Efficacy and safety of antihistamines in allergic skin disorders

Background For patients with urticaria, H₁-antihistamines remain the gold standard medical treatment of choice. They act by blocking H₁ receptors on the vascular endothelial cell surface. Newer, non-sedating antihistamines such as loratadine also act to some extent by blocking the release of histamine from mast cells, basophils and human skin tissue. Efficacy All of the newer antihistamines (loratadine, terfenadine, astemizole and cetirizine) have been shown to have comparable efficacy to the classic sedating antihistamines and to be significantly superior to placebo in terms of symptom improvement. Loratadine has been shown to be at least as effective as the other non-sedating agents and cetirizine. Antihistamines also have a potential benefit in the management of patients with atopic dermatitis. In two studies, loratadine was found to be significantly superior to placebo in the reduction of pruritus. Safety In terms of safety, the newer antihistamines have important differences. Cetirizine, for example, causes dose-related sedation and functional impairment compared to placebo. In contrast, loratadine has no such sedative effects. Terfenadine and astemizole have also been shown to be free of sedative effects, but exceeding the recommended dose of either may increase the risk of a serious cardiac arrhythmia, torsades de pointes. Plasma levels of both terfenadine and astemizole may also be increased as a result of interaction with various drugs. In contrast, loratadine has not been shown to induce ECG changes, even at doses of 40 mg o.d. for 90 days.     

Solar angioedema: an uncommonly recognized condition?

Solar urticaria is a well defined although uncommon photosensitivity disorder, and is said to be the underlying cause of chronic urticaria in approximately 0.5% cases. In contrast, solar angioedema is seldom reported. We describe two patients with postulated solar angioedema, associated with clinical and/or phototest features of solar urticaria. Recognition of solar provocation of angioedema has important consequences for patient management.     

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.     

Synergistic effect of broad-spectrum sunscreens and antihistamines in the control of idiopathic solar urticaria

BACKGROUND: It can be difficult to provide patients with idiopathic solar urticaria adequate protection from sunlight. In a nonrandomized controlled trial, we used a standardized phototest procedure to determine the effects of using sunscreen and antihistamine to control idiopathic solar urticaria. OBSERVATIONS: Three patients with idiopathic solar urticaria underwent phototesting with UV-B and UV-A radiation. The minimal urticarial dose (MUD) was determined 15 minutes after irradiation. The patients were subsequently tested with 5 times the MUD, and the reaction was graded every minute for 15 minutes. The patients were then treated with a high-protection, broad-spectrum sunscreen and a nonsedative antihistamine alone and in combination and underwent similar phototesting. The use of sunscreen allowed the patients to tolerate much higher doses of UV radiation (32-38 times the MUD on untreated skin). Antihistamine use did not increase the patients' MUD but did suppress wheal formation and itch, and only immediate erythema sharply located in the irradiated areas occurred. The combination of sunscreen and antihistamine acted synergistically and increased the tolerance to UV radiation markedly (80-267 times the MUD on untreated skin). Conclusion High-protection, broad-spectrum sunscreens and antihistamines protect patients with solar urticaria in different ways and are highly effective when combined.     

Changes of photosensitivity and action spectrum with time in solar urticaria

BACKGROUND: Solar urticaria is a rare photosensitivity disorder characterized by the rapid onset of a pruritic, erythematous and urticarial rash following sun-exposure. The action spectrum and degree of photosensitivity have been observed to change over time in several isolated reports. METHODS: Monochromator phototesting was performed on multiple occasions on 12 patients with solar urticaria. RESULTS: Six patients demonstrated normal responses in the initial phototest. They remained normal in five patients upon subsequent testing. Seven patients demonstrated abnormal immediate responses, most frequently at UVA wavelengths. Within some individuals, variations in action spectrum and/or degree of photosensitivity were observed over the years, but not over days. CONCLUSION: Significant changes in action spectrum and degree of photosensitivity may occur over years in solar urticaria. However, changes over shorter periods of time are likely to be minor and not have clinical significance.     

Chronic urticaria: a role for newer immunomodulatory drugs?

Chronic urticaria is now recognized as an autoreactive disorder in a substantial fraction of patients. A serologic mediator of whealing has been demonstrated in 50-60% 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 H(1) 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 (7-14) 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 20-50% 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.     

仙特敏、甲氰咪呱和潘生丁联合治疗慢性荨麻疹疗效观察

报道仙特敏、甲氰咪呱和潘生丁联合应用治疗５７例慢性荨麻疹的疗效观察。结果：联合组显效率和总有效率分别为７９％和９１．２％，仙特敏单用组显效率和总有效率分别为５１．４％和７７．１％，两组比较有显著性差异（Ｐ＜０．００１）。本文提示这三种药联用是治疗慢性荨麻疹安全和有效的方法。     

Comparative efficacy of cetirizine and levocetirizine in chronic idiopathic urticaria

H1 receptor antagonists are the mainstay of treatment for chronic idiopathic urticaria. Newer hydroxyzine derivatives such as cetirizine and levocetirizine have been found to be equally efficacious in preclinical studies in patients with chronic idiopathic urticaria. In this study, the clinical efficacy of cetirizine and levocetirizine has been studied sequentially in individual patients. Fifty chronic idiopathic urticaria patients received 10 mg of levocetirizine daily for 6 weeks. Some 45 patients out of these showed reasonably good clinical efficacy on a visual analog scale to qualify for comparison with levocetirizine. A total of 30 patients completed the study period of 6 weeks each of cetirizine and levocetirizine sequentially. Thus, the clinical efficacy of cetirizine and levocetirizine was comparable with a marginal advantage of better antipruritic effect with levocetirizine, probably at the cost of increased sedation.     

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.     

Plasma exchange therapy for solar urticaria

We report two cases of severe idiopathic solar urticaria treated.1 with plasma exchange therapy. Previous treatment which included antihistamines and. in one patient, desensitization with psoralens and ultraviolet A (PUVA) and narrowband ultraviolet B phototherapy produced only partial benefit. The effect of plasma exchange therapy was assessed using monochromator phototesting and intradermal injection of in vitro irradiated serum. One patient responded but relapsed within 2 weeks. We have failed to demonstrate a lasting benefit from plasma exchange therapy (PExT) in the treatment of two patients with idiopathic solar urticaria.     

Treatment of acquired cold urticaria with cetirizine and zafirlukast in combination

Acquired cold urticaria is an infrequent physical urticaria that can provoke severe systemic reactions. Histamine is the primary mediator, but leukotrienes are also involved in the pathogenesis. H(1) antihistamines are recommended as first-choice treatment, but their efficacy is sometimes unsatisfactory. On the basis of pathogenic knowledge, it can be hypothesized that a combination therapy with antihistamines and leukotriene receptor antagonists is more effective than each drug given alone. We tested this hypothesis in 2 patients with severe systemic cold urticaria poorly responsive to conventional therapy. The patients underwent 3 consecutive treatment regimens (each of 2 weeks): cetirizine (10 mg once a day); zafirlukast (20 mg twice a day); and their combination. They were clinically evaluated, after each regimen, by means of a visual analog scale and ice-cube test. The combination therapy was superior to the 2 drugs given alone, as testified by subjective and objective evaluations.     

中药方剂联合西替利嗪问隔疗法治疗慢性荨麻疹36例临床观察

目的观察自拟中药方剂与西替利嗪联合问隔疗法治疗慢性荨麻疹的临床疗效。方法采用随机、阳性对照药平行对照的方法,对72例符合研究方案的患者分别间隔给予自拟中药联合西替利嗪或单纯应用西替利嗪口服治疗,治疗前及治疗第4、第8周记录瘙痒、红晕及风团变化情况。结果治疗前后试验组对瘙瘁、红晕及风团的改善效果优于对照组（P〈0．05）,试验组有效率高于对照组（P〈0．05）。结论中药方剂联合西替利嗪间隔疗法可以明显改善慢性荨麻疹患者撤药过程中的临床症状及复发情况。     

Terfenadine and brompheniramine maleate in urticaria and dermographism

The effects of brompheniramine maleate (12 mg twice daily in sustained release form) and terfenadine (60 mg twice daily) on the symptoms and well-being of 16 adults with urticaria with or without dermographism were assessed by symptom questionnaire. Following an initial 2-week period without therapy, each drug was taken for 2 weeks in a randomised double-blind cross-over study. Both drugs produced significant relief of itch and rash but only brompheniramine produced significant drowsiness. Brompheniramine maleate was more effective than terfenadine in the patients with dermographism.     

依巴斯汀雷尼替丁联合治疗慢性荨麻疹疗效观察

目的观察依巴斯汀、雷尼替丁联合治疗慢性荨麻疹的疗效。方法62例患者随机分成两组,治疗组口服依巴斯汀与雷尼替丁,对照组口服西替利嗪与雷尼替丁,疗程4周,评估疗效,记录不良反应。结果治疗组和对照组有效率分别为84.26%和71.43%,差异无显著性(P>0.05)。结论依巴斯汀、雷尼替丁联合治疗慢性荨麻疹疗效好,安全可靠。     

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.     

Plasmapheresis in solar urticaria

Three patients with solar urticaria were treated with plasmapheresis. By intradermal injection of in vitro irradiated serum the existence of a circulating photoallergen was demonstrated in cases 1 and 2 but not in case 3. Plasmapheresis induced complete remission of solar urticaria in case 1 and transient improvement in case 2. In case 3, however, no beneficial effect was observed. It is suggested that some patients with solar urticaria, probably those with a circulating photoallergen, may benefit from plasmapheresis.     

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.     

Effect of cetirizine on cutaneous reactions to PAF, kallikrein and serum in patients with chronic urticaria

The effects of oral administration of the antihistamine cetirizine on the weal and flare caused by intradermal injection of platelet activating factor (PAF-acether), kallikrein, histamine and the patient's own serum were investigated in 10 patients with chronic urticaria. Cetirizine markedly reduced the weal and flare induced by all these agents as measured 12 min after the injections. The delayed reactions observed after injection of PAF, kallikrein and serum were also inhibited by cetirizine at 6 hours. In addition, reactions which were present 20 h after injection of the agent before administration of cetirizine were found to be inhibited at the same point in time after cetirizine treatment. These effects might explain the good inhibitory clinical effect of cetirizine on the patients' urticaria. No side-effects were noted during the treatment.     

盐酸非索非那定治疗126例慢性特发性荨麻疹

目的:评价盐酸非索非那定片治疗慢性特发性荨麻疹的有效性和安全性。方法:多双盲、随机、平行组对照的临床试验,以盐酸西替利嗪片为对照药。结果:共完成病例126例,试验组63例,对照组63例。试验组有效率为88.89%,对照组有效率为80.95%,两组无显著性差异(P >0.05)。试验组不良反应发生率为4.76%;对照组不良反应发生率为9.52%,两组无显著性差异(P>0.05)。结论：:盐酸非索非那定片治疗慢性特发性荨麻疹的有效性与盐酸西替利嗪片相当。