Naymagon Leonard, Roehrs Philip, Hermiston Michelle, Connelly James, Bednarski Jeffrey, Boelens Jaap-Jan, Chandrakasan Shanmuganathan, Dávila Saldaña Blachy, Henry Michael M, Satwani Prakash, Ray Anish, Walkovich Kelly, Teachey David, Behrens Edward M, Canna Scott W, Kumar Ashish
Mount Sinai School of Medicine, Tisch Cancer Institute, 1470 Madison Avenue, New York, NY, 10029, USA.
Stem Cell Transplant and Cellular Therapies, Division of Hematology and Oncology, Department of Pediatrics, University of Virginia, Charlottesville, VA, USA.
Orphanet J Rare Dis. 2025 Apr 26;20(1):200. doi: 10.1186/s13023-025-03698-0.
Improved awareness of hemophagocytic lymphohistiocytosis (HLH) among clinicians has led to an increase in its diagnosis. Often diagnosis is made based on the HLH- 2004 criteria. While these criteria have considerable strengths, they lack specificity and may be fulfilled in the setting of many pro-inflammatory disorders. Genetic defects affecting cellular cytotoxicity cause familial (primary) HLH. On the other hand, secondary HLH is more a pathophysiologic process common to many conditions, rather than a singular disease entity. Improved genetic, immunologic, and functional testing have changed not only the way we diagnose HLH, but also how we treat it. In 2004, there were few active agents and regimens. In 2024, there are multiple safe and effective targeted therapies. We have begun to understand that routine and immediate use of etoposide-based therapy in secondary HLH is likely not appropriate, and emerging cytokine-directed therapies may be more rational interventions. Moreover, it is recognized that identifying and treating the driver of secondary HLH is at least as important as treating the cytokine storm and immune dysregulation. Unfortunately, over-reliance on, and narrow interpretation of, the HLH- 2004 criteria can lead to overdiagnosis, misdiagnosis, and unneeded exposure to drugs that can be harmful. It is important that clinicians understand the limitations of the current diagnostic paradigms for secondary HLH, and the shortcomings of reflexive use of etoposide-based therapy. Herein we will discuss the pros and cons of the current paradigm for the recognition, diagnosis, and treatment of secondary HLH.
临床医生对噬血细胞性淋巴组织细胞增生症（HLH）的认识提高，导致其诊断率上升。通常根据HLH - 2004标准进行诊断。虽然这些标准有相当大的优势，但它们缺乏特异性，在许多促炎疾病的情况下都可能满足这些标准。影响细胞毒性的基因缺陷会导致家族性（原发性）HLH。另一方面，继发性HLH更多是许多疾病共有的病理生理过程，而不是单一的疾病实体。基因检测、免疫检测和功能检测的改进不仅改变了我们诊断HLH的方式，也改变了我们治疗HLH的方式。2004年，有效的药物和治疗方案很少。到了2024年，有多种安全有效的靶向治疗方法。我们已经开始认识到，在继发性HLH中常规且立即使用依托泊苷为基础的治疗可能不合适，新兴的细胞因子导向治疗可能是更合理的干预措施。此外，人们认识到识别和治疗继发性HLH的驱动因素至少与治疗细胞因子风暴和免疫失调一样重要。不幸的是，过度依赖HLH - 2004标准并对其进行狭义解释可能导致过度诊断、误诊以及不必要地接触可能有害的药物。临床医生了解继发性HLH当前诊断模式的局限性以及反射性使用依托泊苷为基础的治疗的缺点非常重要。在此，我们将讨论当前继发性HLH识别、诊断和治疗模式的优缺点。
