Therapy of acute and chronic urticaria

Background The drug management of chronic urticaria can be divided into three approaches: (i) blockade of released histamine at the receptor sites; (ii) blockade of histamine release from mast cells; and (iii) blockade of other mediators and possible inflammatory and cellular components. The first approach is the most successful and widely used. It primarily involves the use of H₁-antihistamines, although tricyclic antidepressants and H₂-antihistamines also have a place. Treatments The usefulness of classic H₁-antihistamines, such as hydroxyzine, may be limited by side-effects (most notably, sedation). The four most widely used of the newer antihistamines are loratadine, terfenadine, astemizole and cetirizine. These antihistamines are significantly superior to placebo and have similar efficacies comparable with hydroxyzine. Novel agents and methods, including nifedipine, sulphasalazine and plasmapheresis have been tried with some success in refractory patients. Guidelines If acute cases are inadequately controlled, short-term oral corticosteroids may be added. Systemic corticosteroids are occasionally indicated for the management of severe acute urticaria, severe serum sickness, pressure urticaria or urticarial vasculitis, or to break the cycle of a resistant case, but have no place in regular therapy for chronic urticaria. For those with severe acute urticaria with signs of respiratory distress, possible treatments include subcutaneous epinephrine, systemic corticosteroids and intramuscular H₁-antihistamines. Patients with chronic urticaria inadequately controlled on H₁-antihistamines alone may benefit from the addition of a classic antihistamine, a tricyclic antidepressant or an H₂-antihistamine. A short course of systemic corticosteroids may help those with severe chronic refractory disease.     

Treatment of Urticaria

Urticaria is a cutaneous syndrome characterized by dermal edema (wheal) and erythema (flare) that blanches with pressure. The lesions typically last less than 24 hours and are usually pruritic. In 1983, Christensen and Maibach summarized the theory behind the use of histamine H₁ receptor antagonists (antihistamines) in clinical dermatology. These agents remain the mainstay of treatment for urticaria. This article reviews the medical literature on the effectiveness of antihistamines in urticarial syndromes, including acute, chronic idiopathic and the physical urticarias. Older antihistamines, such as chlorpheniramine and hydroxyzine, are effective in the treatment of urticarias, but they also have marked sedative and anticholinergic effects. Newer nonsedating antihistamines (second-generation antihistamines) have been developed that have reduced adverse effects because they do not cross the blood-brain barrier; these agents (acrivastine, cetirizine, loratadine, mizolastine, fexofenadine, ebastine, azelastine and epinastine) cause significantly less sedation and psychomotor impairment than their older counterparts. A review of the literature reveals that there are few studies which document the efficacy of second-generation antihistamines in the treatment of acute urticaria, a biologic entity that usually resolves within 3 weeks. We did not identify controlled studies that suggested superiority of any antihistamine in the treatment of acute urticaria. Loratadine or cetirizine, and possibly mizolastine, appear to be treatments of choice for chronic idiopathic urticaria. For symptomatic dermatographism, the combination of an antihistamine and an H₂ antagonist, e.g. chlorpheniramine and cimetidine, appears to be effective. Very few studies have been conducted on the use of antihistamines in the treatment of cold, cholinergic, and pressure urticaria. Antihistamines are the mainstay of urticarial therapy. This evidence-based review suggests that there are efficacy differences between newer, nonsedating antihistamines and older agents in some forms of the disorder. Clearly, further well-controlled clinical trials in larger numbers of patients are needed to clarify the role of these agents in the treatment of urticaria.     

A comparison of cetirizine and terfenadine in the management of solar urticaria.

Many solar urticaria patients may benefit from the use of antihistamines. Historically, the value of such therapy was limited by sedation. Newer agents such as terfenadine and cetirizine that are relatively non-sedating appear to be better tolerated by patients. The latter drug, in addition to its antihistamine effect, also appears to inhibit eosinophil migration, which terfenadine and other potent H1 antagonists do not significantly affect. Eosinophils have been reported as early migrating cells in induced solar urticaria, raising the possibility that the dual action of cetirizine may provide a greater potential benefit in the management of solar urticaria. Six patients with idiopathic solar urticaria were entered into a double-blind, phototest study to compare cetirizine and terfenadine. Using the minimal urticarial dose as a phototest end-point, both drugs were equally effective in raising the threshold of sensitivity in 4 patients. Two patients failed to respond to either therapy, which is in keeping with the known variable response to histamine blockade in solar urticaria. At the dosage used, cetirizine therapy appears to be no more effective than terfenadine.     

The effects of astemizole, cetirizine and loratadine on the time course of weal and flare reactions to histamine, codeine and antigen

An open cross-over study was performed to assess the effects of astemizole, cetirizine and loratadine on weal and flare reactions to intradermal histamine, codeine and house dust mite antigen. Percentage inhibition of weal area, flare area and weal volume was greatest for cetirizine, then astemizole and smallest for loratadine. Wealing due to mast-cell degranulation with either codeine or antigen was less inhibited by all three antihistamines than that due to histamine itself. Time-course studies revealed similarities between wealing provoked by codeine and histamine but different characteristics to that induced by antigen.     

Comparison of the potency of antihistamines

ABSTRACT: First- and second-generation antihistamines have proven effective in the management of patients with urticaria and allergic rhinitis; however, the efficacy of first-generation antihistamines has been compromised by undesirable side effects such as sedation, dry mouth, and blurred vision. Second-generation antihistamines, on the other hand, are less sedating and have fewer side effects than first-generation agents. Recently second-generation agents have been compared for their pharmacologic activities using an epicutaneous histamine-induced wheal and flare model in normal volunteers. Cetirizine was found to be superior to epinastine, ebastine, fexofenadine, terfenadine, loratadine, and placebo in inhibiting the wheal and flare response. Epinastine had the fastest onset of action at 30 minutes and terfenadine proved to be superior to its metabolite fexofenadine.     

Multiple H1-antihistamine-induced urticaria

H₁‐antihistamines are widely used in the treatment of various allergic diseases. Particularly, a cornerstone of the management of chronic idiopathic urticaria is treatment with H₁‐antihistamines. However, a few cases of H₁‐antihistamine‐induced urticaria have been reported. A 34‐year‐old woman presented with a 4‐month history of recurrent urticaria, which was prominently exacerbated by the administration of H₁‐antihistamines. The patient consented to a provocation test of fexofenadine among drugs including cetirizine and hydroxyzine, which were suspected of inducing severe symptoms in episodes. One hour after challenge with 12 mg fexofenadine (one‐fifth of the therapeutic dose), a urticarial reaction rapidly developed on nearly the entire body with remarkably increased levels of plasma histamine (190 nmol/L) and plasma leukotriene B4 (150 pg/mL). In challenge tests with other antihistamines, generalized urticaria occurred 5 and 1 h after intake of 10 mg loratadine and 10 mg bepotastine, respectively, whereas challenges with chlorpheniramine, mequitazine and azelastine were all negative. Skin prick tests with H₁‐antihistamines used in the challenges were all negative, indicating that the urticarial reactions after challenges with the causative drugs might not be immunoglobulin E‐mediated. Among the causative drugs in our case, cetirizine and hydroxyzine are the piperazine derivatives, whereas fexofenadine, bepotastine, ebastine and loratadine are the piperidine derivatives. The chemical structures of both derivatives are very similar. Therefore, in this case, H₁‐antihistamine‐induced urticaria may have been due to cross‐reactivity between metabolites of these drugs, but not to drugs before metabolization. Hypersensitivity to H₁‐antihistamines should be considered when urticarial lesions worsen after H₁‐antihistamine treatment.     

Use and safety of antihistamines in children

ABSTRACT: Although first-generation antihistamines remain popular for the treatment of seasonal allergic rhinitis, atopic dermatitis, and urticaria in children, second- and third-generation antihistamines hold clear advantages over the first-generation agents, especially for the pediatric patient. The less frequent dosing schedule of the second- and third-generation agents makes administration easier for the parent. With less sedation and lower risk of adverse effects, the safety profile of second- and third-generation agents appears superior to that of first-generation agents. After briefly discussing the use of first-generation antihistamines, the pharmacokinetics, safety, and use of the newer antihistamines loratadine, cetirizine, and fexofenadine in the pediatric patient are reviewed.     

Treatment of chronic urticaria with cetirizine dihydrochloride a non-sedating antihistamine

The efficacy of cetirizine dihydrochloride, a new H₁-antagonist with minimal sedative or anticholinergic side effects was evaluated in 30 patients with chronic idiopathic urticaria. In the first part of the study, cetirizine 10 mg and placebo were compared in a double-blind cross-over trial. In the second part, patients who did not respond adequately in the first part were randomized, still double-blind, to receive 10 mg cetirizine either once daily or twice daily. In the first part, treatment was discontinued by 17 patients on placebo and two patients on cetirizine because of lack of efficacy. Cetirizine dihydrochloride was found significantly to reduce occurrence of weals, erythema and pruritus compared with placebo (P <0.001). Twenty-six of the patients improved on cetirizine and two on placebo. Mild sedation was noted by two patients on cetirizine and by one on placebo.     

Effects of bepotastine, cetirizine, fexofenadine, and olopatadine on histamine-induced wheal-and flare-response, sedation, and psychomotor performance

Although many antihistamines are now in clinical use, few studies directly compare their pharmacodynamic and sedative activities in humans in vivo. We designed a double-blind, placebo-controlled, crossover study to compare the inhibitory effects of bepotastine, cetirizine, fexofenadine, and olopatadine on histamine-induced flare-and-wheal response. Systemic sedative effects and impaired psychomotor activities by these drugs were also evaluated. Bepotastine (10 mg twice a day), cetirizine (10 mg once a day), fexofenadine (60 mg twice a day), and olopatadine (5 mg twice a day) or placebo was given in a double-blind manner to seven healthy volunteers before histamine challenge by iontophoresis. At 0, 1, 2, 4, 8, 12, and 24 h following the oral administration of these drugs, histamine iontophoresis-induced wheal-and-flare response was measured. Sedative effects by the drugs were also evaluated by a visual analogue scale for subjective sedation, and by word processor test for psychomotor activity. Each volunteer was tested with all of the drugs (including placebo), administered in a random order with a washout period of at least 1 week. Histamine iontophoresis induced marked wheal-and-flare response in all participants. Bepotastine, cetirizine, fexofenadine, and olopatadine yielded significant reduction of histamine-induced wheal-and-flare response compared to placebo (P < 0.01). Among the drugs, olopatadine and cetirizine suppressed most markedly and persistently histamine-induced wheal-and-flare response, while bepotastine and fexofenadine produced a significant, but less persistent suppression. Olopatadine, fexofenadine, and cetirizine showed a significant systemic sedative effect in this order with bepotastine showing the least sedative effect. Moreover, olopatadine affected psychomotor performance most markedly, which was followed by fexofenadine and cetirizine. These results indicate that bepotastine, cetirizine, fexofenadine, and olopatadine inhibit histamine-induced wheal-and-flare response of humans in vivo and induce a variable systemic sedative effect and impaired psychomotor activity. Although olopatadine and cetirizine showed the strongest and most persistent suppression of histamine-induced wheal-and-flare response, olopatadine showed a considerable sedative effect with impaired psychomotor performance.     

Effects of loratadine and cetirizine on serum levels of neuropeptides in patients with chronic urticaria

H1‐receptor inhibiting drugs, namely loratadine and cetirizine, were frequently used in treatment of chronic urticaria. Urticarial weal and flare reactions, a neurogenic reflex due to neuropeptides, were reported to be more effectively inhibited by cetirizine than loratadine. The aim of this study was to determine and compare the effects of systemic loratadine and cetirizine treatments on serum levels of selected neuropeptides in chronic urticaria. Treatment groups of either systemic loratadine or cetirizine (10 mg/d), consisting of 16 and 22 patients, respectively, were included. Serum levels of stem cell factor (SCF), neuropeptide Y (NPY), calcitonin gene‐related peptide (CGRP), nerve growth factor (NGF), vasoactive intestinal peptide (VIP), and substance P (SP) were detected before and after one week of treatment with antihistamines. Serum NPY and VIP levels were significantly decreased when compared before and after treatment with antihistamines (P < 0.001 and P < 0.01, respectively). SCF and NGF values were also decreased after antihistamine treatment (P < 0.05). Post‐treatment levels of CGRP were significantly higher compared with pretreatment values, while no significant difference was detected between pre and post treatment levels of SP. Cetirizine was significantly more effective than loratadine on lowering serum levels of SCF among the other neuropeptides. Systemic loratadine and cetirizine treatments in patients with chronic urticaria precisely caused variations in serum levels of neuropeptides. The predominant effect of cetirizine compared to loratadine on reducing serum SCF levels might be explained with anti‐inflammatory properties of cetirizine.     

咪唑斯汀、氯雷他定及西替利嗪对小鼠变应性接触性皮炎作用的比较研究

目的:比较咪唑斯汀、氯雷他定及西替利嗪对小鼠变应性接触性皮炎(ACD)的抑制作用。方法:建立小鼠ACD模型,采用致敏前及诱发后两种给药方法,口服不同剂量咪唑斯汀、氯雷他定及西替利嗪,观察抑制作用。结果:致敏前开始给药,3种药物均能明显抑制ACD小鼠耳肿胀(P<0.05),但咪唑斯汀的抑制作用强于氯雷他定及西替利嗪(P<0.05);诱发后开始给药,咪唑斯汀组小鼠耳肿胀消退快于氯雷他定及西替利嗪(P<0.05)。结论:咪唑斯汀对小鼠ACD抑制作用强于氯雷他定和西替利嗪。     

Novel insights into the molecular mechanism of the cardiac actions of histamine H1 receptor antagonists

ABSTRACT: When compared to older first‐generation antihistamines, second‐generation antihistamines are characterized by improved selectivity for histamine receptors, absence of sedation, and, possibly, antiallergic properties distinct from their antihistaminic activity. Such a pharmacologic profile, arising from specific pharmacodynamic and pharmacokinetic properties, bears an obvious clinical advantage for the therapy of allergic diseases; thus second‐generation antihistamines have become the treatment of choice for chronic urticaria and allergic rhinitis. Despite such a therapeutic advantage, adverse cardiovascular effects associated with the use of some congeners belonging to the class of second‐generation antihistamines (particularly terfenadine and astemizole) have been reported, and a major concern about the therapeutic selection of antihistamines now is represented by their potentially severe arrhythmogenic properties. This article reviews the recent advances in the understanding of the pathogenesis and etiology of the cardiotoxic actions of some second‐generation antihistamines, underlining their molecular actions at the level of K⁺ channels controlling the cardiac action potential. In particular, emphasis is given to the interaction of second‐generation antihistamines with the K⁺ channels encoded by the human ether‐a‐gogo‐related gene (HERG), which is crucially involved in the repolarization process of the cardiac action potential. This review will also focus on the recent concerns over the potential cardiac adverse effects of first‐generation H₁ receptor blockers. The present exploration of the molecular basis of the adverse cardiac effects of antihistamines shows how important contributions in deciphering such complex phenomenon have emerged from disciplines and techniques not traditionally related to immunology, such as molecular genetics and cellular electrophysiology; it seems possible to anticipate that the exchange of results from such different disciplines in the future will provide patients and physicians with medications with improved therapeutic efficacy and safety for the clinical management of allergic diseases.     

Start and end of the effects of terfenadine and astemizole on histamine-induced wheals in human skin

A study was made of effects of two antihistamines, terfenadine (60 mg twice daily) and astemizole (10 mg once daily) on wheals induced by histamine dihydrochloride (10 mg/ml) in the prick test on the upper back of 15 healthy students. The suppressive effects of terfenadine on the histamine wheal appeared earlier (2 h), and disappeared earlier (within 1 day) than those of astemizole (3 days and 28 days, respectively). No difference between the maximal effects of the two drugs was seen.     

Suppression of wheal and flare in histamine test by the main H1 antihistamines commercialized in Brazil

Background:Several dermatoses are mediated by histamine, such as urticaria, angioedema, and papular urticaria. There are no Brazilian studies comparing the potency of antihistamines.Objectives:To evaluate the tolerability and efficacy of the main commercial brand and generic H1 antihistamines, regarding the suppression of the wheal and flare to the histamine test.Methods:A quasi-experimental, open study with 10 healthy adults submitted to the histamine test on the ventral aspect of the forearms. After 20 minutes, wheal and flares were measured. The tests were performed after two hours of intake of dexchlorpheniramine, hydroxyzine, levocetirizine, fexofenadine, cetirizine, loratadine, ebastine, desloratadine, epinastine and rupatadine, as well as generics of loratadine, cetirizine and fexofenadine.Results:All antihistamines presented a reduction in the wheal compared to the control (p <0.02), as well as in the flare, except for rupatadine (p = 0.70). In the internal comparison, cetirizine, fexofenadine, epinastine, levocetirizine, dexchlorpheniramine and hydroxyzine were the most potent, with no difference between them (p > 0.1). As for halo, cetirizine, epinastine, hydroxyzine and fexofenadine were the most potent, with no difference between them (p > 0.1). The most common adverse effect was drowsiness, which was more prevalent among first-generation drugs (p < 0.01). Generic loratadine, fexofenadine and cetirizine halos were higher than their controls (p >0.03)..Study limitations:A single-center study evaluating only aspects related to histamine.Conclusions:Brazilian commercial antihistamines presented different profiles of inhibition of wheal and flares in the histamine test, as well as adverse effects. Generic loratadine, fexofenadine and cetirizine presented larger flares than brand drugs.     

Review of H1 antihistamines in the treatment of chronic idiopathic urticaria

Chronic idiopathic urticaria (CIU) can have a profound effect on patient quality of life (QOL). Ideally, any therapy used to treat CIU should be effective across a wide range of doses without causing unwanted side effects; a wide therapeutic window allows the physician to tailor treatment to the individual. Oral H1 antihistamines are the mainstay of therapy for CIU, but agents within this class diverge in their individual therapeutic indices. The literature was reviewed to compare the currently available oral H1 antihistamines regarding their efficacy and safety at a wide range of doses. If sedation and cognitive impairment are considered relevant to treatment selection due to their effect on QOL and safety, then newer-generation agents should be selected over older-generation antihistamines. There are few well-controlled clinical studies in which newer-generation agents have been directly compared. Moreover, there are no evidence-based data demonstrating statistical superiority of one newer-generation agent over another in the treatment of CIU. However, of the newer agents, those that are labelled nonsedating at recommended doses (fexofenadine, loratadine, and desloratadine) should be selected over cetirizine. In cases where the physician judges that a higher-than-recommended dose should be prescribed, or when the patient is likely to take a higher dose, the relative safety profile of these agents demands detailed consideration.     

Effects of H1 antagonists on the cutaneous vascular response to histamine and bradykinin: a study using scanning laser Doppler imaging

Histamine plays an important part in the cutaneous weal and flare response which underlies many allergic skin conditions. It has a direct effect on the local vasculature to promote vasodilatation and increase microvascular permeability and may also initiate the more widely spread neurogenic flare. Quantification of these responses and studies of the mediator mechanisms underlying them have been limited by the lack of appropriate techniques to investigate them. To address this we have used two relatively new techniques, scanning laser Doppler imaging (LDI) and dermal microdialysis to measure changes in skin blood flow and the release of histamine within the weal and flare, following intradermal injection of histamine or bradykinin. These measurements have been made both in the absence and presence of the H₁ receptor blockers cetirizine and loratadine. Scanning LDI of the inflammatory response revealed marked differences in both the development and steady state responses to the intradermal injection of histamine (1–3 μmol/L) and bradykinin (1 μmol/L). The development of the flare and the weal response to both histamine and bradykinin was significantly reduced by cetirizine but not by loratadine. The histamine-induced flare area fell by 57 ± 4% (mean ± SEM, n = 10, P < 0.001) after cetirizine and the area of the weal fell by 73 ± 11% (P < 0.009). Bradykinin-induced inflammatory responses were similarly reduced by cetirizine, the weal by 60 ± 16% (P < 0.02) and the flare by 61 ± 4% (P < 0.005). Measurement of histamine concentration in skin using microdialysis, in six subjects, confirmed that histamine levels rose in the dialysate collected from the weal to 310 ± 16 nmol/L following injection of histamine. Histamine levels also rose following bradykinin injection in some subjects (mean 147 ± 46 nmol/L, range 18–336). Little increase in histamine concentration was seen in the dialysate from the flare following injection of either histamine or bradykinin. The histamine concentration in dialysate from unprovoked skin was 4.19 ± 0.75 nmol/L. These data reveal differences in the dermal responses to different mediators when assessed using scanning LDI. They confirm that histamine is released within the weal but not the flare response to the intradermal injection of both histamine and bradykinin and that its effects on the local vasculature to cause the oedematous weal and the axon reflex-mediated flare are significantly attenuated by the H₁ antagonist cetirizine and to a lesser extent by the H₁ antagonist loratadine.     

In dermographic urticaria H2 receptor antagonists have a small but therapeutically irrelevant additional effect compared with H1 antagonists alone

Two studies of the additional effect of an H₂ receptor antagonist when given in combination with an H₁ antagonist were undertaken in dermographic urticaria. Using a randomized, double-blind, crossover design in 19 patients, a combination of cetirizine (10 mg at night) and ranitidine (150 mg twice daily) was compared with a combination of cetirizine (10 mg at night) and placebo. The addition of ranitidine did not produce any significant difference in linear analogue scores for weal, Itch or sleep disturbance. There was a significant depression of the frictional force/wealing response curve with an increase in wealing threshold (P<0.0001) following the addition of H₂ blockade. The wealing threshold was 54.7 ± 4.4 (mean ± SEM) g/mm² for the H₁ antagonist alone, and 73.2 ± 5.7 for the combination of H₁ and H₂ antagonists. In a second similar study involving nine different patients, comparing terfenadine (120 mg twice daily) with a combination of terfenadine and ranitidine (150 mg twice daily), the weal threshold was 59.8 ± 6.6 for the H₁ antagonist alone, and 73.0 ± 6.4 for the combination of H₁ and H₂ antagonists. Thus, in dermographic urticaria, adding an H₂ antagonist to treatment with a potent H₁ antagonist gives a small, significant reduction in wealing response, but no symptomatic benefit. We conclude that involvement of the H₂ receptor in this urticarial disease is minimal, and does not justify the use of H₂ receptor antagonists.     

Effects of acrivastine, loratadine and cetirizine on histamine-induced wheal and flare responses

It is accepted that studies evaluating histamine-induced wheal and flare reactions in the skin represent a simple and reliable method for demonstrating pharmacodynamic activity and pharmacokinetics of the H1-receptor antagonists. In this study, the effects of single oral doses of acrivastine (8 mg), loratadine (10 mg) and cetirizine (10 mg) on the histamine-induced wheal and flare reactions were compared in 60 healthy volunteers. The wheal and flare responses were produced by prick test using 1% histamine solution. Measurements were performed before the ingestion of antihistamines (baseline values) and afterwards at 15, 30, 90, 240, 360 min and 24 h. The values obtained for each antihistamine were compared with each other and with baseline values. Cetirizine was found to be superior to acrivastine and loratadine for the suppression of wheal and flare responses at 240, 360 min and 24 h (P < 0.05) and acrivastine was superior to the other two antihistamines for the suppression of flare response at 30 min (P < 0.05). Our results indicate that a single dose of cetirizine provides a more effective and long acting suppression on wheal and flare reactions in urticaria when compared to acrivastine and loratadine.     

Quantitative time course study of the skin response to histamine and the effect of H1 blockers. A 3-week crossover double-blind comparative trial of cetirizine and terfenadine

A controlled, randomized, double-blind, crossover study was performed in 10 healthy volunteers to compare changes of cutaneous blood flow values (CBFV) determined by laser Doppler flowmetry before and after intake of a capsule containing either 10 mg cetirizine or 60 mg terfenadine. After the determination of the initial response to the anti-H1 agents, drugs were taken daily (cetirizine 10 mg, terfenadine 120 mg) over a 3-week period and the cutaneous response to histamine and saline was evaluated weekly, exactly 4 h after the last drug intake. The following significant variations were observed (analysis of variance for repeated measurements, p less than 0.05): (1) there is a decrease of histamine-induced wheal and flare under antihistamines (anti-H1), cetirizine being more potent than terfenadine; (2) CBFV, measured on the usual flare area, i.e. at 1 cm of the site of agonist injection, decreased after drug intake. There was a gradual increase of the CBFV inhibition over the 3-week follow-up, cetirizine being more effective than terfenadine, and (3) at the site of agonist injection, reduction of the edematous wheal was associated with significant increases of CBFV after drug intake. This quantitative pharmacologic in vivo assay on the agonist action indicates that at lower doses, cetirizine has a significantly higher anti-H1 activity than terfenadine and that this effect is maintained over a 3-week period. There was no tachyphylaxis.     

Loratadine and cetirizine in the treatment of chronic urticaria

Aim This study was designed to compare loratadine and cetirizine in controlling the symptoms of chronic urticaria. Subjects One hundred and sixteen adult patients with chronic urticaria. Methods In this double-blind study the patients were randomly divided into three therapeutic groups: 38 received loratadine (10 mg), 40 cetirizine (10 mg) and 38 placebo tablets once daily for 28 days. Steroid-dependent subjects and patients with physical urticaria or with angioncurotic hereditary oedema as well as pregnant or breast-feeding women were excluded from the study. A suitable wash-out period was observed in case of previous treatments for the same disease. Itching, erythema, number of lesions and diameter of the largest one were evaluated according to a scale from 0 (absent) to 3 (severe). The minimum entry study score for itching plus number of lesions had to be at least equal to three. Control visits were scheduled after 3, 7 and 14 days of therapy. Symptoms, disease status, therapeutic response, side effects and compliance were evaluated at each visit. Diary cards were filled in by patients at home. Results Active drugs compared to placebo significantly reduced global clinical symptoms (p < 0.05). Loratadine was more rapid in developing its activity than the other two agents (p < 0.01 at day 3). Each single symptom showed the same trend. At the end of the study 24 (63%) patients treated with loratadine, 18 (45%) with cetirizine and 5 (13%) with placebo were free from symptoms. Four failures occurred with loratadine, six with cetirizine and seventeen with placebo. The tolerability profile was similar for all three groups. One patient receiving cetirizine dropped out due to severe gastric pain. Conclusions Loratadine is more active and safer than cetirizine in the treatment of chronic urticaria.