Tacrolimus-Induced Diffuse Lung Injury

• Published in: Journal of cardiac failure Vol. 30; no. 1; p. 303
• Main Authors: Agarwal, Khushboo, Gupta, Richa, Rodrigo, Maria E., Tangri, Apoorva, Sheikh, Farooq H., Lam, Phillip H.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.01.2024
• ISSN: 1071-9164; 1532-8414
• DOI: 10.1016/j.cardfail.2023.10.444

Tacrolimus is a mainstay of immunosuppression after solid organ transplant to prevent organ rejection. While it has several well-established toxicities including kidney injury and central nervous system disturbances, its association with diffuse lung injury is rare. A 52-year-old man who underwent heart transplantation for genetic cardiomyopathy presented to the clinic three weeks post-transplant with subjective fever, night sweats, and exertional dyspnea. He was maintained on standard immunosuppression with tacrolimus, mycophenolate mofetil, and prednisone taper. Extensive workup for bacterial, viral, and fungal infections was unremarkable. Serial surveillance protocol right heart catheterizations showed normal filling pressures and hemodynamics, with no evidence of rejection on endomyocardial biopsies. CT chest, abdomen, and pelvis (Image A) at eight weeks since the first reported symptom onset was only notable for a new 5 mm lung nodule. The patient had gradually progressive dyspnea and hypoxia for which he underwent serial imaging. At twelve weeks, CT chest showed progression to multiple bilateral pleural-based lung nodules measuring up to 8mm. FDG-PET/CT (Image B) showed low-level activity and FDG uptake in some nodules concerning for malignancy or atypical infection. Given the peripheral location of the nodules, video-assisted thoracoscopic surgery and wedge resection was performed. Histopathology revealed nodules with abscess formation and fibrin deposits with no evidence of malignancy, granuloma, or infection. At six months, CT chest (Image C) revealed new diffuse bilateral ground glass opacities. Bronchoalveolar lavage showed no evidence of atypical microbial growth. After extensive discussions with pulmonology and infectious disease consultants, drug toxicity secondary to Tacrolimus was presumed to be the culprit. He was switched to Cyclosporine. After four weeks of Tacrolimus discontinuation, he had resolution of symptoms, and repeat imaging (Image D) demonstrated complete resolution of lung opacities with decreasing size of nodules. Tacrolimus was discontinued indefinitely. Though described in case series in patients with rheumatoid arthritis, to the best of our knowledge, this is the first reported case of Tacrolimus-associated diffuse lung injury after a cardiac transplant. Extrapolating from data for rheumatoid arthritis, the lung injury is hypothesized to be a result of inflammatory cytokine-mediated endothelial injury. This could potentially explain the FDG uptake seen in our patient. Tacrolimus-associated diffuse lung injury, although rare, should be considered in patients who present with diffuse infiltrates, after appropriate workup to exclude other processes including malignancy and infection.