IgE-mediated facilitated antigen presentation underlies higher immune responses in peanut allergy.

BACKGROUND: Peanut allergy poses significant healthcare problems, because its prevalence is increasing in many countries, and it is rarely outgrown. To explore the immunological mechanisms that underlie peanut allergy and tolerance, we compared the peanut-specific responses of peanut-allergic (PA) and nonallergic (NA) individuals. METHODS: We measured peanut-specific peripheral blood mononuclear cells (PBMC) proliferation using tritiated thymidine. The frequency of peanut-specific T cells amongst PBMC was determined by carboxyfluorescein succinimidyl ester labelling. The role of IgE-dependent facilitated antigen presentation (FAP) in modulating proliferation was investigated by depleting IgE from plasma with anti-IgE-coated beads and then assessing PBMC proliferation in the presence of IgE-depleted or nondepleted plasma. RESULTS: We found that peanut-specific PBMC proliferation is higher and peaks earlier in PA than in NA donors. We investigated the immunological mechanisms that could underlie these differences. We found that both PA and NA have memory responses to peanut, but the frequency of peanut-specific T cells is higher in PA than in NA. Facilitated antigen presentation could cause both the higher proliferation and precursor frequency in PA. Facilitated antigen presentation activity in vitro was confirmed by showing that IgE depletion decreases proliferation, while adding IgE back restores it. CONCLUSION: Our results identify FAP as a mechanism that underlies higher responses to peanut in PA. In these individuals, high levels of peanut-specific IgE could furthermore maintain long-term allergic T-cell responses. We raise the question whether, in the future, therapies targeting IgE such as anti-IgE antibodies may be used to suppress these T-cell responses.

The management of the allergic child at school: EAACI/GA2LEN Task Force on the allergic child at school.

Allergy affects at least one-quarter of European schoolchildren, it reduces quality of life and may impair school performance; there is a risk of severe reactions and, in rare cases, death. Allergy is a multi-system disorder, and children often have several co-existing diseases, i.e. allergic rhinitis, asthma, eczema and food allergy. Severe food allergy reactions may occur for the first time at school, and overall 20% of food allergy reactions occur in schools. Up to two-thirds of schools have at least one child at risk of anaphylaxis but many are poorly prepared. A cooperative partnership between doctors, community and school nurses, school staff, parents and the child is necessary to ensure allergic children are protected. Schools and doctors should adopt a comprehensive approach to allergy training, ensuring that all staff can prevent, recognize and initiate treatment of allergic reactions.

Prevalence and risk factors for allergic contact dermatitis to topical treatment in atopic dermatitis: a study in 641 children.

BACKGROUND: There is little information regarding the risk of sensitization associated with topical atopic dermatitis (AD) treatment. OBJECTIVES: To assess the frequency of sensitization to topical treatment of AD in children and to determine risk factors associated with skin sensitization. METHODS: Six hundred and forty-one children with AD were systematically patch tested with seven agents of common topical treatment: chlorhexidine, hexamidine, budesonide, tixocortol pivalate, bufexamac, sodium fusidate and with the current emollient used by the child. The following variables were recorded: age, sex, age at onset of AD, associated asthma, severity of AD, and history of previous exposure to topical agents used in the treatment of AD. Skin prick tests to inhalant and food allergens were used to explore the IgE-mediated sensitization. RESULTS: Forty-one positive patch tests were found in 40 patients (6.2%). Allergens were emollients (47.5%), chlorhexidine (42.5%), hexamidine (7.5%), tixocortol pivalate and bufexamac (2.5% each). Risk factors associated with sensitization to AD treatment were AD severity [OR: 3.3; 95% confidence interval (CI):1.5-7.1 for moderate to severe AD], AD onset before the age of 6 months (OR: 2.7; 95% CI: 1.2-6.1), and IgE-mediated sensitization (OR: 2.5; 95% CI: 1.1-5.9). CONCLUSIONS: Topical treatment of AD is associated with cutaneous sensitization. Antiseptics and emollients represent the most frequent sensitizers and may be included in the standard series in AD children when contact dermatitis is suspected. Risk factors associated with sensitization to AD topical treatments are AD severity, early AD onset and IgE-mediated sensitization.

Sensitization and allergy to turnip rape: a comparison between the Finnish and French children with atopic dermatitis.

AIM: Finnish children with atopic dermatitis (AD) are frequently sensitized and show positive food challenge to turnip rape. We examined whether French children are also allergic to this oilseed plant and whether mustard could be the cross-reacting allergen. METHODS: Turnip rape and mustard challenge was performed to 14 Finnish and 14 French children with atopic dermatitis and positive skin prick test to turnip rape. Specific IgE antibodies were measured by ImmunoCAP and enzyme-linked immunosorbent assay (ELISA). RESULTS: Open labial or oral challenge to turnip rape was positive in 14 (100%) Finnish and five (36%) French children and mustard challenge in five Finnish and five French children. IgE antibodies to oilseed rape and mustard were slightly more frequent in the Finnish (100% and 93%) than in the French (93% and 71%) children but rare (4%) in the 28 matched controls. The same findings were true for IgE antibodies to purified 2S albumin allergens, which showed similar cross-wise IgE inhibition patterns. CONCLUSION: French children with atopic dermatitis show IgE antibodies to turnip rape, oilseed rape and mustard similarly to the Finnish children. 2S albumin allergens in the seeds of these plants are highly cross-reactive and therefore, they all could be important sensitizers in children with atopic dermatitis.

The prevalence of sensitization to lupin flour in France and Belgium: a prospective study in 5,366 patients, by the Allergy Vigilance Network.

OBJECTIVES: To determine the prevalence of sensitization to lupin flour in patients consulting allergists, in order to evaluate the risk of primary and secondary allergies to lupin. METHODS: A prospective study carried out by members of the Allergy Vigilance Network, using prick-tests with a commercial lupin flour extract in patients with various allergic symptoms. The study design classified patients into four groups: peanut allergy, current atopic disease, latent atopy, no atopy. Data were collected and analysed by Network coordinators. RESULTS: Over a two-month period, 88 French and Belgian allergists tested 5,366 patients: 2,680 children and 2,686 adults aged over 16 years. Of the 2,680 children, 11.15% presented with peanut allergy. The frequency of cross-reactivity with lupin was 17.1% for patients with peanut allergy, 2.5% for children with current atopic disease and 1.7% for healthy children with latent atopy. In the 2,686 adults, peanut allergy was diagnosed in 1.86% of patients with cross-reactivity to lupin in 14.6%. Sensitization to lupin was detected in 3.7% of patients with current atopic disease and in 1.8% of those with latent atopy. CONCLUSION: The relative frequency of latent sensitisation to lupin in patients of all ages presenting with atopic disease is a new factor indicating the likelihood of an increase in primary food allergies to lupin flour. This justifies the recent decision requiring mandatory labelling of lupin, and shows the need to inform consumers who may be unaware that this ingredient is being used increasingly. Sensitization to lupin should be searched by prick-tests in any case of peanut allergy. Prick-test to lupin may be valuable whenever a food allergy is suspected when no current food allergens have been identified.

Oral food challenge in children: an expert review.

Oral food challenges are indicated for the diagnosis of food allergy and the double-blind, placebo-controlled oral food challenge is considered the gold standard diagnostic method in children with suspected food allergy. This practice parameter for oral food challenges in children was prepared by a workgroup at the request of the French Society for Allergology and Clinical Immunology (SFAIC) and the French Paediatric Society for Allergology and Pulmonology (SP2A). We aimed to develop practical guidelines for oral food challenges in children for the diagnosis of suspected food allergy or the evaluation of food tolerance. We also considered the safety measures to be implemented during testing and management of the potentially serious allergic reactions that may arise during the test. The strength of the recommendations was established, using the GRADE evidence-based approach. We considered four issues: (1) the selection of children for oral food challenges (indications and contraindications); (2) the procedure used (material, where the test should be carried out, technique and management of reactions); (3) interpretation of the test and (4) consequences of the test.

["NPAs": a new allergic risk?]. / Les << NAC >> : un risque allergique nouveau ?

In recent years, to the list of classic pet animals (dogs and cats) as allergens we must now add the "new pet animals" (NPAs). This group of animals, referred to by the Anglo-Saxons as "pets", includes both those previously recognized (rabbit, guinea pig, hamster, birds) and the "truly new NPAs"; by general agreement "NPA" will include all animals other than cats and dogs. Some rather rare animals are regularly added to this list. The emergence of "NPAs" can be related to a social phenomenon, in particular, to the fashion and need for the exotic (http://www.aquadesign.be). They are a very diverse group: warm-blooded animals, spiders, batrachia (frogs, toads, salamanders, etc.) and reptiles. Besides the physical risks from their natural aggressive behaviour, the "NPAs" can be an allergic risk factor and this risk has a tendency to increase. Allergists and paediatricians have a role to play in the diagnosis and prevention of these allergies by giving advice on the choice of pet animals. This review concerns allergies to rodents, reptiles, batrachians, spiders, etc.

Low influenza vaccination coverage in asthmatic children in France in 2006-7.

In France, annual seasonal influenza vaccination has been recommended since 2000 for patients suffering from chronic respiratory diseases, including asthma. Since 1988, each year from September to December, a free influenza vaccination voucher is sent by the French Public Health Insurance authorities to patients with chronic respiratory disease, including severe asthma. In November 2006, this measure was extended to all asthmatic patients, irrespective of asthma severity. The present paper examines the 2006-7 influenza vaccination coverage rate (VCR) in 433 asthmatic children aged 6 to 17 years (mean age: 9.5 years; male: 61%) who consulted a paediatric pulmonologist between March and September 2007 in eight hospitals throughout France. The influenza VCR was 15.7% for the 2006-7 season (13.9% for the 2005-6 season and 10.9% for the 2004-5 season). General practitioners vaccinated 72.1% of the children. "Lack of information" (42%) was the most frequently reported reason for non-vaccination. Vouchers (received by 39.6% of the children) significantly increased the VCR (31% versus 5.9%; p<0.001). In France, in 2006-7, the influenza VCR in asthmatic children was far below the national public health objective (at least 75% for the year 2008). Concerted action is needed to improve the influenza VCR in asthmatic children.

[Influenza vaccination coverage in asthmatic children in France in 2006-2007]. / Couverture vaccinale contre la grippe chez les enfants asthmatiques en France en 2006-2007.

In France, an annual seasonal influenza vaccination has been recommended since 2000 for patients suffering from chronic respiratory diseases, including asthma. Each year, a free influenza vaccination voucher is sent by the French Public Health Insurance authorities to patients with chronic respiratory disease, including severe asthma. In November 2006, this measure was extended to all asthmatic patients, irrespective of asthma severity. The present paper examines the 2006-2007 influenza vaccination coverage rate in 433 asthmatic children aged six to 17 years (mean age: 9.5 years; male: 61%) who consulted a pediatric pulmonologist between March and September 2007 in eight hospitals throughout France. The influenza vaccination coverage rate was 15.7% for the 2006-2007 season (13.9% for the 2005-2006 season and 10.9% for the 2004-2005 season). General practitioners vaccinated 72.1% of the children. Lack of information (42%) was the most frequently reported reason for non-vaccination. Free vouchers (received by 39.6% of the children) significantly increased the vaccination coverage rate (31% versus 5.9%; p < 0.001). In France, in 2006-2007, the influenza vaccination coverage rate in asthmatic children was far below the national public health objective to achieve for the year 2008 (at least 75%). Concerted action is needed to improve the influenza vaccination coverage rate in asthmatic children.

The risk of systemic reactions to skin prick-tests using food allergens: CICBAA data and literature review.

Prick-tests to foods are usually carried out as the first step in the diagnosis of food allergy. Severe anaphylaxis accounts for 4.9 % of allergies in children and occurs more frequently in adults, raising the possibility of systemic reactions to prick-tests in highly sensitized people. Several studies published in the literature have used commercial extracts. As for airborne allergens, concentrations causing a skin reaction of 15 mm do not present a risk of systemic reactions. Prick-tests to native foods--prick-in-prick tests--have been less extensively studied. The CICBAA1 data, from 1,138 food allergic patients of all ages, cover 34,905 prick-in-prick tests to foods. The wheal of these prick-tests has been regulary registered. The risk of systemic reactions can be evaluated at 0.008 %. There were no severe reactions and anti-histamine and corticosteroid therapy were sufficient. These results are similar to those of the large study in 2000 carried out by Devenney in neonates (0.005%). A review of the literature reveals only a few severe reactions in adults. The authors draw attention to the necessary precautions: temporary contra-indication for skin prick-tests in children and adults with grade 3 or 4 asthma, with particular attention to such foods as all kinds of nuts, fish, etc.

[What type of avoidance for peanut allergic children?]. / Le régime d'éviction chez les allergique à l'arachide.

We analyzed, from the literature, the balance benefit/risk of a strict avoidance of peanut in children with peanut allergy. The benefits of a strict avoidance diet seem limited: reactions to the low doses and to the peanut oil refined are rare and most often slight. It is not proven that a strict avoidance facilitates the cure of allergy. On the other hand, strict avoidance could induce a worsening of allergy, with deterioration of quality of life, creation of food neophobia. In case of cure of allergy, it is difficult to normalize the diet after a strict avoidance. Outside of the rare sensitive patients to a very low dose of peanut, for which a strict avoidance is counseled, the report benefits risk is in favor of the prescription of adapted avoidance to the eliciting dose. For the majority of the peanut allergic children, it seems to us that the avoidance can and must be limited to the non hidden peanut.

[What is the value of allergologic tests for the diagnosis and management of atopic dermatitis?]. / Quelle est l'utilité des examens complémentaires pour le diagnostic et la prise en charge de la dermatite atopique?

The prevalence of atopic dermatitis (AD) in children has considerably increased in industrialised countries over the past 20-30 years. Determination of the interest of supplementary examinations, notably allergological explorations, is fundamental for all the practitioners who manage children suffering from the disease. ALLERGOLOGICAL TESTS: WHEN AND FOR WHO? Children suffering from eczema and describing concomitant manifestations such as urticaria, an oral syndrome or asthma should benefit from allergological tests. The latter are conducted as markers of the progression in the infant (aged under 24 months) presenting with atopic eczema without any concomitant manifestations. Such tests are aimed at defining the prognosis of AD and specifying the risk of progression towards an asthmatic syndrome. Allergological tests are conducted in the case of severe AD of early onset and in the presence of a family history of atopy. ALLERGOLOGICAL TESTS: WHICH? They explore immediate and delayed hypersensitivity. They include determination of IgE-dependent sensitivity using cutaneous tests or specific IgE measurements with validated methods. Allergy to food concerns very young children of around 2 years old. The diagnosis of such allergies is based on the efficacy of the eviction and oral provocation test, when there is discordance between the clinical history and the results of the determination of a specific IgE-related sensitivity. Prick-tests are performed to search for contact hypersensitivity, more frequent in older children. They are performed for contact allergens, aero-allergens and foodstuff and are supplemented by interrogation data. The pertinence of such tests remains to be determined. ALLERGOLOGICAL TESTS: WHAT FOR? An allergic factor enhances AD in one child out of two. Evictions adapted to the results of the allergological tests always improve the status of the children. They may even modify the natural history of the disease.

Gaucher's disease: a case history with extensive lipid storage in the brain.

Patients with acute infantile or type II neuropathic Gaucher's disease demonstrate neurologic deficits that are seemingly greater than the extent of the central nervous system involvement found at autopsy. Examination of the brain of an affected child shows widespread deposition of lipid in a pattern not recognized heretofore. Based on these observations, the authors hypothesize that widespread deposition of the Gaucher glucocerebroside elicits a mild tissue response, which functionally becomes highly significant.

Sesame seed allergy in children.

BACKGROUND: Sesame seed allergy is becoming more common in childhood. The aim of this study is to define the clinical signs and the results of allergological work-up of this food allergy as well as the demographical data in children. Sesame seed allergy outcome is unknown. MATERIALS AND METHODS: 14 children were recruited from 3 allergy centers in France. The diagnosis of food allergy was based on a convincing clinical history and positive skin prick tests and/or an elevated sesame specific IgE. Food challenge test was done when results of history and allergological work-up were conflicting. A reintroduction test was done when a child seemed to outgrow his (or her) food allergy. RESULTS: The median age at the beginning of sesame seed allergy was 5 years (range from 5 months to 16 years old). All patients reacted immediately after sesame seed consumption and presented as a first manifestation: edema (9 cases, 48%), urticaria (5, 27%), and one of each of the following symptoms (vomiting, rhinitis, conjunctivitis, asthma and anaphylactic shock). One patient had recurrent anaphylactic shocks and another an anaphylactic shock after subsequent sesame seed exposure; these 2 patients were asthmatic. The median of the wheal size was 5 mm (range 3 to 15 mm). The commercial sesame seed extract was less sensitive than the native seed. The median of sesame seed IgE was 5.58 kUA/L (range 0.35 to 100 kUA/L). The follow up lasted from a few months to 6 years. Three patients outgrew their food allergy. All of these patients showed a previous drop of sesame seed IgE and skin prick-tests became negative. CONCLUSION: Sesame seed allergy is not very different than other food allergy. We reported the spontaneous outgrowing of sesame seed allergy without being able to define the predictive criteria for a good outcome.

Severe food anaphylaxis: 107 cases registered in 2002 by the Allergy Vigilance Network.

BACKGROUND: The prevalence of food allergies increases, relating to diet modifications. The consumption of new foods--exotic foods or foods originally used for animal feed, new proteins, neo allergens due to the use of new technologies and soon, Genetically Modified Foods--are in the spotlight. OBJECTIVE: It is essential to develop a system of food allergy vigilance encompassing the full range of foods being consumed. Understanding this imperative leads logically to the suggestion of developing an allergy vigilance network taking advantage of the ongoing experience of allergists "on the ground". METHODS: The French Allergy Vigilance Network is subscribed to by 302 allergologists (267 of whom are French). The aims of the Network are to record cases of severe anaphylaxis, to establish an epidemiological data bank from prospective multicenter studies, and to monitor the allergic risk from novel foods. RESULTS: In 2002, 107 cases of severe anaphylaxis were recorded: anaphylactic shock--59.8% (one fatal), systemic reaction--18.7%, laryngeal angio-edema--15.9%, acute severe asthma--5.6% (one fatal). The main allergens identified were peanuts, nuts, shellfish, lupine flour and wheat flour. Action has been taken as a result: information by industry on inadequate labeling, withdrawal of wrongly labeled batches, and university hospital centers have been encouraged to establish the allergenic safety of their catering services. CONCLUSION: Setting up such a network in other countries would lead to a significant advance in knowledge of the peculiarities of allergies relating to a wide variety of eating habits.

Fatal intravenous drug abuse secondary to streptomycin overdose.

A fatal case of chronic intravenous drug abuse involving the injection of a nonpsychoactive veterinary combination of penicillin G and streptomycin is reported. The circumstances surrounding the death indicate that the decedent died as a result of streptomycin induced paralytic neuromuscular blockade.

Dicyclomine in the sudden infant death syndrome (SIDS)--a cause of death or an incidental finding?

We report a case of a small infant apparently dying of the Sudden Infant Death Syndrome (SIDS) with a postmortem blood dicyclomine level of 200 ng/mL. Review of the literature and the comparison with blood dicyclomine values from four rabbits given equivalent doses suggests that a blood dicyclomine value of 200 ng/mL probably is in the therapeutic range for infants. Although safely used for years for infantile colic, recently, the administration of dicyclomine has been related to acute episodes of apnea, seizures, and coma. In the absence of those acute reactions, we feel that a 200-ng/mL blood dicyclomine level in a child dying of apparent SIDS should not prevent categorization of the death as SIDS.

Peanut hypersensitivity in children.

Peanut is the major allergen in the United States. It is increasing in importance in Europe and has become the principal food allergen affecting children over the age of three years, once hypersensitivity to eggs has resolved. We report 132 pediatric cases of peanut hypersensitivity, confirmed by food challenge. The study group included 86 boys and 46 girls aged between 6 months and 15 years. More than half the children with peanut hypersensitivity were diagnosed before the age of three. The most common symptom was atopic dermatitis (43.1% of cases). The other symptoms observed were hoarseness (34.8%), asthma attacks (13.6%), anaphylaxis (6%), gastrointestinal symptoms (1.5%) and oral syndrome (0.7%). All patients had positive skin prick tests, with a mean wheal diameter of 8 mm (range: 2 to 25 mm). Wheal diameter was significantly smaller in the youngest children (mean 4.5 mm for children under the age of 1 year, p < 0.01). Specific IgE concentration was below 0.75 IU/ml in 16 cases (14.3%), the mean for the entire group being 30.9 IU/ml (range: 0.75 to 100 IU/ml). Food challenges were not performed in three of the eight children with a history of anaphylaxis. Labial food challenge (LFC) was positive in 85 cases (64.8%). An oral food challenge (OFC) was carried out for 45 children (34.3%) and the mean reactive dose was 850 mg (range: 1 mg to 7g). LFC with peanut oil was positive in 2 cases of 50 tested (4%) and 17 of 63 children (29.9%) tested by OFC were also found to be sensitized to peanut oil. Half the children were also hypersensitive to other foods, as demonstrated by oral challenge (53.7%) or sensitized to airborne allergens (62.8%). Hypersensitivity in the very youngest children raises questions about how sensitization occurs. Diagnosis was confirmed by food challenge. Peanut products are very difficult to eliminate from the diet because of inadequate labeling of food products. An ELISA test, available in a number of countries, can be used to detect the allergen.

[What is new in food allergy in 2003?]. / Quoi de neuf dans l'allergie alimentaire en 2003 ?

Food allergies afflict 4-8% of the children and are associated with clinical and familial burdens. The management of food allergy was improved during the last year. Firstly, early diagnosis should lead to early proper treatment. Recommendations were done by the paediatricians group of the EAACI. Diagnosis and outcome of food allergies were improved by the predictive values of in vitro specific IgE testing. The cut-off level permits diagnosis and follow-up of these individual patients. Until newer therapies available, strict food avoidance is needed. Future therapies under investigation include the reduction of IgE by the infusion of anti-IgE antibodies, immunotherapy with mutated proteins or engineered hypoallergenic food. Murine model was developed, and results were encouraging. Intervention efforts must be instituted early in life and primary prevention of food allergy was stated.