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1.  Wheal and flare reactions in skin prick tests of patients treated with montelukast alone or in combination with antihistamines 
Inflammation Research  2013;63:191-195.
Because antileukotrienes may inhibit inflammation, it is plausible that montelukast administered for a long time could suppress skin wheal and flare reaction, and thus, it should be discarded prior to the tests. This study assessed the effect of long-lasting treatment with montelukast alone or in combination with antihistamines on wheal and flare in skin pricks tests (SPT) in patients sensitized to perennial allergens.
We conducted a 32-week, double-blind, placebo-controlled, cross-over and randomized trial that implicated two arms: arm A, 20 patients received levocetirizine, montelukast with or without levocetirizine or placebo; arm B, 20 patients received desloratadine, montelukast with or without desloratadine or placebo. All treatment periods lasted 6 weeks and were separated by 2-week washouts. At baseline and on the last day of each treatment period, SPT were performed in all participants.
Both levocetirizine and desloratadine in monotherapy, or in combination with montelukast, were effective in reducing wheal and flare in SPT. Monotherapy with montelukast did not change the size of the wheal for either histamine or for house dust mites, in either arm of the study, but significantly reduced the size of flare for histamine in arm A. Addition of montelukast to antihistamine did not exceed efficacy of monotherapy with antihistamine in both arms of the study.
Since the size of wheal determines the results of SPT, montelukast, even taken for a long time, does not have to be discarded prior to the tests.
PMCID: PMC3921455  PMID: 24281730
Allergic rhinitis; Montelukast; Antihistamine; Skin prick test; Inflammation
2.  Adjusting wheal size measures to correct atopy misclassification 
Skin prick testing (SPT) is fundamental to the practice of clinical allergy identifying relevant allergens and predicting the clinical expression of disease. Wheal sizes on SPT are used to identify atopic cases, and the cut-off value for a positive test is commonly set at 3 mm. However, the measured wheal sizes do not solely reflect the magnitude of skin reaction to allergens, but also skin reactivity (reflected in the size of histamine reaction) and other random or non-random factors. We sought to estimate wheal sizes exclusively due to skin response to allergens and propose gender-specific cutoff points of atopy.
We developed a Bayesian method to adjust observed wheal sizes by excluding histamine and other factor effects, based on which revised cutoff points are proposed for males and females, respectively. The method is then applied to and intensively evaluated using a study population aged 18, at a location on the Isle of Wight in the United Kingdom. To evaluate the proposed approach, two sample t-tests for population means and proportion tests are applied.
Four common aeroallergens, house dust mite (HDM), grass pollen, dog dander, and alternaria are considered in the study. Based on 3 mm cutoff, males tend to be more atopic than females (P-values are between 0.00087 and 0.062). After applying the proposed methods to adjust wheal sizes, our findings suggest that misclassifications of atopy occur more often in males. Revised allergen-specific cutoff values are proposed for each gender.
To reduce the gender discrepancy, we may have two potentially convenient solutions. One way is to apply allergen-specific and gender-specific cutoff values following the proposed method. Alternatively, we can revise the concentration of allergens in the SPT solutions but keep the cutoff values unchanged, which may be more convenient to clinicians.
PMCID: PMC3160870  PMID: 21887114
SPT; atopy; Bayesian method; joint modeling; misclassification
3.  128 Colour Change in the Human Histamine Wheal; a Sign of Desensitized Histamine Vasoconstrictory Receptors 
The 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.1
Repeated 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.
Histamine 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.
The 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.
PMCID: PMC3512879
4.  The rate of epinephrine administration associated with allergy skin testing in a suburban allergy practice from 1997 to 2010 
Allergy & Rhinology  2012;3(2):e55-e60.
Allergy skin testing is considered a safe method for testing for IgE-mediated allergic responses although anaphylactic events can occur. Reported rates of anaphylaxis per patient are not consistent and range from 0.008 to 4%. The aim of this study was to determine the rate of epinephrine use associated with allergy skin-prick testing (SPT) and intradermal testing (IDT) in a suburban practice over 13 years. This retrospective chart review used billing and procedure coding records during the time period from January 1997 to June 2010 to identify encounters where epinephrine was administered after SPT or IDT. Patient encounters with procedure codes for skin testing plus either parenteral epinephrine, corticosteroid, antihistamine, or i.v. fluid administration were identified. These patient charts were reviewed to determine if epinephrine was administered, whether systemic reactions developed, and rates of epinephrine administration were calculated. There were 28,907 patient encounters for SPT and 18,212 for IDT. Epinephrine was administered in six patient encounters (0.02%) where SPT was performed; no IDT encounters led to epinephrine administration. There were no fatalities. Allergy skin testing to a variety of allergens, when administered by well-trained personnel, is a safe procedure. This study, involving the largest population to date, showed a rate of systemic reactions requiring epinephrine of 20 per 100,000 SPT visits. No epinephrine was given after IDT.
PMCID: PMC3548609  PMID: 23342290
Adverse reactions; allergic rhinitis; anaphylactoid reactions; anaphylaxis; food allergy testing; idiopathic anaphylaxis; intradermal testing; skin-prick testing; systemic reactions; venom allergy testing
5.  How Stress and Anxiety Can Alter Immediate and Late Phase Skin Test Responses in Allergic Rhinitis 
Psychoneuroendocrinology  2009;34(5):670.
Allergic rhinitis (AR) is the fifth most common chronic disease, and the association between allergic disorders and anxiety is well-documented. To investigate how anxiety and stressors modulate skin prick test (SPT) responses and associated inflammatory responses, 28 men and women with AR were selected by clinical history and skin test responses. The participants were admitted twice to a hospital research unit for 4 hours in a crossover trial. Changes in SPT wheals were assessed before and after a standardized laboratory speech stressor, as well as again the following morning; skin responses assessed twice during a lab session without a stressor and again the following morning served as the contrast condition. Anxiety heightened the magnitude of allergen-induced wheals following the stressor. As anxiety increased, SPT wheal diameters increased after the stressor, compared to a slight decrease following the control task. Anxiety also substantially enhanced the effects of stress on late phase responses: even skin tests performed the day after the stressor reflected the continuing impact of the speech stressor among the more anxious participants. Greater anxiety was associated with more IL-6 production by Con A-stimulated leukocytes following the stressor compared to the control visit. The data suggest that stress and anxiety can enhance and prolong AR symptoms.
PMCID: PMC2819057  PMID: 19150180
Allergies; psychoneuroimmunology; stress; anxiety; allergic rhinitis; skin tests
6.  570 Atopy Patch Test to Aeroallergens Extracts is Useful In Allergic Diseases Diagnosis When Skin Prick Test is Negative 
The World Allergy Organization Journal  2012;5(Suppl 2):S197-S198.
The atopic diseases are generally diagnosed by performing skin prick tests (SPTs) to different aeroallergens. However, when this study results negative, it is possible to perform atopy patch test (APT). This technique has been introduced to evaluate sensitization to aeroallergens in patients with atopic eczema dermatitis syndrome. Nevertheless, its role in other allergic diseases has not been proved. Objective: Evaluate aeroallergens response using skin prick test (SPT) and atopy patch test (APT) in patients with allergic diseases.
Retrospective cohort study of individuals who performed SPT and APT as part of allergic diseases study. The study subjects were patch and skin prick tested to house dust mite (Dermatophagoides), trees, grass and fungi mix, cat and dog dander, among others. The tests were performed at the respiratory allergic disease center of Santa Maria Clinic in Santiago, Chile, between January 2010 and April 2011.
Fifty-five patients were included, 18 (33%) males and 37 (67%) females, median age 6 years (range from 3 months to 62 years), with the following diagnosis: atopic dermatitis syndrome (60%), allergic rhinitis (58%), contact allergic dermatitis (16%), asthma (9%), recurrent bronchial obstructive syndrome (7%), allergic rhinoconjuctivitis (4%), chronic cough (4%), recurrent acute otitis media (2%) and recurrent laryngitis (2%). They underwent usual SPTs and APTs with multiple aeroallergens extracts. Of the 55 patients, 22 showed a positive SPT and 32 a positive APT; in 14 (25%) both, SPT and APT were positive. In 8 (15%) the SPT was positive and APT negative, while in 18 (33%) the SPT was negative, but the APT positive. Fifteen (27%) were negative to both tests.
Our results show that APT might be a useful diagnosis test in patients with allergic diseases and that its routine use can improve their diagnosis.
PMCID: PMC3513076
7.  Oropharyngeal angioedema induced by inhaled histamine. 
Journal of Korean Medical Science  2002;17(6):830-832.
Inhaled histamine used to measure airway responsiveness produces some side effects more frequently than does methacholine. It is possible that the inhaled histamine induces the side effects in asthmatics with increased end organ responsiveness to histamine. A 56-yr-old woman with chronic idiopathic angioedema presented with asthma-like symptoms. Methacholine challenge test was performed, with a negative result. Five days later, histamine inhalation test was done. FEV1 fell by 37% after inhalation of histamine concentration of 8 mg/mL. Immediately thereafter, severe angioedema on face, lips, and oropharyngeal area, foreign body sensation at throat, and hoarseness occurred. To assess end organ responsiveness to histamine, skin prick tests with doubling concentrations of histamine (0.03-16 mg/mL) were carried out on the forearm of the patient and six age- and sex-matched asthmatic controls. The wheal areas were measured. The patient showed greater skin responses than the controls. Regression analysis showed that the intercept and slope were greater than cut-off levels determined from six controls. The patient showed an increased skin wheal response to histamine, indicating the enhanced end organ responsiveness to histamine, which is likely to contribute to the development of the oropharyngeal angioedema by inhaled histamine.
PMCID: PMC3054975  PMID: 12483011
8.  Common Whelk (Buccinum undatum) Allergy: Identification of IgE-binding Components and Effects of Heating and Digestive Enzymes 
Journal of Korean Medical Science  2004;19(6):793-799.
In Korea, common whelk (Buccinum undatum) is a popular edible shellfish. The aim of this study was to observe the sensitization rate to common whelk and to characterize its allergens. We carried out skin prick test (SPT) in 1,700 patients with various allergic diseases. Specific IgE were detected by ELISA in the patient sera and ELISA inhibition tests were conducted. IgE-binding components were identified by means of SDS-PAGE and IgE-immunoblotting. The effects of digestive enzymes were evaluated in both raw and thermally treated extracts. SPT to common whelk was positive (≥2+) in 83 (4.9%) patients studied. Twenty-four (38.7%) out of 62 SPT positive patients had high serum specific IgE to common whelk. ELISA inhibition test showed significant inhibitions by abalone as well as by common whelk. IgE-immunoblotting demonstrated three IgE-binding components (40, 71, 82 kDa), which were digested by simulated intestinal fluid and moderately digested by simulated gastric fluid, and the digestibility of allergens remained unchanged after thermal treatment. In conclusion, IgE-sensitization rate to common whelk was 4.9% in allergy patients. IgE-immunoblotting demonstrated three IgE-binding components, which were degraded by digestive enzymes. Further studies are needed to evaluate the clinical significance of the sensitized patients to common whelk.
PMCID: PMC2816299  PMID: 15608387
Mollusca; Shellfish; Common Whelk; Food Hypersensitivity; Skin Tests; Digestion
9.  Variability in Skin Prick Test Results Performed by Multiple Operators Depends on the Device Used 
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.
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.
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.
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.
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.
PMCID: PMC3651175  PMID: 23282421
device; skin prick test; variability
10.  A Case of Occupational Rhinitis Caused by Porcine Pancreatic Extract Developing into Occupational Asthma 
Journal of Korean Medical Science  2008;23(2):347-349.
Porcine pancreatic extracts (PPE), which are widely used as a digestive drug in Korea, are composed of α-amylase and lipase. Such enzymes are commonly described as occupational allergens. This is the first report of occupational rhinitis caused by PPE developing into occupational asthma in a hospital nurse. She showed strong positive response in the skin prick test (SPT) (5+, wheal ratio of allergen to histamine) and had a high serum-specific IgE level to PPE, but showed a negative response in the methacholine bronchial challenge test (MBT). She had been exposed to PPE intermittently with intermittent medications for rhinitis. Two years later, she presented with rhinitis and additional asthmatic symptoms. In contrast to her first visit, she showed a positive response in the MBT, and developed bronchoconstriction in the PPE-bronchial provocation test (BPT). These findings suggest that inhalation of PPE powder can induce IgE-mediated occupational rhinitis in a hospital setting, which will develop into occupational asthma if avoidance is not complete.
PMCID: PMC2526419  PMID: 18437025
Pancreatic Extracts; Occupational Rhinitis; Occupational Asthma, Specific IgE
11.  Basophil activation test compared to skin prick test and fluorescence enzyme immunoassay for aeroallergen-specific Immunoglobulin-E 
Skin prick test (SPT) and fluorescence enzyme immunoassay (FEIA) are widely used for the diagnosis of Immunoglobulin-E (IgE)-mediated allergic disease. Basophil activation test (BAT) could obviate disadvantages of SPT and FEIA. However, it is not known whether BAT gives similar results as SPT or FEIA for aeroallergens.
In this study, we compared the results of SPT, BAT and FEIA for different aeroallergens.
We performed BAT, SPT and FEIA in 41 atopic subjects (symptomatic and with positive SPT for at least 1 of 9 common aeroallergens) and 31 non-atopic subjects (asymptomatic and with negative SPT).
Correlations between SPT and BAT, SPT and FEIA, and BAT and FEIA results were statistically significant but imperfect. Using SPT as the "gold standard", BAT and FEIA were similar in sensitivity. However, BAT had lower specificity than FEIA. False positive (BATposSPTneg) results were frequent in those atopic subjects who were allergic by SPT to a different allergen and rare in non-atopic subjects. The false positivity in atopic subjects was due in part to high levels of serum Total-IgE (T-IgE) levels in atopic individuals that lead to basophil activation upon staining with fluorochrome-labeled anti-IgE.
As an alternative to SPT in persons allergic to aeroallergens, BAT in its present form is useful for distinguishing atopic from non-atopic persons. However, BAT in its present form is less specific than FEIA when determining the allergen which a patient is allergic to. This is due to IgE staining-induced activation of atopic person's basophils and/or nonspecific hyperreactivity of atopic person's basophils.
PMCID: PMC3398323  PMID: 22264407
Allergic disease; Basophil activation test; Fluorescence enzyme immunoassay; Skin prick test; Aeroallergen; Immunoglobulin-E
12.  Randomized, single-blind, crossover comparison of two rupatadine tablet formulations on histamine-induced cutaneous response in healthy adult volunteers 
Background: Rupatadine is a histamine receptor type 1 antagonist that has been used to treat allergic rhinitis and urticaria.
Objective: The aim of this study was to compare the effect of 2 rupatadine tablet formulations on the inhibition of histamine-induced wheal-and-flare cutaneous responses.
Methods: In this single-blind, single oral dose, crossover study, healthy male volunteers were randomized to receive 10 mg of either a rupatadine reference or test formulation after an overnight fast. After a 10-day washout period, the subjects were crossed over to receive the other formulation. Subjects were asked to sit with their arm resting on the table while histamine was injected intradermally. The skin prick test was performed on the upper half of the volunteers' forearms before administration and at 1, 2, 4, 6, 12, and 24 hours after study drug administration. Fifteen minutes after each skin prick test, the wheal-and-flare responses were visualized under a bright lamp. AUC0–24 was the primary end point.The 90% CI of least squares mean ratio (%) of the test: reference formulations for maximum inhibition of histamine-induced wheal-and-flare response (Imax%), Tmax, AUC0–24 mm2/h, and AUC0–24%/hr were expected to be within 80% to 125% of untransformed data and 80% to 120% of log-transformed data for the 2 formulations to be considered pharmacodynamically equivalent. Subjects were monitored for any spontaneously reported adverse event (AE) throughout the study. In addition, they were specifically asked about the occurrence of any AEs on a checklist (ie, drowsiness, dizziness, dryness of mouth, itching sensation, headache, nausea) throughout the study.
Results: Of the 15 subjects assessed for inclusion, 12 healthy male volunteers (mean [SD] age, 30 [5] years; height, 162 [6] cm; weight, 58 [6] kg) participated in the study. Administration of reference and test formulations of rupatadine significantly inhibited the histamine-induced cutaneous responses in all subjects (P <0.001). Wheal Imax% with the reference and test formulations was 67.97% (11.57%) and 66.76% (9.40%), respectively. Flare Imax% was 59.06% (11.95%) and 56.92% (16.31%), respectively. None of the subjects withdrew from the study due to AEs. Both formulations were well tolerated except for an itching sensation on injection of histamine in all patients; no subject complained of any adverse drug reaction.
Conclusion: In this small study of healthy adult males, the test formulation of the rupatadine tablet was found to be pharmacodynamically equivalent to the reference formulation, as measured by inhibition of histamine-induced cutaneous wheal-and-flare responses.
PMCID: PMC3969931
rupatadine; healthy subjects; pharmacodynamic equivalence; histamine-induced cutaneous response
13.  515 Prevalence of Latex Sensitization Between Medicine and Dentistry Students from Nuevo Leon University 
The World Allergy Organization Journal  2012;5(Suppl 2):S180-S181.
Latex allergy has become an important health problem in the last 2 decades. Sensitization in general population is about 1%.1 Healthcare workers have a frequency of 2% to 25%.2 There is not information about this issue in Mexico. Our objective was to know and compare prevalence of latex sensitization in last grade medicine and dentistry students of the Nuevo Leon University.
This was an observational, prospective and comparative study. Last grade medicine and dentistry students were invited to participate. Spanish version of the Latex Allergy Questionnaire (ACAAI recommended) and skin tests for latex: prick test (SPT) (latex extract Allerstand 1:20 w/v), prick by prick (PBPT) (latex gloves) were performed in every patient. Positive control was histamine 10 mg/mL and glycerinated solution for negative control (allerstand) using duotip test disponsable. SPT and PBPT were read 15 min after application and positive result were interpreted as a wheal diameter of 3 mm more than negative control. Data were analyzed for demographics with Statistical Package for Social Sciences (SPSS v16.0), for comparison between groups of sensitized patients fisher exact test was performed.
Study included 378 patients, 213 (56.3%) dentistry students and 165 (43.7%) medicine students. Male/female ratio was 1.2/1 for medicine and 0.36/1 for dentistry. Average age was 23 years in both groups. General sensitization to latex was 7.1% (27), per group medicine was 6% (10) and dentistry 7.9% (17). Almost to all commercial extract, only one patient in each group was positive to gloves PBPT. By questionnaire 10.9% medicine group and 17.3% of dentistry group report symptoms with latex, but only 14.8% of dentistry group was Skin test positive, no one in medicine group. Rhinitis or conjunctivitis symptoms were found in 48.1% of sensitized patients. Most frequent foods associated with symptoms were pineapple (2.6%), fig (2.1%), avocado (1.9%) and kiwifruit (1.6%). There was no statistical difference between both groups sensitization (P = 0.549).
Latex sensitization was more common in healthcare students than references in general population but symptoms referred to latex no always are demonstrated by IgE sensitization, so delayed mechanism must be take in to account to get a better diagnosis and treatment approach.
PMCID: PMC3513166
14.  Exposure-response relations for work related respiratory symptoms and sensitisation in a cohort exposed to α-amylase 
Methods: A prospective cohort study among 300 bakers and millers was followed up for a maximum of seven years. Exposure to α-amylase was estimated by air measurements and questionnaires and classified into three categories. Symptoms were recorded with a self-administered questionnaire and skin sensitisation assessed using skin prick test (SPT).
Results: There were 36 new cases of chest symptoms, 86 of eyes/nose symptoms, and 24 of a positive SPT to α-amylase. There were exposure-response relations for chest and eyes/nose symptoms and for sensitisation, and a significantly increased prevalence ratio for chest symptoms in the highest exposure category.
Conclusion: A reduction in α-amylase exposure is likely to reduce the risk for respiratory morbidity in bakery workers.
PMCID: PMC1763635  PMID: 15150397
15.  The natural history of milk allergy in an observational cohort 
There are few studies on the natural history of milk allergy. Most are single-site and not longitudinal, and these have not identified a means for early prediction of outcomes.
Children aged 3 to 15 months were enrolled in an observational study with either (1) a convincing history of egg allergy, milk allergy, or both with a positive skin prick test (SPT) response to the trigger food and/or (2) moderate-to-severe atopic dermatitis (AD) and a positive SPT response to milk or egg. Children enrolled with a clinical history of milk allergy were followed longitudinally, and resolution was established by means of successful ingestion.
The cohort consists of 293 children, of whom 244 were given a diagnosis of milk allergy at baseline. Milk allergy has resolved in 154 (52.6%) subjects at a median age of 63 months and a median age at last follow-up of 66 months. Baseline characteristics that were most predictive of resolution included milk-specific IgE level, milk SPT wheal size, and AD severity (all P < .001). Baseline milk-specific IgG4 level and milk IgE/IgG4 ratio were not predictive of resolution and neither was expression of cytokine-inducible SH2-containing protein, forkhead box protein 3, GATA3, IL-10, IL-4, IFN-γ, or T-bet by using real-time PCR in CD25-selected, casein-stimulated mononuclear cells. A calculator to estimate resolution probabilities using baseline milk IgE level, SPT response, and AD severity was devised for use in the clinical setting. Conclusions: In this cohort of infants with milk allergy, approximately one half had resolved over 66 months of follow-up. Baseline milk-specific IgE level, SPT wheal size, and AD severity were all important predictors of the likelihood of resolution.
PMCID: PMC3691063  PMID: 23273958
Milk allergy; natural history; food allergy; IgE
16.  Predicting Allergic Disease at Age Four Using an Atopy Predisposition Score at Age Two: The Application of Item Response Theory 
Pediatric Allergy and Immunology  2011;23(2):195-201.
When defining allergic outcomes in epidemiology studies results of the skin prick test (SPT) panel is often dichotomized as positive/negative or categorized based on the number of positive responses. Item Response Theory (IRT) models, however, may prove to be a better alternative with the ability to generate scores that account for both type and number of positive SPTs. IRT was applied to SPT responses administered to 537 children at age two in order to determine predictability of allergic disease at age four. The children received SPTs to 15 aeroallergens and two foods. Atopy predisposition scores were obtained from the IRT model using the posterior distribution of the latent trait, atopy. These scores were used to predict persistent wheeze, rhino-conjunctivitis, and eczema at age four. Results were compared to the dichotomized and categorical (positive to ≥ 2, positive to one, versus negative to all allergens) SPT variables. At age two, 39% of children had at least one positive SPT. All three allergic disease outcomes were significantly associated with IRT atopy scores: persistent wheeze odds ratio (OR)=1.7 (95% confidence interval (CI): 1.2, 2.3); rhino-conjunctivitis OR=1.7 (95% CI:1.2, 2.3); eczema OR=1.6 (95% CI: 1.2, 2.3). In contrast, rhino-conjunctivitis was the only outcome significantly associated with the dichotomized SPT variable with an OR=1.9 (95% CI:1.2, 3.0). For the categorical SPT variable, all three allergic symptoms were significantly associated with positive to ≥ 2 allergens compared to negative to all, but no difference was observed between those with positive to one compared to negative to all. The IRT model proved to be an informative methodology to assess the predictability of early SPT responses and identify the allergens most associated with atopy predisposition.
PMCID: PMC3310291  PMID: 22192382
Item Response Theory; Skin Prick Test; Allergy; Atopy; Asthma; Wheeze; Rhino-conjunctivitis; Eczema; Predicting allergies
17.  Skin prick testing with extensively heated milk or egg products helps predict the outcome of an oral food challenge: a retrospective analysis 
Cow’s milk and hen’s egg are the most frequently encountered food allergens in the pediatric population. Skin prick testing (SPT) with commercial extracts followed by an oral food challenge (OFC) are routinely performed in the diagnostic investigation of these children. Recent evidence suggests that milk-allergic and/or egg-allergic individuals can often tolerate extensively heated (EH) forms of these foods. This study evaluated the predictive value of a negative SPT with EH milk or egg in determining whether a child would tolerate an OFC to the EH food product.
Charts from a single allergy clinic were reviewed for any patient with a negative SPT to EH milk or egg, prepared in the form of a muffin. Data collected included age, sex, symptoms of food allergy, co-morbidities and the success of the OFC to the muffin.
Fifty-eight patients had negative SPTs to the EH milk or egg in a muffin and underwent OFC to the appropriate EH food in the outpatient clinic. Fifty-five of these patients tolerated the OFC. The negative predictive value for the SPT with the EH food product was 94.8%.
SPT with EH milk or egg products was predictive of a successful OFC to the same food. Larger prospective studies are required to substantiate these findings.
PMCID: PMC3394206  PMID: 22591833
18.  CD14 Gene Variants and Their Importance for Childhood Croup, Atopy, and Asthma 
Disease Markers  2013;35(6):765-771.
Background. The CD14 gene has an important role in the detection of inflammatory provoking pathogens and in the ensuing signaling of the innate immune response. We assessed the role of CD14 C-159T, G-1359T in the expression of asthma, croup, and allergy in Canadian school children of ages 6 to 14 years. Methods. Children attending schools in a rural community participated in a cross-sectional survey of respiratory health. Following consent, we conducted clinical assessments to collect buccal swabs for genotyping and perform skin prick testing (SPT) to determine atopic status. Genotyping and SPT results were available for 533 and 499 children, respectively. Separate multivariable analyses that included both polymorphisms were conducted for each phenotype. Results. The prevalence of asthma, allergy, and croup was 18.6%, 22.4%, and 6.6%, respectively. Children with the T/T variant of CD14 G-1359T were more likely to have physician diagnosed asthma (26.8%). Children with C/C variant of CD14 C-159T had a significantly lower prevalence of croup (2.6%). Haplotype analyses of the two CD14 polymorphisms showed that individuals with the T|T haplotype combination were significantly more likely to have asthma (P = 0.014). Conclusions. In this study, CD14 variants are important for the expression of croup and asthma but not atopy.
PMCID: PMC3856132  PMID: 24347797
19.  Mast cell chymase potentiates histamine-induced wheal formation in the skin of ragweed-allergic dogs. 
Journal of Clinical Investigation  1990;86(2):555-559.
Skin mast cells release the neutral protease chymase along with histamine during degranulation. To test the hypothesis that chymase modulates histamine-induced plasma extravasation, we measured wheal formation following intradermal injection of purified mast cell chymase and histamine into the skin of ragweed-allergic dogs. We found that chymase greatly augments histamine-induced wheal formation. The magnitude of the potentiating effect increases with increasing doses of chymase and becomes maximal approximately 30 min after administration. Injection of chymase without histamine does not evoke wheal formation. The chymase potentiation of histamine-induced skin responses is prevented completely by pretreatment with the H1-receptor antagonist pyrilamine, and is prevented by inactivation of chymase with soybean trypsin inhibitor, suggesting that both histamine and preserved catalytic activity are required for the effects of chymase. To examine the effects of histamine and chymase released in situ in further experiments, we measured wheal size following local degranulation of mast cells by intradermal injection of ragweed antigen or compound 48/80. We found that pretreatment with either soybean trypsin inhibitor or pyrilamine markedly reduces ragweed antigen- or 48/80-induced wheal formation, supporting the results obtained by injection of exogenous chymase and histamine. These findings suggest a novel and important proinflammatory role for chymase in modulating the effects of histamine on vascular permeability during mast cell activation.
PMCID: PMC296760  PMID: 2384602
20.  370 Correlation Between Skin Prick Test and Mast Results in Patients with Chronic Rhinitis 
The World Allergy Organization Journal  2012;5(Suppl 2):S135-S136.
Among methods to confirm the allergic causes of chronic rhinitis, the most common and the most reliable method is skin prick test, followed by MAST, which is reported to be compatible to skin prick test, with acceptable sensitivity and specificity. This study was designed to confirm whether MAST is reliable test in diagnosing allergic rhinitis.
Retrospective chart review was conducted with chronic rhinitis patients who visited Yeouido St. Mary's Hospital between January 2010 and June 2011. Subjects were selected with whom the results of skin prick test and MAST were found.
One hundred and ninety three subjects, 111 male and 82 females, were included and the mean age was 30.08 (range 6∼77). MAST was performed for 42 inhalant allergens and skin prick test was performed for 56 allergens including histamine and control.
Subjects who have one or more positive allergen in skin prick test were 132, and positive in MAST were 104. Sensitivity was 63.16%, specificity was 65.57% and efficiency was 63.92%.
Number of positive allergen in skin prick test was 2.42 in average and among positive subjects, 3.53. In MAST, positive allergen count was 2.1 in average and among positive subjects, 4.0. Positive rates per common allergens in skin prick test were as follow; Dermatophagoides farinae 79.69% (106 subjects), Dermatophagoides pteronyssinus 68.42% (91 subjects), oak pollen 12.78% (17 subjects). Positive rates per common allergens in MAST were as follow; Dermatophagoides farinae 69.52% (73 subjects), Dermatophagoides pteronyssinus 59.05% (62 subjects), housedust 50.48% (53 subjects).
Skin prick test result was analyzed as from negative to 6+, according to relative size of the allergen wheal compared with histamine wheal and MAST result was analyzed as from negative to class 6, according to the concentration of the solution. When we defined correlation as difference between positive count in skin prick test and class in MAST were less than 2, the correlation rate in Df was 65.80%, 59.07% in Dp.
The correlation between MAST and skin prick test is not high enough to use MAST as a diagnostic test for allergic rhinitis. The more study to confirm the reliability of MAST should be conducted.
PMCID: PMC3512731
21.  Histamine 50-Skin-Prick Test: A Tool to Diagnose Histamine Intolerance 
ISRN Allergy  2011;2011:353045.
Background. Histamine intolerance results from an imbalance between histamine intake and degradation. In healthy persons, dietary histamine can be sufficiently metabolized by amine oxidases, whereas persons with low amine oxidase activity are at risk of histamine toxicity. Diamine oxidase (DAO) is the key enzyme in degradation. Histamine elicits a wide range of effects. Histamine intolerance displays symptoms, such as rhinitis, headache, gastrointestinal symptoms, palpitations, urticaria and pruritus. Objective. Diagnosis of histamine intolerance until now is based on case history; neither a validated questionnaire nor a routine test is available. It was the aim of this trial to evaluate the usefullness of a prick-test for the diagnosis of histamine intolerance. Methods. Prick-testing with 1% histamine solution and wheal size-measurement to assess the relation between the wheal in prick-test, read after 20 to 50 minutes, as sign of slowed histamine degradation as well as history and symptoms of histamine intolerance. Results. Besides a pretest with 17 patients with HIT we investigated 156 persons (81 with HIT, 75 controls): 64 out of 81 with histamine intolerance(HIT), but only 14 out of 75 persons from the control-group presented with a histamine wheal ≥3 mm after 50 minutes (P < .0001). Conclusion and Clinical Relevance. Histamine-50 skin-prickt-test offers a simple tool with relevance.
PMCID: PMC3658496  PMID: 23724226
22.  Antihistamines as prophylaxis against side reactions to intravenous fluorescein. 
Systemic antihistamines were administered prior to dye injection in 50 patients undergoing fluorescein angiography. The patients were monitored for side effects. Venous blood samples were obtained before and at three, ten and thirty minutes after intravenous administration of sodium fluorescein and analyzed for histamine levels. Three patients (6%) developed minor side effects of nausea or dizziness; this compares to an incidence of 21% in a previous series of patients from our institution untreated with antihistamines. A three-fold increase in plasma histamine levels occurred in 28% of patients following fluorescein and antihistamine injection; this compares with a 26% incidence of increase in plasma histamine in patients receiving fluorescein without antihistamines (as determined in a previous study). Prophylactic antihistamines should be considered in patients undergoing fluorescein angiography if they have a history of previous allergies or side reactions during prior fluorescein studies. However, complete prophylaxis against severe side reactions to fluorescein injections is not assured with antihistamines.
PMCID: PMC1312139  PMID: 7257056
23.  419 IGE-mediated Responses Towards Fish Parasite Anisakis, Crab and House Dust Mite in Norwegian Shrimp Allergic Individuals 
The present study investigated to what extent shrimp allergic individuals were IgE-sensitized to anisakis, crab and house dust mite and whether tropomyosin was responsible for IgE cross-reactivity.
29 Individuals with self reported shrimp allergy were recruited by advertisements in local and national news-papers in Norway. Anamnesis was taken, skin prick tests (SPT) were performed and positive responders to shrimp were studied further with basophile activation test (BAT), ImmunoCAP analyses and western blotting.
Of the 29 persons studied, 10 (34%) had positive SPT against shrimp and house dust mite, 9 (31%) against shrimp tropomyosin and 3 (10%) against anisakis. Individuals with positive SPT to shrimp all showed positive basophilic responses to house dust mite, while 43% responded to shrimp, 25% to anisakis and 36% to crab in BAT. Moreover, SPT, BAT as well as ImmunoCAP analyses showed a positive correlation of IgE-reactivity between anisakis and shrimp, house dust mite and crab. Immunoblot studies indicated that these responses are not completely explained by cross-reactivity towards tropomyosin.
The current study indicates a positive correlation between IgE-mediated reactions to shrimp, anisakis, house dust mite and crab, which may not be completely explained by cross-reactivity against tropomyosin.
PMCID: PMC3513067
24.  575 Photoaging Attenuates Skin Test Response to Histamine More Than Natural Aging 
Clinical experience suggests that skin test reactivity is often decreased in photo-exposed skin versus sun-protected skin in older individuals. The current study was designed to address whether photoaging or natural aging of skin causes a greater diminution in skin test reponse.
Prick-puncture skin tests to histamine were performed on sun-exposed and sun-protected areas in younger (n = 61, age 20–50) and older (n = 63, age 60–87) adult volunteers who were recruited for skin prick testing because of suspect allergic rhinitis and/or allergic asthma. The skin was scored for photoaging by physical examination and coloration was measured by a colorimeter.
There was no observed difference in wheal and flare response to histamine when patients were stratified by age alone. However, photoaging was significantly correlated with decreased skin reactivity to histamine on the upper back (a sun-exposed area) as compared to the lower back (a sun-protected area). In patients with the most severely sun-damaged skin, there was a trend toward decreased skin reactivity in all areas.
Skin test reactivity to histamine is negatively correlated to the degree of photoaging and is independent of patients' chronological age. This result has clinical implications for patients with significant photoaging, suggesting that care should be taken to perform skin testing on anatomic sites in sun-protected areas. In patients with severe photoaging, allergen-specific IgE testing should be considered to avoid possible false-negative interpretation of skin-prick testing.
PMCID: PMC3513004
25.  Both Variability and Level of Mouse Allergen Exposure Influence the Phenotype of the Immune Response in Workers at a Mouse Facility 
The role of natural aeroallergen exposure in modulating allergen-specific immune responses is not well understood.
To examine relationships between mouse allergen exposure and mouse-specific immune responses.
New employees (n=179) at a mouse facility underwent repeated assessment of mouse allergen exposure, skin prick testing (SPT), and measurement of mouse-specific IgG. Relationships between the mean level of exposure, variability of exposure (calculated as log standard deviation), and time to development of immunologic outcomes were examined using Cox proportional hazards models.
By 24 months, 32 (23%) participants had developed a +SPT and 10 (8%) had developed mouse-specific IgG4. The incidence of a +SPT increased as levels of exposure increased from low to moderate, peaking at 1.2 ng/m3 and decreased beyond this point (p=.04). The more variable the exposure was across visits, the lower the incidence of a +SPT (HR [95% CI]: 0.17 [0.07–0.41]). Variability of exposure was an independent predictor of +SPT in a model that included both exposure metrics. In contrast, the incidence of mouse-specific IgG4 increased with increasing levels of mouse allergen exposure (2.9 [1.4–6.0]), and there was evidence of a higher risk of mouse-specific IgG4 with greater variability of exposure (6.3 [0.4–95.2]).
Both level and variability of mouse allergen exposure influence the humoral immune response, with specific patterns of exposure associated with specific immunophenotypes. Exposure variability may be a more important predictor of +SPT, while average exposure level may be a more important predictor of mouse-specific IgG4.
PMCID: PMC3149759  PMID: 21696812
mouse allergen; IgE; IgG4; laboratory animal allergy

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