[Multiple chemical sensitivity: a diagnosis not to be missed]. / Syndrome d'intolérance aux odeurs chimiques (SIOC) : un diagnostic à ne pas manquer. Épidémiologie, diagnostic, traitement.

Multiple chemical sensitivity (MCS) is a chronic condition, which belongs to the group of medically unexplained syndromes. Patients (men as well as women) complain of many subjective symptoms such as nose and mouth irritation, sore throat, dyspnea, tiredness, dizziness, headache and concentration difficulties. Patient typically report at least four or five symptoms occurring when they are exposed to particular substances, at a very low concentration that usually does not cause symptoms or harm in normal individuals. The common feature of products that appear to be responsible (either occupational or domestic) is that they have a strong smell and include: solvent, paint, glue, tar, oil, pesticides, perfume, cosmetics and spray products. MCS is nowadays considered to be one aspect of idiopathic environmental intolerance (IEI) whose other main aspect is hypersensitivity to electromagnetic fields. If the diagnosis is suspected clinically it can be confirmed using the Quick Environmental Exposure and Sensitivity Inventory (QEESI(©)) self-questionnaire. MCS is often misdiagnosed as asthma or an allergic conditions which means that patients are frequently referred to respiratory and allergy specialists. Misdiagnosis can lead to many futile medical investigations. Psychotherapy can improve quality of life in some cases. Preventive measures are often ineffective and do not stop the condition worsening: hypersensitivity can spread to common environmental odors so that a few people become severely disabled and limited in their workplace as well as in private life. In France, 435 cases were registered in the university hospital occupational disease departments network (RNV3P) during the period 2007-2010. It is therefore important that every clinician be able to recognize the condition and ensure that their patients could get compensation when unable to go on working.

Management of young children in contact with an adult with drug-resistant tuberculosis, France, 2004-2008.

SETTING: Drug-resistant tuberculosis (DR-TB) is increasing worldwide and may be a source of diagnostic and therapeutic problems in young exposed children. In France exposed children are systematically treated with 3-month isoniazid-rifampicin prophylaxis. OBJECTIVE: To describe the characteristics and management of children aged <2 years in contact with an adult case of DR-TB in France over a 5-year period (2004-2008). METHODS: Children were retrospectively identified by sending questionnaires to all the members of the Paediatric Infectious Diseases Group and the Paediatric Pulmonology Group of the French Paediatric Society. RESULTS: Ten children, all infants, in contact with an adult case of DR-TB were identified: six cases of DR-TB (mean age 4.6 months), one case of TB infection and three cases of exposure (mean age 3.1 months). The children were mainly in contact with poly- or multidrug-resistant TB. Time to initiation of appropriate treatment was 39 days for TB disease and 58 days for TB infection or exposure. One child with TB infection developed TB disease due to failure to adapt prophylaxis. Treatment was variable and centre-dependent. Short-term follow-up showed complete recovery of all children. CONCLUSION: Management of young children in contact with adult DR-TB requires rapid identification of the drug resistance profile. Molecular techniques should be used to reduce delays in initiating appropriate treatment.

Non-classic cystic fibrosis associated with D1152H CFTR mutation.

BACKGROUND: Limited knowledge exists on phenotypes associated with the D1152H cystic fibrosis transmembrane conductance regulator (CFTR) mutation. METHODS: Subjects with a D1152H allele in trans with another CFTR mutation were identified using the French Cystic Fibrosis Registry. Phenotypic characteristics were compared with those of pancreatic insufficient (PI) and pancreatic sufficient (PS) cystic fibrosis (CF) subjects in the Registry (CF cohort). RESULTS: Forty-two subjects with D1152H alleles were identified. Features leading to diagnosis included chronic sinopulmonary disease (n = 25), congenital absence of the vas deferens (n = 11), systematic neonatal screening (n = 4), and genetic counseling (n = 2). Median age at diagnosis was 33 [interquartile range (IQR, 24-41)] years in D1152H subjects. Median sweat chloride concentrations were 43.5 (39-63) mmol/l in D1152H subjects and were markedly lower than in PI and PS CF subjects (p < 0.05). Bronchiectasis was present in 67% of D1152H subjects, but Pseudomonas aeruginosa colonization and pancreatic insufficiency were present in <30% of subjects. Estimated rates of decline in forced expiratory volume in 1 s (FEV(1)) were lower in D1152H subjects vs PI CF subjects (p < 0.05). None of the D1152H subjects identified since 1999 had died or required lung transplantation. CONCLUSIONS: When present in trans with a CF-causing mutation, D1152H causes significant pulmonary disease, but all subjects had prolonged survival.

Neonatal screening of cystic fibrosis: diagnostic problems with CFTR mild mutations.

Newborn screening (NBS) of cystic fibrosis (CF) was implemented throughout the whole of France in 2002, but it had been established earlier in three western French regions. It can reveal atypical CF with one or two known CFTR mild mutations, with an uncertain evolution. The sweat test can be normal or borderline. In Brittany, from 1989 to 2004, 196 CF cases were diagnosed (1/2885 births). The incidence of atypical CF diagnosed by NBS is 9.7% (19 from 196). The outcome of 17 (2 lost of view) has been studied, with 9 other atypical CF cases diagnosed by NBS in two other regions. The follow-up period extends from 0.25 to 19.8 years (NBS implemented in Normandy in 1980) with mean age 4.6 years. The most frequent mild mutation is R117H ISV8-7T (50%). At the time of the last visit, nutritional status is normal. All these CF patients are pancreatic sufficient. Only one patient exhibits respiratory infections, whereas 7 others have them intermittently. Two of them had intermittent Pseudomonas aeruginosa colonization at 2.8 and 6.5 years. Mean Shwachman score is 96.7, mean Brasfield score is 22.8. Eight children have had lung function tests (mean follow-up of 10 years): mean FVC was 99% of predicted, mean FEV1 101%, but one of them has FEV1 of 48%. Predicting the phenotype of these atypical CF patients remains difficult, thus complicating any genetic counselling. A regular clinical evaluation is necessary, if possible by a CF unit, because CF symptoms may appear later.

[Severe asthma due to an esophageal foreign body in a child]. / Un asthme rebelle en rapport avec un corps étranger oesophagien méconnu.

A 4-year-old boy had infantile bronchial asthma resistant to treatment. He was referred for a febrile respiratory distress which led to the diagnosis of periesophagus mediastinis mass with erosion of both contiguous vertebral discs. The oesophagogram showed a foreign body in an esophageal diverticulum. After its extraction, all pulmonary symptoms disappeared.

Comparing the clinical evolution of cystic fibrosis screened neonatally to that of cystic fibrosis diagnosed from clinical symptoms: a 10-year retrospective study in a French region (Brittany).

Until the year 2000, systematic cystic fibrosis (CF) neonatal screening was only performed in a few regions of France. The Brittany region began in 1989, but not the neighboring region of Loire-Atlantique. The present study compares the clinical evolution of both affected populations 10 years after screening was started. Although the 77 screened and 36 nonscreened children were followed in different CF centers, they were included in similar care protocols. The clinical characteristics at diagnosis and their evolution over a 10-year period of all the children affected with CF and born between January 1, 1989 and December 31, 1998, excluding those with meconium ileus, were compared. There were no significant differences in sex ratio, gestational age, anthropometric data at birth, frequency of deltaF508 homozygotes, proportion of pancreatic-insufficient patients, and mean age between the two populations. Age at diagnosis was lower in the screened group (38 days vs. 472 days, P < 10(-7)), as was the delay in supplementation with pancreatic enzymes (1.7 months vs.15.9 months, P < 10(-7)). The proportion of children who were hospitalized at least once was higher among the nonscreened than the screened patients (86% vs. 49%, P < 10(-4)). Z-scores for weight and height were significantly better in the screened population, not only in the first years of life, but also at 5 years old for height and 8 years old for weight. The Shwachman and Brasfield scores were higher among the screened children during the whole period of follow-up. No significant differences in colonization by Pseudomonas aeruginosa nor in lung function were found. Given the homogeneity in the characteristics and the follow-up of both populations, the benefits in terms of nutrition and clinical well-being of neonatal screening appear to be clear, thus confirming the advantages of its general implementation.

[Does neonatal screening of cystic fibrosis affect outcome? Comparative study of two cohorts in Britanny and Loire-Atlantique with follow-up after ten years]. / Le dépistage néonatal systématique améliore-t-il le pronostic de la mucoviscidose? Etude comparative de deux cohortes en Bretagne et en Loire-Atlantique avec un recul de dix ans.

UNLABELLED: Neonatal screening for cystic fibrosis was started in Brittany in 1989 but not in the adjacent department of Loire-Atlantique. This study compares the outcome from the children of both populations nine years after the beginning of the screening. Those children were seen in different centers but with the same following guidelines. POPULATION AND METHODS: All children with cystic fibrosis born between 01/01/89 and 31/12/97 in Brittany and the Loire-Atlantique, excluding the meconium ileus, were compared for their initial characteristics and their outcome after nine years of follow-up. RESULTS: There was no significant difference between both populations for sex ratio, gestational age, birth biometry, percentage of homozygotes delta F508, and mean age of children. Age at diagnosis was lower in Brittany (37 vs 372 days, P < 10(-7)), as was the delay for starting pancreatic supplementation (1.5 vs 14.3 months, P < 10(-7)). Percentage of children hospitalized at least once was higher in Loire-Atlantique (84.4 vs 40.3%, P < 10(-4)). There was no significant difference for colonization with Pseudomonas aeruginosa. Z-scores for weight and height were better in Brittany, as were Shwachman's and Brasfield's scores. CONCLUSION: The homogeneity of both populations and their follow-up points out that even if the numbers of children are small and the study is retrospective, some benefits of neonatal screening appear, which are already found in other countries where it is partly practiced. This leads us recommend its general use in our populations, which should be associated with the follow-up of the screened children in cystic fibrosis centers to achieve the most of its benefits.

Neonatal screening for cystic fibrosis in Brittany, France: assessment of 10 years' experience and impact on prenatal diagnosis.

BACKGROUND: Neonatal screening for cystic fibrosis has been a subject of debate over the past few years. This study assesses 10 years of neonatal screening in Brittany, France, and examines its impact on prenatal screening of subsequent pregnancies in couples with an affected child. METHODS: The study included all the neonates screened for cystic fibrosis in Brittany from Jan 1, 1989, to Dec 31, 1998. The screening consisted of an immunoreactive trypsinogen assay from dried blood spots, plus, from 1993, mutation analysis. Data were collected on incidence of cystic fibrosis, and genotypic and biochemical characteristics. The use of prenatal screening of subsequent pregnancies in affected families was also investigated. FINDINGS: Of the 343,756 neonates screened, 118 children with cystic fibrosis were identified, giving an incidence of one in 2913. All mutated alleles were characterised: 34 different mutations resulting in 36 genotypes were detected. The introduction of DNA analysis into the protocol greatly reduced the recall rate and increased the sensitivity of the test. The mean cost of the screening programme was US$2.32 per screened child. 39 (34%) of the families identified by neonatal screening opted for subsequent prenatal diagnosis at least once. 12 couples would have benefited from this procedure while their first child was still symptom-free. 42 healthy children were born, and 18 pregnancies were terminated (therapeutic abortion rate of 100%). INTERPRETATION: We have shown the feasibility of neonatal screening for cystic fibrosis in Brittany. Through the detection of a large range of mutations, neonatal screening provides the opportunity for more reliable prenatal diagnosis and cascade screening. The neonatal screening programme described here could provide a good model for other countries intending to initiate such a scheme.

[Contribution of post mortem skull scanning for the study of sudden infant death]. / Contribution du scanner crânien post-mortem à l'étude de la mort subite du nourrisson.

BACKGROUND: Despite post-mortem examination and autopsy, many cases of sudden infant death (SID) remain unexplained. The aim of this study was to assess usefulness of CT-scan in the Sudden Infant Death Syndrome (SIDS). POPULATION: Twenty-three cases of SIDS had a post-mortem CT-scan evaluation of skull and brain. The pictures were retrospectively reviewed by several independent radiologists who were unaware of the circumstances of death and results of autopsy. RESULTS: Aspects of pneumatocele, probably due to lumbar puncture were found in 6 cases. The subarachnoid spaces appeared inexplically hyperdense, as they were not correlated to the results of lumbar puncture and autopsy. The ventricles were normal in size or density. Density of the dural sinuses (superfical and deep) was often increased, an aspect possibly artefactual, due to post-mortem thrombosis. The cerebral parenchyma was often slighty hypodense; microcalcifications due to congenital toxoplasmosis were found in one case. CONCLUSION: There was no correlation between the CT-scan imaging and the delay of death and lumbar puncture. Infants with or without subarachnoid hemorrage had the same CT scan findings. The CT-scan has a poor value when autopsy is performed; in its absence, it could be useful for diagnosing post-traumatic intracerebral hematoma.

Neonatal screening for cystic fibrosis: result of a pilot study using both immunoreactive trypsinogen and cystic fibrosis gene mutation analyses.

We have evaluated a two-tier neonatal cystic fibrosis (CF) screening of immunoreactive trypsinogen (IRT) followed by CFTR gene mutation analysis using a systematic scanning of exons 7, 10, and 11, and, if necessary, by direct DNA sequencing. Over an 18-month period we screened 32,300 neonates born in the western part of Britanny. The first tier, involving IRT screening at 3 days of age, utilizes a low elevation of the trypsinogen level (600 ng/ml), which is highly sensitive. The second tier, which corresponds to the exhaustive screening for mutations in three exons of the gene, is highly specific for this population (Britanny). The false positive rate is very low, and no false negatives have been reported to date. This strategy has allowed the identification of five novel alleles (V322A, V317A, 1806 del A, R553G, G544S).

Is the piglet a useful animal model of sudden infant death syndrome?

A prospective study of early death was conducted in a large population of piglets in order to investigate the causes of mortality and determine whether this species could be useful as an animal model of the sudden infant death syndrome (SIDS). 1,921 live-born piglets were closely monitored from birth to 2 months of age. The cause of death was analyzed in all the animals which died during this period. Complete histological, bacteriological and virological examinations of all sudden death animals were compared to identical examinations performed in age-matched control animals. 384 animals (20%) died during the study period and 8 sudden deaths were observed (0.4%). The principal causes of nonsudden death were overlaying (9.4%), hypotrophy (6%), infection (2%) and acute fetal suffering (1.4%). Bacterial infection was found in 6 of the sudden deaths. There was 1 case of suffocation and 1 unexplained sudden death. Compared to controls, there was a significantly greater prevalence of pathology (p < 0.01) and of positive tissue bacteriology (p < 0.05) in sudden death animals. The 6 sudden deaths due to bacterial infections were clearly different from the human syndrome. Suffocation is a known cause of sudden infant death. In the final analysis, only 1 animal (0.5/1000) had an outcome which could be assimilated with SIDS. It is concluded that although there probably exists a syndrome in the piglet equivalent to SIDS, its incidence is very low and major obstacles related to the high level of early mortality in this species hinder investigation.

[Multicenter study of sodium alginate in the treatment of regurgitation in infants]. / Etude clinique multicentrique de l'alginate de sodium dans le traitement des régurgitations du nourrisson.

An open multicenter study was performed to assess the efficacy and safety of alginic acid in two different dosages in 76 pediatric patients with gastroesophageal reflux confirmed by pH monitoring. Among the 69 patients in whom endoscopy was carried out before treatment, 18 had erythematous esophagitis and 5 had erosive esophagitis. Irrespective of the dosage used, the frequency of regurgitation and vomiting decreased significantly (p < 0.00001 and p = 0.01, respectively). Clinical and biochemical tolerance were outstanding and no adverse effects were recorded. On the basis of these data, the recommended dosage is 1 to 2 ml/kg/day in divided doses after meals.

Tracheal rupture in a newborn during a complicated delivery. Diagnosis and surgical repair.

Rupture of the trachea is an exceptional obstetrical lesion. The infant reported in this paper, at 1 hour of age, developed respiratory distress with pneumomediastinum, bilateral pneumothorax and subcutaneous emphysema. This resulted from the fact that the trachea had ruptured, within 1 cm of the carina, during the difficult delivery. When the child was 23 days old, operation proved necessary because extubation was not feasible. The stenotic portion of the trachea was resected and continuity restored by end-to-end anastomosis. The tracheal lumen at the site of the anastomosis proved normal by bronchoscopic examination 4 months after the operation. There is only one similar case in the literature. The etiology of this rupture is discussed.

[Pharmacologic efficacy of sodium alginate suspension on gastro-esophageal reflux in infants and children]. / Efficacité pharmacologique de l'alginate de sodium suspension sur le reflux gastro-oesophagien du nourrisson et de l'enfant.

Eighty-three children presenting with symptomatic gastro-esophageal reflux (GER) (48 males, 35 females, aged 15 days to 57 months (mean = 7 months) were assessed by pH monitoring. All showed acid pathological GER on the 3 hours post-prandial esophageal pH measurement (% of time at pH less than 4 greater than 4.2) and all had a second pH measurement within the following 3 hours after intake of a single (5 ml) dose of sodium alginate (AGS). AGS administration was followed by a highly significant reduction (p less than 0.00001) of all pH measurement variables: a) Percentage of time spent at pH less than 4 returned to normal with a mean 11.7% to 4.8%; that is a 52.5% improvement (median); b) Total number of reflux reduced on average from 8.9 to 5.0: that is a 35% improvement (median); c) Mean duration of reflux reduced on average for 4 to 2 min; that is a 60% improvement (median). In 76 patients hourly monitoring of % of time spent at pH less than 4 shows that hourly improvement persists.