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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.

Advisory Committees↗

Asthma and atopy in workers with an epoxy adhesive.

Seven workers using an epoxy adhesive cured with pyromellitic dianhydride were studied. Workers both mixed and used the adhesive. Each completed a questionnaire about previous respiratory symptoms, family or personal history of atopy, smoking history and symptoms using the adhesive. FEV1 was measured as a base-line and after working with the adhesive. Skin tests to common allergens were performed on all subjects. Two subjects who stated they wheezed with adhesive had falls in FEV1 of 15% and 18% from base-line. Totally symptom-free subjects had falls of less than 4% from base-line or a rise in FEV1. There was no clear relationship between smoking habits or atopic state or skin rashes with resin and a fall in FEV1. There is no simple way to identify those at risk of developing wheeze. Care should be taken with epoxy adhesives to avoid sensitization and where it occurs a simple questionnaire would provide a screening method.

Adhesives↗

Autoradiographic localization of changes in pulmonary beta-adrenoceptors in an animal model of atopy.

Vaccination of guinea pigs with Haemophilus influenzae leads to an impairment of beta-adrenoceptor function in lung. We have used an autoradiographic technique to study the distribution of changes in lung beta-adrenoceptor density. H. influenzae induced a decrease in beta-adrenoceptors in peripheral lung membranes of 22 +/- 5% (mean +/- S.E.M., n = 7), while the affinity of binding was unaffected. Tracheal beta-adrenoceptor binding was not influenced by H. influenzae. Autoradiography revealed a 27% reduction in beta-adrenergic binding sites on alveolar septa. Bronchial epithelial beta-adrenoceptors were decreased for 36%, and vascular smooth muscle and endothelial beta-adrenoceptors were also reduced. beta-Adrenoceptors on airway smooth muscle were unaffected. H. influenzae affected both the beta 1- and beta 2-subtypes of receptors. It is concluded that in this animal model of atopy beta-adrenoceptors may be decreased on several different cell types within the lungs, which may influence overall airway and vascular reactivity.

Animals↗

Transfer of latent atopy by bone marrow transplantation? A case report.

A previously healthy 8-year old girl was diagnosed with acute myelogenous leukemia, and, while she was in first remission, she received a bone marrow transplant from her atopic brother. Studies 1 to 2 years after transplantation revealed that the marrow recipient had a specific-IgE production of donor-type pattern, indicated by the similar skin prick test results and RAST scores in the donor and recipient demonstrating allergy to animal dander and house dust. The recipient's own immunity had been destroyed by the preparative regimen for marrow transplantation, and no lymphoid cells of host origin could be found after transplantation in the chromosome analysis. A sensitization of the recipient to animal dander after transplantation was very unlikely because no animal contacts were present, and the chronic liver graft-versus-host disease of the patient additionally suggested a delayed immunologic recovery. The case history suggests that atopy can be transferred by bone marrow transplantation from donor to recipient. A possible mechanism appears to be a passive transfer not only of lymphoid precursors but also of mature memory cells within the bone marrow inoculum. The donor memory B cells are presumably capable of starting specific-IgE production when the cells are stimulated in the host environment by factors still unknown.

Bone Marrow Transplantation↗

Allergy to castor bean. I. Its relationship to sensitization to common inhalant allergens (atopy).

The IgE response to castor bean (Ricinus communis) was studied in 96 castor bean-allergic patients from Marseilles, France. All had positive skin tests to castor bean. The IgE response to grass, cat, dust mite, olive, and Parietaria was also measured, and a positive RAST to one or more of these allergens was taken to indicate atopic status. Castor bean-specific IgE antibodies, measured by RAST, were found in 87 (91%) of the castor bean-allergic patients, in two of 13 atopic Marseilles residents living close to the castor bean mills, in three of 42 allergic subjects who had no known contact with castor bean, and in none of a control group of 111 Marseilles blood donors. Very high levels of castor bean-specific IgE (maximum class 4 readings on the Phadebas RAST score) were found in 54 (56%) of the castor bean-allergic patients, but the level of IgE antibody to castor bean was not significantly different in atopic and nonatopic subjects. The frequency of a positive serological test (RAST) for atopy in castor bean-allergic subjects (32%) was very similar to that found in the local population (36%). These data indicate that castor bean is an extremely potent sensitizer for both atopic and nonatopic individuals. The magnitude of the specific IgE antibody response is not related to the atopic status of the patient and may be a function of the physiochemical characteristics of the allergen itself.

Adolescent↗

Characterization of the neutrophil respiratory burst in atopy.

Activated neutrophils may play a part in atopic disorders. In these studies, neutrophils were obtained from atopic and nonatopic adults for assessment of respiratory-burst activity. Superoxide production was measured in the resting state and after stimulation with phorbol myristate acetate, formyl-methionyl-leucyl-phenylalanine (f-met-leu-phe), or calcium ionophore A23187. Inhibition of this response by histamine was also measured. Neutrophils from atopic subjects produced more superoxide in the basal state, or in response to calcium ionophore A23187, or submaximal concentrations of f-met-leu-phe, than cells from control subjects. Histamine inhibition of f-met-leu-phe-stimulated superoxide production was less in atopic subjects than in control subjects. These findings suggest that neutrophils from atopic subjects may be hyperreactive in that they produce more superoxide in response to stimuli of low potency and are less readily inhibited than cells from control subjects. These properties may reflect a general attribute of cellular function in atopy and may contribute directly to tissue damage in allergic diseases.

Calcimycin↗

Effect of combined maternal and infant food-allergen avoidance on development of atopy in early infancy: a randomized study.

The effect of maternal and infant avoidance of allergenic foods on food allergy was examined in a prenatally randomized, controlled trial of infants of atopic parents. The diet of the prophylactic-treated group (N = 103) included (1) maternal avoidance of cow's milk, egg, and peanut during the third trimester of pregnancy and lactation and (2) infant use of casein hydrolysate (Nutramigen) for supplementation or weaning, and avoidance of solid foods for 6 months; cow's milk, corn, soy, citrus, and wheat, for 12 months; and egg, peanut, and fish, for 24 months. In the control group (N = 185), mothers had unrestricted diets, and infants followed American Academy of Pediatrics feeding guidelines. The cumulative prevalence of atopy was lower at 12 months in the prophylactic-treated (16.2%) compared to the control (27.1%) group (p = 0.039), resulting from reduced food-associated atopic dermatitis, urticaria and/or gastrointestinal disease by 12 months (5.1% versus 16.4%; p = 0.007), and any positive food skin test by 24 months (16.5% versus 29.4%; p = 0.019), caused primarily by fewer positive milk skin tests (1% versus 12.4%; p = 0.001). The prevalences of allergic rhinitis, asthma, and inhalant skin tests were unaffected. Serum IgE levels in the prophylactic-treated group were marginally lower only at 4 months. Thus, reduced exposure of infants to allergenic foods appeared to reduce food sensitization and allergy primarily during the first year of life.

Adult↗

Relationships between total serum IgE, atopy, and smoking: a twenty-year follow-up analysis.

BACKGROUND: A number of cross-sectional studies have demonstrated that higher levels of IgE are found in subjects who currently smoke cigarettes and/or who are atopic and that IgE levels decline with age. OBJECTIVE: This report examines the interactions among atopic status, smoking, and IgE with longitudinal data and methods. METHODS: Subjects were participants in the Tucson Epidemiological Study of Airways Obstructive Disease and were 6 years of age and older. Total serum IgE measures and allergen skin test results were obtained during three surveys spanning a period of up to 20 years. RESULTS: The results showed no significant gender differences between nonatopic nonsmoking subjects, who were considered the reference group. Nonatopic current smokers had IgE levels similar to those of the reference subjects initially, but IgE levels did not decline with age at the same rate as in the reference subjects, causing significant differences at older ages. There was a significant relationship between number of cigarettes smoked and IgE level. CONCLUSIONS: Atopy and smoking are both associated with elevated total serum IgE levels. Although the exact mechanism for elevated IgE levels in smokers is not known, the significant dose relationship is suggestive of a causal association.

Age Factors↗

Activation of the classical pathway of human complement in vitro by house-dust extracts is caused by IgM antibodies to polysaccharide antigen(s) and is not related to atopy.

The mechanism of activation of the classical pathway of human complement by house-dust extracts and its relevance to atopic disease was studied. Our results confirm that for most sera of adults, house-dust extract is, on a weight basis, a more potent C-activator than aggregated human IgG or lipopolysaccharide (endotoxin). Naturally occurring IgM antibodies directed against ubiquitous polysaccharides appeared to be the dominant factor in the C1 activation by house-dust extracts in human sera. Large variations were found between sera with respect to the concns of these IgM antibodies as measured by C1 activation or fixation of haemolytic complement. The IgM antibody titre was, however, not associated with atopic disease. Consequently, we do not support the hypothesis put forward by Berrens et al. (1978) (Allergol. Immunopath. 6, 45-54) that there might be a relation between atopy and enhanced reactivity of serum complement with allergenic extracts. More than 90% of the C-activating potential of allergen extracts like house dust was found in the fractions with high mol. wt material (mol. wt greater than 100 K). Therefore, these antigens are easily separated from the known IgE-binding major allergens of house-dust mite and cat dander.

Adolescent↗

Immunoprophylaxis of atopy: light at the end of the tunnel?

Current research in the field of atopy is directed almost exclusively towards treatment of established allergic disease. In particular, treatment has concentrated on controlling the release and actions of various mediators, such as cytokines, from the allergy effector cells at the end of the immuno-inflammatory cascade. Here, Patrick Holt argues that a potentially more-effective and achievable goal may be the prevention of initial T helper 2 (Th2)-cell sensitization to environmental allergens during infancy. This might be achieved via amplification of the endogenous 'immune deviation' mechanism(s) that normally facilitate discrimination between pathogenic and non-pathogenic antigens at the mucosal surfaces of the body.

Animals↗

Reduced levels of prostaglandin precursors in the blood of atopic patients: defective delta-6-desaturase function as a biochemical basis for atopy.

In the plasma phospholipids of a group of 50 young adults with atopic eczema, there was an elevation of cis-linoleic acid associated with a deficit of gamma-linolenic acid and of the prostaglandin precursors, dihomogammalinolenic acid and arachidonic acid. This suggests that atopics have a deficit in the function of the delta-6-desaturase enzyme which converts linoleic acid to gamma-linolenic acid. Carriers of cystic fibrosis tend to be phenotypically atopic, supporting previous suggestions that in homozygote cystic fibrosis patients the key defect may be in the delta-6-desaturase enzyme. Atopic patients may be exceptionally sensitive to side effects of non-steroidal anti-inflammatory agents. They fail to flush in response to application of niacin compounds to the skin, a reaction mediated by prostaglandins. A deficit of prostaglandin precursors would explain both of these observations. That the observed biochemical deficit plays a causative role in the manifestations of atopy was indicated by the fact that in a double-blind, placebo-controlled crossover trial, gamma-linolenic acid in the form of evening primrose oil (Efamol), partially corrected both the biochemical abnormalities and the clinical state.

Dermatitis, Atopic↗

Comparative study of ocular herpes simplex virus in patients with and without self-reported atopy.

PURPOSE: To compare the characteristics of ocular herpes simplex virus (HSV) in patients with and without atopy. DESIGN: Retrospective cohort comparative study. METHODS: Patients who presented at the Cornea Service, Wills Eye Hospital, between March 2003 and March 2004 who had been previously diagnosed in the same institution as having ocular HSV diagnosis or were just diagnosed as having the disease were asked to complete a study questionnaire that enabled categorization into atopic and nonatopic. In April 2005, 223 patients who agreed to be in the study had their charts reviewed, and 125 patients were excluded according to exclusion criteria: immunosuppression, follow-up less than one year, previous history of penetrating keratoplasty (PK) out of the Cornea Service, and no active HSV episode during follow-up. MAIN OUTCOME MEASURES: Incidence of all types of HSV recurrences. SECONDARY OUTCOME MEASURES: Bilaterality, visual loss, need for PK , and secondary bacterial infection in both groups. HSV episodes were classified into infectious, inflammatory, and mixed for analysis. RESULTS: Ninety eight patients (110 eyes) were included in the study. Atopic/nonatopic (P value): the mean follow-up was 11.6 (+/- 10.6)/8.8 years (+/- 8.4) (P = .14); the mean incidence of HSV episodes per year of follow-up was: total episodes 0.32 (+/- 0.36)/0.28 (+/- 0.33) (P = .14), infectious 0.16 (+/- 0.22)/0.10 (+/- 0.14) (P < .01), inflammatory 0.11 (+/- 0.19)/0.11 (+/- 0.19) (P < .01), and mixed 0.09 (+/- 0.20)/0.07 (+/- 0.16) (P = .06); bilateral HSV was present in 9/3 patients (P = .22); the mean loss of vision was four lines of Snellen in both groups; PK was performed in 14 of 16 eyes (P = .45); secondary bacterial infection was present in two of four eyes (P = .26). CONCLUSIONS: Atopic patients had considerably more infectious and fewer inflammatory episodes when compared with nonatopics.

Adult↗

Efficacy of oral antiviral prophylaxis in preventing ocular herpes simplex virus recurrences in patients with and without self-reported atopy.

PURPOSE: To compare the efficacy of oral antiviral prophylactic treatment for herpes simplex virus (HSV) recurrences in patients with and without self-reported atopy. DESIGN: Retrospective cohort comparative study. METHODS: setting: Cornea Service, Wills Eye Hospital. study population: Patients who presented with previously diagnosed ocular HSV between March 2003 and March 2004. From 244 patients invited, 54 patients (58 eyes) were included. One hundred and ninety patients were excluded according to exclusion criteria: no active episode during follow-up, immunosuppression, less than one year of follow-up, or previous history of penetrating keratoplasty. The Questionnaire regarding history of atopic disease, considers: presence of allergic rhinitis, asthma or atopic dermatitis, and chart review of ocular history. main outcome measures: Incidence of all types of HSV recurrences with and without antiviral prophylaxis within each group and between groups. HSV episodes were classified into infectious, inflammatory, and mixed for analysis. RESULTS: Atopic/nonatopic (P value): mean follow-up without prophylaxis 8.1 (+/- 8.2)/7.3 years (+/- 8.6) (P = .71); mean follow-up with prophylaxis 2.9 (+/- 2.3)/2.6 years (+/- 2.2) (P = .51); the effect of prophylaxis significantly reduced the all recurrences in both groups except in the inflammatory recurrences in the atopic group and in the mixed recurrences in both groups. Prophylaxis decreased infectious episodes by 44% in nonatopic and 76% in atopics and decreased inflammatory manifestations by 69% in the nonatopic group and 8% in the atopic group. CONCLUSION: Antiviral prophylaxis for HSV recurrences was more effective in reducing infections in atopics and less effective in reducing inflammatory episodes in atopics versus nonatopics.

2-Aminopurine↗

Phenotype definition, age, and gender in the genetics of asthma and atopy.

When studying genetics of complex diseases it is important to have a clearly described and objective phenotype. When drawing conclusions in association studies, age and gender of the population should be considered. Until we know what causes phenotypic differences between males and females and between children and adults, we should try to study longitudinal cohorts with phenotype assessment at different time points and stratify our analyses for gender. To acquire sufficient power for these types of analyses, international collaboration may be the only way to elucidate the intricate, gene-environmental interactions in atopy and asthma in an age- and gender-dependent manor.

Age Factors↗

The diagnostic accuracy of the atopy patch test in diagnosing hypersensitivity to cow's milk and hen's egg in unselected children with and without atopic dermatitis.

BACKGROUND: Previous studies have suggested that the atopy patch test (APT) may make oral challenge superfluous in diagnosing children with food hypersensitivity. OBJECTIVE: To investigate the clinical relevance of APT in predicting hypersensitivity to cow's milk and hen's egg in 486 unselected children 3 years of age. METHOD: The children were examined by APT, skin prick (SPT), histamine release (HR), and specific IgE followed by oral challenge when hypersensitivity to cow's milk or hen's egg was suspected. RESULTS: Food hypersensitivity confirmed by oral challenge was 1.6% to hen's egg and 0.6% to cow's milk. No hypersensitivity to cow's milk or hen's egg was predicted by APT alone. CONCLUSION: APT could not predict food hypersensitivity not predicted by SPT, HR, or specific IgE. Thus, APT cannot be recommended in daily practice for the diagnosis of hypersensitivity to cow's milk and hen's egg in children 3 years of age.

Basophils↗

Viral infections, atopy, and asthma: is there a causal relationship?

Respiratory syncytial virus (RSV) remains the chief cause of hospitalization for lower respiratory tract illnesses in both infants and young children, and can produce severe outcomes. In addition, several studies have suggested that infants in whom RSV bronchiolitis develops may have recurrent wheezing and asthma later in childhood. Further complicating the picture is the question of whether there is a link between RSV infection in infancy and the development of atopy later in childhood. This review will discuss existing data on RSV infection and respiratory complications later in life, as well as the link between RSV and allergic disease.

Asthma↗

Effect of body mass on exercise-induced bronchospasm and atopy in African children.

BACKGROUND: Sensitization to allergen is common in rural populations in less affluent countries, but atopic disease is less frequent than in richer countries. Variables explaining this dichotomy may provide insight into underlying mechanisms of atopic diseases like asthma. OBJECTIVE: To test whether risk of exercise-induced bronchospasm (EIB) in urbanized African populations is increased in association with greater skin sensitivity or increased body mass. METHODS: A total of 3322 children were enrolled in a prevalence survey of EIB in urban and rural South Africa. Children responding positively to an exercise challenge and a random sample of children responding negatively were recruited into a case-control study (393 controls, 380 cases). Subjects were investigated by using allergen skin prick testing, anthropometry, and assay of IgE. Stools were analyzed for parasite infestation. RESULTS: The prevalence of EIB was higher in urban (14.9%) than rural (8.9%) areas (P < .0001). The difference in risk of EIB between urban and rural subjects was associated with atopy (odds ratio [OR] for upper tertile of skin wheal diameter, 2.65; 95% CI, 1.43-4.89; P < .0001), increasing weight (OR for upper tertile of body mass index [BMI], 2.17; 95% CI, 1.45-3.26; P = .001), and affluence. Increasing BMI was also associated with a greater strength of association between specific IgE and the corresponding skin test (Dermatophagoides pteronyssinus, OR for a positive skin test result in presence of specific IgE: heavier subjects, OR, 34.6; 95% CI, 0.9-109.3; P < .0001; lighter subjects, OR, 8.05; 95% CI, 2.74-23.6; P < .001). CONCLUSION: Increases in BMI of rural children in subsistence economies may lead to an increased prevalence of atopic disease. This observation merits further investigation in prospective studies.

Animals↗

A pilot study of the usefulness and safety of a ready-to-use atopy patch test (Diallertest) versus a comparator (Finn Chamber) during cow's milk allergy in children.

BACKGROUND: Patch testing is used in the diagnosis of food allergy, especially during delayed manifestations. OBJECTIVE: A ready-to-use atopy patch test (APT), the Diallertest, was compared with another APT device, the Finn Chamber, in pediatric cow's milk allergy. METHODS: This prospective study involved 49 children (34.3 +/- 17 [mean +/- SD] months of age), with cow's milk allergy manifested by atopic dermatitis (10.2%), digestive manifestations (40.8%), or both (49%). All children underwent both APT techniques, with a reading 72 hours after application, followed by a milk elimination diet for 4 to 6 weeks and open cow's milk challenge. RESULTS: A positive result was seen in 22 (44.8%) versus 13 (26.5%) patients with the ready-to-use and the comparator APTs, respectively. No side effects were recorded. Both techniques were concordant in 67.3% of patients. Of the total 41 open cow's milk challenges, 60.9% had positive results, with 8 patients lost to follow-up. The performances of the ready-to-use and comparator APTs were as follows: sensitivity, 76% (95% CI, 59.2% to 92.7%) versus 44% (95% CI, 24.5% to 63.4%; P = .02); specificity, 93.8% (95% CI, 81.9% to 100%) versus 93.8% (95% CI, 81.9% to 100%); positive predictive value, 95% (95% CI, 85.4% to 100%; 1 false-positive result) versus 91.7% (95% CI, 76% to 100%; 1 false-positive result); negative predictive value, 71.4% (95% CI, 52% to 90.7%; 6 false-negative results) versus 51.7% (95% CI, 33.5% to 69.8%; 14 false-negative results); and test accuracy, 82.9% (95% CI, 71.3% to 94.5%) versus 63.4% (95% CI, 48.6% to 78.1%; P = .05). CONCLUSION: The ready-to-use APT exhibited a good sensitivity and specificity, with no side effects.

Child↗