Pulmonary Fibrosis in Hermansky-Pudlak Syndrome

Ann Am Thorac Soc. 2016 Oct;13(10):1839-1846. doi: 10.1513/AnnalsATS.201603-186FR.


Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive genetic disorder characterized by oculocutaneous albinism and a bleeding diathesis due to platelet dysfunction. More than 50% of cases worldwide are diagnosed on the Caribbean island of Puerto Rico. Genetic testing plays a growing role in diagnosis; however, not all patients with HPS have identified genetic mutations. In Puerto Rico, patients with HPS are often identified shortly after birth by their albinism, although the degree of hypopigmentation is highly variable. Ten subtypes have been described. Patients with HPS-1, HPS-2, and HPS-4 tend to develop pulmonary fibrosis in Puerto Rico; 100% of patients with HPS-1 develop HPS-PF. HPS-PF and idiopathic pulmonary fibrosis are considered similar entities (albeit with distinct causes) because both can show similar histological disease patterns. However, in contrast to idiopathic pulmonary fibrosis, HPS-PF manifests much earlier, often at 30-40 years of age. The progression of HPS-PF is characterized by the development of dyspnea and increasingly debilitating hypoxemia. No therapeutic interventions are currently approved by the U.S. Food and Drug Administration for the treatment of HPS and HPS-PF. However, the approval of two new antifibrotic drugs, pirfenidone and nintedanib, has prompted new interest in identifying drugs capable of reversing or halting the progression of HPS-PF. Thus, lung transplantation remains the only potentially life-prolonging treatment. At present, two clinical trials are recruiting patients with HPS-PF to identify biomarkers for disease progression. Advances in the diagnosis and management of these patients will require the establishment of multidisciplinary centers of excellence staffed by experts in this disease.

Keywords: Hermansky–Pudlak syndrome; genetics; oculocutaneous albinism; pulmonary fibrosis.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomarkers
  • Disease Progression
  • Hermanski-Pudlak Syndrome / complications*
  • Hermanski-Pudlak Syndrome / ethnology*
  • Hispanic or Latino
  • Humans
  • Indoles / therapeutic use
  • Lung Transplantation
  • Membrane Proteins / genetics
  • Mice
  • Mutation
  • Puerto Rico / ethnology
  • Pulmonary Fibrosis / therapy*
  • Pyridones / therapeutic use
  • Randomized Controlled Trials as Topic
  • Tomography, X-Ray Computed


  • Biomarkers
  • HPS1 protein, human
  • Indoles
  • Membrane Proteins
  • Pyridones
  • pirfenidone
  • nintedanib