Refractory cutaneous manifestations constitute a significant unmet need in patients with cutaneous lupus (CLE), even in the setting of systemic lupus erythematosus (SLE) with otherwise good control of inflammatory manifestations. Anifrolumab, an anti-interferon I receptor monoclonal antibody has recently been approved for serologically positive SLE with or without CLE, but real-life efficacy and safety data are currently limited. In addition, relatively limited evidence exists about the spectrum of cutaneous manifestations potentially benefitting from anifrolumab treatment and about the optimal clinimetrics to monitor treatment efficacy. While summarising current evidence on the topic in the literature, we report on four patients with SLE and refractory CLE who were successfully treated with anifrolumab. We also describe the potential usefulness and complementarity of the cutaneous lupus activity investigator’s global assessment (CLA-IGA) in assessing cutaneous activity in patients treated with anifrolumab.

Systemic lupus erythematosus (SLE) is characterised by generalised immune dysfunction, including infection susceptibility. Infection-associated flares (IAFs) are common and might rapidly self-resolve, paralleling infection resolution, but their specific clinical phenotype is poorly understood. Therefore, we screened 2039 consecutive visits and identified 134 flares, defined as a loss of the lupus low disease activity state (LLDAS), from 1089 visits at risk spanning over multiple follow-up years, yielding an average yearly LLDAS deterioration rate of 17%. Thirty-eight IAFs were isolated from the total flares and were mostly related to bacterial and herpesvirus infections. When compared to other flares (OFs; n = 98), IAFs showed no milder patterns of organ involvement and similar rates of long-term damage accrual, as estimated by conventional clinimetrics. Arthritis in IAFs was more severe than that in OFs [median (interquartile range) DAS-28 2.6 (2.3–4.1) vs. 2.0 (1.6–2.7); p = 0.02]. Viral IAFs were characterised by atypically lower levels of anti-DNA antibodies (p < 0.001) and possibly abnormally high complement levels when compared to flares of different origin. These data suggest that IAFs are of comparable or even higher severity than OFs and may subtend distinct pathophysiological mechanisms that are poorly tackled by current treatments. Further research is needed to confirm these data.

Non-viral myocarditis is rare but relatively more frequent in patients with systemic autoimmune diseases (such as systemic lupus erythematosus, SLE, and allied conditions) than in the general population. In rare cases, mRNA-based vaccines can also trigger non-viral myocarditis. Limited data are available about the cardiac safety of mRNA vaccines in this subset of patients. Here, we report data from a third-level hospital on long-term safety, leveraging on a previously described cohort of 13 consecutive patients with SLE, Undifferentiated (UCTD) and Mixed Connective Tissue disease (MCTD), and a history of myocarditis, who had received anti-COVID-19 vaccination between April 2021 and January 2022. Demographics and clinical data (including validated clinometric for SLE) were collected at baseline, at the first available visit following the primary vaccination cycle, after an additional 12 months, and at the last available follow-up after at least 36 months. Twelve patients, seven females, ten with SLE, one MCTD, and one UCTD, had a median follow-up of 41 (35–45) months. One patient was lost at follow-up. No disease flare or sign of myocarditis recurrence were observed. At last visit, all patients were in a low disease activity state (LLDAS), and all but one were in remission, according to the Definition of Remission in SLE (DORIS) criteria. No significant variations in disease activity or damage accrual nor in markers of inflammation and myocardial injury were observed. Our data suggest that mRNA-based anti-COVID-19 vaccines in patients with previous autoimmune myocarditis in the context of SLE and allied conditions have a good long-term safety profile.