Authors
C. SCHOONJANS (1), A. GEERTS (2), H. DEGROOTE (2), H. VAN VLIERBERGHE (2), E. VAN BRAECKEL (3), X. VERHELST (2) / [1] UZ Gent, Gent, Belgium, gastroenterology, [2] UZGent, Gent, Belgium, gastroenterology, [3] UZGent, Gent, Belgium, Pulmonology
Christophe Schoonjans, Anja Geerts, Helena Degroote, Hans Van Vlierberghe, Eva Van Braeckel, Xavier Verhelst. UZ Gent A 68-year old patient was admitted to the hospital because of shortness of breath and a dry cough, starting right after a trip to Dubai. Six years ago, he underwent an orthotopic liver transplantation because of alcoholic liver cirrhosis with a small HCC (2 cm), taking immunosuppressive medication (everolimus and mycophenolic acid). Three years ago, he had a coronary artery bypass graft. Blood examination showed minimal inflammation, with no signs of cardiac ischemia. Arterial blood gas showed hypoxia. Chest radiograph showed an interstitial lung pattern, with reticulonodular opacities. CT scan confirmed this with the image of a fibrotic end stage of an interstitial pneumonia. Echocardiography showed minimal decrease in systolic function, inferior akinesia and slightly elevated pulmonal pressure (36 mmHg + CVP). Pulmonary function test was restrictive (being normal pre-transplantation), with TLC of 57% and DLCO of 37%. Everolimus drug level was subtherapeutic (1.3 ng/ml). Infectious serology (including chlamydia/mycoplasma pneumoniae), Mantoux test, autoimmune serology and bronchoscopy with bronchoalveolar lavage (with PCR for Pneumocystis Jirovecii Pneumoniae) was negative. No anamnestic arguments for hypersensitivity pneumonitis. Based on exclusion of other causes, an everolimus-induced interstitial lung disease was suspected. For that matter, everolimus was replaced by tacrolimus. Gradually the oxygen dependence of our patient decreased, as did the symptoms. Five months later chest CT showed decrease of the interstitial/fibrotic findings, lung function tests improved (TLC 63% and DLCO 46%) and our patient did not need oxygen therapy anymore. During the course the persisting normal liver enzymes proved no arguments for liver rejection. In the literature case reports of interstitial lung disease (ILD) under treatment with mTOR (mammalian target of rapamycin) inhibitors were published in solid organ transplant patients (mainly renal), breast and neuro-endocrine tumours. Most of the data come from sirolimus, with better toleration for everolimus. Typically, there is no correlation to the everolimus concentration (as in our case with subtherapeutic levels). Immediate withdrawal of the drug is indicated, and there is no clear benefit from the addition of steroids in terms of improvement of symptoms. To our knowledge this is only the second case of everolimus induced ILD reported in a liver transplant patient, and the first one in which the outcome is not fatal. [1,2] Therefore, clinical suspicion needs to be high in every patient treated with a mTOR inhibitor (sirolimus as well as everolimus) presenting with new onset of pulmonary symptoms. Representative lung CT images can be shown during case presentation. References 1. Lopez et al. Interstitial lung disease associated with mTOR inhibitors in solid organ transplant recipients: results from a large phase III clinical trial program of everolimus and review of the literature. J Transplant, 2014 (2014), p. 305931 2. J. Schrader et al. Everolimus-induced pneumonitis: report of the first case in a liver transplant recipient and review of treatment options, Transplant International, vol. 23, no. 1, pp. 110–113, 2010.
