Open Access Open Badges Research article

Ultrasonographic assessment reveals detailed distribution of synovial inflammation in Blau syndrome

Kei Ikeda1*, Naotomo Kambe2, Syuji Takei34, Taiji Nakano5, Yuzaburo Inoue5, Minako Tomiita6, Natsuko Oyake7, Takashi Satoh2, Tsuyoshi Yamatou3, Tomohiro Kubota3, Ikuo Okafuji8, Nobuo Kanazawa9, Ryuta Nishikomori10, Naoki Shimojo5, Hiroyuki Matsue2 and Hiroshi Nakajima1

Author Affiliations

1 Department of Allergy and Clinical Immunology, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba 260-8677, Japan

2 Department of Dermatology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan

3 Division of Pediatric Rheumatology, Pediatric Medical Center, Kagoshima University Hospital, 8-35-1 Sakuragaoka, Kagoshima, Kagoshima 890-8520, Japan

4 School of Health Sciences, Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, Kagoshima 890-8520, Japan

5 Department of Pediatrics, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan

6 Department of Allergy and Rheumatology, Chiba Children’s Hospital, 579-1 Hetacho, Midori-ku, Chiba 266-0007, Japan

7 Department of Pediatrics, Hitachinaka General Hospital, 20-1 Ishikawacho, Hitachinaka, Ibaraki 312-0057, Japan

8 Department of Pediatrics, Kobe City Medical Center General Hospital, 2-1-1 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan

9 Department of Dermatology, Wakayama Medical University, 811-1 Kimiidera, Wakayama, Wakayama 641-0012, Japan

10 Department of Pediatrics, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan

For all author emails, please log on.

Arthritis Research & Therapy 2014, 16:R89  doi:10.1186/ar4533

Published: 8 April 2014



Arthritis is the most frequent manifestation of Blau syndrome, an autoinflammatory disorder caused by the genetic mutation of NOD2. However, detailed information on arthritis in Blau syndrome on which the therapeutic strategy should be based on is lacking. This multi-center study aimed to accurately characterize the articular manifestation of Blau syndrome and also to demonstrate the utility of musculoskeletal ultrasound in Blau syndrome.


Patients who had been diagnosed with Blau syndrome by genetic analysis of NOD2 were recruited. A total of 102 synovial sites in 40 joints were assessed semiquantitatively by ultrasound for gray-scale synovitis and synovial power Doppler (PD) signal.


In total, 10 patients whose age ranged from 10 months to 37 years enrolled in this study. Although only 4 joints (0.8%) were tender on physical examination, 81 joints (16.9%) were clinically swollen. Moreover, 240 (50.0%), and 124 (25.8%) joints showed gray-scale (GS) synovitis and synovial PD signal on ultrasound, respectively. Importantly, GS synovitis was present in 168 out of 399 non-swollen joints, in which 61 also exhibited synovial PD signal. Among 40 joint regions, the ankle, the wrist, and the proximal interphalangeal joints were the most frequently and severely affected joints. Comparisons between different synovial tissues demonstrated a significantly higher proportion of the joints with tenosynovitis as compared with that with intra-articular synovitis (41.5% versus 27.9%, P < 0.0001). In respect of age and treatment, synovial PD signals were minimal in the youngest patient and in the oldest two patients, and were relatively mild in patients receiving treatment with methotrexate plus TNF antagonists. In two patients who underwent the second ultrasound examination, total PD scores markedly decreased after initiating the treatment with a tumor necrosis factor (TNF) antagonist.


The detailed information on synovial inflammation obtained by ultrasound confirms the dissociation between pain and inflammation and the frequently involved joint regions and synovial tissue in the arthritis of Blau syndrome. Our data also demonstrate that ultrasonography can be a potent tool in monitoring the activity of synovial inflammation and in investigating the pathophysiology of arthritis in this rare but archetypical autoinflammatory condition.