Kawasaki syndrome: an intriguing disease with numerous unsolved dilemmas.

More than 40 years have passed since Kawasaki syndrome (KS) was first described. Yet KS still remains an enigmatic illness which damages the coronary arteries in a quarter of untreated patients and is the most common cause of childhood-acquired heart disease in developed countries. Many gaps exist in our knowledge of the etiology and pathogenesis of KS, making improvements in therapy difficult. In addition, many KS features and issues still demand further efforts to achieve a much better understanding of the disease. Some of these problem areas include coronary artery injuries in children not fulfilling the classic diagnostic criteria, genetic predisposition to KS, unpredictable ineffectiveness of current therapy in some cases, vascular dysfunction in patients not showing echocardiographic evidence of coronary artery abnormalities in the acute phase of KS, and risk of potential premature atherosclerosis. Also, the lack of specific laboratory tests for early identification of the atypical and incomplete cases, especially in infants, is one of the main obstacles to beginning treatment early and thereby decreasing the incidence of cardiovascular involvement. Transthoracic echocardiography remains the gold-standard for evaluation of coronary arteries in the acute phase and follow-up. In KS patients with severe vascular complications, more costly and potentially invasive investigations such as coronary CT angiography and MRI may be necessary. As children with KS with or without heart involvement become adolescents and adults, the recognition and treatment of the potential long term sequelae become crucial, requiring that rheumatologists, infectious disease specialists, and cardiologists cooperate to develop specific guidelines for a proper evaluation and management of these patients. More education is needed for physicians and other professionals about how to recognize the long-term impact of systemic problems related to KS.

Cross-sectional and longitudinal evaluation of bone mass in children and young adults with juvenile idiopathic arthritis: the role of bone mass determinants in a large cohort of patients.

OBJECTIVE: To assess the prevalence of reduced spine bone mineral apparent density (BMAD), and to identify the main predictors of reduced spine BMAD in a cross-sectional and longitudinal evaluation of the same large cohort of patients with juvenile idiopathic arthritis (JIA). There are few prospective data on bone mass evaluation in a large number of patients with JIA, and with enthesitis-related arthritis onset. METHODS: Two hundred nineteen patients with JIA (median age 8.7 yrs, range 6.1-13.1 yrs; 104 oligoarticular JIA, 61 polyarticular, 20 systemic, and 34 enthesitis-related arthritis onset) were retrospectively evaluated. A dual-energy x-ray absorptiometry (DEXA) scan at the lumbar spine was performed in all subjects. Of these, 89 consecutive patients were followed up randomly and longitudinally with a second and a third DEXA evaluation. The data obtained were compared with 80 age-matched and sex-matched healthy subjects. RESULTS: At the first DEXA, patients with JIA showed a reduced spine BMAD standard deviation score (SDS) in comparison to controls (p < 0.001). These results were confirmed when the subjects were divided into JIA subtypes (p < 0.005) with the exception of enthesitis-related arthritis onset. Spine BMAD SDS significantly correlated with JIA onset type (p < 0.01), age at JIA onset (p < 0.005), and flares (p = 0.008). The longitudinal evaluation showed that spine BMAD SDS did not significantly improve at the followup in comparison to controls, in all subsets with JIA except for systemic onset (p < 0.05). Spine BMAD correlated with sex (p < 0.01), systemic corticosteroid exposure (p < 0.01), the number of intraarticular corticosteroid injections (p < 0.01), the interval from last steroid injection (p < 0.05), erythrocyte sedimentation rate (p < 0.005), and C-reactive protein levels (p < 0.005). CONCLUSION: Patients with JIA have a low bone mass and, after a first increase due to therapy, do not reach a healthy condition over time despite our current more effective drugs. These patients have a high risk of osteoporosis in early adulthood. To reduce the risk and improve the bone mass, close monitoring of bone mineral density, better control of disease activity, physical activity, and intake of calcium and vitamin D are recommended. In patients with osteoporosis, therapeutic approaches including bisphosphonates should be considered.

Serum osteopontin as a predictive marker of responsiveness to methotrexate in juvenile idiopathic arthritis.

OBJECTIVE: To evaluate if serum concentrations of osteopontin (OPN) at baseline in patients with juvenile idiopathic arthritis (JIA) represent a potential predictor of responsiveness to methotrexate (MTX). METHODS: At diagnosis, 60 children with active JIA received MTX in addition to nonsteroidal antiinflammatory drugs. After 12 months of MTX treatment, 30 patients were defined as responders; the 30 nonresponders received anti-tumor necrosis factor-alpha therapy (etanercept) in addition to MTX; this group was then enrolled for an additional 12-month study period. No patient had received steroids within 6 weeks before entering the study. Fifty healthy children matched for sex and age acted as controls. OPN serum levels were measured at baseline, before MTX, and then at 6 and 12 months. In the nonresponder patients, OPN was evaluated again after 6 and 12 months of etanercept treatment. RESULTS: At baseline, OPN values were significantly higher (p = 0.0003) in JIA patients than in controls, with no significant differences among the different JIA subtypes. At baseline, OPN levels were lower in responders than in nonresponder patients (14.16 +/- 10.1 microg/ml vs 33.2 +/- 18.1 microg/ml, respectively). After 12 months of MTX treatment, OPN levels were significantly reduced in comparison to baseline in both responder and nonresponder groups (p = 0.0017, p = 0.0048, respectively). In nonresponders, etanercept significantly reduced OPN levels at 6 and 12-month followup in comparison to baseline (p = 0.002, p = 0.008, respectively). No significant differences were found among OPN levels and disease activity. CONCLUSION: Serum levels of OPN at baseline represent a possible marker to predict the responsiveness to MTX in patients with JIA.