Chediak-Higashi syndrome

Rare autosomal recessive immunodeficiency characterized by partial oculocutaneous albinism, recurrent pyogenic infections, and peripheral neuropathy. Hallmark: giant intracytoplasmic granules in leukocytes due to a LYST gene mutation disrupting lysosomal trafficking.

• CHS is often fatal in childhood without early intervention. Patients can develop a life-threatening accelerated phase (hemophagocytic lymphohistiocytosis) with overwhelming infections and organ failure. Recognizing the classic triad (albinism, infections, neuropathy) and giant granules on smear allows timely curative therapy.

• Infant or child with silvery hair, light skin (partial albinism) and frequent severe infections (skin, mucous membranes, respiratory) by *Staph aureus* or *Strep*; may have nystagmus and easy bruising.
• Labs: often neutropenia; peripheral smear shows neutrophils with giant azurophilic granules (pathognomonic).
• Progressive peripheral neuropathy (weakness, sensory loss) becomes apparent in later childhood.
• An accelerated phase (hemophagocytic syndrome) may occur, with fever, lymphadenopathy, hepatosplenomegaly, and pancytopenia due to lymphohistiocytic infiltration.

1. Suspect CHS in a child with albinism + recurrent bacterial infections (especially *S. aureus*); order a blood smear to look for giant granules in leukocytes.
2. Confirm diagnosis with LYST genetic testing. Evaluate for organ involvement and hemophagocytic lymphohistiocytosis if fevers or cytopenias are present.
3. Initiate prophylactic antibiotics and rigorous infection control. Consider G-CSF for neutropenia to boost neutrophil counts.
4. Plan for allogeneic hematopoietic stem cell transplant (HSCT) as early as possible – the only cure for the immune and hematologic defects.

1. Allogeneic bone marrow transplant is the definitive treatment (ideally performed before progressive neurologic degeneration).
2. Aggressive antimicrobial therapy for active infections; use granulocyte colony-stimulating factor (G-CSF) for neutropenia as needed.
3. If in accelerated phase (HLH): initiate an HLH protocol (etoposide-based chemoimmunotherapy) to control hyperinflammation, then proceed to transplant.
4. Supportive: high-dose vitamin C has been reported to partially improve neutrophil function and bleeding; give platelet transfusions for bleeding, and provide vision aids/rehabilitation for neurologic sequelae.

• Mnemonic – 3 P's of CHS: Partial albinism, Pyogenic infections, Peripheral neuropathy.
• Think Chediak = Colossal granules – neutrophils show giant fused lysosomal granules on smear.

• Unexplained fever, organomegaly, and cytopenias in a CHS patient → suspect accelerated HLH phase, a medical emergency requiring prompt treatment.
• Delayed HSCT: ongoing neurologic decline in CHS is irreversible – even after transplant the immune defects are cured but neuropathy can progress.

1. Recognize: Albinism + recurrent infections → suspect CHS; obtain CBC and peripheral smear for giant granules.
2. Confirm: Genetic testing for LYST mutation; consider screening siblings (autosomal recessive inheritance).
3. Stabilize: Treat active infections (broad-spectrum antibiotics, drain abscesses) and provide supportive care (G-CSF for neutropenia, vitamin C, transfusions as needed).
4. Definitive: Arrange hematopoietic stem cell transplant as early as possible (curative); if HLH has developed, treat with HLH protocol before transplant.

• Pale-skinned, light-haired child with recurrent skin and lung infections (often *Staph aureus*) and giant granules in neutrophils on peripheral smear → Chediak-Higashi syndrome.
• Patient with known CHS develops high fever, hepatosplenomegaly, pancytopenia, and coagulopathy → Accelerated phase (hemophagocytic lymphohistiocytosis).