1 To date, there have been only a few case reports of granulomatous
interstitial pneumonitis associated with sirolimus. We describe a patient with polycystic kidney disease with renal transplantation who was switched to sirolimus two months before developing granulomatous interstitial pneumonitis. A 53-year-old woman, a non smoker with a past medical history of hypertension and ESRD secondary to polycystic kidney disease, underwent deceased donor kidney transplantation in 2006. Her medications were changed from mTOR inhibitor tacrolimus and mycophenolic acid to cyclosporine 25 mg twice a day and sirolimus 3 mg daily approximately two months before admission. She presented with fever, malaise, progressive shortness of breath, and cough with minimal sputum for 2 weeks. She did not have any other symptoms. Physical examination showed stable vital signs, O2 saturation 96% on room air, and bilateral basilar fine crackles. Lab tests showed a Hb 8.4 g/dl, Hct 24%, MCV 77 fL, WBC 2.5 kU/l, neutrophils 55%, lymphocytes 32%, eosinophils 0.1%, platelets 141 kU/l, sodium 136 mmol/l, see more potassium 4.2 mmol/l, chloride 102 mmol/l, bicarbonate 22 mmol/l, BUN 15 mg/dl, creatinine 0.9 mg/dl, and normal liver enzyme. Her sirolimus level was high at 28.5 ng/dl. Urinalysis did not show pyuria or hematuria.
Chest radiograph revealed bilateral thickened interstitial markings (Fig. 1). Computed tomography scan of the chest without contrast showed ill-defined patchy ground glass opacities in both lungs (Fig. 2). Cultures were obtained, and antibiotic drugs were started to cover
community-acquired pneumonia. The patient remained tachypneic and desaturated. Broad spectrum antibiotic drugs were continued with Amobarbital an antifungal drug (Mycamine) and trimethoprim and sulfamethoxazole. BAL fluid studies were negative for bacteria, viruses, AFB, and fungi. BAL culture for mycobacteria was also negative at eight weeks. The direct antigen for PCP was negative. She underwent video-assisted thoracoscopic biopsy which showed granulomas, interstitial fibrosis, and focal organizing pneumonia (Fig. 3). She has a normal angiotensin converting enzyme level. The results were highly suspicious for sirolimus induced granulomatous interstitial pneumonitis, and sirolimus was stopped. The patient was started on methylprednisolone 40 mg IV every 12 h. She improved and was discharged on prednisone 30 mg/day, cyclosporine 200 mg/day, and leflunomide 15 mg/day. She was remarkably better two weeks later. Repeat computed tomography scan of the chest one month later showed near complete resolution of the previously seen interstitial lung disease, but some mild interstitial lung disease remained with peripheral interlobular septal thickening (Fig. 4). Sirolimus, initially known as rapamycin, is a macrolide antibiotic derived from the actinomycete “Streptomyces hygroscopicus”.