Abstract Introduction Organizing pneumonia (OP) is defined as a clinico-pathological syndrome of lung diseases. Cryptogenic OP (COP) accounts for more than half of the cases. Secondary causes are rare, with a mean annual incidence of secondary OP at 0.87/100,000. The most frequent secondary causes are infections (45%), drug-related toxicity (20%), and malignancy (15%). Sirolimus, a mammalian target of rapamycin (mTOR) inhibitor discovered in 1972, is widely used for immunosuppression after solid-organ transplantation, particularly as an alternative to calcineurin inhibitors in patients with renal dysfunction, graft vascular disease, or malignancy. Case We report the case of a 70-year-old female, who received a heart transplant 7 years ago. Her clinical course was complicated by difficulty optimizing immunosuppression due to medications adverse events. Two months after initiation of sirolimus therapy, the patient underwent imaging to exclude lymphoproliferative disorders due to elevated Epstein Barr virus (EBV) titers. A positron emission tomography (PET) scan ruled out EBV-related diseases, however it incidentally demonstrated extensive right-sided ground-glass opacities (GGOs) with peripheral metabolic activity. The patient was entirely asymptomatic. Repeat computed tomography (CT) scans at 3 and 6 months showed spatiotemporal migrating GGOs. Extensive infectious workup was negative. Bronchoscopy with bronchoalveolar lavage and transbronchial biopsies showed focal chronic inflammation, increased pigmented macrophages, no granulomas and no dysplastic cells. These findings were consistent with an organizing pneumonia. Given the temporal association with sirolimus and the lack of alternative etiologies, Sirolimus-induced OP was presumptively diagnosed. After a multidisciplinary discussion, sirolimus was discontinued and replaced with an alternative regimen. Six months later, repeat CT scan demonstrated complete radiographic resolution, confirming causality. Discussion To our knowledge, this is the first reported case of asymptomatic sirolimus-induced OP in a heart-transplant recipient. Only 6% of OP patients are asymptomatic, typically detected incidentally. Although the mechanism of mTOR-inhibitor pulmonary toxicity remains unclear, pneumonitis is the most frequent manifestation; OP is rare. Late conversion to sirolimus and pre-existing renal impairment increase the risk of pulmonary toxicity, both present in this case. Clinicians should think of drug-induced pulmonary toxicity in transplant recipients receiving mTOR inhibitors. The significance and outcomes of an asymptomatic disease remain unclear, but early discontinuation of the offending agent remains the mainstay management to avoid progression of disease. This abstract is funded by: None
Azzam et al. (Fri,) studied this question.