Allergy screening including a comparison of prick test results with allergen-coated lancets (Phazet®) and liquid extracts

During an allergy screening of families with a history of allergy in one or more subjects, skin prick tests (SPT) were performed in duplicate in 314 adults. The tests were performed with a new type of lancet with a 0.9 mm long point, loaded either with allergen (Phazet) or used together with standardized extracts (10,000 and 100,000 BU/ml). Wheals obtained with both methods were compared, and related to total IgE concentrations and history. A wheal area of 3 and 7 mm2 was used as cut-off limit. Results with Phazet were close to those with Pharmalgen 100,000 BU/ml. With both methods precision was good for allergens, but less for Phazet histamine than for the corresponding wet test. SPT results obtained with Phazet and 100,000 BU/ml correlated better with history than the results with 10,000 BU/ml. Using a wheal size of 7 mm2 as cut-off limit the efficiency for five tested allergens was 91%. "False positive" tests, possibly indicating an unobserved or latent type of allergy, were found more often with higher serum IgE concentrations. The safety of SPT was confirmed and Phazet was well accepted by nurses and tested subjects.     

Bronchial allergen challenge in subjects with low levels of allergic sensitization to indoor allergens

BACKGROUND: Low skin reactivity to common inhalant allergens is frequently found in asymptomatic individuals as well as in patients with respiratory complaints. However, most studies on bronchial allergen challenge concern patients with high levels of allergic sensitization. The present study was directed to bronchial reactions after allergen challenge in subjects with low skin reactivity to Dermatophagoides pteronyssinus or cat dander. METHODS: Titrated intracutaneous skin tests, skin prick tests, specific IgE assays, histamine release on washed leukocytes, and bronchial histamine and allergen-challenge tests were performed in 20 subjects with an intracutaneous skin test threshold for cat dander (Felis domesticus) or D. pteronyssinus above 0.1 BU/ml (mean wheal diameter in skin prick test with 10000 BU/ml: 4.4mm). Ten of the 20 patients had specific IgE below the detection limit in at least one of the three IgE assays which were done. Fifteen patients had a specific IgE level below 2 kU/I in all three tests. As a positive control group, the same parameters were studied in seven moderately sensitized patients with an intracutaneous skin test threshold below 0.1 BU/ml (mean wheal diameter with 10000 BU/ml: 7.2mm). RESULTS: The 20 subjects with low levels of allergic sensitization had an early decrease in FEV1 of 8.6% (P<0.01) and a mean late decrease of 6.3% (P<0.05). There was a trend for decrease in PC20 histamine 24h after allergen challenge (-0.4 doubling doses, P=0.09). CONCLUSIONS: In this group of subjects with low levels of allergic sensitization, a statistically significant early and late decrease in FEV1 was found. However, the decrease in lung function was small and unnoticed by most patients. The increase in nonspecific bronchial hyperresponsiveness after bronchial allergen challenge did not reach statistical significance in the study group. The results indicate that allergen exposure in patients with low levels of allergic sensitization may lead to airways changes in the absence of acute symptoms.     

Optimization of skin testing

Standardized extracts of Phleum pratensis (grass) and Dermatophagoides pteronyssinus (house-dust mite) were used as test allergens for multiple regression in order to determine optimum concentrations and cutoff values with regard to diagnostic capacity and safety. If a RAST value of class 1 or more was taken as an indication of sensitization, it was found that the optimum concentrations for the detection of sensitization are in the range 10–100 BU/ml and 1500–10000 BU/ml for intracutaneous tests (ICT) and skin prick tests (SPT), respectively. The skin test results were expressed as histamine ratios. Using allergen concentrations of 30 and 3000 BU/ml, we found cutoff values of 0.87 and 0.53 and predictive values of 87.1% and 19.1% for ICT and SPT, respectively. The maximum wheal size (mean wheal size + 2 SD) to be expected in 95% of the population was 26.6 mm (ICT) and 10.9 mm (SPT), sizes regarded as safe by most clinicians. In conclusion, by using this method with a limited number of patients, one can probably improve the diagnostic precision and safety of the skin test. In the second part of this study, these hypotheses were prospectively tested in a multicenter study.     

Skin Prick Testing and the Use of Histamine References

The skin prick test is a fundamental test in biological allergen standardization and in evaluation of changes in skin sensitivity due to treatment. The allergen concentration eliciting a wheal equal to that produced by histamine 1 mg/ml is generally accepted as the skin sensitivity. Using a standardized quantitative skin prick test, 25 mould allergic patients were tested with quadruplicate determinations of five 10-fold allergen concentrations of highly purified and standardized extracts. Histamine 1 and 10 mg/ml were used as positive references. The 10-fold increase of histamine resulted in a doubling of the histamine reaction and increased the mean wheal diameter from 4 to 7 mm. The correlation between skin sensitivity estimated by histamine 1 and 10 mg/ml is significant, but with a dissociation between the two ways of estimating the sensitivity of 0.25 log step in the low sensitivity range and 1.8 log step in the high sensitivity range (the difference at median sensitivity is 1 log step). No correlation was found between histamine- and allergen-induced wheal area increase, and the discrepancy might be caused by a difference in the endogenous histamine release and/or difference in the number of histamine receptors at different degrees of sensitivity. With the use of median values it is possible to perform biological standardization with histamine 10 mg/ml and interpolate to histamine 1 mg/ml. However, the response in individual patients varies, and because of the small wheal area and the low reproducibility with histamine 1 mg/ml we recommend the exchange of histamine 1 mg/ml to histamine 10 mg/ml as an international positive reference.     

Results of biological standardization with standardized allergen preparations

The aim of biological standardization (BS) is to equilibrate the activity (potency) of allergen extracts from different source materials. This was done by performing skin prick tests (SPT) on patients who were sensitive to one of the following 10 allergens: Birch, alder, hazel, timothy, rye grass, velvet grass, cultivated rye, mugwort, D. farinae and Cladosporium herbarum. Patient sensitivity varied within a range of three to four powers of ten for each allergen investigated. The weal size in each patient corresponding to that elicited by histamine 1 mg/ml was calculated using the model log (mean weal diameter) = a + b log (concentration). The correlation coefficients of the regression lines of the allergen dose response relationship were found to be greater than 0.85 in most cases. The median slope for all extracts was 0.24. The slope for Cladosporium was significantly steeper than that for pollens. The amount of material in microgram dry weight (d.w./ml) equal to 1000 biological units/ml (BU/ml) varied within a factor of three between species for all tested purified allergen preparations but Cladosporium. For Cladosporium, about 30 times more material was needed than for D. farinae. When using crude rather than purified material, it was necessary to use five to ten times more to elicit a reaction corresponding to 1000 BU/ml, but the difference was significant only for Cladosporium. The narrow range of allergen concentrations used by us as well as other investigators does not assure positive skin prick test results in all patients with clinical symptoms due to the allergen in question. Skin prick testing should therefore be done over a wide range of concentrations to improve the methods for BS.     

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)     

Reliability of skin prick tests during terfenadine treatment in adults with pollen rhinitis

The variation in skin prick test (SPT) results was evaluated clinically during terfenadine treatment in 39 adult patients with pollen rhinitis. A change in the perceived state of the patient as regards sensitization to a specific pollen allergen or atopic constitution was judged to be clinically important. A randomized, double-blind, crossover design was used, comprising 2 weeks on terfenadine 120 mg once a day and 2 weeks on placebo. SPT for two pollen allergens and histamine (10mg/ml) were evaluated at the start of the study and at the end of each period. When SPT was used as a discovery test and liberal definitions were applied, predictive values for a positive test were 100%. 1-Sensitivity ranged between 10 and 54% with substantially lower values when a histamine wheal reaction was noted. The inhibitory effect of terfenadine was detectable 2 weeks after withdrawal as a reduction in the median of the mean diameter for the histamine-induced wheal response of 1 mm (0–1.5). The data implied that a positive SPT is reliable when liberal definitions are adopted for sensitization and atopy; a negative SPT is presumably reliable when the measurement artifact is considered and the wheal reaction to histamine is detectable.     

Influence of skin prick test criteria on estimation of prevalence and incidence of allergic sensitization in children

In a prospective cohort study on atopy in childhood, three skin prick tests (SPT) were performed in 1135 primary schoolchildren over a 2–year period. We studied the development of average sizes of allergen wheals in reactive children and of average sizes of histamine wheals in all children, and we investigated the influence of choice of SPT criterion on the prevalence and incidence of sensitization. A year-to-year increase of average allergen wheal sizes as well as of average histamine wheal sizes was observed. These increases seemed to be related to the natural growth of the children. Furthermore, an observer bias effect of the person who did the pricking on average wheal sizes was found. There were considerable differences in estimations of prevalences and incidences depending on the definition of SPT criterion. Estimations using a criterion based solely on the allergen wheal size were affected by variation of allergen wheal sizes caused by growth and observer effects. The ratio criterion was not influenced by observer effects, nor did it seem to be affected by aging effects. In conclusion, our data suggest that the ratio criterion, which relates the size of the allergen wheal to the size of the histamine wheal, is the most appropriate SPT criterion because it is not affected by growth of allergen wheals in childhood and it appears to compensate for possible observer bias.     

Time of onset of action of acrivastine in the skin of pollen-allergic subjects

The purpose of this study was to assess the time of onset of action of acrivastine in suppressing the wheal response to histamine (10 mg/ml) and allergen (10000 and 100000 BU/ml) in the skin prick test. Ten subjects with a well-documented allergy to pollen received single doses of 8 mg of acrivastine and placebo according to a randomized, double-blind, placebo-controlled, crossover treatment design. Duplicate skin prick tests were performed 0, 15, 20, 25, 30, and 60 min after medication. The results demonstrated a statistically significant suppression of the wheal reactions 15–20 min after medication, depending on the reaction producers used. The sum of all three producers showed a statistically significant effect on the wheal reaction 15 min after medication. The upper 95% confidence limit for time lag from dosing of acrivastine until reduction from placebo level commences was 6.5 min. The study substantiates that orally administered acrivastine has a rapid onset of action in the skin of allergic subjects. The results indicate that allergen SPT is a more sensitive tool for studying antihistaminergic activity than histamine SPT.     

Selection of patients for biological standardization as exemplified by standardization of mugwort, goosefoot and English plantain pollen allergen extracts/preparations

The biological activity of a partly purified, biochemically/immunochemically characterized mugwort pollen allergen preparation and crude pollen extracts of mugwort, goosefoot and English plantain was determined by means of skin prick test (SPT). The patient inclusion criteria with mugwort were a well-defined positive clinical history and a positive SPT. Symptoms related to goosefoot/English plantain pollens are difficult to define, as these weeds flower during the grass pollen season. Thus patients tested with these allergens did not fulfill the most important inclusion criterion for so-called biological standardization. To elicit a wheal of the same size as that produced by histamine 1 mg/ml required 100 to 10,000 times more material from these weeds, than from mugwort and other pollen allergen extracts investigated earlier. One thousand Biological Units/ml (BU/ml) corresponded to 8.3 micrograms dry weight (dw/ml) of the crude and 1.8 micrograms dw/ml of the purified mugwort pollen allergen preparation. Only 7/22 goosefoot-and English plantain-tested patients were positive at conjunctival or nasal challenge. All three weeds showed a similar composition with 5-10 allergens by CIE/CRIE analysis and 10-13 by immunoblotting analysis. One dominating allergen (approx. 15,000 d), could be identified for each weed species by protein gel blot after separation by SDS g-PAGE. There was no other explanation for the difference in biological activity than the criteria of selection. If there is no obvious clinical history, which is the main patient inclusion criterion in biological standardization, then additional criteria should be used.     

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 results of skin prick testing in patients with allergic rhinitis: a comparison between a multiple lancet device and a single lancet

Skin prick testing (SPT) is widely used in the assessment of allergic disorders. Different SPT techniques are widely used. The aim of this study was to compare the response to SPT using a multiple lancet device (MLD) with the results of a single lancet (SL). Fifty patients with allergic rhinitis were included in this study. Initially, SPT was performed by a SL technique. After one week SPT was repeated using the MLD on all patients. The patients were tested with a panel containing 19 specific allergens including grass pollen, tree pollen, house dust mites, weed pollen allergen extracts, histamine and a negative control. The skin responses were recorded after 15 minutes for each device by measuring the diameter of the wheal and the erythema. The skin wheal responses for grass pollen, tree pollen, weed pollen and house dust mite allergen extracts obtained using the SL were generally significantly larger than those using the MLD. The comparison between the MLD and the SL methods revealed that SPT was positive with SL and negative with MLD in 176 tests (15.3%), and on the contrary SPT was positive with MLD and negative with SL in only 13 tests (1%). In conclusion, we claim that SPT using SL shows a higher degree of sensitivity and reproducibility.     

Changes in Allergen Sensitization Over The Last 30 Years in Korea Respiratory Allergic Patients: A Single-Center

Purpose

Determining the culprit allergen is important for the diagnosis and management of allergic diseases. The skin prick test (SPT) has been widely used to identify culprit allergens. Skin reactivity to allergens has changed due to changes in lifestyle and outdoor environments. Therefore, the aim of the present paper was to examine changes in allergen sensitization in Korea.

Methods

We enrolled 1,135 patients with respiratory allergic diseases who were diagnosed at Severance Hospital from January 2010 to December 2011. SPTs were performed with inhalant allergens, and were compared to our previous studies of the SPTs in the 1980s and the 1990s.

Results

In the 2010s, the SPT positive rate of allergic rhinitis or allergic conjunctivitis was higher than asthma without allergic rhinitis or allergic conjunctivitis. The SPT positive rate was decreased by increments of age (P value <0.01). Skin reactivity to tree pollens was significantly increased to 36.4% in the 2010s from 19.0% in the 1990s and 8.8% in the 1980s. Among tree pollens, skin reactivity to oak (4.7%->14.4%), birch (7.1%->13.6%), alder (6.3%->13.4%) and pine (2.9%->14.3%) was significantly increased in the 2010s compared with the 1990s, respectively. Current skin reactivity to grass pollens (13.9%) and weed pollens (27.0%) has significantly decreased since the 1990s (20.3%, 40.9%, respectively). Skin reactivity to house dust mites showed no difference between the 1990s (55.2%) and the 2010s (55.6%). Skin reactivity to dog (27.3%->20.7%) and cockroach (25.3%->12.3%) have significantly decreased in the 2010s in comparison with the 1990s.

Conclusions

In light of the above results, we revealed the changes in skin reactivity to inhalant allergens that have occurred in Korean allergic patients over the past three decades. Since outdoor environmental factors such as the amount of pollen, global warming and plant distribution causes the changes in skin reactivity, further study and continuous close observation will be needed.     

The links between allergen skin test sensitivity, airway responsiveness and airway response to allergen

BACKGROUND: The allergen-induced early asthmatic response [provocation concentration (PC)20, the concentration causing a 20% forced expiratory volume in 1 s (FEV)1 fall] depends on the level of IgE sensitivity and the degree of nonallergic airway hyperresponsiveness (AHR) and can be predicted from histamine PC20 and allergen skin test endpoint. OBJECTIVES: We examined the relationships between allergen PC20, methacholine PC20, and allergen skin test endpoint and assessed the accuracy of both the histamine PC20-based prediction of allergen PC20 (using methacholine) and a new methacholine PC20-based prediction equation. METHODS: From 158 allergen challenges, the allergen PC20, the methacholine PC20, and the skin test endpoint were recorded and relationships between these three were sought. We compared the measured allergen PC20 to that predicted from the previous histamine PC20-based and the new methacholine-based formulae. RESULTS: In single regressions, allergen PC20 correlated with both methacholine PC20 (r=0.25, P=0.0015) and skin test endpoint (r=0.52, P <0.00005). The relationship was improved by multiple regression of log-allergen PC20vs. log-methacholine PC20 and log-endpoint (r=0.61, P <0.00005). The histamine-based formula predicted allergen PC20 to within 2 doubling concentrations in 80% and within 3 in 92%. The new methacholine-based formula to within 2 and 3 concentrations in 81% and 94%, respectively; only nine of 158 subjects were outside the 3 concentrations. CONCLUSIONS: We have confirmed the dependence of the allergen-induced early asthmatic response upon the level of allergic sensitivity and the degree of AHR, the latter as assessed by methacholine challenge. The allergen PC20 can be predicted to within 3 doubling concentrations in 94% of cases.     

Dose response relationship of allergen, histamine, and histamine releasers in skin prick test and precision of the skin prick test method

The aim of the present investigation was to study the dose response relationship of allergen, histamine and histamine releasers in skin prick test (SPT) and the precision of the SPT method. In one experiment timothy allergen, histamine HCl, rabbit anti-human-IgE and compound 48/80 were studied in seven patients. In a second experiment timothy allergen and histamine and dog allergen and histamine were investigated in two groups of 10 patients. Histamine HCl 1 and 10 mg/ml induced weals about 15 and 25 mm2 (4.5 and 5.5 mm in diameter), respectively. The precision as expressed by the coefficient of variation was about 25% for histamine and 40% for allergen for weal areas greater than 10 mm2. Calculations of the regression lines to test the dose response relationships were based on the method of least squares. The best fit was to a log/log model. The slopes of allergen, histamine and histamine releasers were essentially parallel within patients. The median slope of allergen was estimated to about 0.4 based on weal areas and 0.2 based on mean weal diameters. Furthermore, no significant differences were found between the lower and upper parts of the dose response curves of allergen and histamine, although there was a tendency towards steeper slopes at lower concentrations. These results show that histamine concentrations greater than or equal to 1 mg/ml should be used as positive control in SPT and that histamine releasers do not offer advantages over histamine as reference substances in SPT. A common slope for the dose response relationship of allergen and histamine can be used for the estimation of skin sensitivity.     

Inhibition of human allergic skin reactions in vivo by pretreatment with cromolyn (disodium cromoglycate)

The effect of cromolyn on allergen-induced allergic skin reactions was studied. Two patients with allergic rhinitis, two patients with bronchial asthma and atopic dermatitis and two patients with allergic rhinitis and atopic dermatitis were included in this study. They were allergic to cedar pollen, house dust mite and house dust, respectively. Scratching with allergen induced wheal and erythema reactions in each patient. Simultaneous application of allergen and cromolyn solution did not modulate allergic reactions; however, pretreatment with cromolyn solution inhibited allergen-induced wheal and erythema reactions significantly.     

The prevalence of skin-test-positive allergic rhinitis in Danish adults: two cross-sectional surveys 8 years apart. The Copenhagen Allergy Study

BACKGROUND: It is disputed whether increases in self-reported respiratory allergy represent a true increase or merely increased recognition. We aimed to investigate whether the prevalence of skin-prick-test (SPT)-positive allergic rhinitis had increased in an adult general population in Copenhagen, Denmark. METHODS: Two cross-sectional surveys were carried out in 1990 and 1998. A screening questionnaire on respiratory symptoms in random samples of 15-41-year-olds preceded both surveys. Among the responders, random samples were invited to a health examination including SPT. Totals of 312 (participation rate 74.6%) and 482 (participation rate 53.4%) subjects were examined in 1990 and 1998, respectively. Diagnoses of SPT-positive allergic rhinitis were based on a history of nasal symptoms on exposure to allergens and SPT positivity to allergens. RESULTS: The prevalence of a diagnosis of SPT-positive allergic rhinitis increased from 12.9% to 22.5% (adjusted odds ratio 1.94, 95% CI 1.30-2.90), whereas the prevalence of a positive SPT (allergen histamine wheal ratio > or = 0.5) to one or more of 10 allergens increased from 27.7% to 33.9% (adjusted odds ratio 1.47, 95% CI 1.05-2.05). CONCLUSIONS: The prevalence of SPT-positive allergic rhinitis has increased significantly. Our findings indicate that a true increase in respiratory allergy has occurred.     

Mustard allergy in children

BACKGROUND: Mustard allergy is not well known. This study aimed to assess its clinical features and other associated allergies, and to define skin prick tests (SPT), specific IgE, and dose response by oral food challenge. METHODS: Our study investigated 36 children with positive mustard SPT. The diagnosis of mustard allergy was based on open or single-blind, placebo-controlled food challenge (SBPCFC). We compared the subjects to 22 controls. RESULTS: The initial clinical features were atopic dermatitis (51.8%), and urticaria and/or angioedema (37%). Fifteen children were allergic (positive SBPCFC) and 21 children were nonallergic (negative SBPCFC). Symptoms after mustard ingestion started under 3 years of age in 53.3% of the subjects. There was no significant difference in the food allergies and associated inhalant allergen sensitizations between the two groups. In the allergic group, the mean wheal diameter for mustard SPT was 8.8 mm and the median concentration of mustard serum (s) IgE 14.8 kU/l. The mean cumulative reactive dose were 153 mg. CONCLUSIONS: Allergic reactions to mustard started early in life. Clinical symptoms were not severe in children. Mustard should be included in screening tests of food allergy in children.     

Plasma histamine changes during provoked bronchospasm in asthmatic patients

Seven patients with bronchial asthma underwent bronchial inhalation challenge with aerosolized allergen extracts and methacholine. Simultaneously, venous blood samples were collected and histamine was measured. Each patient was challenged on successive days with an allergen extract to which he had no skin-sensitizing antibody (skin test-negative allergen), followed by methacholine and skin test-positive allergen. Bronchospasm was not induced by inhalation of skin test-negative allergens but was observed in all patients after methacholine and in the majority of patients after skin test-positive allergens. No changes in plasma histamine were detected after challenges with methacholine and skin test-negative allergens. After challenge with skin test-positive allergens, significant rises in plasma histamine were detected in 5 of 7 patients. Plasma histamine was elevated within the first 5 min after inhalation of aerosolized allergen, and elevations persisted as long as 30 min. These studies showing that histamine increases significantly in the plasma during allergen-induced asthma in man suggest that histamine should be considered as at least one of the mediators of bronchospasm in allergic asthma. Bronchospasm induced by the cholinergic drug methacholine, unlike allergen-induced bronchospasm, is not associated with changes in plasma histamine.     

Immediate and late phase allergic cutaneous reactions are not inducers of unspecific or specific local hyperreactivity

The present study evaluates the possibility of allergen-induced unspecific and specific dermal hyperreactivity with special reference to the presence of late cutaneous reactions and allergen-induced nasal hyperreactivity. Twenty-six patients with strictly seasonal allergic rhinitis participated. All had a positive skin prick test for birch (Betula verrucosa) and/or timothy (Phleum pratense). Ten patients had previously displayed an allergen-induced nasal hyperreactivity and six patients a late cutaneous reaction. An initial skin prick test with a relevant pollen allergen was done in triplicate. The immediate skin reactions were recorded after 15 min and any late-phase reaction after 6 h. Twenty-four hours later the patients were retested. The same pollen allergen was sited in the first flare reaction from the previous day. A histamine prick test was sited in the weal as well as in the third reaction from day 1. A histamine control was also performed in a previously unaffected area. The allergen-induced weal reactions decreased significantly at rechallenge compared with the results from the previous day (P less than 0.05). The histamine tests resulted in similar skin reactions regardless of whether or not they were done on a previous allergen test site. This was true for both specific and unspecific reactions when the subgroups of patients with previously demonstrated allergen-induced nasal hyperreactivity or late-phase skin reactions were evaluated separately. These results indicate that allergen-induced hyperreactivity is not a general feature of allergic inflammation but is a phenomenon restricted to specific sites, such as the airway mucosa.