Sirolimus (SRL) is a potent immunosuppressant drug being used with increasing frequency in solid organ transplant patients. Pulmonary toxicity secondary to SRL has been shown to cause interstitial pneumonitis, BOOP, alveolar hemorrhage and noncardiogenic pulmonary edema. Pulmonary alveolar proteinosis (PAP) is a rare pulmonary toxicity of SRL. There are only three reported cases, two in lung and one in renal transplant patient, of PAP secondary to SRL. We present a case of PAP in a 54 yr old man with cadaveric renal transplant which was treated by discontinuing Sirolimus.
A 54 year-old male with a history of cadaveric renal transplant presented with 1 month history of increasing dyspnea, 4 pillow orthopnea and dry cough. His medications included mycophenolate, SRL, prednisone and Bactrim. A month prior to his admission he was treated for presumed pneumonia with multiple courses of antibiotics including doxycycline and moxifloxacin. His history was significant for ESRD secondary to PCKD and a 45 pack year history of tobacco use. On examination he was afebrile and dyspenic requiring 12L high flow nasal cannula. Lung examination revealed crackles throughout. Labs included a WBC count of 8.2 with 79% granulocytes. ABG was 7.43/28/61/91% on 60 % FiO2. A CXR showed diffuse patchy infiltrates bilaterally. A CT of the chest with contrast demonstrated diffuse ground glass opacities with interlobular septal thickening (crazy paving pattern). He was started on Zosyn, vancomycin and azithromycin. A TEE showed an EF of 65% with diastolic dysfunction. Bronchoalvoelar lavage was positive for milky fluid which was hypocellular and contained rare vacuolated alveolar macrophages that stained positive for PAS. He underwent video assisted thoracoscopic surgery (VATS) with right upper and lower lobe wedge resection. Pathology revealed pulmonary alveolar proteinosis. SRL was discontinued. All cultures were negative for infection hence antibiotics were also discontinued. Respiratory status improved and he was discharged home on supplemental oxygen. At follow-up two months later he only required supplemental oxygen with activity and CXR showed significant improvement.
Pulmonary Alveolar Proteinosis (PAP) is a rare disorder characterized by accumulation of PAS-positive phospholipoproteinaceous material within alveoli with minimal interstitial inflammation or fibrosis. It has a variable clinical presentation and course. Most cases are acquired but it can also be congenital or secondary. The secondary causes include inhalation syndromes immunodeficiency disorders and hematopoietic disorders. Patients usually present with non-productive cough, dyspnea on exertion and low grade fever. Physical examinations often reveals inspiratory crackles and clubbing in up to one third of cases. Patients with advanced disease may have central and peripheral cyanosis. Pulmonary function test show a restrictive ventilatory defect. CXR finding can range from perihilar (bat’s wing pattern) to predominantly peripheral or basal consolidation. High resolution computed tomographic (HRCT) scan show widespread consolidation with thickened interlobular septa producing the so called “crazy paving” pattern. Diagnosis can be made with confidence on the basis of the appearance of HRCT scan of images in conjunction with alveolar lavage. Tissue pathology is another modality that can be used for a more definitive diagnosis. The treatment depends on the distinct class of PAP. Our patient was successfully treated with discontinuation of the offending agent with marked improvement in respiratory status.
Pulmonary alveolar proteinosis can present as a complication of Sirolimus. Effort should be made to rule out infections but early recognition of this association may avoid invasive investigations. Discontinuation of SRL may lead to complete resolution of PAP.
Kapil Dhawan, No Financial Disclosure Information; No Product/Research Disclosure Information