Comparison of standard and modified SPT method

BACKGROUND: The aim of our study was to compare clinical significance and economical factors of commonly used standard skin prick tests (SPT) method with new, modified and more handy way of performing SPT. METHODS: Twenty-one subjects [with an average age of 23 years (SD +/- 2.72)] with known sensitivity to examined allergen extracts were tested with histamine, negative control solution and standard allergen extracts (Allergopharma, Reinbeck, Germany). SPT were applied to the volar surface of randomly assigned forearm with two methods: standard technique using lancet needle to prick the epidermis under small drop of extract and tested method using lancet needle which was dipped in extract before prick. In this method all extracts were placed in marked, small, plastic chambers. RESULTS: Mean wheal to histamine was 5.49 (standard method) and 5.01 (modified method). There was no statistical difference between the standard and modified method for size of wheal to histamine (P = 0.654) and to allergen extracts (n = 36, P = 0.824, Wilcoxon test). Economical analysis revealed that examined SPT technique is cheaper than standard method. CONCLUSION: Examined method may be considered to be an alternative for performing SPT as it is safe, cheaper and more convenient than standard technique. Summary statement: Comparison of standard and modified SPT method revealed the new method to be more economical.     

The 3 mm skin prick test (SPT) threshold criterion is not reliable for Tyrophagus putrescentiae: the re-evaluation of SPT criterion to dust mites

Background: The mean wheal diameter ≥ 3 mm is the usual criterion for positive skin prick test (SPT) reaction to dust mites. The study assessed the accuracy of this SPT criterion with respect to specific IgE values of above 0.35 kU_A/l (+ sIgE). Methods: Specific IgE (ImmunoCAP, Pharmacia AB Diagnostics, Uppsala, Sweden) and standard SPT to Dermatophagoides pteronyssinus (DP) and farinae (DF), Lepidoglyphus destructor (LD) and Tyrophagus putrescentiae (TP) (ALK, Hørsholm, Denmark) were performed in a random sample of 457 subjects, of whom 273 men (mean age 35.3 ± 11.0 years) and 184 women (mean age 37.9 ± 9.5 years). Statistical analysis was performed using the chi‐square test, regression analysis and discriminant analysis. Results: When the mean wheal diameter of ≥ 3 mm was considered positive (+ SPT), the correlation between + SPT and + sIgE was 0.47 for DP (P < 0.001), 0.43 for DF (P = 0.004), 0.35 for LD (P = 0.03) and 0.37 for TP (P = 0.014). Regarding + sIgE, this SPT criterion has a specificity of 92.2% for DP, 82.3% for DF, 80.8% for LD and 70.1% for TP. When the value 4.5 mm was taken as the threshold for the positive SPT reaction to TP, specificity increased significantly from 70.1% to 86.4% (χ² = 32.04, P < 0.001). Conclusions: The 3 mm SPT threshold criterion is not reliable in evaluating sensitization to TP due to an insufficient specificity of the allergen extract to this mite. It is advisable either to re‐evaluate the TP allergen extract or change the threshold criterion for positive SPT reaction to TP.     

The allergenic properties of fresh and preserved Hevea brasiliensis latex protein preparations

The allergenic properties of the proteins of two lyophilized fractions of fresh natural rubber latex obtained by ultracentrifugation, the C serum and the sedimented bottom or lutoid fraction, have been compared with those of the serum proteins of two samples of high ammonia latex (HAL), [A]HALS obtained from HAL stored for more than 1 year, and [M]HALS derived from HAL stored for 6 weeks before ultracentrifugation and lyophilization. The most potent source of allergenic polypeptides both for skin prick testing of latex-sensitive patients and for immunoblots of their blood serum was the lutoid fraction of fresh latex. Skin prick tests and immunoblots of patients' sera showed that the allergenicity of the ammoniated latex decreased during storage. Skin prick tests using fractions of [A]HALS, C serum and lutoid proteins obtained after passage through a Sephacryl S300 column showed that the components of all three preparations which eluted in the largest volumes were almost equally effective in provoking the largest number of responses. Immunoblots of the sera of 43 latex-sensitive individuals showed that the majority (66%) of sera of the adult allergic patients reacted with a polypeptide of 19 kD. No characteristic pattern of binding latex polypeptides could be recognized in the sera from patients who were also asthmatic or from those who had had an anaphylactic response to latex proteins.     

The prevalence of latex allergy in children seen in a university hospital allergy clinic

Natural rubber latex allergy is responsible for a wide spectrum of clinical symptoms, ranging from rhinoconjunctivitis to severe anaphylaxis, in both adults and children. An association between allergy to latex and allergy to various fruits has been reported. This study investigated the prevalence and clinical significance of latex sensitization in children seen in a university hospital allergy clinic. A total of 453 consecutive children were screened in a 7-month period. A detailed clinical history with particular attention to the past surgical history and the eventual presence of latex- or food-induced allergic symptoms was obtained. Skin prick tests (SPT) for the more important inhalant allergens and foods were performed on all children. In patients with positive latex SPT, latex challenge and additional SPT for some fresh foods (avocado, pineapple, apricot, grape, banana, pear, apple, orange, almond, and chestnut) were also performed. RAST for the same food antigens, as well as patch test with latex and a standard battery of contact allergens, was also done. Of 326 atopic children, 10 (3%) presented positive skin test to latex, but only five (1.5%) also had a positive clinical history to latex exposure. Latex challenge was positive in 3/9 positive-latex-SPT children. None of the nonatopic children had positive skin test to latex or symptoms to latex exposure. A history of previous surgery was found in 5/10 positive-latex-SPT children, in 63/316 negative-latex-SPT atopic children (P<0.05), and in 23/127 nonatopic children. RAST to latex was positive in 5/10 positive-latex-SPT children. Associated fruit-specific IgE (SPT and/or RAST) were found in all latex-symptomatic children and in 2/5 latex-asymptomatic children. Apple, kiwi, and chestnut were the most common SPT-positive foods. Only one patient with clinical allergy to latex and positive skin tests to fruits had a history of clinical symptoms after ingestion of kiwi and orange. The natural history of the positive-latex-SPT children without clinical reactions to latex exposure and the clinical significance of the association of latex and fruit sensitivity require further studies.     

Percutaneous reactivity to natural rubber latex proteins persists in health-care workers following avoidance of natural rubber latex

BACKGROUND: Long-term avoidance of natural rubber latex [Hevea brasiliensis (Hev b)] is currently recommended for health-care workers (HCWs) with established natural rubber latex (NRL) allergy. Percutaneous sensitivity to eight Hev b NRL allergens was evaluated in HCWs in 2000. To date, no studies have evaluated the longitudinal effects of NRL avoidance on percutaneous sensitivity to NRL allergens. OBJECTIVE: The aims of this study were to evaluate changes in percutaneous reactivity to non-ammoniated latex (NAL) and NRL allergens in HCWs 5 years after a recommendation to avoid NRL and to evaluate factors that predict the persistence of in vivo sensitivity to NAL and NRL allergens. METHODS: Skin prick testing was performed with NAL, seven NRL allergens (Hev b 1, 2, 3, 4, 6.01, 7.01, and 13), and recombinant Hev b 5 (rHev b 5) in 34 HCWs who were initially evaluated in 2000 for occupationally related NRL allergy. Serial 10-fold dilutions of NAL and NRL allergens were employed in skin testing. Sera from the HCWs were assayed for latex and enhanced latex (rHev b 5-enriched allergosorbent)-specific IgE antibodies using the ImmunoCAP assay. RESULTS: The prevalence of work-related symptoms significantly decreased between 2000 and 2005 with avoidance of NRL (P<0.05). A >/=100-fold reduction in percutaneous sensitivity to Hev b 2 and Hev b 7 was less likely in those with prior history of systemic reactions to NRL (P=0.0053), reported history of reaction to cross-reactive foods (P=0.014), continued local reactions to NRL gloves (P<0.0001), or high NRL glove exposure since the initial study (P=0.0075). The diagnostic sensitivity and specificity of the latex-specific IgE serology was 54% and 87.5%, respectively, in comparison with NAL skin tests. The addition of rHev b 5 to the ImmunoCAP (enhanced latex) allergosorbent altered the diagnostic sensitivity and specificity of the ImmunoCAP to 77% and 75%, respectively. CONCLUSION: While symptoms may resolve quickly with NRL avoidance therapy, detectable IgE indicating continued sensitization remains beyond 5 years, and thus continued avoidance of NRL should be recommended.     

Immunoglobulin E reactivity to latex antigens in the sera of patients from Finland and the United States

Background: Patients with latex sensitivity and latex antigens from the United States and Finland, two countries where allergic reactions to latex have been widely reported, were evaluated to determine the spectrum of immune responses.Methods: Sera from 27 patients from Finland and 18 from the United States with latex allergy and control sera from nonsensitive individuals were studied for latex-specific IgE antibodies. Four antigen preparations were used: two extracted from gloves and one each extracted from rubber tree sap from Malaysia and India. All 45 patients had skin prick test results that were positive to latex antigens, and all sera were evaluated by enzyme-linked immunosorbent assay (ELISA) with the various antigens.Results: There were considerable differences in the reactivity of patient sera with the different antigens. Only 50% of the sera from patients with latex allergy from Finland demonstrated significant levels of IgE to latex as determined by enzyme-linked immunosorbent assay. These patients showed more reactivity with rubber tree sap antigens than with glove antigens. However, 72% of the patients from the United States demonstrated antibodies to latex, and no marked differences were noted between the antigen extracts.Conclusions: The results indicate that reagents such as rubber tree sap, which contain multiple clinically significant antigenic components, should be included in evaluation of latex allergy and that differences in patient populations may result in serologic variances.     

Standardization of the Prick Test

The different needles and methods used in the prick test give rise to disparate results. This has significance when carrying out multi-centre studies and when using the technique in the standardization of allergenic extracts. With test reliability as our objective, prick tests were carried out on 30 subjects: 10 patients sensitive to Dermatophagoides pteronyssinus received a glycerine extract of known allergenic potency, 10 healthy individuals 2.5% codeine phosphate in a glycerine solution, and another 10, histamine 1/1000. The total prick tests per individual was 27 with each of the needles employed (Allergy Pricker, the Morrow-Brown needle and Insulin needle in accordance with Pepy's procedure). The tests were carried out systematically by three different testers, and the total number of prick tests performed was 810. With the Allergy Pricker, no differences were observed among results obtained by the same tester, nor when the results of the three testers were compared. With the Morrow-Brown needle, the results varied in the same person and from one tester to another, and on many occasions the test was negative. With the Pepys method, no falsely negative results were obtained, but there was considerable variation in the size of the wheal. The variation coefficient is 41% with the Allergy Pricker, and 115% and 64% with the Morrow-Brown and Pepys method, respectively. In conclusion, the results obtained clearly indicate that the highest degree of reproducibility is obtained with the Allergy Pricker.     

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.     

Immediate contact allergy from hydrolyzed wheat in a cosmetic cream

Immediate contact allergy to cosmetics seems to be rare, since only a few case reports on it have been published. We report on a case of IgE-mediated allergic contact urticaria caused by hydrolyzed wheat in a body cream.     

Natural rubber latex allergy in children: a follow-up study.

BACKGROUND: Natural rubber latex (NRL) allergy occurs frequently in children with spina bifida and other children with disorders requiring multiple operations. Also atopic children who have not undergone surgery can be sensitized to NRL, but the outcome of these children has not been studied. OBJECTIVE: To study how NRL-allergic children manage at home and whether their skin prick test (SPT) reactivity, latex RAST or IgE antibody levels to NRL allergens change during the follow-up. METHODS: Twenty-four NRL-allergic children who had not undergone surgery and eight children with histories of multiple operations were followed up for a mean of 2.8 years. Clinical symptoms were recorded and all children were re-examined with SPT, latex RAST and ELISA for IgE antibodies to prohevein (Hev b 6.01), hevein (Hev b 6.02) and rubber elongation factor (REF, Hev b 1). RESULTS: Nineteen of the 24 NRL-allergic children (79%) who had not undergone surgery had occasionally contacts to balloons and other NRL products at home, and 10 of them experienced symptoms ranging from contact urticaria to systemic reactions. Three of the eight NRL-allergic children with a history of multiple operations had contacts to rubber balloons without any symptoms, and five children underwent 1-8 uneventful operations in a latex-free environment. SPT reactivity to NRL allergens, latex-RAST or IgE antibody levels to prohevein or hevein did not change in either group of NRL-allergic children during the follow-up. CONCLUSIONS: Occurrence of clinical symptoms and no decrease in SPT reactivity or IgE levels to NRL allergens in the course of the present follow-up study imply that more attention should be paid to the protection of NRL-allergic children from rubber contacts in the home environment.     

Latex allergy diagnosis: in vivo and in vitro standardization of a natural rubber latex extract

For the diagnosis of IgE-mediated (immediate) hypersensitivity to natural rubber latex (NRL), skin prick testing with extracts of latex gloves has been widely used, but such extracts are difficult to standardize. The present study aimed to produce on an industrial scale an NRL extract from freshly collected NRL and to evaluate, calibrate, and standardize the extract by both in vivo and in vitro testing. The source material, latex of the rubber tree, Hevea brasiliensis (clone RRIM 600), was frozen immediately after collection in Malaysia and shipped in dry ice to Stallergènes SA, France. Protein and allergen profiles were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), immunoblotting, isoelectric focusing (IEF), crossed immunoelectrophoresis (CIE), and crossed radioimmunoelectrophoresis (CRIE). Allergen quantification was effected by RAST inhibition. The capacity of the preparation to elicit immediate hypersensitivity reactions in vivo was measured by skin prick testing in 46 latex-allergic patients and 76 nonallergic control subjects. SDS-PAGE and immunoblot profiles of the extract and an NRL standard (E8) provided by the US Food and Drug Administration were almost identical, disclosing several distinct IgE-binding proteins with apparent molecular weights of 14, 20, 27, 30, and 45 kDa, conforming to reported molecular weights of several significant NRL allergens. An arbitrary index of reactivity (IR) of 100 was assigned to the extract at 1:200 dilution (w/v), having a protein content of 22 μg/ml. Skin prick testing of latex-allergic patients and controls using the extract at 100 IR revealed 93% sensitivity, 100% specificity, 100% negative predictive value, and 96% positive predictive value. In conclusion, a skin prick test reagent for diagnosis of type I NRL allergy was successfully standardized. The reagent was demonstrated to contain most, if not all, of the currently known clinically significant NRL allergens, and it showed high sensitivity and specificity.     

Quantitative skin prick testing

Dose-response curves of histamine- and allergen-induced wheal areas were evaluated in seven normals (defined as negative skin prick test (SPT) to inhalant allergens and no clinical signs of allergy), seven latent allergics (positive SPT without allergic symptoms), and 20 manifest allergics (positive SPT and allergic symptoms). Three concentrations of histamine HCl (1, 10 and 100 mg/ml) and three 10-fold concentrations of nine inhalant allergens (birch, timothy, mugwort, horse, dog, cat, house dust mite, Cladosporium and Alternaria) in concentrations 1,000 10,000 and 100,000 BU/ml were used and linear regression was performed on the skin reactions. Only tests with an SD% less than 40%, a log slope greater than 0.1, and a correlation coefficient greater than 0.95 were accepted. In normals a significantly higher concentration of histamine was needed to elicit a wheal reaction of 2 mm2 (end-point) compared with allergics. Likewise, normals had a significantly higher slope i.e. steeper dose-response curve of histamine than manifest allergics. The slope of the allergen-induced wheal area was significantly higher than the histamine slope. No relation between corresponding slope of histamine and allergens was found (Rho = 0.15). The skin sensitivity equivalent to histamine calculated as the allergen concentration eliciting a wheal equal to histamine showed a median increase of 5-6 fold in allergen concentration by a 10-fold increase of histamine concentration. The highest correlation between the wheal area of a single allergen concentration and the skin sensitivity was found for allergen concentration 100,000 BU.(ABSTRACT TRUNCATED AT 250 WORDS)     

A prospective study of cancer incidence in a cohort examined for allergy

In order to assess the association between atopy and cancer risk, a cohort of 6593 skin-prick-tested patients was established. Among atopic subjects, no overall increased cancer risk was found, but the incidence of both breast cancer (standardized incidence ratio (SIR) 2.50, 95% CI 1.01–5.16) and malignant lymphomas (SIR 4.40, 95% CI 1.20–11.3) was significantly enhanced. Atopic subjects with asthma showed a decreased overall cancer risk (SIR 0.73, 95%, CI 0.27–1.60), as compared with the other asthmatic subjects (SIR 1.46, 95% CI 1.03–2.04). The cancer risk for subjects with rhinitis was near unity (SIR 1.11), irrespective of whether the subjects were atopic or not. An almost significant risk increase for cancer was observed among subjects with urticaria (SIR 1.70, 95% CI 0.99–2.80). Our results support neither the original hypothesis of an overall cancer protective effect of atopy, nor that of an opposite effect; rather, they strengthen the view that the association between atopic diseases and cancer is complex.     

Measurement of natural rubber latex allergen levels in medical gloves by allergen-specific IgE-ELISA inhibition, RAST inhibition, and skin prick test

Exposure to natural rubber latex (NRL) medical gloves poses risks to patients sensitized to NRL and to users of protective gloves. Previous studies have shown that extractable allergen levels of the gloves vary widely. Since most of the available laboratory methods of NRL allergen measurement lack adequate validation, we wanted to evaluate the performance of a recently developed competitive IgE-ELISA-inhibition method in relation to the skin prick test (SPT) and RAST inhibition, as well as to extractable protein quantification and an immunochemical latex antigen assay (LEAP). Twenty samples of surgical (n = l4) and examination gloves (n=6), covering >90% of medical gloves marketed in Finland in 1994–5. were collected by the Finnish National Research and Development Centre for Welfare and Health, coded, extracted, and analyzed by the five methods. The IgE-ELISA inhibition correlated highly significantly with SPT (r=0.94) and RAST inhibition (r=0.96). Likewise, ELISA inhibition and RAST inhibition showed highly significant correlation (P=0.96, P<0.0001 in all three instances). Protein quantification by a modified Lowry method also correlated highly significantly with SPT (r=0.80). RAST inhibition (r=0.82), and ELISA inhibition (r=0.81. P100 AU/ml) in seven of the 20 glove brands analyzed. In conclusion, the results of a novel IgE-ELISA-inhibition method of measuring NRL allergen levels in medical gloves correlated highly significantly with those of SPT TTie ELISA method was found to be sensitive, reproducible, technically easy, inexpensive, and suitable for the analysis of large numbers of NRL products. The results of extensive market surveys in 1994 and 1995, communicated to the medical community in Finland, appear to have had a clear effect in moving glove purchasing policies toward the use of low-allergen gloves.