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=Volume 9 - 2021

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=Background:  Arthritis occurs 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 in our tertiary center and literature review to differentiate KD-related arthritis from systemic-onset juvenile idiopathic arthritis (SoJIA). 
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 (P=0.002) and higher rate of intravenous immunoglobulin (IVIG) resistance (P<0.001, 86%) in comparison to those without arthritis. 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, 0.02). 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 SoJIA requiring biologics), and overlapping arthritis, suggesting the pathophysiological continuity of autoinflammation between KD and JIA.