POS1133 WHEN LUPUS IS ON FIRE: SEVERE, HYPER-INFLAMMATORY FLARES IN A MONOCENTRIC COHORT OF SYSTEMIC ERYTHEMATOSUS LUPUS (SLE)
Authors: D. Schilirò, E. Elefante, M. Maffi, C. Stagnaro, V. Signorini, L. Gualtieri, D. Zucchi, C. Cardelli, L. Carli, F. Ferro, C. Tani, M. Mosca
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> C-Reactive Protein (CRP) elevation in SLE is considered as strongly suggestive of infection. In clinical practice, however, it is not uncommon to observe an increase of inflammatory biomarkers related to SLE disease activity, namely to arthritis and serositis. <h3>Objectives:</h3> To characterize severe SLE flares with hyper-inflammatory stigmata and to compare them to severe, no-hyper-inflammatory flares. <h3>Methods:</h3> This is a retrospective analysis of prospectively collected data about severe disease flares occurred in the last five years in a monocentric cohort of SLE inpatients fulfilling 2019 ACR/EULAR classification criteria. In all cases concomitant infections, hematological or oncological conditions were excluded. The following data were collected from clinical charts: demographics, comorbidities, disease duration, cumulative organ involvement and damage accrual (SLICC-DI), disease activity (SLEDAI 2K, BILAG 2004), immunological profile, laboratory, imaging, histology, and treatment data at the time of the flare (T0), treatment and disease status at 3-, 6- and 12-months of follow-up. Hyper-inflammatory (HI) flares were defined by CRP serum levels ≥ 5 mg/dL and/or circulating ferritin levels ≥ 500 µg/L and were compared with flares without HI characteristics (no-HI), hospitalized in the same period in our Centre. Chi-square and t-tests were used for univariate analysis and a logistic regression model was used for multivariate analysis. <h3>Results:</h3> Among 122 severe flares hospitalized in the study period, based on the previously defined criteria, 22 flares, in 21 patients, were HI flares while 100, in 89 patients, were no-HI flares. No patient was found to belong to both groups. Patient and flare characteristics are summarized in Table 1. HI flares presented more frequently fever, pericarditis, arthritis and large vessels vasculitis and less frequently renal involvement, according to SLEDAI definitions. Lymphadenopathies and splenomegaly were also significantly associated with HI flares. According to the BILAG index, patients in the HI group presented more frequently a BILAG A score in the constitutional, cardiopulmonary, and hematological domains. As for laboratory data HI flares showed significantly higher levels of all the inflammatory biomarkers and higher C3 complement levels. Moreover, patients in the HI group presented more frequently a Lupus anticoagulant (LAC) positivity. At the multivariate analysis, cardiopulmonary, constitutional, and hematological involvement, splenomegaly, LAC+ and higher levels of fibrinogen confirmed to be independently associated with the HI phenotype (Table 2). Having a HI flare resulted significantly associated with an overall higher number of diagnostic procedures performed and to a longer duration of hospitalization. With exception of colchicine, no other significant differences were found with respect to therapeutic choices (Table 3); achievement of treatment targets at the different time-points and damage accrual at 12 months was also similar in the 2 subgroups. <h3>Conclusion:</h3> We identified a subgroup of SLE flares that defines a "hyper-inflammatory" phenotype whose severity seems to be mainly driven by marked constitutional symptoms. Interestingly, HI flares were associated with an underlying large vessels vasculitis in 3 cases. HI flares may represent a challenge for rheumatologists, particularly for the difficulty in differential diagnosis with infections and hematological conditions, leading to a higher number of diagnostic procedures and a longer duration of hospitalization. In view of the association with large vessel vasculitis, the clinician should consider performing a PET-CT scan in patients with HI phenotype to properly establish immunosuppressive therapy. This work suggests that severe SLE flares may present with proteiform and unexpected clinical characteristics. Further studies are needed to better outline clinical phenotypes, from "<i>bedside to bench</i>", looking for new biomarkers and tailored treatment strategies. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>