Case Report: Hermansky–Pudlak syndrome type 1 with pulmonary involvement in a 62-year-old Caucasian woman with rheumatoid arthritis

Introduction Hermansky–Pudlak syndrome (HPS) is a rare autosomal recessive disorder characterized by oculocutaneous albinism (OCA), ocular nystagmus, bleeding diathesis and, in certain forms, pulmonary fibrosis (PF). We report a case of genetically confirmed HPS type 1 (HPS-1) with pulmonary involvement in a patient with rheumatoid arthritis (RA). Patient concerns and clinical findings A 62-year-old Caucasian woman, former smoker, was referred for progressive pulmonary fibrosis (PPF) documented since 2019. History included chronic kidney disease and RA diagnosed in 2022, treated with hydroxychloroquine, prednisone, and abatacept. On presentation, she exhibited exertional dyspnea. Distinctive features included OCA, ocular nystagmus, and recurrent non-traumatic bruises, consistent with a bleeding tendency. Diagnostic assessment Between 2021 and 2024, spirometry documented a decline in forced vital capacity - percent of predicted (FVC%) from 86% to 61% and a reduction in diffusing capacity of carbon monoxide - percent of predicted (DLCO%) from 60% to 37%. The six-minute walking test (6MWT) revealed exertional desaturation. High-resolution computed tomography (HRCT) showed PPF characterized by reticular thickening, ground-glass opacities (GGO), honeycombing, and traction bronchiectasis. Platelet aggregation study revealed impaired function with reduced CD41a expression, while transmission electron microscopy (TEM) confirmed rarefaction-to-absence of platelet dense granules. Genetic analysis identified a homozygous c.355del p.(His119ThrfsTer5) pathogenic variant in HPS1, confirming HPS-1. Interventions and outcomes Abatacept was discontinued and rituximab initiated for RA management. Antifibrotic therapy was not pursued due to renal impairment and limited supporting evidence. Supportive measures included supplemental oxygen during exertion, pulmonary rehabilitation, and vaccination. Lung transplantation was deemed infeasible owing to renal failure and active autoimmune disease. The patient remains under follow-up. Conclusion In patients presenting with PF, OCA, and bleeding diathesis, HPS should be suspected. Diagnostic workup begins with platelet aggregation study and TEM of platelets, and the diagnosis is confirmed by molecular genetic testing. No disease-modifying therapies exist for HPS-associated PF (HPS-PF); pirfenidone has uncertain benefit, while lung transplantation remains the only option for end-stage disease. This case underscores the need for early suspicion of HPS to guide investigations, counseling, and referral to specialized care. Moreover, the unusual association with RA is emphasized, as it may have contributed to PF.