Risk of Serious Infections Associated with Biologic Agents in Juvenile Idiopathic Arthritis: A Systematic Review and Meta-Analyses.

OBJECTIVE: To assess whether treatment with biologic response modifying agents during clinical trial study periods increases the risk of serious infections in children with juvenile idiopathic arthritis (JIA). STUDY DESIGN: A systematic literature review using Medline, Embase, Cochrane library, and the clinical trial registry was performed up to July 2017. Random effects meta-analyses were used to compare rates of serious infections in children with JIA given biologic agents compared with controls, and the pooled relative risk calculated. Subanalyses were performed for different biologic agent classes. RESULTS: In total, 19 trials accounting for 21 individual studies were included (11 for tumor necrosis factor-alpha inhibitors [n = 814 patients], 3 for interleukin-6 inhibitors [n = 318], 6 for interleukin-1 inhibitors [n = 353], and 1 for selective T-lymphocyte costimulation modulators [n = 122]). Patients (68% female) had a mean age of 10.8 years. Seventeen serious infections were reported among 810 children receiving biologic agents and 15 among 797 controls. The most frequent infections were bronchopulmonary and varicella. No statistically significant difference in risk of serious infections was found between children receiving biologic agents compared with control groups (pooled relative risk = 1.13; 95% CI [0.63, 2.03]) during the trial study periods. The risk remained nonsignificant when evaluating the different classes of biologic agents separately. However, the analyses were underpowered to detect differences in the risk of serious infections overall or differences between classes of biologic agents. CONCLUSIONS: In this systematic review and meta-analyses, serious infections were uncommon and not significantly increased among patients with JIA receiving biologic agents compared with controls. However, the analyses were underpowered and study periods were relatively short. Ongoing careful monitoring for serious infections remains necessary for all patients with JIA, and particularly those receiving biologic agents.

Pediatric Idiopathic Intervertebral Disc Calcification: Single-Center Series and Review of the Literature.

OBJECTIVE: To review pediatric idiopathic intervertebral disc calcification (PIIVDC) within a single center and within the literature to outline the disease course, management, and outcome. STUDY DESIGN: A retrospective chart review was performed spanning the period between January 2001 and February 2016 for diagnoses of PIIVDC. Patient age, sex, symptoms, and history and physical and neurologic findings were reviewed. Laboratory and imaging findings, management, follow-up, and outcome also were studied. RESULTS: Nine cases of PIIVDC were identified; they included 6 male and 3 female patients, with an age range of 23 months to 12 years. Two patients were asymptomatic, and PIIVDC was discovered incidentally. Of the remaining 7 patients, 5 presented with neck and/or back pain, 1 with painless torticollis, and 1 with painful torticollis. One patient reported neurologic symptoms of pain radiating along 1 dermatome. Disc spaces affected were 5 cervical, 4 thoracic, and 2 lumbar, with 2 patients having more than 1 space affected. All patients were managed conservatively. In 1 case, symptoms and lesions persisted after 5 years, but the remainder had complete symptom resolution, generally within 6 months. CONCLUSIONS: The etiology of PIIVDC remains unknown but appears to occur spontaneously, without preceding trauma or underlying medical condition. A conservative approach to patients without severe neurologic deficit with outpatient follow-up is supported.

Chronic recurrent multifocal osteomyelitis: clinical outcomes after more than five years of follow-up.

OBJECTIVE: To determine the clinical outcomes of children with chronic recurrent multifocal osteomyelitis (CRMO). STUDY DESIGN: Inception cohorts of children with CRMO were established at two tertiary pediatric centers. Outcome data were obtained through review of hospital charts, interview and examination of patients, and completion of questionnaires by patients. RESULTS: Of 45 eligible subjects, 23 (51%) were assessed. Median time since diagnosis was 13 years (range, 6-25). At evaluation, 6 (26%) had active disease; 18 (78%) had Health Assessment Questionnaire scores of 0 (no/minimal physical disability), and 5 had scores >0. Some impairment was seen in all domains of measurement of quality-of-life test, especially those concerning nonphysical aspects of health. Six (26%) subjects continued to have pain as a result of CRMO. Associated medical problems included arthritis in 6, sacroiliitis in 3, psoriasis in 5, recurrent pustular rashes in 2, and inflammatory bowel disease in 3. CONCLUSIONS: Long-term clinical outcomes for children with CRMO appear to be generally good, with most subjects having no evidence of disease activity or sequelae. However, a number of subjects had persistent disease and, therefore, remain at risk of physical and psychologic complications. Further research is required to identify patients at risk for persistent disease, and to determine therapies that may prevent morbidity.