Non-sedating H1-antihistamines Research Articles

Challenges in the management of chronic urticaria.

The term "chronic idiopathic urticaria" denotes a spectrum of conditions with different poorly understood pathogenetic mechanisms in which the release of histamine plays a role. Nonsedating second-generation H1 antihistamines are postulated to be the first line of treatment of chronic idiopathic urticaria by national and international guidelines, but as control is not always achievable with the usually recommended doses, first-generation sedating antihistamines like hydroxyzine and diphenhydramine at high daily doses (200 mg) have been proposed as an alternative before resorting to treatment with systemic corticosteroids and other potentially hazardous agents. Our long time experience and recent research give us grounds to believe that increasing the doses of nonsedating H1 antihistamines up to fourfold improves significantly the chances of successful treatment. Our data suggest that the urticaria-associated discomfort is relieved by higher than conventional doses of levocetirizine and desloratadine in about 75% of the patients and that sedation/somnolence does not seem to be a major deterrent. The dose increase also improves the urticaria-specific quality of life. Contrary to the belief that individual patients may benefit from one antihistamine or another, we demonstrate that the drug with better ability to suppress the histamine skin effects in experiments in healthy volunteers (levocetirizine) is also superior in improving the different aspects of control of chronic urticaria (subjective and objective symptoms, quality of life) and that increasing its dose of up to fourfold may even paradoxically reduce the sense of sedation/somnolence in parallel with the relief of urticaria discomfort.

Alexithymia in chronic urticaria patients

Alexithymia has been described as an important dimension in several medical and psychiatric diseases. Chronic urticaria (CU) is a chronic condition, in which treatment is difficult. Our aim is to determine the prevalence of alexithymia traits in patients with CU, and to identify the relationships between alexithymia and psychological variables and quality-of-life dimensions. Fifty-five sequential CU patients in a faculty ambulatory specialized consultation, with an average age of 44.92, were compared with 31 healthy volunteers. Both groups were studied by means of validated scales for alexithymia (Toronto Alexythimia Scale [TAS-20]), attachment (Adult Attachment Scale-R [AAS-R]), psychopathology (Brief Symptom Inventory [BSI]), personality dimensions (The NEO Five-Factor inventory [NEO-FFI]) and quality of life (Short Form-36 [SF-36]). The classification of CU reactions was obtained from the patient's history, physical examination, laboratory assessment and histopathologic findings. All the patients were under treatment with sedating H1-antihistamines, non-sedating H1-antihistamines combination of H1 and H2 blocker, 2 H1-antihistamines and 3 H1-antihistamines. High traits of alexithymia were found on CU patients (56.9%) as well as high symptom rates of anxiety. Alexithymia traits were significantly positively correlated with insecure attachment styles, with psychopathological symptoms, and with the defense mechanism turn against self. We also reported a significant negative correlation between alexithymia traits and the dimensions of quality of life. Insecure attachment styles were positively correlated with psychopathological symptoms and negatively correlated with quality of life. We did not find significant statistical correlations between alexithymia and clinical variables. CU patients present serious difficulty in dealing with emotion arousal. There is strong evidence of a psychosomatic specificity in CU, with marked alexithymic traits

Persistent Allergic Rhinitis and the XPERT Study

Allergic rhinitis (AR) is a chronic disease with an increasing trend in most of the Western Countries. It may significantly impair the individual quality of life (QoL) and also represents a social burden for its economic costs. Levocetirizine (XYZAL; UCB Pharma) as a second generation, nonsedating H1-antihistamine, has been shown to be clinically effective in patients with AR in different randomized controlled trials. The XPERT (XYZAL in Persistent Rhinitis Trial) is the first large, long-term clinical study involving patients with persistent rhinitis as defined by ARIA (Allergic Rhinitis and its Impact on Asthma). The XPERT was a 6-month double-blind, placebo-controlled, multicenter, multinational trial in 551 subjects. Adults with persistent rhinitis sensitized to both grass pollen and house dust mites were randomized to receive levocetirizine 5 mg/d or placebo. Two primary objectives were considered: comparison of the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) overall score and Total 5 Symptoms Score (rhinorrhea, sneezing, nasal congestion, and nasal and ocular pruritus) (T5SS) between active and control group over a period of 4 weeks. As secondary endpoints, similar evaluations at 1 week and 3, 4, 5, and 6 months, summary scores for a general health status questionnaire (Medical Outcomes Survey Short Form 36), comorbidities, pharmacoeconomic and safety evaluations. Levocetirizine significantly improved both the RQLQ overall score and the T5SS from week 1 to 6 months (P < .001). Medical Outcomes Survey Short Form 36 summary scores were also improved in the group treated with levocetirizine with respect to placebo. Treatment cessation because of lack of efficacy, comorbidities, and overall costs of disease, and comorbidities per working patient per month (160.27 vs 108.18) were lower in the levocetirizine group. In conclusion, levocetirizine resulted to improve the quality of life and the symptoms related to AR and also to reduce the overall costs of the disease after 6 months treatment.

Persistent Allergic Rhinitis and the XPERT Study

Allergic rhinitis (AR) is a chronic disease with an increasing trend in most of the Western Countries. It may significantly impair the individual quality of life (QoL) and also represents a social burden for its economic costs. Levocetirizine (XYZAL; UCB Pharma) as a second generation, nonsedating H1-antihistamine, has been shown to be clinically effective in patients with AR in different randomized controlled trials. The XPERT (XYZAL in Persistent Rhinitis Trial) is the first large, long-term clinical study involving patients with persistent rhinitis as defined by ARIA (Allergic Rhinitis and its Impact on Asthma). The XPERT was a 6-month double-blind, placebo-controlled, multicenter, multinational trial in 551 subjects. Adults with persistent rhinitis sensitized to both grass pollen and house dust mites were randomized to receive levocetirizine 5 mg/d or placebo. Two primary objectives were considered: comparison of the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) overall score and Total 5 Symptoms Score (rhinorrhea, sneezing, nasal congestion, and nasal and ocular pruritus) (T5SS) between active and control group over a period of 4 weeks. As secondary endpoints, similar evaluations at 1 week and 3, 4, 5, and 6 months, summary scores for a general health status questionnaire (Medical Outcomes Survey Short Form 36), comorbidities, pharmacoeconomic and safety evaluations. Levocetirizine significantly improved both the RQLQ overall score and the T5SS from week 1 to 6 months (P < .001). Medical Outcomes Survey Short Form 36 summary scores were also improved in the group treated with levocetirizine with respect to placebo. Treatment cessation because of lack of efficacy, comorbidities, and overall costs of disease, and comorbidities per working patient per month (160.27 vs 108.18) were lower in the levocetirizine group. In conclusion, levocetirizine resulted to improve the quality of life and the symptoms related to AR and also to reduce the overall costs of the disease after 6 months treatment.

Challenges in the Management of Chronic Urticaria

The term "chronic idiopathic urticaria" denotes a spectrum of conditions with different poorly understood pathogenetic mechanisms in which the release of histamine plays a role. Nonsedating second-generation H1 antihistamines are postulated to be the first line of treatment of chronic idiopathic urticaria by national and international guidelines, but as control is not always achievable with the usually recommended doses, first-generation sedating antihistamines like hydroxyzine and diphenhydramine at high daily doses (200 mg) have been proposed as an alternative before resorting to treatment with systemic corticosteroids and other potentially hazardous agents. Our long time experience and recent research give us grounds to believe that increasing the doses of nonsedating H1 antihistamines up to fourfold improves significantly the chances of successful treatment. Our data suggest that the urticaria-associated discomfort is relieved by higher than conventional doses of levoce-tirizine and desloratadine in about 75% of the patients and that sedation/somnolence does not seem to be a major deterrent. The dose increase also improves the urticaria-specific quality of life. Contrary to the belief that individual patients may benefit from one antihistamine or another, we demonstrate that the drug with better ability to suppress the histamine skin effects in experiments in healthy volunteers (levocetirizine) is also superior in improving the different aspects of control of chronic urticaria (subjective and objective symptoms, quality of life) and that increasing its dose of up to fourfold may even paradoxically reduce the sense of sedation/somnolence in parallel with the relief of urticaria discomfort.

Challenges in the Management of Chronic Urticaria

The term "chronic idiopathic urticaria" denotes a spectrum of conditions with different poorly understood pathogenetic mechanisms in which the release of histamine plays a role. Nonsedating second-generation H1 antihistamines are postulated to be the first line of treatment of chronic idiopathic urticaria by national and international guidelines, but as control is not always achievable with the usually recommended doses, first-generation sedating antihistamines like hydroxyzine and diphenhydramine at high daily doses (200 mg) have been proposed as an alternative before resorting to treatment with systemic corticosteroids and other potentially hazardous agents. Our long time experience and recent research give us grounds to believe that increasing the doses of nonsedating H1 antihistamines up to fourfold improves significantly the chances of successful treatment. Our data suggest that the urticaria-associated discomfort is relieved by higher than conventional doses of levoce-tirizine and desloratadine in about 75% of the patients and that sedation/somnolence does not seem to be a major deterrent. The dose increase also improves the urticaria-specific quality of life. Contrary to the belief that individual patients may benefit from one antihistamine or another, we demonstrate that the drug with better ability to suppress the histamine skin effects in experiments in healthy volunteers (levocetirizine) is also superior in improving the different aspects of control of chronic urticaria (subjective and objective symptoms, quality of life) and that increasing its dose of up to fourfold may even paradoxically reduce the sense of sedation/somnolence in parallel with the relief of urticaria discomfort.

Consensus statement on the management of urticaria

This consensus statement was developed by Special Interest Group – Urticaria (IADVL). Urticaria, a heterogeneous group of diseases, often cannot be recognized by its morphology. Due to non-specific and non-affordable diagnosis, management of urticaria, especially chronic urticaria, is very challenging. This guideline includes definition, causes, classification and management of urticaria. Urticaria has a profound impact on the quality of life and causes immense distress to patients, necessitating effective treatment. One approach to manage urticaria is identification and elimination of the underlying cause(s) and/or eliciting trigger(s), while the second one is treatment aimed at providing symptomatic relief. This guideline recommends use of second-generation non-sedating H1 antihistamines as the first-line treatment. The dose can be increased up to four times to meet the expected results. In case patients still do not respond, appropriate treatment options can be selected depending on the cost.

Allergy is not the main trigger of urticaria in children referred to the emergency room

Urticaria is the disease that has the highest impact on quality of life and requires the most visits to the emergency room. To investigate the clinical presentation of acute urticaria in children referred to the paediatric emergency room of our hospital and to define possible related aetiologies. We included 814 children consecutively referred to the emergency room between January 2006 and December 2007 with a diagnosis of acute urticaria, isolated or associated with other clinical symptoms. Only 2.0% of the cases studied were associated with severe clinical pictures. In 437 cases (53.7%), the cause of urticaria was not determined. The infections of the respiratory tract were the most frequently suspected aetiological factor. The diagnosis of allergic urticaria is more defined, but belongs to a minority group (10.8%). The first level treatment includes the use of non-sedating oral H1-antihistamine. The children with urticaria are frequently referred to the paediatric emergency room, but only in a few cases were associated with severe clinical manifestations or allergy. The evidence of an inverse relationship between the number of accesses and the patients' age may be explained by the higher prevalence of this disease in early childhood and possibly also by a higher concern of the parents of the younger patients.

The use of a responder analysis to identify clinically meaningful differences in chronic urticaria patients following placebo- controlled treatment with rupatadine 10 and 20 mg

According to the EAACI/GA(2)LEN/EDF guidelines for urticaria management, modern non-sedating H1-antihistamines are the first-line symptomatic treatment for chronic urticaria. Two previous randomized clinical trials demonstrated rupatadine efficacy and safety in chronic urticaria treatment. However, a responder analysis to identify clinically meaningful differences in patients with chronic urticaria has not yet been performed. This analysis includes the pooled data from two randomized, double-blind, placebo-controlled, multicentre studies in which chronic urticaria patients were treated with rupatadine at different doses. Responder rates were defined as the percentage of patients after 4 weeks of treatment who exhibited a reduction of symptoms by at least 50% or 75% as compared to baseline. The variables analysed were as follows: Mean Pruritus Score (MPS), Mean Number of Wheals (MNW), and Mean Urticaria Activity Score (UAS). A total of 538 patients were included. This responder analysis, using different response levels, shows that the efficacy of rupatadine 10 mg and 20 mg is significantly better as compared to placebo in the treatment of chronic urticaria patients. Notably, treatment with rupatadine 20 mg daily resulted in a higher percentage of patients with response of 75% symptom reduction or better than rupatadine 10 mg. Our results support the use of higher than standard doses of non sedating antihistamines in chronic urticaria. We strongly recommend performing and reporting responder analyses for established and new drugs used by patients with chronic urticaria.

Efficacy of leukotriene receptor antagonist with an anti-H1 receptor antagonist for treatment of chronic idiopathic urticaria

Background: Chronic idiopathic urticaria (CIU) is often difficult to treat. Although histamine-releasing activity is detectable for up to 50% of CIU patients, antihistamine therapy provides only a limited response. Objective: This study aimed to assess the clinical efficacy of combined leukotriene receptor antagonist (LRA) and H1 antihistamine, H1 and H2 antihistamine, and two H1 antihistamines as a synergistic therapeutic regimen for treating CIU compared with a matched placebo modality. Methods: A total of 120 newly diagnosed adult patients were evaluated. Patients were single blinded and randomly assigned to one of four medication groups that received the following regimens for 4 weeks: Group A, combination of sedating H1 antihistamine and non-sedating H1 antihistamine; Group B, combination of H1 antihistamine and H2 antihistamine; Group C, combination of H1 antihistamine and LRA; and Group D, matched placebo medication. The primary measure of treatment efficacy was the daily urticaria activity score (UAS) of ‘wheal and itch’. A positive therapeutic response was defined as a reduction to < 25% of baseline weekly UAS, while a relapse was a return to > 75% of baseline weekly UAS. Results: In all, 107 patients completed the trial medication. At the end of 4 weeks, the UAS score as a response to treatment was 23.3% for Group A, 63.3% for Group B, 53.3% for Group C, and no real change for the placebo treatment group. Conclusions: The combination of LRA and H1 receptor antagonist is promising for CIU treatment and is reasonably well tolerated by patients. The combination of H1- and H2-receptor antagonists provided the greatest treatment efficacy by the measures used in this small study.

Management of persistent allergic rhinitis in the tropics: Singapore experiences

SummaryAllergic rhinitis (AR) is a common manifestation of allergic diseases, affecting 10–25% of the world's population. In the tropics, the majority of AR is persistent. The year‐round warm, humid climate is conducive for the proliferation of dust mites and moulds, two of the most common aeroallergens implicated in persistent allergic rhinitis (PAR). The management of AR includes patient education, allergen avoidance, pharmacological treatment, and specific immunotherapy. Patient education, especially regarding dust and mould exposure reduction, can be effective but is often under‐utilized. Second generation, non‐sedating H1‐antihistamines rapidly relieve most nasal symptoms because they effectively block the histamine H1‐receptors that trigger plasma exudation and oedema. Congestion is most effectively controlled by intranasal glucocorticosteroids (INSs), which are currently the most potent AR drug treatment. The beneficial effects of steroids depend on their long‐term, multi‐pathway anti‐inflammatory effects, unlike H1‐antihistamines, which directly block neural and vascular H1 receptors. However, especially in PAR, patients' compliance with INS therapy has a significant impact on treatment efficacy, because year‐round treatment is required. Subcutaneous inhalant allergen immunotherapy (SCIT) is effective against a broad range of AR symptoms, and may be able to alter the natural course of allergy and prevent asthma onset. SCIT can significantly reduce the severity of allergic disease, including nasal obstruction, and decrease the need for anti‐allergic drugs. Immunotherapy (IT) can also be given as sublingual drops (SLIT). Recent studies have shown the SLIT to be effective in reducing AR symptoms and medication use. Both types of IT require long‐term patient compliance for successful treatment. Drug and IT interventions may not be economically feasible in certain patients. In conclusion, the type of AR most prevalent in the tropics is PAR, which must be treated year round. Improvement of educational programmes for the public and physicians alike seems to be the most effective treatment strategy.

Urticaria: Current Opinions about Etiology, Diagnosis and Therapy

In the last few decades an increasing understanding of the pathomechanisms involved in urticaria has highlighted the heterogeneity of different subtypes. According to the new European Academy of Allergology and Clinical Immunology/Global Allergy and Asthma European Network/European Dermatology Forum (EAACI/GA(2)LEN/ EDF) guidelines, urticaria subtypes can be grouped into spontaneous urticaria, which includes acute urticaria and chronic urticaria, the physical urticarias, and other urticaria disorders, including, for example, contact urticaria. Clarity of nomenclature is required not only to choose the correct measures in diagnosis and management, but also to compare data from different studies. Urticaria has a profound impact on quality of life and performance. Effective treatment is thus required in all cases where avoidance of eliciting factors is not feasible. For symptomatic relief, non-sedating H1-antihistamines are the first choice in most subtypes of urticaria; however, double-blind controlled studies have shown that the dosages required may exceed those recommended for other diseases, e.g. allergic rhinitis. The current guidelines therefore suggest increasing the dosage up to four-fold, whereas alternative treatments should be reserved as add-on therapy for unresponsive patients.

EAACI/GA2LEN/EDF guideline: management of urticaria

This guideline is the result of a consensus reached during a panel discussion at the second International Consensus Meeting on Urticara, Urticaria 2004, a joint initiative of the EAACI Dermatology Section and GA2LEN. Urticaria has a profound impact on the quality of life, and effective treatment is therefore required. The recommended first line treatment are nonsedating H1 antihistamines. They have proven to be effective in double-blind controlled studies, but dosages increased up to fourfold over the recommended doses may be necessary. However, for different urticaria subtypes and in view of individual variation in the course of the disease and response to treatment, additional or alternative therapies may be required. Immunosuppressive drugs like cyclosporin A and corticosteroids are not recommended for long-term treatment due to unavoidable severe adverse effects. This guideline was, in addition, accepted by the European Dermatology Forum (EDF) and formally approved by the European Union of Medical Specialists (UEMS).

Chronic urticaria: assessment of current treatment

Chronic urticaria is heterogenous, long-persisting and has a severe impact on quality of life and daily work. Effective treatment is essential but remains a confounding problem. This review summarizes available treatment strategies for chronic urticaria and their strength of evidence. Besides treatment of identified triggering factors such as chronic persistent bacterial infections (e.g., with Helicobacter pylori, streptococci, staphylococci or yersinia), standard treatment consists of nonsedating H1-antihistamines. Most patients require increasing (off-label) dosages that should be taken daily and regularly, however, this still fails in a third of cases. Reliable alternatives in the world literature are rare and the level of evidence is low. Certain subgroups may display benefit from additional treatment with cyclosporine A, cysteinyl leukotriene receptor antagonists, chloroquine, dapsone or other alternatives. A practicable step-wise treatment approach is given to optimize and individualize the treatment of patients with chronic urticaria.

Evaluation of pharmacokinetic interaction between cetirizine and ritonavir, an HIV-1 protease inhibitor, in healthy male volunteers

Serious adverse effects have been observed with some non-sedative H1-antihistamines (terfenadine and astemizole) when they were associated with drugs known to inhibit their metabolism. However, this is not a class effect, and this interaction should be considered on a case-by-case basis. The aim of this study was to evaluate the potential of pharmacokinetic interaction between cetirizine and ritonavir, the most potent cytochrome P450 (CYP) inhibitor. An open-label, single-center, one-sequence crossover pharmacokinetic study was conducted in three running periods: cetirizine (CTZ) alone, ritonavir (RTV) alone and then CTZ plus RTV. For each period, steady-state pharmacokinetics were obtained. RTV and CTZ plasma concentrations were determined using validated liquid chromatography methods. The statistical method was based on a 90% confidence interval (CI) for the ratio of population geometric means (combination/drug alone) for each drug and for each parameter [area under the plasma concentration versus time curve (AUC(0-tau,ss)), value of maximum plasma concentration (C(max,ss))] and compared to bioequivalence ranges 80-125% and 70-143% for AUC(0-tau,ss) and C(max,ss), respectively. Among the 17 male subjects enrolled (26.4 +/- 8.6 years), 16 completed the study (1 withdrawal after the first period). The RTV pharmacokinetic parameter values were not affected by CTZ co-treatment. With RTV, a 42% increase in the CTZ AUC(0-tau,ss) (3406 versus 4840 microgh/l, 90% CI of 128-158%), a 53% increase in the CTZ elimination half-life (7.8 h versus 11.9 h, P = 0.001), a slight increase (15%) in the CTZ apparent volume of distribution (V(d,ss)/f) (34.7 l versus 39.8 l, P = 0.035), a 29% decrease in the CTZ apparent total body clearance (49.9 ml/min versus 35.3 ml/min, P < 0.001) and bioequivalent C(max,ss) (374 microg/l versus 408 microg/l) were observed. No serious drug related adverse effects were notified. CTZ does not significantly affect the pharmacokinetic parameters of RTV, and the association does not, thus, require a modification of the dosage of the protease inhibitor. The increased extent of exposure to CTZ in healthy subjects, in the presence of RTV administered at high doses, remained in the same range as previously observed in the elderly or in mildly renally impaired subjects.

Idiopatic angioedema treated with dapsone

The most commonly identified causes of angioedema are medications, allergens and physical agents, but most cases of angioedema are idiopathic. Treatment depends on identification of the causative agent and, especially when the mechanism is not identified, on the clinician's knowledge and experience with innovative therapeutic regimens. Case report A 48-year-old man presented with a 3-month history of recurrent severe episodes of angioedema affecting the lips, tongue and throat. A fiberoptic examination revealed laryngeal edema during some episodes. He did not report abdominal pain, nausea or vomiting. No precipitating factors were identified. The patient was not receiving angiotensin-converting enzyme inhibitors. For the previous 4 years, the patient had been receiving levothyroxine for autoimmune thyroiditis. There was no history of facial palsy or hereditary angioedema. Allergy study Skin prick test with aeroallergens, food, latex, Anisakis and patch test to a standard series (true test) were negative. Laboratory investigations revealed normal complete blood count (CBC), erythrocyte sedimentation rate, urinalysis, blood biochemistry, serum protein electrophoresis and serum immunoglobulins. IgE concentration was 30 UI/ml. Antiperoxidase antibodies were positive (535 UI/ml). Antinuclear antibodies serum immune complexes and rheumatoid factor were negative. Complement study during acute and asymptomatic periods revealed normal values of C1 esterase inhibitor, C1q, C3, C4, functional activity of C1 inhibitor and CH50. No pathologic findings were observed in a lip biopsy. The patient was treated with sedating and nonsedating H1 antihistamines and corticosteroids (prednisone 30 mg/day for 3 months) with no clinical improvement and treatment with 50 mg of dapsone daily was started. Glucose 6 phosphate dehydrogenase deficiency had previously been ruled out. The patient improved and antihistamine and corticoid treatment was withdrawn 1 month after starting the dapsone regimen. No episodes of angioedema appeared during the subsequent year. No reductions in hematologic parameters or adverse events were detected. Dapsone may be an alternative drug in extreme cases of idiopathic angioedema in patients with poor response to conventional therapy.

Norpiperidine Imidazoazepines as a New Class of Potent, Selective, and Nonsedative H1 Antihistamines

Clinical doses of available H(1) antihistamines are limited mainly by sedative side effects. However, higher doses are often required to obtain optimal therapeutic activity, especially in dermatology. We report the synthesis of three norpiperidine imidazoazepines representative of a new class of selective and nonsedating H(1) antihistamines. The compounds were at least as potent as cetirizine and loratadine as measured by H(1) receptor binding affinity, by protection against compound 48/80- and histamine-induced lethality in rats and guinea pigs, respectively, and by skin reaction tests in rats, guinea pigs, and dogs. The compounds, in particular 3a, were less prone than the reference compounds to penetrate the brain and to occupy central H(1) receptors, suggesting absence of sedative side effects. In vitro and in vivo cardiovascular safety tests showed that 3a had no intrinsic potential to prolong ventricular repolarization or induce cardiac arrhythmias. Compound 3a has been selected for further clinical development, mainly for application in dermatology.

Urticaria.

Urticaria has been known as a disease since antiquity. However, in the last decades an increasing understanding of the mechanisms involved in its pathogenesis has shown the high heterogeneity of different urticaria subtypes. Clear distinction of the subtypes is required not only to choose the correct measures in diagnosis and management, but also to interpret the available data in research. The subtypes can be grouped into spontaneous urticaria, which includes acute urticaria and chronic urticaria, the physical urticarias, special types of urticaria including, e.g. contact urticaria, and diseases related to urticaria for historical reasons, e.g. urticaria pigmentosa. Most urticaria subtypes have a profound impact on the quality of life and effective treatment is thus required in case the diagnostic procedures do not reveal a cause which can be treated. Although, for symptomatic relief, nonsedating H1-antihistamines are the first choice in most subtypes of urticaria, double-blind controlled studies have shown that dosages required may exceed those recommended for other diseases, e.g. allergic rhinitis. Alternative treatments should be reserved for unresponsive patients.

Efficacy and safety of desloratadine in the treatment of perennial allergic rhinitis

Background: The evidence base for the use of H1-antihistamines in the treatment of perennial allergic rhinitis is considerably smaller than it is in the treatment of seasonal allergic rhinitis. Objective: We hypothesized that desloratadine, a new, nonsedating selective H1-antihistamine, would be efficacious and safe in the treatment of perennial allergic rhinitis. Methods: In a multicenter, randomized, placebo-controlled, double-blind, parallel-group study, 676 patients with symptomatic perennial allergic rhinitis were randomly assigned to 4 weeks of treatment with either 5 mg of desloratadine once daily or placebo. Efficacy was assessed by using a morning-evening instantaneous total symptom score (TSS), which was composed of scores for 4 individual nasal symptoms (rhinorrhea, itching, sneezing, and postnasal drip) and 3 individual nonnasal symptoms (itching eyes, watering eyes, and itching of the ears or palate). Secondary outcome measures included a morning-evening reflective TSS, total nasal and nonnasal symptoms scores, and individual symptom scores. Safety evaluations, including 12-lead electrocardiograms, were performed. Results: Six hundred thirty-four patients completed the study. Desloratadine consistently diminished perennial allergic rhinitis symptoms, reducing the morning-evening instantaneous TSS (P = .005), the morning-evening reflective TSS (P = .007), the morning-evening reflective total nonnasal score (P = .023), and the individual nasal symptom scores for rhinorrhea, nasal itching, sneezing, and postnasal drip/drainage (P = .05 to P = .013) during weeks 1 through 4. Improvement in symptoms was observed after the first dose. Dropouts, and the type and frequency of adverse events (headache, viral infection, pharyngitis, and upper respiratory tract infection), were similar in both treatment groups. No clinically significant changes in QTc intervals were observed. Conclusions: Desloratadine rapidly and safely reduced the symptoms of perennial allergic rhinitis, and its efficacy did not diminish during 4 weeks of treatment. (J Allergy Clin Immunol 2003;111:617-22.)

Allergy: a global problem. Quality of life.

Allergy: a global problem. Quality of life.