One‐year safety and efficacy study of bilastine treatment in Japanese patients with chronic spontaneous urticaria or pruritus associated with skin diseases

A number of second‐generation non‐sedating antihistamines are used in clinical practices over the world. However, long‐term safety and efficacy have not been proved high level evidence based medicine. We have performed an open‐label, multicenter, phase III study to evaluate the long‐term safety and efficacy of bilastine, a novel non‐sedating H₁‐antihistamine for patients with chronic spontaneous urticaria (CSU) or pruritus associated with skin diseases (trial registration no. JapicCTI‐142528). Patients aged 18–74 years were treated with bilastine 20 mg once daily for up to 52 weeks. Safety and tolerability were assessed on the basis of adverse events (AE), bilastine‐related AE, laboratory tests and vital signs. Efficacy was assessed based on rash score, itch score, overall improvement and quality of life. One hundred and ninety‐eight patients enrolled, 122 of whom (61.6%) completed the 52‐week treatment period. AE were reported in 64.5% and bilastine‐related AE in 2.5% of patients throughout the 52‐week treatment period. All AE were mild to moderate in severity. AE associated with the nervous system occurred in 10 patients (5.1%) including seven patients (3.6%) with headache. Somnolence reported in two of these patients (1.0%) was related to bilastine. All efficacy variables improved during treatment with bilastine. In conclusion, long‐term treatment with bilastine 20 mg once daily for 52 weeks is safe and well tolerated in Japanese patients with CSU or pruritus associated with skin diseases. Bilastine improved disease symptoms of both conditions early in treatment, and the efficacy was maintained throughout the treatment.     

Updosing nonsedating antihistamines in patients with chronic spontaneous urticaria: a systematic review and meta‐analysis

There is a lack of large, randomized, double‐blind studies that address antihistamine updosing for chronic spontaneous urticaria (CSU). The objective of this systematic review is to explore and analyse available data to provide clinical evidence for the efficacy of antihistamine updosing. We searched the literature in Medline, Scopus, Google Scholar, Embase, Web of Science and Cochrane databases using the keywords ‘chronic, urticaria, antihistamines’ to identify studies published between January 1990 and November 2014. We assessed quality using the Jadad score that evaluates quality of randomization, double‐blinding and losses to follow‐up. We identified 1042 articles and 15 articles were included in the final evaluation. We performed two meta‐analyses, one that included studies that analysed treatment response among groups receiving different antihistamine dosages vs. placebo, and another that analysed antihistamine updosing in those patients who did not respond to standard dosages. Only five articles obtained a high quality level score. We did not find significant differences in response rates or number of weals in those patients who received a standard dosage vs. a high dosage. We found a significant improvement only in the pruritus variable of the Urticaria Activity Score scale. The estimated relative risk for improvement by increasing the antihistamine dosage was 2·27 [95% confidence interval (CI) 1·68–3·06]; however, there was significant heterogeneity. The proportion of nonrespondent patients with CSU who responded to antihistamine updosing was 63·2% (95% CI 57–69·6). We found that updosing antihistamines significantly improved control of pruritus but not weal number. However, the relative weakness of the studies and the significant heterogeneity among them made it difficult to reach a final conclusion.     

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.     

Critical temperature threshold measurement for cold urticaria: a randomized controlled trial of H(1) -antihistamine dose escalation

Summary Background  Cold urticaria is a rare but severe and potentially lethal condition. It is primarily treated symptomatically with H₁‐antihistamines. However, patients have a variable response to these drugs and, to date, it has not been possible to predict readily the response to therapy of individual patients. Objectives  To assess the severity of the cold urticaria in naive patients and the response to therapy of patients treated with increasing doses of an H₁‐antihistamine by measurement of critical temperature thresholds (CTT) for producing weals on the forearm. Methods  This was a two‐centre, hospital‐based, double‐blind, randomized, parallel‐group study of patients with a confirmed diagnosis of cold urticaria of at least 6 months’ duration. Patient groups received either a constant dose of desloratadine 5 mg daily for 6 weeks (n = 13), or escalating doses of desloratadine: 5 mg daily for the first 2 weeks, 10 mg daily for the second 2 weeks and 20 mg daily for the final 2 weeks (n = 15). Only one adverse event that appeared to be drug related was reported: mild fatigue after treatment with desloratadine 10 mg that lasted for about 3 weeks and resolved at the end of the study. Results  The desloratadine 5 mg daily dose produced a submaximal reduction of mean CTT which remained relatively constant over 6 weeks. Dose escalation increased efficacy, the reduction in mean CTT at four‐times the standard daily dose being significantly greater (P = 0·03) than with the standard dose. Individually, no patient became symptom free (CTT < 4 °C) on 5 mg, while two became symptom free on 10 mg and a further three on 20 mg desloratadine daily. Conclusions  Measurement of CTT allows for individualized risk management and therapy in patients with cold urticaria.     

Treatment of chronic spontaneous urticaria with an inadequate response to H<Subscript>1</Subscript>-antihistamines: an expert opinion

Chronic spontaneous urticaria (CSU) is characterized by the sudden, continuous or intermittent appearance of pruritic wheals (hives), angioedema, or both for six weeks or more, with no known specific trigger. The international EAACI/GA²LEN/EDF/WAO urticaria guideline advises standard-dose, second-generation H₁-antihistamines as firstline therapy. However, H₁-antihistamine treatment leads to absence of symptoms in fewer than 50% of patients. Updosing of secondgeneration H₁-antihistamines (up to fourfold) as recommended by the EAACI/GA²LEN/EDF/WAO urticaria guideline as second-line therapy, can improve response, but many patients remain symptomatic. Definitions of response are often subjective and a consensus is needed regarding appropriate treatment targets. There is also an unmet need for biomarkers to assess CSU severity and activity and to predict treatment response. The EAACI/GA²LEN/EDF/WAO urticaria guideline recommends addon omalizumab, ciclosporinA(CsA), or montelukast third-line treatment in patients with an inadequate response to high-dose H₁-antihistamines. Omalizumab is currently the only licensed systemic biologic for use in CSU. Both omalizumab and CsA are effective third-lineCSUtreatments; montelukast appears to have lower efficacy in this setting. Omalizumab carries a label warning for anaphylaxis, although no cases of anaphylaxis were reported in the phase III trials of omalizumab in CSU and it is generally well tolerated in patients with CSU. Omalizumab arguably has a better safety profile than CsA.     

Selected urticaria patients benefit from a referral to tertiary care centres – results of an expert survey

Background Urticaria is a frequent reason for consultations. Recently, it has been demonstrated that the management of chronic spontaneous urticaria (csU) in the practice setting does not fully comply with published guidelines. In addition, it was shown that one of four csU patients is referred to specialized centres. Objective To analyse the management of urticaria patients in tertiary referral centres. Methods During a standardized expert‐to‐expert interview, 41 specialists from German tertiary care centres were asked for different aspects of urticaria patient care with a special focus on csU. Results On average, the participating centres saw 25 csU patients per month. All ran programmes for the identification of underlying causes with an average success rate of 45 ± 3% which is considerably higher as has been found in the practice setting. In those patients where an identification succeeds, infections, drugs, intolerance and autoreactivity were reported to be causes in 41%, 20%, 17% and 16%. In their symptomatic treatment the majority of centres (71%) followed the guidelines by using regular dosed non‐sedating H₁‐antihistamines as first line and higher doses (61%) as second line option. In contrast to the practice setting, meaningful experience also existed for alternative therapies in antihistamine‐resistant patients, such as dapsone, cyclosporin and omalizumab. The expenditure of time, laboratory costs and frequency of follow‐up visits was reported to be above average in case of csU. Conclusion This study indicates that some urticaria patients, especially those with unknown causes or with an H₁‐antihistamine‐resistant disease, may benefit from a referral to tertiary care centres.     

比拉斯汀在荨麻疹治疗中的应用

比拉斯汀是一种新型的H1受体拮抗剂,口服可治疗过敏性鼻炎和荨麻疹,其吸收较快,但食用食物和果汁后吸收减慢.已有数据证实,相比其他受体,比拉斯汀对H1的亲和力更高,并能降低组胺和细胞因子水平.在由组胺引起的皮肤风团和红斑上,比拉斯汀20 mg与西替利嗪10 mg相比具有等同疗效,可能有更快的抑制作用.比拉斯汀无抗胆碱作用,不影响驾驶,除此之外,比拉斯汀还具备良好的耐受性,无镇静作用、心脏毒性和肝脏毒性等优点.     

From regulatory limitations to new opportunities: Real‐life experience on the effectiveness of short courses of omalizumab in the treatment of chronic idiopatic urticaria

Economic sustainability of long‐term continuous treatment of antihistamine refractory chronic urticaria with omalizumab may be an issue. We assessed the efficacy of relatively short courses (5–6 months) of omalizumab in patients with chronic idiopathic urticaria (CIU). We retrospectively studied 40 patients (observed between June 2015 and January 2019) affected by moderate‐to‐severe CIU refractory to anti‐H1 antihistamines (up to fourfold doses). Omalizumab was administered every 4 weeks for 24 weeks, then for 20 weeks in case of a relapse of moderate‐to‐severe degree, then again for 24 weeks in case of a second relapse. Monthly clinical evaluations were performed. Mean disease severity significantly dropped after 1 month and further decreased thereafter, with 30 complete remissions after the first course of treatment. In 2–4 months, 18 patients had a relapse of moderate‐to‐severe degree. The profile of response to the second course of omalizumab was similar to the first. A third course was necessary for seven patients. No adverse effects were recorded. Courses of 5–6 months of omalizumab may induce rapid significant improvement of urticaria and many prolonged complete remissions. In case of relapse, further courses show a similar profile of response and may induce additional long‐term complete remissions.     

Evaluation of six antihistamines in vitro and in patients with urticaria

Six commonly prescribed antihistamines have been ranked according to their relative potencies in blocking H₁ and muscarinic receptors by an in vitro method on the myenteric plexus-longitudinal muscle preparation of the guinea pig ileum. Calculation of the ratios of K_e against acetyl choline to K_c against histamine suggested that mepyramine was the drug which discriminated most clearly between histamine H₁ and acetyl choline receptors. In contrast, using a self-assessment method in patients with chronic urticaria, cyproheptadine was the highest ranked antihistamine in terms of both effectiveness and relative freedom from side-effects. It is concluded that in vitro evaluation of antihistaminic and antimuscarinic potencies may produce misleading results in terms of clinical usefulness of a given antihistamine.     

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.     

Pharmacological rationale for the treatment of chronic urticaria with second‐generation non‐sedating antihistamines at higher‐than‐standard doses

Chronic urticaria (CU) is a long‐lasting and distressing condition that impairs patient quality of life (QoL) by disrupting sleep and diminishing work/school productivity. Thus treatment should not only be safe and effective but also not add to this impairment or increase risks to health or safety. Non‐sedating second‐generation antihistamines, with their long duration of action, pharmacodynamic properties that allow once‐daily dosing and lack of drug–drug interactions and sedative effects, are the first‐line symptomatic treatment option, but some patients have no adequate response to standard doses of these medications. Other therapeutic approaches to refractory urticaria have been suggested but have been limited by sparse clinical data and/or significant adverse effect profiles. Although discouraged by treatment guidelines, sedating antihistamines are frequently prescribed for nighttime use when urticaria symptoms are severe as add‐on therapy to a non‐sedating antihistamine. However, their pronounced effects on rapid eye movement sleep and hangover negatively impact QoL, learning and performance, and limit their use for patients in occupations that require alertness. For patients who do not respond adequately to standard doses of non‐sedating second‐generation antihistamines, increasing the dose of non‐sedating antihistamines thus may represent the safest therapeutic approach. Given the fact that only few controlled studies have assessed the efficacy and safety of high‐dose non‐sedating antihistamines in CU, patient safety should be a key consideration when choosing a specific antihistamine.     

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.     

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.     

Pharmacology of Antihistamines

H_1-antihistamines, the mainstay of treatment for urticaria, were developed from anticholinergic drugs more than 70 years ago. They act as inverse agonists rather than antagonists of histamine H₁-receptors which are members of the G-protein family. The older first generation H_1-antihistamines penetrate readily into the brain to cause sedation, drowsiness, fatigue and impaired concentration and memory causing detrimental effects on learning and examination performance in children and on impairment of the ability of adults to work and drive. Their use should be discouraged. The newer second-generation H₁-antihistamines are safer, cause less sedation and are more efficacious. Three drugs widely used for symptomatic relief in urticaria, desloratadine, levocetirizine and fexofenadine are highlighted in this review. Of these levocetirizine and fexofenadine are the most potent in humans in vivo. However, levocetirizine may cause somnolence in susceptible individuals, whereas fexofenadine has a relatively short duration of action and may be required to be given twice daily for all round daily protection. Although desloratadine is less potent, it has the advantages of rarely causing somnolence and having a long duration of action.     

Analysis of the long‐term economic burden of omalizumab on patients with chronic spontaneous urticaria

Omalizumab (OMA) is highly effective for refractory chronic spontaneous urticaria (CSU), but its high cost exerts a great economic burden on patients and society. Current knowledge is lacking regarding the economic impact of long‐term administration of OMA on patients with CSU in the real‐world setting. We retrospectively investigated drug costs relevant to CSU treatment during the period before through to 12 months after starting OMA in actual clinical practice. This study involved 32 patients who received at least two injections of OMA (300 mg/4 weeks) and achieved good responses of urticaria control test score of 12 or more and/or weekly urticaria activity score of 6 or less within 12 weeks. Median drug costs of the overall patient cohort increased from ¥14 496/month to ¥104 522 after starting OMA, but reduced to ¥48 810 in 12 months along with reduced amount of OMA administration and concomitant medication use. In patients pretreated with antihistamine alone or plus alternative medicines such as H₂ blocker and antileukotriene prior to OMA, the increased drug costs by adding OMA decreased to approximately 30% in 12 months mainly due to the OMA dose reduction and interval extension of OMA. The drug cost reduction was also observed in patients pretreated with intensive multi‐agents, due to discontinuation of expensive immunosuppressants. In conclusion, the introduction of OMA significantly increased the total drug costs relevant to CSU management, but the costs decreased to half in 12 months, along with dose‐reduced and interval‐extended OMA and discontinued concomitant drugs in patients with CSU who responded well to OMA.     

[Artículo traducido] El papel de la terapia adyuvante en el tratamiento de la urticaria crónica espontánea

Recent guideline on the management of urticaria recommends second-generation H1-antihistamine as the first-line therapy, with dose increases of up to fourfold if inadequately controlled. However, the treatment of chronic spontaneous urticaria (CSU) is often disappointing, so additional adjuvant therapies are needed to increase the effectiveness of first-line therapy, especially in patients who are refractory to the increase of antihistamine doses. Recent studies recommend various adjuvant therapy modalities for CSU, such as biological agents, immunosuppressants, leukotriene receptor antagonists, H2-antihistamine, sulfones, autologous serum therapy, phototherapy, vitamin D, antioxidants, and probiotics. This literature review was made to determine the effectiveness of various adjuvant therapies in managing CSU.     

Doxepin in difficult‐to‐treat chronic urticaria: A retrospective,cross‐sectional study from Turkey

Doxepin is an old tricyclic antidepressant, whose efficacy in chronic urticaria had been well documented until 1990. However, over the past three decades, there has been limited data on its use. We aimed to assess the efficacy and safety of doxepin in the treatment of patients with chronic urticaria who were poorly responsive to antihistamines. In this retrospective, cross‐sectional, single‐center study from Turkey, data were examined from patients with chronic urticaria who had poor antihistamine responses and received doxepin therapy from 1998 to 2017. Patient data were analyzed with regard to the duration of the disease, age, sex, treatment outcomes using a weekly urticaria activity score (UAS7), and adverse effects of doxepin therapy. A reduction of ≥90% in UAS7 was defined as “complete response,” 30–89% as “partial response” and <30% as “no significant response.” Thirty‐six patients were included in this study. Doxepin was effective in a majority (n = 27, 75%) of the patients with a short onset time. Sixteen patients (44.4%) showed a complete response. Mild sedative and anticholinergic side effects were well tolerated. Doxepin seems to be a reasonable, efficient, and affordable alternative for the treatment of chronic urticaria in patients who respond poorly to antihistamine therapy.     

Narrowband ultraviolet B (311 nm, TL01) phototherapy in chronic ordinary urticaria

Background Chronic ordinary urticaria (COU) can severely reduce quality of life and be difficult to control. Ultraviolet (UV) A and UVB phototherapy has been reported to decrease the release of histamine from either mast cells and/or basophils. Previous small studies have suggested that UVB phototherapy is a good alternative treatment for COU. Objectives The purpose of this study was to assess the efficacy of narrow‐band UVB (NB‐UVB) phototherapy for COU. Materials and methods Twenty‐two patients (three male, 19 female) received NB‐UVB phototherapy. These patients had not responded to at least two H1 antihistamines, and most had been treated with a variety of antihistamine combinations. Clinical responses were assessed according to an outcome scoring scale. During both visits, patients were administered the following: the visual analogue scale (VAS) on present pruritus and/or whealing; chronic urticaria impact on patients’ quality of life according to the interference with daily activities, quality of sleep, and flare‐up rates. Results The median number of treatments was 31.4 (9–44), and the mean top dose was 9.46 J/cm² (1.1–16.4 J/cm²). NB‐UVB treatment led to clearance in 10 patients (45%), marked improvement in five (22%), and moderate improvement in seven (31%) patients according to an outcome scoring scale. Mild side effects were observed in two patients. Six patients who cleared or observed marked improvement remained clear at follow‐up for a period of six months to one year, and other patients had a few recurrent lesions that did not need retreatment. For VAS scores and total chronic urticaria impact on patients’ quality of life scores, the differences between baseline and after treatment scores were significantly lower (P < 0.001, P < 0.001, respectively). Conclusion Narrow‐band UVB (NB‐UVB) therapy is an effective, well‐tolerated treatment option in second‐line therapy for COU. This therapy can lead to subjective relief of pruritus and whealing and objective reduction of whealing. Further larger studies with longer follow‐up periods are necessary to determine the proper clinical response and long‐term complications of this therapy in COU.     

Evaluation of the antihistamine effects of olopatadine and levocetirizine during a 24‐h period: A double‐blind,randomized, cross‐over,placebo‐controlled comparison in skin responses induced by histamine iontophoresis

The antihistamine effects of olopatadine and levocetirizine, in standard‐dose application described in their information (5 mg twice a day for olopatadine; 5 mg once daily for levocetirizine), were examined from 11.5 to 24 h after application. The test was designed in a double‐blind, randomized, cross‐over, placebo‐controlled study of 12 healthy volunteers on histamine‐induced flare and wheal response using an iontophoresis technique. The suppressive effect of olopatadine on the wheals induced by a 0.1‐mA histamine iontophoresis lasted for 24 h after dosing. Both drugs inhibited flare induced by histamine iontophoresis almost completely until 24 h after the first administration. Suppression of the 0.2‐mA‐induced wheal response by levocetirizine, taken once daily, decreased with time, although 0.1‐mA‐induced flare was almost completely suppressed by the drug. Olopatadine completely suppressed even the wheal response induced by a 0.2‐mA histamine iontophoresis. Compared with the placebo, the two drugs significantly suppressed the subjective itching assessed by visual analog scale at all intervals. There were no significant differences in subjective drowsiness and objective cognitive function between drug‐ and placebo‐treated subjects. These results demonstrate that olopatadine seems to be more potent than levocetirizine when administrated in a standard dose. In conclusion, mild to moderate urticaria could be controlled by standard application as described in their information. On the other hand, severe urticaria could be managed by a standard application of olopatadine, but levocetirizine may need an additional dose to control severe urticaria.     

Management of chronic spontaneous urticaria in real life – in accordance with the guidelines? A cross‐sectional physician‐based survey study

Background Recently, the updated EAACI/GA²LEN/EDF/WAO guidelines for urticaria have been published. Objective To examine how chronic spontaneous urticaria (csU) patients in Germany are diagnosed and treated, and to compare the outcome to the guideline recommendations. Methods During this cross‐sectional survey study, most dermatologists, paediatricians and 5149 general practitioners in private practice in Germany were asked to participate. All physicians who agreed were requested to complete a standardized questionnaire about their diagnostic and therapeutic management of csU. Results A total of 776 questionnaires were available for analysis. Most physicians (82%) were attempting to identify underlying causes in their csU patients, but with only limited success. More than 70% reported to check for total serum IgE and to do skin prick testing (not suggested in first line by guideline). In contrast, only 10% applied the autologous serum skin test. The most common first‐line treatments were non‐sedating antihistamines in standard or higher doses (as recommended). However, many physicians reported still using first generation sedating antihistamines (23%) (not recommended) or systemic steroids (18%). Experience with alternative options was low. Less than one‐third of the participants reported to be familiar with the guidelines. Those who did, were found to be more likely to check for underlying causes, to be more experienced with antihistamine updosing and to be more reluctant to use sedating antihistamines or systemic steroids. Conclusion The diagnostic and therapeutic management of csU by private practice physicians does not sufficiently comply with the guidelines. Awareness of the guidelines can lead to improved care.