HLH:
Navigating a hyperinflammatory threat
Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of hyperinflammatory immune dysregulation associated with a variety of overlapping conditions, including genetic predisposition, chronic inflammation, malignancies, rheumatological conditions, or infectious triggers.1,2
Primary HLH is a term used to describe hyperinflammation in patients with genetic mutations affecting the cytotoxic function of natural killer (NK) cells and T cells.1,3
Macrophage activation syndrome (MAS) is another subset of HLH that may occur as a complication of rheumatic disease, most commonly in patients with Still’s disease, including systemic juvenile idiopathic arthritis (sJIA).4
The role of IFNγ in hyperinflammation
Primary HLH and MAS are both characterized by excessive T-cell and macrophage activation, resulting in the overproduction of proinflammatory cytokines. High interferon gamma (IFNγ) levels are a key driver of disease pathology, and a biomarker of IFNγ activity known as CXCL9 is an indicator of severity in both conditions.5
Recognizing how IFNγ contributes to the clinical features of primary HLH and MAS can help you diagnose and start effective treatment sooner.5
For patients with HLH, prompt diagnosis is crucial
The clinical presentation of HLH is heterogeneous, rapidly progressive, and can be fatal if untreated. It’s critical to ensure that patients are diagnosed as soon as possible.1
It’s also essential to identify any underlying triggers that can be associated with the development of HLH in patients.1
The presence or absence of certain triggers may influence the management strategies you will pursue.6
References: 1. Jordan MB, Allen CE, Weitzman S, Filipovich AH, McClain KL. How I treat hemophagocytic lymphohistiocytosis. Blood. 2011;118(15):4041-4052. doi:10.1182/blood-2011-03-278127 2. Shakoory B, Geerlinks A, Wilejto M, et al. The 2022 EULAR/ACR points to consider at the early stages of diagnosis and management of suspected haemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS). Arthritis Rheumatol. 2023;75(10):1714-1732. doi:10.1002/art.42636 3. Canna SW, Marsh RA. Pediatric hemophagocytic lymphohistiocytosis. Blood. 2020;135(16):1332-1343. doi:10.1182/blood.2019000936 4. Sen ES, Clarke SL, Ramanan AV. Macrophage activation syndrome. Indian J Pediatr. 2016;83(3):248-253. doi:10.1007/s12098-015-1877-1 5. De Benedetti F, Prencipe G, Bracaglia C, Marasco E, Grom AA. Targeting interferon-γ in hyperinflammation: opportunities and challenges. Nat Rev Rheumatol. 2021;17(11):678-691. doi:10.1038/s41584-021-00694-z 6. George MR. Hemophagocytic lymphohistiocytosis: review of etiologies and management. J Blood Med. 2014;5:69-86. doi:10.2147/JBM.S46255
