Five-year outcome of children with idiopathic nephrotic syndrome: the NEPHROVIR population-based cohort study.

BACKGROUND: The optimal therapeutic regimen for children at onset of idiopathic nephrotic syndrome (INS) is still under debate. A better knowledge of the disease's course is necessary to design more appropriate and/or personalized treatment protocols. METHODS: We report the 5-year outcome of patients included from December 2007 to May 2010 in the prospective multicentric and multiethnic population-based NEPHROVIR study. Patients were treated at onset according to the French steroid protocol (3990 mg/m2, 18 weeks). Data were collected at 5 years or last follow-up. RESULTS: Out of the 188 children with nephrotic syndrome (121 boys, 67 girls; median age 4.1 years), 174 (93%) were steroid-sensitive. Six percent of steroid-sensitive patients required intravenous steroid pulses to get into remission. Relapse-free rate for steroid-sensitive patients was 21% (36/174) at last follow-up (median 72 months). A first relapse occurred in138 steroid sensitive patients (79%) with a median time of 8.3 months (IQ 3.4-11.3). Out of the 138 relapsers, 43 were frequent relapsers. Age at onset below 4 years was the only predictive factor of relapse, while gender, ethnicity, and delay to first remission were not. At 96 months of follow-up, 83% of frequent relapsers were still under steroids and/or immunosuppressive drugs. CONCLUSIONS: The treatment of the first flare deserves major improvements in order to reduce the prevalence of relapsers and the subsequent long-lasting exposure to steroids and immunosuppression.

Clinical characteristics and outcomes of childhood-onset ANCA-associated vasculitis: a French nationwide study.

BACKGROUND: Data on anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis are scarce in children. The current study is aimed at describing the clinical features and outcomes of childhood-onset ANCA-associated vasculitis (AAV). METHODS: We conducted a retrospective French multicentre study involving patients in whom AAV was diagnosed before the age of 18 years. Inclusion criteria were (i) granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) according to classification criteria of the European League Against Rheumatism/Paediatric Rheumatology European Society, and (ii) ANCA positivity. Patient and renal survival were analysed. RESULTS: Among 66 children included, 80% were female, 42% had GPA and 58% MPA including renal-limited vasculitis, 67% were pANCA+ and 33% cANCA+. The mean incidence of reported cases increased to 0.45 per million children/year in the period 2006-10. Median age at diagnosis was 11.5 years, and median time to diagnosis was 1 month. Initial symptoms included fever and fatigue (79%), skin lesions (41%), arthritis (42%), pulmonary (45%) and renal involvement (88%). Clinical features were similar between GPA and MPA with the exception of upper airway impairment (28%) specific of GPA. Ninety percent of the patients achieved remission after induction treatment. After a median follow-up of 5.2 years, 4 patients (6%) died, corresponding to a mortality rate of 1.2 per 100 person-years, and 22 patients (34%) developed end-stage renal disease (ESRD). Renal survival was 74, 70 and 59% at 1, 5 and 10 years, respectively. In a multivariable Cox regression model, baseline glomerular filtration rate, ethnic origin, histopathological classification and era of treatment were associated with the occurrence of ESRD. Relapse-free survival was 57% at 5 years and 34% at 10 years of follow-up. Patient and renal outcome did not significantly differ between GPA and MPA. CONCLUSION: Childhood-onset AAV is a rare disease characterized by female predominance, delayed diagnosis, frequent renal impairment and a high remission rate. Baseline GFR and new histopathological classification system are strong predictors of ESRD. Renal survival in childhood AAV has improved over time.

Ciprofloxacin prevents myelination delay in neonatal rats subjected to E. coli sepsis.

OBJECTIVE: Perinatal infections and the systemic inflammatory response to them are critical contributors to white matter disease (WMD) in the developing brain despite the use of highly active antibiotics. Fluoroquinolones including ciprofloxacin (CIP) have intrinsic anti-inflammatory effects. We hypothesized that CIP, in addition to its antibacterial activity, could exert a neuroprotective effect by modulating white matter inflammation in response to sepsis. METHODS: We adapted an Escherichia coli sepsis model to 5-day-old rat pups (P5), to induce white matter inflammation without bacterial meningitis. We then compared the ability of CIP to modulate inflammatory-induced brain damage compared with cefotaxime (CTX) (treatment of reference). RESULTS: Compared with CTX, CIP was associated with reduced microglial activation and inducible nitric oxide synthase (iNOS) expression in the developing white matter in rat pups subjected to E. coli sepsis. In addition to reducing microglial activation, CIP was able to prevent myelination delay induced by E. coli sepsis and to promote oligodendroglial survival and maturation. We found that E. coli sepsis altered the transcription of the guidance molecules semaphorin 3A and 3F; CIP treatment was capable of reducing semaphorin 3A and 3F transcription levels to those seen in uninfected controls. Finally, in a noninfectious white matter inflammation model, CIP was associated with significantly reduced microglial activation and prevented WMD when compared to CTX. INTERPRETATION: These data strongly suggest that CIP exerts a beneficial effect in a model of E. coli sepsis-induced WMD in rat pups that is independent of its antibacterial activity but likely related to iNOS expression modulation.

Clinical Characteristics of Acne Fulminans Associated With Chronic Nonbacterial Osteomyelitis in Pediatric Patients.

OBJECTIVE: Acne fulminans (AF) is a rare, explosive systemic form of acne. Chronic nonbacterial osteomyelitis (CNO) or chronic recurrent multifocal osteomyelitis (CRMO) is a primarily pediatric autoinflammatory disorder characterized by sterile osteolytic bone lesions. Concomitant occurrence of CNO/CRMO and AF is very rare, and little is known about the epidemiological and clinical particularities of this association. The aim of this retrospective observational study was to describe the characteristics of pediatric patients with CNO/CRMO associated to AF. METHODS: Electronic mailing lists of French medical societies were used to call for patients with CNO/CRMO and AF. A search for published patients with CNO/CRMO and AF was performed by screening PubMed. RESULTS: We identified 5 original patients and 10 patients from the literature. All patients were adolescent boys. Mean age at disease onset was 14.8 years. Nine of 15 patients had received isotretinoin before the sudden onset of AF. Osteoarticular symptoms appeared within < 1-3 months after the onset of AF. The mean numbers of clinical and radiological bone lesions were 3.6 and 5.6, respectively. The percentages of patients with involvement of vertebrae, pelvis, chest, and cranial were 40%, 40%, 33.3%, and 6.6%, respectively. Arthritis was observed in 69.2% of patients and sacroiliac arthritis in 46.2%. CONCLUSION: CNO/CRMO associated to AF occurs predominantly in male adolescents and is characterized by frequent involvement of the axial skeleton and arthritis. Epidemiological and clinical features of these patients differ from general CNO/CRMO cohorts. Clinical management requires careful handling of isotretinoin doses.

QuantiFERON to diagnose infection by Mycobacterium tuberculosis: performance in infants and older children.

OBJECTIVES: QuantiFERON value to diagnose tuberculosis (TB) in young children remains to be clarified. To this aim QF-TB-IT performance was evaluated in a large series of immunocompetent children that were stratified according to age and clinical conditions. METHODS: QF-TB-IT reactivity was analyzed in 226 immunocompetent children (0-15 years old): 31 were uninfected despite TB contact; 51 presented TB disease; 39 had Latent TB (LTBI) and 105 had TB disease suspected but an alternative diagnosis (TB excluded). RESULTS: QF-TB-IT specificity was 100% in TB excluded. In TB disease, low sensitivity of QF-TB-IT in infants (40%) increased with aging (77% in 1-<5 years and 82% in 5-<15 years old subgroups). In LTBI, agreement between TST and QF-TB-IT was 0% in infants, 40% in 1-<5 years and 57% in children >5 years old. Finally, the incidence of indeterminate results was high (24%) in children <5 years old with TB excluded, especially with non-TB pneumonitis (61%), but was low (0-6%) regardless of age group in TB disease, LTBI and uninfected contact cases. CONCLUSIONS: In our low burden country, i) QF-TB-IT specificity was 100%, ii) QF-TB-IT sensitivity was low in infants but commensurable to adult values in older children, and iii) indeterminate results mostly relied on ongoing infections unrelated to TB.