New friend, old foe: Anti-interleukin-6 agents increase risk of Pneumocystis jirovecii pneumonia

Abstract

Introduction Anti-interleukin-6 agents such as Tocilizumab (Actemra) are increasingly being used in patients with rheumatoid arthritis who did not have good clinical response to TNF (Tumor necrosis factor) inhibitors. Interleukin-6 is a key cytokine in the pathogenesis of several autoimmune disorders. Pneumocystis jirovecii is an opportunistic pathogen that causes pneumonia in immunocompromised patients such as HIV positive individuals with low CD4 count. There is limited data about the risk of pneumocystis pneumonia associated with newer biological agents. We report a rare case of Pneumocystis jirovecii pneumonia in a rheumatoid arthritis patient without HIV, associated with anti-interleukin-6 agent. Case description A 65-year-old female with rheumatoid arthritis, presented with progressive shortness of breath over a period of 3 weeks. She was receiving methotrexate and a biological interleukin-6 receptor blocker (Tocilizumab). She had a non productive cough and gradually progressing shortness of breath. She did not have fever or rigors. CT Chest angiogram was negative for pulmonary embolism, but did note extensive diffuse ground-glass opacity throughout both lungs, predominantly in the upper lobe. Hemoglobin was 14.9g/dL, White count 13.4X10(9)/L, platelet count 147X10(9)/L, Creatinine 0.83mg/dL, CRP 8.8mg/L. Results and conclusions Her clinical picture was suggestive of Pneumocystis jirovecii pneumonia. Bronchoalveolar lavage cultures, bacterial, fungal, viral and mycobacterial were negative. Pneumocystis jirovecii PCR was negative. Serum Beta-D-Glucan, a component of cell wall of Pnemocystis jirovecii was high (>500pg/ml) and elevated levels have been reported to have high sensitivity and specificity in its diagnosis. Clinical picture, radiological findings and elevated serum Beta-D-Glucan (Fungitell) supported the diagnosis of Pneumocystis jirovecii. Patient recovered with oral Atovaquone for 21 days and tapering course of oral Prednisone. Repeat imaging showed complete resolution and Serum Beta-D-Glucan level trended down. Take-home message Interleukin-6 receptor blocker, used in patients with rheumatoid arthritis increase the risk of pneumocystis pneumonia, an opportunistic infection. Serum Beta-D Glucan test can be used as non-invasive testing modality to diagnose pneumocystis pneumonia in non-HIV patients with good sensitivity and specificity. Serial Beta-D Glucan levels may be used to monitor with clinical progress. Molecular methods such as Pneumocystis jirovecii PCR (Polymerase chain reaction) may be falsely negative in non-HIV patient.