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

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.

Clinical Manifestations and Laboratory Findings of Kawasaki Disease: Beyond the Classic Diagnostic Features

“…Several studies have found a small proportion (0.2-0.5%) of KD patients who subsequently developed systemic-onset juvenile idiopathic arthritis (sJIA) [75,76]. Interestingly, Kanemasa et al has reported that KD-related arthritis involved both interval-type (KD-reactive) and continued-type (true sJIA) requiring biologics, may have a similar immunopathology with sJIA as there were overlapping clinical features between KD and sJIA [77]. There were cases where the KD patients have presented with myositis with a normal or mild elevation of the muscle enzymes, which causes proximal muscle weakness that requires the use of glucocorticoid as a treatment [78][79][80].…”

Systemic Juvenile Idiopathic Arthritis/Pediatric Still’s Disease, a Syndrome but Several Clinical Forms: Recent Therapeutic Approaches

“…The differential diagnosis is particularly complex in the early phases of the disease, particularly with Kawasaki disease and post-Covid19 multisystem inflammatory syndrome [ 28 ].…”

Overlapping clinical features of systemic juvenile idiopathic arthritis and SARS-CoV-2-related multisystem inflammatory syndrome in children

“…The search for diagnostic markers aimed to make it possible to produce timely diagnosis of sJIA and prescribe appropriate treatment has attracted substantial attention in recent years [ 1 , 3 , 4 , 29 , 30 , 33 – 35 ] ( Table I ). Some studies focus on clinical signs [ 1 , 3 – 5 , 7 , 14 , 15 , 17 , 19 ], and others on laboratory indicators [ 24 , 29 , 30 ]. Fever refractory to intravenous immunoglobulin ( i.v.…”

“…Differential diagnosis of rheumatic diseases, especially of the systemic onset of juvenile idiopathic arthritis (sJIA), is often difficult because of the variability of clinical presentation in the absence of specific clinical and laboratory signs [ 1 , 2 ].…”