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

Hideto Kameda; Hitoshi Tokuda; Fumikazu Sakai; Takeshi Johkoh; Shunsuke Mori; Yuji Yoshida; Noboru Takayanagi; Hirofumi Taki; Yoshinori Hasegawa; Kazuhiro Hatta; Hisashi Yamanaka; Makoto Dohi; Shu Hashimoto; Hidehiro Yamada; Shinichi Kawai; Tsutomu Takeuchi; Kazuhiro Tateda; Hajime Goto

doi:10.2169/internalmedicine.50.4508

ORIGINAL ARTICLES

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

Hideto Kameda, Hitoshi Tokuda, Fumikazu Sakai, Takeshi Johkoh, Shunsuke Mori, Yuji Yoshida, Noboru Takayanagi, Hirofumi Taki, Yoshinori Hasegawa, Kazuhiro Hatta, Hisashi Yamanaka, Makoto Dohi, Shu Hashimoto, Hidehiro Yamada, Shinichi Kawai, Tsutomu Takeuchi, Kazuhiro Tateda, Hajime Goto

Author information

Hideto Kameda
Division of Rheumatology, Department of Internal Medicine, School of Medicine, Keio University, Japan
Hitoshi Tokuda
Department of Internal Medicine, Social Health Insurance Central General Hospital, Japan
Fumikazu Sakai
Department of Diagnostic Radiology, Saitama International Medical Center, Saitama Medical University, Japan
Takeshi Johkoh
Department of Radiology, Kinki Central Hospital of Mutual Aid Association of Public Teachers, Japan
Shunsuke Mori
Clinical Research Center for Rheumatic Disease and Department of Rheumatology, NHO Kumamoto Saishunsou National Hospital, Japan
Yuji Yoshida
Division of Rheumatic Diseases, National Center for Global Health and Medicine, Japan
Noboru Takayanagi
Department of Respiratory Medicine, Saitama Cardiovascular and Respiratory Center, Japan
Hirofumi Taki
The First Department of Internal Mediceine, University of Toyama, Japan
Yoshinori Hasegawa
Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Japan
Kazuhiro Hatta
Department of General Internal Medicine, Tenri Hospital, Japan
Hisashi Yamanaka
Institute of Rheumatology, Tokyo Women's Medical University, Japan
Makoto Dohi
Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Japan
Shu Hashimoto
Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, Japan
Hidehiro Yamada
Division of Rheumatology and Allergy, Department of Medicine, St. Marianna University School of Medicine, Japan
Shinichi Kawai
Division of Rheumatology, Department of Internal Medicine, Toho University School of Medicine, Japan
Tsutomu Takeuchi
Division of Rheumatology, Department of Internal Medicine, School of Medicine, Keio University, Japan
Department of Rheumatology/Clinical Rheumatology, Saitama Medical Center, Saitama University, Japan
Kazuhiro Tateda
Department of Microbiology and Infectious Diseases, Toho University School of Medicine, Japan
Hajime Goto
Department of Respiratory Medicine, Kyorin University School of Medicine, Japan

Keywords: β-D-glucan, high-resolution computed tomography, Pneumocystis pneumonia, rheumatoid arthritis, tumor necrosis factor inhibitor

JOURNAL OPEN ACCESS

2011 Volume 50 Issue 4 Pages 305-313

DOI https://doi.org/10.2169/internalmedicine.50.4508

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Abstract

Objective Acute-onset diffuse interstitial lung disease (AoDILD) in patients with rheumatoid arthritis (RA) has been a serious concern, especially for those under treatment with biological agents which may affect the presentation and outcome of AoDILD, including Pneumocystis pneumonia (PCP). Therefore, we conducted a retrospective, multi-center study of AoDILD in RA patients receiving biological agents.
Methods Patients who developed AoDILD while receiving biological agents (infliximab, etanercept, adalimumab and tocilizumab) were enrolled in the study. Definite PCP was defined as patients who showed either P. jirovecii organisms in their respiratory samples by microscopic examination, or positive tests for both P. jirovicii DNA-PCR with respiratory samples and an elevated serum 1,3-β-D-glucan level above the cut-off value. Probable PCP was defined as either a positive test for P. jirovicii PCR or an elevated serum β-D-glucan level. Chest HRCT findings were evaluated and scored by two board-certified radiologists.
Results The final diagnoses for 26 patients examined were definite PCP for 13 patients, probable PCP for 11, and methotrexate-associated pneumonitis in 2 patients. Definite and probable PCP cases were clinically indistinguishable. Generalized, diffuse ground-glass opacity (GGO) is the characteristic HRCT finding in patients with definite or probable PCP, which was different from our previous findings in RA patients, mostly without biologics, showing GGO distributed in a panlobular or multilobular manner. The clinical outcome was favorable by treatment with trimethoprim-sulfamethoxazole and glucocorticoids.
Conclusion The possibility of PCP should be intensively investigated in RA patients developing AoDILD while receiving biological agents.

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