RESUMEN

Background Idiopathic recurrent pericarditis (IRP) is an orphan disease that carries significant morbidity, partly driven by corticosteroid dependence. Innate immune modulators, colchicine and anti-interleukin-1 agents, pioneered in monogenic autoinflammatory diseases, have demonstrated remarkable efficacy in trials, suggesting that autoinflammation may contribute to IRP. This study characterizes the phenotype of patients with IRP and monogenic autoinflammatory diseases, and establishes whether autoinflammatory disease genes are associated with IRP. Methods and Results We retrospectively analyzed the medical records of patients with IRP (n=136) and monogenic autoinflammatory diseases (n=1910) attending a national center (London, UK) between 2000 and 2021. We examined 4 genes (MEFV, MVK, NLRP3, TNFRSF1A) by next-generation sequencing in 128 patients with IRP and compared the frequency of rare deleterious variants to controls obtained from the Genome Aggregation Database. In this cohort of patients with IRP, corticosteroid dependence was common (39/136, 28.7%) and was associated with chronic pain (adjusted odds ratio 2.8 [95% CI, 1.3-6.5], P=0.012). IRP frequently manifested with systemic inflammation (raised C-reactive protein [121/136, 89.0%] and extrapericardial effusions [68/136, 50.0%]). Pericarditis was observed in all examined monogenic autoinflammatory diseases (0.4%-3.7% of cases). Rare deleterious MEFV variants were more frequent in IRP than in ancestry-matched controls (allele frequency 9/200 versus 2932/129 200, P=0.040). Conclusions Pericarditis is a feature of interleukin-1 driven monogenic autoinflammatory diseases and IRP is associated with variants in MEFV, a gene involved in interleukin-1ß processing. We also found that corticosteroid dependence in IRP is associated with chronic noninflammatory pain. Together these data implicate autoinflammation in IRP and support reducing reliance on corticosteroids in its management.

Asunto(s)

Enfermedades Autoinflamatorias Hereditarias , Pericarditis , Corticoesteroides , Enfermedades Autoinflamatorias Hereditarias/diagnóstico , Enfermedades Autoinflamatorias Hereditarias/tratamiento farmacológico , Enfermedades Autoinflamatorias Hereditarias/genética , Humanos , Pericarditis/diagnóstico , Pericarditis/tratamiento farmacológico , Pericarditis/genética , Pirina/genética , Derivación y Consulta , Estudios Retrospectivos

RESUMEN

OBJECTIVES: The systemic autoinflammatory diseases are rare conditions; to date, data on coronavirus disease 2019 (COVID-19) infection and vaccination safety are scarce. Agents targeting innate immune pathways have transformed the management of affected patients, and their outcomes are of wider interest given the role of inflammation in both viral clearance and severe COVID-19 disease. We surveyed patients with systemic autoinflammatory disease on biologic therapy to determine the prevalence and outcomes of COVID-19 infection and to gather early safety data on vaccination. METHODS: Electronic medical records of 248 patients with systemic autoinflammatory disease on biologic therapy at a national centre were reviewed. Patients were then surveyed in clinic or using a Web-based survey. RESULTS: In the cohort of 248 patients, no deaths were recorded. One hundred and seventy-five survey responses were received. Among the respondents, 27 reported suspected COVID-19 infection, of which 14 were confirmed by testing (8.0%). Two patients required hospital admission owing to dehydration. No patient required respiratory support or intensive care. One hundred and thirty-eight doses of COVID-19 vaccine had been administered to 130 patients. Side effects were reported after 71 of 138 (51.4%) administrations and were consistent with a flare of the underlying disease in 26 of 138 (18.8%) instances. No serious adverse events or hospital admissions were reported after vaccination. CONCLUSION: These data, including the largest published series of patients on anti-IL-1/6 biologics to receive any adenoviral vector or messenger RNA vaccine, show no serious early concerns regarding vaccination and will provide an urgently needed resource to inform decision-making of these patients and their clinicians.