Background: SITRAME (Systemic Inflammatory Truncular Recurrent Acute Macular Eruption) syndrome is a newly described disease [1]. Patients present in adulthood with recurrent flares of the disease associated with stereotypical truncal macular eruption, fever and fatigue. Flares are most commonly triggered by viral infection or injection of the mRNA vaccine against SARS-CoV2. When colchicine was introduced empirically, its efficacy was poor. On the other hand, the introduction of omalizumab led to a reduction in the frequency of flares in two patients.

Objectives: In this study, we aim to determine the pathophysiological mechanism of the disease.

Methods: 12 patients were recruited to perform a multi-level characterisation of the disease. This characterisation includes phenotypic analysis of peripheral blood mononuclear cells (PBMC) by flow cytometry, assessment of plasmatic cytokine levels by ELISA, assessment of cellular cytokine production by flow cytometry and transcriptomic analysis using a NanoString panel. All analyses were performed on blood from basal and flare patients, except for the transcriptomic analysis, which was performed on basal patients only. Statistical analyses were performed using Wilcoxon test for transcriptomic data and Kruskal-Wallis test for all other analyses.

Results: Patients show high inter-individual heterogeneity without differences in major cellular phenotypes compared to healthy donors. Transcriptomic analysis revealed a common inflammatory signature with a high proportion of interferon-induced genes (32% of upregulated genes). Flare patients showed significantly higher plasmatic levels of CXCL10 and CCL19 compared to healthy donors ( p=0.0384 and p=0.0208 , respectively). Without any in vitro stimulation, monocytes from flare patients show increased interferon-α production compared to patients with a basal state ( p=0.0382 ). Without in vitro stimulation, plasmacytoid dendritic cells from flare patients show increased interferon-α production compared to healthy donors ( p=0.0438 ).

Conclusion: The upregulation of CXCL10, a chemokine that is highly induced by interferon-α, and higher levels of interferon-α production in cells from patients with a flare of the disease suggest a role for interferon-α in the SITRAME syndrome. In addition, the common inflammatory molecular signature of patients in the basal state of the disease supports pathological processes in SITRAME patients, even when the disease is quiescent.

REFERENCES: [1] Soria A, Amsler E, Garel B, Moguelet P, Tieulié N, Cordoliani F, et al. Systemic inflammatory trunk recurrent acute macular eruption ( SITRAME ): A new auto-inflammatory syndrome in adult? Acad Dermatol Venereol. 2022 Nov 30;jdv.18771.

Acknowledgements: NIL.

Disclosure of Interests: None declared.