Diagnostic guidelines for familial hemophagocytic lymphohistiocytosis revisited

作者：Jan‐Inge Henter, Elena Sieni, Julia A. Eriksson, Elisabet Bergsten, Ida Hed Myrberg, Scott Canna, Maria Luisa Coniglio, Randy Quentin Cron, Kate F. Kernan, Ashish R. Kumar, Kai Lehmberg, Francesca Minoia, Ahmed Naqvi, Angelo Ravelli, Yongmin Tang, Matteo Bottai, Yenan Troi Bryceson, AnnaCarin Horne, Michael B. Jordan · 发表于：Blood · 年份：2024 · DOI：10.1182/blood.2024025077 · 被引用次数：99 · 研究领域：Autoimmune and Inflammatory Disorders Research、Adolescent and Pediatric Healthcare、Immune Cell Function and Interaction

ABSTRACT: Current hemophagocytic lymphohistiocytosis 2004 (HLH-2004)-based diagnostic criteria for familial hemophagocytic lymphohistiocytosis (FHL) are based on expert opinion. Here, we performed a case-control study to test and possibly improve these criteria. We also developed 2 complementary expert opinion-based diagnostic strategies for FHL in patients with signs/symptoms suggestive of HLH, based on genetic and cellular cytotoxicity assays. The cases (N = 366) were children aged <16 years with verified familial and/or genetic FHL (n = 341) or Griscelli syndrome type 2 (n = 25); 276 from the HLH-94/HLH-2004 databases and 90 from the Italian HLH Registry. All fulfilled the HLH-94/HLH-2004 patient inclusion criteria. Controls were 374 children with systemic-onset juvenile idiopathic arthritis (sJIA) and 329 + 361 children in 2 cohorts with febrile infections that could be confused with HLH and sepsis, respectively. To provide complete data sets, multiple imputations were performed. The optimal model, based on 17 variables studied, revealed almost similar diagnostic thresholds as the existing criteria, with accuracy 99.1% (sensitivity 97.1%; specificity 99.5%); the original HLH-2004 criteria had accuracy 97.4% (sensitivity 99.0%; specificity 97.1%). Because cellular cytotoxicity assays here constitute a separate diagnostic strategy, HLH-2004 criteria without natural killer (NK)-cell function was also studied, which showed accuracy 99.0% (sensitivity, 96.2%; specificity, 99.5...