Clinical and Radiological Features of Acute-Onset Diffuse Interstitial Lung Diseases in Patients with Rheumatoid Arthritis Receiving Treatment with Biological Agents: Importance of <i>Pneumocystis</i> 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.

Risk Factors for <i>Pneumocystis jiroveci</i> Pneumonia in Glomerulonephritis Patients Receiving Immunosuppressants

“…Therefore, we cannot completely exclude the possibility of false negative results in the remaining 66 cases. On the other hand, serum β-D-glucan is a reliable diagnostic marker for PJP (23)(24)(25). Because the sensitivity for PJP is very high, serum β-D-glucan can be used as a screening tool for PJP, especially for patients who are not suitable for the BAL procedure (23,24).…”

Comorbidities in interstitial lung diseases

“…For instance, acute-onset diffuse ILD in patients with rheumatoid arthritis on treatment with biological agents is commonly due to Pneumocystis jirovecii infection [24]. The dilemma for the clinician is whether to increase or decrease the level of immunosuppression and institute intensive treatment for infection, tailored to cultured microorganisms.…”

Clinical Manifestations and Prognostic Factors of <b><i>Pneumocystis jirovecii</i></b> Pneumonia without HIV

“…Some have documented that high A-aΔO 2 , combined bacteremia, elevated BUN, and preexisting lung disease are independent factors for a poor prognosis [21,22]. It has also been reported that early diagnosis and treatment initiation could lead to improved survival in non-HIV PCP [14,15,16,17,18,19,20,21,23,24]. Other studies evaluated by multivariate analyses that low serum albumin levels and mechanical ventilation are independent predictors of mortality [25,26].…”

“…The diagnosis of PCP was made according to the following criteria: (1) a positive PCR of P. jirovecii on samples of sputum or BAL fluid (BALF), (2) radiological findings on high-resolution chest computerized tomography (HRCT) such as unilateral or bilateral ground-grass opacity (GGO), and/or patchy consolidation, which are compatible with PCP [14,15,16], (3) compatible clinical symptoms including fever, cough, sputum, and dyspnea. Patients who had neither radiological findings nor clinical symptoms compatible with PCP, with a positive PCR of P. jirovecii but negative conventional staining (Grocott's stain or Diff-Quik), were considered as colonization cases and excluded from the study.…”