SUCCESSFUL TRANSPLANTATION DEFIES GENETICS: A CASE OF RAPIDLY-PROGRESSIVE PULMONARY FIBROSIS DUE TO HERMANSKY-PUDLAK SYNDROME

Abstract

SESSION TITLE: Pulmonary Manifestations of Systemic Disease SESSION TYPE: Fellow Case Reports PRESENTED ON: 10/08/2018 11:00 AM - 12:00 PM INTRODUCTION: Hermansky-Pudlak syndrome (HPS) is an extremely rare autosomal-recessive condition that devastates young victims with highly penetrant pulmonary fibrosis. We present a case of a middle-aged woman with clinically characteristic HPS and severe respiratory failure due to interstitial destruction, who was successfully cured with the first bilateral lung transplantation done at this institution. CASE PRESENTATION: Our patient is a 47-year old Puerto-Rican female, never-smoker, who was referred for lung transplant evaluation in the setting of quickly progressing and functionally limiting fibrosis. A previously healthy woman with a medical history solely of menorrhagia and occasional heavy bleeding with dental work, presented to us as a very ill and dyspneic patient. Over the course of one year, a bothersome cough turned into debilitating exertional fatigue and air-hunger, significant hypoxia requiring supplemental oxygen, marked weight reduction, and a loss of independence. Her presenting physical exam was notable for horizontal saccades, pale skin coloring, and coarse diffuse rales. Radiographic findings and open lung biopsy proved significant pulmonary fibrosis, which in addition to her ethnic background and the clinical history suggested HPS. This was ultimately confirmed with gene testing and platelet electron microscopic analysis.After thorough discussion and formal evaluation, the patient was listed for and successfully underwent bilateral lung transplantation, complicated only by (as expected) moderate bleeding. Her respiratory symptoms completely resolved, and she resumed her usual activities, oxygen-free. DISCUSSION: In a small section of Northwest Puerto-Rico, 1 in 21 persons carries the mutation for HPS, subjecting roughly 1 in 1800 to the above syndrome. Diagnostic criteria include 1) tyrosine positive oculocutaneous albinism (OCA); and 2) a bleeding disorder due to platelet dysfunction. HPS gene products are ubiquitously expressed and highly important in lysosome trafficking, which is thought to be causative of pulmonary fibrosis. Patients with HPS subtype-1 universally develop lung fibrosis, often in the 3rd or 4th decade of life. Radiographic findings include increased reticular opacities, thickened intralobular septa, traction bronchiectasis, and honeycombing, with a heterogenic course of lung function decline across patients. There are no known therapies for HPS-related pulmonary fibrosis, but as in this case, there are several cases of successful transplantation despite a bleeding risk. CONCLUSIONS: HPS is a rare but recognizable cause of interstitial lung disease. Clinical and epidemiologic factors should prompt appropriate diagnostic work-up and early referral for transplantation. There are several ongoing clinical trials to further define molecular characteristics of HPS, which holds great promise to expand our limited understanding of pulmonary fibrosis. Reference #1: El-Chemaly, S. and Young L. "Hermansky-Pudlak Syndrome.” Clin Chest Med, 2016; 37 (3) 505-511. Reference #2: Vicary G, et al. "Pulmonary Fibrosis in Hermansky-Pudlak Syndrome.” Ann Am Thorac Soc, 2016; 13 (10) 1839-1846. DISCLOSURES: Chief Medical Officer relationship with BiO2 Medical Please note: >$100000 Added 03/01/2018 by Luis Angel, source=Web Response, value=Intellectual Property No relevant relationships by Jessica Riggs, source=Web Response