Lessons from atopy patch testing in Atopic Dermatitis

The exposure of atopic eczema (AE) patients to their relevant protein allergens (eg, from house dust mite, cat dander, grass pollen, or food allergens) can trigger an exacerbation or maintain the disease. Diagnostic procedures are needed to specify allergen avoidance recommendations for the individual patient. Skin prick tests and specific serum IgE tests might be helpful in pointing out potential trigger factors, but relevance needs to be confirmed (eg, with food provocation tests). The atopy patch test (APT) involves the epicutaneous application of intact protein allergens in a diagnostic patch test setting with an evaluation of the induced eczematous skin lesions after 24 to 72 hours. The APT targets the cellular component of AE and helps round out the AE test spectrum. As a number of apparently minor test modifications greatly influence the sensitivity, specificity, and reproducibility of the APT, the European Task Force on Atopic Dermatitis (ETFAD) has developed a standardized APT technique. It consists of purified allergen preparations in petrolatum, applied in 12-mm diameter Finn chambers mounted on Scanpor tape to non-irritated, non-abraded, or tape-stripped skin of the upper back. The APT is read at 48 and 72 hours according to the test criteria and reading key of the ETFAD for appearance of erythema, and number and distribution pattern of the papules. In contrast with skin prick tests, the APT might even detect a relevant sensitization in the absence of specific IgE. Many studies have been undertaken to objectify the sensitivity and specificity of the APT to show its diagnostic use in clinical practice.     

The atopic eczema/dermatitis syndrome. Epidemiology, natural course, and immunology of the IgE-associated ("extrinsic") and the nonallergic ("intrinsic") AEDS.

According to the position paper from the EAACI nomenclature task force, the term "Atopic eczema/dermatitis syndrome" (AEDS) should be used as the "umbrella" term to cover the different subtypes of atopic dermatitis (AD). The new nomenclature (AEDS) underlines the fact that AD is not one, single disease, but rather an aggregation of several diseases with certain clinical characteristics in common. The so-called "intrinsic" type of AD (now termed nonallergic AEDS) fulfills the most commonly used diagnostic criteria for AD. These patients have no associated respiratory diseases, such as bronchial asthma or allergic rhinitis, show normal total serum IgE levels, no specific IgE, and negative skin-prick tests to aeroallergens or foods. Immunologic differences between the IgE-associated type of AD and the nonallergic type can be found in the cell and cytokine pattern in peripheral blood and in the affected skin, and also by phenotyping characterization of epidermal dendritic cells. The current explanation of this distinction is based on differences in genetics and/or environmental conditions. The classification into an allergic, IgE-associated (AAEDS) and a nonallergic type (NAAEDS) at each stage of life, i.e., infancy, childhood, teenage, and adult, is essential for the allergological management of patients as to allergen avoidance, secondary allergy prevention, and immunotherapy. The risk of an "atopy march" is significantly lower in children with the non-IgE-associated type.     

"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.     

Skin Barrier-Related Molecules and Pathophysiology of Asthma

The concept of “atopic march” has been well appreciated both by physicians and by dermatologists; eczema (atopic dermatitis) often precedes the development of airway diseases such as asthma and allergic rhinitis in atopic subjects. However, the underlying mechanisms for atopic march are less elucidated. It has been conceived that genetic susceptibility to atopy determines the phenotype of allergic diseases progressive from the skin to the airways, but recent discovery of filaggrin gene mutations that disturb the barrier function of the skin in patients with asthma and eczema now suggests the crucial role of epicutaneous sensitization as a precursory event for the development of asthma. In the present review, we describe updated genetic and immunological evidences that suggest the relationship between skin barrier-related molecules and the pathology of asthma.     

The relationship between HIV infection and atopic dermatitis

Patients with HIV infection exhibit a wide range of skin pathology, including bacterial, fungal, and viral infections, skin tumors, inflammatory and eczematous eruptions, and drug rashes. HIV-infected adults commonly develop a condition that strongly resembles atopic dermatitis and is sometimes called “atopic-like dermatitis”; moreover, atopic dermatitis and other atopic disorders have been described as common manifestations of pediatric HIV infection. Conditions such as sinusitis, asthma, and hyper-IgE syndrome, and laboratory abnormalities, eg, elevated IgE levels, eosinophilia, and possible Th1-Th2 imbalances, suggest a predilection for atopic disorders in these patients. It is of interest to examine the immune perturbations intrinsic to HIV infection, and their possible role in triggering atopic dermatitis, and to consider whether other abnormalities, such as xerosis, bacterial or viral superantigens, or epidermal barrier disruption with altered presentation of cutaneous aeroallergens, might play a significant role.     

Dissecting the causes of atopic dermatitis in children: less foods, more mites

Atopic dermatitis (AD) is a common, chronic or chronically relapsing, multifactorial skin disease that mainly occurs in children but affects also adults. AD usually begins early in life and often concerns people with a personal or family history of asthma and allergic rhinitis. AD is characterized by eczematous changes in the epidermis and originates from a late, T-cell mediated reaction associated to the formation and production of memory T-cell of TH2 type, occurrence of homing receptor at skin level and cutaneous lymphocyte-associated (CLA) antigens. Extrinsic or allergic AD, but not intrinsic AD, shows high total serum IgE levels and the presence of specific IgE for environmental and food allergens. A pivotal role in the pathogenesis of AD is played by filaggrin, a protein contained in the granular layer of the epidermis regulating the aggregation of keratin filaments. Mutation in the filaggrin gene causes decreased barrier function of the corny layers of the epidermis. This favours the enter through the skin of environmental allergens, especially the house dust mite, that further facilitates such entering by the proteolytic activity of its major allergen Der p 1. In fact, recent advances suggest that the dust mite, more than foods, is the major cause of allergic AD. As far as the causal diagnosis of AD is concerned, there is notable evidence supporting the capacity of the atopy patch test (APT) to reproduce the pathophysiologic events of AD. This makes APT a valuable diagnostic tool for AD.     

A Study of Relation between BCG Scar and Atopy in Schoolchildren of Zanjan City

The prevalence of atopic disease in recent decades has been dramatically increased. It has been suggested that BCG vaccination may protect against development of allergic diseases.The purpose of this study was to identifying relation between scar of BCG vaccine and atopy. This cross-sectional study was done in 1000 children, 10-15 years of age, in Zanjan city. One thousand children (501 girls and 499 boys) were recruited in this study, 137, 121 and 141 cases of asthma, atopic dermatitis and allergic rhinitis, respectively were detected.Three hundred and three subjects had at least one of these disorders, which were diagnosed as atopy. There was reverse correlation between BCG scar and asthma (P=0.013), atopic dermatitis (P<0.01), and atopy (P<0.01). We did not find any association between the diameter of BCG scar and allergic rhinitis. Reverse correlation of asthma, atopic dermatitis and atopy with BCG scar are significant. This relied on history and symptoms of patients. Further studies with skin tests, measurements of total and specific IgE levels and spirometery are recommended.     

Is There a Need for Repetition of Skin Test in Childhood Allergic Diseases? Repetition of Skin Test and Allergic Diseases

Background: Skin prick tests are widely used to determine sensitivity in allergic diseases. There is limited information about the natural history of skin sensitization tests and factors that affect them. It was aimed to determine the changes in skin test results and the factors affecting the reactivity of skin tests after a period of approximately four years in children with allergic disease.Methods: SPT of 170 patients among 2485 children with asthma and/or allergic rhinitis and/or atopic dermatitis, who underwent SPT between 2005 and 2007, were repeated after an interval of at least 3 years.Results: The mean age was 10.7 ± 3.1 (5-18) years and 70% of the patients were male. In total 66 (39.0% of the study population) had a different skin tests result in follow-up. Alterations: loss of sensitivity in 18 (11%) patients, the formation of a new sensitivity in 37 (22%) patients, and 11 (6%) both gained and lost sensitization. The presence of atopy in the family, the presence of allergic rhinitis and IgE elevation significantly predicted the incidence of new sensitization. The presence of sensitization to multiple allergens significantly predicted the incidence of loss of sensitization.Conclusions: It is found that there was an alteration of sensitization in 4/10 children at the end of the average 4-year period. The presence of family atopy, the presence of allergic rhinitis and serum total IgE elevation were risk factors for the development of new sensitization. On the other hand sensitization to multiple allergens was risk factors for the loss of sensitization.     

Définitions des termes utilisés en allergologie alimentaire chez l’enfant

In so far as there are no recent medical references that specify terms used in allergy, and particularly terms dealing with food allergy, it seemed to us that it would be of use to compile a glossary that would be helpful in daily practice. The defined terms (plus comments) have been retained according to sequences that correspond to steps in a food allergy work-up. The following terms are entered successively in this review: atopic dermatitis; SCORAD; asthma; pulmonary function tests; medications for children; symptoms and severity of food allergies; immediate skin tests; intradermal tests or “atopy patch-tests”; allergen-specific and total serum IgE levels; oral provocation test; labial provocation test; other tests used in allergy work-ups; allergy, hypersensitivity, atopy; allergens, allergies, sensitizations, allergic cross-reactions; treatment of an allergic reaction.     

Immunoglobulin e-bearing antigen-presenting cells in atopic dermatitis

Human antigen-presenting cells (APCs) bind monomeric immunoglobulin E (IgE) via the high-affinity IgE receptor, FcaRI. Surface expression of this trimeric structure is strongly associated with the atopic status of the donors, and maximal levels are observed on Langerhans cells (LC) and inflammatory dendritic epidermal cells (IDEC) in atopic dermatitis (AD). Although intracellular expression of the FcaRI α-chain is induced by interleukin-4 (IL-4), the upregulation of surface levels on dendritic cells (DC) from atopics is due to enhanced expression of the FcaRIγ -chain and stabilization by binding of its ligand IgE. A characteristic function of FcaRI-bearing APCs is the specific uptake and processing of IgE-bound allergens, which is followed by T-cell stimulation. In AD, DC-mediated presentation of aeroallergens penetrating the epidermis is thought to induce an IgE-mediated, delayed-type hypersensitivity reaction. In addition, different FcaRI-bearing APC subsets in AD skin might regulate inflammatory processes through the production of Th1/Th2-polarizing signals, proinflammatory cytokines, chemokines, and factors that are involved in the induction of tolerance.     

Eczema phenotypes and IgE component sensitization in adolescents: A population-based birth cohort

BackgroundEczema patients are commonly immunoglobulin (Ig)E polysensitized. Although atopic dermatitis (AD) phenotypes have been recognized, IgE sensitization patterns based on AD phenotypes have not been well illustrated. We aimed to investigate how eczema phenotypes impact IgE component sensitization patterns.MethodsThis birth cohort study investigated a general population in the Tokyo Children's Health, Illness, and Development Study (T-Child Study) until children reached the age of 13 years. Eczema was assessed using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Allergen component specific IgE antibody titers were measured using a multiplex array ImmunoCAP ISAC.ResultsPersistent eczema phenotype until adolescence was strongly associated with allergic march symptoms, such as wheezing and hay fever, and oral allergy symptoms, and IgE component sensitizations of airborne (Japanese cedar, house dust mite, Timothy, cat, and dog) and cross-reactive allergens (Bet v 1 family) compared to early-remission and late-onset eczema. On the other hand, late-onset eczema did not show any strong associations with allergic symptoms and IgE sensitization. Adolescents with persistent eczema have high comorbidity of symptoms of pollen-food allergy syndrome.ConclusionsEarly-onset eczema is deeply connected with the later allergic march, and late-onset eczema differs from the phenotype of allergic march. Early-onset eczema characterizing IgE sensitization was likely to be an extrinsic type, and late-onset eczema, which was not related to IgE sensitization, was likely an intrinsic type. Pollen-Food Allergy Syndrome is one of the allergic features in allergic march.     

The atopic march: from skin to the airways

Many patients with atopic eczema (AE) would "march" to develop allergic rhinitis (AR) and asthma. Physicians, patients and their families often do not appreciate the significance of these diseases as co-morbidities of atopy.The aim of this study was to evaluate the prevalence and severity of airway atopies in patients with AE. AR and asthma severity were assessed in consecutive AE patients seen at a pediatric dermatology clinic by ARS (allergic rhinitis score) and ACT (asthma control test). Eczema severity (SCORAD and Nottingham Eczema Severity Score: NESS) were recorded.110 patients with AE and 42 patients without AE were recruited. Allergic rhinitis and asthma were significantly more prevalent in patients with AE [odds ratio for AR was 2.9 (CI: 1.3 - 6.5) and for asthma 4.3 (CI: 1.3 - 16.10)]. 23 (45%) of the AE patients with AR reported that they were currently on oral antihistamine whereas none of the non-AE group reported such usage. Both groups reported relatively higher sneezing and nasal congestion scores and low "eye watering" score. Comparing mild with moderate-to-severe AE, there was essentially no difference between the prevalence of allergic rhinitis and asthma, or severity of symptoms by ARS and ACT, but females reported more severe symptoms of sneezing and itching nose.We conclude that allergic disorders of airway are very common among AE patients independent of the eczema severity. Most of the patients have mild-to-moderate AR and asthma. There is a lot of room for parent/patient education, and childhood eczema may prompt early awareness of these airway co-morbidities of atopy.     

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

Introduction and objectivesSince 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 methodsIn 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.ResultsIn 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.ConclusionOur study showed that APT provided reliable diagnostic accuracy in atopic dermatitis patients. However, APT had low sensitivity in patients with gastrointestinal symptoms.     

Relationship between skin prick and atopic patch test reactivity to aeroallergens and disease severity in children with atopic dermatitis

BackgroundThe immunological mechanism in aetiology of atopic dermatitis (AD) shows significant differences from other allergic diseases. Allergen inhalation exacerbates AD lesions and AD patients’ complaints decrease in house dust mite (HDM) low level environments, which reveals the importance of inhalant allergens.ObjectiveWe evaluated the skin prick test (SPT) and atopy patch test (APT) positivity rates with aeroallergens and studied the effect of test results, and aimed to determine the value of allergic test reactivity on the clinical characteristics of children with AD.MethodsForty-five children aged 2–15 years with AD were included to study between May 2006 and May 2007 in GATA Haydarpasa Teaching Hospital, Allergy Department. The reactivity to inhalant allergens using SPT and APT was evaluated. The severity of AD, which was assessed with SCORAD, was compared with aeroallergen hypersensitivity.ResultsThe highest positivity of APT was seen against HDM (48.9%). HDM SPT positivity and subjective symptoms score were statistically correlated (P < 0.05). Patients with strong SPT positivity to HDM had a higher total SCORAD score (P < 0.05). Although there was no statistical correlation between HDM APT and SCORAD parameters, APT positive patients had generally higher SCORAD parameters. The statistical significance was only shown between the extent of the disease and strong APT positive reactions to Dermatophagoides pteronyssinus.ConclusionHDM allergens play an important role in determining the clinical severity of AD and strong APT positivity could be more meaningful clinically.     

Patch Testing for Noncontact Dermatitis: The Atopy Patch Test for Food and Inhalants

The atopy patch test (APT) is defined as a patch test procedure to assess delayed type hypersensitivity reactions against those protein allergens known to elicit IgE-mediated type I reactions in atopic patients. This patch test procedure uses intact protein allergens instead of haptens in an optimized test setting and with a special reading key. It may be clinically useful especially for atopic dermatitis, as the currently available test procedures either target the wrong reaction type (type I and not type IV) or use the wrong allergens (haptens and not protein allergen). A positive APT reaction correlates with a positive lymphocyte transformation test and allergen-specific Th2 cells in the peripheral blood. As even small changes in the test procedure influence the sensitivity, specificity, and reproducibility of the APT, the European Task Force on Atopic Dermatitis (ETFAD) has developed a standardized APT technique: Intact protein allergens, purified in petrolatum, are applied in 12-mm-diameter Finn chambers mounted on Scanpor tape for 48 h to non-irritated, non-abraded, or tape-stripped skin of the upper back for 48 h; the evaluation of the test reaction is done after 48 and 72 h using the ETFAD reading key, assessing erythema as well as number and distribution pattern of the papules. The APT may reveal type IV sensitization in patients who are negative for the respective type I tests. Limited availability of the expensive test substances and limited reimbursement is among the factors restricting the routine use of the APT.     

How now,brown cow,vaccine or extract?

Conclusions In summary, the word “allergen vaccine” should be used to denote FDA-approved preparations of therapeutic allergens used to treat allergic diseases. The term “allergen extract” should be used for preparations of allergens that are not yet FDA-approved, are FDA-approved but not yet incorporated into a therapeutic vaccine for an individual patient, or are used for experimental purposes. The term “diagnostic allergens”, in this case also approved by the FDA or its equivalent is appropriate when these products are used for skin testing. The use of these terms by physicians in allergy/immunology will enhance the specialty and be useful to patients who do not and never did understand the term “allergen extract”.     

Assessment of indoor allergen exposure

Of the four modes of treating human allergic disease, avoidance or separation of the allergic patient from the allergen source is most effective and least expensive. The clinical immunology laboratory has established efficient and inexpensive “reservoir” dust sampling and processing procedures to obtain a surface dust specimen that reflects the allergen burden of the environment. Following extraction, allergens are quantified by reproducible, validated immunoenzymetric assays for the quantification of “indicator” aeroallergen levels in home, school, and work environments. In this paper, the strategies and methods for collecting and processing dust samples are discussed, and assays are reviewed for quantifying indoor aeroallergen exposure from dust mites (Der p 1 and 2, Der f 1 and 2), animals (cat: Fel d 1; dog: Can f 1; mouse: Mus m 1; rat: Rat n 1), and insects (cockroach: Bla g 1 and 2). Accurate quantification of the levels of allergen in indoor environments facilitates avoidance therapy by identifying environmental risk factors for asthma and allergy exacerbation and allowing the allergic patient to monitor the effectiveness of environmental remediation actions.     

Recent advancement to prevent the development of allergy and allergic diseases and therapeutic strategy in the perspective of barrier dysfunction

Therapeutic strategy in late 20th century to prevent allergic diseases was derived from a conceptual framework of allergens elimination which was as same as that of coping with them after their onset. Manifold trials were implemented; however, most of them failed to verify the effectiveness of their preventive measures. Recent advancement of epidemiological studies and cutaneous biology revealed epidermal barrier dysfunction plays a major role of allergen sensitization and development of atopic dermatitis which ignites the inception of allergy march. For this decade, therapeutic strategy to prevent the development of food allergy has been confronted with a paradigm shift from avoidance and delayed introduction of allergenic foods based on the theoretical concept to early introduction of them based on the clinical and epidemiological evidences. Especially, prevention of peanut allergy and egg allergy has been established with the highest evidence verified by randomized controlled trials, although application in clinical practice should be done with attention. This paradigm shift concerning food allergy was also due to the discovery of cutaneous sensitization risk of food allergens for an infant with eczema revealed by prospective studies. Here we have recognized the increased importance of prevention of eczema/atopic dermatitis in infancy. Two randomized controlled trials using emollients showed successful results in prevention of atopic dermatitis in infancy; however, longer term safety and prognosis including allergy march should be pursued. To establish more fundamental strategy for prevention of the development of allergy, further studies clarifying the mechanisms of interaction between barrier dysfunction and microbial milieu are needed with macroscope to understand the relationship between allergic diseases and a diversity of environmental influences.     

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.     

Specific IgE to Common Food Allergens in Children with Atopic Dermatitis

Background: Atopic dermatitis is a major public health problem, often starting in early childhood and sometimes followed by other allergic diseases. Although hypersensitivity to foods is assumed to play an essential role in the development of atopic dermatitis in some patients, little is known about common food allergens in Iranian children with atopic dermatitis. Objectives: This study was designed to identify probable food allergens in Iranian children with atopic dermatitis and find the relationship between food sensitization and the severity of atopic dermatitis. Methods: This study included 90 children aged 2-48 months with atopic dermatitis. Skin prick tests for cow's milk, hen's egg, almond, potato and soybean were done. Serum specific IgE to 20 food allergens was also screened. Results: Among children with atopic dermatitis, the frequency of food sensitization was 40% by skin prick test and 51% by food-specific IgE. Children with atopic dermatitis were most commonly sensitized to cow's milk (31%), hen's egg (17.7%), tree nuts (17.7%), wheat (12.2%), potato (11.1%), tomato (8.8%) and peanut (8.8%). In 42 children with moderate to severe eczema, sensitivity to food allergens was 78.5% by skin prick test and 88% by serum specific IgE evaluation. Conclusion: Our results showed that cow's milk, hen's egg and tree nuts were the most common food allergens in Iranian children with atopic dermatitis. Sensitization to foods was much higher in patients with moderate to severe atopic dermatitis. Determining specific IgE in children with atopic dermatitis can be helpful in managing these patients.