Drug-Induced Lung Injury: A Case of Pneumonitis Caused by Leflunomide

Abstract

Drug-induced lung injury includes a wide spectrum of diseases. Disease-modifying antirheumatic drugs (DMARDs), especially methotrexate, are a well-known cause of lung damage. An association between leflunomide and lung toxicity has been reported in the literature, but actual incidence remains unknown. CASE PRESENTATION:A 66-year-old Caucasian female presented to the emergency department with worsening dyspnea on exertion for 3 days and chest pressure for 1 day. She had a history of right nephrectomy for renal cell cancer 13 years ago, rheumatoid arthritis (RA), and stage 3 chronic kidney disease. She was started on Leflunomide 1 month ago for RA. She was a nonsmoker. Vital signs on presentation were pulse 102/min, blood pressure 156/95mmHg, respiratory rate 24/min, oral temperature 98.5 F, and SpO2 88-90% breathing on room air. Lung exam revealed bilateral rales more on left than right. Blood work showed normal cell count and metabolic panel other than elevated creatinine 1.19 mg/dl (N: 0.6-1.0 mg/dl). Cardiac workup was unremarkable. Chest X-ray showed right basal atelectasis. CT angiography of the chest did not show pulmonary embolism but bilateral apical mosaic attenuation and right middle and left lower lobe alveolar opacities were noted. The patient was started on antibiotics for community-acquired pneumonia and supplemental oxygen via nasal cannula. Further workup including serum ANA, ANCA panel, ESR, CRP, procalcitonin, and respiratory pathogen panel was unremarkable. Despite getting antibiotics patient's symptoms did not improve. She was started on methylprednisone 62.5 mg IV followed by oral prednisone 40 mg daily due to concern of drug-induced lung injury. The patient's respiratory status improved, and she was discharged in the next 48 hours with oral prednisone taper. Leflunomide was discontinued. A repeat CT scan of the chest in 3 months showed resolution of the above-mentioned abnormalities.DISCUSSION: RA is a multisystem disease and has various pulmonary manifestations. DMARDs used to treat RA are also known to cause lung damage. Determining the relationship between these medications and adverse pulmonary events is challenging. Leflunomide-induced ILD generally occurs after a duration of 2-13 weeks of treatment. Common imaging findings are bilateral diffuse, patchy ground-glass opacities or consolidation usually in upper, anterior, and central fields. Honeycombing can also be seen. Factors that increase the risk of ILD are a history of methotrexate use, pre-existing ILD, and cigarette smoking. Management involves drug discontinuation, high-dose corticosteroids, and cholestyramine washout.CONCLUSIONS: Leflunomide can cause pneumonitis either as monotherapy or in conjunction with methotrexate. A high degree of suspicion is required to suspect this complication so that it can be managed effectively.