Proposed guidelines for quantitative skin prick test procedure to determine the biological activity of allergenic extracts using parallel line assay

Guidelines are proposed for determining the potency of allergenic extracts in relation to a reference extract using parallel line bio-assay. The practical performance, limitations, and advantages of skin prick test are discussed.     

Prediction of challenge test results by flour-specific IgE and skin prick test in symptomatic bakers

Background:  Wheat and rye flours are among the most important allergens causing occupational asthma. Usually, the diagnosis of baker's asthma is based on inhalation challenge tests with flours.
Aims of the study:  To evaluate the relevance of flour-specific serum immunoglobulin E (IgE) and skin prick test (SPT) in the diagnosis of baker's asthma and to define flour-specific IgE concentrations and wheal sizes that allow a prediction of the outcome of challenge testing.
Methods:  Bronchial and nasal challenge tests with wheat (rye) flour were performed in 71 (95) symptomatic bakers. Determinations of flour-specific IgE as well as SPTs were performed in all subjects. Analyses included the calculation of sensitivity, specificity, positive (PPV) and negative predictive values (NPV) at different IgE concentrations and different wheal sizes, and receiver-operating characteristics (ROC) plots with the challenge result as gold standard.
Results:  Thirty-seven bakers were positive in the challenge with wheat flour, while 63 were positive with rye flour. Depending on the flour-specific IgE concentrations (wheal size), PPV was 74–100% (74–100%) for wheat and 82–100% (91–100%) for rye flour, respectively. The minimal cut-off values with a PPV of 100% were 2.32 kU/l (5.0 mm) for wheat flour and 9.64 kU/l (4.5 mm) for rye flour. The shapes of the ROC plots were similar for wheat and rye flour.
Conclusion:  High concentrations of flour-specific IgE and clear SPT results in symptomatic bakers are good predictors for a positive challenge test. Challenge tests with flours may be avoided in strongly sensitized bakers.     

Occupational asthma caused by soybean hull: a workplace equivalent to epidemic asthma

A case showing that soya hull exposure at work causes occupational asthma without flour-related bronchoconstriction.     

Estimation of skin prick test reactions with a scanning program

We evaluated a new method of computer-based scanning of skin prick test wheal areas. To test the calibration of the program, we scanned five constructed circles of exactly defined areas between 5 and 255 mm². One of these circles was scanned in different degrees of contrast (modes), the middle mode being used in the other experiments. We also investigated the inter-and intraoperator variation. Finally, results obtained by measuring diameters of wheals and by the new method of area determination were compared for 82 histamine and 75 egg wheals. The areas found agreed well with the real areas (P<0.01) (mean 97.4–100.8%), except for the smallest wheal (5 mm^') (NS). Areas obtained in the "middle position" closely resembled the real area. The intraoperator coefficient of variation (C.,) was 1.4% (0.3–4.3), the day-to-day C.V. was 1.9% (0.2–5.3), and the interoperator C.V. was 2.3% (0.7–5.7), with a higher C.V. for small areas. Histamine and egg wheals were significantly larger with the diameter method (126% and 129%, respectively) than with the area method. The difference between the methods was most pronounced for small wheal areas. The C.V. of the scanning method was significantly lower than that of the diameter method. The new program is precise and is recommended for registration of skin test reactions in scientific trials. Although the scanner works well and has high precision, the major problem in skin testing seems still to be the reproducibility of the skin test technique employed.     

Reproducibility of the skin prick test

Reproducibility of the skin prick method of testing for allergy was studied in 20 subjects examined by four nurses. Hypodermic needles were used for pricking and the test panel included a histamine control, a diluent control, and nine allergens. The reproducibility of the method was best when the size of the weal reaction caused by an allergen was expressed as the geometric area of the weal. When the weal reaction was expressed as the ratio of the weal reaction caused by an allergen to that caused by histamine, the reproducibility of the method was decreased considerably. When the ratios were further classified into three class ratings, reproducibility was very low. The reduction in reproducibility was due to the low reproducibility of histamine reactions. According to these results, at least in epidemiological studies the weal reactions should be expressed as geometric areas. In clinical practice it might also be preferable to express prick test results as the diameters of the weals without adjusting them by histamine reactions.     

Evaluation of the prevalence of skin prick test positivity to Alternaria and Cladosporium in patients with suspected respiratory allergy

D'Amato G, Chatzigeorgiou G, Corsico R, Gioulekas D, Jäger L, Jäger S, Kontou-Fili K, Kouridakis S, Liccardi G, Meriggi A, Palma-Carlos A, Palma-Carlos ML, Pagan Aleman A, Parmiani S, Puccinelli R Russo M, Spieksma FThM, Torricelli R, Wüthrich B. Evaluation of the prevalence of skin prick test positivity to Alternaria and Cladosporium in patients with suspected respiratory allergy. A European multicenter study promoted by the Subcommittee on Aerobiology and Environmental Aspects of Inhalant Allergens of the European Academy of Allergology and Clinical Immunology.
This trial was undertaken to study, in several geographically spread European countries, the prevalence of skin prick test (SPT) positivity to Alternaria (A) and Cladosporium (C) in subjects with nasal and/or bronchial symptoms of suspected allergic cause. Each patient completed an anamnestic questionnaire and underwent SPT with a panel of common inhalant allergens and also A and C supplied by three different laboratories, to allow for manufacturer bias. Specific scrum IgE determination was carried out only in subjects with SPT positivity to A and/or C with an immunoassay system. In nine European allergology centers, a total of 877 subjects was enrolled in the trial; 83 of them showed SPT positivity to A and/or C; only nine patients showed monosensitization to A , and none to C The highest percentage of positive subjects was found in Spain (20%); the lowest in Portugal (3%). In the other seven centers, the variation was 7–10%. The age range of mold-positive subjects was 5–60 years. Rhinitis was by far the most common symptom, whether associated or not with asthma and/or conjunctivitis.     

Reproducibility of skin prick test results in epidemiologic studies: a comparison of two devices

The reproducibility of skin prick tests under field conditions is essential for comparing prevalences between centers in epidemiologic multicenter studies. This study aimed to evaluate and compare the reproducibility of two widely used skin prick test devices: the Multi-Test and the ALK lancet. The subjects were 28 children, aged 6–14 years, with known sensitivities Dermatophagoides pteronyssinus (D. pter). Both devices were applied to each subject on two occasions, 1 week apart, by different, randomly assigned fieldworkers, using histamine, negative control, and the D. pter. allergen extract. For all three tested solutions, mean wheal sizes were larger for the Multi-Test than for the ALK lancet. The coefficient of variation for histamine was 21.8% for the Multi-Test and 17.3% for the ALK lancet. The coefficients of variation for the allergen D. pter. amounted to 47.4% for the Multi-Test and to 24.6% for the ALK lancet. The percentage of concordant test results was 92.6% for the Multi-Test and 100.0% for the ALK lancet for a cutoff point of wheal size equal to or greater than 1 mm. The results of this study suggest that the single ALK lancet performs slightly better than the Multi-Test device with respect to reproducibility under conditions of epidemiologic field studies.     

Reproducibility of skin prick testing with allergen extracts from different manufacturers

Allergen extracts for skin prick testing (SPT) are available from several manufacturers. Although these solutions are specified according to well-defined internal company standards, there is no generally accepted overall standardization. To assess the comparability of skin prick test solutions of various manufacturers, we compared extracts of nine different allergens from four companies by SPT in 29 children sensitive to one or more of the allergens, in a double blind fashion. RAST (Pharmacia) and EAST (Kallestad) were determined in simultaneous blood samples. Allergen extracts were also examined by rocket immunoelectrophoresis for their content of major allergens. Skin reactions, assessed by mean diameter of wheals, to identical allergen extracts varied significantly between the four vendors (P less than 0.05-0.001). Correlation between RAST and EAST was good for all allergens except birch pollen and mugwort. Content of the major allergen in corresponding extracts varied significantly between the different companies (less than 1%-2000%). These data underline the need for international reference extracts as intracompany standardization of test solutions alone is not enough to yield general reproducibility of skin prick test results.     

Comparison of wheat and rye flour skin prick test solutions for diagnosis of baker's asthma

BACKGROUND: Skin prick tests (SPTs) play an important role in the diagnosis of baker's asthma and in the investigation of sensitization frequencies in field studies. It was the aim of our study to compare different SPT solutions for wheat and rye flour sensitization and to assess the validity of test results. METHODS: Skin prick tests with wheat and rye flour were performed in parallel with extracts from different companies and compared with the results of bronchial challenge tests with both flours (69 rye flour and 51 wheat flour challenge tests). Additionally, specific immunoglobulin E (sIgE) to wheat and rye flour were tested. SPT solutions were analysed for protein content and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). RESULTS: Skin prick test solutions for diagnosis of wheat and rye flour sensitization from three companies differed in protein concentrations and composition with the consequence of widely differing SPT results. Sensitivity of SPTs in comparison with allergen-specific bronchial challenge as a gold standard was between 40 and 67%, specificity was between 86 and 100%, the positive predictive value (PPV) ranged from 81 to 100% and the negative predictive value (NPV) from 44 to 70%. These numbers were only marginally affected by using a combination of challenge test result and sIgE value as a more specific gold standard. CONCLUSION: Improvement and standardization of SPT extracts for wheat and rye flour is highly recommended.     

Practical guide to skin prick tests in allergy to aeroallergens

This pocket guide is the result of a consensus reached between members of the Global Allergy and Asthma European Network (GA(2) LEN) and Allergic Rhinitis and its Impact on Asthma (ARIA). The aim of the current pocket guide is to offer a comprehensive set of recommendations on the use of skin prick tests in allergic rhinitis-conjunctivitis and asthma in daily practice. This pocket guide is meant to give simple answers to the most frequent questions raised by practitioners in Europe, including 'practicing allergists', general practitioners and any other physicians with special interest in the management of allergic diseases. It is not a long or detailed scientific review of the topic. However, the recommendations in this pocket guide were compiled following an in-depth review of existing guidelines and publications, including the 1993 European Academy of Allergy and Clinical Immunology position paper, the 2001 ARIA document and the ARIA update 2008 (prepared in collaboration with GA(2) LEN). The recommendations cover skin test methodology and interpretation, allergen extracts to be used, as well as indications in a variety of settings including paediatrics and developing countries.     

上海地区过敏患者皮肤点刺试验临床分析

为了解上海地区过敏性疾病的主要过敏原,探讨过敏患者过敏原的分布情况及变化规律,收集1 407例过敏患者的皮肤点刺试验资料。结果显示,阳性率位于前五位的过敏原依次为粉尘螨64.89%、屋尘螨58.56%、热带螨40.58%、德国小蠊21.32%和美洲大蠊20.90%。以尘螨(粉尘螨、屋尘螨和热带螨)的阳性率最高。过敏患者对尘螨(粉尘螨、屋尘螨和热带螨)、蟑螂(德国小蠊和美洲大蠊)、狗毛屑、猫毛屑及虾过敏与年龄有关。呼吸道过敏性疾病患者对尘螨、蟑螂、狗毛屑、猫毛屑和花粉过敏的阳性率均明显高于过敏性皮肤病患者(P<0.05)。提示上海地区以尘螨为主要过敏原,对尘螨、蟑螂、狗毛屑、猫毛屑及虾过敏与患者年龄有关,但与性别无关。呼吸道过敏性疾病患者较过敏性皮肤病患者有更高的阳性率。     

Skin prick test can identify eczematous infants at risk of asthma and allergic rhinitis

BACKGROUND: Assessment of allergic sensitization is not routinely performed in infants and young children with eczema. OBJECTIVE: To determine whether infants who have atopic eczema (with sensitization) are at a greater risk of developing asthma and allergic rhinitis (AR) than those with non-atopic eczema (without concurrent sensitization). METHODS: The presence of eczema was prospectively documented until 2 years of age in a birth cohort of 620 infants with a family history of atopic disease. Sensitization status was determined by skin prick tests (SPTs) at 6, 12, and 24 months using six common allergens. Interviews were conducted at 6 and 7 years to determine the presence of asthma and AR. RESULTS: Within the first 2 years of life, 28.7% of the 443 children who could be classified had atopic eczema: 20.5% had non-atopic eczema, 19.0% were asymptomatic but sensitized and 31.8% were asymptomatic and not sensitized. When compared with children with non-atopic eczema in the first 2 years of life, children with atopic eczema had a substantially greater risk of asthma [odds ratio (OR)=3.52, 95% confidence interval=1.88-6.59] and AR (OR=2.91, 1.48-5.71). The increased risk of asthma was even greater if the infant had a large SPT (OR=4.61, 2.34-9.09) indicative of food allergy. There was no strong evidence that children with non-atopic eczema had an increased risk of asthma or AR compared with asymptomatic children. CONCLUSION: In children with eczema within the first 2 years of life, SPT can provide valuable information on the risk of childhood asthma and AR.     

Prevalence of positive skin prick tests, allergic asthma, and rhinoconjunctivitis in teenagers in northern Sweden

The prevalence of positive skin prick tests (SPT) for common allergens and symptoms of allergic rhinoconjunctivitis or asthma was investigated in Umeå in northern Sweden in 1987. Skin prick tests with 10 allergens common in Sweden and a questionnaire were used to examine 1112 teenagers. All subjects with a positive skin prick test or symptoms were interviewed, and they were further investigated by a serum specific IgE test, a ventilatory lung function test, and a physical examination. At least one skin prick test was positive in 43% of the subjects. Ninety-three percent had at least one positive skin prick test to one of the three most common allergens: cat, timothy grass, and birch. The prevalence of current allergic rhinoconjunctivitis was 17%, current allergic asthma 2.8%, and current asthma (both allergic and nonallergic) 6.8%. Multiple logistic regression analysis showed that the most important risk factors for current asthma were sex (being a girl) and atopy. Heredity of asthma or rhinoconjunctivitis and being born in the winter (October-March) also increased the risk. In atopic subjects, having a mother who smoked and heredity of asthma increased the risk. For allergic rhinoconjunctivitis, heredity increased the risk of getting rhinoconjunctivitis.     

Comparison of wheat and rye flour solutions for skin prick testing: a multi‐centre study (Stad 1)

Background Skin prick testing (SPT) is the basic method for diagnosing IgE‐mediated allergies. However, skin reactivity is related to the quality of allergen extracts, which are often poorly defined for occupational allergens. Objective To compare wheat and rye flour SPT solutions from different producers. Materials and methods Standardized SPTs were performed in seven allergy centres with wheat and rye flour solutions from four producers in 125 symptomatic bakers. Optimal cut‐off levels for weal sizes were assessed with the Youden Index. Comparisons between SPT results of different solutions were made with flour‐specific IgE (sIgE) as the gold standard. Sensitivities, specificities, positive and negative predictive values, and test efficiencies were calculated and compared with McNemar and χ²‐tests. The influence of the choice of the gold standard (sIgE or challenge) test was examined for 95 subjects. Additionally, SPT solutions were analysed for protein and antigen content. Results The optimal cut‐off level for all SPT solutions was a weal size of 1.5 mm. While differences between wheat and rye flours were small, differences between producers were important. Variability of sensitivities (0.31–0.96), negative predictive values (0.42–0.91), and test efficiencies (0.54–0.90) were higher than variations of specificities (0.74–1.00) and positive predictive values (0.88–1.00). Similar results were obtained when using challenge test results as the gold standard. Variability could be explained by the different antigen contents of the SPT solutions. Conclusion There is a wide variability of SPT solutions for wheat and rye flour from different producers, mainly with respect to sensitivities, negative predictive values, and test efficiencies. Improvement and standardization of SPT solutions used for the diagnosis of baker's asthma are highly recommended.