AUTHOR=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 

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

JOURNAL=Frontiers in Pediatrics

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2021.597458

DOI=10.3389/fped.2021.597458

ISSN=2296-2360

ABSTRACT=<p><bold>Background:</bold> Arthritis may occur after the diagnosis of Kawasaki disease (KD). Most cases are self-limiting; however, some patients require prolonged treatment.</p><p><bold>Method:</bold> 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.</p><p><bold>Results:</bold> 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, <italic>P</italic> = 0.002) and higher rate of intravenous immunoglobulin (IVIG) resistance in comparison to those without arthritis (86 vs. 17%, <italic>P</italic> &lt; 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%, <italic>P</italic> = 0.02) and had a higher 2-year off-treatment rate (100 vs. 43%, <italic>P</italic> = 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 (<italic>n</italic> = 7 and <italic>n</italic> = 11, respectively), the former subgroup had higher ferritin and interleukin-18 levels (<italic>P</italic> = 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.</p><p><bold>Conclusion:</bold> 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.</p>