Overlapping Features in Kawasaki Disease-Related Arthritis and Systemic-Onset Juvenile Idiopathic Arthritis: A Nationwide Study in Japan

• Published in: Frontiers in pediatrics 2021-07, Vol.9, p.597458-597458
• Main Authors: Kanemasa, Hikaru, Nanishi, Etsuro, Takada, Hidetoshi, Ishimura, Masataka, Nishio, Hisanori, Honjo, Satoshi, Masuda, Hiroshi, Nagai, Noriko, Nishihara, Takahiro, Ishii, Tohru, Adachi, Takenori, Hara, Satoshi, Lin, Lisheng, Tomita, Yoshie, Kamizono, Junji, Komiyama, Osamu, Kohdera, Urara, Tanabe, Saori, Sato, Atsuo, Hida, Shinya, Yashiro, Mayumi, Makino, Nobuko, Nakamura, Yosikazu, Hara, Toshiro, Ohga, Shouichi
• Format: Article
• Language: English
• Subjects: arthritis; biologics; immunosuppressive therapy; juvenile idiopathic arthiritis; Kawasaki disease; Pediatrics
• ISSN: 2296-2360; 2296-2360
• DOI: 10.3389/fped.2021.597458

Background: Arthritis may occur after the diagnosis of Kawasaki disease (KD). Most cases are self-limiting; however, some patients require prolonged treatment. Method: To characterize KD-related arthritis, 14 patients who required arthritis treatment within 30 days after the diagnosis of KD were recruited from the 23rd KD survey in Japan. Twenty-six additional patients were included from our tertiary center and literature review cohorts. Results: The estimated prevalence of KD-related arthritis in Japan was 48 per 100,000 KD patients. Patients with KD-related arthritis had an older age at onset (52 vs. 28 months, P = 0.002) and higher rate of intravenous immunoglobulin (IVIG) resistance in comparison to those without arthritis (86 vs. 17%, P < 0.001). Among 40 patients, 18 had arthritis in the acute phase KD (continued fever-onset type) and 22 did in the convalescent phase (interval fever-onset type). Both showed a similar rate of complete KD or IVIG response. Interval-type patients required biologics for arthritis control less frequently (5 vs. 39%, P = 0.02) and had a higher 2-year off-treatment rate (100 vs. 43%, P = 0.009) than continued-type ones. Interval-types showed lower serum ferritin and interleukin-18 levels than continued-types. When continued-types were grouped according to whether or not they required biologics ( n = 7 and n = 11, respectively), the former subgroup had higher ferritin and interleukin-18 levels ( P = 0.01 and 0.02, respectively). A canonical discriminant analysis differentiated interval-type from continued-type with the combination of age, time to arthritis, and the ferritin and matrix metalloproteinase-3 levels. Conclusion: Arthritis requiring treatment is a rare complication of KD. KD-associated arthritis includes interval-type (KD-reactive) and continued-type (true systemic-onset juvenile idiopathic arthritis [JIA] requiring biologics), and overlapping arthritis, suggesting the pathophysiological continuity of autoinflammation between KD and JIA.