Diagnostic tests for patients with suspected allergic disease. Utility and limitations

STUDY OBJECTIVE: To evaluate the clinical efficacy of diagnostic tests used for persons with suspected allergic disease. DESIGN: Information synthesis based on historical review of developments in the understanding of the pathophysiology of allergic diseases and on selected recent literature on efficacy of specific diagnostic tests. MAIN RESULTS: Skin testing is most effective when based on clues from the patient's history. The sensitivity and specificity of skin testing methods are compared: skin prick testing alone is often sufficient to identify or exclude immunoglobulin E (IgE)-mediated hypersensitivity, including food allergy. Except for penicillin and certain macromolecules, skin testing is not useful for evaluating drug allergy. Skin test titration may be useful for determining the starting dose for immunotherapy; otherwise it is rarely necessary. The patch skin test helps identify the cause of allergic contact dermatitis. Bronchial provocation testing is useful in special cases. Oral provocation testing may be used to identify allergy or other intolerance to suspected foods, food additives, and certain drugs. Provocation testing is time-consuming and requires special precautions. In-vitro methods for identifying allergen-specific IgE are especially useful when skin testing is unreliable, equivocal, or cannot be done. In-vitro tests should be used as adjuncts to the clinical interview and examination. CONCLUSIONS: Tests that are effective for identifying allergenic substances usually can be determined from a careful patient interview. Clinicians should be aware of nonspecific test results and allergy tests of unproven effectiveness.     

Phenotypes of IgE-mediated food allergy in Turkish children

Data on food allergy-related comorbid diseases and the knowledge on factors associating specific food types with specific allergic outcomes are limited. The aim of this study was to determine the clinical spectrum of IgE-dependent food allergy and the specific food-related phenotypes in a group of children with IgE-mediated food allergy. Children diagnosed with IgE-mediated food allergy were included in a cross-sectional study. IgE-mediated food allergy was diagnosed in the presence of specific IgE or skin-prick test and a consistent and clear-cut history of food-related symptoms or positive open provocation test. Egg (57.8%), cow's milk (55.9%), hazelnut (21.9%), peanut (11.7%), walnut (7.6%), lentil (7.0%), wheat (5.7%), and beef (5.7%) were the most common food allergies in children with food allergy. The respiratory symptoms and pollen sensitization were more frequent in children with isolated tree nuts-peanut allergy compared with those with egg or milk allergy (p < 0.001); whereas atopic dermatitis was more frequent in children with isolated egg allergy compared with those with isolated cow's milk and tree nuts-peanut allergy (p < 0.001). Children with food allergy were 3.1 (p = 0.003) and 2.3 (p = 0.003) times more likely to have asthma in the presence of allergic rhinitis and tree nuts-peanut allergy, respectively. Interestingly, children with atopic dermatitis were 0.5 (p = 0.005) times less likely to have asthma. Asthma (odds ratio [OR], 2.3; p = 0.002) and having multiple food allergies (OR, 5.4; p < 0.001) were significant risk factors for anaphylaxis. The phenotypes of IgE-mediated food allergy are highly heterogeneous and some clinical phenotypes may be associated with the specific type of food and the number of food allergies.     

Arachide,fruits secs oléagineux : réalité clinique,conséquences sociales

The frequency of allergic reactions to peanut and tree nuts has increased. The cumulated prevalence of peanut allergy is high, 0.5 to 1.2% in American and Western European children; the prevalence of tree nut allergy is 0.5%. Allergic reactions to peanut and tree nuts can be life threatening. This problem is widely discussed in the media. Sensitization to tree nuts should be investigated in children with allergy to peanut or to any other nut. Evaluation  of the patient must take into account the clinical data and the results of skin tests, specific IgE assays and labial provocation tests. The decision of whether to perform a provocation challenge should be individualized. Children, particularly adolescents, at risk for severe reactions include those with multiple allergies, asthma, especially uncontrolled asthma, or facilitating factors such as drugs (including aspirin), alcohol and exercice. At present, prevention calls for avoidance of peanuts and tree nuts. Global management and careful education are essential and should be tailored to each child and its family. Management of severe food allergies must be comprehansive and must consist of more than just epinephrine.     

What are the links between food allergy and atopy ?

Food allergy and atopy are closely linked. In children, food allergy is often the first clinical manifestation of atopy and involved in flares of atopic dermatitis. It is usually disappearing with ageing except for some particular allergens. Asthma and/or allergic rhinitis might develop later particularly if there are some risk factors as familial history of atopy or sensitization to aeroallergens. However some food allergies as allergy to peanut or tree nuts may persist in adulthood sometimes inducing severe clinical manifestations especially in asthmatic patients. In adult, food allergy is mostly associated with oral syndrome linked to cross reactivity between pollen and raw food (fruits or vegetables). Systemic manifestations are more frequent in patients living in the Mediterranean area in relation to direct sensitization (without pollen allergy) to lipid transfer proteins that are particularly resistant.     

"Atopy patch tests" in the diagnosis of delayed food hypersensitivity

The prevalence of atopic diseases is increasing worldwide. Food allergies are the earliest manifestation of atopy. Atopic eczema affects about 18% of infants in the first 2 years of life and the main cause is allergy to multiple foods. A strong association has been shown between atopic eczema and IgE mediated allergy to milk, egg or peanut, but more than two-thirds of patients intolerant to food proteins have no evidence of IgE sensitization to the relevant food protein. Recently, patch testing with proteins has been found to be helpful in diagnosing food allergy in cases where skin prick tests and estimation of specific antibodies have failed. The methodology of atopy patch test (APT) is unstandardized, and contradictory results have been reported. In contrast to the more standardized APT methodology with aeroallergens, the sensitivities and specificities of food allergens can easily be estimated with food challenge tests. With multiallergic children adding of APTs to the skin prick tests and specific antibody estimation tests give more information for planning a wide enough elimination diet to get the skin and gastrointestinal tract symptomless in order to perform the challenge test which remains the only reliable test for food allergy. Standardization of the APT materials and reading procedure will add to the reliability of this new test method.     

Allergie aux laits de chèvre et de brebis sans allergie associée au lait de vache : revue générale à propos d'une observation à rebondissements

We report the case of an 11-year-old adolescent who had severe allergic reactions to goat and sheep milk but not to cow milk. The diagnosis was based on a convincing clinical history, positive skin tests and serum IgE antibody assay results. This sort of allergy, now being encountered more and more frequently, has all the characteristics of a severe allergic reaction. Extensive homology between the structure of goat and sheep caseins accounts for the coexistence of these two allergies. Our patient had experienced anaphylaxis induced by effort followed by ingestion of a cow milk-containing product. An oral provocation test with cow milk after physical effort reproduced this reaction. While avoidance is still the best method of prevention, an anaphylaxis emergency kit should be prescribed in all similar cases.     

Exploration des conjonctivites allergiques : comment explorer ?

The management of allergic conjunctivitis requires a specific approach, which can be divided into three particular schemes: (1) faced with a benign acute seasonal or chronic conjunctivitis, the workup should include skin prick-tests and assays for specific IgE antibodies. The allergens to use and the criteria for a positive reaction should be adapted to the condition of the ocular surface. When not clinically evident, the pertinence of the tests to be used will depend on the results of conjunctival provocation tests; they can be done on an ambulatory basis ; (2) contact allergy should be suspected in another context, that is, when the patient is older and the lesion looks more like blepharitis than conjunctivitis. Patch tests or open testing can detect many allergies, such as eye drop additives, various cosmetics and occupational allergens ; (3) when confronted with vernal or atopic kerato-conjunctivitis, arguments in favour of an allergy of the ocular surface may be obtained by comparing results of lachrymal and blood assays (eosinophils, ECP, total IgE). When sensitization is obvious, conjunctival allergen challenge is indicated with the suspected allergen in a specialized clinic. Then specific allergic treatment can be evaluated.     

Study on Patients Who Underwent Suspected Diagnosis of Allergy to Amide-Type Local Anesthetic Agents by the Leukocyte Migration Test

Background:There are problems in diagnosis of allergy to amide-type local anesthetic agents (ALAs), because definitive diagnosis is not obtained by in vivo tests, which are used for the diagnosis. Consequently, patients may be exposed to risk. There are few diagnoses based on in vitro tests, and there are almost no relevant studies.Methods:Authors examined involvement of allergic reaction using the leukocyte migration test (LMT) through multiple standpoints in 43 patients who underwent suspected diagnosis of allergy to ALAs.Results:Rate of LMT-positives was 54%, and especially the positive rate of lidocaine hydrochloride preparations was significantly high. In 15 positives to lidocaine hydrochloride preparations, all cases were indicated as positive in a test with drugs containing antiseptic agent, but only 3 cases were indicated as positive in a test with lidocaine hydrochloride alone. In addition, test with paraben was conducted in 4 cases; 2 cases were confirmed as positive. In relevance of histories of drug or food allergies, development rates of ALAs-allergies were the highest in both allergies, and were 35% and 13%, respectively.Conclusions:There is a high possibility that these adverse reactions were caused by pseudoallergy to drug. Even by allergic reactions, it was assumed that 80% of them might be caused by antiseptic agents such as paraben. In addition, it was suggested that ALAs, especially lidocaine hydrochloride preparations have high antigenicity (sensitizing property). Furthermore, it was considered that patients with past history of drug or food allergies have a high potential for manifestation of the reactions.     

Etiologic implication of foods in atopic dermatitis: evidence against

Atopic dermatitis is a typical chronic inflammatory skin disease that usually occurs in individuals with a personal or family history of atopy. Children with atopic dermatitis frequently present IgE-mediated food sensitization, the most commonly involved foods being egg and cow's milk. However, controversy currently surrounds whether food allergy is an etiological factor in atopic dermatitis or whether it is simply an associated factor, accompanying this disease as one more expression of the patient's atopic predisposition. Approximately 40 % of neonates and small children with moderate-to-severe atopic dermatitis present food allergy confirmed by double-blind provocation tests but this allergy does not seem to be the cause of dermatitis since in many cases onset occurs before the food responsible for allergic sensitization is introduced into the newborn's diet.Studies of double-blind provocation tests with food in patients with atopic dermatitis demonstrate mainly immediate reactions compatible with an IgE-mediated allergy. These reactions occur between 5 minutes and 2 hours and present mainly cutaneous symptoms (pruritus, erythema, morbilliform exanthema, wheals) and to a lesser extent, digestive manifestations (nausea, vomiting, abdominal pain, diarrhea), as well as respiratory symptoms (wheezing, nasal congestion, sneezing, coughing). However, these reactions do not indicate the development of dermatitis.Some authors believe that responses to the food in provocation tests may also be delayed, appearing mainly in the following 48 hours, and clinically manifested as exacerbation of dermatitis. However, delayed symptoms are difficult to diagnose and attributing these symptoms to a particular foodstuff may not be possible.Delayed reactions have been attributed to a non-IgE-mediated immunological mechanism and patch tests with food have been proposed for their diagnosis. In our experience and in that of other authors, the results of patch tests with cow's milk do not seem very specific and could be due, at least in part, to the irritant effect of these patches on the reactive skin of children with atopic dermatitis.The involvement of foods in atopic dermatitis will always be difficult to demonstrate given that an exclusion diet is not usually required for its resolution. Food is just one among several possible exacerbating factors and consequently identification of its precise role in the course of the disease is difficult. Further double-blind prospective studies are required to demonstrate the effectiveness of exclusion diets in the treatment of atopic dermatitis.Apart from the controversy surrounding the etiological role of foods, the most important point in atopic dermatitis is to understand that the child is atopic, that is, predisposed to developing sensitivity to environmental allergens; in the first few years of life to foods and subsequently to aeroallergens. Consequently, possible allergic sensitization to foods should be evaluated in children with atopic dermatitis to avoid allergic reactions and to prevent the possible development of allergic respiratory disease later in life.     

Gastrointestinal food hypersensitivity: Symptoms, diagnosis and provocation tests.

As many as 25% of the general population in Western countries believe that they suffer from adverse reactions to food. However, the actual prevalence of food allergy is much lower. Food-induced allergic reactions cause a variety of symptoms including cutaneous, gastrointestinal and respiratory tract. Food allergy might be caused by IgE-mediated, mixed (IgE and/or non-IgE) or non-IgE-mediated (cellular) mechanisms. The clinical diagnosis is based on a careful history, laboratory findings (total and specific IgE), skin prick test, elimination diet and food challenges. New intestinal provocation tests have also been applied to pick up the allergic response of the duodenal mucosa by endosonography and external ultrasound. The management of food allergy continues to be a strict avoidance of the offending food item.     

Modèles animaux d’allergie alimentaire. Application aux protéines de blé

The allergens responsible for wheat food allergy are beginning to be characterized. Nevertheless, animal models that produce highly-specific IgE and clinical symptoms comparable to those observed in allergic patients are of great interest for precise studies of allergens and of the mechanisms involved in wheat allergy. The aim of our research was to develop, in the first instance, a mouse model of allergy to a total extract of gliadins, then to use this model to study two major wheat allergens involved in wheat food allergy on children and adults, namely, the lipid-transfer protein (LTP) and the omega-5 gliadins.

Methods

First, we determined the mouse strain and the allergen dose required to induce an optimal allergic reaction to wheat. Three strains of mice (Balb/cJ, B 10.A ND c3 h/hEj) received four successive intraperitoneal injections of a total-gliadin extract (10 or 20 μg) adsorbed on alum. The level of sensitization was determined by assay of gliadin-specific IgE and IgG1 and by the level of cytokines secreted by splenocytes activated in vivo by the gliadins; in vitro basophil (RBL) degranulation tests were also done. In addition, the intensity of the allergic reaction was evaluated in vivo by analysis of the production of type Th2 cytokines and the influx of eosinophils in bronchoalveolar fluid (BAF) after intranasal gliadin extract provocation. Sensitization assays and provocation tests with LTP and omega-5 gliadins were done subsequently.

Results

The highest level of sensitization was observed in the Balb/cJ mice, whatever the dose of gliadins used. After the provocation test, these mice developed an intense-allergic reaction, as demonstrated by the strong production of type Th2 cytokines and the influx of eosinophils in the BAF. In contrast, a weak or no reaction was observed in the other two mouse strains. While sensitization of Balb/cJ mice by omega-5 gliadins was not very effective, administration of LTP induced significant production of specific IgE and IgG1 as well as specific degranulation of RBL cells, but little or no secretion of type Th2 cytokines by activated splenocytes. Induction of an allergic response after intranasal introduction of LTP was not very effective, in spite of the cellular influx in the BAF.

Conclusion

Balb/cJ mice, sensitized by intraperitoneal injection of a total-gliadin extract, appeared to produce some of the markers of wheat allergy, but the results of the sensitization studies with the purified allergens appear to be more complex.     

Prevalence of atopy in chronic fatigue syndrome

BackgroundSeveral hypotheses have been postulated to explain the etiopathogenesis of chronic fatigue syndrome (CFS). Among these, immunologic dysfunction has been proposed. Up to 30 % of these patients have a history of allergic disease. The aim of this study was to investigate whether allergic sensitization is higher in patients with CFS than in the general population.MethodsTwenty-five patients with CFS and 20 controls were evaluated. A clinical history for allergy was taken and immediate hypersensitivity tests were performed.ResultsTwelve patients (48 %) and eight controls (40 %) had a family history of atopy. Personal histories of atopy were as follows: rhinoconjunctivitis: 12 patients (48 %), seven controls (35 %); asthma: five patients (20 %), two controls (10 %); food allergy: three patients (12 %); atopic dermatitis: two patients; contact dermatitis: two patients. No statistically significant differences were found between the groups in any of the variables (p > 0.05). In the CSF group, 3.4 % (15/441) of the inhalant prick tests were positive, and in the control group 3.8 % (16/420) were positive. None of the tests for hypersensitivity to food or latex were positive.ConclusionsIn our study atopy was not more prevalent in patients with CFS than in healthy controls, although the CSF group tended to report more respiratory symptoms and drug allergies.     

Rhinite allergique chez l’enfant

Allergic rhinitis has for a long time been considered to be a relatively minor allergic symptom, much less important than anaphylaxis and asthma. Its true frequency was unknown. Its management remained empiric. Its association with asthma was not clearly determined, although concerning adults, this association was rather well-known. A number of studies in children have now made more certain the association between asthma and allergic rhinitis, the impact of rhinitis on the child's quality of life, and the significance of allergic rhinitis in the natural history of allergy and asthma. This review will cover some current aspects of allergic rhinitis: its association with asthma and food allergy, quantification of atopy, and its impact on daily life. It leads to recommendations for everyday practice of allergy in pediatrics. Given that allergic rhinitis probably begins earlier and earlier, children with this condition need to be followed closely and, if necessary, have their allergy tests repeated. Specific immunotherapy certainly merits to be used more frequently.     

Quoi de neuf en allergologie pédiatrique en 2000 ?Revue de la littérature internationale dˈoctobre 1999 à octobre 2000

The relation between maternal and childhood atopy may result from an increased intrauterine Th2 environment and high levels of Th2 cytokines in the milk of atopic mothers. The value of in vitro tests for early prediction of atopy is low, but high levels of eosinophil-derived proteins in nasal secretions of neonates may predict respiratory allergy. The prevalence of respiratory allergy has decreased in children living in rural areas, especially on farms. This may be related to exposure to mycobacterias, but the development of allergic conditions is independent of tuberculin reactivity and history of tuberculosis infection; however, the prevalence of asthma is decreased in young adults infected by Mycobacterium tuberculosis during childhood. High levels of eosinophils in the blood of children with bronchiolitis predict the development of persistent wheezing and asthma. Inhaled, oral and intravenous corticosteroids do not prevent relapses of bronchiolitis and persistent wheezing, but early hyposensitization has long-term beneficial effects on asthmatic symptoms. Results of prick-tests and specific IgE determinations are correlated with the severity of food allergy, and several studies confirm the diagnostic value of patch-tests with foods in children with atopic dermatitis associated with food allergy. Interesting cases of unexpected food allergies are reported (carob-induced anaphylaxis, and exercise-induced anaphylaxis to snails). Finally, children with spina bifida demonstrate a progressive sensitization to latex, in spite of a latex-free environment after the first surgical procedure(s), and the gelatin included in vaccines is highly immunogenic and allergenic.     

Skin tests for trophallergens and asthma

The place of trophallergens in the allergy investigation of asthmatic children is controversial. Asthma is only rarely the isolated manifestation of food allergy. The clinical history is essential for research of the associated signs that reveal a food allergy. In the absence of these associated signs, the presence of a positive test for trophallergens only rarely reflects a true food allergy, of which the presence can only be assured by a double blind oral provocation test. In addition, in nurslings, the presence of a positive skin test to a trophallergen indicates atopy in the infant, but is only a mediocre predictive factor of eventual asthma, in the absence of an associated clinical allergy.     

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在过去的几十年中,食物过敏的发病率逐渐增高。而目前食物过敏的诊断尚未完全明确,多以进行点刺试验、激发试验和特异性IgE的综合结果来评判。食物过敏的治疗方法在国际上亦尚未得到一致认可,大多都为探索阶段。文章主要介绍目前所采取的诊断和治疗方法。     

Aliments et dermatite atopique

Food allergy plays a pathogenetic role in subset of patient with atopic dermatitis, as proven over the past decade by laboratory and clinical investigations. Likely 40% of infants and young children may present with food allergy, whatever the severity of atopic dermatitis. The identification of the subset of patient with relevant food allergy requires a thorough a clinical history, the appropriate laboratory tests, food allergy being proven in all cases by elimination diets followed by provocation tests. Atopic dermatitis may be cured or largely improved by elimination diets, but the latter need a peculiar education of patient and physicians because the common causal foods involved (egg, milk, wheat, soil, peanut) are ubiquitous in industrial foods and since elimination diets are at risk of nutritional imbalances. Most food allergies resolve following early childhood and atopic dermatitis in older children and adults is largely less related to food allergy.     

Genetics of food allergy

Allergic reactions to foods are an important medical problem throughout the industrialized world. The occurrence of food allergy appears to be strongly in.uenced by genetics, but the basis of the genetic predisposition to food allergy has not been differentiated from that for atopy in general. In addition, genetic susceptibility alone does not explain the prevalence of food allergy satisfactorily, leaving ample room to consider the importance of environmental in.uences (external, maternal, and gastrointestinal environment) and interactions between the host and the environment. Several features of food allergy are highlighted in this review: 1) patients with severe food allergies are overwhelmingly atopic, but food allergy occurs only in approximately 10% of patients with other atopic diseases; 2) most patients are clinically reactive to a single food, and although a substantial minority have multiple food allergies, the variety of bonefide food allergies in a given individual is limited; 3) foods contain multiple proteins whereas only a small subset are allergenic; 4) there is likely an important contribution of the environment, becoming manifest in genetically susceptible individuals.     

Food allergy: one only finds what one seeks

We report three observations of food allergy to Penicillium. A systematic approach has allowed the retention of the surprising diagnosis in the first observation that we met. For those following we were content with a diagnosis of strong suspicion, without making a provocation test. The indications of provocation tests are discussed. As in these observations, it is possible that certain food allergens which are considered as rare are in fact more frequent than those reported in the literature; when an allergy does not bother the patient, when exclusion of the food is easy, food allergy is "forgotten" and not reported to the physician.