Clinical Case Pulmonary Fibrosis in HermanskyPudlak Syndrome

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Clinical Case Pulmonary Fibrosis
inHermansky-Pudlak Syndrome
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History

• A 28-year-old Mexican man presented with
  exertional dyspnea and chronic dry cough
• He also complained of arthralgia and morning
  stiffness
• Clubbing of extremities was not present
• He denied a history of fever, hemoptysis, or
  smoking

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History (cont)

• Albinism diagnosed in childhood
• Nystagmus and decreased visual acuity
• Frequent nose bleeds, easy bruising and several
  episodes of protracted hemorrhagic colitis since
  the age of 17
• Albino sister with ecchymosis, but no pulmonary
  symptoms. A paternal great-great grandmother
  was said to be albino, but history of pulmonary
  disease and age of death were unknown

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History (cont)

• Father reportedly of Mexican descent, unrelated
  to his Mexican mother
• No known Puerto Rican ancestry
• Neither parents nor 2 other siblings affected
• Patient is childless
• Family history of diabetes mellitus and
  hypertension

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Chest Radiography

• A chest radiograph was abnormal showing diffuse
  reticulonodular interstitial infiltrates
• HRCT demonstrated prominent diffuse reticular
  opacities and ground-glass opacity (indicated on
  next slide)
• Distribution bases and right middle lobe, also
  lingual and anterior portions of upper lobes

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High Resolution CT
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Tests

• Pulmonary function tests showed a restrictive
  pattern
• Video-assisted thoracic surgery revealed minimal
  pleural effusion and mild pleural adhesions
• Lung parenchyma was pink and diffusely thickened
• Wedge resection of the left lingula was obtained
  for cultures and histopathologic evaluation
  (cultures negative)

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Pathology Summary

• Microscopic sections showed advanced lung
  remodeling with architectural distortion and
  fibrosis appreciated
• Chronic inflammatory cells were numerous and
  peculiar patchy clusters of clear vacuolated
  cells were distinctive

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Diagnosis

• On the basis of these findings, a diagnosis of
  Hermansky-Pudlak Syndrome (HPS) was made

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What is Hermansky-Pudlak Syndrome?

• Findings
• Oculocutaneous albinism
• Bleeding diathesis
• Pulmonary disease
• Visual impairment
• Systemic ceroid lipofuscin deposition
• Mutated proteins function in organelle biogenesis
  and transport lysosomes, lysosome-related
  organelles (LROs), melanosomes, and platelet
  dense bodies are affected
• HPS has GI features of both Crohns disease and
  ulcerative colitis with frequent GI bleeds
• Majority of HPS patients with pulmonary findings
  have HPS-1 and usually have Puerto Rican ancestry

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HPS Genetics
Pierson DM, et al. Respiration. 200673382395.
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HPS Mechanism

• There is limited understanding of the mechanisms
  involved in secretory and endocytic lysosomal
  pathways
• Human mutations such as those associated with HPS
  may aid elucidation of vesicle biology
• Mice bearing similar mutations may also help
  investigation of basic mechanisms and analysis of
  drug candidates

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Clinical Update

• Sister has experienced no pulmonary symptoms
• At the age of 30, the patients pulmonary status
  has progressively decompensated low flow
  continuous oxygen by nasal cannula was required
• Patient is hopeful of receiving a lung transplant
• Before transplantation, patient suffers
  pneumothorax, inanition, respiratory failure and
  death

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Conclusions

• Pulmonary radiographs of HPS may mimic findings
  of UIP/IPF, especially when HPS is end-stage
• Histopathologic findings such as clear cells do
  not support a diagnosis of IPF despite other
  features of UIP
• Not all HPS patients manifest the classical
  features of albinism, GI symptoms and frequent
  bleeding
• History of bruisability, epistaxis, metrorrhagia
  (females), family history and provenance may
  provide clues to diagnosing HPS
• Surgical lung biopsy can cause fatal bleeding in
  HPS patients