Using a Minimal Parameter Set for Early Diagnosis of Hemophagocytic Lymphohistiocytosis in Non-European Children

Abstract

Case series Patients: Male, 4-day-old • Male, 29-day-old Final Diagnosis: Hemophagocytic lymphohistiocytosis (HLH) Symptoms: Fever Medication: — Clinical Procedure: — Specialty: Hematology • Immunology Objective: Challenging differential diagnosis Background: Children with hemophagocytic lymphohistiocytosis require rapid diagnosis for timely treatment. However, diagnostic delays may arise in settings with limited clinical resources. To address this issue, a simplified rule for diagnosing hemophagocytic lymphohistiocytosis has recently been proposed. We retrospectively applied this diagnostic rule in 2 infants to evaluate its generalizability to non-European children. Case Reports: We present 2 cases of hemophagocytic lymphohistiocytosis, involving an Asian neonate with secondary hemophagocytic lymphohistiocytosis subsequent to echovirus infection and an African infant with familial hemophagocytic lymphohistiocytosis caused by PRF1 mutation. Limitations on time and clinical resources prevented tissue biopsy and measurement of natural killer cell activity in either case at our center. The Asian case did not meet HLH-2004 criteria, but both cases met a rapid diagnostic rule on admission to our center. Both cases were transported to a tertiary center and diagnosed with hemophagocytic lymphohistiocytosis based on HLH-2004 criteria. Although treatment suppressed disease activity, the Asian neonate died of multiple-organ failure at age 6 months. The African infant remains in remission after allogenic cord blood stem cell transplantation. Conclusions: A simplified diagnostic rule for hemophagocytic lymphohistiocytosis may be useful for early diagnosis of hemophagocytic lymphohistiocytosis in Asian and African children, especially in resource-limited clinical settings. Further investigation is required to elucidate whether early diagnosis with a simplified diagnostic rule improves treatment outcomes for children with hemophagocytic lymphohistiocytosis.

Neonatal hemophagocytic lymphohistiocytosis: A meta‐analysis of 205 cases

“…Studies were excluded if they did not discuss nHLH ( n = 280); aggregated nHLH patient data with all ages ( n = 83); provided insufficient detail and/or data describing a case of nHLH ( n = 28); and for other reasons ( n = 8). Two‐hundred‐five cases of nHLH from 142 articles were included in our analysis 12–152 …”

Secondary hemophagocytic lymphohistiocytosis in children (Review)

“…In order to accelerate diagnosis, rapid screening by flow cytometry has been used to identify some forms of p-HLH through the assessment of expression of intracellular perforin, SAP, and XIAP protein in peripheral blood cells ( 42 ) while waiting for the results of the genetic tests. Moreover, some simplified clinical algorithms have been proposed, for example, the ‘H score’ ( 43 , 44 ) scoring system and the ‘Minimal Parameter set’ ( 45 ), but none of these scores are conclusive in differentiating secondary HLH forms that might benefit from a different treatment.…”