Rumiko Kurosawa

Clinical Study of Tocilizumab in Children With Systemic-Onset Juvenile Idiopathic Arthritis

Systemic-onset juvenile idiopathic arthritis (sJIA) is a severe and steroid-dependent disease of unknown etiology that sometimes progresses to a fatal disease known as the macrophage activation syndrome. The investigation of inflammatory cytokines and receptor levels revealed an increase in interleukin (IL)-6 and soluble IL-6 receptor (sIL-6R) in serum of patients with active sJIA. The clinical symptoms and signs of the disease are presumably attributable to the continuous elevation of IL-6 and sIL-6R levels in serum. The characteristic fever spikes parallel IL-6 levels. In children, a long-term exposure to high levels of IL-6 causes severe growth impairment, as suggested by recently established studies of IL-6 transgenic mice.The biological functions of IL-6 are expressed through the binding of IL-6/IL-6R complex to gp130. The administration of tocilizumab (a recombinant humanized anti-IL-6R monoclonal antibody) exerts its action by preventing the binding of IL-6 to its receptor and, therefore, preventing the activation of gp130.After a few cases of compassionate use of tocilizumab, phase I and II studies of tocilizumab were conducted in children with sJIA, revealing that tocilizumab abruptly reduced the typical symptoms of inflammation and improved laboratory abnormalities. This article describes the experience in Japan regarding the treatment of sJIA with tocilizumab and supports the hypothesis that high levels of IL-6 may play an important role in the pathogenesis and maintenance of this disease. A confirmation of the role of tocilizumab in the treatment of sJIA will be provided by the results of the ongoing phase III study in Japan.

Two-generation Kawasaki Disease: Mother and Daugher

Evidence that the incidence of Kawasaki disease (KD) in siblings is much higher than general incidence, indicates that genetic factors may contribute to the susceptibility. We report a girl with KD whose mother also suffered from KD with the precise medical record when she was a child. Case Reports:Mother (27 years old); At 6 years of age, she was admitted to the reginal hospital because of persistent high fever for 4 days and cervical lymphadenitis. According to the medical record of 21 years ago, she fulfilled the revised criteria of KD. After admission, acetylsalicylate (ASA) was administered and became afebrile within 2 weeks, and then desquamation of fingertips was observed. Two months later, she was admitted for investigation of coronary artery lesion (CAL). The angiographic examination indicated normal coronary arteries, no aneurysms, and no abnormal dilatation of abdominal artery. ASA was ceased without any coagulation problems. Daughter (1 year old); A 1 year-old girl was admitted to the regional hospital with high fever for 3 days and cervical lymphadenitis. On admission, she fulfilled the revised criteria of KD. The BCG-injected site was reactivated and inflamed. And, the combination therapy of oral ASA and the high-dose intravenous gamma-globulin (1 g/kg for 2 days) was administered. However, high fever was still persisted, and she was estimated at the highest risk for CAL, and transferred to our hospital to be subjected to plasma exchange (PE) therapy on day 7 according to our inclusion criteria of PE. After the PE therapy both clinical manifestation and laboratory data were improved to normal ranges. The serial echocardiography revealed intact coronary arteries. Discussion: Two-generation KD may be an appropriate example to analyze the genetic predisposition of KD. It may be important to take a careful history of childhood diseases in the parents of children with KD.