a 38-year - old female from puerto rico with complaints of hypoxia was transferred to our facility .
she had been diagnosed 5 years earlier with hermansky - pudlak syndrome ( hps ) subtype 1 , complicated by pulmonary fibrosis .
she had experienced a slow deterioration in pulmonary function , manifesting as worsening dyspnea , cough , and increasing oxygen dependence .
in addition to pulmonary fibrosis , she had other manifestations of hps , including multiple major bleeding episodes requiring blood transfusions , and oculocutaneous albinism with legal blindness .
she required 24 h supplemental home oxygen with a baseline flow requirement of 6 l / min via nasal cannulae and was under evaluation for lung transplantation prior to her terminal hospital admission .
pulmonary function tests [ table 1 ] showed increasing severe restrictive ventilatory deficit over the 2 years prior to admission , with total lung capacity going from 64% in 2010 to 57% in 2011 and 44% in 2012 .
pulmonary function test results over a course of 2 years revealing progressive worsening of restrictive ventilatory deficit the patient presented with increasing dyspnea , pleuritic chest pain , and cough .
she was transferred to the intensive care unit due to hypoxia , with an oxygen saturation of 44% on 6 l nasal cannula .
she was started on empiric antibiotics and supported with noninvasive ventilation , but continued to desaturate and was subsequently intubated .
the patient developed multiorgan failure as evidenced by elevated creatinine , transaminitis , and right heart failure .
blood and urine cultures on admission were negative , and white blood cell count was normal at 10.9  10 cells / l .
chest x - ray upon terminal admission demonstrated diffuse reticular interstitial opacities throughout the lungs [ figure 1 ] .
baseline ct of the chest obtained 16 months [ figure 2a ] and 3 months before admission [ figure 2b ] demonstrated progressive worsening of pulmonary fibrosis , as evidenced by increasing traction bronchiectasis , interlobular septal thickening , and consolidative opacities .
chest ct upon admission showed multifocal ground glass opacities , subpleural cysts , septal and peribronchovascular thickening , reticulation , and traction bronchiectasis involving greater than two - thirds of the lungs .
also , there was new honeycombing in the bilateral upper lobes suggesting end - stage fibrosis [ figure 2c ] .
38-year - old female with a known history of hermansky  pudlak syndrome complicated by pulmonary fibrosis , admitted with hypoxia .
posteroanterior chest radiograph performed on admission demonstrates bilateral , mid to lower lung predominant , diffuse reticular interstitial opacities ( arrows ) .
38-year - old female diagnosed with hermansky  pudlak syndrome complicated by pulmonary fibrosis , as evidenced by worsening dyspnea , cough , and increasing oxygen dependence .
baseline high - resolution ct ( hrct ) of the chest : ( a ) axial image on lung windows at the level of the carina demonstrates scattered , predominantly peripheral , ground glass opacities with associated fine peripheral reticulation in the lungs bilaterally ( curved arrows ) ; ( b ) high - resolution ct of the chest from the same level obtained 13 months later demonstrates progression of the peripheral opacities that have become more consolidative ( curved arrows ) with more conspicuous subpleural opacity in the right upper lobe ( straight thin arrow ) ; there is new bronchiectasis ( arrowhead ) and septal thickening along the left main fissure ( thick arrow ) ; and ( c ) axial ct of the chest on lung windows at terminal admission , performed as part of a ct pulmonary angiogram protocol ( 16 months after initial imaging ) , demonstrates further progression with increased size of peripheral consolidative opacities and increasing bronchiectasis .
there is new honeycombing in the upper lobes bilaterally ( curved arrow ) . of note ,
both lungs were found to be heavy with diffuse nodular parenchymal fibrosis [ figure 3a and 3b ] .
there was end - stage remodeling , characterized by cystic spaces lined by bronchial epithelium and surrounded by well - developed fibrosis on microscopic examination .
the cysts , airspaces , and bronchioles were filled with mucus , suppurative exudate , and abundant vacuolated macrophages [ figure 4a and b ] .
38-year - old female with history of hermansky  pudlak syndrome and end -stage pulmonary fibrosis , admitted with hypoxia and was terminally extubated after sustaining multiorgan failure .
( a and b ) photographs of coronal cut sections of a lung demonstrate diffuse nodular parenchymal fibrosis ( arrows ) with apparent bronchiolocentric distribution .
38-year - old female with history of hermansky  pudlak syndrome and end - stage pulmonary fibrosis , admitted with hypoxia .
photomicrographs of postmortem microscopic examination of lung tissue stained with hematoxylin  eosin stain : ( a ) 200 magnification demonstrates end - stage remodeling , with honeycomb cystic spaces lined by metaplastic bronchial epithelium and surrounded by well - developed fibrosis ( arrows ) ; ( b ) 400 magnification shows alveolar septal thickening associated with prominent diffuse vacuolization of type ii pneumocytes ( arrow ) .
chest x - ray upon terminal admission demonstrated diffuse reticular interstitial opacities throughout the lungs [ figure 1 ] .
baseline ct of the chest obtained 16 months [ figure 2a ] and 3 months before admission [ figure 2b ] demonstrated progressive worsening of pulmonary fibrosis , as evidenced by increasing traction bronchiectasis , interlobular septal thickening , and consolidative opacities .
chest ct upon admission showed multifocal ground glass opacities , subpleural cysts , septal and peribronchovascular thickening , reticulation , and traction bronchiectasis involving greater than two - thirds of the lungs .
also , there was new honeycombing in the bilateral upper lobes suggesting end - stage fibrosis [ figure 2c ] .
38-year - old female with a known history of hermansky  pudlak syndrome complicated by pulmonary fibrosis , admitted with hypoxia .
posteroanterior chest radiograph performed on admission demonstrates bilateral , mid to lower lung predominant , diffuse reticular interstitial opacities ( arrows ) .
38-year - old female diagnosed with hermansky  pudlak syndrome complicated by pulmonary fibrosis , as evidenced by worsening dyspnea , cough , and increasing oxygen dependence .
baseline high - resolution ct ( hrct ) of the chest : ( a ) axial image on lung windows at the level of the carina demonstrates scattered , predominantly peripheral , ground glass opacities with associated fine peripheral reticulation in the lungs bilaterally ( curved arrows ) ; ( b ) high - resolution ct of the chest from the same level obtained 13 months later demonstrates progression of the peripheral opacities that have become more consolidative ( curved arrows ) with more conspicuous subpleural opacity in the right upper lobe ( straight thin arrow ) ; there is new bronchiectasis ( arrowhead ) and septal thickening along the left main fissure ( thick arrow ) ; and ( c ) axial ct of the chest on lung windows at terminal admission , performed as part of a ct pulmonary angiogram protocol ( 16 months after initial imaging ) , demonstrates further progression with increased size of peripheral consolidative opacities and increasing bronchiectasis .
there is new honeycombing in the upper lobes bilaterally ( curved arrow ) . of note ,
at postmortem examination , both lungs were found to be heavy with diffuse nodular parenchymal fibrosis [ figure 3a and 3b ] .
there was end - stage remodeling , characterized by cystic spaces lined by bronchial epithelium and surrounded by well - developed fibrosis on microscopic examination .
the cysts , airspaces , and bronchioles were filled with mucus , suppurative exudate , and abundant vacuolated macrophages [ figure 4a and b ] .
38-year - old female with history of hermansky  pudlak syndrome and end -stage pulmonary fibrosis , admitted with hypoxia and was terminally extubated after sustaining multiorgan failure .
( a and b ) photographs of coronal cut sections of a lung demonstrate diffuse nodular parenchymal fibrosis ( arrows ) with apparent bronchiolocentric distribution .
38-year - old female with history of hermansky  pudlak syndrome and end - stage pulmonary fibrosis , admitted with hypoxia .
eosin stain : ( a ) 200 magnification demonstrates end - stage remodeling , with honeycomb cystic spaces lined by metaplastic bronchial epithelium and surrounded by well - developed fibrosis ( arrows ) ; ( b ) 400 magnification shows alveolar septal thickening associated with prominent diffuse vacuolization of type ii pneumocytes ( arrow ) .
hps is a heterogeneous group of autosomal recessive disorders characterized by oculocutaneous hypopigmentation , platelet dysfunction ( easy bruising and prolonged bleeding time despite normal platelet count ) , and lysosomal accumulation of ceroid - lipofuscin in the lungs , which primarily accounts for the associated morbidity . in north america , most patients with hps are from puerto rico , where the prevalence is estimated to be 1 in 1800 or occurring in 5 of every 6 albinos .
groups of affected individuals have also been identified in japan and a small village in switzerland .
patients usually present in childhood , often with recurrent epistaxis or prolonged bleeding after dental procedures .
nine subtypes of hps are described , most of which are associated with a mutation in the hps gene on the long arm of chromosome 10 .
this genotype leads to a high risk of pulmonary disease , hemorrhage , and , in approximately 15% of patients , granulomatous colitis .
only type 4 approaches type 1 in severity , with the remaining subtypes behaving more mildly clinically and with little risk of restrictive lung disease .
while most patients with hps1 die of pulmonary complications , approximately 13% die of complications from bowel inflammation , with this granulomatous colitis mimicking crohn 's disease and often occurring in adolescence or early adulthood .
the pathophysiology is believed to be impaired intracellular trafficking of melanosomes , platelet dense bodies , and lysosomes .
impaired formation of platelet - dense bodies leads to the bleeding dyscrasia , whereas impaired intracellular trafficking of melanin in the melanosomes of the skin and retina is postulated to be the cause of oculocutaneous albinism .
systemic complications are associated with accumulation of ceroid - lipofuscin , an amorphous lipid  protein complex in multiple organs and the reticuloendothelial system , leading to pulmonary fibrosis , granulomatous colitis , cardiomyopathy , and renal failure .
ceroid - lipofuscin accumulation in the pulmonary alveolar macrophages is believed to be the primary mechanism for the development of pulmonary fibrosis .
recurrent hemorrhage with resulting hemosiderosis and inflammatory response is also suggested as an alternative mechanism .
pulmonary fibrosis in hps is twice as common in women , occurring between the third and fifth decades .
it initially presents as dyspnea on exertion or restrictive lung disease on pulmonary function tests , and is the most common cause of death in affected patients .
the radiographic appearance of hps is nonspecific and chest radiographs may be normal at presentation .
various radiographic abnormalities have been described , including reticular or reticulonodular opacities , pleural thickening , interstitial infiltrates , and perihilar fibrosis .
chest radiograph in our patient at the time of admission demonstrated symmetric reticular opacities throughout both lungs [ figure 1 ] .
as chest radiographs sometimes underestimate the extent of disease , high - resolution ct is the imaging modality of choice for characterizing the parenchymal abnormalities and evaluating the extent of pulmonary involvement .
early stages of the disease are characterized by subtle reticulations , interlobular septal thickening , and peripheral ground glass opacities . in more advanced stages
, there are more severe reticulations , peribronchovascular thickening , subpleural cysts , and bronchiectasis involving central airways .
abnormalities on high - resolution ct tend to be evenly distributed throughout the lungs , with a slight predilection for the middle and lower lungs .
chest ct from our patient demonstrated diffuse septal thickening and ground glass opacities throughout both lungs , while honeycombing was predominantly seen in the bilateral upper lobes [ figure 2a  c ] .
hps is more likely than the usual interstitial pneumonias or collagen diseases to also involve the upper lobes , particularly later in the course of the disease
. pulmonary hemorrhage , which typically presents with diffuse ground glass opacity on ct , should be considered in these patients given the underlying platelet dysfunction .
other entities that might have overlapping appearance on ct images include idiopathic pulmonary fibrosis ( ipf ) , which features irregular reticulation , fibrosis and honeycombing in the posterior subpleural lung bases , and nonspecific interstitial pneumonitis ( nsip ) , which has bilateral and symmetric ground glass opacity and less honeycombing .
however , ipf most commonly occurs in older patients and nsip is not a progressive process .
hps has been classified by the american thoracic society and the european respiratory society as a mimic of ipf and one of the few diseases that has histological features similar , but not identical to usual interstitial pneumonia . a prior imaging study examining patients with hps used a four - point score to grade the severity of ct appearance of disease .
grade 1 showed minimal changes ( thickened interlobular septa , reticular disease , subpleural cysts , and areas of ground glass ) .
grade 2 had moderate disease ( traction bronchiectasis , peribronchovascular thickening , and tracheal retraction in one - third or two - thirds of the lungs ) .
grade 3 had the findings of grades 1 and 2 , but involved more than two - thirds of the lungs .
the study found that patients under 20 years of age typically had no ct findings ( grade 0 ) and those between 20 and 29 years had minimal ct changes ( average grade 0.25  0.16 ) . among patients older than 30 years
, those with hps1 mutations had significantly more severe disease on ct compared with those patients without this mutation ( p = 0.001 ) .
worsening ct appearance correlated highly with poorer pulmonary function ; as ct severity score increased , the forced vital capacity ( fvc ) fell dramatically ( p < 0.001 ) . also , higher ct severity score correlated with time to death , with over half the patients with grade 3 disease dying within 4 months .
our patient had a chest ct 16 months prior to admission , which showed grade 2 findings [ figure 2a ] .
subsequent chest ct 3 months before admission showed significant worsening of fibrosis , now involving greater than two - thirds of the lungs and meeting the criteria for grade 3 disease [ figure 2b ] .
final chest ct upon admission revealed extensive traction bronchiectasis , peribronchovascular thickening , and honeycombing , consistent with end - stage fibrosis [ figure 2c ] . there is no effective treatment for pulmonary fibrosis due to hps , besides lung transplantation .
high - dose corticosteroids are administered to patients with advanced disease , though their efficacy has not been proven
. cigarette smoke and other pulmonary irritants must be avoided , and the antibiotic pirfenidone may slow the progression of pulmonary fibrosis in patients with significant residual lung .
our patient had an objective and symptomatic decline over the last 12 months of her life , which rendered her oxygen dependent with a baseline requirement of 6 l / min and was under evaluation for lung transplantation prior to her terminal admission .
in summary , hps is a rare congenital disorder , most often seen in puerto ricans , that manifests as easy bruising , epistaxis , prolonged bleeding , granulomatous colitis , and a high risk of pulmonary fibrosis .
patients with mutations in hps1 are much more likely to develop more severe disease , typically after 30 years of age .
ct correlates well with pulmonary function , and more severe ct changes significantly correlate with time to death .
 hermansky  pudlak syndrome ( hps ) is a rare autosomal recessive disorder characterized by oculocutaneous hypopigmentation , platelet dysfunction , and in many cases , life - threatening pulmonary fibrosis . 
 we report the clinical course , imaging , and postmortem findings of a 38-year - old female with hps - related progressive pulmonary fibrosis , highlighting the role of imaging in assessment of disease severity and prognosis . 
INTRODUCTION
Radiologic features
Pathologic features
DISCUSSION
CONCLUSION