Chromosomal Integration of HHV-6 in a Preterm Neonate: A Rare Case of Hyperleukocytosis and Clinical Implications

Leukocytosis in neonates can occur because of infectious, inflammatory, malignant, or physiological processes. Hyperleukocytosis is defined as a total leukocyte count (TLC) exceeding 100,000 per mm3, warranting immediate evaluation. Neonates with hyperleukocytosis are at risk of leukostasis and the associated severe complications, including respiratory distress, myocardial ischemia, hyperuricemia, acute renal failure, infarction, and hemorrhage. Differentiating leukemia and leukemoid reactions in neonates presenting with elevated TLC is challenging but critical. We present a unique case of a preterm male neonate with hyperleukocytosis, initially suspected to have an underlying malignancy. The neonate’s clinical course was complicated by respiratory distress syndrome and anemia of prematurity, necessitating neonatal intensive care unit management. Further investigation revealed high human herpesvirus 6 (HHV-6) DNA levels in the whole blood, leading to a chromosomally integrated HHV-6 (ciHHV-6) diagnosis. CiHHV-6 is characterized by HHV-6 DNA integration into the host genome. Accurate diagnosis relies on whole-blood quantitative PCR, distinguishing ciHHV-6 from an active infection. The neonate remained asymptomatic, and antiviral treatment was deemed unnecessary. This case underscores the importance of recognizing ciHHV-6 as a potential cause of hyperleukocytosis in neonates and highlights the value of whole-blood PCR for differentiation. Understanding the spectrum of HHV-6 infection in neonates is vital for appropriate management and prognostication.