Arthritis in Kawasaki disease after responding to intravenous immunoglobulin treatment

Abstract

Pathologically, Kawasaki disease (KD) is a systemic vasculitis which can show some complications as arthritis during the natural course. It is observed usually in the acute or subacute stage of 15%–45% of KD patients [3, 4, 5]. The 5 children, out of 217 patients with KD, who presented with arthritis after defervescence on intravenous immunoglobulin (IVIG) treatment were retrospectively reviewed. All patients met the diagnostic criteria of KD at the initial time of presentation and patients 1, 2, 4 and 5 were readmitted because of arthritis. Initially, all patients were treated with IVIG at a dose of 2 g/kg, and with acetylsalicylic acid (30– 50 mg/kg). Two patients (numbers 3 and 4) failed to respond the first dose of IVIG and became afebrile after the second dose of IVIG (1 g/kg). The arthritis was observed at mean of 10.4±1.3 days (range 8 to 13 days) after the onset of fever, and at a mean of 5.8±1.8 days (range 3 to 10 days) after defervescence after the final dose of IVIG. For the types of arthritis, the polyarticular cases showed involvement of all phalangeal joints of both hands with additional involvement of at least one other joint including the left knee joint in patient 1, and bilateral knee, wrist and ankle joints in patient 3. In the pauciarticular types, there was bilateral involvement of hip joints in patient 2, right hip joints and the right third interphalangeal joint in patient 4, and the left knee joint in patient 5. All patients with arthritis responded effectively to high doses of acetylsalicylic acid (80 mg/kg/day for 10–14 days, patients 1 and 2) or ibuprofen (30 mg/ kg/day for 2–4 weeks, patients 4 and 5) or corticosteroids (patient 3). One child (patient 3), after responding to the second dose of IVIG therapy, showed an acute onset of polyarthritis with relapsed fever and elevated laboratory values. She was unresponsive to ibuprofen and received the methylprednisolone pulse therapy (15 mg/kg for 3 days) with ibuprofen for 2 months. There has been no relapse for 6 months after treatment. HLA B27 was negative for all three cases which were examined (Table 1). Children with KD in the acute stage commonly present with oedematous hands and feet, especially in young infants. Considering the pathogenesis of KD as a systemic vasculitis, the swelling and tenderness of extremities may be combined with arthritis. However, in this study, we selected those patients with arthritis which occurred after defervescence with IVIG treatment. Among 217 KD patients observed over a 6-year period (1998–2003), only 5 (2%) showed this type of arthritis. IVIG therapy in KD is more effective than high dose acetylsalicylic acid therapy in inducing defervescence, normalising the laboratory findings and preventing cardiac complication [2, 6]. Because the anti-inflammatory effect of IVIG on arthritis also is more effective than that of acetylsalicylic acid, the incidence of arthritis in the subacute stage of KD has decreased in the IVIG era. Arthritis after infection with Streptococcus, Shigella or Chlamydia is known as reactive arthritis or postinfectious arthritis. Reactive arthritis develops within 1–4 weeks after the primary infection and some patients are positive for HLA B27 [1]. The fact that arthritis occurs regardless of high dose acetylsalicylic acid therapy in the subacute stage [3] and after high dose IVIG therapy suggests that this type of arthritis in KD is a reactive arthritis due to an unknown pathogen.