Multiple Emergency Department Visits for a Diagnosis of Kawasaki Disease: An Examination of Risk Factors and Outcomes.

OBJECTIVES: To determine predictors of >1 emergency department (ED) visit for a Kawasaki disease diagnosis in a quaternary care pediatric hospital and compare outcomes between patients with 1 vs >1 visit for Kawasaki disease diagnosis. STUDY DESIGN: Medical records of patients evaluated for Kawasaki disease between January 2006 and August 2018 at Boston Children's Hospital were abstracted for demographic and clinical data. Predictors of >1 visit were explored using logistic regression and classification and regression tree analysis. RESULTS: Of 530 patients diagnosed with Kawasaki disease, 117 (22%) required multiple ED visits for Kawasaki disease diagnosis. Multivariable regression and classification and regression tree analysis identified ≤2 Kawasaki disease criteria (OR 33.9; 95% CI 18.1-63.6), <3 days of fever at the first visit (OR 3.47; 95% CI 1.77-6.84), and non-White race (OR 2.15; 95% CI 1.18-3.95) as predictors of >1 visit. There were no significant differences in duration of hospitalization, day of illness at initial Kawasaki disease treatment, intravenous immunoglobulin resistance, need for adjunctive therapies, or coronary artery outcomes between patients diagnosed with Kawasaki disease at initial visit vs subsequent visits. CONCLUSIONS: Incomplete Kawasaki disease criteria, fewer days of fever, and non-White race were significant predictors of multiple ED visits for Kawasaki disease diagnosis in this single institution study. Our findings underscore the importance of maintaining a high index of suspicion for Kawasaki disease in patients with <4 Kawasaki disease criteria. Further research is needed to determine causes for increased healthcare use in non-White patients to receive a Kawasaki disease diagnosis.

Pediatric CNS-isolated hemophagocytic lymphohistiocytosis.

Objective: To highlight a novel, treatable syndrome, we report 4 patients with CNS-isolated inflammation associated with familial hemophagocytic lymphohistiocytosis (FHL) gene mutations (CNS-FHL). Methods: Retrospective chart review. Results: Patients with CNS-FHL are characterized by chronic inflammation restricted to the CNS that is not attributable to any previously described neuroinflammatory etiology and have germline mutations in known FHL-associated genes with no signs of systemic inflammation. Hematopoietic stem cell transplantation (HCT) can be well tolerated and effective in achieving or maintaining disease remission in patients with CNS-FHL. Conclusions: Early and accurate diagnosis followed by treatment with HCT can reduce morbidity and mortality in CNS-FHL, a novel, treatable syndrome. Classification of evidence: This study provides Class IV evidence that HCT is well tolerated and effective in treating CNS-FHL.

Infliximab for intravenous immunoglobulin resistance in Kawasaki disease: a retrospective study.

OBJECTIVE: To test the hypothesis that first re-treatment with infliximab, compared with intravenous immunoglobulin (IVIG), might improve outcomes in IVIG-resistant Kawasaki disease. STUDY DESIGN: In a two-center retrospective review from January 2000 to March 2008, we compared duration of fever and coronary artery dimensions in patients with IVIG-resistance whose first re-treatment was with IVIG compared with infliximab given for fever ≥38.0°C beyond 36 hours after first IVIG completion. RESULTS: Patients in the IVIG group (n = 86, 2 g/kg) and infliximab group (n = 20, 5 mg/kg) were similar in demographics, days of fever at diagnosis, and baseline coronary artery dimensions. Patients had similar coronary dimensions 6 weeks after diagnosis, both in univariate and multivariate analysis. The infliximab group had fewer days of fever (median 8 days versus10 days, P = .028), and in a multivariate analysis, the infliximab group had 1.2 fewer days of fever (P = .033). Patients who received infliximab had shorter lengths of hospitalization (median 5.5 days versus 6 days, P = .040). Treatment groups did not differ significantly in adverse events (0% versus 2.3%, P = 1.0). CONCLUSIONS: In our retrospective study, patients with IVIG-resistant Kawasaki disease whose first re-treatment was with infliximab, compared with IVIG, had faster resolution of fever and fewer days of hospitalization. Coronary artery outcomes and adverse events were similar; the power of the study was limited.

Chronic minocycline-induced autoimmunity in children.

OBJECTIVE: To report our experience with minocycline-induced autoimmunity (MIA) in children, with an emphasis on the potential for chronicity. STUDY DESIGN: Retrospective cohort study of patients with development of rheumatologic symptoms while receiving minocycline between 1996 and 2006. RESULTS: Twenty-seven children were diagnosed with MIA at a single pediatric rheumatology practice. The mean age at onset was 16.5 +/- 1.39 years. The mean duration of minocycline use before diagnosis was 13.0 +/- 10.8 months. All patients presented with constitutional symptoms. Twenty-two had polyarthralgia, and 17 had polyarthritis, mostly affecting hands and feet. On the basis of disease duration after discontinuation of minocycline, we divided subjects into 3 categories: transient, intermediate, and chronic. Seven patients had development of chronic autoimmune disease that was still active at last follow-up, a mean of 31.6 +/- 13.0 (13-48) months after onset. Six patients followed an intermediate course, with resolution of symptoms within 12 months, and 14 patients had symptoms that resolved rapidly on discontinuation of minocycline. All patients with a chronic course had evidence of arthritis at presentation. CONCLUSION: A substantial proportion of children with MIA had development of chronic symptoms with the potential for significant morbidity. Physicians who prescribe minocycline should be aware of its propensity for inducing potentially serious autoimmune phenomena.

Clinical effects and safety of rituximab for treatment of refractory pediatric autoimmune diseases.

OBJECTIVE: To evaluate the safety, tolerability, and clinical effects of rituximab, an anti-CD20 monoclonal antibody, in the treatment of severe pediatric autoimmune diseases. STUDY DESIGN: We reviewed the records of 10 patients treated with rituximab for severe, refractory autoimmune diseases at a single tertiary care children's hospital. Adverse events as well as treatment effects were recorded. RESULTS: All patients received 4 weekly doses of rituximab at 375 mg/m2 per dose. One patient died as the result of complications of her underlying systemic lupus erythematosus 7 weeks after rituximab therapy. Three patients had serious infections, all of which resolved with standard therapy. Rituximab led to transient or sustained improvement in clinical and laboratory parameters in nine subjects. At a median follow-up of 9 months, the median prednisone dose was reduced in the responders by 0.75 mg/kg per day (mean decrease of 63%), and four patients were able to discontinue corticosteroids entirely. With longer follow-up (median, 22 months), we found that 5 of 9 patients remained clinically stable after rituximab therapy, whereas 4 patients had recurrent or new features of their underlying autoimmune disorders requiring additional corticosteroids or other immunosuppressive medications. CONCLUSIONS: Rituximab had an acceptable toxicity profile in this group of patients with severe, refractory autoimmune diseases, although there were three serious infections and one patient death. Rituximab appears to be beneficial for patients with refractory autoimmune diseases and may reduce corticosteroid exposure. Although rituximab therapy provided a durable clinical benefit for some patients in this population, other patients had reemergence of their underlying autoimmune disease.

Thalidomide for severe systemic onset juvenile rheumatoid arthritis: A multicenter study.

Thirteen children with difficult systemic onset juvenile rheumatoid arthritis were treated with thalidomide. At 6 months, 11 of the 13 were able to reduce their use of prednisone ( P < .002), with a concurrent improvement in erythrocyte sedimentation rate ( P < .0001) and an increase in hemoglobin level ( P < 0.005). Juvenile rheumatoid arthritis improvement scores >/=50% were obtained by 10 of the 13 children.

Rituximab therapy for multisystem autoimmune diseases in pediatric patients.

OBJECTIVE: To evaluate the effects of rituximab (anti-CD20 monoclonal antibody) on the disease course in pediatric patients with multisystem autoimmune diseases. METHODS: Four patients with multisystem autoimmune diseases refractory to conventional immunosuppressive medications, each with central nervous system (CNS) involvement, were treated with four weekly infusions of rituximab. Their clinical and laboratory responses were evaluated. RESULTS: Each of the patients had improvement in clinical symptoms and laboratory parameters. One patient with autoimmune cytopenias and autoimmune CNS and peripheral nervous system disease had resolution of the cytopenias and marked improvement in neurologic symptoms; he currently receives no immunosuppressive medications. Two half-siblings with lymphoplasmacytic colitis, pulmonary nodules, and CNS disease had improvement of their symptoms. A fourth patient with chorea and seizures secondary to primary antiphospholipid antibody syndrome had improvement in fine and gross motor function and reduced seizure frequency. There were no serious adverse events. CONCLUSIONS: The biologic response modifier rituximab, designed to eliminate B lymphocytes, was safe and effective in four pediatric patients with multisystem autoimmune disorders. It appears to be beneficial in autoimmune conditions presumably mediated by a variety of B-cell-related mechanisms, and may decrease or eliminate the need for other immunosuppressive medications.

Corticosteroids in the initial treatment of Kawasaki disease: report of a randomized trial.

OBJECTIVE: We conducted a prospective randomized trial to determine whether the addition of corticosteroids to intravenous immunoglobulin (IVIG) might improve outcomes in Kawasaki disease (KD). STUDY DESIGN: Subjects were randomized to receive IVIG, 2 gm/kg over 10 hours, with or without pulsed-dose intravenous methylprednisolone (IVMP), 30 mg/kg. All patients received standard doses of aspirin (ASA). Groups were similar in baseline demographic and laboratory data. RESULTS: Patients in the IVMP plus ASA/IVIG group, compared with those in the ASA/IVIG alone group, had a shorter mean duration of fever >/=38.3 degrees C after initiation of therapy (1.0 +/- 1.3 vs 2.4 +/- 1.9 days, mean +/- SD, P =.012), shorter hospital stays (1.9 +/- 0.7 vs 3.3 +/- 2.1 days, P =.010), and at six weeks, lower mean erythrocyte sedimentation rate (11.1 +/- 5.7 vs 19.4 +/- 12.4, P =.027) and median c-reactive protein (0.03 vs 0.08, P =.011, Wilcoxon). No significant differences between treatment groups were noted in coronary dimensions, but statistical power was limited. IVMP was well tolerated; transient hypertension developed in one child, but it did not require treatment. CONCLUSIONS: Treatment of acute KD with IVMP plus ASA/IVIG, compared with ASA/IVIG alone, resulted in faster resolution of fever, more rapid improvement in markers of inflammation, and shorter length of hospitalization. Adverse effects were infrequent. Steroid therapy should be further assessed in a multicenter, placebo-blind trial.