Sirolimus-induced interstitial lung disease following pediatric stem cell transplantation Garrod AS, Goyal RK, Weiner DJ. (2015) Sirolimus-induced interstitial lung disease following pediatric stem cell transplantation. Pediatr Transplant, 00: 1–3. DOI: 10.1111/petr.12438. Abstract: Sirolimus-induced ILD is a known but rare complication in adults who have undergone SOT. However, little is known about this adverse effect in children. Diagnosis of sirolimus-induced ILD can be challenging, especially in patients who have difficulty participating in lung function testing. We present a case of presumed sirolimus-induced ILD in a pediatric stem cell transplant patient who developed polycythemia and hypoxemia. To our knowledge, no other cases of sirolimus-induced pulmonary toxicity in children after HCT have been reported. Andrea S. Garrod 1 , Rakesh K. Goyal 2 and Daniel J. Weiner 3 1 Division of Pediatric Respiratory Medicine, Department of Pediatrics, University of Virginia, Charlottesville, VA, USA, 2 Blood and Marrow Transplantation and Cellular Therapies, Department of Pediatrics, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA, 3 Divisions of Pulmonary Medicine, Allergy and Immunology, Department of Pediatrics,Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA Key words: pediatrics – hematopoietic stem cell transplantation – sirolimus – interstitial lung disease – lung function tests Daniel J. Weiner, MD, Division of Pulmonary Medicine, Children’s Hospital of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA 15224, USA Tel.: +1 412 692 5630 Fax: +1 412 692 6645 E-mail: Daniel.weiner@chp.edu Accepted for publication 9 January 2015 Sirolimus is an immunosuppressive medication used commonly for prophylaxis and treatment of graft-versus-host disease in SOT and allogeneic HCT patients (1). Side effects include thrombo- cytopenia, hyperlipidemia, and rarely pulmonary toxicity (2). The vast majority of the respiratory complications have been reported in adult SOT patients (3) and have never been reported in a pediatric HCT patient. When interstitial pneu- monitis develops, patients present with symp- toms including dyspnea, fatigue, fever, and rarely hemoptysis (3). Chest radiography and computed tomography scans are characterized by bilateral interstitial infiltrates. Bronchoalveo- lar lavage fluid typically indicates a lymphocytic alveolitis and rarely shows evidence of hemor- rhage. Pulmonary function testing demonstrates a restrictive defect reflecting the interstitial findings (2). Case history An eight-yr-old boy with a history of acute lym- phoblastic leukemia and subsequent myelodys- plastic syndrome underwent allogeneic matched HCT. His post-transplantation course was com- plicated by severe acute and chronic graft-versus- host disease of the skin and gut which was trea- ted with sirolimus. Two yr after transplant, he was noted to have nocturnal hypoxemia and polycythemia while hospitalized for Clostridium difficile colitis. He reported dyspnea and dry cough with exercise, and examination was notable for digital club- bing. A bronchoalveolar lavage was performed which did not detect any pathogens but con- tained a lymphocytic predominance. Chest radio- graph revealed diffuse reticulonodular opacities (Fig. 1a). Computed tomography of the chest demonstrated a non-specific pattern of interstitial prominence in both lungs sparing the apices and the extreme periphery (Fig. 1b). Spirometry and lung volumes were suggestive of a restrictive defect that worsened over time (Table 1). Due to concerns about his technique, he underwent a Abbreviations: HCT, hematopoietic stem cell transplanta- tion; ILD, interstitial lung disease; SOT, solid organ trans- plant. 1 Pediatr Transplantation 2015 © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Pediatric Transplantation DOI: 10.1111/petr.12438