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

Hikaru Kanemasa,Satoshi Hara,Shinya Hida,Hidetoshi Takada,Lisheng Lin,Nobuko Makino,Yosikazu Nakamura,Yoshie Tomita,Etsuro Nanishi,Hisanori Nishio,Takenori Adachi,Shouichi Ohga,Noriko Nagai,Osamu Komiyama,Masataka Ishimura,Satoshi Honjo,Atsuo Sato,Hiroshi Masuda,Junji Kamizono,Saori Tanabe,Urara Kohdera,Mayumi Yashiro,Takahiro Nishihara,Toshiro Hara,Tatsuya Ishii

doi:10.3389/fped.2021.597458

Abstract

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.

Highlights

Kawasaki disease (KD) is an acute febrile vasculitis of unknown etiology that primarily occurs in infants and children [1]
In order to facilitate the optimal treatment of KD-related arthritis after the early exclusion of SoJIA, the present study aimed to investigate the prevalence, clinical expression, and treatment of arthritis by a recent nationwide survey of KD in Japan
A total of 1,456 of the 1,943 eligible institutions replied to the initial questionnaire about KD-related arthritis in the 23rd nationwide KD survey, in which 31,679 patients received a diagnosis of KD in 950 institutions (Supplementary Figure 1)

Summary

Introduction

Kawasaki disease (KD) is an acute febrile vasculitis of unknown etiology that primarily occurs in infants and children [1]. The systemic vasculitis affects small- and medium-sized arteries, predominantly the coronary arteries. The advent of intravenous immunoglobulin (IVIG) reduced the incidence of coronary artery abnormalities (CAAs) in patients from 20 to 25% to

Methods

Results

Discussion

Conclusion