Background/Purpose

Arthritis is the most frequent manifestation of Blau syndrome, an autoinflammatory disorder caused by the genetic mutation of NOD2. However, the detailed information on arthritis in Blau syndrome which the therapeutic strategy should be based on was 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.

Methods

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.

Results

Ten patients whose age ranged from 10 months to 37 years enrolled in this study. Although only four 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 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 (Figure). 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 % vs. 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 2^nd ultrasound examination, total PD scores markedly decreased after initiating the treatment with a TNF antagonist.

Conclusion

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.

Figure. Mean gray-scale and power Doppler scores for intra-articular- and teno-synovitis in each joint

Mean ultrasound scores for each joint in 10 patients are shown in color grades. Only 1^st ultrasound examinations in Patient 5 and 6 are included.

* Ultrasound scores for tenosynovitis are not applicable in elbows and knees where typical tenosynovium does not exist.