The effect of H1 and H2 blockade on cutaneous histamine response in man

Histamine-induced cutaneous wheal responses were measured in 10 healthy subjects. The effect of the potent H1 blocker, hydroxyzine HCl, the H2 blocker, cimetidine, and the two drugs in combination was determined. The H1 blocker alone produced a mean wheal suppression of 75% (p less than 0.001). The H1 plus H2 blocker produced 84% suppression. The augmented suppression of H1 plus H2 blocker vs H1 blocker was statistically significant (p less than 0.02). The H2 blocker alone produced suppression that was not statistically significant. The results provide additional evidence that H2 receptors are present in the human cutaneous microcirculation, and add support to the clinical observation of therapeutic efficacy of H1 plus H2 blockers seen in some patients with chronic urticaria.     

Successful treatment of chronic idiopathic urticaria and angioedema with cimetidine alone

We have studied a 50-year-old white man with chronic urticaria and angioedema who has responded to treatment with cimetidine alone for over 2 yr. In a double-blind, placebo-controlled study, cimetidine alone was at least as effective as chlorpheniramine in relief of urticaria and angioedema. Additionally, cimetidine significantly inhibited (p less than 0.01) the wheal response to histamine when it was compared to placebo. The inhibition of wheal response to histamine by cimetidine was significantly higher (p less than 0.05) than chlorpheniramine. The presence of predominantly H2- rather than H1-histamine receptors in the cutaneous blood vessels may be responsible for the therapeutic effects of cimetidine in this patient.     

Controlled trial of H1 antagonists in the treatment of chronic idiopathic urticaria.

The efficacy of astemizole, diphenhydramine, and hydroxyzine hydrochloride in the treatment of chronic idiopathic urticaria was evaluated in this 3-month double-blind, randomized, parallel group study. Thirty-six adult patients were randomly assigned, 13 to the astemizole group (10 mg daily), 12 to the diphenhydramine group (25 mg t.i.d.), and 11 to the hydroxyzine hydrochloride group (25 mg t.i.d.). Demographic data were statistically similar for all variables assessed in the three treatment groups. Seven (58%) of the diphenhydramine patients withdrew before the end of the study, six because of lack of efficacy and one because of drowsiness. Two (18%) of the hydroxyzine hydrochloride patients withdrew, one because of lack of efficacy and one because of drowsiness. Two patients (15%) in the astemizole group withdrew, one because of adverse reaction, and the other because of lack of efficacy. Mean total symptom scores and mean individual symptom scores were lower in the astemizole group than in the other two groups. Wheal area measurements (0.1 mg/mL histamine challenge) decreased more in the astemizole and hydroxyzine hydrochloride groups than in the diphenhydramie group (P = .02). With regard to symptoms, 12/13 patients in the astemizole group improved clinically during their treatment period, versus 8/11 in the hydroxyzine hydrochloride group and 5/12 in the diphenhydramine group. The mean time to first observed therapeutic effect (maintained for three consecutive days) was 5.5 days in the astemizole group, 10.9 days in the hydroxyzine hydrochloride group, and 7.2 days in the diphenhydramine group. In this study, astemizole was as effective as hydroxyzine in patients treated for chronic idiopathic urticaria.     

The pathology of the autologous serum skin test response in chronic urticaria resembles IgE-mediated late-phase reactions

The wheal-and-flare response to intradermal autologous serum in chronic urticaria offers a model for study of the pathogenesis of the disorder. Serial biopsies of autologous serum induced wheals were performed in 5 chronic urticaria patients to assess the evolution of the cellular inflammatory response and to look for evidence of mast cell degranulation. Perivascular neutrophils and eosinophils were seen as early as 30 min, becoming more intense and diffuse over 2 h. T lymphocyte numbers were increased by 2 h, CD4+ cells outnumbering CD8+ cells at 24 h. By 48 h, the neutrophils were clearing, but eosinophils and lymphocytes persisted. The histology of compound 48/80-induced wheals was similar to serum-induced wheals, but there was little or no response to physiological saline (0.16 M). Stainable mast cells were reduced in compound 48/80- and serum-induced wheals when compared to saline skin tests. Mast cell granules appeared swollen and had lost their characteristic lamellar substructure on electron microscopy of a serum-induced wheal biopsied at 10 min. Eosinophil degranulation was also observed at 2 h. The resemblance of the inflammation to the late phase of IgE-mediated immediate hypersensitivity reactions in atopics supports the concept that a circulating factor causes mast cell degranulation in chronic urticaria and may be important in the pathogenesis of the disorder.     

Inhibiting effect of cetirizine on histamine-induced and 48/80-induced wheals and flares, experimental dermographism, and cold-induced urticaria

A single oral dose of cetirizine, 10 mg, a new H1 antagonist with minimal sedative effects and devoid of anticholinergic activities, was administered to eight healthy subjects. It markedly inhibited the wheal and flare induced 4 hours later by intracutaneously injected histamine and compound 48/80. Dermographism was produced by different pressures (100 to 500 gm/15 mm2) in 10 patients with factitial urticaria. Four hours after 10 mg of cetirizine, the whealing was absent in eight patients and markedly reduced in the other two subjects. In 12 patients with cold urticaria, wheals were induced by 30 seconds to 12 minutes application of an ice cube. Four hours after 10 mg of cetirizine, the urticarial reaction had disappeared in five patients and was decreased in the other patients. No itching was experienced in any of the patients after cetirizine, but the tested areas had an erythema lasting for 20 to 60 minutes.     

Preliminary report on the effects of tiaramide on the ice cube test in patients with idiopathic cold urticaria

Three subjects diagnosed as having idiopathic acquired cold urticaria were studied to assess the ability of orally administered tiaramide to inhibit the wheal induced following cold challenge with ice cubes placed in contact with the skin, and to establish the safety of multiple doses of 250 mg, q.i.d., for one week administered after a single oral dose of 500 mg. Two subjects completed the study. One subject was known to be unresponsive to antihistamines for allergy and the second was intolerant of antihistamines due to side effects. A third subject discontinued treatment due to an adverse reaction experienced while on the study medication. The skin of the forearm of each subject was exposed to cold stimuli for 1, 2, 3, 4, and 5 minutes by placing five ice cubes on the ventral surface at one minute intervals, and removing all simultaneously five minutes after contact with the first cube. The challenge sites were observed for ten minutes and the area of the wheal, intensity of edema and the time of contact necessary to induce the skin response were recorded. The results of this provocative test following the single and multiple dosage administration of tiaramide were compared to baseline skin responses. After one week of tiaramide treatment at 250 mg, q.i.d., both subjects who completed the study had a markedly attenuated skin response to cold challenge and no adverse effects. Our results suggest that absorbable compounds that can inhibit mast cell degranulation may be efficacious in cold urticaria and of particular value in treating patients who do not respond to standard therapy.     

Multicentric study of beclomethasone dipropionate nasal aerosol in adults with seasonal allergic rhinitis

A double-blind, parallel-design multicentric study, in two phases, was conducted to examine the safety and efficacy of 2-wk treatment with various doses of beclomethasone dipropionate nasal aerosol (BDNA) and placebo in adults with seasonal allergic rhinitis. In phase I, 162 patients received BDNA, 33.5 μg/burst (o.d., b.i.d., t.i.d., q.i.d.), or placebo; in phase II, 189 patients received BDNA 42, μg/burst (b.i.d., q.i.d.), or placebo. In both phases, statistically significant (p < 0.05) differences favoring BDNA over placebo were found for all efficacy measures (global evaluation and total and individual symptom scores). In phase I, response to treatment increased as BDNA dosage increased, with a leveling off at t.i.d. dosage. In both phases, marked improvements were seen by week 1, with maximum improvement during week 2. Eighty-seven patients had adverse reactions—sneezing and nasal burning were most common. No suppression in morning cortisol levels was seen, nor were Candida infections promoted. A 2-wk treatment with BDNA was safe and effective in the treatment of seasonal allergic rhinitis in adults.     

Effects of a pseudoallergen-free diet on chronic spontaneous urticaria: a prospective trial

Background:  Chronic spontaneous urticaria is a skin disorder that is difficult to manage and can last for years. 'Pseudoallergens' are substances that induce hypersensitive/intolerance reactions that are similar to true allergic reactions. They include food additives, vasoactive substances such as histamine, and some natural substances in fruits, vegetables and spices. Eliminating pseudoallergens from the diet can reduce symptom severity and improve patient quality of life.
Aim:  To assess the effects of a pseudoallergen-free diet on disease activity and quality of life in patient's chronic spontaneous urticaria.
Methods:  Study subjects had moderate or severe chronic spontaneous urticaria that had not responded adequately to treatment in primary care. For 3 weeks, subjects followed a pseudoallergen-free diet. They kept a clinical diary, which recorded their wheal and pruritus severity each day, to yield a clinical rating of chronic spontaneous urticaria severity (the UAS4 score). The subjects also completed the DLQI, a validated quality-of-life instrument. Use of antihistamines and glucocorticoids was minimized, recorded, and analysed. Subjects were classified into nine response categories, according to the changes in symptom severity (UAS4), quality of life (DLQI) and medication usage.
Results:  From the 140 subjects, there were 20 (14%) strong responders and 19 (14%) partial responders. Additionally, there were nine (6%) subjects who made a substantial reduction in their medication without experiencing worse symptoms or quality of life.
Conclusions:  Altogether the pseudoallergen-free diet is beneficial for one in three patients. The pseudoallergen-free diet is a safe, healthy and cost-free measure to identify patients with chronic spontaneous urticaria that will benefit from avoiding pseudoallergens.     

Effects of loratadine (SCH 29851) in suppression of histamine-induced skin wheals

The efficacy and safety of single oral doses (10, 20, 40, and 80 mg) of loratadine (SCH 29851) in suppressing formation of histamine-induced wheals were assessed in a crossover study in 29 healthy male subjects. One hour prior to dosing and 1, 2, 3, 4, 6, 8, 12, 16, 24, 28, 32, 36, 40, and 48 hours after dosing, histamine and saline were injected intradermally into opposite arms. Measurements of resulting wheal areas showed loratadine suppressed wheal formation significantly better than placebo; suppression was dose related. The mean suppression over 48 hours was 16% in placebo-treated subjects and 35%, 45%, 51%, and 67% in the 10, 20, 40, and 80 mg loratadine-treated subjects, respectively. The onset of action occurred within the first hour. Duration of suppression was dose related, ranging from 12 hours with the lowest dose (10 mg) to 48 hours with the higher doses (40 and 80 mg). Incidence of sedation and other side effects were comparable among all doses of loratadine and placebo.     

Pharmacokinetics and pharmacodynamics of terfenadine and chlorpheniramine in the elderly

In a double-blind, randomized, crossover study, the H1-receptor antagonists, terfenadine and chlorpheniramine, were investigated in eight healthy, fasting female subjects, aged 67.8 +/- SD 0.8 years, who ingested single doses of terfenadine, 1 mg/kg (mean dose, 69.6 +/- 11.2 mg), and chlorpheniramine, 0.12 mg/kg (mean dose, 8.4 +/- 1.3 mg). The mean serum-elimination half-life of terfenadine metabolite I was 8.7 +/- 3.7 hours. After terfenadine ingestion, significant wheal suppression occurred from 2 to 24 hours compared to predose wheal size, with maximum wheal suppression, 42 +/- 13% to 60 +/- 16% from 2 to 12 hours. Significant flare suppression occurred from 2 to 24 hours, with maximum flare suppression, 75 +/- 15% to 78 +/- 13% from 4 to 8 hours. The mean serum-elimination half-life of chlorpheniramine was 22.6 +/- 11.0 hours. After chlorpheniramine ingestion, significant wheal suppression occurred from 1 to 10 hours, inclusive, compared to predose wheal size, with maximum wheal suppression, 36 +/- 11% to 37 +/- 11% from 5 to 6 hours. Significant flare suppression occurred from 1 to 12 hours, with maximum flare suppression of 43 +/- 14% to 46 +/- 19% at 2, 5, and 6 hours (p less than 0.01). Adverse effects, chiefly sedation, occurred in five of eight patients after receiving terfenadine, and in all eight patients after receiving chlorpheniramine; but, since no placebo control was administered, these adverse effects could not be definitely attributed to H1-receptor-antagonist ingestion.     

Immunotherapy with short ragweed fraction A: d-glutamic acid: d-lysine polymer in ragweed hay fever

We report the first human trial of immunotherapy employing the nonimmunogenic carrier, d-glutamic acid: d-lysine linked to short ragweed (SRW) fraction A (fraction A:d-GL). Twelve SRW-sensitive patients with no immunotherapy during the previous 19 yr received a 2-mo ($\text{7}\text{79}$ to $\text{9}\text{79}$) course of fraction A: d-GL (average dose 49.5 mg, range 21 to 78 mg). We compared their symptom scores and serologic changes with two control groups of SRW-sensitive patients. Patients receiving fraction A: d-GL demonstrated at least a tenfold decrease in skin-test sensitivity to SRW and had statistically lower mean seasonal symptom scores (p < 0.02) than untreated controls. Mean seasonal symptom scores did not differ statistically from those of control patients on year 4 of immunotherapy. In contrast to the expected suppression of IgE, we found that fraction A:d-GL stimulated both IgE and IgG responses to SRW and SRW-antigen E. These increases in IgE and IgG antibodies were significantly greater than in the control groups and appeared to be due largely to injection of fraction A: d-GL. Though fraction A: d-GL was generally well tolerated, we noted mild generalized urticaria in three patients, and large local reactions in five others. The differences between our results and the earlier results in mice may reside in the particular characteristics of this preparation of fraction A: d-GL.     

Zafirlukast has no beneficial effects in the treatment of chronic urticaria

BACKGROUND: Leukotriene receptor antagonists have shown some efficacy in t he treatment of asthma. Injection of LTC4, LTD4 and LTE4 into the skin leads to a weal-and-flare reaction, suggesting an involvement of leukotrienes in the pathogenesis of urticaria. Indeed, various reports have indicated a beneficial effect for leukotriene receptor antagonists in patients with chronic urticaria. OBJECTIVE: To determine the therapeutic effect of the leukotriene receptor antagonist zafirlukast in patients with chronic urticaria. METHODS: The study was a double-blind, placebo-controlled, cross-over study lasting for 12 weeks. Fifty-two patients with chronic urticaria were investigated at a university hospital. The patients were randomized to receive 20 mg zafirlukast b.i.d. or placebo and cross-over was scheduled after 6 weeks. The efficacy of the treatment was evaluated by a daily symptom score, six physical examinations, the requirement of rescue antihistamines (acrivastine) and an overall assessment by the patient andthe investigating physician. RESULTS: Forty-six patients completed the study: zafirlukast was well tolerated without alteration of the investigated laboratory parameters. In comparison with placebo, treatment with zafirlukast resulted in no significant positive effect for any of the efficacy measures. Moreover, we were unable to identify any subgroup of patients with chronic urticaria responding with a therapeutic benefit. CONCLUSIONS: The leukotriene receptor antagonist zafirlukast does not provide a significant therapeutic benefit at a dose of 20 mg b.i.d. in patients with chronic urticaria.     

A double-blind, placebo-controlled trial of fexofenadine HCl in the treatment of chronic idiopathic urticaria.

BACKGROUND: Symptoms of chronic idiopathic urticaria (CIU) include relentless itching and painful wheals, which can be physically and psychologically debilitating. Half of all patients with urticaria have angioedema, which is often disfiguring. OBJECTIVE: To evaluate the safety and efficacy of fexofenadine HCl for the treatment of CIU symptoms. METHODS: In this 4-week, multicenter, placebo-controlled study, 439 patients with moderate to severe pruritus and urticaria received 1 of 4 oral doses of fexofenadine HCl (20, 60, 120, or 240 mg twice a day) or placebo. Patients reflectively assessed (over the previous 12 hours) the severity of pruritus, the number of wheals, and the interference with sleep (7 AM) and normal activities (7 PM) due to urticaria. Efficacy measures included a change from baseline of daily mean pruritus score (MPS), daily mean number of wheals (MNW) score, daily mean total symptom score (MTSS) (ie, the sum of the wheal and pruritus scores), and mean interference with sleep and daily activities due to urticaria. RESULTS: All 4 doses of fexofenadine were statistically superior to placebo (P 相似文献   

Cutaneous responses to histamine, compound 48/80, and codeine in patients with chronic renal failure

Pruritus is a common symptom associated with chronic renal failure (CRF). But increased plasma histamine levels and skin mast cell proliferation previously reported in these patients did not correlate with the intensity of the pruritus. Since increased mast cell releasability was described in chronic idiopathic urticaria, we attempted to examine whether this mechanism could explain pruritus in patients with CRF. Twenty-five patients with end stage renal failure were skin tested with histamine, codeine, and compound 48/80. There were nine patients on continuous ambulatory peritoneal dialysis, eight patients on hemodialysis, (tested both before and after dialysis) and eight patients with advanced CRF. Wheal area after intradermal injection of three concentrations of the above substances was measured. In general, the wheal areas in all patients with CRF were either similar to or smaller than those of the control group who were without renal impairment. In conclusion, patients with CRF with or without dialysis therapy demonstrated unchanged or decreased skin test responses to histamine, codeine, and compound 48/80. Increased mast cell releasability cannot explain the pruritus in patients with CRF.     

Use of cetirizine to investigate non-H1 effects of second-generation antihistamines.

In addition to their increased potency as H1 blockers and their nonsedating effects, the second-generation antihistamines have other unusual and potentially beneficial properties. Evidence is accumulating from several laboratories that at least one of these agents under investigation, cetirizine, may be effective in inhibiting the late reaction. The Johns Hopkins group showed that during the cutaneous late phase response (LPR), histamine release was not altered by cetirizine, 20 mg, pretreatment. The most dramatic effect of cetirizine was attenuation of inflammatory cell migration into the chamber. Eosinophils, neutrophils, and basophils were reduced by about 75% during hours 6 to 8. It can be concluded that cetirizine influences the LPR by causing a reduction in the inflammatory cell infiltrate. Cetirizine, 10 mg, orally once a day also induced a significant decrease in the wheal and flare skin reactions caused by pollen, histamine, and compound 48/80. Cetirizine inhibited eosinophil recruitment and platelet-activating factor (PAF) in skin chambers 24 hours after pollen challenge. We and others have studied the mechanisms of this effect. The release of eosinophil peroxidase induced by PAF and formyl-methionyleucyl/phenylalanine was not attenuated by cetirizine. At therapeutic concentrations, however, cetirizine has a potent inhibitory action in vitro on eosinophil chemotaxis induced either by formyl-methionyleucyl/phenylalanine or PAF and also on IgE-dependent stimulation of platelets. In a separate study in patients with chronic urticaria, cetirizine markedly reduced both the immediate wheal and flare induced by PAF and the delayed reaction at six hours. These results suggest that cetirizine acts on eosinophil migration to inhibit the late reaction.     

Skin responses to intradermal histamine and leukotrienes C4, D4, and E4 in patients with chronic idiopathic urticaria and in normal subjects

Mast cell inflammatory mediators, such as histamine, and newly formed compounds, such as the leukotrienes, cause wheal and flare when they are injected intradermally into normal subjects and may therefore play a role in the formation of urticaria. The effects of intradermal injections (50 microliters) of six different concentrations of histamine (range, 3.3 x 10(-4) to 3.3 x 10(-9) mol/L) and the leukotrienes C4, D4, and E4 (range, 2 x 10(-4) to 2 x 10(-9) mol/L) have been compared in 10 normal subjects and in 10 patients with chronic idiopathic urticaria. Wheal-and-flare sizes were measured at timed intervals up to 4 hours, and area under the curve for each response over time was calculated. There were no significant differences in leukotriene-induced responses between groups. Maximum sizes of histamine-induced wheal and flare were similar in each group of subjects. There were, however, significant increases in mean areas under the response curve of histamine wheal and flare in the patients with urticaria (wheal, p less than 0.001; flare, p less than 0.001; analysis of variance). These findings demonstrate a prolongation of skin responses to histamine in patients with urticaria and suggest an impaired clearance of histamine (or other vasoactive agents released by histamine) from the skin of these patients.     

Significance of tartrazine sensitivity in chronic urticaria of unknown etiology

Of 38 patients with chronic urticaria of unknown etiology who were evaluated for food and drug additive sensitivity, 53% (20/38) had urticaria for 1 yr or more. Total eosinophil counts ware not elevated in most patients, and the frequency of atopy was found to be similar to that in a general population. Of these 38 patients, 10 (26%) had a personal history of aspirin intolerance, but elimination of aspirin did not relieve the urticaria. In a double-blind crossover challenge with 0.22 mg of tartrazine and a control, tartrazine sensitivity was found in 8% (3/38) of patients with chronic urticaria and 20% (2/10) of patients with aspirin intolerance.     

The addition of zafirlukast to cetirizine improves the treatment of chronic urticaria in patients with positive autologous serum skin test results

BACKGROUND: Because leukotrienes have potent local effects on cutaneous vasculature, leukotriene antagonists might be effective in the treatment of chronic urticaria. OBJECTIVE: A double-blinded, placebo-controlled trial comparing cetirizine 10 mg daily in combination with zafirlukast 20 mg twice a day versus cetirizine 10 mg daily and placebo was conducted to determine whether subjects with chronic urticaria benefit from add-on therapy with a leukotriene-modifying agent. METHODS: Patients 12 years or older with a history of chronic urticaria (more than 6 weeks in duration) required diary documentation of 6 or more hives on at least 2 days/week and a suboptimal response to H(1)-antagonist therapy for enrollment. At baseline, all subjects were skin tested to autologous serum to assess for the potential presence of FcepsilonRI or IgE autoantibodies. Subjects meeting the initial entry criteria were treated with cetirizine 10 mg a day and placebo twice daily for 1 week. Those patients with persistent hives were randomized to receive cetirizine 10 mg daily and zafirlukast 20 mg twice a day or cetirizine 10 mg daily and placebo. At each successive weekly visit, physician and patient treatment effectiveness score (TES) and visual analog scale (VAS) ratings were recorded. Statistical analysis used generalizing estimating equations to compare the effect of combination therapy versus monotherapy on TES and VAS ratings. Results were adjusted for baseline rating, recruiting center, and autologous serum skin test (ASST). A separate analysis evaluated patients with positive ASST results receiving combination therapy versus monotherapy. RESULTS: Combination therapy with zafirlukast demonstrated a modest but significantly greater improvement compared with cetirizine monotherapy in physician and patient recorded VAS ratings at visit 4 and across treatment visits 4 through 6 (P <.05 unless stated otherwise). Subjects with ASST positive results receiving combination therapy as compared with subjects with negative ASST results exhibited a significant improvement in patient recorded VAS ratings across visits 4 through 6. Subgroup analysis of subjects with ASST positive results receiving combination therapy versus monotherapy showed improvement in physician recorded TES at visit 5, physician recorded VAS at visits 4 and 5 and across visits 4 through 6, as well as for patient recorded VAS at visit 5. There were no significant results for patients with ASST negative results. CONCLUSION: The results of this study indicate that only patients with autoimmune (ASST positive) chronic urticaria refractory to H(1)-antagonist monotherapy might benefit from the addition of the leukotriene D(4)-receptor antagonist zafirlukast to their treatment regimen. These results also suggest that routine screening of patients with chronic urticaria with the ASST might be useful in formulating therapeutic algorithms in the management of chronic urticaria.     

How to assess disease activity in patients with chronic urticaria?

Background:  The current EAACI/GA²LEN/EDF guidelines recommend assessing disease activity in chronic urticaria (CU) by using an established and well-defined symptom score, i.e. the urticaria activity score (UAS), which combines daily wheal numbers and pruritus intensity. However, this UAS has never been formally tested for its suitability in assessing CU activity.
Aim:  To determine the UAS correlation with quality of life (QoL) in CU patients and to compare the UAS to other symptom scores.
Methods:  Chronic urticaria symptoms (wheals, erythema, angioedema, pruritus) were assessed on seven consecutive days in 111 CU patients for their numbers, duration, size, and/or intensity. Quality of life was assessed by using the Dermatology Life Quality Index. Both, urticaria activity and QoL were determined before and after a 3-week period, in which the patients followed a pseudoallergen-low diet.
Results:  Urticaria activity score values correlated positively, albeit weakly, with QoL impairment in CU patients ( r ² = 0.31, P  < 0.05). Also, changes in QoL following a pseudoallergen-low diet were reflected by the changes observed in the UAS ( r ² = 0.30, P  < 0.05). No significant differences were found comparing the QoL correlation of the UAS and other symptom scores combining up to four CU symptom qualities. Quality of life correlation with UAS values increased with the number of days the UAS was assessed and plateaued starting from the fourth consecutive day.
Conclusions:  Our findings back the current guideline recommendations to use the UAS for monitoring disease activity in CU patients. Urticaria activity score mean values of at least four consecutive days should be used.     

Cetirizine inhibits bradykinin-induced cutaneous wheal and flare in atopic and healthy subjects

BACKGROUND: Kinins are vasoactive mediators involved in allergic reactions. When applied on the skin or in the nose, bradykinin (BK) elicits inflammation that is poorly affected by previous H1-blockade. The aim of this study was to compare the possible effect of cetirizine (an H1-antagonist) on wheal and flare responses to BK, histamine, and compound 48/80 in atopic and healthy subjects. METHODS: In a randomized, double-blind, crossover study, eight atopic and eight healthy subjects received cetirizine (10 mg/day) or placebo for 3 days before cutaneous tests. Intradermal tests (IDT) and prick tests (PT) were performed with BK (20 nmol/ml for IDT and 20 micromol/ml for PT), histamine (100 microg/ml IDT and 100 mg/ml PT), and compound 48/80 (100 microg/ml IDT and 100 mg/ml PT) as positive controls and saline as negative control. The skin responses were monitored by measurement of wheal and flare areas. RESULTS: BK, histamine, and 48/80 induced wheal and flare reactions in all placebo-treated subjects. Histamine elicited larger wheal and flare reactions than BK and 48/80. IDT with BK induced four- to sixfold larger wheal and flare reaction than PT. No differences in BK-induced wheal and flare were observed between atopic and healthy subjects. In atopic subjects, cetirizine induced a significant reduction of flare reactions after the BK test (80% for IDT, and 94% for PT [P < 0.01]). Moreover, cetirizine reduced significantly BK-induced wheals by 70% for IDT (P < 0.01) and 65% for PT (P < 0.01). A similar inhibiting effect of cetirizine was also observed in healthy subjects. CONCLUSIONS: These findings showed that the wheal and flare reactions induced by BK challenge were markedly inhibited by previous intake of cetirizine. The mechanism by which this effect is mediated cannot be established at present.