Sirolimus

Abstract

Lung injury: case report A 67-year-old man developed lung injury during immunosuppressive treatment with sirolimus. The man had a kidney transplant from a living-related donor for end-stage renal disease caused by hypertension and diabetes 12 years previously. Subsequently, he was hospitalised with cough, exertional dyspnoea and fever. Before the presentation, he had received immunosuppressive treatment with mycophenolate and tacrolimus. However, due to complications of chronic allograft dysfunction, his treatment with tacrolimus was switched to sirolimus [route and dosage not stated]. His sirolimus level was stable, except for few weeks prior to the presentation, when the sirolimus was at a higher therapeutic range. Upon evaluation, he had tachypnoea with low oxygen saturation. Chest auscultation showed basal fine crackles. He had a normal WBC count, except for a high level of CRP. The CT scan and chest radiography showed several areas of ground glass and patchy densities. His sputum culture was negative. Empirical unspecified broad-spectrum antibiotics did not reveal radiological or clinical response. The fluorodeoxyglucose positron emission tomogram (FDG-PET) scan revealed elevated uptake in the area of lung opacities with a standard uptake value of 4.7, suggestive of intense inflammation. Transbronchial biopsy, bronchoscopy and bronchoalveolar lavage were performed. In lavage fluid, cell counts were as follows: neutrophils: 54%, lymphocytes: 12%, monocytes: 14%, eosinophils: 3% and lining cells: 5%. The fluid cultures, cytology and bronchoalveolar lavage aspergillus galactomannan test showed negative results. No signs of virus cytopathy, virus or atypical bacteria were observed. His serum TB-QuantiFERON test was non-reactive. Based on transbronchial biopsy, post-transplant lymphoproliferative disorders were ruled out. The transbronchial biopsy revealed alveolated lung tissue and infiltration of foamy macrophages without any evidence of malignant cells. In-situ hybridization showed negative results for the Epstein-Barr virus. His serum sirolimus range was normal. However, in the weeks before the symptoms of lung toxicity, his sirolimus level was in the range of high normal. After ruling out infection, a diagnosis of sirolimus-induced lung injury was made [duration of treatment to reaction onset not stated]. Therefore, the man’s treatment with sirolimus was changed to tacrolimus, which resulted in the improvement of clinical symptoms. His oxygen saturation also became normal. On follow-up after six weeks, he became asymptomatic. The chest CT scan revealed complete resolution of lung opacities, and his CRP level became normal.