MEDLINE Abstracts: Treatment of Chronic Urticaria

September 16, 2003

What's new concerning treatment of chronic urticaria? Find out in this easy-to-navigate collection of recent MEDLINE abstracts compiled by the editors at Medscape Allergy & Clinical Immunology.

Maurice-Tison S, Pouyanne J, Doutre MS
Ann Dermatol Venereol. 2003;130 Spec No 1:1S160-73

This report presents the results of a national study realized in June and July 2002 to describe dermatologists, allergists, and general practitioners' clinical intentions of practice in front of chronic urticaria, before the consensus conference on this topic. A total of 75% of general practitioners (112/148), 73% of dermatologists (131/180), and 90% of allergists (58/64) completed the interview by phone. Health authorities and medical associations furnished the lists for drawing of lots. General practitioners realize few diagnostic investigations and prescribe in most cases antihistamines. In case of persistence, they resort to specialists, dermatologists or allergists. Dermatologists and allergists seemed to have similar practices for management of chronic urticaria, even if allergists realize more allergy skin tests. Chronic urticaria remains unexplained in about 60% of the observations. When an aetiology was identified, it is a physical urticaria for allergists and drug-induced urticaria for dermatologists. For all the physicians, non-sedating and/or sedating anti-histamines are the principal treatment, sometimes associated with others drugs, in case of resistance. Most of the physicians perceived psychological factors as important. Sometimes, they suggest a specific therapy. This questionnaire survey will be done again some months after publication of recommendations to appreciate its impact on physicians.

Buffet M
Ann Dermatol Venereol. 2003;130 Spec No 1:1S145-59

Introduction: Chronic idiopathic urticaria (CIU) is a frequent disease in which treatment is often disappointing. Psychological factors seem to be frequently associated with it. In which cases should one consider psychological treatment? And according to what modalities?
Method: This study was a review of the literature in search of articles in both French and English concerning psychological factors associated with chronic urticaria, either as responsible factors, or as aggravating factors, or as a consequence of the urticaria, with the study of the impact on the quality of life. We also studied articles analyzing various types of psychology-targeted treatments. We use a series of keywords on following data banks: Medline (1970-2002), Embase, Pascal, and Cochrane Library (period 1995-2002).
Results: Very few controlled studies were published. Various studies are found reporting an association between stress, anxiety, or depressive symptomatology and CIU, but none can assert a causality. Three controlled, opened studies show significantly more anxiety and\or depression in the chronic urticaria patients. Three studies analyze the psychopathological personalities of the patients with urticaria. Two studies focus specifically on the impact of the CIU on the quality of life. Various psychotropic drugs (mainly tricyclic antidepressants) have been tested, mostly because of their anti-H1 activity. There is no study on psychological support, psychotherapies, behavioral therapies, technique of biofeedback, and group therapies. Particular attention is focused on hypnosis and relaxation techniques because of the improvement of the urticarial wheals reported in studies of cutaneous ability to react in subcutaneous injections of histamine.
Conclusion: A complementary psychological treatment of patients suffering from CIU seems necessary, because of the high frequency of psychological symptoms. Published studies concern essentially the prescription of psychotropic drugs and the use of therapies with suggestion of relaxation under hypnosis. Prospective studies on the impact of an adapted psychological treatment on the CIU evolution are not available.

Mateus C
Ann Dermatol Venereol. 2003;130 Spec No 1:1S129-44

Treatment of CIU is a difficult and often frustrating problem for physicians. Due to the lack of definitive medical therapeutic programs to relieve the symptoms and prevent from their recurrence, several pharmacologic approaches to the management of CIU are proposed. The chronic urticaria pharmacologic therapy is therefore fit to abrogate effects of histamine and other mediators on cutaneous vasculature and inflammatory cells that participate in the pathogenesis of the urticaria. The most common approach is to avoid all aggravating factors and to block histamine. The mainstay therapy is H1 antihistamines. A significant number of patients may remain unresponsive even after an increase in the dose or a change in the type of H1 antihistaminic drug. In these cases, several therapies can be associated: combinations of H1 antihistamines, nonsedating one tablet (morning) and one sedating (evening), this approach is very usual but no study has confirmed it rational. The addition of an H2 antagonist to the previous treatment for some patients may improve control of their symptoms; alternatively, the tricyclic antidepressant, doxepin, is usually prescribed. The results of other drugs reported in the literature are unpredictable, to include them in a strategy therapy. The results with beta2-adrenergic agents, nifedipine, ketotifen, leukotriene antagonists, and tranexamic acid are variable and do not appear better than therapy with H1 antagonists. The efficiency of danazol has to be confirmed by other controlled studies. Warfarin, sulfasalazine, and ultraviolet radiation have been used apparently successfully, but no controlled study has been published. If the above treatments have failed then immunosuppresive therapies, intravenous immunoglobulin, and plasmapheresis can be proposed for CIU.

Ortonne JP
Eur J Intern Med. 2003;14:148-157

Chronic idiopathic urticaria (CIU) manifests as frequently occurring, short-lived wheals, surrounded by a bright-red flare, and often accompanied by angioedema. The cause of CIU is undefined and its diagnosis requires exclusion of other conditions with somewhat similar symptoms. Recent evidence has indicated that immunoglobulin (Ig) G autoantibodies directed against high-affinity IgE receptors (FcepsilonRI) may be involved in the pathophysiology of CIU. Following the release of mast cell or basophil-derived histamine, this mediator binds to H1 and H2 receptors, leading to vasodilatation and increased vascular permeability. Individuals with CIU may be unable to conduct normal daily activities; therefore, prompt initiation of effective treatment is essential. General management of patients should include avoidance of substances likely to trigger or intensify episodes. Treatment with antihistamines is the mainstay of pharmacotherapy for CIU. Selection of antihistamine therapy for patients with CIU should be based on the following key properties: (1) proven clinical efficacy in providing a high rate of symptom improvement; (2) rapid onset of action and a long-lasting response; and (3) an excellent safety profile and a high degree of tolerability. The benefit of some second-generation antihistamines is limited by sedation, drug-drug interactions, or a variable therapeutic response. The H(1)-receptor antagonist desloratadine is a new, once-daily treatment option that is potent and nonsedating, and has a low potential for drug-drug interactions. Desloratadine has a rapid onset of action and has been shown to effectively and safely reduce pruritus and the number and size of hives in patients with CIU, leading to improvements in quality of life.

Nordness M, Zacharisen MC
Cutis. 2003;71:396

We report the case of a 46-year-old man who tolerated 50 mg per day of cetirizine for the treatment of CIU. The patient denied any sedation or somnolence and had no difficulty performing routine daily functions including driving. He had tried other antihistamines, including fexofenadine, loratadine, and hydroxyzine without improvement.

Tedeschi A, Airaghi L, Lorini M, Asero R
Am J Clin Dermatol. 2003;4:297-305

Chronic urticaria is now recognized as an autoreactive disorder in a substantial fraction of patients. A serologic mediator of whealing has been demonstrated in 50% to 60% of patients with chronic urticaria; and autoantibodies against the high-affinity IgE receptor or IgE have been detected in about half of these patients. The demonstration that chronic urticaria is frequently autoimmune has encouraged a more aggressive therapeutic approach, with the use of immunomodulatory drugs. A step-by-step approach to the management of chronic urticaria is proposed, based on our personal experience and review of current medical literature, identified through Medline research and hand searching in medical journals. The non- or low-sedating H1 receptor antagonists (antihistamines), such as cetirizine, fexofenadine, loratadine, mizolastine, and, more recently, levocetirizine, desloratadine, and ebastine, represent the basic therapy for all chronic urticaria patients. Older sedating antihistamines, such as hydroxyzine and diphenhydramine, may be indicated if symptoms are severe, are associated with angioedema, and if the patient is anxious and disturbed at night. Corticosteroid therapy with prednisone or methylprednisolone can be administered for a few days (7 to 14) if urticarial symptoms are not controlled by antihistamines and a rapid clinical response is needed. In cases of relapse after corticosteroid suspension, leukotriene receptor antagonists, such as montelukast and zafirlukast, should be tried. In our experience, remission of urticarial symptoms can be achieved in 20% to 50% of chronic urticaria patients unresponsive to antihistamines alone. When urticaria is unremitting and is not controlled by combined therapy with antihistamines and leukotriene receptor antagonists, prolonged corticosteroid therapy may be needed. Long-term corticosteroid therapy should be administered at the lowest dose able to control urticarial symptoms, in order to minimize adverse effects. In a few patients, however, high-dose corticosteroid therapy may have to be administered for long periods. In these patients, immunosuppressive treatment with low-dose cyclosporine can be started. This type of treatment has a corticosteroid-sparing effect and is also generally effective in patients with severe, unremitting urticaria, but requires careful monitoring of cyclosporine plasma concentration and possible adverse effects. Other immunomodulating drugs that have been tried in chronic urticaria patients include hydroxychloroquine, dapsone, sulfasalazine, and methotrexate; but their efficacy has not been proven in large controlled studies. Warfarin therapy may also be considered in some patients with chronic urticaria and angioedema unresponsive to antihistamines.

Monroe E, Finn A, Patel P, Guerrero R, Ratner P, Bernstein D; Desloratadine Urticaria Study Group
J Am Acad Dermatol. 2003;48:535-541

Background: CIU has a major impact on patient well-being. Antihistamines are the first-line treatment for CIU; however, some cause sedation.
Objective: Our purpose was to study the efficacy and safety of desloratadine, 5 mg, a new H1-receptor antagonist, in patients with moderate to severe CIU.
Methods: This study was a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial of 6 weeks' duration.
Results: Compared with placebo, desloratadine significantly improved the total CIU symptom score as well as pruritus, the number of hives, and the size of the largest hive. Overall therapeutic response and global CIU status improved significantly with desloratadine; interference with sleep was reduced and the performance of daily activities improved. Statistically and clinically significant improvements were seen within the first 24 hours of treatment and were sustained throughout the full duration of the study. The incidence of adverse events, including somnolence, was similar in the desloratadine and placebo groups.
Conclusion: Desloratadine is a well-tolerated and effective treatment of CIU.

Grattan CE
Clin Exp Dermatol. 2003;28:123-127

The relationship of aspirin sensitivity to urticaria is complex. Aspirin sensitivity can cause acute urticaria in some individuals, aggravate pre-existing chronic urticaria in others, or, rarely, act as a cofactor with food or exercise to provoke anaphylaxis. Individuals who react with urticaria appear to come from a different population to those who react with asthma, although there is some overlap. Aspirin-sensitive chronic urticaria patients may also react adversely to some food additives. The pharmacological mechanisms of aspirin-sensitive urticaria are not fully understood but probably involve diversion of arachidonic acid metabolism from prostaglandin to cysteinyl leukotriene formation leading to direct effects on blood vessels and delayed mast cell degranulation with release of histamine. Cross-reactivity amongst all nonsteroidal drugs is common in aspirin-aggravated chronic urticaria, but appears not to occur with selective cyclo-oxygenase 2 inhibitors.

Grattan CE, Dawn G, Gibbs S, Francis DM
Clin Exp Allergy. 2003;33:337-341

Background: The basopenia of chronic urticaria relates to histamine releasing autoantibodies in the serum of patients with autoimmune urticaria. This reduction in circulating basophils may be due to active recruitment into weals. If so, it might be expected that numbers in blood would be reduced when urticaria is active and increased after treatment. The primary aim of this study was to look at diurnal variation of basophil numbers in patients with chronic ordinary urticaria (not physical or vasculitic) in relation to disease activity, and the effect of treatment with antihistamines and corticosteroids, and to compare the results with healthy controls. A secondary aim was to compare a standard manual counting method with automated basophil counts and to look at numbers of other circulating leucocytes that might be relevant to urticaria pathogenesis.
Methods: Manual basophil counts using a toluidine blue stain and automated 5-part differentials (Coulter Gen. S) were performed at 4-hourly intervals from 08.00 to 20.00 in 10 healthy controls (six women, age 24 to 63 years) and seven chronic urticaria patients (five women, 24 to 50 years). All chronic urticaria patients had severe daily or almost daily urticaria. Only one of six chronic urticaria sera showed in vitro basophil histamine releasing activity. Counts were performed without treatment, after a week of taking loratadine 10 mg daily and after 3 days of adding prednisolone at 0.6 mg/kg/day (maximum 40 mg). Daily urticarial activity scores (UAS) were derived from weal numbers and itch, maximum 7.
Results: There was no significant overall diurnal variation of basophil numbers in healthy controls or chronic urticaria patients. Mean (SE) manually counted basophils were higher in healthy controls than chronic urticaria (43.4/ microL (2.1) vs. 4.4 (0.8), P < .001). Basophil counts were reduced in healthy controls on steroids (19.2 (1.9), P < .001), but increased in chronic urticaria (8.9 (1.9), P < .001). Loratadine did not influence them. UAS fell on treatment (3.3 [0.4] baseline, 1.4 [0.5] on loratadine and 0.5 [0.2] on prednisolone with loratadine, P < .001). There was a negative linear correlation between basophil numbers and UAS in untreated chronic urticaria patients (P = .001, Spearman rank correlation). Manual and automated basophil counts showed poor agreement. Lymphocyte numbers were lower in chronic urticaria than healthy controls. Neutrophils increased whereas lymphocytes and eosinophils decreased in all subjects on prednisolone. They were unaffected by loratadine.
Conclusion: The results are consistent with the hypothesis that circulating basophils may be recruited from blood into urticarial weals during disease activity. Automated counts are not suitable for assessing basophil numbers in chronic urticaria. The relevance of reduced lymphocyte numbers in chronic urticaria needs to be explored.