269–2274 | Cite as

Differences in clinical Pneumocystis pneumonia in rheumatoid arthritis and other connective tissue diseases suggesting a rheumatoid-specific interstitial lung injury spectrum

  • Kota ShimadaEmail author
  • Kyoko Yokosuka
  • Takahiro Nunokawa
  • Shoji Sugii
Brief Report


To compare Pneumocystis pneumonia (PCP) in patients with rheumatoid arthritis (RA) with PCP in patients with non-RA connective tissue diseases (CTDs) in order to clarify the characteristics of the former. We extracted consecutive patients satisfying the following criteria for “clinical PCP”: (1) positive plasma β-d-glucan, (2) PCP-compatible computed tomography findings of the lung, and (3) successful treatment with antipneumocystic antibiotics. Patients who underwent methylprednisolone “pulse” therapy or sufficient antibiotics to cure bacterial pneumonia were excluded. We used the t test, U test, or Fischer’s exact probability test to compare the two groups and Jonckheere-Terpstra’s test and Ryan’s procedure for the trend test. Thirty-five cases were extracted. The underlying rheumatic diseases were RA in 25 and non-RA CTDs in ten. At the onset of clinical PCP, the lymphocyte counts were 884 vs 357/mm3 (p < 0.001), PC-PCR positivity 64% vs 100% (p = 0.029), glucocorticoid dose 4.0 vs 17.5 mg PSL/day (p < 0.001), and methotrexate dose 8 vs 0 mg/week (p = 0.003). The PC-PCR-negative patients, observed only in the RA group, were all receiving methotrexate (MTX) therapy except one patient who was receiving high-dose prednisolone alone. All PC-PCR-positive patients were receiving glucocorticoid, TNF inhibitor, or a non-MTX immunosuppressant. No patient with MTX alone had positive PC-PCR results. Clinical PCP in RA patients differed from that in non-RA CTD patients and may be understood as only a part of the rheumatoid-specific interstitial lung injury spectrum influenced by multiple, synergistic factors including MTX, Pneumocystis, and RA itself.


Interstitial lung disease MTX-induced lung injury Pneumocystis pneumonia Rheumatoid arthritis β-d-glucan 



We thank Mr. James Robert Valera for his editorial assistance.

Compliance with ethical standards

The ethical board of Tokyo Metropolitan Tama Medical Center approved this study, and all the procedures were in accordance with the Helsinki Declaration of 1975.




  1. 1.
    Catherinot E, Lanternier F, Bougnoux ME, Lecuit M, Couderc LJ, Lortholary O (2010) Pneumocystis jirovecii pneumonia. Infect Dis Clin N Am 24:107–138CrossRefGoogle Scholar
  2. 2.
    Tasaka S, Hasegawa N, Kobayashi S, Yamada W, Nishimura T, Takeuchi T, Ishizaka A (2007) Serum indicators for the diagnosis of pneumocystis pneumonia. Chest 131:1173–1180CrossRefPubMedGoogle Scholar
  3. 3.
    Tokuda H, Sakai F, Yamada H, Johkoh T, Imamura A, Dohi M, Hirakata M, Yamada T, Kamatani N, Kikuchi Y, Sugii S, Takeuchi T, Tateda K, Goto H (2008) Clinical and radiological features of Pneumocystis pneumonia in patients with rheumatoid arthritis, in comparison with methotrexate pneumonitis and Pneumocystis pneumonia in acquired immunodeficiency syndrome: a multicenter study. Intern Med 47:915–923CrossRefPubMedGoogle Scholar
  4. 4.
    Wakefield AE, Pixley FJ, Banerji S, Sinclair K, Miller RF, Moxon ER, Hopkin JM (1990) Detection of Pneumocystis carinii with DNA amplification. Lancet 336:451–453CrossRefPubMedGoogle Scholar
  5. 5.
    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 50:305–313CrossRefPubMedGoogle Scholar
  6. 6.
    Yasuoka A, Tachikawa N, Shimada K, Kimura S, Oka S (1996) (1-->3) beta-D-glucan as a quantitative serological marker for Pneumocystis carinii pneumonia. Clin Diagn Lab Immunol 3:197–199PubMedPubMedCentralGoogle Scholar
  7. 7.
    Salerno D, Mushatt D, Myers L, Zhuang Y, de la Rua N, Calderon EJ, Welsh DA (2014) Serum and bal beta-D-glucan for the diagnosis of Pneumocystis pneumonia in HIV positive patients. Respir Med 108:1688–1695CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    de Boer MG, Gelinck LB, van Zelst BD, van de Sande WW, Willems LN, van Dissel JT, de Jonge R, Kroon FP (2011) β-D-glucan and S-adenosylmethionine serum levels for the diagnosis of Pneumocystis pneumonia in HIV-negative patients: a prospective study. J Inf Secur 62:93–100Google Scholar
  9. 9.
    Limper AH, Offord KP, Smith TF, Martin WJ 2nd (1989) Pneumocystis carinii pneumonia. Differences in lung parasite number and inflammation in patients with and without AIDS. Am Rev Respir Dis 140:1204–1209CrossRefPubMedGoogle Scholar
  10. 10.
    Ohosone Y, Okano Y, Kameda H, Fujii T, Hama N, Hirakata M, Mimori T, Akizuki M, Ikeda Y (1997) Clinical characteristics of patients with rheumatoid arthritis and methotrexate induced pneumonitis. J Rheumatol 24:2299–2303PubMedGoogle Scholar
  11. 11.
    Katzenstein AA (2006) Katzenstein and Askin’s surgical pathology of non-neoplastic lung disease, 4th edn. Saunders, New YorkGoogle Scholar
  12. 12.
    Alarcón GS, Kremer JM, Macaluso M, Weinblatt ME, Cannon GW, Palmer WR, St Clair EW, Sundy JS, Alexander RW, Smith GJ, Axiotis CA (1997) Risk factors for methotrexate-induced lung injury in patients with rheumatoid arthritis. A multicenter, case-control study. Methotrexate-Lung Study Group. Ann Intern Med 127:356–364CrossRefPubMedGoogle Scholar
  13. 13.
    Harigai M, Koike R, Miyasaka N, Pneumocystis Pneumonia under Anti-Tumor Necrosis Factor Therapy (PAT) Study Group (2007) Pneumocystis pneumonia associated with infliximab in Japan. N Engl J Med 357:1874–1876CrossRefPubMedGoogle Scholar
  14. 14.
    Lee SH, Huh KH, Joo DJ, Kim MS, Kim SI, Lee J, Park MS, Kim YS, Kim SK, Chang J, Kim YS, Kim SY (2017) Risk factors for Pneumocystis jirovecii pneumonia (PJP) in kidney transplantation recipients. Sci Rep 7:1571CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Sanno K, Hatanaka N, Yamagishi T, Kamemura H, Hirano Y, Kodaka N, Miura A, Kitahara A, Sawata T, Hosaka K, Nakazawa I (2007) Pneumocystis pneumonia in a patient with type 2 diabetes mellitus. Intern Med 46:1131–1133CrossRefPubMedGoogle Scholar
  16. 16.
    Kameda H, Fujii T, Nakajima A, Koike R, Sagawa A, Kanbe K, Tomita T, Harigai M, Suzuki Y, Japan College of Rheumatology subcommittee on the guideline for the use of methotrexate in patients with rheumatoid arthritis (2018) Japan College of Rheumatology guideline for the use of methotrexate in patients with rheumatoid arthritis. Mod Rheumatol.

Copyright information

© International League of Associations for Rheumatology (ILAR) 2018

Authors and Affiliations

  • Kota Shimada
    • 1
    Email author
  • Kyoko Yokosuka
    • 1
  • Takahiro Nunokawa
    • 1
  • Shoji Sugii
    • 1
  1. 1.Department of Rheumatic DiseasesTokyo Metropolitan Tama Medical CenterFuchu CityJapan

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