Diagnosis and Immunotherapy of Mould Allergy

To determine reproducibility and the optimal way of expressing skin sensitivity, simultaneous skin prick tests (SPT) and intradermal tests (ICT) were performed on 25 mould-allergic patients. The patients had a well-documented history of allergy to Cladosporium and Alternaria and were tested with partially purified standardized extracts of these two mould species. Skin prick tests were carried out on the volar side of the forearm and intradermal tests on the backs of the patients. The skin tests were performed as titration using quadruplicate determinations of 10-fold allergen dilutions. The area of the skin reactions measured by planimetry were plotted in a log-log system as a function of the allergen concentration. The reproducibility (SD/mean area X 100%) of the ICTs was significantly higher than that of the SPTs (17% versus 29%). A very low reproducibility was found with wheal areas less than 5 mm2. The dose response curve of the SPT wheal area was steeper than that obtained with ICT, both concerning ICT wheal and flare. Increasing the allergen concentration with a factor 10 resulted in a doubling of the wheal area in SPT, in contrast to a factor 1.7 using ICT. The coefficient of correlation using linear regression on the dose response curve was always higher than 0.9 with SPT and ICT wheal, but significantly lower with ICT flare. Skin sensitivity was estimated as end-point and histamine equivalent reaction. No significant correlation between SPT and ICT end-point titration was found contrary to the histamine equivalent reaction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diagnosis and Immunotherapy of Mould Allergy

Thirty-three adult asthmatic patients suspected of mould allergy were investigated by in vivo and in vitro tests in order to establish a specific diagnosis of asthma caused by the mould species Cladosporium. The patients were evaluated by daily symptom scores in the peak Cladosporium season, bronchial provocation test (BPT), skin prick test (SPT), RAST, histamine release from basophil granulocytes (HIST), and crossed radioimmunoelectrophoresis (CRIE), and the results were scored as negative (score 0), equivocal (score 1) or positive (score 2). Based on daily symptom scores and the result of BPT the patients were classified as being manifest allergic (asthma) to Cladosporium (positive allergy), inconclusive or negative. Positive allergy was defined as asthma symptoms oscillating with the spore concentration and a BPT score 2 (positive at allergen concentration less than 10,000 BU). Negative allergy was defined as no asthma symptoms and a negative BPT (score 0) and inconclusive in the case of symptoms and BPT sum of score 1-3. According to the classification a final diagnosis (positive or negative) could be established in 85% of the patients. "False positive" tests were found: for BPT in 27%, SPT 18%, RAST 0%, HIST 18%, and CRIE 0%. The corresponding figures for "false negative" were: BPT 0%, SPT 0%, RAST 27%, HIST 18%, and CRIE 23%. The relative risk of being allergic in spite of a negative test result was 0% for BPT and SPT, and 25-30% with RAST, HIST, and CRIE. In the case of positive test the risk was 90-100%. Excluding BPT, SPT was found to be the optimal single test to predict/rule out clinical allergy. A stepwise combination of positive SPT and positive RAST was found exclusively in patients clinically evaluated as positive, and does not call for an additional BPT. Using a potent allergenic extract a negative SPT excluded clinically important allergy. The primary conclusion of the study, however, is that the final diagnosis of Cladosporium asthma could not be based on a positive BPT alone (due to "false positive"), but only on a combination of clinical symptoms during the spore season and a positive BPT.     

Diagnosis and Immunotherapy of Mould Allergy

A placebo-controlled, double-blind study of immunotherapy with the mould species Cladosporium was performed in 22 adult asthmatics. The diagnosis of Cladosporium allergy was based on a combination of bronchial provocation test and daily symptom score in the Cladosporium season. An aqueous preparation of a potent, biologically standardized and purified extract was used in a clustered dose-increase regimen. The clinical efficacy was evaluated by a combination of symptoms (asthma score + peak flow) and consumption of antiasthmatic medication. The mean changes in symptoms and medication consumption over a 10-week registration period (peak Cladosporium season) in 1982 after 5-7 months of immunotherapy were compared with the corresponding 1981 pretreatment 10-week period. A significant (P = 0.03) difference in terms of "improved", "unchanged" and "deteriorated" patients in favour of Cladosporium treatment was found. Approximately 80% in the Cladosporium group showed improved/unchanged symptoms contrary to 30% of the placebo treated. Side effects were observed frequently but only in the Cladosporium-treated. About 70% experienced a large local reaction and 100% had episodes of asthma during dose-increase phase. Only a few severe systemic reactions occurred. Based on the clinical efficacy of the treatment we consider immunotherapy with Cladosporium feasible for highly specialized clinics.     

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.     

Immunotherapy with partially purified and standardized tree pollen extracts

Patients allergic to tree pollen entered a 3-year course of immunotherapy (1980-83) with either birch pollen extracts alone (n = 26) or patient-tailored extracts of birch, alder and hazel pollen (n = 27). The clinical and immunological results of this study are published elsewhere. This paper contains an evaluation of skin prick test and nasal provocation test results. There were no significant differences between the two treatment groups concerning these two parameters. In both groups the allergen-specific sensitivity in the skin showed seasonal variations but a significant decrease. During the years of treatment there was also a significant decrease in the specific sensitivity of the nasal mucosa. With the present demands for purification and standardization of allergen extracts it is of practical and economic interest to know that tree pollen-allergic patients showing positive reactions to birch, alder and hazel extracts can be effectively treated using birch pollen extract alone.     

Skin test concentrations for systemically administered drugs – an ENDA/EAACI Drug Allergy Interest Group position paper

Skin tests are of paramount importance for the evaluation of drug hypersensitivity reactions. Drug skin tests are often not carried out because of lack of concise information on specific test concentrations. The diagnosis of drug allergy is often based on history alone, which is an unreliable indicator of true hypersensitivity.To promote and standardize reproducible skin testing with safe and nonirritant drug concentrations in the clinical practice, the European Network and European Academy of Allergy and Clinical Immunology (EAACI) Interest Group on Drug Allergy has performed a literature search on skin test drug concentration in MEDLINE and EMBASE, reviewed and evaluated the literature in five languages using the GRADE system for quality of evidence and strength of recommendation. Where the literature is poor, we have taken into consideration the collective experience of the group.We recommend drug concentration for skin testing aiming to achieve a specificity of at least 95%. It has been possible to recommend specific drug concentration for betalactam antibiotics, perioperative drugs, heparins, platinum salts and radiocontrast media. For many other drugs, there is insufficient evidence to recommend appropriate drug concentration. There is urgent need for multicentre studies designed to establish and validate drug skin test concentration using standard protocols. For most drugs, sensitivity of skin testing is higher in immediate hypersensitivity compared to nonimmediate hypersensitivity.     

Allergy to Pollen from Different Deciduous Trees in Sweden

92 adult patients with springtime allergy were investigated with skin tests, provocation tests and the RAST. Allergen extracts from 12 different deciduous trees were used.
Positive reactions, often of high intensity, were most often found with birch, alder, bog-myrtle, beech and hazel allergens whereas oak, aspen, linden, elm, sallow, maple and poplar allergens more often gave negative or only weak positive test results. Cross sensitizations were found between botanically related as well as between less related species of the trees. Almost all patients with a clinically relevant tree pollen allergy had positive provocation tests with birch pollen. No patient had positive reactions to all the 12 allergens included in the study. 68% had positive provocation tests with the combination birch, alder and hazel.
It is concluded that for diagnostic screening purposes it is sufficient to use birch pollen allergen. If the majority of relevant tree pollens are to be included in a diagnostic or therapeutic programme in Western Sweden it should contain birch, alder, hazel, beech and bog-myrtle allergens.     

Frequency and significance of immediate contact reactions to peanut in peanut-sensitive children

BACKGROUND: Parents of atopic children frequently report, and are alarmed by, contact reactions to foods. Some schools restrict foods due to concerns regarding possible systemic reactions following contact in allergic children. OBJECTIVE: We aimed to determine the frequency with which peanut-sensitive children exhibited contact sensitivity to peanut butter and to assess the significance of such reactions. METHODS: One gram of peanut butter was applied directly to the skin of 281 children who were skin prick test (SPT) positive to peanut (immediate skin application food test; I-SAFT). The test was considered positive if one or more weals were present when the patch was removed after 15 min. A subset of children then underwent an open-label oral challenge with graded amounts of peanut protein. RESULTS: During 3515 clinic visits, 330 I-SAFT tests for peanut contact sensitivity were performed; 136 (41%) were positive. The mean SPT diameter was 10 mm in the I-SAFT-positive children and 8.5 mm in the I-SAFT-negative children (t-test, P<0.0001). No child had a systemic reaction following topical application of peanut butter. Eighty-four children had 85 oral challenges after blinded, placebo-controlled I-SAFT testing. Challenge was positive in 26/32 of those with a positive I-SAFT and negative in only 6/32. Challenge was also positive in 26/53 but negative in 27/53 of those with a negative I-SAFT (sensitivity 50%, specificity 82%, chi2, P=0.003). CONCLUSION: A minority of children sensitized to peanut (positive SPT) develop localized urticaria from prolonged skin contact with peanut butter. No tested subjects, including ones with systemic reactions upon oral challenge, developed a systemic reaction to prolonged skin exposure to peanut. Therefore, systemic reactions resulting from this mode of contact with peanut butter appear highly unlikely.     

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.     

Allergen skin test reactivity in an unselected Danish population

The aim of this study was to assess the distribution of allergen skin test reactivity in an unselected Danish population. A total of 793 subjects, aged 15–69 years, were invited, and 599 (75.5%) attended. The skin prick test was performed with standardized allergen extracts of high potency. Skin reactivity occurred in 28.4% of the subjects. The frequency of skin reactivity to the specific allergens ranged from 1.5% ( Cladosporium ) to 12.5% ( Dermatophagoides pteronyssinus ), and the frequencies of skin reactivity to the allergen groups (pollen, animal dander, house-dust mites, and molds) were 17.6%, 8.7%, 14.0%, and 3.2%, respectively. Young women appeared to reflect the average skin reactivity. When compared with young women, skin reactivity to animal dander was more probable in young men (odds ratio (OR) value = 2.6; 95% confidence interval (CI) of odds ratio value = 1.1–6.1). Current smokers were less likely than nonsmokers to be skin-reactive to pollen (OR = 0.4; 95%, CI = 0.3–0.7). In conclusion, allergen skin test reactivity was common, and was related to sex, age, smoking history, and probably genetic predisposition.     

Venom Immunotherapy in Hymenoptera Sting Allergy

42 patients with confirmed hypersensitivity to honey bee (HBV) and/or yellow jacket (YJV) were treated with the respective venoms (7 with HBV, 5 with YjV and 30 with both venoms). Treatment tolerance, skin tests (ST), specific IgE- and specific IgG-antibodies were monitored before, after 3, 6, 12, 24 and 36 months. 21 patients had ash and 21 a conventional treatment schedule. Maintenance dose was 100 μg. Adverse effects occurred as large local (8 patients), slight systemic (12 patients) and moderate to severe systemic reactions (4 patients). Of 24 re-exposed patients 17 had no reaction at all, six a markedly decreased and one an unchanged reaction. After 3 years of treatment ST became negative in nine of 31 patients on HBV and in seven of 26 patients on YJV. RAST became negative in three of 30 patients on HBV and 17 of 29 patients on YJV treatment. Both ST and RAST became negative in five HBV- and 10 YJV-treated patients. Loss of venom hypersensitivity according to diagnostic tests may correspond to actual desensitization and enable discontinuation of immunotherapy.     

Oral Immunotherapy of Children with Rhinoconjunctivitis due to Birch Pollen Allergy A Double Blind Study

Thirty children with rhinoconjunctivitis due to birch pollinosis were treated in a double blind manner for 10 months with enteric-coated capsules containing either a birch pollen preparation (n = 14) with doses up to 1.4 X 10(6) biologic units per day or placebo (n = 16). Compared with the placebo group the actively treated children had less symptoms during the birch pollen season after 3 months of therapy (P = 0.035). Skin prick reactions decreased significantly more in the active group than in the placebo group after 10 months (P = 0.01). Conjunctival sensitivity was lower in the active group than in the placebo group after 3 months of treatment (P = 0.01) but not after 10 months. Compared with the placebo group the treated children more often increased their levels of IgG (P = 0.007) and pre-seasonal IgE (P = 0.001) against birch. There was a seasonal increase of IgE antibody level against birch in the placebo but not in the treatment group (P less than 0.001). None of the treated children developed asthma, compared with five of the untreated children. No general reactions occurred and few side effects were seen during the treatment period. We conclude that in children with birch pollinosis oral immunotherapy with high doses of a biologically potent preparation in enteric-coated capsules is effective, easy to perform, economic and safe.     

Diagnosis of Alternaria alternata sensitization with natural and recombinant Alt a 1 allergens

BACKGROUND: Diagnosis of Alternaria alternata sensitization is hampered by the variability and complexity of fungal extracts, and thus simplification of the diagnostic procedures with purified allergens should be pursued. OBJECTIVE: We sought to compare A alternata extract and purified natural Alt a 1 (nAlt a 1) and recombinant Alt a 1 (rAlt a 1) allergens for their diagnostic value. METHODS: Forty-two patients allergic to A alternata , 10 atopic patients with negative skin prick test responses to A alternata extract, and 10 healthy subjects were investigated. Skin prick tests and determination of specific IgE levels were performed with nAlt a 1 and 2 different types of rAlt a 1: rbAlt a 1, expressed in Escherichia coli , and ryAlt a 1, expressed in the yeast Yarrowia lipolytica . RESULTS: Prevalence for Alt a 1, Alt a 2, and Alt a 11 by IgE dot-blot testing was 98%, 0%, and 15%, respectively, and therefore Alt a 1 was used as a marker for A alternata sensitization. Immunoblotting and inhibition analysis showed no IgE-binding differences between nAlt a 1 and rAlt a 1. The whole group of patients with allergy to A alternata had positive skin test reactions to purified allergens at 100 microg/mL, whereas no false-positive reactions were detected. Natural or ryAlt a 1 elicited a similar response in skin tests compared with A alternata extract, although a reduced reactivity was observed with rbAlt a 1. Specific IgE levels to nAlt a 1 or rAlt a 1 showed significant correlation and similar sensitivity and specificity. CONCLUSIONS: Alt a 1, either in its natural or recombinant form, is sufficient for a reliable diagnosis of A alternata sensitization and induces skin prick reactivity comparable with that produced by A alternata extract.