Quantitative Skin Prick Tests Research Articles

Correlation of skin prick testing to environmental allergens

BackgroundTo diagnose and adequately treat allergies, identification of sensitizing allergens is crucial. Skin prick or serum immunoglobulin E testing determines sensitization to potential allergens. Consensus varies regarding degree of cross-reactivity between aeroallergens. ObjectiveTo quantify correlations between aeroallergen skin prick test results. MethodsA total of 11,832 patients’ quantitative skin prick test results and basic characteristics were obtained from a tertiary academic center’s electronic medical record and deidentified. Data were analyzed using Spearman’s rank correlation coefficients to detect nonlinear associations between wheal sizes of skin prick test results. ResultsThe highest correlation among grasses was 0.903 (fescue and red top). Of note, 13 more grass pairs had correlation more than 0.8, and 19 had correlation between 0.7 and 0.8. The Northern grass comparative results are from a satellite clinic that tested more grasses than the main clinic, in which only Kentucky blue and Bermuda were tested (correlation 0.768; n = 9348). Highest correlation among weeds was 0.74 (lambs quarter and pigweed). In addition, 6 more weed pairs had correlation more than 0.7. Highest correlation among trees was 0.724 (palm and alder) and 6 more tree pairs had correlation more than 0.7. Highest correlation among molds was 0.711 (Helminthosporium and Epicoccum). Dust mite correlation between Dermatophagoides farinae and Dermatophagoides pteronyssinus was 0.848 (n = 10,022). ConclusionThis study confirmed the expected high degrees of correlation not only between skin prick test results of related environmental allergens but also between less closely related Northern grasses and Bermuda grass. This has implications for simplification of testing and immunotherapy protocols in the future.

Toll-like receptor gene polymorphisms are associated with allergic rhinitis: a case control study

BackgroundThe Toll-like receptor proteins are important in host defense and initiation of the innate and adaptive immune responses. A number of studies have identified associations between genetic variation in the Toll-like receptor genes and allergic disorders such as asthma and allergic rhinitis. The present study aim to search for genetic variation associated with allergic rhinitis in the Toll-like receptor genes.MethodsA first association analysis genotyped 73 SNPs in 182 cases and 378 controls from a Swedish population. Based on these results an additional 24 SNPs were analyzed in one Swedish population with 352 cases and 709 controls and one Chinese population with 948 cases and 580 controls.ResultsThe first association analysis identified 4 allergic rhinitis-associated SNPs in the TLR7-TLR8 gene region. Subsequent analysis of 24 SNPs from this region identified 7 and 5 significant SNPs from the Swedish and Chinese populations, respectively. The corresponding risk-associated haplotypes are significant after Bonferroni correction and are the most common haplotypes in both populations. The associations are primarily detected in females in the Swedish population, whereas it is seen in males in the Chinese population. Further independent support for the involvement of this region in allergic rhinitis was obtained from quantitative skin prick test data generated in both populations.ConclusionsHaplotypes in the TLR7-TLR8 gene region were associated with allergic rhinitis in one Swedish and one Chinese population. Since this region has earlier been associated with asthma and allergic rhinitis in a Danish linkage study this speaks strongly in favour of this region being truly involved in the development of this disease.

Occupational immediate‐type asthma and rhinitis due to rhodium salts

Whereas platinum salts are well known occupational allergens, rhodium salts have not been identified as inhalative sensitizing substances. A 27-year-old atopic operator of an electroplating plant developed work-related shortness of breath and runny nose with sneezing after exposure to rhodium salts. Quantitative skin prick tests (SPT) and bronchial challenge tests with a dosimeter protocol were performed with quadrupling doses of the sodium chloride salts of rhodium (Na(3)RhCl(6)) and platinum (Na(2)PtCl(6)). The patient showed positive SPT reactions and positive bronchial immediate-type reactions with rhodium and platinum salts. Sensitivity to rhodium salt was much higher than to platinum salt; the molar concentrations differed by a factor of 256 in SPT and a factor of 16 in bronchial challenges. Rhodium salts should be considered as occupational immediate-type allergens.

Asthma bronchiale bei Allergie gegen Vorratsmilben

In a multicenter study (7 participating centres) 132 patients with bronchial asthma (grade II or III) and sensitization to storage mites (SM) and/or house dust mites (HSM) were screened and asked to undergo further allergological evaluation. 90 patients agreed. In addition to routine skin prick tests and RAST, quantitative skin prick tests (QSPT) and bronchial provocation tests (BPT) were also performed with the suspected mite allergens. The results were correlated with aspects of the domestic and working environments. Furthermore we questioned whether the outcome of BPT could be predicted from the results of the routine skin tests/RAST and QSPT respectively. Out of a total of 145 BPTs there were 79 positive results with SM and/or HSM. Three patients were mono-allergic to SM. The correlation with the domestic environment was unremarkable. Correlation with occupational factors revealed a strong predominance of farmers (42 of 90) and suggested the same for professions involved in work in dust-laden environments like bakers (5 of 90) and workers in wood- and paper industry (7 of 90). This also means, that SM-allergy occurs in persons not occupationally exposed to dust. A prediction as to the allergological relevance of SM-allergen was not possible from viewing the routine skin prick test however positive RAST data showed a significant correlation with positive BPT to SM Lepidoglyphus. Similarly it was possible to draw an inference from QSPT as to the relevant allergy. With a positive QSPT to the SM Lepidoglyphus destructor a positive result with a BPT was highly probable. Due to small numbers it is not possible to make a similar statement for the other SM species (Acarus and Tyrophagus).

Do skin prick and conjunctival provocation tests predict symptom severity in seasonal allergic rhinoconjunctivitis?

In the investigation of seasonal allergic rhinoconjunctivitis (SAR), quantitative skin and conjunctival allergen challenge tests are used to measure individual allergen sensitivity. These tests are reproducible and relate well to prevalence but their relationship to symptom severity is less well established. We wished to determine if quantitative skin prick tests (QSPT) and conjunctival provocation tests (CPTs) using a single grass pollen allergen extract are reproducible and predict symptom severity in SAR. We retrospectively analysed data from 91 participants in a previously published randomized placebo controlled study of low dosage allergen immunotherapy who were randomized to receive placebo treatment. We examined the relationship between pre-seasonal QSPT, CPT and SAR symptoms. We found a high level of reproducibility when repeated measures were compared for both the QSPT (P < 0.001) and the CPT (P < 0.001) and moderate correlation (0.49) between the standard skin prick test (SPT) and the QSPT (P < 0.001). We found weak negative correlation (-0.27) between the QSPT and the CPT (P < 0.001). We found no correlation between seasonal symptom, use of rescue medication or quality of life (QOL) scores and pre-seasonal QSPT or CPT. Conclusion In the assessment of seasonal rhinoconjunctivitis, quantitative skin and conjunctival allergen challenge tests are strongly reproducible, although there is no correlation between these tests and seasonal symptom, use of rescue medication or QOL scores.

Specific Immunotherapy with Standardized Latex Extract versus Placebo in Latex-Allergic Patients

Background: Allergy to natural rubber latex proteins continues to be an important medical problem among health care professionals, but also in multioperated children. Clinical manifestations range from urticaria to angioedema, rhinoconjunctivitis, bronchial asthma and anaphylactic shock. Methods: The aim of this study was to investigate the efficacy and safety of a 12-month latex-specific immunotherapy in sensitized patients, most often health care workers. Twenty-three patients with latex rhinoconjunctivitis (20 of whom also had asthma) were included in this randomized, double-blind, placebo-controlled trial (11 in the active group, 12 in the placebo group). Treatment efficacy was assessed by means of symptom and medication scores. Conjunctival provocation tests and quantitative skin prick tests were also performed. Results: The clinical index (derived by combining changes from baseline of six efficacy variables during the treatment period) did not differ significantly between treatment groups. Change from baseline of rhinitis, conjunctivitis, skin symptoms, asthma symptoms, medication score and cutaneous reactivity were not significantly different between the two groups. A nonsignificant difference in conjunctival reactivity was observed in favor of the active group (p = 0.09). Systemic reactions were much higher in the specific immunotherapy than in the placebo group. Conclusions: The present study failed to show a significant improvement of symptoms and medication scores, probably because of the low level of symptoms at baseline and the low maintenance dose of therapy, even if allergen-specific conjunctival reactivity decreased in the active group. Moreover, the incidence of systemic reactions was very high in the active group.

DIFFERENCES IN THE SENSITISATION TO RAGWEED POLLEN AND OCCURRENCE OF LATE SUMMER ALLERGIC SYMPTOMS BETWEEN NATIVE AND IMMIGRANT WORKERS OF THE NUCLEAR POWER PLANT OF HUNGARY

Regular medical screening including allergic symptoms of workers of the Nuclear Power Plant in Paks, Hungary, offered a unique opportunity to study the influence of the environmental factors on the development of allergy. The city Paks has been one the areas of the country most heavily exposed to ragweed pollen allergens. The occurrence and extent of sensitisation assessed by skin prick test to common allergens and prevalence of seasonal and perennial allergic symptoms were compared among 880 workers (695 immigrants, 185 natives) with self-reported allergic symptoms. The percentage of sensitised people against common allergens (ragweed, grass, D. pteronyssinus) was almost the same in the natives and immigrants. When, however, the strength of sensitivity to ragweed was determined by quantitative skin prick test and specific IgE determination, significantly (P<0.0001) more immigrants (69%) than native workers (20%) exhibited high sensitivity to ragweed and the titres of specific IgE antibodies was also significantly (p<0.0001) higher in the former group. Similar differences were found in the occurrence and type of allergic symptoms. Seasonal symptoms alone occurred in 69% and 38% of the immigrant and native workers (p<0.0001). This difference was mostly due to those with late summer symptoms characteristic to ragweed allergy. These symptoms occurred in 57% of the immigrant workers, much more frequently (p<0.0001) than in the natives (18%). Our findings indicate that the length of exposure to an inhalant allergen does affect the extent of sensitisation to ragweed allergen and markedly influences the clinical symptoms that develop in the ragweed allergic patients upon allergen exposure. It can be assumed that the natives who have been living with ragweed pollen for a long time (that is were exposed to natural immunotherapy), developed a natural tolerance to it.

Standardization of Alternaria alternata: Extraction and quantification of Alt a 1 by using an mAb-based 2-site binding assay

Background: Alternaria alternata is recognized as an important cause of allergic disease. As with other molds, the extracts of A alternata used for diagnosis and therapy are highly heterogeneous, and there is a need for improved standardization. The major allergen Alt a 1 is well characterized and has been produced as a recombinant protein, but very few data are available on the Alt a 1 content in extracts. Objective: An assay for the quantification of Alt a 1 was developed and used for monitoring batch-to-batch consistency of A alternata extracts, and the correlation between skin prick test responses and Alt a 1 concentrations was studied. Methods: A 2-site binding assay based on an Alt a 1–specific mAb was developed and used for the quantification of Alt a 1 in allergen extracts. Quantitative skin prick tests were performed on 16 A alternata –sensitive patients and correlated with the Alt a 1 concentration. Results: The Alt a 1–specific mAb was found to be suitable for affinity purification, as well as for a 2-site binding quantification assay. In allergen extracts the Alt a 1 content was estimated as 2% to 4.7% of total protein. Quantitative skin prick tests showed an Alt a 1 concentration-dependent response. Conclusion: Quantification of Alt a 1 in A alternata extracts reflects their batch-to-batch consistency. Skin prick test responses to a standardized A alternata extract correlate with the Alt a 1 contents. An extract containing 3.7 μg/mL Alt a 1 caused a response equal to that of a 1% histamine dihydrochloride solution. (J Allergy Clin Immunol 1999;103:128-35.)

Quantitative skin prick and bronchial provocation tests with platinum salt.

Occupational asthma due to platinum salts is a frequent disease in platinum refineries. The diagnosis is based upon a history of work related symptoms and a positive skin prick test with platinum salts. Bronchial provocation tests have not been performed in epidemiological studies because the skin test is believed to be highly specific and sensitive. As no reliable data about this issue currently exist, this study assesses the use of skin prick and bronchial provocation tests with methacholine and platinum salt in platinum refinery workers. Twenty seven of 35 workers, who were referred to our clinic with work related symptoms and nine control subjects with bronchial hyperreactivity underwent a skin prick test and bronchial provocation with methacholine and platinum salt. For skin prick and bronchial provocation tests with platinum salt a 10(-2)-10(-8) mol/l hexachloroplatinic acid solution, in 10-fold dilutions was used. Four of the 27 subjects and all controls showed neither a bronchial reaction nor a skin reaction. Twenty three subjects were considered allergic to platinum salt; 22 of these showed a fall of 50% or more in specific airway conductance after inhalation of the platinum salt solution. Four workers experienced a positive bronchial reaction despite a negative skin prick test. No correlation of responsiveness to methacholine with responsiveness to platinum salt was found, but the skin prick test correlated with the bronchial reaction to platinum salt (rs = 0.50, p less than 0.023, n = 22). One dual reaction was seen in bronchial provocation tests. Side effects of both skin tests and bronchial provocation tests with platinum salt were rare and were not encountered in workers without a skin reaction to platinum salt. It is concluded that bronchial provocation tests with platinum salts should be performed on workers with work related symptoms but negative skin tests with platinum salts.

Changes in skin reactivity, specific IgE and IgG levels after one year of immunotherapy in olive pollinosis

Changes in specific skin reactivity, specific IgE and specific IgG after immunotherapy (IT) were investigated in olive pollinosis. Thirty patients, receiving IT with commercial extracts, were studied in comparison with a control group of seven patients, receiving only drug therapy. Skin reactivity, IgE and IgG were assessed before starting IT and 1 year later. Definite changes in the three considered parameters occurred in patients given IT with Olea europaea extracts; no variation was observed in the control group. The specific skin reactivity, evaluated by means of quantitative skin prick tests, significantly decreased (Skin Index geometrical mean from 2.73 to 0.88, P less than 0.001); the specific IgE, measured by RAST, were surprisingly decreased (from 7.76 to 4.74 PRU/ml, P less than 0.001); the specific IgG, measured by ELISA, in basic conditions were detectable only in nine patients of 30, while, after IT, they were found in almost all patients with a remarkable increase (from 5.48 to 266.89 AU/ml, P less than 0.001). No correlation was found among the changes in the considered parameters, suggesting that, at least in olive pollinosis, specific skin reactivity, specific IgE and specific IgG are three variables depending on IT but reciprocally independent.

Changes in skin reactivity, specific IgE and IgG levels after one year of immunotherapy in olive pollinosis

Changes in specific skin reactivity, specific IgE and specific IgG after immunotherapy (IT) were investigated in olive pollinosis. Thirty patients, receiving IT with commercial extracts, were studied in comparison with a control group of seven patients, receiving only drug therapy. Skin reactivity, IgE and IgG were assessed before starting IT and 1 year later. Definite changes in the three considered parameters occurred in patients given IT with Olea europaea extracts; no variation was observed in the control group. The specific skin reactivity, evaluated by means of quantitative skin prick tests, significantly decreased (Skin Index geometrical mean from 2.73 to 0.88, P &lt; 0.001); the specific IgE, measured by RAST, were surprisingly decreased (from 7.76 to 4.74 PRU/ml, P &lt; 0.001); the specific IgG, measured by ELISA, in basic conditions were detectable only in nine patients of 30, while, after IT, they were found in almost all patients with a remarkable increase (from 5.48 to 266.89 AU/ml, P &lt; 0.001). No correlation was found among the changes in the considered parameters, suggesting that, at least in olive pollinosis, specific skin reactivity, specific IgE and specific IgG are three variables depending on IT but reciprocally independent.

Nasal challenge with pollen grains, skin-prick tests and specific IgE in patients with grass pollen allergy.

Nasal challenges with pollen grains are as close as possible to natural pollen exposure, but they are not well documented in grass pollen allergy. Forty-four grass pollen allergic patients and ten non-allergic volunteers were tested by means of nasal challenge, quantitative skin-prick tests with a standardized orchard grass pollen extract and serum-specific IgE. Nasal challenges were performed with lactose and increasing concentrations of orchard grass pollen grains (15-3645 grains, three-fold increase). The test was considered to be positive when a symptom score over 5 was obtained, since this score had been previously correlated with the release of PGD2 in nasal secretions. All control subjects and 3/44 patients had a negative challenge. The number of orchard pollen grains required to elicit a positive challenge was 332 +/- 440 (range: 15-1215 grains) and the distribution was Gaussian. This number is higher than expected according to pollen calendars performed during the season, but owing to the priming effect of the nasal mucosa by allergens it is compatible to natural exposure. The correlation between nasal provocation tests and skin-prick test end-points was significant (P less than 0.005, Spearman rank test). Conversely there was no correlation between nasal challenge or skin-prick test end-point and serum-specific IgE.

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.

Glycoprotein allergens in pollen of timothy. III. Immunochemical and biological properties of a basic glycoprotein.

Crossed immunoelectrophoresis (CIE) and tandem CIE indicated that a basic glycoprotein allergen isolated from pollen of timothy is immunochemically identical to the allergen formerly denoted as antigen 30. The glycoprotein gave one band in SDS-PAGE and agarose isoelectric focusing. After transfer to nitrocellulose by electroblotting or by capillary blotting, the allergen specifically bound IgE from persons allergic to timothy pollen. The single allergen inhibited about 15% of the IgE binding to radioallergosorbent test discs of whole timothy pollen extract. Sera from patients investigated also contained detectable amounts of IgG towards the allergen. In quantitative skin prick tests, the mean activity of 2 micrograms/ml purified allergen in 7 patients was equivalent to that of a timothy pollen extract containing 10,000 BU/ml (assayed relatively to histamine in skin prick test). The ability of the allergen to form a precipitate in rocket immunoelectrophoresis was lost when it was heated to 80 degrees C or incubated with 4 M guanidine hydrochloride.

Diagnosis and Immunotherapy of Mould Allergy

Twenty-four adult asthmatics with autumnal asthma and positive bronchial provocation test to the mould species Cladosporium were evaluated by daily symptoms scores during 11 weeks in the peak mould spore season. A significant association with fluctuation in Cladosporium spore count was found regarding the relative weekly symptom score (mean of subjective asthma and peak flow scores), relative use of antiasthmatic medication and the combined (total) score (mean of symptom and medication scores). The median weekly symptom, medication, and total scores were positively correlated to Cladosporium spore count, but only significantly so in the medication score. Eighteen patients were allergic to both Cladosporium and Alternaria, but asthma symptoms were not associated to Alternaria spore counts; on the contrary, a negative correlation indicated that Alternaria only played a minor role in eliciting asthma. Neither mugwort nor house dust mites seemed to be of importance. The results of diagnostic tests (bronchial provocation test, quantitative skin prick test, RAST and histamine release) were correlated to the mean absolute symptom score of the spore season. The highest correlation to asthma score, peak flow score, medication score, and the combined score was found with the bronchial provocation test. The data indicate that autumnal asthma, to a high degree, is elicited by Cladosporium spores, and further, that the specific allergic diagnosis can only be established by a combination of positive diagnostic tests and careful recording of symptoms elicited by the causative allergen.

Reproducibility of skin sensitivity using a quantitative skin prick test.

The reproducibility of repeated quantitative skin prick test titrations was evaluated in seven asthmatic patients tested 2-4 times within 6 weeks. The skin sensitivity was estimated as endpoint titration and histamine equivalent reaction using both 1 and 10 mg/ml histamine dihydrochloride. The histamine equivalent reaction had a significantly higher reproducibility compared to endpoint titration, with a coefficient of variation less than 10% for histamine 10 mg/ml. Further, using this histamine concentration, the deviation in repeated testing was for practical purposes less than 0.5 log step. The same constancy in skin sensitivity was found in one patient tested 3 times and then retested another 3 times 6 months later by a different tester. The results indicate that the quantitative skin prick test and histamine-estimated skin sensitivity have a clinical application in the assessment of pharmacologically or immunotherapy-induced changes in the releasability of skin mast cells.

Immunochemical and biological characterization of a mugwort (Artemisia vulgaris) pollen extract.

A reference extract of mugwort pollen (Artemisia vulgaris) was characterized by crossed immunoelectrophoresis (CIE), crossed radio immunoelectrophoresis (CRIE) and quantitative skin prick test (QSPT). CIE revealed that the extract contained at least 42 distinct antigens of which 24 migrated towards the anode and 18 towards the cathode at pH 8.6. A CRIE analysis of the crude mugwort pollen extract, performed with sera from 29 mugwort-allergic patients, showed that 10 antigens may be considered allergens; one was classified as a major allergen, five as intermediate allergens, and four as minor allergens. The QSPT performed on the same 29 allergic patients established that 17.4 micrograms lyophilised reference mugwort pollen extract per ml had a biological potency of 1 HEP (histamine equivalent by prick test).