Epidermolysis bullosa-associated nevi are recently described dysplastic nevi found in patients with epidermolysis bullosa. These lesions display clinical features of unusual nevi suggestive of malignancy but thus far cases with malignant transformation have not been reported. We describe a case of epidermolysis bullosa-type nevi developing in a child with pyoderma gangrenosum. The nevi in our patient were found in areas previously affected by pyoderma gangrenosum and were clinically concerning for malignancy. However, they were only moderately atypical on light and confocal microscopy. This case demonstrates that pediatric patients with cutaneous inflammation, bullae formation, or both, are at risk for developing unusual nevi at previous sites of skin involvement. Considering the absence of malignant change in these nevi, we suggest that close observation can be employed in cases where this diagnosis can be confirmed both clinically and microscopically.

OBJECTIVE: Inflammatory markers such as C-reactive protein (CRP) are related to obesity in adults, but the association is less clear in children. Our objective was to examine relationships between multiple markers of inflammation and children's weight status; we hypothesized that the prevalence of inflammatory markers would increase as weight status increased. METHODS: We conducted a cross-sectional analysis of children in the United States aged 1 to 17 years in the National Health and Nutrition Examination Survey, 1999–2006. Children were categorized using weight-for-length when age <2 years and BMI for ≥2 years, as very obese (≥99th percentile), obese (<99th and ≥95th percentile), overweight (<95th and ≥85th percentile), and healthy weight (>5th to ≤85th percentile) according to expert consensus. Our main outcome measures were high-sensitivity CRP and absolute neutrophil count, in addition to a novel third measure: ferritin controlled for iron status using a ferritin/transferrin ratio. We used Cox proportional hazards models to examine risk of abnormal values of inflammatory markers according to weight. RESULTS: Increased risk of a CRP level of >1.0 mg/L was evident among very obese children from ages 3 to 5 years (hazard ratio [HR]: 2.29; P < .01) through 15 to 17 years (HR: 4.73; P < .01). Increased risk of abnormal neutrophil count among very obese children began at 6 to 8 years (HR: 2.00; P = .049), and increased prevalence of abnormal ferritin/transferrin ratio began at 9 to 11 years (HR: 7.06; P < .001). CONCLUSIONS: Multiple inflammatory markers are strongly and positively associated with increasing weight status in children, and this relationship starts as young as age 3. Elevated inflammatory markers in very young obese children are particularly concerning, because inflammation may cause long-term, cumulative vascular damage. This deserves additional research via longitudinal design.

In this report, we describe a brother and sister who presented at birth with short-limb skeletal dysplasia, polyhydramnios, prematurity, and generalized edema. Dysmorphic features included broad nose, thick ears, thin lips, micrognathia, inverted nipples, ulnar deviation at the wrists, spatulate fingers, fifth finger camptodactyly, nail hypoplasia, and talipes equinovarus. Other features included short stature, microcephaly, psychomotor retardation, B-cell lymphopenic hypogammaglobulinemia, sensorineural deafness, retinal detachment and blindness, intestinal malrotation with poor gastrointestinal motility, persistent hyponatremia, intermittent hypoglycemia, and thrombocytopenia. Cardiac anomalies included PDA, VSD, hypertrophic cardiomyopathy, and arrhythmias. The brother had a small penis with hypospadias, hypoplastic scrotum, and non-palpable testes. Skeletal findings included absent ossification of cervical vertebral bodies, pubic bones, knee epiphyses, and tali. Both sibs died before age 2 years, one of overwhelming sepsis and the other of cardiorespiratory failure associated with her cardiomyopathy. Metabolic studies showed a type 1 pattern of abnormal serum transferrin glycosylation. Fibroblasts synthesized truncated LLOs, primarily Man(7)GlcNAc(2), suggestive of CDG-Ig. Both sibs were compound heterozygotes for a novel 301 G > A (G101R) mutation and a previously described 437 G > A (R146Q) mutation in ALG12. Congenital disorders of glycosylation should be considered for children with undiagnosed multi-system disease including neurodevelopmental delay, skeletal dysplasia, immune deficiency, male genital hypoplasia, and cardiomyopathy.

Background: Influenza can cause significant morbidity and mortality in subjects at high risk for complications, including the elderly (age >= 65 years) and those with chronic respiratory, cardiovascular, or metabolic conditions. Effective prophylaxis can significantly reduce the disease burden in this population. Previous studies conducted primarily in non-high-risk subjects have reported the efficacy of inhaled zanamivir in preventing influenza.Objective: This study investigated the efficacy and safety of zanamivir in preventing influenza in community-dwelling adult and adolescent subjects at high risk for complications of influenza.Methods: This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group study in community-dwelling subjects aged >= 12 years who were at high risk for developing complications of influenza, were able to use the Diskhaler device (Glaxo Group Limited, Research Triangle Park, North Carolina), and were able to take the first dose of study medication within 5 days of laboratory-confirmed local influenza activity. Eligible subjects were randomized to receive inhaled zanamivir 10 mg or placebo once daily for 28 days. The primary end point was the proportion of randomized subjects who developed symptomatic influenza during prophylaxis, as confirmed by culture and/or serology. All adverse events (AEs) occurring after the first dose of study medication were recorded.Results: The study enrolled 3363 subjects, of whom 58% were female and 93% were white; the mean age of participants was 60.4 years (range, 12-94 years), and 4% were adolescents. Significantly fewer zanamivir-treated subjects developed symptomatic, laboratory-confirmed influenza during prophylaxis compared with placebo recipients (4/1678 vs 23/1685, respectively), representing a relative risk (RR) of 0.17 (95% CI, 0.07-0.44; P < 0.001) and a protective efficacy of 83%. The incidence of complications was reduced in zanamivir-treated subjects compared with placebo recipients (1/1678 and 8/1685), representing an RR of 0.12 (95% CI, 0.02-0.73; P = 0.042) and a protective efficacy of 88%. The numbers of zanamivir recipients (151/1678 [9%]) and placebo recipients (169/1685 [10%]) who developed symptomatic influenza-like illness regardless of laboratory confirmation did not differ significantly (RR = 0.86; 95% CI, 0.70-1.06), indicating that zanamivir was not effective in preventing influenza-like illness that was not caused by influenza infection. Similarly, there was no significant difference in the numbers of zanamivir and placebo recipients who developed laboratory-confirmed infection regardless of symptoms (39/1678 [2%] and 5211685 [3%],respectively; RR = 0.76; 95% CI, 0.50-1.15). Of these, 64 subjects (35 and 29) were asymptomatic; serocon-version occurred in all but 1 subject, indicating that zanamivir prophylaxis did not prevent asymptomatic serocon-version. During prophylaxis, 51% of subjects in both treatment groups reported at least 1 AE. There were no major differences in the frequency or nature of AEs between groups. The most commonly reported AEs ( >= 3% of subjects in each treatment group) were consistent with upper respiratory viral infection (headache: 17% zanamivir, 18% placebo; cough: 14% and 15%, respectively; throat and tonsil discomfort/pain: 13% and 14%). There were no differences between groups in the overall incidence of viral respiratory infections (5% in both groups) or ear, nose, and throat infections (2% in both groups). None of the analyzed isolates from confirmed cases of influenza exhibited reduced susceptibillty to zanamivir or genotypic evidence of resistance.Conclusions: Zanamivir, administered once daily for 28 days, was efficacious in preventing infection with the predominant circulating strains in the 20002001 influenza season in the Northern Hemisphere (influenza A/New Calendonia/20/99-like and influenza B/Sichuan/379/99-like) in these high-risk community-dwelling subjects aged >= 12 years. Zanamivir was well tolerated, with a safety profile comparable to that of placebo. No emergence of resistant virus was detected. (Clin Ther. 2007;29:1579-1590) Copyright (c) 2007 Excerpta Medica, Inc.

Olsen, Brian; Henderson, Frederick W; Muhlebach, Marianne S; Willis, Tina Schade Author Information

BACKGROUND:Inflammatory processes at the mucosal surface may play a role in maintenance of asthma pathophysiology. Cross-sectional studies in asthmatic patients suggest that chemokines such as interleukin 8 (IL-8) are overproduced by respiratory epithelium.OBJECTIVE:To test the hypothesis that chemokine levels are persistently elevated in the respiratory secretions of asthmatic children at a stable baseline.METHODS:We measured nasal lavage fluid (NLF) levels of chemokines and other mediators at 3- to 4-month intervals in a longitudinal study of asthmatic children, with nonasthmatic siblings as controls.RESULTS:In a linear mixed-model analysis, both family and day of visit had significant effects on nasal mediators. Thus, data for 12 asthmatic-nonasthmatic sibling pairs who had 3 or more same-day visits were analyzed separately. For sibling pairs, median eosinophil cationic protein levels derived from serial measurements in NLF were elevated in asthmatic patients compared with nonasthmatic patients, with a near-significant tendency for elevation of total protein and eotaxin levels as well. However, no significant differences were found for IL-8 or several other chemokines. Ratios of IL-13 or IL-5 to interferon-gamma released by house dust mite antigen-stimulated peripheral blood mononuclear cells, tested on a single occasion, were significantly increased for asthmatic patients.CONCLUSIONS:Substantial temporal and family-related variability exists in nasal inflammation in asthmatic children. Although higher levels of eosinophil cationic protein are usually present in NLF of patients with stable asthma compared with patients without asthma, chemokines other than eotaxin are not consistently increased. Eosinophil activation at the mucosal surface is a more consistent predictor of asthmatic symptoms than nonspecific elevation of epithelium-derived inflammatory chemokine levels.

In 2001, 80% of children <6 years of age were in out-of-home child care an average of 40 hours per week. More than 1.2 million persons (primarily women) were paid to care for these children in childcare centers or homes. Childcare workers are among the lowest paid segment of the workforce. They are exposed to a number of occupational hazards, including stress, injuries, and occupational exposures to infectious diseases.

A phase 2 evaluation of live attenuated parainfluenza type 3 (PIV3)-cold passage mutant 45 (cp45) vaccine was conducted in 380 children 6-18 months old; 226 children (59%) were seronegative for PIV3. Of the 226 seronegative children, 114 received PIV3-cp45 vaccine, and 112 received placebo. No significant difference in the occurrence of adverse events (i.e., runny nose, cough, or temperature > or =38 degrees C) was noted during the 14 days after vaccination. There was no difference between groups in the occurrence of acute otitis media or serous otitis media. Paired serum samples were available for 109 of the seronegative vaccine recipients and for 110 of the seronegative placebo recipients; 84% of seronegative vaccine recipients developed a > or =4-fold increase in antibody titers. The geometric mean antibody titer after vaccination was 1 : 25 in the vaccine group and <1 : 4 in the placebo group. PIV3-cp45 vaccine was safe and immunogenic in seronegative children and should be evaluated for efficacy in a phase 3 field trial.

OBJECTIVE:Otitis media with effusion (OME) is a common health care problem for children. The purpose of this study was to examine factors that place children at risk for OME such as age, type of child care, number of people in the household, and smoking in the household.METHODS:Eighty-six African American children, enrolled in center-based child care in infancy, entered the study at a mean age of 8.2 months and were followed prospectively until 48 months of age. Ear status was documented biweekly using pneumatic otoscopy and tympanometry. Data on risk factors were collected every 6 months.RESULTS:Results indicated that children had a marked decrease in the proportion of time with OME between 6 and 48 months. The rate of OME decline was faster in the first 2.5 years than in subsequent years. Children in center-based child care showed a slightly slower rate of decline than did children in non-center-based care. Longitudinal analysis indicated that the age of the child and the number of other children in the household were significant predictors of OME. For each additional child under 12 years of age in the home, there was a 2% increase in the proportion of time with OME.CONCLUSION:While attendance in group child care predicted a risk for OME, children's age and the number of other children in the household were still contributing risk factors for OME.

This study measured chemokines in nasal lavage fluids (NLF) from infants with respiratory syncytial virus (RSV) bronchiolitis, defined by lung hyperinflation and wheezing. Comparison was made to RSV-positive infants without bronchiolitis and RSV-negative infants with acute respiratory illnesses. RSV-positive illnesses were associated with increased epithelial shedding, increased RANTES/protein ratios, and increased IL-8/protein ratios in NLF compared to RSV-negative illnesses. Among RSV-positive infants, bronchiolitics had greater total cell counts and percentage epithelial cells in NLF than nonbronchiolitics. Bronchiolitics also had roughly twice the NLF RANTES/IL-8 ratio than nonbronchiolitics (P =.043). Semiquantitative reverse transcriptase-polymerase chain reaction of nasal epithelium suggested similar RANTES/IL-8 ratio increases among bronchiolitics. A more mildly affected, RSV-positive outpatient population showed none of these differences. We conclude that RSV bronchiolitis is associated with a shift toward relatively more RANTES in nasal secretions of infants sick enough to require hospitalization, and mucosal epithelium may contribute to this process. Similar processes in the lower airways may enhance inflammation due to RANTES-responsive cell types and affect clinical manifestations.

Mycoplasma pneumoniae (Mp) infection is associated with asthma exacerbation in children. We hypothesized that Mp infection may cause airway inflammation by inducing the release of cytokines by respiratory epithelial cells. The levels of chemokines interleukin-8 (IL-8) and released upon activation, normal t cell expressed and secreted (RANTES) released by nasal epithelial cell (NEC) cultures established from asthmatic and nonasthmatic children were measured by ELISA at 4, 24, 48, and 72 hr after cells were inoculated with Mp, and were compared with baseline release of these factors. The presence of MP on apical membranes of NEC after infection was confirmed by transmission electron microscopy, and adherence was shown to be inhibited by erythromycin. Mp infection did not alter NEC release of IL-8 or RANTES at any time point. In contrast, tumor necrosis factor alpha (TNF-alpha) stimulated increased IL-8 at all time points, and respiratory syncytial virus (RSV) infection stimulated RANTES release at 48 and 72 hr by NEC. These results were not significantly different between NEC from asthmatic and nonasthmatic children. As a comparison, peripheral blood mononuclear cells from normal human volunteers were also incubated with Mp and had significantly increased release of IL-2, IL-6, and TNF-alpha. We conclude that Mp, unlike viral pathogens such as RSV, is unlikely to directly stimulate early airway surface cytokine responses via mechanisms involving epithelial cells. We speculate that the chronic presence of mononuclear cells at the airway surface of asthmatics provides a target for Mp-triggered cytokine production.

BACKGROUND:Influenza infection rates are higher in children than in other age groups. This study evaluated the efficacy, safety and tolerability of a 5-day course of twice daily inhaled zanamivir, 10 mg, compared with placebo in the treatment of symptomatic influenza A and B viral infections among children 5 to 12 years of age. METHODS:This double blind, randomized, placebo-controlled, parallel group, multicenter study conducted in the Northern Hemisphere during the 1998 and 1999 influenza season enrolled 471 patients with influenza-like symptoms for < or = 36 h. Patients were randomly assigned to zanamivir (n = 224) or placebo (n = 247). Symptoms were recorded on diary cards twice daily during treatment, for 9 days after treatment and for 14 additional days (if still reporting moderate/severe cough and/or taking relief medication). FINDINGS:A total of 346 (73%) patients were influenza-positive by culture, serology or polymerase chain reaction (65% influenza A, 35% influenza B). Zanamivir reduced the median time to symptom alleviation by 1.25 days compared with placebo among patients with confirmed influenza infection (P < 0.001). Zanamivir-treated patients returned to normal activities significantly faster and took significantly fewer relief medications than placebo-treated patients. Zanamivir was well-tolerated, demonstrating adverse event profiles similar to those of placebo and no clinically significant changes in laboratory findings. Viral susceptibility testing revealed no zanamivir-resistant strains of influenza A or B. CONCLUSIONS:Zanamivir was effective in shortening the duration and severity of influenza symptoms and was well-tolerated among children 5 to 12 years of age.

To show the frequent association of synovial cysts and facet effusion. MR studies of 26 patients with lumbar synovial cysts were reviewed for sex/age incidence, anatomic location, multiplicity of cysts and associated pathologies. All studies were reviewed for presence of facet effusion. 26 patients had 39 MRI documented synovial (17 females, 9 males). Age distribution: 41 – 79 years. Location of cysts: L4/5 = 29, L3/4 = 6, L5/S1 = 3, L1/2= −;1. 36 synovial cysts showed facet effusion. 19 patients also had facet effusions at adjoining motion segments or at contralateral joints. Synovial cysts were found in anterior (n=20), posterior (n=13), anterior-posterior (n=3) positions. 18 patients had cysts localized to one single facet joint, 8 patients showed synovial cysts at multiple facet joints. The frequent coexistence of synovial cysts and facet effusion in our material suggests a causal relationship. External herniation of synovium from a fluid expanded joint space appears to be the most plausible pathologic mechanism.