Clinical Update on Patients with Hermansky-Pudlak Syndrome at Risk of Pulmonary Fibrosis Entered into a Prospective Surveillance Pathway

Abstract

Introduction: Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder that affects lysosome-related organelles, including platelet dense granules and melanosomes, resulting in the common clinical characteristics of bleeding and oculocutaneous albinism. Of the 11 genetic subtypes, patients with HPS-1, HPS-2, and HPS-4 are also at risk of pulmonary fibrosis (HPS-PF). The typical age of onset of HPS-PF is 30-40 years; however, there are childhood cases of HPS-PF reported in HPS-2. Life expectancy with HPS-PF is approximately 10 years from diagnosis, however anti-fibrotic medications can slow the rate of fibrosis progression. Therefore, early identification of at-risk patients has the potential to prolong survival. Method(s): Patients with HPS registered in our centre were genotyped, and those at risk of HPS-PF were enrolled into a new prospective pulmonary surveillance pathway. Patients aged 25- years-old and above were stratified based on specialist respiratory assessment and chest x-ray to either an upfront high-resolution computed tomography scan of the chest, or if there was no evidence of established lung disease, to annual lung function test surveillance. Result(s): In our centre, we care for nine patients with HPS-1, five with HPS-3, 3 with HPS-6, and one patient with HPS-8, of which the nine patients with HPS-1 are at risk of developing HPS-PF. This HPS-1 cohort comprises seven females and two males, with a median age of 28 years (range 9-42 years). The five patients aged 25 years and older have entered our pulmonary surveillance pathway, and all are having annual lung function tests. To date, no patients in our pathway have either radiological abnormalities or a restrictive ventilatory defect orreduced gas diffusion capacity suggestive of HPS-PF. Discussion/Conclusion: Progressive pulmonary fibrosis is a fatal complication of HPS-1, HPS-2 and HPS-4. Our prospective screening and surveillance pathway aims to identify and monitor the patients at risk of HPS-PF in order to detect this complication early. There are no current guidelines as to when anti-fibrotic medication, such as the tyrosine kinase inhibitor nintedanib, should be initiated for patients at risk of HPS-PF, and we aim to address this through close surveillance of at-risk patients with HPS.