Histamine Skin Prick Test Research Articles

Colour change in the human histamine wheal made visible by LYYN: a technique to enhance colour differences

Colour differences in photographs can be enhanced using a digital image-processing technique called LYYN. To investigate colour changes in the histamine wheal after skin prick tests (SPTs). Histamine SPTs were performed on the forearm of six medical students, and the reactions of the skin were photographed every 2min for 30min. Colour differences in the photographs were then enhanced using the LYYN technique. These images were processed using ImageJ to yield numerical values. In the LYYN-processed images, there was a rapid colour change in the histamine wheals between the 18th and the 20th minute (P<0.01). Histamine perfusion in isolated rabbit ears indicated vasodilatation in post-capillary vessels and desensitized histamine 1 (H1) receptors after a mean of 17min. It is possible that a similar desensitization takes place in the human histamine wheal, and a study of two histamine SPTs 90 min apart at the same site supports this hypothesis. The LYYN technique was sensitive enough to discover a rapid colour change in the histamine wheal, a change that has not been described before.

H1-antihistamines suppress wheal-and-flare reaction and skin blood perfusion measured by Laser Dopppler flowmetry: randomized, double-blind, placebo-controlled, crossover design study

H1-antihistamines suppress wheal-and-flare reaction and skin blood perfusion measured by Laser Dopppler flowmetry: randomized, double-blind, placebo-controlled, crossover design study The aim of our study was to compare the influence of pre-treatment with H1-antihistamines (levocetirizine, desloratadine, clemastine, quifenadine, and sequifenadine) and a placebo on the histamine-induced weal and flare reaction, increase of skin blood perfusion and sedation. Thirty healthy volunteers were enrolled in the study. The study design was a prospective, randomised, double-blind, placebo-controlled, crossover, balanced clinical trial. Volunteers in randomised and double-blind order were treated with oral levocetirizine 5 mg, desloratadine 5 mg, clemastine 1 mg, quifenadine 50 mg, sequifenadine 50 mg or a placebo. Two hours after intake of medication, the histamine skin prick test was performed and skin blood perfusion was registered with further evaluation of sedative effect. We conclude that levocetirizine induced a significant and pronounced decrease of weal and flare reaction and skin blood perfusion compared to the placebo and the other H1-antihistamines. The effect of quifenadine and sequifenadine on weal reaction area was similar to desloratadine and clemastine. Regarding the sedative effect, we can conclude that second generation antihistamines appear to be not non-sedative but the least impairing, and the first generation antihistamines appear to be the most impairing on central nervous system function. There is a necessity to consider the sedating potential of antihistamines, along with other factors such as efficacy, when prescribing antihistamines to patients.

Comparison of inhibition of cutaneous histamine reaction of ebastine fast-dissolving tablet (20 mg) versus desloratadine capsule (5 mg): A randomized, double-blind, double-dummy, placebo-controlled, three-period crossover study in healthy, nonatopic adults

Background:Ebastine is a long-acting, second-generation, selective histamine H1-receptor antagonist. A fast-dissolving tablet formulation of ebastine has been developed at 10- and 20-mg doses, with the intention of facilitating administration to patients experiencing problems with swallowing, including those confined to bed and elderly people, as well as those who may need to use ebastine when they do not have easy access to water to aid swallowing a tablet. Objectives:This study was conducted to assess the pharmacodynamic effects (ie, inhibition of wheal response to cutaneous histamine challenge, and subjective assessments of itching, flare, and pain) and tolerability of the fast-dissolving 20-mg ebastine tablet formulation compared with desloratadine 5-mg capsule and placebo. Acceptability and convenience of the fast-dissolving tablet were also evaluated. Methods:This double-blind, double-dummy, randomized, placebo-controlled, 3-period crossover study was conducted at the Drug Research Centre, Department of Clinical Pharmacology, the Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. Healthy, nonatopic, white adults aged 18 to 40 years were randomly assigned to 1 of 6 study sequences: ABC, ACB, BAC, BCA, CBA, or CAB, where A was the ebastine fast-dissolving 20-mg tablet, B was the desloratadine 5-mg capsule, and C was placebo. All study drugs were given orally once daily (8–9 AM) on days 1 to 5 of each study period. Study periods were separated by a washout period of 7 to 10 days. Histamine skin-prick test (SPT) challenge was performed before study drug administration on day 1 of each period (baseline), and then every 20 minutes for 2 hours after administration and again after 24 hours. The final SPT was 24 hours after the day-5 dose was administered. The primary end point was inhibition of the histamine response, defined as the percentage reduction from baseline wheal area 24 hours after 5 days of administration. Subjective symptoms (itching, flare, and pain) were assessed by subjects using visual analog scales every 20 minutes for 2 hours after administration on day 1. At study end, acceptability (taste, convenience, and overall preference) of the fast-dissolving tablet and capsule formulations were assessed using a questionnaire completed by subjects. Tolerability was assessed using physical examination, laboratory analysis, physician questioning, and spontaneous reporting. Results:Thirty-six people were randomized (22 women, 14 men; mean [SD] age, 24.7 [4.1] years; mean [SD] weight, 63.2 [9.9] kg); 35 completed the study (1 subject was lost to follow-up after the second study period). Unadjusted mean (SD) wheal areas 24 hours after dose administration on day 5 were 72.9 (29.5), 115.0 (32.1), and 146.7 (32.2) mm2, for ebastine, desloratadine, and placebo, respectively. Mean differences in reduction from baseline in wheal area were 29.0% for ebastine versus desloratadine and 43.7% for ebastine versus placebo (both, P < 0.001). Corresponding unadjusted mean (SD) wheal areas 24 hours after administration of the first dose on day 1 were 76.5 (22.5), 128.9 (24.0), and 140.5 (33.1) mm2. Mean itching, flare, and pain ratings were not significantly different between study drugs. Results from the preference questionnaire indicated that the majority (80%) preferred the ebastine fast-dissolving tablet to the desloratadine capsule (and hypothetically also to tablets and oral solution, which were not tested in this study). Ninety-seven percent of subjects were of the opinion that compliance in the home setting would be facilitated by the fas-tdissolving tablet formulation. Fourteen adverse events (AEs) were reported in 9 (25%) volunteers; all AEs were of mild or moderate intensity. Five occurred with ebastine 20 mg (intermittent somnolence, back pain, pharyngolaryngeal pain, pyrexia, and oral pain [1 patient each]), 5 occurred with desloratadine 5 mg (asthenia [2 patients] and dry mouth, somnolence, and back pain [1 patient each]), and 4 occurred with placebo (diarrhea [2 patients] and somnolence and headache [1 patient each]). The relationship with the study drugs was considered unlikely in 6 cases and possible in the remaining 8 cases. An additional AE (back pain) occurred during a washout period. Conclusions:In this small study in healthy, nonatopic white subjects, inhibition of the response to histamine injection was significantly greater with the ebastine 20-mg fast-dissolving tablet compared with desloratadine 5-mg capsule and placebo after 1 and 5 days of administration. Most participants expressed an overall preference for the fast-dissolving tablet formulation over capsules. All study drugs were well tolerated.

Circadian variations of histamine binding to lymphocytes and neutrophils and skin reactivity to histamine in atopic and healthy subjects

Numerous pathophysiological conditions change during 24-hour periods. Histamine, the main mediator in allergic reactions, exerts a multiplicity of pathophysiological actions through binding to specific receptors on effector cells. Nocturnal exacerbation of symptoms occurs in many atopic diseases in which histamine is an important mediator. Nocturnal wheezing is a very common symptom of asthma. The aim of this study was to determine whether the binding of (fluorescein-labeled) histamine to cells participating in allergic-inflammatory processes (lymphocytes, neutrophils) and skin reactivity to histamine undergo circadian changes and to compare these phenomena in atopic asthmatic and healthy subjects. Blood samples were collected at 8 am, 2 pm, 8 pm, 2 am, and 8 am the next day. Histamine skin-prick tests were performed at the same times. It was found that skin reactivity to histamine (wheal, erythema) in healthy subjects underwent significant circadian changes with acrophase at 8 am (wheal) or 8 pm (erythema), the lowest values being at night (2 am, p = 0.017), in contrast to atopics, in whom the highest reactivity was found at night (2 am, p = 0.002). Significant differences in the binding of fluorescein-labeled histamine between day (8 am-2 pm) and night (2 am) were observed for lymphocytes (p = 0.006) and neutrophils (p = 0.018). In the asthmatic group these changes were not significant. Circadian changes in both the binding of histamine by effector cells and skin reactivity to histamine were different in healthy and asthmatic subjects, and this may play a role in the pathomechanism, course, and chronopharmacotherapy of atopic diseases.

A comparison of levocetirizine and desloratadine in the histamine-induced wheal and flare response in human skin in vivo

The histamine-induced wheal and flare response was used to compare quantitatively the antihistaminic potency of levocetirizine and desloratadine. In this double-blind, placebo-controlled crossover study, 24 healthy male non-atopic volunteers received weekly single doses of 1.25, 2.5 or 5 mg levocetirizine, 2.5, 5 or 10 mg desloratadine, or placebo. Four hours after dosing, histamine (100 mg/ml) skin prick tests were performed on the volar surface of both forearms. The diameters of the wheals and flares were measured 10 minutes later. Sedation was evaluated using a visual analogue scale and a motricity test. The effects of individual drug doses were compared using Student's t-test for paired data and the overall effects of the two drugs by ANOVA. All doses of levocetirizine significantly (P < 0.0001) inhibited both wheals and flares in a dose-related manner. Only the 10 mg dose of desloratadine achieved significant inhibition of response. ANOVA showed levocetirizine to be significantly (P < 0.0001) more active than desloratadine. Neither drug caused significant sedation or loss of motricity. Levocetirizine is significantly more effective than desloratadine in inhibiting wheal and flare responses to histamine in human skin in vivo, with 1.25 mg levocetirizine being more effective than 10 mg desloratadine.

Antiallergic and antihistaminic effect of two extracts of Capparis spinosa L. flowering buds

The antiallergic properties of two lyophilized extracts obtained from Capparis spinosa L. flowering buds (capers) by methanol extraction, carried out at room temperature (CAP-C) or with heating at 60 degrees C (CAP-H), were investigated. The protective effects of CAP-H and CAP-C, orally administered (14.28 mg[sol ]kg), were evaluated against Oleaceae antigen challenge-induced and histamine-induced bronchospasm in anaesthetized guinea-pigs. Furthermore, the histamine skin prick test was performed on humans, applying a gel formulation containing 2% CAP-C (the only extract able to protect against histamine-induced bronchospasm) on the skin for 1 h before histamine application and monitoring the erythema by reflectance spectrophotometry. The CAP-H showed a good protective effect against the bronchospasm induced by antigen challenge in sensitized guinea-pigs; conversely, a significant decrease in the responsiveness to histamine was seen only in CAP-C pretreated animals. Finally, the CAP-C gel formulation possessed a marked inhibitory effect (46.07%) against histamine-induced skin erythema. These two caper extracts displayed marked antiallergic effectiveness; however, the protective effect of CAP-H was very likely due to an indirect mechanism (for example, inhibition of mediator release from mast cells or production of arachidonic acid metabolites); conversely, CAP-C is endowed with direct antihistaminic properties. The different mechanisms of action of CAP-H and CAP-C may be related to a difference in the extraction procedure and, thus, in their qualitative[sol ]quantitative chemical profile.

Bimodal skin reactivity to histamine in atopic children in Singapore: influence of specific sensitizations

Histamine skin prick test (SPT) is used as the 'golden standard' for positive control in in vivo immediate type hypersensitivity testing. The skin reactivity to histamine can, however, be modulated by a bevy of extraneous factors. We aimed to define whether histamine skin reactivity in atopic children in Singapore is influenced by age, ethnic origin, gender, environmental exposure or specific sensitization patterns. A retrospective analysis of children, with specific aeroallergen sensitization (as measured by at least one allergen-specific SPT with a wheal size > 3 mm compared with the negative control) from the outpatient speciality clinic of the KK Children's Hospital, during 06/2002-06/2003. A total of 315 patients were included, 235 (75%) were males, 252 (80%) were Chinese, age mean was 7.7 yr (range: 2-15). Patients were referred to the SPT with a diagnosis of one or more of: allergic rhinitis 287 (91%), asthma 112 (36%) or atopic dermatitis 60 (19%). The mean histamine response showed a bimodal distribution, independent of age, ethnic origin, gender or phenotypical expression of allergic disease. Histamine skin reactivity was higher in atopic patients with polysensitization (mean 5.0 mm vs. 2.9 mm in monosensitized patients, p < 0.001), and in patients with mould sensitization (mean 5.1 mm vs. 3.3 mm in patient not sensitized to moulds, p < 0.001). The presence of passive smoking increased the likelihood of a diminished histamine skin response. Histamine skin response data strongly suggested the presence of two heterogeneous subpopulations. Children with polysensitization and mould sensitization were more likely to show a large significant histamine response, whereas children with passive smoke exposure, showed a diminished skin reactivity to histamine.

Changes over 13 years in skin reactivity to histamine in cohorts of children aged 9-13 years.

Several studies report substantial differences in the prevalence of skin test reactivity to allergens in children from adjacent geographic areas; others report an increased prevalence over time. To find out whether these differences depend on variations in skin reactivity to histamine, we determined the time trend of histamine wheal sizes in successive cohorts of unselected children living in the same area (Viterbo, Italy). We conducted three epidemiologic surveys, each including children aged 9 and 13 years. The 1983-7 study investigated 170 children (150 were tested twice); the 1992 study, 158 children; and the 1996 study, 208 children. In both age groups, the mean diameter of the wheal induced by histamine skin prick tests (10 mg/ml) increased significantly over time (9-year-olds: 3.25 mm in 1983, 4.68 in 1992, and 5.89 in 1996; 13-year-olds: 3.89 mm in 1987, 5.18 in 1992, and 6.50 in 1996) (P < 0.001 between subsequent studies). The distribution of the wheal diameters for both ages showed a trend to a right shift in the three successive studies (P < 0.001). The dose-response curves for three histamine concentrations (0.2, 1, and 10 mg/ml) had significantly steeper slopes in 1996 than in 1983-7 (P < 0.001). The marked time-related increase in the size of the histamine wheals could help to explain the trend toward an increased prevalence of positive allergen skin test reactions reported during the past years. The causes of increased skin reactivity to histamine remain conjectural.

Activity of ebastine (10 and 20 mg) and cetirizine at 24 hours of a steady state treatment in the skin of healthy volunteers

We have compared the inhibitory effects of ebastine (10 mg), ebastine (20 mg) and cetirizine (10 mg) on histamine-induced wheal and flare skin reactions 24 h following a 6-day-long treatment. This was a double-blind, randomised, crossover, placebo-controlled study involving 24 healthy volunteers (18-65 years) with negative skin prick tests and the absence of specific IgEs to common allergens. Subjects were randomised to receive each of the following treatments once daily for 6 days: ebastine (10 mg), ebastine (20 mg), cetirizine (10 mg) or placebo with a washout period of 5 days. Twenty-four hours after the last dose of each treatment, histamine skin prick tests were performed (0, 0.5, 1, 2.5, 5, 10, 20, 50, 100 and 200 mg/mL), and wheal and flare responses were measured. All active treatments produced significant inhibition of the wheal responses compared to placebo (P < 0.001). Wheal response inhibition was significantly better with 20 mg of ebastine compared with 10 mg of ebastine and 10 mg of cetirizine. In a comparison to histamine concentrations required to produce a wheal surface area of 10 mm2, 20 mg of ebastine was also significantly better than ebastine 10 mg and cetirizine (P < 0.001), and 10 mg ebastine was significantly better than cetirizine (P < 0.05). Highly significant (P < 0.001) effects on the flare response were observed with each active treatment compared to placebo, with no difference between groups. The frequency of adverse events, primarily somnolence, was similar among the four treatment groups. Our results clearly indicate that ebastine, at either recommended dosage of 10 and 20 mg, and cetirizine produced significant inhibition of the histamine-induced wheal and flare reaction compared to placebo for up to 24 h. A superior efficacy of 20 mg of ebastine is observed compared with 10 mg of ebastine and 10 mg of cetirizine on the skin wheal response 24 h after the last dose of a 6-day-long treatment. This study clearly proves ebastine to be an effective, truly once-daily antihistamine.

Double-blind, parallel, randomized pilot study comparing the efficacy and tolerance of cetirizine 10 mg, mequitazine 2 � 5 mg and placebo in the treatment of patients suffering from chronic urticaria: Comparison of suppressive effects on histamine-induced weals and flares

In a double-blind, randomized, parallel-group study, 29 adult patients suffering from chronic urticaria were treated with either cetirizine 10 mg od (n = 10), mequitazine 5 mg bid (n = 10), or placebo (n = 9) for 3 weeks. Three symptoms (weals, erythema, pruritus) were rated according to severity (none, mild, moderate, severe) by the investigator at each of the four visits (days 1, 3, 14, 21). At each visit the investigator and patients also assessed the patients' general condition using a 5-point scoring system (very bad, bad, moderate, good, very good). On day 21 the global evaluation of efficacy and tolerance was assessed by the investigator and patients on a 4-point scale (excellent, good, moderate, bad). Also, a histamine skin-prick test was performed on days 3, 14, and 21. Evaluation of safety was based on the frequency of patients reporting adverse events as well as the clinical laboratory results. The cetirizine, mequitazine, and placebo groups of patients were comparable at inclusion. Overall compliance with the trial schedule was excellent for all groups. After 3 days of treatment a significant improvement in control of all urticaria symptoms was observed in the cetirizine group. Cetirizine elicited a statistically significant better control of pruritus (P = 0.006) and erythema (P = 0.018) than mequitazine on day 21. A trend in favor of cetirizine vs. mequitazine was also observed regarding control of weals (P = 0.114). Cetirizine clearly and rapidly improved the general condition of the patient as evaluated by both patients and investigator compared to the baseline results. The differences vs. mequitazine as well as vs. placebo were statistically significant on every visit, starting from day 3. After three weeks of treatment, the clinical efficacy results in the cetirizine group were rated by both patients and investigator as excellent or good, which was statistically significantly better than the results obtained in the mequitazine and placebo group (P > 0.05). The histamine skin-prick test results revealed a marked difference for the group treated with cetirizine compared to the two other groups in favor of CTZ. On day 3, cetirizine produced a statistically significant suppression of the weals (98%) and flares (74%), compared to 24% and 3%, respectively, by mequitazine. With respect to the tolerance results, no statistically significant differences were observed between the three groups. The safety profile was similar for all groups. No serious adverse event has been reported during the present study, nor did the treatments induce any clinically significant abnormal changes in the laboratory tests. It can be concluded from the present study that the effect of cetirizine was statistically and clinically significantly superior to that of mequitazine. On the other hand, of all parameters studied there were no marked differences between the patients of the mequitazine group and the patients of the placebo group. Drug Dev. Res. 43:185–192, 1998. © 1998 Wiley-Liss, Inc.

Double‐blind, parallel, randomized pilot study comparing the efficacy and tolerance of cetirizine 10 mg, mequitazine 2 × 5 mg and placebo in the treatment of patients suffering from chronic urticaria: Comparison of suppressive effects on histamine‐induced weals and flares

In a double-blind, randomized, parallel-group study, 29 adult patients suffering from chronic urticaria were treated with either cetirizine 10 mg od (n = 10), mequitazine 5 mg bid (n = 10), or placebo (n = 9) for 3 weeks. Three symptoms (weals, erythema, pruritus) were rated according to severity (none, mild, moderate, severe) by the investigator at each of the four visits (days 1, 3, 14, 21). At each visit the investigator and patients also assessed the patients' general condition using a 5-point scoring system (very bad, bad, moderate, good, very good). On day 21 the global evaluation of efficacy and tolerance was assessed by the investigator and patients on a 4-point scale (excellent, good, moderate, bad). Also, a histamine skin-prick test was performed on days 3, 14, and 21. Evaluation of safety was based on the frequency of patients reporting adverse events as well as the clinical laboratory results. The cetirizine, mequitazine, and placebo groups of patients were comparable at inclusion. Overall compliance with the trial schedule was excellent for all groups. After 3 days of treatment a significant improvement in control of all urticaria symptoms was observed in the cetirizine group. Cetirizine elicited a statistically significant better control of pruritus (P = 0.006) and erythema (P = 0.018) than mequitazine on day 21. A trend in favor of cetirizine vs. mequitazine was also observed regarding control of weals (P = 0.114). Cetirizine clearly and rapidly improved the general condition of the patient as evaluated by both patients and investigator compared to the baseline results. The differences vs. mequitazine as well as vs. placebo were statistically significant on every visit, starting from day 3. After three weeks of treatment, the clinical efficacy results in the cetirizine group were rated by both patients and investigator as excellent or good, which was statistically significantly better than the results obtained in the mequitazine and placebo group (P > 0.05). The histamine skin-prick test results revealed a marked difference for the group treated with cetirizine compared to the two other groups in favor of CTZ. On day 3, cetirizine produced a statistically significant suppression of the weals (98%) and flares (74%), compared to 24% and 3%, respectively, by mequitazine. With respect to the tolerance results, no statistically significant differences were observed between the three groups. The safety profile was similar for all groups. No serious adverse event has been reported during the present study, nor did the treatments induce any clinically significant abnormal changes in the laboratory tests. It can be concluded from the present study that the effect of cetirizine was statistically and clinically significantly superior to that of mequitazine. On the other hand, of all parameters studied there were no marked differences between the patients of the mequitazine group and the patients of the placebo group. Drug Dev. Res. 43:185–192, 1998. © 1998 Wiley-Liss, Inc.

Histamine skin prick testing: evaluation of various container materials for long-term storage of histamine solutions

Histamine skin prick testing: evaluation of various container materials for long-term storage of histamine solutions

Does the histamine skin prick test identify patients at risk for toxicity after the ingestion of astemizole?

Astemizole is a widely prescribed nonsedating antihistamine that suppresses wheal and flare reactions from histamine prick testing. We report a two-year-old girl with a serum concentration-proven overdose of astemizole who nonetheless exhibited a significant wheal and flare reaction after histamine skin prick testing for at least 22 hours after the ingestion. These findings suggest that histamine skin prick testing should not be used as a screening test to evaluate whether an ingestion of astemizole has occurred.

Modulation of type I immediate and type IV delayed immunoreactivity using direct suggestion and guided imagery during hypnosis.

Cutaneous reactivity against histamine skin prick test (Type I) and purified tuberculin protein derivative (Mantoux reaction, Type IV) was studied in eight volunteers under hypnosis. Types I and IV immunoreactivity were modulated by direct suggestion (Type I) and guided imagery (Type IV). The volunteers were highly susceptible subjects, selected by means of the Harvard Group Scale of Hypnotic Susceptibility, Form A. When the volunteers underwent hypnotic suggestion to decrease the cutaneous reaction to histamine prick test, a significant (P less than 0.02) reduction of the flare reaction (area of erythema) was observed compared with control histamine skin prick tests. The wheal reaction did not respond to hypnotic suggestion. Neither wheal nor flare reaction could be increased in size by hypnotic suggestion compared with control histamine skin prick tests. A hypnotic suggestion of increasing the Type IV reaction on one arm and decreasing the reaction on the other revealed a significant difference in both erythema size (P less than 0.02) and palpable induration (P less than 0.01). In two cases the reactions were monitored by laser doppler blood flowmetry and skin thickness measurement by ultrasound. The difference between the suggested increased and decreased reaction was 19% for the laser doppler bloodflow (in favor of the augmented side), and 44% for the dermal infiltrate thickness. This study objectively supports the numerous uncontrolled case reports of modulation of immunoreactivity in allergic diseases involving both Type I and Type IV skin reactions following hypnotic suggestions.