Accelerated Phase of Chediak–Higashi Syndrome with Hemophagocytic Lymphohistiocytosis (HLH): Insights from a Pediatric Case

Introduction: Chediak–Higashi syndrome (CHS) is a rare autosomal recessive disorder, presenting in early childhood, characterized by immune system dysfunction and recurrent infections due to mutations in the lysosomal trafficking regulator (LYST) gene. On average, around 85% of CHS cases progress to an accelerated phase known as hemophagocytic lymphohistiocytosis (HLH). This case provides new insights into CHS, presenting in accelerated phase initially, obscuring the initial diagnosis of the genetic condition due to the non-specific immune dysfunction.

Case: We report a case of CHS in an accelerated phase in a 6-year-old boy with a history of recurrent infections, presenting with pancytopenia, fever and neck swelling in June 2024. He was born to consanguineous parents. Examination revealed non-tendered lymphadenopathy. Initial investigation findings were indicative of bicytopenia. Thereafter, concerns for HLH were raised due to significant alterations in inflammatory and HLH-associated markers. Subsequent laboratory findings revealed cytoplasmic granules in leukocytes on peripheral blood smear and cervical lymph node biopsy revealing necrotizing lymphadenitis. A bone marrow biopsy showed neutrophils and myeloid precursors containing abnormal intracytoplasmic granules. Moreover, final diagnosis of HLH was made via bone marrow trephine which showed hypercellular ill-defined granulomas with eosinophilic debris and focal areas of necrosis. Ultimately, HLH-directed therapy with dexamethasone and etoposide was prescribed. Meanwhile genetic tests revealed homozygous nonsense LYST gene mutation, confirming the diagnosis of CHS. Further admissions for jaundice, gum bleeds, pan-resistant bacterial infections and seizures followed, but the patient's health deteriorated, and he succumbed to his illness.

Conclusion: Our case highlights the diagnostic challenges and importance of considering CHS among the differentials for HLH, especially in consanguineous backgrounds. This case emphasizes the importance of early peripheral smear review and genetic testing for children presenting with ambiguous immunodeficiency and history of recurrent infections to avoid delay in diagnosis as reported in our case.