SESSION TYPE: ILD Global Case Report Posters
PRESENTED ON: Tuesday, October 23, 2012 at 01:30 PM - 02:30 PM
INTRODUCTION: : Sirolimus (SRL) is a macrolide antibiotic with potent immunosuppressant effects. It inhibits G1- to S-phase cell division and, therefore, cell proliferation. It is used in chronic transplant rejection. It has rarely been associated with pulmonary toxicity. Pulmonary Alveolar Proteinosis (PAP) is a rare disease which has been described as a side effect of Sirolimus. We describe a case of PAP developed in a renal transplant following treatment with Sirolimus for chronic graft rejection
CASE PRESENTATION: We present a 34-year-old woman who had renal transplant in childhood in India. The primary cause of renal failure is not known. She has developed chronic rejection and chronic allograft dysfunction. Her immunosuppressant therapy were modified to include SRL .Three years after initiating SRL, she presented complaining of generalized fatigability, low grade fever, nausea and vomiting for 6 months duration followed by progressive dyspnoea and nonproductive cough of 1 month duration. Her examination showed tachypnea, emaciation and bilateral inspiratory rales (crackles) on chest examination. Biochemical profile showed chronic renal impairment (chronic rejection) with hypocalcaemia. She had been treated as lower respiratory tract infection but later presented in respiratory failure and was intubated and mechanically ventilated. The CXR showed bilateral infiltrate but her computed tomography (CT) of the chest showed ground-glass opacification with ‘‘Crazy paving’’ pattern. Bronchoscopy with bronchoalveolar lavage was done and showed Periodic acid-Schiff (PAS) positive material suggestive of PAP .Diagnosis of pulmonary alveolar proteinosis (PAP) was made and drug-induced toxicity was suspected. SRL was withdrawn with marked improvement in the patients’ clinical and radiological status . Other potential causes like atypical infections had been excluded.
DISCUSSION: Pulmonary alveolar proteinosis (PAP) is a rare disease, described first by Rosen in 1958. It is characterized by abnormal alveolar accumulation of lipoproteinaceous surfactant-like material in alveoli and distal bronchioles due to defective surfactant clearance by macrophages.SRL has been described to cause PAP in few reports in the English Literature. The treatment of PAP includes whole lung lavage (WLL), Macrophage-Granulocyte Colony stimulating factor (MG-CSF) inhaled or subcutaneously. In SRL-associated PAP, due to paucity of data , there is no consensus on treatment and so we elected to stop the drug and WLL was not done due to patient morbidity although a partial lobar lavage was done. Stopping Sirolimus and replacing it with a different immunosuppressant like Tacrolimus may lead to resolve the disease. Time to develop the disease has been reported up to 2 years and to resolve it after stopping Sirolimus up to three months
CONCLUSIONS: Sirolimus is associated with various manifestations of pulmonary toxicity. It is mandatory to exclude infections as a cause of lung disease first. Alveolar proteinosis is a rare disease and requires vigilance to diagnose it and so avoid the morbidity and mortality associated with it. Sirolimus is associated with different pulmonary manifestations of which pulmonary alveolar proteinosis is rare but still gives further insight to the pathophysiology of PAP. Our patient recovered after stopping the medication which gave further evidence that Sirolimus was the cause of the PAP.
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2) Kadikoy H, Paolini M, Achkar K, et al. Pulmonary alveolar proteinosis in a kidney transplant: a rare complication of sirolimus. Nephrol Dial Transplant. Aug 2010;25(8):2795-2798.
3) Pedroso SL, Martins LS, Sousa S, et al. Pulmonary alveolar proteinosis: a rare pulmonary toxicity of sirolimus. Transpl Int. Mar 2007;20(3):291-296.
DISCLOSURE: The following authors have nothing to disclose: Abdelhaleem Bella, Hatem Qutub, Rakesh Gupta, Maryam Aleissa, Essam Syed
No Product/Research Disclosure InformationDammam University, Khobar, Saudi Arabia