INTRODUCTION: Hermansky-Pudlak syndrome is a rare autosomal recessive group of mutations involving intracellular trafficking of vesicles and organelles. It presents with the triad of oculocutaneous albinism, bleeding diathesis, and pulmonary fibrosis.
CASE PRESENTATION: A 29 year old male with oculocutaneous albinism(OCA) presented to the ER with a four year history of dyspnea, worsened over the past month. It was initially noted while playing sports, but more recently had occurred with performing household tasks. It was accompanied by a dry cough that was non-productive, without hemoptysis or accompanying chest pain, and without nasal congestion or fevers. The cough was exacerbated by cold weather, exercise, and dusts in the workplace. On questioning, he admitted to frequent bouts of epistaxis, mostly as a child, and admitted to easy bruising. He had a 7 pack-year tobacco history and quit 2 years ago. He denied alcohol or drug abuse. On exam, he appeared comfortable and was afebrile, with BP 125/72, pulse 72, respiratory rate of 20, and O2 saturation of 90% on room air. Notable physical exam findings included a red reflex, horizontal nystagmus, mild central cyanosis, a loud second heart sound, velcro rales at the right lung base not cleared by cough, digital clubbing, and creamy white skin without ecchymoses or petichiae. Chest radiography showed diffuse bilateral reticulonodular infiltrates. Thoracic CT showed extensive bilateral bronchovascular thickening, subpleural fibrosis, and bronchiectasis. Transthoracic echocardiogram showed right ventricular and atrial hypertrophy, pulmonary artery systolic pressure of 100mmHg, and a PFO. All sputum and blood cultures were negative, including fungal and AFB cultures were negative. Fungal, HIV, hepatitis and rheumatologic serolgies were unrevealing. A right-heart catheterization revealed severe pulmonary hypertension with pulmonary artery systolic pressure of 70 mmHg and a wedge pressure of 7 mmHg. Pulmonary function tests showed severe restriction and a severely reduced diffusion capacity. A 6 minute walk test showed correlation with spirometric parameters and diffusion capacity. There was also significant arterial oxygen desaturation to 71% during the test. Electron microscopy of a whole-mount blood preparation revealing absence of platelet dense bodies confirmed the diagnosis of Hermansky-Pudlak syndrome (HPS).
DISCUSSIONS: HPS is a rare heterogeneously inherited autosomal recessive group of disorders with the triad of oculocutaneous albinism, bleeding diathesis and pulmonary disease. It is thought to occur as a consequence of disturbed formation or trafficking of intracellular organelles, most importantly melanosomes, platelet dense granules and lysosomes. It presents with oculocutaneous albinism, bleeding diathesis, pulmonary fibrosis, and occasional hemorrhagic granulomatous colitis. Pulmonary fibrosis is thought to occur due to ceroid accumulation in Type-II pneumocytes and alveolar macrophages, causing chronic inflammation. HRCT findings include ground-glass opacities, bronchiectasis, peribronchovascular thickening, septal lines, and reticulation. These abnormalities initially predominate in the peripheral lower lung zones, then become more central and diffuse. It is diagnosed by finding absence of platelet dense bodies on whole mount blood electron microscopy. Mortality is high with onset of pulmonary fibrosis, with 50% mortality at 10 years after diagnosis. There is no effective treatment, though pirfenidone is showing promise in delaying progression of pulmonary disease. There have only been two documented cases of lung transplantation for HPS.
CONCLUSION: HPS is a rare disease that should be suspected in a patient who presents with oculocutaneous albinism, bleeding diathesis, and pulmonary disease. There is no effective treatment, but lung transplantation shows some promise.
DISCLOSURE: Isabel Pedraza, None.