The role of the atopy patch test in the diagnostic work-up of non-IgE gastrointestinal food allergy in children: a systematic review.

The "Atopy Patch Test" (APT) has been proposed as a diagnostic tool for food allergies (FA), especially in children with FA-related gastrointestinal symptoms. However, its diagnostic accuracy is debated, and its usefulness is controversial. The aim of this systematic review was to evaluate the APT diagnostic accuracy compared with the diagnostic gold standard, i.e., the oral food challenge (OFC), in children affected by non-IgE mediated gastrointestinal food allergies, including the evaluation in milk allergic subgroup. Both classical non-IgE mediated clinical pictures and food induced motility disorders (FPIMD) were considered. The search was conducted in PubMed and Scopus from January 2000 to June 2022 by two independent researchers. The patient, intervention, comparators, outcome, and study design approach (PICOS) format was used for developing key questions, to address the APT diagnostic accuracy compared with the oral food challenge (OFC). The quality of the studies was assessed by the QUADAS-2 system. The meta-analysis was performed to calculate the pooled sensitivity, specificity, DOR (diagnostic odds ratio), PLR (positive likelihood ratio), and NLR (negative likelihood ratio) with their 95% confidence intervals (CI). Out of the 457 citations initially identified via the search (196 on PubMed and 261 on Scopus), 37 advanced to full-text screening, and 16 studies were identified to be included in the systematic review. Reference lists from relevant retrievals were searched, and one additional article was added. Finally, 17 studies were included in the systematic review. The analysis showed that APT has a high specificity of 94% (95%CI: 0.88-0.97) in the group of patients affected by FPIMD. Data showed a high pooled specificity of 96% (95% CI: 0.89-0.98) and the highest accuracy of APT in patients affected by cow's milk allergy (AUC = 0.93).      Conclusion: APT is effective in identifying causative food in children with food-induced motility disorders.  What is Known: • Atopy patch test could be a useful diagnostic test for diagnosing food allergy, especially in children with food allergy-related gastrointestinal symptoms. What is New: • Atopy patch test may be a useful tool in diagnosing non IgE food allergy, especially in children with food-induced gastrointestinal motility disorders and cow's milk allergy.

Diagnostic accuracy of atopy patch test in children with cow's milk allergy.

BACKGROUND: The accuracy of an atopy patch test (APT) for fresh cow's milk allergy is controversial. Few studies have focused on commercial extract solutions. We aimed to evaluate the diagnostic performance of the APT in cow's milk allergic children using fresh cow's milk and commercial extracts of cow's milk and its components including casein, α-lactalbumin, and ß-lactoglobulin. METHODS: A prospective study was carried out in children with a history of cow's milk allergy. Children underwent the skin prick test (SPT) and APT with fresh cow's milk, powdered cow's milk, and commercial extracts of cow's milk, casein, α-lactalbumin, and ß-lactoglobulin. Oral food challenge (OFC) was confirmed in all children. RESULTS: A total of 37 patients participated (mean age 13.14 ± 7.26 months). Only 5 (13.51%) patients had positive OFC to cow's milk. The sensitivity of the APT using fresh cow's milk was 40%, specificity was 65.6%, PPV was 15.4%, and NPV was 87.5%. The sensitivity of the APT using powdered cow's milk was 40%, 60.7% for specificity, 15.4% for PPV, and 58% for NPV. The sensitivity and PPV of the APT using commercial solutions of cow's milk, casein, α-lactalbumin, and ß-lactoglobulin were zero. The specificities were 90.6%, 93.8%, 100%, and 100% for α-lactalbumin, cow's milk, casein, and ß-lactoglobulin, respectively. CONCLUSIONS: APT using commercial solutions showed higher specificity than fresh milk. The specificity increased using a protein component allergen.

Immunological Pathomechanisms of Spongiotic Dermatitis in Skin Lesions of Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic pruritic skin disease with a complex pathogenesis underlying its heterogeneous clinical phenotypes and endotypes. The skin manifestation of AD reflects the cytokine milieu of a type-2-dominant immunity axis induced by genetic predisposition, innate immunity dysregulation, epidermal barrier defects, and allergic inflammation. However, the detailed pathomechanism of eczematous dermatitis, which is the principal characteristic of AD, remains unclear. This review examines previous studies demonstrating research progress in this area and considers the immunological pathomechanism of "spongiotic dermatitis", which is the histopathological hallmark of eczematous dermatitis. Studies in this field have revealed the importance of IgE-mediated delayed-type hypersensitivity, the Fas/Fas-ligand system, and cell-mediated cytotoxicity in inducing the apoptosis of keratinocytes in spongiotic dermatitis. Recent studies have demonstrated that, together with infiltrating CD4 T cells, IgE-expressing dendritic cells (i.e., inflammatory dendritic epidermal cells and Langerhans cells) that capture specific allergens (i.e., house dust mites) are present in the spongiotic epidermis of lichenified eczema in patients with IgE-allergic AD. These findings suggest that IgE-mediated delayed-type hypersensitivity plays a pivotal role in the pathogenesis of spongiotic dermatitis in the skin lesions of AD.

Atopy patch test in children with cow's milk and hen's egg allergy: Do clinical symptoms matter?

INTRODUCTION AND OBJECTIVES: Since early 2000s, atopy patch test (APT) has been used to determine non-IgE and mixed-type food allergies. Previous studies have reported conflicting results about the diagnostic value of APT in food allergies, due to non-standardized methods. We aimed to determine the diagnostic efficacy of APT compared to open oral food challenge (OFC) in patients diagnosed with cow's milk allergy (CMA) and hen's egg allergy (HEA) manifesting as atopic dermatitis (AD) and gastrointestinal system symptoms. MATERIALS AND METHODS: In patients with suspected AD and/or gastrointestinal manifestations due to CMA and HEA, the results of OFC, APT, skin prick test (SPT) and specific IgE (sIgE) were reviewed. Specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of sIgE, SPT, APT and SPT+APT were calculated. RESULTS: In total 133 patients with suspected CMA (80) and HEA (53) were included in the study. In patients with CMA presenting with gastrointestinal symptoms, APT had sensitivity of 9.1%, specificity of 100%, PPV of 100% and NPV of 48.7%. In atopic dermatitis patients, sensitivity of APT was 71.4%, specificity 90.6%, PPV 62.5% and NPV 93.6%. In patients diagnosed with HEA, the sensitivity, specificity, PPV and NPV values of APT were 72.0%, 78.6%, 47.2% and 75.0%, respectively. In patients diagnosed with HEA presenting with AD, sensitivity of APT was 87.5%, specificity 70.6%, PPV 73.7% and NPV 85.7%. Atopy patch test had lower sensitivity (44.4%) and higher specificity (90.9%) in patients diagnosed with HEA presenting with gastrointestinal symptoms than those presenting with AD. CONCLUSION: Our study showed that APT provided reliable diagnostic accuracy in atopic dermatitis patients. However, APT had low sensitivity in patients with gastrointestinal symptoms.

The diagnostic value of APT for food allergy in children: a systematic review and meta-analysis.

BACKGROUND: The role of atopy patch test (APT) in the diagnosis of food allergy (FA) remains largely controversial. In our meta-analysis, we aimed to evaluate the accuracy of APT for diagnosing FA in children. METHODS: Pubmed, Embase and Cochrane Library were searched for studies regarding the diagnostic value of APT for FA in children compared to oral food challenge (double-blind placebo-controlled food challenge and/or open food challenge). The last search was conducted on November 11, 2017. Two reviewers independently screened relevant studies and assessed the quality by QUADAS-2. Meta-analysis was performed to calculate the pooled sensitivity, specificity, DOR (diagnostic odds ratio), PLR (positive likelihood ratio), NLR (negative likelihood ratio) with their 95% confidence intervals (CIs). Subgroup analyses were conducted according to different food allergens, atopic dermatitis, gastrointestinal symptoms, and age younger than 3 years. RESULTS: Forty-one studies were included in the meta-analysis. The pooled sensitivity, specificity, PLR, NLR and DOR were 50.30% (95% CI 48.40%-52.30%), 86.60% (95% CI 85.30%-87.80%), 3.405 (95% CI 2.594-4.470), 0.545 (95% CI 0.469-0.634) and 7.528 (95% CI 5.507-11.206), respectively. However, for children with FA-related gastrointestinal symptoms, the pooled sensitivity and specificity were 57.40% (95% CI 52.10%-62.50%) and 91.50% (95% CI 88.30%-94.10%) respectively. CONCLUSIONS: Our findings suggest that APT is specific but not sensitive for diagnosing FA in children, especially in children with FA-related gastrointestinal symptoms.

Low efficacy of atopy patch test in predicting tolerance development in non-IgE-mediated cow's milk allergy.

BACKGROUND: The food atopy patch (APT) test has been used in previous studies to help the diagnosis of non-IgE mediated food allergies (FA). The aim of this study was to evaluate the efficacy of different cow's milk APT preparations to predict oral tolerance in children with previous non-IgE-mediated cow's milk allergy (CMA) diagnosis. METHODS: Thirty-two patients non-IgE-mediated CMA diagnosed by oral food challenge (OFC) were enrolled to perform APT with three different cow's milk preparations (fresh, 2% in saline solution, 2% in petrolatum) and comparing with a new OFC after at least three months of diet exclusion. RESULTS: Only six (18.7%) subjects presented positive OFC to cow's milk. No differences in gender, onset symptoms age, OFC age, Z-score, and exclusion period were found between positive and negative OFC patients. Preparations using fresh milk and powdered milk in petrolatum presented sensitivity equal to zero and specificity 92.3% and 96.1%. The preparation using powdered milk in saline solution showed sensitivity and specificity of 33.3% and 96.1%. Two patients presented typical IgE symptoms after OFC. CONCLUSION: Cow's milk APT presented a low efficacy to predict tolerance in patients with previous non-IgE-mediated CMA and should not be used in clinical routine. The presence of typical IgE reactions after OFC hallmark the necessity of previous IgE-mediated investigation for this patient group.

Dust mite induces multiple polar T cell axes in human skin.

BACKGROUND: House dust mite/HDM atopy patch test/APT elicits positive reactions in a high fraction of atopic dermatitis/AD and healthy individuals. Experimental systems for new-onset/chronic AD are needed to support rapid therapeutic development, particularly since animal models representing human AD are lacking. While HDM APT has been considered to simulate AD, its suitability to model AD's emerging Th2/Th22 phenotype with Th1 and Th17 components is unknown. OBJECTIVE: To assess whether HDM APT reproduces AD. METHODS: Positive HDM APTs (n = 15) from patients with and without AD were evaluated, using genomic and immunohistochemistry studies, against intrapersonal control skin. RESULTS: APT lesions showed higher T cell and dendritic cell infiltrates vs. CONTROLS: Seven hundred and forty-three up- and 326 downregulated genes were differentially expressed in HDM APT (fold change >2 and false discovery rate < 0.05), with increased expression of Th2, Th9, Th17/Th22 polar cytokines (i.e. IL-5, IL-13, IL-9, IL-17, IL-22). CONCLUSION: While HDM caused significant Th2 skewing, it also illustrated differences in Th2 induction and barrier defects; thus, HDM APT does not fully simulate AD. Given its widespread availability and sensitization rates, HDM may potentially be a useful tool that represents select aspects of AD, psoriasis, or contact dermatitis.

Diagnostic accuracy of patch test in children with food allergy.

BACKGROUND: The gold standard test for confirming whether a child has clinical hypersensitivity reactions to foods is the oral food challenge. Therefore, there is increasing interest in simpler diagnostic markers of food allergy, especially in children, to avoid oral food challenge. The goal of this study was to assess the diagnostic accuracy of atopy patch test in comparison with oral food challenge. METHODS: We investigated 243 children (mean age, 51 months) referred for evaluation of suspected egg or cow's milk allergy. Skin prick test and atopy patch test were carried out, and after a 2 weeks elimination diet, oral food challenge was performed. RESULTS: Two hundred and forty-three children underwent OFC to the suspected food. We found clinically relevant food allergies in 40 (65%) children to egg and in 22 (35%) to cow's milk. The sensitivity of skin prick test for both milk and egg was 92%, specificity 91%, positive predictive value 35%, and negative predictive value of 93%. Sensitivity, specificity, positive predictive value, and negative predictive value of atopy patch test for both milk and egg were 21%, 73%, 20%, and 74%, respectively. CONCLUSION: Our study suggests that there is insufficient evidence for the routine use of atopy patch test for the evaluation of egg and cow's milk allergy. OFC remains gold standard for the diagnosis of egg and milk allergy even in the presence of high costs in terms of both time and risks during application.

Role of atopy patch test for diagnosis of food allergy-related gastrointestinal symptoms in children.

BACKGROUND: Double-blind, placebo-controlled food challenge is the gold standard for diagnosing food allergy. However, it is a time-consuming procedure and requires onsite medical supervision and resuscitating medicines and devices on hand. The objective of this study was to compare the atopy patch test (APT) with the oral food challenge test (OFC) in children with suspected food allergy-related gastrointestinal (GI) symptoms. METHODS: A prospective self-controlled study enrolled children with a history of suspected food allergy-related GI symptoms. Skin prick test (SPT) and APT using lyophilized and commercial allergen extracts for cow's milk, egg, wheat, soy, and shrimp were evaluated, and OFC was performed. RESULTS: Thirty-nine patients (25 boys, median age 2.4 yrs) with 76 events of suspected food allergy-related GI symptoms were enrolled. SPT was positive in 11/76 events (14.5%). Sensitivity, specificity, predictive values, and likelihood ratio were calculated related to the food challenge outcome. Of 41 OFC, 30 (73.2%) were positive. APT using lyophilized allergen extracts yielded high sensitivity (80%) and high positive predictive value (85.7%). APT using commercial allergen extracts yielded low sensitivity (30%) but high specificity (90%). The negative predictive value of APT using lyophilized and commercial allergen extracts was 53.8% and 32.2%, respectively. All cases with positive APT using lyophilized allergen extracts together with positive SPT also had positive OFC. CONCLUSION: In contrast to commercial extracts, APT with lyophilized allergen extracts is reliable, safe, and maybe useful for the diagnosis of suspected food allergy-related GI symptoms in children. OFC is still needed in most of the cases.

Recombinant allergen-based provocation testing.

Over the last 25 years, recombinant allergens from all important allergen sources have been cloned and are now available as recombinant proteins. These molecules can be produced in practically unlimited amounts without biological or batch-to-batch variability. It has been shown in provocation tests that recombinant allergens have similar clinical effects as their natural counterparts. With the help of these tools it is possible to reveal the precise reactivity profiles of patients and to uncover and differentiate cross-reactivity from genuine sensitization to an allergen source. Although it has been shown some time ago that it would be possible to replace crude allergen extracts with recombinant allergens for skin prick testing, and even though the use of allergen components can improve routine diagnosis, these tools are still not available for clinical routine applications. The use of provocation tests is a crucial step in the development of new, hypoallergenic vaccines for therapy of allergic disease. Here we describe important provocation methods (skin prick test, intradermal test, atopy patch test, nasal provocation, colonoscopic provocation test) and give an overview of the clinical provocation studies which have been performed with recombinant allergens so far.

Prevalence of positive atopy patch test in an unselected pediatric population.

BACKGROUND: In the latest decades, epidemiological studies on allergic disorders in children, including atopic dermatitis, rhinitis and asthma, demonstrated a continuous increase in prevalence. However, such studies are usually performed by questionnaires and, sometimes, by skin prick test or in vitro IgE tests, while the portion of allergy sustained by the cell-mediated mechanism is neglected, because the essential test, i.e. the atopy patch test is not performed. METHODS: This cross-sectional survey studied by a specific questionnaire, skin prick test and atopy patch test, an unselected population, represented by the entire scholastic population attending a Primary school and a Junior Secondary school in the rural town of San Marco in Lamis, 12.000 inhabitants (Puglia, Italy). RESULTS: Among the 456 subjects included, 78 (17.1 %) had a positive skin prick test and 57 (12.5 %) had a positive atopy patch test. In particular, 13.4 % of subjects were positive only to skin prick test and 8.8 % were positive only to atopy patch test. The allergen most frequently positive was the house dust mite, with 41 positive results to skin prick test and 55 to atopy patch test, while for pollen positive results concerned almost exclusively the skin prick test. CONCLUSIONS: This survey on an unselected population of children detected a prevalence of positive results to atopy patch test not so distant from the positive results to skin prick test, and in 8.8 % of subjects the atopy patch test was the only positive test. This would suggest to add the atopy patch test in future epidemiological studies on allergy, in order to avoid to overlook the not negligible portion of patients with T-cell-mediated allergy.

Factors associated with different results of allergy tests in children with dust mite-induced atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a public health problem, with an increasing prevalence worldwide. AD is a chronic inflammatory disease characterised by skin lesions and severe itching. Immunologically, AD has two forms, IgE-mediated and cell-mediated, but it may also be idiopathic. In the pathogenesis of AD, the gene mutations for filaggrin, a filament-aggregating protein present in the epidermis, are of pivotal importance, but other genetic factors are also operating, including those linked to family atopy. METHODS: We evaluated the role of family atopy, and of the results of the atopy patch test (APT) in parents, in children with mite-induced AD. 64 children, 38 males and 26 females, mean age 4.97 years, were included for the diagnosis of AD and underwent APT and skin prick test (SPT) with dust mite extracts, with evaluation of atopy and result of APT also in parents. RESULTS: A positive family history of atopy was shown for children with positivity to both APT and SPT compared to those with negative or only one positive result to APT or SPT (p=0.08). Significant associations were found concerning APT results in children and parents. In particular, children of a positive-APT parent had an 18-fold higher risk of APT-positivity in comparison with children of negative-APT parents, while the risk was 6.6-fold higher if APT was positive in father. CONCLUSION: Family atopy and a positive APT in fathers are risk factors to develop cell-mediated AD, as assessed by the APT, in children.

Food allergy: Epidemiology, pathogenesis, diagnosis, and treatment.

This review focuses on advances and updates in the epidemiology, pathogenesis, diagnosis, and treatment of food allergy over the past 3 years since our last comprehensive review. On the basis of numerous studies, food allergy likely affects nearly 5% of adults and 8% of children, with growing evidence of an increase in prevalence. Potentially rectifiable risk factors include vitamin D insufficiency, unhealthful dietary fat, obesity, increased hygiene, and the timing of exposure to foods, but genetics and other lifestyle issues play a role as well. Interesting clinical insights into pathogenesis include discoveries regarding gene-environment interactions and an increasing understanding of the role of nonoral sensitizing exposures causing food allergy, such as delayed allergic reactions to carbohydrate moieties in mammalian meats caused by sensitization from homologous substances transferred during tick bites. Component-resolved diagnosis is being rapidly incorporated into clinical use, and sophisticated diagnostic tests that indicate severity and prognosis are on the horizon. Current management relies heavily on avoidance and emergency preparedness, and recent studies, guidelines, and resources provide insight into improving the safety and well-being of patients and their families. Incorporation of extensively heated (heat-denatured) forms of milk and egg into the diets of children who tolerate these foods, rather than strict avoidance, represents a significant shift in clinical approach. Recommendations about the prevention of food allergy and atopic disease through diet have changed radically, with rescinding of many recommendations about extensive and prolonged allergen avoidance. Numerous therapies have reached clinical trials, with some showing promise to dramatically alter treatment. Ongoing studies will elucidate improved prevention, diagnosis, and treatment.

The diagnosis of food allergy: a systematic review and meta-analysis.

BACKGROUND: We investigated the accuracy of tests used to diagnose food allergy. METHODS: Skin prick tests (SPT), specific-IgE (sIgE), component-resolved diagnosis and the atopy patch test (APT) were compared with the reference standard of double-blind placebo-controlled food challenge. Seven databases were searched and international experts were contacted. Two reviewers independently identified studies, extracted data, and used QUADAS-2 to assess risk of bias. Where possible, meta-analysis was undertaken. RESULTS: Twenty-four (2831 participants) studies were included. For cows' milk allergy, the pooled sensitivities were 53% (95% CI 33-72), 88% (95 % CI 76-94), and 87% (95% CI 75-94), and specificities were 88% (95% CI 76-95), 68% (95% CI 56-77), and 48% (95% CI 36-59) for APT, SPT, and sIgE, respectively. For egg, pooled sensitivities were 92% (95% CI 80-97) and 93% (95% CI 82-98), and specificities were 58% (95% CI 49-67) and 49% (40-58%) for skin prick tests and specific-IgE. For wheat, pooled sensitivities were 73% (95% CI 56-85) and 83% (95% CI 69-92), and specificities were 73% (95% CI 48-89) and 43% (95% CI 20-69%) for SPT and sIgE. For soy, pooled sensitivities were 55% (95% CI 33-75) and 83% (95% CI 64-93), and specificities were 68% (95% CI 52-80) and 38% (95% CI 24-54) for SPT and sIgE. For peanut, pooled sensitivities were 95% (95% CI 88-98) and 96% (95% CI 92-98), and specificities were 61% (95% CI 47-74), and 59% (95% CI 45-72) for SPT and sIgE. CONCLUSIONS: The evidence base is limited and weak and is therefore difficult to interpret. Overall, SPT and sIgE appear sensitive although not specific for diagnosing IgE-mediated food allergy.

Diagnostic accuracy of atopy patch tests for food allergy in children with atopic dermatitis aged less than two years.

BACKGROUND: Atopy patch tests (APT) have been introduced as a valuable tool for the diagnosis of food allergy. However, interpretation of the readout of APT requires further clarification. OBJECTIVE: To investigate the accuracy of APT in identifying atopic sensitisation to hen's eggs (HE), cow's milk (CM), soybean and wheat in Chinese children with atopic dermatitis (AD) aged less than two years and to evaluate skin signs of APT for accurate diagnosis of food allergy. METHODS: APT was performed and food allergy confirmed by open oral food challenges with HE, CM, soybean and wheat in 150 Chinese AD children aged less than two years. The sensitivity, specificity, positive (PPV) and negative (NPV) predictive values, positive (LR+) and negative likelihood ratio (LR-) of APT were calculated. RESULTS: Erythema and infiltration were not sufficiently indicative of a positive APT. The PPV increased with the appearance of indurations and the number of papules. The true positive APT rate increased from scores of + to +++. The PPV and specificity were 100% while APT scores of +++ were obtained with HE, CM and wheat. The sensitivity of APT with HE, CM, soybean and wheat allergy ranged from 59.6% to 90.5%, while the specificity ranged from 82.1% to 92.4%. CONCLUSION: The APT is a suitable method for the diagnosis of AD in Chinese children aged less than two years with food allergies. Erythema and infiltration are not sufficient indicators of APT positivity. The PPV increases with indurations and the number of papules.

Subendotyping of Dermatophagoides pteronyssinus-Induced Rhinitis and Its Impact on Respiratory Comorbidities.

BACKGROUND: The impact of delayed hypersensitivity to Dermatophagoides pteronyssinus (DP) on comorbidities of allergic rhinitis (AR) is unknown. OBJECTIVE: The primary end point was to test the hypothesis that DP-induced AR could be divided into 2 subendotypes on the basis of presence or absence of a delayed-type mite sensitization detected by the positive result of atopy patch test for DP (DP-APT). The second end point was to evaluate differences in the long-term risk of respiratory comorbidities and nasal airway response to mite exposure. METHODS: In a prospective observational study, we included 472 patients with DP-induced AR. A total of 343 patients had positive results of skin prick test/serum specific IgE and DP-APT and were assigned to a subendotype with both IgE- and T-cell-mediated mite sensitization (BMSS). The remaining 129 patients without delayed-type mite sensitization were included in the subendotype with only IgE-mediated mite sensitization. Nasal allergen provocation test with active anterior rhinomanometry, paranasal sinuses computed tomography scan, nasal endoscopy, and spirometry were performed. RESULTS: At baseline, BMSS showed a larger increase in nasal airway resistance, total nasal score, and visual analogue scale score to mite exposure. During a 15-year follow-up, 56 patients developed chronic rhinosinusitis with nasal polyps, with higher incidence in BMSS than in the subendotype with only IgE-mediated mite sensitization (50 patients, 14.6% vs 6 patients, 12.4%; P < .001). BMSS also showed a higher incidence of conjunctivitis (25.7% vs 12.4%; P < .01). The rate of adult-onset asthma did not differ between groups, but patients with BMSS showed a more frequent link to chronic rhinosinusitis with nasal polyps (6 of 29 patients, 20.7% vs 0 of 10 patients, 0%). DP-APT independently predicted chronic rhinosinusitis with nasal polyps and conjunctivitis. CONCLUSIONS: Two subendotypes with significantly different clinical outcome can be identified among patients with DP-induced AR according to the presence of delayed-type mite sensitization detected by positive DP-APT result.

[Patch test in the diagnosis of food allergy]. / Prueba de parche en el diagnóstico de alergia alimentaria.

Food allergens are capable of producing adverse reactions through multiple mechanisms of an allergic or non-allergic nature, and through different routes of exposure; generally by ingestion or contact, as in protein contact dermatitis or contact urticaria, including inhalation. Food allergy reactions, in turn, can be mediated by immediate hypersensitivity mechanisms, delayed hypersensitivity or mixed immediate-delayed mechanisms. The reference diagnostic method in food allergy is the double-blind placebo-controlled food challenge test (DBPCFC), but skin and serological tests are important in the clinical context. The diagnosis of immediate food allergy depends on well-standardized allergological tests, such as the skin prick test (SPT) or specific IgE dosing, which are ideally tested by food challenge testing. However, the diagnosis of delayed mechanism food allergy and mixed allergies, which combine both immune mechanisms, is more complex. Delayed hypersensitivity reactions are evaluated with the epicutaneous patch test, or patch testing, for the diagnosis of contact dermatitis. The atopy patch test is initially used for the investigation of inflammatory reactions, which may be linked to food allergens in patients with atopic dermatitis. It was later applied in other diseases, whose pathogenesis is mainly mediated by a mechanism of delayed hypersensitivity to protein allergens: eosinophilic esophagitis, enterocolitis induced by food proteins, protein contact dermatitis, contact urticaria, among other disorders.

Los alergenos alimentarios son capaces de producir reacciones adversas por múltiples mecanismos de naturaleza alérgica o no, y mediante distintas vías de exposición; generalmente por ingestión o por contacto, como en la dermatitis por contacto a proteínas o urticaria por contacto, incluso por inhalación. Las reacciones de alergia alimentaria, a su vez, pueden ser mediadas por mecanismos de hipersensibilidad inmediata, hipersensibilidad retardada o mecanismos mixtos inmediato-retardados. El método diagnóstico de referencia en alergia alimentaria es la prueba de desafío con alimentos a doble ciego controlado con placebo (DBPCFC), pero las pruebas cutáneas y serológicas son importantes en el contexto clínico. El diagnóstico de alergia alimentaria inmediata depende de pruebas alergológicas bien estandarizadas, como la prueba de prick (skin prick test-SPT) o la dosificación de IgE específica, que idealmente se comprueban mediante la prueba de provocación con alimentos. Sin embargo, el diagnóstico de alergia alimentaria de mecanismo retardado y alergias mixtas, que combinan ambos mecanismos inmunes, resulta más complejo. Las reacciones de hipersensibilidad retardada se evalúan con la prueba de parche epicutáneo, o patch testing, para el diagnóstico de las dermatitis por contacto. La prueba de parche de atopia se utiliza, inicialmente, para la investigación de reacciones inflamatorias, que pueden vincularse con alergenos alimentarios en pacientes con dermatitis atópica. Posteriormente fue aplicada en otras enfermedades, cuya patogenia es principalmente mediada por un mecanismo de hipersensibilidad retardada a alérgenos proteicos: esofagitis eosinofílica, enterocolitis inducida por proteínas alimentarias, dermatitis por contacto a proteínas, urticaria por contacto, entre otras alteraciones.

Atopy patch testing and associations with atopic conditions and specific IgE tests: a population-based study in adolescents

Background: The clinical usefulness of the atopy patch test (APT) is unclear for investigating aeroallergen- and food-triggered atopic dermatitis (AD). Objectives: This study aimed to assess the prevalence of positive APT reactions in a population of adolescents and investigate possible associations between the APT, specific serum (s) immunoglobulin E (IgE) tests, self-reported atopic conditions and health-related quality of life. Materials & Methods: A population-based study was performed on 211 adolescents (13-14 years old). Collected data included questionnaires, an APT with food and aeroallergens and s-IgE tests. Results: Positive APT reactions were observed in 9.0% (19/211) of the adolescents. Timothy grass was the top allergen with 11 (5.2%) positive reactions, followed by cat dander (2.8%) and house dust mites (2.4%). Rhinoconjunctivitis increased the odds of any positive APT (crude odds ratio: 3.32; 95% confidence interval [CI]: 1.17­9.40), particularly when an APT was positive for aeroallergens (odds ratio: 5.02, 95% CI: 1.54-16.42). There was no association between a positive APT and AD. Four adolescents without AD and no IgE-sensitization had a positive APT. Conclusion: Based on a population of adolescents, the APT is associated with rhinoconjunctivitis but not AD. This finding should be taken into consideration in further attempts to clarify the role of the APT in the clinical setting.

Risk of Chronic Rhinosinusitis With Nasal Polyps in Endotypes of Dermatophagoides pteronyssinus-Induced Rhinitis.

BACKGROUND: Observation of the natural history of two emerging endotypes of allergic rhinitis, local-sensitization rhinitis (LAR) and dual-allergic rhinitis (DAR), compared with systemic-sensitization rhinitis (AR), could improve knowledge of the role of allergy in chronic rhinosinusitis with nasal polyps (CRSwNP). OBJECTIVE: To test the hypothesis that endotypes of Dermatophagoides pteronyssinus (DP)-induced rhinitis were risk factors for CRSwNP and adult-onset asthma and to investigate whether delayed hypersensitivity to DP, assessed by atopy patch test, could be a contributing factor. METHODS: We conducted a prospective observational study over 15 years on a cohort of 999 patients: 468 with AR, 333 with LAR, and 198 with DAR. The latter endotype was characterized by the coexistence of seasonal disease caused by systemic sensitization to pollen in patients with DP-induced LAR. The study design included a physical visit; ear, nose, and throat examination with anterior rhinoscopy; skin prick test; serum-specific IgE; DP-atopy patch test; nasal allergen provocation test with DP; paranasal sinuses computed tomography scan; nasal endoscopy; and spirometry. RESULTS: During 15 years of follow-up, 194 patients developed CRSwNP with a higher rate of LAR (28.2%) and DAR (22.2%) than AR (12%). For LAR and DAR, 7.5% and 10.6% of patients developed adult-onset asthma temporally linked to CRSwNP in 68% and 71.4% of cases, respectively. A total of 858 patients with rhinitis had delayed hypersensitivity to DP. Moreover, DP-ATP was an independent predictive factor for CRSwNP and had elevated positive and negative predictive values for localized allergic disease of the nasal mucosa. CONCLUSIONS: Endotypes of DP-induced allergic rhinitis represent risk factors for CRSwNP. Patients with local-sensitization rhinitis and DAR are more at risk than those with AR. In these emerging endotypes, progression toward CRSwNP is often associated with the development of adult-onset asthma. Chronic rhinosinusitis with nasal polyps shows several possible indicators for type 2 endotype. Delayed hypersensitivity to DP is an independent predictive factor for CRSwNP.

Non-IgE- or Mixed IgE/Non-IgE-Mediated Gastrointestinal Food Allergies in the First Years of Life: Old and New Tools for Diagnosis.

non-IgE and mixed gastrointestinal food allergies present various specific, well-characterized clinical pictures such as food protein-induced allergic proctocolitis, food protein-induced enterocolitis and food protein-induced enteropathy syndrome as well as eosinophilic gastrointestinal disorders such as eosinophilic esophagitis, allergic eosinophilic gastroenteritis and eosinophilic colitis. The aim of this article is to provide an updated review of their different clinical presentations, to suggest a correct approach to their diagnosis and to discuss the usefulness of both old and new diagnostic tools, including fecal biomarkers, atopy patch tests, endoscopy, specific IgG and IgG4 testing, allergen-specific lymphocyte stimulation test (ALST) and clinical score (CoMiss).