Objectives To collect clinical information and NOD2 mutation data on patients with Blau syndrome and to evaluate their prognosis.
Methods Fifty patients with NOD2 mutations were analysed. The activity of each NOD2 mutant was evaluated in HEK293 cells by reporter assay. Clinical information was collected from medical records through the attending physicians.
Results The study population comprised 26 males and 24 females aged 0–61 years. Thirty-two cases were sporadic, and 18 were familial from 9 unrelated families. Fifteen different mutations in NOD2 were identified, including 2 novel mutations (p.W490S and D512V); all showed spontaneous nuclear factor kappa B activation, and the most common mutation was p.R334W. Twenty-six patients had fever at relatively early timepoints in the disease course. Forty-three of 47 patients had a skin rash. The onset of disease in 9 patients was recognised after BCG vaccination. Forty-five of 49 patients had joint lesions. Thirty-eight of 50 patients had ocular symptoms, 7 of which resulted in blindness. After the diagnosis of Blau syndrome, 26 patients were treated with biologics; all were antitumour necrosis factor agents. Only 3 patients were treated with biologics alone; the others received a biologic in combination with methotrexate and/or prednisolone. None of the patients who became blind received biologic treatment.
Conclusions In patients with Blau syndrome, severe joint contractures and blindness may occur if diagnosis and appropriate treatment are delayed. Early treatment with a biologic agent may improve the prognosis.
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Handling editor Josef S Smolen
Collaborators PIDJ (Primary Immunodeficiency and Autoinflammatory Diseases Database Project) members in the JSIAD (Japanese Society for Immunodeficiency and Autoinflammatory Diseases): Shigeaki Nonoyama, Kohsuke Imai, Katsuhiro Arai, Kazushi Izawa, Takashi Ishige, Masataka Ishimura, Hiroaki Ida, Norimitsu Inoue, Hidenori Ohnishi, Satoshi Okada, Nobuo Kanazawa, Hirokazu Kanegane, Toshinao Kawai, Naotomo Kambe, Tomohiro Koga, Yoji Sasahara, Hidetoshi Takada, Ichiro Takeuchi, Ryuta Nishikomori, Takahiko Horiuchi, Kiyoshi Migita, Tomoyuki Mizukami, Takako Miyamae Hideki Muramatsu, Kunihiko Moriya, Takahiro Yasumi, Takashi Yamazaki, Masafumi Yamada and Taizo Wada.
Contributors All authors have made substantial contribution to the conception or design of the work or acquisition, analysis or interpretation of data. All authors were involved in drafting the work, revising it critically and have read final approval of the version.
Funding This study was supported in part by a research grant from MHLW, Japan and AMED under Grant Numbers JP17ek0109100 and JP18ek0109237.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, conduct, reporting or dissemination plans of this research.
Patient consent for publication Not required.
Ethics approval The study protocol was in accordance with the guidelines of the Institutional Review Board of Kansai Medical University (2018204).
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement No data are available. There are no additional unpublished data.
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