Clinical Case Pulmonary Fibrosis in HermanskyPudlak Syndrome

About This Presentation

Title:

Description:

Number of Views:186

Avg rating:3.0/5.0

Slides: 18

Provided by: thefrancef

Category:

more less

Transcript and Presenter's Notes

Title: Clinical Case Pulmonary Fibrosis in HermanskyPudlak Syndrome

1
Clinical Case Pulmonary Fibrosis
inHermansky-Pudlak Syndrome
2
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

3
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

4
History (cont)

5
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

6
High Resolution CT
7
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)

8
NL
mb
F
9
(No Transcript)
10
(No Transcript)
11
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

12
Diagnosis

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

13
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

14
HPS Genetics
Pierson DM, et al. Respiration. 200673382395.
15
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

16
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

17
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