Histamine Skin Prick Test Research Articles

Targeting histamine receptor 4 in cholinergic urticaria with izuforant (LEO 152020): results from a phase IIa randomized double-blind placebo-controlled multicentre crossover trial.

Cholinergic urticaria (CholU) is a common subtype of chronic inducible urticaria, where signs and symptoms (e.g. pruritic wheals and angioedema) are triggered by sweating due to physical exercise, passive warming and by other sweat-inducing situations. While guidelines recommend treatment with second-generation H1 antihistamines, approximately 90% of patients report uncontrolled disease. Targeting the histamine 4 receptor (H4R) has shown promise in preclinical/clinical studies of allergic/inflammatory diseases. Izuforant (LEO 152020) is a selective oral H4R antagonist with expected dual antipruritic and anti-inflammatory effects. To assess the effects of izuforant in adults with CholU, a common type of chronic urticaria driven by histamine and characterized by high skin levels of H4R expression. This was a phase IIa randomized double-blind placebo-controlled multicentre crossover trial where patients with CholU with an inadequate response to ≥ 1 standard dose of H1 antihistamine received izuforant 100 mg twice daily or placebo (EUCTR2020-004961-38-DE; NCT04853992). The primary endpoint was change from baseline in Urticaria Activity Score. Exploratory endpoints included CholU activity score over 7 days, urticaria control test, Physician Global Assessment, patient global assessment of severity (PGA-S), provocation tests, Dermatology Life Quality Index and CholU quality of life (CholU-QoL). Pharmacokinetic and pharmacodynamic parameters, and serum biomarkers were assessed, as well as safety and tolerability. Nineteen patients were randomized and included in the full analysis set; 18 completed treatment [mean (SD) age 29.5 (9.8) years; mean (SD) CholU duration 8.0 (6.3) years]. The primary and most of prespecified exploratory endpoints were not met; there were significant improvements in PGA-S for izuforant vs. placebo (P = 0.02), and nonsignificant improvements for other endpoints in quality of life and histamine skin prick test. All adverse events (AEs) experienced with izuforant were considered mild. The most frequently reported (> 1 patient) were nausea (three patients) and upper abdominal pain (two patients), occurring more frequently with izuforant vs. placebo (one patient each). There were no treatment-related serious AEs and no patient receiving izuforant discontinued the study. Treatment with izuforant did not cause downregulation of H4R. This is the first study to explore the role of H4R as a therapeutic target in urticaria. Targeting H4R with izuforant was well tolerated but did not demonstrate significant improvements vs. placebo in the primary endpoint and all but one prespecified exploratory endpoint in CholU.

Functional brain alterations in symptomatic dermographism patients-An exploratory magnetoencephalography study.

Symptomatic dermographism (SD) is a common form of urticaria, which is triggered by stroking the skin. Brain involvement in its aetiology was investigated by means of magnetoencephalography (MEG) after provocation with histamine and dermography. Wheals were induced by histamine skin prick test and dermography in twelve SD patients and fourteen controls. Itch severity was scored on a Visual Analogue Scale (VAS). Relative power and functional connectivity (FC) were measured using a 306-channel whole-head MEG system at baseline and 10 min after histamine and dermography, and contrasted between groups and conditions. Furthermore, wheal diameter and itch scores after these procedures were correlated with the MEG values. SD patients had higher itch scores after histamine and dermography. No significant group-differences were observed in relative power or FC for any condition. In both groups, power decreases were mostly observed in the beta band, and power increases in the alpha bands, after provocation, with more regions involved in patients compared to controls. Increased FC was seen after histamine in patients, and after dermography in controls. In patients only, dermography and histamine wheal size correlated with the alpha2 power in the regions of interest that showed significant condition effects after these procedures. Our findings may be cautiously interpreted as aberrant itch processing, and suggest involvement of the central nervous system in the aetiology of SD.

Placebo-Controlled Histamine Challenge Disproves Suspicion of Histamine Intolerance

Histamine intolerance (HIT) is frequently diagnosed in patients with polysymptomatic otherwise unexplained symptoms. To exclude HIT by a single-blind placebo-controlled histamine challenge (SBPCHC), to study clinical features of patients with positive challenge, and to examine the predictability of HIT by biomarkers. SBPCHC was performed in 59 patients with suspected HIT. History and clinical data, including serum diamine oxidase (DAO) and histamine skin test wheal size of patients with positive versus negative SBPCHC, were compared. Patients were predominantly middle-aged women (84.7%). Three-quarters reported improvement but never resolution of symptoms during a histamine-low diet. Histamine provocation was safe; only 1 patient was treated with antihistamines. Thirty-seven patients (62.7%) displayed symptoms to placebo. HIT was excluded in 50 patients (84.7%). Objective symptoms occurred in 4 of 59 cases (6.8%) after histamine but not after placebo challenge. These were diagnosed with "plausible HIT" because reactions occurring by chance could not be excluded. Another 5 patients (8.5%) were diagnosed with "possible HIT" after case-dependent detailed analysis. Patients with plausible/possible HIT had reported more gastrointestinal symptoms (P= .01), but comparable diet response and equal histamine skin prick test wheal sizes to those without HIT. Serum DAO activity tended to be lower in patients with HIT (P= .08), but was highly variable in those without, limiting its value as a biomarker. SBPCHC disproves HIT in the majority of patients. Placebo-controlled challenges are needed as placebo reactions were frequent. Gastrointestinal symptoms after food intake and reduced DAO levels are markers for HIT; however, specificity is not sufficient enough for making the diagnosis.

Histamine Skin Prick Tests: From Established Diagnostic Technique to Advanced Experimental Biomarker

Introduction: Skin prick tests have a long history as diagnostic and pharmacodynamic biomarker. Besides visual assessments of the wheal and flare, objective blood flow measurements using laser Doppler imaging (LDI) and laser speckle contrast imaging (LSCI) have been reported. In light of these advancements, an up-to-date characterization of the histamine-evoked response is worthwhile. Methods: A single-centre study was completed in healthy males. Two parameters were addressed: (1) dermal blood flow (DBF) within a 7.65-mm ring encircling the skin prick site (DBF_ring), and (2) surface area of the flare (AREA_flare). First, the dose response was assessed using placebo (0.9% sodium chloride) or histamine (histamine dihydrochloride 1, 3, or 10 mg/mL) skin pricks on the volar surface of subjects’ (n = 12) forearm. The DBF_ring was measured by LDI, and the AREA_flare by LDI and by ruler. Secondly, the inter-arm and inter-period reproducibility of the DBF_ring and AREA_flare, as evoked by histamine (10 mg/mL) and measured by LDI and LSCI, was examined (n = 14). Lastly, the effect of aprepitant (125 mg), ketotifen (1 mg), and a single (5 mg) and fourfold (20 mg) dose of desloratadine and levocetirizine on the histamine-induced (10 mg/mL) DBF_ring and AREA_flare was evaluated with LSCI (n = 13 or 12). Results: All three histamine doses induced a time-dependent vasodilation. Ruler recordings did not conclusively correlate with LDI assessments of the AREA_flare. The DBF_ring and AREA_flare were reasonably reproducible when measured by using LDI or LSCI, with negligible bias between arms and study periods and poor to moderate within-subject reproducibility (0.23 ≤ ICC ≤ 0.71). While the fourfold dose of desloratadine (p = 0.0041) and the single and fourfold dose of levocetirizine (p < 0.0001) managed to reduce the AREA_flare, only the fourfold dose of levocetirizine (p = 0.0052) reduced the DBF_ring. Conclusion: Caution is warranted when translating years of clinical experience with histamine skin prick tests to objective recordings of the associated changes in skin perfusion. Ruler and LDI assessments of the AREA_flare do not consistently correlate, and the reproducibility and histamine dependency of the measurements are not obvious. While 10 mg/mL histamine may be a good choice for qualitative diagnostic evaluations, a lower dose may be better suited to use as a quantitative biomarker.

"Harnessing the placebo effect: Exploring the influence of physician characteristics on placebo response": Correction.

Research on placebo/nocebo effects suggests that expectations can influence treatment outcomes, but placebo/nocebo effects are not always evident. This research demonstrates that a provider's social behavior moderates the effect of expectations on physiological outcomes. After inducing an allergic reaction in participants through a histamine skin prick test, a health care provider administered a cream with no active ingredients and set either positive expectations (cream will reduce reaction) or negative expectations (cream will increase reaction). The provider demonstrated either high or low warmth, or either high or low competence. The impact of expectations on allergic response was enhanced when the provider acted both warmer and more competent and negated when the provider acted colder and less competent. This study suggests that placebo effects should be construed not as a nuisance variable with mysterious impact but instead as a psychological phenomenon that can be understood and harnessed to improve treatment outcomes. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Limosilactobacillus reuteri DSM-17938 for preventing cough in adults with mild allergic asthma: A double-blind randomized placebo-controlled cross-over study.

Cough is a common troublesome symptom in asthma which is neuronally mediated. Limosilactobacillus reuteri DSM-17938 (L.reuteri DSM-17938) is a probiotic shown to be effective in pre-clinical models at suppressing neuronal responses to capsaicin, a transient receptor potential vanilloid agonist (TRPV1). Investigate the effects of DSM-17938 versus matched placebo on capsaicin-evoked coughs in mild allergic asthmatics. We performed a 4-visit, randomized, double-blind, placebo-controlled, two-way cross-over study comparing full dose cough responses with inhaled capsaicin in mild allergic asthmatics after 1month of treatment with DSM-17938 compared with matched placebo. Randomization and allocation to trial group were carried out by a central computer system. Histamine skin prick testing, airway hyper-responsiveness and inflammatory cells in induced sputum were measured at every visit. Blood was collected to extract PBMCs and stimulated with CD3/CD28 to ascertain the effects of DSM-17938 /placebo on T-cell cytokine responses. Seventeen subjects were recruited and 15 completed the study (8 females, mean age 27.3years). There was no difference in the change in maximum capsaicin-evoked coughs (Emax) after treatment with L.reuteri DSM-17938 compared with placebo [mean difference 2.07 coughs (95% CI -2.77 to 6.91, p=.38) or relative changes in geometric mean ratios for the dose evoking at least half the Emax (ED50) [1.05 (95% CI 0.31-3.58, p=.94)], concentration evoking 2 coughs (C2) [0.63 (0.26-1.53), p=.28] and 5 coughs (C5) [0.79 (0.25-2.50), p=.67]. There was no effect on histamine skin prick wheal size, intensity of itch sensation, methacholine PC20, airway inflammation or T-cell responses after stimulation with CD3/CD28. There were no serious adverse events. One subject developed a mild upper respiratory tract infection and another mild transient nausea whilst on DSM-17938. In this small study in adults with mild allergic asthma, we found no evidence that L.reuteri DSM-17938has any systemic effects on airway nerves, smooth muscle, sputum inflammatory cells, skin responses or T-cell responses after oral consumption. Clinicaltrials.gov Identifier: NCT03603522.

The role of patient beliefs in open-label placebo effects.

Recent research on open-label placebos, or placebos administered without deception or concealment, suggests that they can be effective in a variety of conditions. The current research sought to unpack the mechanisms underlying the treatment efficacy of open-label placebos. A health care provider induced an allergic reaction in 148 participants via a histamine skin prick test. Participants were then exposed to 1 of 4 conditions additively leveraging various mechanisms of open-label placebo treatments: a supportive patient-provider relationship, a medical ritual, positive expectations, and a rationale about the power of placebos. There were no main effects of condition on allergic responses. However, participant beliefs about placebos moderated the effect of open-label placebo treatment condition on physiological allergic reactions: the condition including all 4 components of open-label placebos (a supportive patient-provider relationship, a medical ritual, positive expectations, and a rationale about the power of placebos) significantly reduced physiological allergic reaction among participants with a strong belief in placebos compared with participants in the control group. Participants' beliefs about placebos interact with information from the provider to reduce physiological allergic reactions in response to an open-label placebo treatment. This study underscores the importance of measuring and understanding how participants' beliefs influence outcomes of treatment, and furthers our understanding of when and how open-label placebo treatments work. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Impaired resolution of wheals in the skin prick test and low diamine oxidase blood level in allergic patients.

IntroductionHistamine is the major mediator of IgE- and non-IgE-mediated allergic reactions upon allergen or hapten contact. Reduced histamine degradation capacity was associated with atopic eczema as well as with non-immunological histamine intolerance. Higher blood serum histamine level concomitant with decreased intestinal diamine oxidase activity were observed in patients with food allergy.AimTo evaluate the relationship between patients’ blood diamine oxidase (DAO) activity/histamine status and their reactivity to time-resolved histamine skin prick test in respect to vulnerability to allergic diseases.Material and methodsFifty-three patients were examined with skin prick tests (SPT) and patch tests for suspected presence of either IgE- or non-IgE-mediated allergy. All individuals were skin prick tested with histamine and the resolution of the wheal was monitored for 50 min. Blood DAO activity and histamine concentration were measured with a radio-extraction radioimmunoassay.ResultsTime-resolved histamine skin prick testing revealed presence of wheals which were 35% larger in diameter in 47% of examined subjects at 20 min of the test. These patients exhibited significantly compromised time-course wheal resolution (wheal ≥ 3 mm at 50 min) compared to a group of patients with the normal-rate of wheal resolution (wheal = 0 mm at 50 min). Within a group of subjects exhibiting impaired wheal resolution, 61% of patients were diagnosed allergic compared to 50% in a group of patients with a normal rate of wheal resolution. Finally, allergic patients were characterized by a significantly lower DAO activity and higher histamine content compared to healthy subjects.ConclusionsThe results of this study indicate that patients with IgE- or non-IgE-mediated allergy are likely to have low DAO blood activity and may concomitantly suffer from histamine intolerance. Furthermore, our results suggest that allergic patients are more likely to develop an excessive SPT reaction. Our results emphasize caution in interpretation of the SPT results in allergic patients with diagnosed histamine intolerance or histamine/DAO activity imbalance.

DIURNAL VARIATIONS IN SKIN PRICK TESTING

Introduction Skin prick testing (SPT) can reliably diagnose food and environmental allergies. Previous studies have shown mixed results on the diurnal pattern for SPT, which has not been evaluated in food allergens. Methods Retrospective chart review of pediatric patients at one institution from 6/2008- 6/2017 who received SPT to food and/or environmental allergens. Our hypothesis was that SPT wheal and erythema size would be higher in PM (12:00-19:30) vs. AM (7:00-11:59). Results We reviewed 15,960 charts; 13,077 had adequate histamine response without antihistamine use within 5 days of SPT (58% male, PM µ±SD=6.3±4.4 years vs. AM 5.7±4.2). Wheal size for histamine SPT was not significantly increased in PM vs. AM (µ±SD=5.7± 1.9 mm, n=6562 vs. 5.7±1.9, n=6388; p=0.76), nor for the most common food allergens. Significantly increased erythema for histamine SPT was noted in PM vs. AM (µ±SD=14.6±6.3, n= 6501 vs. 14.2±6.1, n=6352; p14.7(14.3-14.5). There was no significant difference in wheal size in this sub-analysis. Conclusions SPT in the PM is associated with increase erythema size for histamine and several other allergens, but without a significant difference in wheal size. Diurnal cortisol variations likely influence erythema size, but do not influence clinical outcomes of SPT. Thus, SPT can be reliably performed at any time of day. Skin prick testing (SPT) can reliably diagnose food and environmental allergies. Previous studies have shown mixed results on the diurnal pattern for SPT, which has not been evaluated in food allergens. Retrospective chart review of pediatric patients at one institution from 6/2008- 6/2017 who received SPT to food and/or environmental allergens. Our hypothesis was that SPT wheal and erythema size would be higher in PM (12:00-19:30) vs. AM (7:00-11:59). We reviewed 15,960 charts; 13,077 had adequate histamine response without antihistamine use within 5 days of SPT (58% male, PM µ±SD=6.3±4.4 years vs. AM 5.7±4.2). Wheal size for histamine SPT was not significantly increased in PM vs. AM (µ±SD=5.7± 1.9 mm, n=6562 vs. 5.7±1.9, n=6388; p=0.76), nor for the most common food allergens. Significantly increased erythema for histamine SPT was noted in PM vs. AM (µ±SD=14.6±6.3, n= 6501 vs. 14.2±6.1, n=6352; p14.7(14.3-14.5). There was no significant difference in wheal size in this sub-analysis. SPT in the PM is associated with increase erythema size for histamine and several other allergens, but without a significant difference in wheal size. Diurnal cortisol variations likely influence erythema size, but do not influence clinical outcomes of SPT. Thus, SPT can be reliably performed at any time of day.

Harnessing the placebo effect: Exploring the influence of physician characteristics on placebo response.

Research on placebo/nocebo effects suggests that expectations can influence treatment outcomes, but placebo/nocebo effects are not always evident. This research demonstrates that a provider's social behavior moderates the effect of expectations on physiological outcomes. After inducing an allergic reaction in participants through a histamine skin prick test, a health care provider administered a cream with no active ingredients and set either positive expectations (cream will reduce reaction) or negative expectations (cream will increase reaction). The provider demonstrated either high or low warmth, or either high or low competence. The impact of expectations on allergic response was enhanced when the provider acted both warmer and more competent and negated when the provider acted colder and less competent. This study suggests that placebo effects should be construed not as a nuisance variable with mysterious impact but instead as a psychological phenomenon that can be understood and harnessed to improve treatment outcomes. (PsycINFO Database Record

Inhibitory effect of Phlai capsules on skin test responses among allergic rhinitis patients: a randomized, three-way crossover study

BackgroundZingiber cassumunar Roxb., commonly known as Phlai in Thai, has been used as a traditional medicine in Thailand for the treatment of various diseases, including inflammation and chronic airway disease. ObjectiveThe purpose of this study was to assess the antihistaminic effect of Phlai on skin testing. Design, Setting, Participants and InterventionThis was a randomized, open-label, three-way crossover study. Twenty allergic rhinitis (AR) patients were enrolled. In randomized sequence, patients received a single dose of Phlai capsules (100 or 200 mg) or loratadine (10 mg) with a washout period of 1 week between each treatment. Main Outcome MeasuresSkin prick testing for histamine and common aeroallergen (house dust mite) were performed before treatment and after 1, 2, 3, 4, 6, 8, 12 and 24 hours of treatment. The main treatment outcomes were the mean wheal and flare responses to the skin prick test after treatment. ResultsBoth 100 mg and 200 mg Phlai doses suppressed wheal and flare responses to house dust mite allergen, but only 200 mg of Phlai capsules significantly suppressed wheal and flare responses to histamine. Repeated measures analysis of variance showed that loratadine caused more wheal and flare suppression than Phlai capsules in responses to the histamine skin prick test. However, there were no significant differences among the effects of 100 mg Phlai capsules, 200 mg Phlai capsules and loratadine in suppression of wheal and flare induced by the mite skin prick test. Both doses of Phlai were well-tolerated with no adverse events. ConclusionBoth 100 mg (compound D 4 mg) and 200 mg (compound D 8 mg) Phlai capsules, when taken as a single therapeutic dose, inhibited skin reactivity to histamine and mite skin prick tests in AR patients. Trial RegistrationThai clinical trial registry (TCTR20160510001).

The histamine skin prick test: An analysis of the method for use in clinical trials

The histamine skin prick test: An analysis of the method for use in clinical trials

Prediction of the Efficacy of Antihistamines in Chronic Spontaneous Urticaria Based on Initial Suppression of the Histamine- Induced Wheal.

Antihistamines are the first line of treatment for chronic spontaneous urticaria. However, there is no effective method to predict whether an antihistamine will have a beneficial clinical effect or not. To assess whether the change in histamine-induced wheal and flare measurements 24 hours after administration of antihistamine can predict the efficacy of treatment. We performed a multicenter, triple-blind, randomized study. Patients received a daily oral dose of cetirizine, fexofenadine, bilastine, desloratadine, or ebastine over 8 weeks. After 4 weeks, a higher dose of antihistamine was administered to patients who did not experience a clinical response. A histamine skin prick test was carried out at baseline and 24 hours after the first dose of antihistamine. Disease severity (Urticaria Activity Score [UAS]), response to the histamine skin prick test, and impact on the patient's quality of life (Dermatology Life Quality Index [DLQI]) were determined every 2 weeks. The study population comprised 150 patients (30 per group) and 30 controls. Twenty-four hours after administration of antihistamine, inhibition of the histamine wheal by >75% was significantly associated with better UAS and DLQI scores. The safety and efficacy of the 5 antihistamines were similar. After updosing, rates of disease control (DLQI score <5) increased from 58.7% to 76.7%. Measurement of the histamine-induced wheal can predict which patients will have a strong clinical response to antihistamines but has limited utility for identifying nonresponders. The clinical significance of these data could be relevant in the search for new urticaria treatment regimens.

Diminution of signal transducer and activator of transcription 3 signaling inhibits vascular permeability and anaphylaxis

During IgE-mediated immediate hypersensitivity reactions, vascular endothelial cells permeabilize in response to mast cell mediators. We have demonstrated previously that patients and mice with signal transducer and activator of transcription 3 (STAT3) mutations (autosomal dominant hyper-IgE syndrome [AD-HIES]) are partially protected from anaphylaxis. We sought to study the mechanism by which STAT3 contributes to anaphylaxis and determine whether small-molecule inhibition of STAT3 can prevent anaphylaxis. Using unaffected and STAT3-inhibited or genetic loss-of-function samples, we performed histamine skin prick tests, investigated the contribution of STAT3 to animal models of anaphylaxis, and measured endothelial cell permeability, gene and protein expression, and histamine receptor-mediated signaling. Although mouse mast cell degranulation was minimally affected by STAT3 blockade, mast cell mediator-induced anaphylaxis was blunted in Stat3 mutant mice with AD-HIES and in wild-type mice subjected to small-molecule STAT3 inhibition. Histamine skin prick test responses were diminished in patients with AD-HIES. Human umbilical vein endothelial cells derived from patients with AD-HIES or treated with a STAT3 inhibitor did not signal properly through Src or cause appropriate dissolution of the adherens junctions made up of the proteins vascular endothelial-cadherin and β-catenin.Furthermore, we found that diminished STAT3 target microRNA17-92 expression in human umbilical vein endothelial cells from patients with AD-HIES is associated with increased phosphatase and tensin homolog (PTEN) expression, which inhibits Src, and increased E2F transcription factor 1expression, which regulates β-catenin cellular dynamics. These data demonstrate that STAT3-dependent transcriptional activity regulates critical components for the architecture and functional dynamics of endothelial junctions, thus permitting vascular permeability.

Prevention of pruritus with ethyl-chloride in skin prick test: a double-blind placebo-controlled prospective study.

BackgroundEthyl-chloride (EC) spray was recently shown to be an effective antipruritic agent, when given 15 min after histamine skin-prick test (SPT), without changing the wheal and flare reaction. We aimed to investigate the antipruritic effect of EC on SPT, when given prior to SPT.MethodsA double-blind placebo-controlled prospective study. Overall, 44 volunteers underwent histamine SPT on both arms to trigger local pruritus. Prior to test, they were randomly treated with EC spray on one arm and saline spray (placebo) on the other. Subjects as well as researchers were blinded to the type of applied sprays. The wheal and flare reaction was measured after the SPT and subjects reported the intensity of pruritus following EC/placebo using a validated pruritus questionnaire (indexes 1–3) and a visual analog scale (VAS).ResultsSignificant improvement in pruritus was reported following treatment with EC compared with placebo for all four studied parameters. Index 1 in EC 3.7 ± 2.3 versus 5 ± 3.5 (p = 0.007) in placebo, index 2 in EC 2.6 ± 2.1 versus 3.8 ± 2.8 (p = 0.002) in placebo, index 3 of EC 6.3 ± 3.8 versus 8.8 ± 5.8 (p = 0.03) and VAS in EC 3.7 ± 1.9 versus 4.4 ± 2.3 (p = 0.003). There were no significant differences between EC and placebo in terms of the wheal and flare indurations area.ConclusionsEthyl-chloride has an effective antipruritic agent, when given before histamine SPT. Its use did not change the wheal and flare reaction, making it ideal for prevention of pruritus, secondary to allergy skin test, without masking the results.

Omalizumab in the treatment of aspirin-exacerbated respiratory disease

Omalizumab in the treatment of aspirin-exacerbated respiratory disease

Intradermal Tests for Diagnosis of Drug Allergy are not Affected by a Topical Anesthetic Patch.

The use of topical anesthesia to perform intradermal tests (IDTs) for drug allergy diagnosis was never investigated. We aimed to determine the effects of a topical anesthetic patch containing prilocaine-lidocaine on wheal size of IDT with drugs. Patients who had positive IDT as part of their investigation process of suspected drug hypersensitivity were selected. IDT were performed according to guidelines. Anesthetic patch (AP) was placed and the same prior positive IDT, as well as positive histamine skin prick test (SPT) and negative (saline IDT) controls, were performed in the anesthetized area. Patients with negative IDT were also included to check for false positives with AP. Increase in wheals after 20 minutes both with and without AP was recorded and compared. 45 IDT were performed (36 patients), of which 37 have been previously positive (14 antibiotics, 10 general anesthetics, 6 non-steroidal anti-inflammatory drugs, 3 iodinated contrasts, 3 anti-Hi-histamines and 1 ranitidine). Mean histamine SPT size without the AP was 4.7 mm [95%CI (4.4-5.1]), and 4.6 mm [95%CI(4.2-5.0)] with anesthesia. Mean wheal increase in IDT for drugs without the anesthesia was 4.5 mm [95%CI(3.3-5.7)] and with anesthesia was 4.3 mm [95%CI(2.8-5.8)]. No statistical significant differences were observed between skin tests with or without AP for histamine SPT (P=0.089), IDT with saline (P=0.750), and IDT with drugs (P=0.995). None of the patients with negative IDT showed positivity with the AP, or vice-versa. The use of an AP containing prilocaine-lidocaine does not interfere with IDT to diagnose drug allergy, and no false positive tests were found.

128 Colour Change in the Human Histamine Wheal; a Sign of Desensitized Histamine Vasoconstrictory Receptors

BackgroundThe aim was to find the cause and consequences of a colour change in histamine wheals found after ordinary histamine skin prick tests (SPTs) (10 mg/mL). A rapid change to a darker red colour from the 18th and to the 20th minute has been demonstrated by using a digital image-processing technique called LYYN and ImageJ to yield numerical values.1MethodsRepeated histamine SPTs in the middle of the site for earlier performed histamine SPTs in humans. Calculations of the sizes of photographed wheals. Histamine solutions perfused in isolated rabbit ears.ResultsHistamine SPT performed 90 minutes or 6 hours apart from initial histamine SPTs evoked a ring of wheal peripherally around the site of the initial wheal or no wheal at all. The initial wheals had at those times disappeared. Histamine perfusion in isolated rabbit ears indicated first vasoconstriction and after a mean of 17 minutes vasodilatation in post-capillary vessels despite continued histamine perfusion.ConclusionsThe results indicate that total desensitization of histamine-1 receptors in the wheal is the cause of the colour change in human histamine SPTs and that such desensitization lasts long time. If histamine released at allergen provocations also evokes such a long-lasting desensitization and post-capillary vasodilatation it opens new aspects on vascular events in allergic reactions.

Variability in Skin Prick Test Results Performed by Multiple Operators Depends on the Device Used

Background The variability of skin prick test results when carried out by multiple users has not previously been assessed across different devices or between different sites on the body. Such multiuser variability has important implications for clinical practice.Objectives We assessed the variability of measurements from 4 commonly used single-headed skin test devices when used by multiple operators and examined whether the variability in performance was different on the back compared with the forearm.Methods Eight adult volunteer "operators" were trained in the use of 4 devices: Greer Pick, Quintip, Stallergenes Lancet, and Feather Lancet. Each operator performed a histamine skin prick test with all devices on the backs and forearms of 5 volunteer "receivers." Variability in results was assessed using a multilevel (random effects) regression model.Results After controlling for variation between users and receivers, the residual variability or "measurement error" was least for the Stallergenes Lancet, closely followed by the Quintip. The Greer Pick had the greatest variability. There was greater variability in measurements on the arm compared with the back.Conclusions The devices using the "puncture" method (Stallergenes Lancet, Quintip) provide less variability in results than those using a "prick" method when carried out by multiple users (Greer Pick and Feather Lancet). Testing on the back also gives less variable results compared with the arm.

Ethyl Chloride as an Antipruritic Agent: A Double-Blind Placebo-Controlled Prospective Study

Background: Ethyl chloride (EC) is usually used as a topical anesthetic spray agent. However, its antipruritic effects have never been studied, to the best of our knowledge. Methods: A double-blind placebo-controlled prospective study. Overall, 51 healthy volunteers underwent a histamine skin prick test on both arms in order to trigger local pruritus. Thereafter, the affected areas were treated with an EC spray on one arm and a saline spray (placebo) on the other. Subjects as well as researchers were blind to which sprays were used. Subjects reported improvement in pruritus following EC/placebo and rated the intensity of pruritus by using a validated questionnaire and a visual analog scale. The flare and wheal reactions were measured in both arms before and following treatment with EC/placebo. Results: Significant improvement in pruritus was reported more frequently following treatment with EC compared with placebo (84 vs. 16%; p < 0.0001). Significant reduction in pruritus intensity was reported immediately and 15 min following treatment with EC compared with placebo (p < 0.05). There was no significant difference between EC and placebo in terms of the flare and wheal reactions. Conclusions: EC is an effective antipruritic agent, and it does not change the wheal and flare reactions, making it ideal for treating pruritus secondary to allergy skin tests without masking their results.