X-linked thrombocytopenia and Wiskott-Aldrich syndrome are allelic diseases with mutations in the WASP gene.

X-linked thrombocytopenia (XLT) is a rare recessive hereditary disorder characterized by isolated thrombocytopenia with small-sized platelets. The XLT locus has been located to chromosome Xp11 by linkage analysis, which is also where the recently cloned Wiskott-Aldrich syndrome (WAS) gene, maps. The relationship between XLT and WAS has long been debated; they might be due to different mutations of the same gene or to mutations in different genes. We now show that mutations in the WAS gene, different from those found in WAS patients, are present in three unrelated male patients with isolated thrombocytopenia and small-sized platelets. Our results demonstrate that XLT and WAS are allelic forms of the same disease, but the causes of the differences need to be further investigated.

Performance of a component-based allergen-microarray in the diagnosis of cow's milk and hen's egg allergy.

BACKGROUND: The food challenge test (FCT) is the gold standard for the diagnosis of food allergy. This procedure is time consuming, costly and can induce potentially severe symptoms. An ideal in vitro test should allow to avoid the FCT. Objective To assess the clinical performance of microarray for specific IgE (sIgE) detection in children with challenge-proven/excluded cow's milk (CM) or hen's egg (HE) allergy. METHODS: One-hundred and four children with suspected IgE-mediated hypersensitivity to CM or HE were studied. In all patients, skin prick test, ImmunoCAP, microarray and FCT were performed. RESULTS: The microarray components Bos d 8 for CM (27/58 patients) and Gal d 1 (20/46 patients) and Gal d 2 (24/46) for HE were the most frequently recognized allergens. Using the FCT results as the reference parameter, sIgE to Bos d 8 and Gal d 1 had the highest area under the curves. These were not significantly different from those obtained using the ImmunoCAP. Use of 95% clinical decision points (CDP) for sIgE to Bos d 8 and Gal d 1 resulted in higher negative predictive values (78% and 79%, respectively) than those obtained with the ImmunoCAP (57% and 59%). CONCLUSIONS: Our results show that in children with suspected CM or HE allergy, the microarray has a good ability to predict the FCT results. In a clinical application perspective, the microarray could be used as a second-level assay, if the ImmunoCAP sIgE is <95% CDP. This approach would lead to a decrease in the number of the FCT to be performed, as well as of positive FCTs with a subsequent decrease in severe reaction risk.

Increased nasal eosinophils in children with otitis media with effusion.

The pathogenesis of otitis media with effusion is still under debate, but allergic sensitization has been suggested in some cases. We investigated whether nasal cytology may indicate an allergic pathogenesis for otitis media with effusion. Atopic symptoms, results of skin prick tests to common aeroallergens, and nasal cytology by nasal scraping were evaluated in 40 children with current otitis media with effusion and compared with findings in a group of 40 healthy children. The presence of nasal eosinophils was significantly more frequent in children with otitis media with effusion than in the control group (p < 0.05). Nasal eosinophils were significantly associated with both allergic rhinitis (p < 0.001) and positive skin prick test results (p < 0.001). Allergic rhinitis with nasal eosinophilia was found in six children of the study group and in one child of the control group (p < 0.05). Our data suggest that nasal allergic inflammation may play a role in a subset of patients with otitis media with effusion. Therefore the possibility of allergic sensitization must always be considered in patients with serous otitis media.

Treating asthma in children with beclomethasone dipropionate: Pulvinal versus Diskhaler.

Seventy-two children (mean age, 10.1 years) with stable moderate asthma who completed a 7-day run-in period were randomized to receive a 4-week treatment with beclomethasone dipropionate (200 micrograms twice daily) administered through two different powder inhalers (Pulvinal; Chiesi Farmaceutici S.p.A, Parma, Italy and Diskhaler; Glaxo-Wellcome, Evreux, France) in a parallel group design. Sixty-nine patients completed the study. Morning and evening peak expiratory flow values, the use of rescue salbutamol, and the severity of clinical symptoms were recorded daily on a diary card. Pulmonary function tests were performed at baseline and then after 2 and 4 weeks of treatment. Pulmonary function values, daily morning and evening peak expiratory flow, and most of the clinical symptoms significantly improved, although the use of rescue salbutamol significantly decreased from the second week of treatment until the end of the study in both groups. Equivalence of efficacy between groups was demonstrated for both pulmonary function and clinical parameters. We conclude that the Pulvinal inhaler is as efficacious as the Diskhaler in beclomethasone-based therapy of asthmatic children.

IgG subclasses to food antigens.

Involvement of sub-classes of IgG that are specific for food allergens in anaphylactoid reactions and some manifestations of atopy no longer needs to be shown. Accordingly, sub-classes of IgG specific for ovalbumin (OVA) and beta-lactoglobulin (BLG) were compared in healthy subjects and those who presented with an intolerance or food allergy to OVA and BLG to decide whether a restrictive diet was necessary. The four sub-classes of IgG1, IgG2, IgG3 and IgG4 were isolated in all the groups. IgG4 was highest in the allergic subjects and the IgG sub-class values were modified by the diet differently in each group. Unfortunately, the small number of subjects does not allow the formation of a definite conclusion to this study.

[Allergy to cow's milk proteins in childhood: the authors' personal experience and new diagnostic and therapeutic proposals]. / L'allergia alle proteine del latte vaccino nell'infanzia: esperienze personali e nuove proposte di diagnosi e di terapia.

Cow's milk protein is quite commune in infancy (2-3% in first year of age). Casein, beta-lactoglobulin and alpha-lactalbumin are the main allergens of cow's milk. The authors describe the immunological reaction involved in IgE synthesis and consequential inflammation after ingestion of cow's milk proteins and present soy and protein extensive hydrolysates as alternative diets for children with cow's milk allergy. Moreover, the authors present their studies on immunogenicity of hydrolysed formulae. At the end they suggest the therapeutic strategy in the cow's milk protein allergy.

[Evaluation of markers in pediatric allergies]. / Valutazione dei markers in allergologia pediatrica.

Atopic diseases are more and more frequent (10-20%) in childhood with high social costs. The Author decided to analyze the markers useful to forecast the risk and development of atopic diseases in newborns by perusing the existing literature and personal experience, in order to evaluate the possibilities of adopting, first, a mass screening and, subsequently, precautionary measures suitable to avoid the onset of atopic diseases. A family history of atopic disease and the total serum IgE from the umbilical cord are the markers which are easiest to investigate. They allow detecting 80% of the subjects at allergological risk. But they are not sufficient to program a screening and a primary prevention in children at allergological risk.

[From atopic eczema to respiratory allergy]. / Dall'eczema atopico all'allergia respiratoria.

The prevalence of atopic eczema in childhood is increasing. This is probably related with a deviation of immune system to Th2 directed to allergen instead of Th2 directed to microorganisms. Atopic eczema is genetically linked, but its expression is principally determined by environmental factors, allergens and infections. In children with atopic eczema, the immune system is altered. The number of Langheran's cells is augmented. Th2 cells infiltrate the skin and produce cytokines which mediate both immediate and late allergic reaction. Most of eczematous children is allergic to food. A IgE-mediated reaction take place at the mucosal intestinal site. The food challenge test is the most reliable mean to identify offending foods. Soy formula can be used in the treatment of cow milk allergy. The tolerance of formulae based on cow milk hydrolysed protein should be tested under medical supervision in children with cow milk allergy. Prevention of atopic disease with dietary interventions has not been successful. To prevent asthma, the administration of immunotherapy in children with allergic rhinitis seems to be promising. In eczematous children with elevated total IgE and specific IgE to inhalant allergens, cetarizine seems to prevent onset of asthmatic symptoms.

Anaphylaxis induced by exercise and related to multiple food intake.

In some patients, exercise-induced anaphylactic (EIAn) reactions occur only when a particular food is eaten before exercise. We describe three patients with EIAn induced by different foods. Patients who presented episodes of EIAn performed exercise challenges after fasting and 1 hour after a meal without foods suspected of predisposing the reaction. Subsequently, patients performed exercises after separate intake of each suspected food. Patients underwent skin prick tests (SPT) with food extracts. Serum total and specific IgE antibodies to food were determined. No reactions were provoked by exercise tests without prior intake of suspected foods. Eight of 30 food-exercise combination challenges were positive. In Patient 1, tomato, zucchini, and wheat resulted in adverse reactions: in Patient 2, potato, peanuts, and tomato; in Patient 3, rice and peanuts. SPTs and RASTs to foods predisposing the reaction were positive. Food-exercise combined challenge may be useful in identifying foods that favor EIAn in children with multiple food-dependent EIAn.

Food related, exercise induced anaphylaxis.

Four children under 12 years of age with food dependent, exercise induced anaphylaxis (EIAn) were investigated. These children and five controls performed exercise challenges when fasting and one hour after a meal without food suspected to predispose to the reaction. Patients then performed exercise tests after intake of each suspected food. Three out of 15 food-exercise combination challenges were positive, but no reactions were provoked after exercise without prior intake of suspected foods. Patients underwent skin prick tests to foods and serum total and specific IgE antibodies were measured. Skin prick test results were positive and RAST results were positive in two of three instances. In case 3, food-exercise combination challenges did not provoke any clinical reaction. The diagnosis of food dependent EIAn should be considered in young children with EIAn of unknown origin.

Preseasonal local allergoid immunotherapy to grass pollen in children: a double-blind, placebo-controlled, randomized trial.

BACKGROUND: We assessed the efficacy of preseasonal local allergoid immunotherapy in a group of children with asthma and/or rhinitis and/or rhinoconjunctivitis due to grass pollen. METHODS: We randomly assigned 24 children allergic to grass pollen to receive local allergoid immunotherapy for 3 months before the pollen season and 24 such patients to receive identically appearing placebo. The immunotherapy consisted of tablets of monomeric allergoid grass pollen allergens held in the mouth until they dissolved and then swallowed. The study was double-blind. Symptoms and medications were scored on diary cards during the pollen season. Nasal eosinophil cationic protein levels were measured by the monoclonal antibodies EG1 and EG2 outside the pollen season and at low and at high pollen concentration during the pollen season. RESULTS: The active-treatment group had a statistically significant reduction of total symptoms (P<0.05), especially bronchial symptoms (P<0.05), in comparison with the placebo group. Immunotherapy was well tolerated and compliance was good. Nasal levels of EG2 and EG1 increased significantly during the pollen season, but there was no difference between groups. EG2/EG1 increased significantly only in the placebo group during natural allergen exposure (P<0.01). CONCLUSIONS: Our results suggest that this immunotherapy is effective for the treatment of asthma due to grass pollen in children.

Atopy in children with otitis media with effusion.

BACKGROUND: Contrasting data have been found on the prevalence of atopy in children with otitis media with effusion (OME). A major issue would be to determine whether screening for atopy should be recommended. Setting Centre for Study of Otitis Media with Effusion, Tabiano Terme, Parma, Italy. OBJECTIVE: The purpose of this study was to investigate the relation of OME to atopy. METHODS: The subjects were 172 children with OME and a control group of 200 children. The protocol included a questionnaire survey of diseases associated with atopy, a skin-prick test and a clinical evaluation of allergic symptoms and hypersensitivity to aeroallergens. RESULTS: No significant difference between patients and control group was observed for family history of atopy or positive skin-prick test reactions. Symptoms associated with atopy occurred significantly more frequently in the group with OME (P<0.001), though only the presence of rhinitis or atopic eczema was significantly associated with OME. CONCLUSIONS: Prevalence of positive skin-prick tests results is not enhanced in children with OME. Nevertheless, the association of OME with symptoms associated with atopy suggests that such concomitant diseases may play a part in the pathogenesis of the disorder. Children with allergic rhinitis or atopic eczema should be investigated by tympanometry for OME.

Gastrointestinal symptoms in atopic eczema.

AIMS: To determine the prevalence of gastrointestinal symptoms in children with eczema and the association of such symptoms with the extent of eczema or skin prick test results. METHODS: Sixty five children with atopic eczema and a control group matched for age and sex were recruited. Their parents completed a questionnaire about the children's gastrointestinal symptoms. The children's skin was examined; their weight, height, and abdominal circumference were measured; and skin prick tests were carried out. RESULTS: Gastrointestinal symptoms, especially diarrhea, vomiting, and regurgitation, were more common in the children with eczema. Diarrhea appeared to be associated with the ingestion of specific foods. Gastrointestinal symptoms were related to diffuse eczema and positive skin prick tests to foods. There was no anthropometric differences between the patient and control groups. CONCLUSIONS: A gastrointestinal disorder is common in children with eczema, especially with diffuse distribution. This may be responsible for substantial symptoms and may play a part in the pathogenesis of the disease and in the failure to thrive with which it is sometimes associated.

"Food allergy in children: an attempt to improve the effects of the elimination diet with an immunomodulating agent (thymomodulin). A double-blind clinical trial".

During 90 days of elimination diet nineteen children with food allergy manifesting atopic dermatitis were treated with either 120 mg/day of thymomodulin (10 subjects) or placebo (9 subjects) in a double blind design. After this period an improvement in skin lesions was observed in both groups. Subsequently a food challenge was performed for two weeks: in the group treated with thymomodulin skin lesions did not modify while they worsened in the placebo group and the comparison was statistically significant (p less than 0.01). Before the beginning of the trial laboratory assessments evidenced an increase in total and specific IgE serum levels, which decreased by the end of the study only in the group receiving the thymic derivative (p less than 0.05).

Duodenal IgE-positive cells and elimination diet responsiveness in children with atopic dermatitis.

BACKGROUND: Parameters for identifying eczematous children who could respond to an elimination diet are needed. In children with food allergy, duodenal IgE-containing cells are enhanced. OBJECTIVE: To determine the presence of duodenal mucosal IgE-positive cells in atopic dermatitis and to determine whether duodenal IgE-positive cells may identify eczematous children who will benefit from an elimination diet. METHODS: Thirty-one children with severe eczema underwent gastrointestinal endoscopy because of gastrointestinal symptoms and were treated with an elimination diet. A clinical score to skin lesions was given before and after diet. All subjects were skin-prick tested with food antigens and aeroallergens. Serum IgE levels were measured. Duodenal IgE-positive cells were investigated in 18 control subjects and in all eczematous children before diet. RESULTS: The number of duodenal IgE-positive cells in children with atopic dermatitis was significantly increased compared with that of control group (P < 0.001). Nineteen (61%) eczematous children improved on a few food diet. Diet-responsive children had significantly higher IgE-positive cells compared with both nondiet-responsive and controls. Positive predictive accuracy of duodenal IgE-positive cells was poor, whereas negative predictive accuracy was high at the cutoff level of 50 IgE-positive cells/10 visual fields. Diagnostic accuracy both of SPT reactions with foods and of food-specific serum IgE antibodies was poor. CONCLUSIONS: An intestinal IgE-mediated reaction occurred in children with severe atopic dermatitis who underwent intestinal endoscopy because of gastrointestinal symptoms. In these eczematous children, the number of IgE-positive cells in the duodenal mucosa might be helpful for excluding a positive response to the elimination diet.

Elimination diet and intestinal permeability in atopic eczema: a preliminary study.

We measured small intestinal permeability to lactulose and rhamnose in 18 healthy children and in 15 children with atopic eczema, before and after a 14-day elimination diet. The children with atopic eczema had higher initial urinary lactulose/rhamnose ratios than the controls. After dietary restriction, there was no overall change in permeability. Dietary therapy did however result in a large reduction in permeability in three of the nine children whose skin disease was improved, but a statistically significant decrease in permeability was not observed in the diet-responsive group as a whole. Larger studies would be required to confirm that dietary restrictions can reduce intestinal permeability in some children with atopic eczema.

[The use of thymopentin in the prevention of recurrent infections of the respiratory system. Multicenter study]. / Impiego della timopentina nella prevenzione delle infezioni ricorrenti dell'apparato respiratorio. Ricerca multicentrica.

Eighty children, between 1-12 years, suffering from recurrent respiratory infections were admitted to a multicentre study and treated with thymopentin, an immunomodulating compound that represents the active site of the natural thymic hormone thymopoietin. Thymopentin efficacy, measured as reduction in the number of infective episodes, and tolerability were assessed and, at the end of the study a global evaluation was made by each investigator. Moreover, the following factors were recorded: clinical course, duration of symptoms/signs, frequency of administration of antipyretic, antibiotic, anti-inflammatory and mucolytic therapy, school attendance and hospitalization. Thymopentin treatment resulted in a statistically significant decrease of infective recurrences. The use of symptomatic and antibiotic drugs was also reduced. Side effects were few and mild. The investigators' overall evaluation of thymopentin's efficacy and tolerability was favourable. In conclusion, thymopentin, administered subcutaneous for 5 weeks in winter, may be useful in the treatment of children with recurrent infections of the respiratory tract.