Leflunomide/methotrexate/prednisone

Abstract

Invasive pulmonary aspergillosis: case report A 56-year-old woman developed invasive pulmonary aspergillosis during immunosuppression therapy with leflunomide, methotrexate and prednisone. The woman, whose medical history was notable for juvenile rheumatoid arthritis and cavitary lung disease secondary to Mycobacterium avium-intracellulare infection, for which she had been previously treated with clarithromycin, ethambutol and rifabutin, with left upper lobectomy in 2017, subsequently presented to hospital with new-onset productive cough. She had been receiving leflunomide, methotrexate and prednisone 2.5mg daily [routes not stated; not all dosages stated]. CT scan showed a new cavitary lesion in her right upper lobe, with worsening airway inflammation. Sputum culture showed Mycobacterium chimaera. Therefore, leflunomide and methotrexate were discontinued, and the woman resumed clarithromycin, ethambutol and rifabutin. Two months later, CT scan revealed improvement, with almost complete resolution of the cavity. However, at 6 months, her symptoms progressed; CT scan showed enlargement of the cavity. Notably, β-D-glucan and aspergillus galactomannan were found to be negative. Thereafter, she underwent electromagnetic navigation bronchoscopy with brushing, bronchoalveolar lavage and transbronchial biopsy. Analysis of tissue specimen revealed necrotising granulomas. Multiple sputum cultures performed over a span of 4 months, and the bronchoscopic specimens tested negative for bacterial, fungal and acid-fast bacilli. Amikacin was added to her ongoing regimen. Six weeks later, CT scan revealed further enlargement of the cavity. She was admitted and robotic right upper lobectomy with right middle lobe wedge resection was performed for diagnosis and control of disease. Growth of Aspergillus fumigatus was observed on tissue culture, and pathology showed eosinophilic pneumonia and fungal forms, compatible with invasive fungal infection. The development of the invasive pulmonary aspergillosis was attributed to the immunosuppression caused by leflunomide, methotrexate and prednisone [times to reaction onset not stated]. She was subsequently treated with voriconazole with good outcome.