ArticleBlood2024
Diagnostic guidelines for familial hemophagocytic lymphohistiocytosis revisited.
Article in Blood, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
58 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Guidelines on the Use of Therapeutic Apheresis in Clinical Practice-Evidence-Based Approach From the Writing Committee of the American Society for Apheresis: The Tenth Special Issue.Journal of clinical apheresis · 2026Guideline
- HLHRUXO: a prospective trial of a ruxolitinib-containing regimen for children with hemophagocytic lymphohistiocytosis.Blood advances · 2026Trial
- Machine learning for prediction in secondary hemophagocytic lymphohistiocytosis: real progress, real limits, and the potential of synthetic data.Intensive care medicine · 2026Article
- Two novel kindreds with autosomal recessive STAT2 deficiency.Journal of human immunity · 2026Article
- Diagnostic performance of HScore for macrophage activation syndrome complicating Still's disease in adults: a multicentre case-control study.Rheumatology (Oxford, England) · 2026Article
- Beyond the Storm: CXCL9 and the New Era of Precision Hemophagocytic Lymphohistiocytosis Diagnostics.Diagnostics (Basel, Switzerland) · 2026Review
- Neonatal Aicardi-Goutières syndrome presenting with macrophage activation syndrome-like hyperinflammation and severe congenital glaucoma: a case report.Pediatric rheumatology online journal · 2026Article
- Hyperferritinemia: Pathophysiology, Etiologies, and Diagnostic Approach.European journal of haematology · 2026Review
- Article
- Simultaneous onset of familial hemophagocytic lymphohistiocytosis and T-cell large granular lymphocytic leukemia in an adult.Annals of hematology · 2026Article
- Secondary hemophagocytic lymphohistiocytosis following bacterial pneumonia managed with dexamethasone monotherapy: a case report.Annals of medicine and surgery (2012) · 2026Article
- The HLH-Risk-Calculator is a machine learning-based tool to predict course & mortality of secondary hemophagocytic lymphohistiocytosis.Intensive care medicine · 2026Article
- Clinical characteristics and an admission-time predictive model for severe scrub typhus and secondary HLH in adults.BMC infectious diseases · 2026Article
- Reactive and therapy induced bone marrow changes linked to systemic infectious and non-infectious disorders including MAS/HLH report from the European association for haematopathology, Dubrovnik 2024.Virchows Archiv : an international journal of pathology · 2026Article
- Variants in human CD48 lead to impaired T cell immunity and increased inflammation.The Journal of clinical investigation · 2026Article
- First Infant Desensitization to Liposomal Amphotericin B.The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG · 2026Article
- Natural Killer Cell Assays: Clinical Applications and Future Directions.Annals of laboratory medicine · 2026Review
- Prevalence and Diagnostic Challenge of Hemophagocytic Lymphohistiocytosis Syndrome in Critically Ill Patients.European journal of haematology · 2026Article
- Identifying Hemophagocytic Lymphohistiocytosis and Describing Outcomes Using Computable Phenotypes: Retrospective Cohort Study.JMIR cancer · 2026Article
- CXCL9 as a novel prognostic marker to identify high-risk adults with hemophagocytic lymphohistiocytosis.Blood · 2026Article
Corrections and comments
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Authors and funding
19 authors.
Funding
Abstract
abstractCurrent 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%). Thus, we conclude that the HLH-2004 criteria (without NK-cell function) have significant validity in their current form when tested against severe infections or sJIA. It is important to exclude underlying malignancies and atypical infections. In addition, complementary cellular and genetic diagnostic guidelines can facilitate necessary confirmation of clinical diagnosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.