[Allergic and pseudo-allergic reactions to antibiotics in children: a review based on a dozen of clinical cases].
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Biomedical subjects
Publications and source records attributed to P Scheinmann.
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BACKGROUND: Food challenge is considered an excellent clinical tool for the diagnosis of specific food allergy. However in the case of peanut allergy it may be difficult to perform because of the severity of the reactions. The quantitation of a specific immunoglobulin E (IgE) response to different peanut allergens could also contribute to the improvement of the diagnosis. We characterized the IgE response to a whole peanut protein extract and to Ara h 1 and Ara h 2 in different groups of patients classified according to the severity of their allergic reactions. METHODS: Specific serum IgE were analyzed in 96 children by enzyme-linked immunosorbent assay tests using a whole protein extract or purified peanut proteins and anti-human IgE monoclonal antibodies labeled with acetylcholinesterase. RESULTS: A parallel was observed between levels of peanut-specific IgE and the classification in five groups and subgroups of patients upon increasing severity of symptoms, especially within the group of highest severity. Moreover, the highest frequency of positive response and the highest levels of specific IgE were observed with whole peanut protein extract. CONCLUSION: In a retrospective evaluation of peanut allergy in children, we have shown that quantitation of peanut-specific IgE could be used to avoid a food challenge particularly in the case of severe reactions. When compared to Ara h 1 and Ara h 2, whole peanut protein extract appeared to be the most appropriate allergen to perform the test.
The links between food allergy and asthma are becoming more clear. The association of food allergy and asthma in the same child is unusual (less than 10% in atopic subjects). This association is however a sign of gravity leading to more severe manifestations of food allergy in asthmatic children. Compared with the non-asthmatic child, the asthmatic child has a 14-fold higher risk of developing a severe allergic reaction to the ingestion of food. The most commonly cited foods are fruits with a rind, cow's milk and, of course, nuts. Epidemiological data established from methodologically sound studies should enable a definition of the current allergic environment. Formal diagnosis is established with standardized tests. Treatment is oriented towards prevention associating a restricted diet, asthma control, patient education, and prescription of an emergency first aid kit with epinephrine. Supplementary inquiries are needed to determine the outcome in children with food allergy and respiratory symptoms.
A 22-month-old infant developed purulent pleurisy caused by Streptococcus pneumoniae and a hemolytic uremic syndrome. The diagnosis was suggested by the classical triad: hemolytic anemia, renal failure and thrombocytemia confirmed by renal biopsy which demonstrated extensive cortical necrosis. Renal involvement was severe, justifying an indication for renal transplantation.
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BACKGROUND: Sublingual immunotherapy (SLIT) has been demonstrated to be a viable alternative to injection immunotherapy. Administration of high doses of allergens to ensure efficacy has been shown to be well tolerated. The aim of the present study was the first step to address the issue of fast-induction regimens using various induction SLIT regimens in paediatric and adult patients. METHODS: Sixty-four patients (age range 5-46 years) with grass pollen rhinoconjunctivitis were enrolled in an 8-month double-blind, placebo-controlled trial of SLIT. Sixty-three patients were randomized to four groups and evaluated at the end of the study. One group received placebo (n = 16) and the other three groups (n = 47) received five grass pollen extracts according to three different induction regimens: regimen 1 starting with 3 IR tablets (n = 15), regimen 2 starting with 10 IR (n = 16) and regimen 3 starting with 30 IR (n = 16). The maintenance phase was made with sublingual-swallow drops at the same concentration of 300 IR/ml for all the patients. Adverse events were recorded on diary cards. RESULTS: During induction phase, 25/47 patients in the SLIT groups had adverse reactions in comparison to 2/16 patients in the placebo group (p < 0.05). The rate of adverse reactions was 33.3% (11.8-61.6) (95% CI) for regimen 1, 31.3% (11.0-58.7) for regimen 2, 43.8% (19.8-70.1) for regimen 3 and 12.5% (1.6-38.3) for placebo. Fifty-seven reactions were local reactions involving the oral region (54 SLIT, 3 placebo) and 13 were systemic reactions (all in the SLIT groups). 11/13 reactions were mild (gastrointestinal disorders, rhinoconjunctivitis), 1/13 consisted of moderate asthma and 1/13 consisted of severe abdominal pain. No urticaria, angioedema or life-threatening events were observed. CONCLUSIONS: These preliminary data showed that various induction regimens for SLIT are generally well tolerated and could allow a fast build-up phase of SLIT.
Complications of flexible bronchoscopy (FB) were prospectively evaluated during 1,328 diagnostic procedures in children, not in intensive care units. A total 92.8% of the procedures were performed in conscious patients under sedation and 7.2% under deep sedation. Supplementary oxygen was provided in approximately 80% of cases via endoscopic face mask (n=783) or nasal prongs (n=290). At least one complication was recorded in 91 cases (6.9%). Minor complications (n=69; 5.2%) included moderate and transient episodes of desaturation (n=15), isolated excessive coughing (n=22), excessive nausea reflex with coughing (n=20), transient laryngospasm (n=6) and epistaxis (n=6). Major complications (n=22; 1.7%) included oxygen desaturation to <90%, either isolated (n=10) or associated with laryngospasm (n=6), coughing (n=4), bronchospasm (n=1), and pneumothorax (n=1). Major complications involving oxygen desaturation were associated with age <2 yrs (13 of 529 versus 8 of 778) and laryngotracheal abnormalities (7 of 85 versus 14 of 1,222). The overall frequency of complications was similar in conscious (6.7%) but sedated patients and patients under deep (7.3%) sedation. However, the frequency of transient desaturation was significantly higher in children undergoing FB under deep sedation. Transient fever after bronchoalveolar lavage was observed in 52 of 277 cases (18.8%). Flexible bronchoscopy is a safe procedure with <2% major complications. Careful analysis of indications and clinical status for each patient, and proper anaesthesia and monitoring during the examination ensure that the procedure is successful, with a minimum of complications.
PROBLEM: To analyse the paediatric data from the AIRE study (Asthma insights and reality in Europe) describing the standard of asthma control in Europe. MATERIAL AND METHODS: Among the 73,880 households contacted by telephone in 7 countries 753 children under the age of 16 were identified. An interview was conducted with a close relative to determine the frequency and severity of symptoms during the recent month, visits to casualty and hospital admissions during the past year, the medications used, the effects on the lives of the children, the opinions of the parents on the level of control of asthma and the monitoring methods used. RESULTS: 38.2% of children reported diurnal symptoms and 28% disturbance of sleep at least once a week. The consequences were important: limitation of sporting activities (29.5%) and absence from school (42.7% in the past year). Treatment was inadequate: 26% of children used inhaled steroids yet 45.9% had persistent asthma. The level of control was overestimated: 61% of parents of children with severe persistent asthma considered the asthma to be well controlled. CONCLUSION: European asthmatic children are poorly controlled, under-treated and rarely followed up. The consequences, particularly absence from school, should stimulate an improvement in their therapeutic and educational management.
Recurrent illness involving wheezing during the first years of life is transient in most children. The role of bronchial hyperresponsiveness as a factor influencing the persistence of wheezing from infancy to school age remains unknown. In a prospective study we investigated whether infants who wheezed and subsequently developed persistent asthma differed from infants who wheezed and later became asymptomatic either in the initial degree of bronchial hyperresponsiveness or in the persistence of bronchial hyperresponsiveness with age. One hundred and twenty-nine infants with three or more wheezing episodes before 2 yr of age were followed during 4 yr with a clinical evaluation and a methacholine challenge performed every 6 mo until the child was 4 yr old and once per year thereafter. The clinical score significantly improved with time in most children. The proportion of children with persistent wheezing after 2 and 4 yr of follow-up was only 31% and 20%, respectively. Persistent wheezers had significantly lower VmaxFRC values at initial evaluation and higher SRaw values at the end of follow-up than infants who became asymptomatic. We used transcutaneous oxygen tension (PtcO(2)) to measure the response to methacholine. No significant difference in PD(15) PtcO(2) between groups with subsequently different clinical progression was observed at initial evaluation. Bronchial hyperresponsiveness persisted 4 yr later in all children but children with persistent wheezing showed significantly lower PD(15) PtcO(2) values than children who became asymptomatic, as early as 30 mo of age. However, an acceptable early PD(15) PtcO(2) cut-off point predictive for subsequent clinical progression could not be identified. The level of bronchial hyperresponsiveness in infants who wheezed was not predictive of the persistence of asthma 4 yr later.
Injections of the 23-valent pneumococcal vaccine are usually well tolerated. Skin tests (prick and intradermal) and a self-made RAST with pneumococcal vaccine and phenol were performed in a child reporting a severe anaphylactic reaction induced by a 23-valent pneumococcal vaccine, and in ten control children, including one child with a well-tolerated vaccination, and nine non-vaccinated children. Skin tests and RAST with the vaccine were positive in the child reporting anaphylaxis, and negative in nine of the control children. Intradermal test with the vaccine was slightly positive in a non-vaccinated child with negative RAST. Skin tests and RAST with phenol were negative in all the children. These results suggest that immediate responses in skin tests and specific IgE determination have a good diagnostic value in children reporting severe reactions suggestive of IgE-dependent hypersensitivity to pneumococcal vaccine.
Specific immunotherapy shifts immune responses towards a Th0/Th1 response. Production of chemokines is also decreased early after the initiation of rush venom immunotherapy. We aimed to investigate in vivo whether cytokine plasma levels reflect the shift towards a Th0-Th1 pattern of immune response as seen in vitro in lymphocytes from patients undergoing venom immunotherapy. Therefore, we studied plasma levels of various cytokines before (day 1), during (day 2), and after (day 4) rush immunotherapy in nine wasp-allergic children. The levels of interleukin-5 and IFN-gamma were below the detection threshold. No variations were observed in levels of interleukin-4, interleukin-10, and TNF-alpha. In contrast, mean levels of RANTES transiently increased at day 2, and decreased below the pretreatment levels at day 4. Those alterations were significant in five children with high levels of RANTES at day 1, and reporting severe anaphylaxis. In the four other children, the levels of RANTES were not significantly increased at day 4. These results suggest that RANTES plasma levels are positively correlated with the severity of the reaction to hymenoptera venom, and that a significant decrease in the levels of RANTES occurs only in children with high pretreatment levels. However, the kinetics of RANTES plasma levels correlated neither with the results of allergological tests, nor with the outcome of venom immunotherapy.
SUMMARY. Spontaneous pneumomediastinum (SPM) is rare in children, mainly affecting male adolescents. It is usually secondary to alveolar rupture in the pulmonary interstitium, followed by dissection of gas towards the hilum and mediastinum. Many pathological and physiological events can lead to alveolar rupture, but the most common cause in children is asthma. The clinical diagnosis is based on the symptom triad of chest pain, dyspnea, and subcutaneous emphysema, and is also based on Hamman's sign. The diagnosis is confirmed by chest radiography. The main differential diagnosis is esophageal perforation, which requires an esophagogram with contrast when there is the slightest doubt in the diagnosis. Spontaneous pneumomediastinum generally resolves spontaneously within a few days, meaning that ambulatory treatment is usually appropriate. Management consists of treating the underlying cause (if identified), rest, analgesics, and simple clinical monitoring. Predisposing factors should be identified and controlled to prevent recurrence. Cases of idiopathic SPM necessitate diagnostic pulmonary function tests after the acute episode, to establish whether the child has asthma.
Although studies examining the serum suggest a role for eosinophils in wheezing episodes in infants and toddlers, the presence of a chronic eosinophilic inflammation within their airways remains to be demonstrated. In this study we investigated whether eosinophil cationic protein (ECP) levels are increased in BAL fluid (BALF) from infants and toddlers with recurrent wheezing episodes, during an asymptomatic period. The levels of ECP in BALF were quantitated by radioimmunoassay in 61 children (36 with severe recurrent episodes of wheezing and 25 who were non-wheezy), aged 6-36 months, in whom flexible bronchoscopy was clinically indicated. BALF eosinophil counts were < or = 1% in all patients and did not differ in wheezers, compared to non-wheezers. In contrast, ECP levels in BALF were > or = 2.2 micrograms/l in 18 of 36 (50%) wheezy infants but in only three of 25 (12%) control infants (p < 0.01). Neutrophil counts were significantly higher in the wheezer group than in the non-wheezer group (8.1 x 10(3) cells/ml vs. 3.0 x 10(3) cells/ml). ECP levels in the BALF were not correlated with the absolute number of eosinophils (r = 0.03; p = 0.8) but were correlated with the absolute number of neutrophils (r = 0.54; p = 0.001). There was no association between high ECP levels in BALF and the atopic status of the wheezers. In conclusion, ECP levels are increased in BALF from young children with recurrent wheezing episodes, even during relatively quiescent periods, suggesting a chronic increased cell activation in the lower airways.
Episodes of wheezing are very common in infancy but, despite their high prevalence, their mechanism is still poorly understood. To better understand the airway inflammation of wheezing infants, we examined cells of the bronchoalveolar lavage (BAL), focusing on the phenotype of lymphocytes and macrophages by using cytofluorimetry. Twenty-one wheezers (mean age 15.4 months) and seven non-wheezers (mean age 24.1 months) were studied. BAL was collected at fiberoptic bronchoscopy. Total and differential cell counts were similar in both populations. Eosinophils were not detected in the BAL fluid. The cell-surface markers CD2, CD3, CD4, CD7, CD8, CD19, and CD45 were studied for the lymphocyte sub-population analysis. The cell-surface markers CD14, CD54, CD62L, and human leucocyte antigen (HLA)-DR were studied for the macrophage sub-population analysis. A significant increase in the CD8(+) lymphocyte population (p = 0.03) was observed in wheezers (median 43.1%, 25-75% percentile: 30.1-54.9%), as compared to non-wheezers (median 29.3%, 25-75% percentile: 13.5-34.7%). A significantly (p = 0.04) decreased expression of HLA-DR (mean fluorescence intensity [MFI]) was detected in the macrophage population of the wheezers (median MFI, 7,016; range 2135-7986), as compared to non-wheezers (median MFI, 8,369; range: 6478-8860). The results of the present study suggest that viral infection may have induced a CD8(+) response in BAL cells.
BACKGROUND: Blood histamine levels are decreased after severe allergic reactions and in various chronic diseases. AIMS: To study blood histamine levels in infants and children with acute infectious and non-infectious, non-allergic, disease. METHODS: Blood histamine levels were investigated by a fluorometric method in infants and children admitted to hospital with bronchiolitis, non-wheezing bronchitis, acute infections of the urinary tract, skin and ear-nose-throat, gastroenteritis, or hyperthermia of unknown aetiology. Results of blood histamine levels and white blood cell counts were compared with those obtained for children recovering from benign non-infectious, non-allergic illnesses. RESULTS: As compared with control children, white blood cell numbers were significantly increased in children with acute infections of the urinary tract, skin and ear-nose-throat, and were significantly decreased in children with gastroenteritis. Blood histamine levels were significantly lower in children with gastroenteritis and hyperthermia than in children with other diseases and control children. It was not possible to correlate blood histamine levels and the number of blood basophils. CONCLUSIONS: BHL are significantly decreased in infants and children with acute gastroenteritis and hyperthermia of unknown aetiology. The mechanisms responsible for the decrease in blood histamine levels in children with gastroenteritis and hyperthermia are discussed.
OBJECTIVES: To investigate the feasibility of individualized workload increments, as used in adults, for exercise testing in children; and to investigate whether this individualized protocol makes it possible to satisfy the usual criteria for maximal exercise (clinical exhaustion, predicted maximum heart rate [HRmax], oxygen uptake [O(2)] plateau, maximal respiratory exchange ratio > 1.1). DESIGN: Prospective clinical study. SETTING: Pediatric exercise testing laboratory. SUBJECTS: Ninety-two children aged 5 to 17 years with various cardiac and respiratory diseases (33 with asthma, 11 with bronchopulmonary dysplasia, 6 with cystic fibrosis, 10 with congenital heart disease, and 32 miscellaneous). INTERVENTIONS: Individualized maximal incremental exercise testing. The increase in workload was adapted to the individual and was calculated from predicted maximal oxygen uptake (O(2)max) for each child. The test lasted 10 to 12 min. RESULTS: The exercise test was well tolerated by all children and was maximal in all but seven patients. A total of 65.7% of children reached the predicted O(2)max and 68.4% satisfied the criteria for a O(2) plateau at peak exercise. The predicted HRmax was achieved in all but two children. The mean maximal respiratory exchange ratio was 1.06. CONCLUSION: The individualized protocol for increasing workload, based on O(2) rather than power, was well tolerated by children. In our view, the best two criteria for assessing the maximality of the tests were clinical exhaustion and HRmax, especially if the O(2) plateau was not reached. These results suggest that individualized protocols could be used instead of standardized tests for exercise testing in children.
BACKGROUND: The EGEA study combines a case-control study and a family study to assess genetic and environmental risk factors and their interactions for asthma, bronchial hyperresponsiveness and atopy. Information is scanty regarding potential selection biases, in particular regarding familial ressemblance in epidemiological surveys of this kind. METHODS: Asthmatic probands (adult and paediatric) were recruited in chest clinics of six clinical centres. Controls were mostly population-based (electoral rolls) for adults and recruited in surgery departments for children. RESULTS: The population examined includes 348 nuclear families ascertained by one asthmatic and 416 controls, totalling 1847 subjects (EGEA I) and an additional sample of 40 families ascertained by two asthmatic siblings (EGEA II). Potential biases for the various types of analyses have been studied. Quantification of the consequences of the greater participation of probands with a parental history of asthma shows it does not introduce a major bias in the estimates of familial resemblance. Cases and controls showed a good comparability regarding sex, age, area of residence and familial geographical origin, allowing proper associations studies for environmental and candidate genetic factors. CONCLUSIONS: The case-control component of the study will allow to perform studies on environmental factors and association studies for various genetic polymorphisms. Using the family base collected, segregation and genetic linkage/association analyses with DNA markers may be performed.
A series of 82 children and adolescents with moderate and severe persistent asthma was studied. Their psychopathological problems were compared to those of 82 healthy subjects, matched for age, sex and socio-economic status. The patients completed the Child Depression Inventory, an inventory of fears and anxiety (ECAP) and the Coopersmith Self Esteem Inventory. Parents of asthmatic children filled in the Child Behavior Check List to assess their social competence. The patients were examined with the revised Kiddie Schedule for Affective Disorders and Schizophrenia. There were more anxiety symptoms in the asthmatic group than in the control group. Asthmatics were not significantly more depressed than controls and their self-esteem was as good. We found 29 anxiety disorders, four affective disorders and four disruptive behavior disorders. Generalized anxiety disorder was the main diagnosis (n=24). The asthmatic subgroup presenting anxiety and affective disorders had poorer self esteem, fewer activities and worse social competence than other asthmatics and controls. Adolescents did not seem to have more emotional disturbances than younger patients. Girls did not have more DSM IV anxiety or affective disorders than boys.