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.
Keywords: NLRP3; chronic infantile neurological cutaneous and articular syndrome; etanercept; interleukin-1; tumor necrosis factor-α.
© 2020 Japanese Dermatological Association.