Tumor necrosis factor‐alpha blockade ameliorates inflammatory response in two children with chronic infantile neurological, cutaneous and articular syndrome

Chronic infantile neurological, cutaneous and articular (CINCA) syndrome is a rare autoinflammatory disease caused by monogenic defects in the NLRP3 gene. Pro‐inflammatory cytokines such as interleukin (IL)‐1β play a crucial role in the pathogenesis, and IL‐1 receptor antagonists have been regarded as the mainstay therapy. Endogenous tumor necrosis factor (TNF)‐α was found recently to be involved in the onset of the disease. Here, we report two Chinese children with CINCA syndrome who had elevated serum levels of TNF‐α, with one carrying a novel mutation of c.1330T/G (p.444Phe/Val) in exon 3 of the NLRP3 gene. Anti‐TNF‐α (etanercept) therapy successfully alleviated both clinical symptoms and systemic inflammation after 6 months. These results suggest the complexity of the mechanisms of the disease and that TNF‐α blockade will broaden the therapeutic approach for a subset of patients.