What is Hermansky-Pudlak syndrome pulmonary fibrosis?
Hermansky-Pudlak syndrome (HPS) is a group of inherited disorders affecting tiny storage compartments inside cells. This causes:
- Oculocutaneous albinism: reduced pigment in the skin, hair and eyes, with reduced vision and involuntary eye movements (nystagmus).
- A bleeding tendency, because platelets lack the granules needed to form clots normally.
- Pulmonary fibrosis in certain subtypes, notably HPS-1, HPS-2 and HPS-4.
The lung fibrosis usually appears in the thirties or forties and progresses, behaving in some ways like idiopathic pulmonary fibrosis but at a younger age. HPS is ultra-rare worldwide, though more common in some populations, such as north-west Puerto Rico. Some patients also develop inflammatory bowel disease (granulomatous colitis).
Symptoms
Lung symptoms
- Breathlessness on exertion, slowly worsening.
- Dry cough.
- Fatigue and reduced exercise tolerance.
- Crackles heard at the lung bases and, sometimes, finger clubbing.
Other features
- Light skin and hair, visual impairment and nystagmus from birth.
- Easy bruising, nosebleeds, prolonged bleeding after dental work or surgery, and heavy periods.
- Abdominal pain, diarrhoea or rectal bleeding in those with colitis.
Early lung fibrosis may cause no symptoms, which is why monitoring starts before breathlessness appears.
Cause and inheritance
HPS is caused by mutations in one of at least eleven genes, and is inherited in an autosomal recessive pattern: both parents carry one altered copy, and each of their children has a one-in-four chance of being affected. It is therefore more likely when parents are blood relatives, which is relevant to some families in India. The lung disease is linked to faulty processing of surfactant in the cells lining the air sacs, leading to cell injury and scarring. Smoking and other lung irritants may accelerate damage and should be avoided.
How it is diagnosed
The combination of albinism and a bleeding tendency suggests HPS. Diagnosis and lung assessment involve:
| Test | What it shows |
|---|---|
| Genetic testing | The specific HPS gene and subtype, which predicts lung risk |
| Platelet electron microscopy | Absent dense granules in platelets, confirming the platelet defect |
| High-resolution CT chest | Reticulation, ground-glass change, traction bronchiectasis and thickening around the airways, often in the periphery |
| Lung function tests | A restrictive pattern and reduced gas transfer (DLCO), tracked over time |
| Six-minute walk test | Exercise capacity and oxygen levels on exertion |
| Echocardiography | Pulmonary hypertension in advanced disease |
Lung biopsy is avoided where possible because of the bleeding risk. The diagnosis rests on genetics, CT and lung function, reviewed in an interstitial lung disease multidisciplinary discussion.
Treatment
Slowing the fibrosis
There is no cure. Pirfenidone has been studied in HPS with some suggestion of benefit in milder disease, and nintedanib is used for progressive pulmonary fibrosis of various causes. Either may be considered after discussion of potential benefits and risks. Steroids are not effective for the fibrosis.
Supportive care
Pulmonary rehabilitation, oxygen when levels fall, influenza and pneumococcal vaccination, treatment of reflux, and strict avoidance of smoking all help preserve function.
Managing bleeding risk
Before any procedure, including bronchoscopy, dental work or surgery, a plan is made with haematology. Desmopressin or platelet transfusion may be used. Aspirin and other drugs that affect platelets are avoided.
Lung transplantation
Lung transplantation is the definitive treatment for advanced HPS pulmonary fibrosis and has been performed successfully. Early referral allows time to plan around the bleeding risk. Care is coordinated with genetics, haematology, ophthalmology, gastroenterology and transplant centres.
Outlook and follow-up
Once established, HPS pulmonary fibrosis tends to progress over several years. People with lung-risk subtypes benefit from baseline CT and lung function tests in early adulthood and regular monitoring thereafter, so that changes are identified early. Family members can be offered genetic counselling and carrier testing. Patients in Hyderabad are reviewed at Apollo Hospitals, Financial District, with onward referral to transplant services when appropriate.
When to seek urgent care
Seek emergency care for a sudden increase in breathlessness, chest pain, fever with worsening cough, coughing up blood, bleeding that will not stop, or bluish lips. Always tell emergency staff that you have Hermansky-Pudlak syndrome and a platelet bleeding disorder.
Frequently asked questions
Does everyone with Hermansky-Pudlak syndrome develop lung fibrosis?
No. Lung fibrosis mainly occurs in certain subtypes, especially HPS-1, HPS-2 and HPS-4. Genetic testing identifies the subtype and helps decide how closely the lungs need monitoring.
At what age does the lung disease start?
It typically appears in the thirties or forties, though it can begin earlier, particularly in HPS-2 where it may start in childhood.
Can a lung biopsy be done?
Biopsy is generally avoided because of the bleeding tendency. Diagnosis usually relies on genetic testing, CT and lung function tests.
Are antifibrotic drugs used in HPS?
Pirfenidone and nintedanib may be considered, although evidence specifically in HPS is limited. Your specialist will discuss the potential benefits and side effects.
Is lung transplantation possible with a bleeding disorder?
Yes. Lung transplantation has been carried out successfully in HPS with careful planning between the transplant team and haematology.
Should my brothers and sisters be tested?
Because HPS is recessively inherited, siblings may be affected or be carriers. Genetic counselling can guide testing for the family.
Related conditions and procedures
Consult Dr. Gogineni Ratnakara Rao
Apollo Hospitals, Financial District: Monday to Saturday, 8:30 AM to 5:00 PM. Anything in Lung Clinic, Chanda Nagar: Monday to Saturday (Thursday closed), 6:00 PM to 9:00 PM.