Clinical and transcriptional response to the long-acting interleukin-1 blocker canakinumab in Blau syndrome-related uveitis.

Sporadic nucleotide-binding oligomerization domain–containing protein 2 (NOD-2)–associated pediatric granulomatous arthritis (Blau syndrome) (MIM ID #186580) is the genetic form of what was previously known as early-onset sarcoidosis, now better defined as pediatric granulomatous arthritis (1,2). It is characterized clinically by the triad of arthritis, skin rash, and uveitis, and histologically by the presence of noncaseating epithelioid granulomas in the affected sites (3). Genetic studies have shown that the disease is due to mutations in the nucleotide-binding domain of the NOD-2 (CARD-15) gene (4). The course of the disease is variable, but in many cases the prognosis is poor, with severe disabilities and sequelae in a high percentage of patients (5). Eye involvement is frequently progressive and can lead to panuveitis and severe complications up to legal blindness (5,6). The pathogenesis of Blau syndrome is not well known, but the disease is believed to belong to the spectrum of autoinflammatory disorders, for which interleukin-1 (IL-1) inhibition is now an effective treatment option. Canakinumab is an anti–IL-1β monoclonal antibody that is effective in the treatment of cryopyrin-associated periodic syndromes (7) and currently approved for that indication. Herein we report on the case of a patient with Blau syndrome whom we have followed up since early infancy (8). The patient developed sight-threatening, drug-resistant panuveitis, which responded quite well to canakinumab. During the first 6 months of treatment we also determined his gene expression profile, which showed down-regulation of several IL-1–related transcripts over time.