What is the management approach for Hermansky-Pudlak Syndrome (HPS)?

Hermansky-Pudlak Syndrome: Management Approach

Management of Hermansky-Pudlak Syndrome requires a multidisciplinary surveillance strategy focused on preventing life-threatening complications, particularly pulmonary fibrosis in HPS types 1,2, and 4, with pirfenidone as the primary pharmacologic therapy and lung transplantation reserved for advanced disease. 1

Initial Diagnostic Confirmation and Subtype Classification

• Confirm the diagnosis through genetic testing to identify the specific HPS subtype (HPS1-9), as this directly determines prognosis and surveillance intensity. 2, 1
• HPS type 2 specifically presents with hypopigmentation, thrombocytopenia, neutropenia, and recurrent infections due to immune deficiency. 2
• Only HPS types 1,2, and 4 develop lethal pulmonary fibrosis requiring intensive monitoring. 1, 3
• HPS type 2 is associated with severe neutropenia and marked defects in antigen presentation and T-cell cytotoxicity. 2

Hematologic Management

• Avoid all antiplatelet agents (aspirin, NSAIDs) and anticoagulants due to severe platelet storage pool deficiency causing bleeding diathesis. 1, 4, 5
• Prepare for bleeding complications by having platelet transfusions readily available for any invasive procedures or surgeries. 6
• Coordinate with hematology for perioperative management, particularly in pregnancy where peripartum hemorrhage risk is substantial. 6
• Monitor for neutropenia in HPS type 2 and treat bacterial infections aggressively with appropriate antibiotics. 2

Pulmonary Surveillance and Treatment (HPS Types 1,2,4)

• Begin annual pulmonary function testing and high-resolution chest CT starting in early adulthood (age 20-25 years) to detect ground-glass opacities, reticulation, and traction bronchiectasis before symptomatic decline. 1
• Initiate pirfenidone immediately upon detection of pulmonary fibrosis progression, as this is the only FDA-approved antifibrotic therapy that may slow disease progression. 1
• Refer for lung transplantation evaluation when forced vital capacity (FVC) declines below 60% predicted or diffusing capacity (DLCO) falls below 40% predicted. 1
• Avoid environmental exposures that accelerate lung injury, including smoking, occupational dust, and known pulmonary toxins. 1

Immunodeficiency Management (HPS Type 2)

• Recognize that HPS type 2 can progress to an "accelerated phase" resembling hemophagocytic lymphohistiocytosis (HLH), which is fatal without standard chemotherapy and immunosuppression. 2
• Monitor for acute presentations with high fever, toxic appearance, lymphadenopathy, and hepatosplenomegaly suggesting HLH acceleration. 2
• Treat pyogenic bacterial infections promptly, as these primarily affect respiratory tract, skin, and other organs. 2
• Consider immunoglobulin replacement therapy if hypogammaglobulinemia develops. 2

Gastrointestinal Surveillance

• Screen for granulomatous colitis with colonoscopy if patients develop chronic diarrhea, abdominal pain, or gastrointestinal bleeding. 5, 3
• Manage colitis with standard inflammatory bowel disease protocols, including corticosteroids and immunomodulators as needed. 5
• Monitor for ceroid lipofuscin accumulation in reticuloendothelial cells, which can affect multiple organ systems. 5, 6

Ophthalmologic Care

• Refer to ophthalmology for management of oculocutaneous albinism complications, including nystagmus, photophobia, and reduced visual acuity. 1, 4
• Provide UV-protective eyewear and recommend avoidance of excessive sun exposure. 1

Dermatologic Protection

• Implement strict photoprotection with high-SPF sunscreen, protective clothing, and sun avoidance due to oculocutaneous albinism and increased skin cancer risk. 3
• Perform annual full-body skin examinations for early melanoma and non-melanoma skin cancer detection. 3

Cardiac and Renal Monitoring

• Screen for cardiomyopathy with baseline echocardiography and repeat every 2-3 years, as ceroid deposition can cause cardiac dysfunction. 5, 6
• Monitor renal function annually with serum creatinine and urinalysis, as renal failure has been rarely reported. 5

Critical Pitfalls to Avoid

• Never perform regional anesthesia (epidural/spinal) without hematology consultation due to severe bleeding risk from platelet dysfunction. 6
• Do not delay genetic subtyping, as HPS types without pulmonary fibrosis risk (types 3,5-9) require less intensive surveillance. 1, 3
• Avoid assuming normal immune function based on screening tests in HPS type 2, as immunologic abnormalities are variable and may not appear until the accelerated HLH phase. 2
• Do not miss the accelerated phase presentation, which requires immediate chemotherapy and immunosuppression to prevent mortality. 2

Pregnancy Considerations

• Coordinate care with maternal-fetal medicine, hematology, and anesthesia teams before conception or early in pregnancy due to high peripartum hemorrhage risk. 6
• Plan delivery at a tertiary center with blood bank capabilities for massive transfusion protocols. 6
• Avoid neuraxial anesthesia; prepare for general anesthesia if cesarean delivery is required. 6