Hepatic Manifestations of Pediatric Hemophagocytic Lymphohistocytosis
Manal Hamdy El Sayed, Fatma Soliman Ebeid, Salwa Mostafa Abd El Kader, Fatma Mohamed El-Shorbay, Iman Ahmed Ragab- General Medicine
Background
Hemophagocytic lymphohistiocytosis (HLH) is a rare hyper-inflammatory disorder.it is caused by benign systemic overgrowth of macrophages in the reticulo-endothelial system, leading to cytokine storm. The main features of HLH are; fever, splenomegaly, bi/pancytopenia; hyperferritinemia, hyper-triglyceridemia and hypofibrinogenemia; which if not diagnosed and early treated progresses to disseminated intravascular coagulopathy (DIC), multi-organ dysfunction with dismal outcome. Hepatic manifestations are not well recognized primary presentation in pediatric patients with HLH. This presentation mandates high levels of suspicious for early diagnosis.
Aim of the Work
To study the hepatic involvement clinical, laboratory, and pathological in patients with Familial/primary (1ry) HLH and in patients with secondary (2ry) acquired HLH.
Patients and Methods
A 6 month retrospective cohort study included 35 patients with genetically confirmed HLH divided into familial HLH by its types, X linked lymphoproliferative syndrome, HLH with partial albinism and secondary HLH; following at pediatric hematology/oncology clinic, Ain Shams University. By detailed review of clinical and laboratory data that include hepatic transaminases and synthetic liver function done at the time of presentation, at week 2, 8 from treatment start and at time of reactivation; Liver biopsy results and genetic analysis were recorded. Biochemical liver involvement was considered when alanine aminotransferase was three folds the upper level of normal at presentation. Overall and reactivation free survival were analyzed according to liver involvement
Results
Thirty five patients with HLH were recruited with age range of 2-108 months, 20(57.1%) of patients with HLH were genetically confirmed and 12(34.3%) of them had MUNC13D mutations, 3(8.6%) had STXBP2 mutation and 5(14.3%) had RAB27A mutation while 4(11.4%) had secondary HLH. 29(82.9%) had liver enlargement at diagnosis with hepatic reactivation in 18(51.4%). 8(22.8%) of patients had biochemical liver involvement; there was no significant difference in their demographic data or their clinical presentation, their final outcome or the type of mutant gene according to liver involvement.
Conclusion
HLH is a frequently lethal disease with a high variability in clinical presentation .it must be considered a differential in patients presenting with clinical signs of hepatic dysfunction especially when it is accompanied by cytopenias. Significant biochemical liver involvement is an under recognized presentation of HLH. Hepatic involvement did not impact response to treatment and disease outcome.