Two articles this week focus on Erdheim-Chester disease (ECD), a rare histiocytosis that mainly affects adults. Clonal somatic mutations primarily involving proteins in the BRAF and MPAK pathways have established ECD as a myeloid neoplasm, with targeted therapies now available for patients. In the first paper, an international panel presents new consensus recommendations for evaluation and treatment of ECD. In the second paper, Pegoraro and colleagues present long-term outcomes of patients with ECD treated with sirolimus, with responses in patients both with and without BRAF mutations.

Interleukin 1 (IL-1), a central mediator of innate immunity, is considered a master cytokine of local and systemic inflammation. IL-1 has emerged as pivotal in the pathogenesis of autoinflammatory diseases (AIDs), and blockade of its pathway has become a crucial target for therapy. Anakinra (ANA), a recombinant IL-1β receptor antagonist, was the first anti-IL-1 agent employed in clinical practice. ANA is currently approved for the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis, adult-onset Still’s disease, and cryopyrin-associated autoinflammatory syndrome. It has also been successfully used for off-label treatment of various monogenic, polygenic, or undefined etiology systemic AIDs. This review describes currently available evidence for the off-label use of ANA in pediatric rheumatologic diseases. Specifically, the use of ANA in Kawasaki disease, idiopathic recurrent pericarditis, Behçet disease, monogenic AIDs, undifferentiated AIDs, chronic non-bacterial osteomyelitis, macrophage activation syndrome, and febrile infection-related epilepsy, in terms of its safety and efficacy. In selected pediatric rheumatic disorders, the off-label administration of ANA appears to be effective and safe. In order to control severe and/or relapsing disease, ANA should be considered as a valuable treatment option in children suffering from rare inflammatory diseases. However, currently available data consist of retrospective studies and short case series; thus, randomized controlled trials and larger series with long-term follow up are mandatory to better assess the efficacy and cost effectiveness of ANA in these challenging patients.

This narrative review aims to report the main clinical manifestations, therapeutic strategies, outcomes, and complications of acute SARS-CoV-2 infection in childhood and to summarize the data relating the SARS-CoV-2 vaccination efficacy and safety in pediatric age. SARS-CoV-2 infection mostly occurs asymptomatically in the pediatric population, while multisystem inflammatory syndrome in children (MIS-C) represents the most severe coronavirus disease 2019 (COVID-19)-related illness, a life-threatening event with a high morbidity rate. After the development of SARS-CoV-2 vaccines and their subsequent approval in children, the rate of infection as well as the number of its related complications have shown a drastic decrease. Fully vaccinated children are protected from the risk of developing a severe disease and a similar protective role has been observed in the reduction of complications, in particular MIS-C. However, long-lasting immunity has not been demonstrated, booster doses have been required, and reinfection has been observed. With regards to vaccine safety, adverse events were generally mild to moderate in all age groups: local adverse events were the most commonly reported. Nevertheless, a potential association between SARS-CoV-2 vaccine and the subsequent development of inflammatory manifestations has been suggested. Myocarditis has rarely been observed following vaccination; it appeared to be more frequent among adolescent males with a mild clinical course leading to a complete recovery. SARS-CoV-2 vaccine-related MIS-C cases have been described, although a univocal definition and an exact time interval with respect to vaccination has not been reported, thus not establishing a direct causal link. Current evidence about COVID-19 vaccination in children and adolescents suggest that benefits outweigh potential risks. Long-term data collection of the post-authorization safety surveillance programs will better define the real incidence of SARS-CoV-2 vaccine-related complications in the pediatric population.