Family history of atopy in infants with cow's milk protein allergy: A French population-based study.

OBJECTIVES: This French multicenter, cross-sectional, observational study aimed to describe the family history of atopy in infants with cow's milk protein allergy (CMPA), and the related diagnostic approaches used by specialists in a real-life ambulatory setting. PATIENTS AND METHODS: In total, 1674 infants with suspected CMPA [median age 4.5 months (range: 0.1-18.0), males 54%] were enrolled in the study by 466 private physicians (pediatricians: 97%). Family history of atopy was defined as a known history of atopy in at least one first- (father, mother, and/or sibling) and/or second-degree relative (grandparents, uncles, and aunts), as reported by parents to physicians. RESULTS: Atopy in a first-degree relative was more common among infants with documented or high probability of CMPA (in 84% and 80% of cases, respectively, vs. the other subgroups, P=0.005). Most infants experienced digestive (92%) and skin (61%) symptoms suggestive of CMPA. Delayed reactions were reported in 64% of infants. According to a post-classification based on the results of previous diagnostic tests and procedures, 1133 infants (68%) had highly probable (52%) or documented CMPA (16%). In these infants, a history of atopy was reported in first- and/or second-degree relative(s) in 86% of cases (81% in first-degree relatives). Whatever the family history of atopy, the characteristics of the infants were similar, except for fewer pets in the case of negative family atopy (14% vs. 25%, P<0.001). Atopy in a parent was more frequent in infants who presented with the first signs suggestive of CMPA within the first 6 months of life vs. those with later first symptoms (75% vs. 65%, P=0.063). CONCLUSION: This French study confirms the high rate of family history of atopy in first-degree relatives of infants with probable or documented CMPA.

Treatment of gastric eosinophilia by epicutaneous immunotherapy in piglets sensitized to peanuts.

BACKGROUND: Eosinophilic gastrointestinal disorders (EGIDs) are hypersensitivity disorders frequently triggered by food allergy and manifested by mucosal eosinophilic infiltration at any level of the gastrointestinal tract. This study established a model of gastric eosinophilia in peanut-sensitized piglets to evaluate the efficacy of epicutaneous immunotherapy (EPIT) for its treatment. METHODS: Experiments were carried out in piglets first sensitized by three intra-peritoneal injections of peanut protein extract (PPE) with adjuvant, and then given PPE orally for 10 days, a sequence leading to gastric eosinophilia assessed by endoscopy. For 3 months, eight piglets received active EPIT, using Viaskin® loaded with PPE, applied daily on the ear, while eight received placebo EPIT (Placebo). Piglets were exposed to a second 10-day period of PPE orally. Lesions were scored by endoscopy on the last day of PPE exposure. After killing, all parts of the digestive tract were analysed by a pathologist unaware of the piglets' status. IgE response was measured, and mechanistic parameters were analysed in the spleen. RESULTS: After sensitization, a significant increase of total IgE was observed in sensitized compared to naive animals (61.1 ± 13.3 vs 27.8 ± 6 ng/mL, P < .01). Following oral intake of PPE, sensitized piglets developed moderate gastritis compared to naive piglets (1.5 vs 1.0, median score). After 3 months of immunotherapy, median IgE was significantly reduced in EPIT vs placebo piglets (61.4 ± 16.3 vs 105.9 ± 25.6 ng/mL, P < .01). Active EPIT significantly reduced gastric mucosal lesions induced by PPE oral intake (macroscopic score 0 [0-2] vs 2 [1-3], P < .01, respectively, active vs placebo) and gastric mucosa eosinophils counts (239 eosinophils/mm2 [59-645] vs 2554 eosinophils/mm2 [462-8057], P < .01, respectively active vs placebo). GATA-3, IL-5 and eotaxin mRNA expression decreased significantly after EPIT (P < .05). CONCLUSIONS: This study describes a large animal model of gastric eosinophil in peanut-sensitized piglets. Utilizing this model, we demonstrated the efficacy of EPIT in treating peanut-induced EGIDs.

Joint ESPGHAN/NASPGHAN guidelines for the management of helicobacter pylori in children and adolescents (Update 2016)

BACKGROUND: Because of the changing epidemiology of Helicobacter pylori infection and low efficacy of currently recommended therapies, an update of the European Society for Paediatric Gastroenterology Hepatology and Nutrition/North American Society for Pediatric Gastroenterology, Hepatology and Nutrition recommendations for the diagnosis and management of H pylori infection in children and adolescents is required. METHODS: A systematic review of the literature (time period: 2009-2014) was performed. Representatives of both societies evaluated the quality of evidence using GRADE (Grading of Recommendation Assessment, Development, and Evaluation) to formulate recommendations, which were voted upon and finalized using a Delphi process and face-to-face meeting. RESULTS: The consensus group recommended that invasive diagnostic testing for H pylori be performed only when treatment will be offered if tests are positive. To reach the aim of a 90% eradication rate with initial therapy, antibiotics should be tailored according to susceptibility testing. Therapy should be administered for 14 days, emphasizing strict adherence. Clarithromycin-containing regimens should be restricted to children infected with susceptible strains. When antibiotic susceptibility profiles are not known, high-dose triple therapy with proton pump inhibitor, amoxicillin, and metronidazole for 14 days or bismuth-based quadruple therapy is recommended. Success of therapy should be monitored after 4 to 8 weeks by reliable noninvasive tests. CONCLUSIONS: The primary goal of clinical investigation is to identify the cause of upper gastrointestinal symptoms rather than H pylori infection. Therefore, we recommend against a test and treat strategy. Decreasing eradication rates with previously recommended treatments call for changes to first-line therapies and broader availability of culture or molecular-based testing to tailor treatment to the individual child.

Paediatric epidemiology of Pasteurella multocida meningitis in France and review of the literature.

We report on six cases of Pasteurella multocida (P. multocida) meningitis occurring between 2001 and 2011 by a French nationwide active surveillance network of paediatric bacterial meningitis (ACTIV/GPIP). The cases accounted for 0.15 % of the paediatric meningitis cases reported between 2001 and 2011 in France, all in infants <4 months old. A review of the literature allowed us to gather information on 42 other cases of P. multocida meningitis in infants <1 year old reported since 1963. Among all 48 cases, 44 % were newborns. An animal source of the infection, including 39 household dogs and cats, was suspected or identified in 42 of 48 cases. A traumatic contact between the child and a pet occurred in 8 % of cases, and a vertical transmission from mother to child during birth in 10.4 %. Most of the time, the infection resulted from non-traumatic contact between the child and the pet, through licking or sniffing. The absence of host risk factors suggests that an immature immune system is responsible, given the young age of the children. Although complications, especially neurological lesions, were not rare (37.5 %), the long-term outcome was usually good. Four infants died of meningitis. This rare disease could be prevented by reducing contact between infants and household pets, and by performing simple hygiene measures before handling babies.

[Cutaneous polymorph manifestations of familial Mediterranean fever in a child]. / Atteinte cutanée polymorphe de la fièvre méditerranéenne familiale chez un enfant.

We describe the case of a 4-year-old child with Mediterranean fever characterized by cutaneous features. Familial Mediterranean fever is an autosomal recessive disorder characterized by recurrent attacks of fever and polyserositis including peritonitis, pleuritis, and arthritis. Skin involvement is less common. In our case, the successively patient presented erysipelas-like erythema, edemas of the palmar and plantar regions, and purpuric lesions. From these clinical observations, several diagnoses were raised: infectious erysipelas, Kawasaki disease, Henoch-Schönlein purpura, and familial Mediterranean fever. Only the latter diagnosis was confirmed after exploration and then confirmed with genetic analysis, which found a M694V homozygous mutation. Erysipelas-like erythema is the most frequent cutaneous sign reported in the literature and the only one to be associated with the M694V homozygous mutation. The originality of this case is the dominancy and polymorphism of the skin lesions.

Helicobacter pylori infection in children in Madagascar: risk factors for acquisition.

AIM: The aim of our study was to assess the prevalence, risk factors for acquisition and the clinical characteristics of H. pylori infection in Malagasy children. METHODS: A 2 year prospective study was conducted among 434 children from a rural (group A) and an urban area (group B). H. pylori status was evaluated by an ELISA serological test. Various demographic and clinical characteristics were recorded and subjected to statistical analysis. RESULTS: The prevalence of H. pylori infection was 39.6% and increased significantly from 18.1% for children <1 year old to 61.5% for children >10 years old. It was significantly higher in group B (46.9%) than in group A (26.4%). Using multivariate logistic regression modelling, a significant association was found between H. pylori infection and drinking spring water. Exposure to antibiotics during the previous year had no observable effect on H. pylori. CONCLUSION: The overall prevalence of H. pylori infection among Malagasy children was 39.6%. A significant association between H. pylori infection and drinking spring water was found.

New effective treatment regimen for children infected with a double-resistant Helicobacter pylori strain.

BACKGROUND: The increasing number of pediatric patients infected with multiresistant Helicobacter pylori strains calls for evaluation of treatment regimens. Second-line antibiotics such as tetracycline or quinolones are not licensed for children. Because in vivo resistance to metronidazole may be overcome in vivo by a high dose and prolonged intake, we evaluated the eradication rate and side effects of a high-dose triple therapy in pediatric patients with culture-proven double resistance. PATIENTS AND METHODS: In this open multicentre trial, 62 children (<18 years, body weight >15 kg) infected with an H pylori strain resistant to metronidazole and clarithromycin were treated according to body weight classes with amoxicillin (∼ 75 mg/kg/day), metronidazole (∼ 25 mg/kg/day) and esomeprazole (∼ 1.5 mg/kg/day) for 2 weeks. Adherence and adverse events were assessed by a 2-week diary and telephone interviews at days 7 and 14 of treatment. Primary outcome was a negative C-urea breath test after 6 weeks. RESULTS: Of 62 patients, 5 were lost to follow-up, 12 were nonadherent, and 45 treated per protocol. Eradication rates were 66% (41/62) [confidence interval 54-78] (intention to treat) and 73% (33/45) [confidence interval 60-86] (per protocol). Success of treatment was not related to dose per kilogram body weight. Mild to moderate adverse events were reported by 21 patients, including nausea (10.8%), diarrhoea (8.9%), vomiting (7.1%), abdominal pain (5.4%), and headache (3.6%), and led to discontinuation in 1 child. CONCLUSION: High-dose amoxicillin, metronidazole, and esomeprazole for 2 weeks is a good treatment option in children infected with a double resistant H pylori strain.

[Health of gypsy children: medical perinatal care until 6-year-old in Lille]. / La santé des enfants des gens du voyage : suivi périnatal et jusqu'à 6 ans dans la métropole lilloise.

AIM: This study investigated the health of gypsy children, aged 0-6 years. We focused on pregnancy, birth, medical care, growth, and vaccinations. PATIENTS AND METHODS: This study was conducted between May and December 2004, comparing a gypsy population group (GP) to a sedentary control group with a relatively low socioeconomic level. Both groups were covered by the CMU (French universal health coverage). This study was based on an oral investigation and each child's health records. RESULTS: The population consisted of 241 children: 120 GP children and 121 CMU children. In the GP children, pregnancy care was lacking, whereas the CMU group received consistent care at regional university hospital centers. For both populations, 85% of births occurred after a mean 38 weeks and 5 days of amenorrhea by ordinary delivery. GP infants were more often transferred to neonatology centers. They were born and were shorter and weighed less than the CMU infants until 6 years of age. They were breast fed more often. They were hospitalized more often, usually for ORL and gastrointestinal infections. Siblings were more numerous. GP child medical care was deemed satisfactory in 40% of cases vs. 70% for CMU children. The vaccinations status was insufficient, particularly in the GP children. CONCLUSION: Follow-up of GP should be improved.

Eosinophil counts in upper digestive mucosa of Western European children: variations with age, organs, symptoms, Helicobacter pylori status, and pathological findings.

AIM: The aim of the study was to measure the number of eosinophils per high-power field (eos/HPF) according to age, organs, and clinical symptoms and to compare the results to histological characteristics of the upper digestive tract mucosa in children. PATIENTS AND METHODS: A systematic prospective assessment of 284 esophagus, 342 antrum, 453 corpus, and 167 duodenum biopsies was carried out in 316 girls and 366 boys referred for endoscopy (median age 9 months), eos/HPF, and histological analysis. RESULTS: Counts (mean-max SD) were as follows: esophagus 1.73 to 50 eos/HPF (5.35), antrum 3.27 to 40 (4.7), corpus 2.11 to 38 (3.76), and duodenum 4.80 to 46 (7.7). Counts >15 eos/HPF were found in 2.8% esophagi, 3.5% corpora, 4.9% antra, and 10.7% duodena. Duodenal eos/HPF were significantly higher than those of esophageal, corporeal, and antral. Mucosal eos/HPF increased with age in esophagus and antrum. The highest esophageal eos/HPF were significantly associated with recurrent abdominal pain, and with anemia in antrum, corpus, and duodenum. Major and/or minor histological features of eosinophilic esophagitis were seen in 9 of 10 esophagi with 5 to 15 eos/HPF and 7 of 8 esophagi with >15 eos/HPF. Eosinophils per high-power field were significantly correlated with histological antral and corporeal gastric inflammation. Helicobacter pylori-positive children had higher eosinophils per high-power field than H pylori negative ones both in esophagus and in antrum. CONCLUSIONS: The present study shows that in a western European country mucosal hypereosinophilia is rare. Mucosal eosinophil counts increase from esophagus to duodenum, and also with age in esophagus and antrum. The highest eos/HPF in the esophagus are associated with recurrent abdominal pain and in the corpus, antrum, and duodenum with anemia. Features of eosinophilic esophagitis are rare but detectable in association with counts as low as 6 eos/HPF.

Fecal expression of human ß-defensin-2 following birth.

BACKGROUND: Newborns display high intestinal permeability and a naive adaptive immune system, but infections are rare, indicating strong innate defense mechanisms. OBJECTIVE: To measure the kinetics of fecal ß-defensin-2 (HBD2), an inducible endogenous antimicrobial peptide produced by intestinal epithelial cells, in full-term and preterm infants. METHODS: As a first step of this bicentric study, we enrolled 30 healthy full-term infants and 20 healthy preterm infants, with fecal samples collected at days 3, 7, 12 and 30 in full-term infants and at days 15, 30 and 60 in preterm infants. As a second step, we enrolled 10 preterm infants with intestinal distress, either necrotizing enterocolitis (NEC) Bell's stage III (n = 3) or isolated rectal bleeding (n = 7) and 20 controls, cross-matched for gestational age and age at sampling. RESULTS: HBD2 decreased significantly from day 3 to day 7 (227 ng/g; 14-440 vs. 117 ng/g; 30-470, p = 0.01) then moderately until day 30 (84 ng/g; 10-500) in healthy full-term infants. Healthy preterm infants showed similar high levels between days 15 and 60 (82 ng/g; 30-154 and 85 ng/g; 26-390, respectively). No significant variation of fecal HBD2 levels was observed between infants with clinical features of intestinal distress (77 ng/g, 2-1,271) and cross-matched controls (56 ng/g, 31-164). However, 2/3 infants with NEC and 1/7 infants with isolated rectal bleeding had HBD2 levels above the maximal level observed in controls. CONCLUSIONS: The kinetics of fecal HBD2 in the neonatal period indicate that this inducible defensin can be detected at high level in the feces of full-term and preterm infants, independently of gestational age or mode of feeding. The potential role of fecal HBD2 in detecting NEC is suggested.

Atopy patch test for early diagnosis of cow's milk allergy in preterm infants.

Atopy patch test may help early diagnosis of cow-milk allergy in preterm infants. In the retrospective analysis of 5 girls and 9 boys, born at 31 +/- 2 (mean +/- SD) weeks of gestation and presenting digestive symptoms at age 42 +/- 18 days, 10 had a complete recovery following the shift to an exclusive feeding with an amino acid-based formula. Cow-milk-skin prick tests and specific immunoglobulin E were always negative, whereas the atopy patch test was positive in 7 of the 10 infants with complete recovery.

[Pneumococcal conjugate vaccine coverage in a hospital center of the Metropolis of Lille in 2008]. / Couverture vaccinale par le vaccin pneumococcique heptavalent conjugué dans un centre hospitalier de la métropole lilloise en 2008.

OBJECTIVE: To describe the vaccine coverage of Prevenar(®), follow its evolution since its universal recommendation from 2006 and search the influence of certain socio-economic factors. METHOD: A prospective descriptive study by a questionnaire enrolled the first 250 children born after 2001 and aged more than 2 months admitted at our hospital emergency room with their health record. RESULTS: 77.11% of children from any age merged received the first dose of Prevenar(®); 89.51% of those less than 24 months versus 60.38% of those more than 24 months, p<0.0001. The follow-up by a paediatrician and the high mother educational level influenced positively the vaccination by Prevenar(®). CONCLUSION: Prevenar(®) vaccine coverage evolved well since its universal recommendation achieving a 89.51% rate for the first dose. The chase of a brought closer follow-up seems important to assess the impact of this new vaccine strategy.

Gastric atrophy and Helicobacter pylori infection in children.

AIM: To assess the prevalence of gastric atrophy (GA) in Tunisia (a high prevalence region for Helicobacter pylori), and describe its histological, clinical and endoscopic features in children. METHODS: 345 children, 151 male and 194 female, mean age 8.6 +/- 3.7 years, underwent upper gastrointestinal (UGI) endoscopy with gastric biopsies for recurrent abdominal pain (n=232, 67.2%), vomiting (n=72, 20%) associated with or without upper gastrointestinal bleeding (n=59, 17.1%) and miscellaneous causes (n=53, 15.4 %). Biopsies performed both in the gastric antrum (n=2) and corpus (n=2) were analysed for histological assessment according to the updated Sydney classification system and bacterial culture. A positive result was recorded where histology and/or culture were positive, confirming the presence of H. pylori infection (H. pylori +ve). A negative result was recorded when both tests were concomitantly negative (H. pylori -ve). RESULTS: 9.3% (32/345) of the total population, and 14.5% (32/221) of chronic gastritis patients exhibited GA, M/F: 16/16, mean age (SD) 9.4 (3.4) years. Amongst the 32 children with GA, 30 (93.7%) were H. pylori +ve and 2 (6.3%) were H. pylori -ve. GA was localised in the antrum (n=26, 81.2%), the fundus (n=2, 6.3%) and was also seen in both (n=4, 12.5%). GA was categorised as mild, grade 1 (n=18, 56.3%); moderate, grade 2 (n=13, 46.6%); and severe, grade 3 (n=1, 3.1%). GA was associated with mild active gastritis in 18 cases (56.3%). The prevalence of moderate or severe antral GA was detected in 9/26 (34.6%) of H. pylori +ve vs. any of H. pylori -ve (p=0.4), whereas GA in the corpus was detected in 1/2 (50%) vs. none, respectively. None exhibited intestinal metaplasia. There were no clinical features specific to this pathology. UGI endoscopy in GA patients showed nodular gastritis (n=17, 53.1%), congestive gastritis (n=9, 28.1%), and normal tissue (n=6, 18.8%). GA was significantly associated with H. pylori infection (p<0.0001) and nodular gastritis (p<0.005). CONCLUSION: GA was found in 9.3% of Tunisian children undergoing UGI endoscopy and was significantly associated with H. pylori infection and nodular gastritis.

In French children, primary gastritis is more frequent than Helicobacter pylori gastritis.

The aim of this study was to analyze the histological characteristics according to the updated Sydney classification (intensity of gastritis, degree of activity, gastric atrophy, intestinal metaplasia, and Helicobacter pylori) in symptomatic children referred for upper gastrointestinal endoscopy. A 4-year retrospective descriptive study was carried out in 619 children (282 females and 337 males), median age 3.75 years (15 days to 17.3 years) referred for endoscopy. Six gastric biopsies were done (three antrum and three corpus) for histological analysis (n = 4), direct examination and H. pylori culture (n = 2). H. pylori status was considered positive if at least two out of three tests were positive and negative if all three tests were negative. The results showed that only 66 children (10.66%) were H. pylori positive. Histological antral and corpus gastritis was detected in, respectively, 53.95% and 59.12% of all cases, most of them of mild grade 1. Antral and corpus activity was grade 1 in 18.57% and 20.03% of cases. H. pylori-positive versus H. pylori-negative children did differ in terms of moderate and marked histological gastritis and grade 2 or 3 activities. One girl had moderate gastric atrophy and another one moderate intestinal metaplasia, both being H. pylori negative. The findings indicate that primary antrum and corpus gastritis is 5.3 and 6.9 times, respectively, more frequent than H. pylori gastritis in French children, with usually mild histological gastritis and activity. Gastric atrophy and intestinal metaplasia are rare.

Ready-to-use house dust mites atopy patch test (HDM-Diallertest), a new screening tool for detection of house dust mites allergy in children.

AIM: to assess the accuracy and safety of a ready-to-use atopy patch test (HDM-Diallertest, DBV Technologies, Paris) in the diagnosis of sensitization to house-dust mite (HDM) allergens in children with or without atopic dermatitis. PATIENTS AND METHODS: prospective analysis of a systematic allergic work-up was carried out in 47 children, age 57.4+42 months (mean + SD, range 7 to 176 mo), presenting with isolated or combined atopic dermatitis (AD, n = 28) or other symptoms without AD (control group, n = 19). Children were routinely tested for specific HDM-IgE [against D. pteronyssinus (DPT) and D. farinae (DF)], and skin testing based on HDM (DPT & DF) skin prick test (SPT) and ready-to-use HDM-ATP (HDM-Diallertest), with a reading at 72 hours. RESULTS: 15 children (31.9%) exhibited specific IgE against both DPT and DF, 16 children (34.04%) exhibited positive SPT against DPT and 17 (36.1%) against DF. HDM-Diallertest was positive in 15 cases (31.9%). Among these, 9 exhibited with an eczematous reaction showed an excellent correlation with both SPT and specific IgE for DPT and DF, respectively 93.3%, 97.77%, 90.47%, and 90.47%. The different diagnostic techniques of HDM sensitization neither differ between groups, nor correlated specifically with the different clinical manifestations. No side effect was observed during and after patch testing, except for a local reaction without diffusion outside the local test area. CONCLUSION: The 3 diagnostic techniques exhibited a comparable level of accuracy for the diagnosis of HDM allergens sensitization. The excellent concordance of the highest class reactions of HDM-Diallertest with the other diagnostic techniques indicates a potential role as a screening tool for the detection of HDM sensitization in infancy.