P013 Haemophagocytic lymphohistiocytosis triggered by rheumatological disease in adults: is this a distinct disease entity? Results from a single-centre retrospective registry

Background/Aims Historically, haemophagocytic lymphohistiocytosis (HLH) associated with rheumatological disease has been termed macrophage activation syndrome (MAS). Inconsistent nomenclature is confusing and may hinder patient care and research. This study aims to determine whether rheumatic-triggered HLH has distinct clinical features from other causes of HLH. Methods We conducted a single-centre retrospective cohort study of adult patients admitted to UCLH between April 2019 and December 2024. Ethical approval was obtained. Patients were categorised according to the relationship between HLH and rheumatological disease: rheumatic-triggered HLH (RT-HLH), where rheumatic disease was judged to be the primary trigger; rheumatic-background HLH (RB-HLH), where a rheumatic diagnosis was present but not considered causative; and non-rheumatic HLH (NR-HLH), with no known underlying rheumatological condition. Laboratory values were taken at first peak ferritin. Results 147 admissions corresponding to 139 patients were identified: 113 NR-HLH, 17 RT-HLH, and 17 RB-HLH. Among RT-HLH cases, 76.5% had Still’s disease and 23.5% had systemic lupus erythematosus (SLE). In 9 (52.9%) cases, HLH represented the first presentation of a rheumatic disease. In RB-HLH, underlying diagnoses included rheumatoid arthritis (23.5%), Still’s disease (17.6%), SLE (17.6%), and sarcoidosis (17.6%). Infection was the most common trigger in RB-HLH (64.7%), followed by lymphoma (17.6%). Median age was lower in RT-HLH (32 years) than RB-HLH (35 years; p = 0.458) and significantly lower than NR-HLH (47 years; p = 0.001). ITU admission rates were lower in RT-HLH (53%) compared with RB-HLH (71%) and NR-HLH (76%), although differences were not significant. Cytopenias were more common in NR-HLH with two-lineage cytopenias observed in 83.2% of NR-HLH compared with 41.3% and 58.8% of RT-HLH and RB-HLH, respectively (p = 0.000, p = 0.044). Other HScore parameters did not differ significantly between groups. Ferritin was similar between RT-HLH and NR-HLH (18,736 vs 18,139 µg/L; p = 0.753). CRP distinguished RT-HLH from RB-HLH (22 vs 63 mg/L; p = 0.046) and NR-HLH (111 mg/L; p < 0.001). ESR was lower in RT-HLH (22 mm/hr) than RB-HLH (52 mm/hr; p = 0.028) and lower than NR-HLH (35 mm/hr; p = 0.071). 28-day mortality did not differ significantly between groups. Kaplan-Meier analysis showed comparable early mortality during the first 7 days, followed by higher late mortality in NR-HLH. ICU admission, low eGFR, thrombocytopenia, multi-lineage cytopenia, and prior immunosuppression were significantly associated with mortality (p < 0.01) across all groups. Conclusion In our cohort, Stills disease and SLE were the only rheumatic triggers of HLH and should be considered early in the management of patients with HLH. Whilst RT-HLH patients are likely to be younger, with the exception of cytopenias, there were no significant differences in HScore parameters compared with other causes of HLH. Mortality was not significantly different, although limited sample sizes may limit interpretation. In those patients with underlying rheumatic disease, infection is the likely trigger for HLH not their underlying rheumatic disease. Disclosure A. Holloway: Grants/research support; UCLH Charity Grant 2024 (7253). N. Kvam: None. Z. Li: None. A.E. Oppong: None. N. Sah: None. D. Shah: None. G. Woodward: None. C. Moezinia: None. J. Nouza: None. E.C. Jury: None. J.J. Manson: Grants/research support; Supported by the National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre, and is part of the MRC Rare Disease Platform Node for Histiocytic Disorders [MR/Y008189/1]. A. Jones: None.