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Kawasaki disease‐related arthritis with synovial involvement

Some patients with Kawasaki disease (KD) develop arthritis. The differentiation between KD and systemic juvenile idiopathic arthritis (s-JIA) is often difficult because the clinical features and laboratory findings tend to overlap. In addition, magnetic resonance imaging (MRI) of the lesion has not been compared between patients developing arthritis during the acute phase of KD and those with s-JIA. Although the measurement of serum interleukin (IL)-18 is important for the differentiation between KD and s-JIA, its level in KD-related arthritis with synovial involvement is unknown. A previously healthy 2-year-old girl was transferred to the present hospital for the treatment and evaluation of KD-related arthritis on the 9th day of illness. All six symptoms included in the diagnostic criteria for KD had been observed by the third day of illness. Despite treatment with high-dose i.v. immunoglobulin (IVIG) and oral aspirin at our affiliated hospital, the symptoms remained, and pain on leg motion emerged on the fourth day of illness. The major symptoms of KD except for fever improved after re-treatment with IVIG, but the leg pain worsened until the patient was ultimately unable to walk. On admission to the present hospital, edema of the foot remained as a physical finding of KD. No joints were hot or swollen, although Patrick sign was positive in the bilateral legs. On complete blood count, leukocytes were 25.9 9 10/L with 87% neutrophils, with a hemoglobin concentration of 8.5 g/dL, and a platelet concentration of 285 9 10/L. On blood chemistry analysis, albumin was 1.6 g/ dL, aspartate aminotransferase was 119 U/L, C-reactive protein was 20.7 mg/dL, ferritin, 495 ng/mL (reference range, 39.9– 465.0; ng/mL); and matrix metalloproteinase-3, 116 ng/mL (reference range, 17.3–59.7 ng/mL). There were no findings suggestive of disseminated intravascular coagulation on coagulation studies. Rheumatoid factor and anti-cyclic citrullinated peptide antibody were undetectable. Coronary artery abnormality (CAA) was undetected on echocardiogram. Gadolinium-enhanced fatsuppressed T1-weighted MRI showed enhanced synovial membranes in the bilateral hip, knee, and ankle joints (Fig. 1). There was neither erosion nor bone marrow edema. Oral cyclosporine A (CsA) was added as the third-line therapy for KD from the 10th day of illness. The patient rapidly became afebrile, and the leg pain disappeared on the 14th day of illness. Aspirin was reduced to a low dose, and the patient was discharged from hospital on the 25th day of illness. CsA and aspirin had been used for 1 and 1.5 months, respectively. The abnormal MRI findings disappeared 3 months after the initial treatment. No symptoms recurred, and CAA were not noted during the 6 months after the onset of KD. We serially measured serum IL-18. The maximum IL-18 level was 1127.9 pg/mL on the ninth day of illness, and it did not increase markedly (231.5–1127.9 pg/mL) compared with that in s-JIA patients during the clinical course. The patient was diagnosed with KD-related arthritis with synovial involvement. Early onset (<10th days of illness) KD-related arthritis is characterized by a polyarticular disease with systemic inflammation, whereas late-onset arthritis tends to have an oligoarticular involvement. The articular symptoms improve with treatment for KD, and a non-steroidal anti-inflammatory drug (NSAID) is not necessary in most patients with early-onset arthritis. In the present case the symptoms improved without NSAID, unlike patients with late-onset arthritis. The mechanism underlying KD-related arthritis may vary depending on the time of onset. As in KD patients with late-onset arthritis, neither erosions of the bone nor bone marrow edema, characteristic of JIA, were detected on MRI in the present case. Severe joint lesion destruction may not be caused in KD-related arthritis because of its self-limiting nature. Although it is impossible to differentiate KD-related arthritis from s-JIA completely based on solely on MRI, the findings of KD-related arthritis may be milder than those of s-JIA. Serum IL-18 level was useful for the differentiation of KD and s-JIA in the present case. The cellular source of IL-18 production in s-JIA is suggested to be bone marrow macrophages, and the T-helper 1 response is activated by the marked production of IL-18. Serum IL-18 level might play an important role in differentiating s-JIA from other diseases with synovitis. We additionally used CsA, which is used for the treatment of IVIG-resistant KD. We considered that the further control of systemic inflammation with specific treatment for KD took priority in the present patient with early-onset arthritis resistant to IVIG. Meanwhile, in the first case series of successful infliximab use for IVIG-resistant KD, 16 of the 17 patients had arthritis. Further clinical studies will be needed to clarify the optimal treatment for IVIG-resistant KD-related arthritis.