Association of hypothalamic-pituitary-adrenal axis-related polymorphisms with stress in asthmatic children on inhaled corticosteroids.

OBJECTIVE: Long-term treatment of asthmatic children with low and moderate doses of inhaled corticosteroids (ICS) may result in mild adrenal suppression. Various associations have been shown between adrenal reactivity and single nucleotide polymorphisms (SNPs) related to the hypothalamic-pituitary-adrenal (HPA) axis. We aimed to investigate the genetic contribution of four HPA axis-related SNPs to the individual stress response when on ICS. METHODS: The low dose Synacthen test was performed in 62 asthmatic children (43 males, median age 7.9 years) before and after 3 months of treatment with inhaled fluticasone (200 µg/day) or budesonide (400 µg/day). The SNPs determined were: rs1876828 and rs242941 in the corticotropin-releasing hormone receptor 1 (CRHR1) gene, T(-2C) in the promoter region of the melanocortin receptor 2 (MC2R) gene and BclI restriction fragment length polymorphsism in the glucocorticoid receptor (GR) gene. RESULTS: Homozygotes for the variant rs242941 (TT) demonstrated a delayed cortisol response after treatment with ICS compared to heterozygotes (GT) (p = 0.033) and those with the wild-type (GG) genotype (p = 0.018). Homozygotes for the variant rs1876828 (AA) manifested lower baseline cortisol levels before treatment (p = 0.009) compared to the GG genotype and delayed cortisol response after treatment compared to the GA genotype (p = 0.05). BclI heterozygotes for the G allele (GC) demonstrated higher basal cortisol levels before and after treatment with ICS compared to homozygotes (CC) (p = 0.024, p = 0.018). Three SNP interactions were associated with serum cortisol levels. CONCLUSION: There is evidence of a contribution of HPA axis-related genetic variation to the stress response of asthmatic children on ICS. The clinical importance of this finding needs further elucidation.

Asthma symptoms and bronchial reactivity in school children sensitized to food allergens in infancy.

Food allergy in infancy usually disappears but is followed primarily by respiratory allergy. We hypothesized that children allergic to common food allergens in infancy are at increased risk of wheezing illness and bronchial hyperresponsiveness during school age. In a case-control study 69 children 7.2 to 13.3 years of age allergic to egg (N = 60) and/or fish (N = 29) in early life (first 3 years) who attended our allergy outpatient clinic were recruited. They received follow-up for 1 year and were evaluated by parental questionnaire, skin prick testing, spirometry, and metacholine bronchial challenge. Another 154 children (70 sensitized to inhaled allergens) recruited selectively from a general population sample with no history of food allergy during their first 3 years served as control subjects. Twenty-three children (38.3%) maintained their sensitization to egg and 19 (65.5%) to fish; the prevalence of sensitization to > or = 1 inhaled allergen(s) increased from 59.4% to 71% during childhood. Current asthma symptoms were reported more frequently in the study group than in either control groups, sensitized to inhaled allergens and non-sensitized. Children of the study group showed a significantly increased frequency of positive response to metacholine bronchial challenge compared to the control group as a whole; the difference was statistically indicative when study groups separately were compared to the sensitized control subjects. Multivariate logistic regression analysis showed that bronchial hyperresponsiveness, as well as reported current asthma symptoms were associated with early wheezing and early sensitization to inhaled allergens but not with atopic dermatitis in infancy or persistence of egg or fish allergy. Children allergic to egg or fish in infancy are at increased risk for wheezing illness and hyperactive airways in school age; asthma and bronchial hyperresponsiveness development is mostly determined by wheezing and senzitization to inhaled allergens in early life regardless of atopic dermatitis in infancy or retention of food allergy.

Pediatric inflammatory bowel disease in Greece: 30-years experience of a single center.

BACKGROUND: Significant advances have been made in the care of children with inflammatory bowel disease (IBD). We aimed to describe the trends during the last 3 decades in the clinical presentation, management, and outcome of pediatric IBD at a single center. METHODS: Medical records of children with IBD referred to a pediatric gastroenterology unit from January 1981 to December 2011 were reviewed retrospectively. RESULTS: A total of 483 children were diagnosed with IBD, with mean age at diagnosis of 9.6 years (range 6 months - 18 years). Ulcerative colitis (UC) was diagnosed in 267 (55.2%), Crohn's disease (CD) in 167 (34.5%), and IBD unclassified (IBDU) in 49 (10.1%). Children with UC and IBDU were younger than those with CD [mean age at diagnosis 9.2, 8.9, and 10.5 years respectively; P (UC vs. CD)<0.01 and P (IBDU vs. CD)=0.028]. Patients received 5-ASA (96.6%), steroids (77.0%), thiopurines (50.2%), biological agents (14%), and 10% underwent surgical intervention. The cohort was divided into three subgroups according to the date of diagnosis; Group A: 1981-1989, Group B: 1990-1999, and Group C: 2000-2011. During the last two decades a significant increase in CD (Group A 18.5%, Group B 23.8%, Group C 48.8%; P<0.01) compared with the first decade with parallel decrease in UC (Group A 79.6%, Group B 71.9%, Group C 33.2%; P<0.001) was observed. CONCLUSIONS: Most children received 5-ASA, steroids, and immunomodulators. Patients with UC and IBDU were younger than those with CD. A significant increase in CD with parallel decrease in UC during the last decade was found.

Teeth and tongue discoloration after linezolid treatment in children.

We describe 3 children who developed teeth and tongue discoloration while receiving intravenous linezolid for 2 to 3 weeks. Linezolid was coadministered with piperacillin-tazobactam or meropenem. Teeth and tongue discoloration was reversible with dental cleaning after discontinuation of linezolid. We review the published pediatric and adult cases regarding teeth and tongue discoloration after linezolid administration.

Inflammatory bowel disease in children: the role of a positive family history.

OBJECTIVES: The aim of this study was to evaluate any potential influence of a family history of inflammatory bowel disease (IBD) on the clinical phenotypes and the course of IBD in children. METHODS: In this retrospective study, the notes of 411 children with the diagnosis of IBD, 244 (59.4%) with ulcerative colitis, 129 (31.4%) with Crohn's disease and 38 (9.2%) with IBD unclassified, who were admitted to our department between 1 January 1981 and 31 December 2007 were reviewed. The aim was to assess the prevalence of familial IBD and its impact on the age of disease onset, clinical phenotypes according to the Montreal classification, course and outcome of disease. The control group consisted of IBD children without a family history of IBD, who were admitted to the hospital during the same time period. RESULTS: Thirty five (8.5%) children had a family history of IBD, (ulcerative colitis 6.6%, Crohn's disease 10.9% and IBD unclassified 13.2%). Sixty-eight percent of the 22 pairs of first-degree relatives were concordant for the clinical phenotype of disease. Significantly, more children with familial IBD had symptom onset and/or disease diagnosis before 5 years of age compared with sporadic IBD (P = 0.01 and P = 0.014, respectively); however, no differences were seen in sex, clinical phenotypes, need for aggressive treatment and/or surgery. CONCLUSION: Children with familial IBD had earlier onset of disease compared with those with sporadic IBD. However, this had no significant impact on the clinical phenotypes, the course and/or the outcome of disease.

Abrupt and durable remission of Henoch-Schönlein purpura nephritis with cyclosporine A.

Henoch-Schönlein purpura glomerulonephritis (HSP-GN) is a common form of systemic small vessel vasculitis in children. Although prognosis is usually favourable, the disease is occasionally associated with a risk of renal insufficiency. Various immunosuppressive agents have been used in patients with severe HSP-GN, but none have shown convincing favourable effects. We report a case of biopsy-proven HSP-related GN in a 4-year-old girl that responded remarkably well to cyclosporine A (CsA), following failure to respond to other immunosuppressive agents. At 8 months post-CsA treatment, repeat renal biopsy findings were consistent with histological improvement. We conclude that CsA treatment not only exerts beneficial effects on resistant HSP-related GN but may also arrest progression of the disease.

Different effects of sensitization to mites and pollens on asthma symptoms and spirometric indices in children: a population-based cohort study.

BACKGROUND: We have previously shown that long-term exposure of children to a highly polluted urban compared with a rural environment is associated with subclinical airway narrowing and increased prevalence of atopy. OBJECTIVE: To test the hypothesis that sensitization to indoor perennial, compared with seasonal, aeroallergens has distinct effects on asthma symptoms and/or spirometric indices. METHODS: We evaluated the respiratory health of 478 and 342 children aged 8 to 10 years living in an urban and a rural area, respectively, during a period of 8 years. Children were evaluated by parental questionnaire in 3 phases, 1995 to 1996 (phase 1), 1999 to 2000 (phase 2), and 2003 to 2004 (phase 3), and by spirometry and skin prick testing to 9 common local aeroallergens in phases 1 and 2. RESULTS: Sensitization to pollens was associated with current wheezing in phase 1 of the study (odds ratio [OR], 3.36; 95% confidence interval [CI], 1.71 to 6.62; P < .001) but not with spirometric indices. Sensitization to mites was negatively associated with forced expiratory volume in 1 second (95% CI, -7.26 to -0.90; P = .01) and forced expiratory flow at 50% of forced vital capacity (95% CI, -10.80 to -1.33; P = .01) in study phase 1 but not in phase 2. CONCLUSIONS: Our results indicate that sensitization to mites is associated with insidious involvement of large and small airways, whereas sensitization to pollens is associated with childhood wheezing at the age of 8 to 10 years. Subsequent loss of these associations implies that risk factors other than allergy influence airway disease at a later age.

Factors associated with asthma symptoms in schoolchildren from Greece: the Physical Activity, Nutrition and Allergies in Children Examined in Athens (PANACEA) study.

To evaluate whether dietary habits and anthropometric and lifestyle characteristics are associated with the prevalence of asthma symptoms, a sample of 700 Greek schoolchildren were evaluated through a standardized questionnaire. Body height and weight were measured, and body mass index was calculated. Multiple logistic regression and multivariate techniques (principal components analysis) were performed. Overall lifetime prevalence for asthma symptoms was found to be 23.7%. Increased body weight, sedentary lifestyle, and consumption of sulphur-dioxide-enriched foods and beverages seem to promote asthma symptoms, while avoidance of this chemical preservative and physical activity was associated with reduced odds of reporting asthma symptoms.

Aseptic meningitis in children: analysis of 506 cases.

BACKGROUND: Non-polio human enteroviruses are the leading cause of aseptic meningitis in children. The role of enterovirus PCR for diagnosis and management of aseptic meningitis has not been fully explored. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective study was conducted to determine the epidemiological, clinical, and laboratory characteristics of aseptic meningitis and to evaluate the role of enterovirus PCR for the diagnosis and management of this clinical entity. The medical records of children who had as discharge diagnosis aseptic or viral meningitis were reviewed. A total of 506 children, median age 5 years, were identified. The annual incidence rate was estimated to be 17/100,000 children less than 14 years of age. Most of the cases occurred during summer (38%) and autumn (24%). The dominant clinical symptoms were fever (98%), headache (94%) and vomiting (67%). Neck stiffness was noted in 60%, and irritation in 46% of the patients. The median number of CSF cell count was 201/mm(3) with polymorphonuclear predominance (>50%) in 58.3% of the cases. Enterovirus RNA was detected in CSF in 47 of 96 (48.9%) children tested. Children with positive enterovirus PCR had shorter hospitalization stay as compared to children who had negative PCR or to children who were not tested (P = 0.01). There were no serious complications or deaths. CONCLUSIONS: Enteroviruses accounted for approximately one half of cases of aseptic meningitis. PCR may reduce the length of hospitalization and plays important role in the diagnosis and management of children with aseptic meningitis.