title: 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.
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.
  
  
  CONCLUSIONS
  The possibility of PCP should be intensively investigated in RA patients developing AoDILD while receiving biological agents.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, School of Medicine, Keio University, Japan. kamehide@z6.keio.jp
authors.forename: Hideto
authors.initials: H
authors.lastname: Kameda
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tokuda
authors.forename: Fumikazu
authors.initials: F
authors.lastname: Sakai
authors.forename: Takeshi
authors.initials: T
authors.lastname: Johkoh
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Mori
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Noboru
authors.initials: N
authors.lastname: Takayanagi
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Taki
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Hatta
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yamanaka
authors.forename: Makoto
authors.initials: M
authors.lastname: Dohi
authors.forename: Shu
authors.initials: S
authors.lastname: Hashimoto
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Yamada
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kawai
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tateda
authors.forename: Hajime
authors.initials: H
authors.lastname: Goto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects; D018501:Antirheumatic Agents / Q000009:adverse effects; D001172:Arthritis, Rheumatoid / Q000150:complications* / Q000628:therapy*; D001688:Biological Products / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007564:Japan; D017563:Lung Diseases, Interstitial / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000209:etiology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011020:Pneumonia, Pneumocystis / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000209:etiology* / Q000628:therapy; D012189:Retrospective Studies; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D001688:Biological Products