The EAACI/GA²LEN/EDF/WAO guideline for the definition,classification, diagnosis and management of urticaria

This evidence‐ and consensus‐based guideline was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. The conference was held on 1 December 2016. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the EU‐founded network of excellence, the Global Allergy and Asthma European Network (GA²LEN), the European Dermatology Forum (EDF) and the World Allergy Organization (WAO) with the participation of 48 delegates of 42 national and international societies. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell‐driven disease, presenting with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic forms of urticaria are disabling, impair quality of life and affect performance at work and school. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors and pathomechanisms. In addition, it outlines evidence‐based diagnostic and therapeutic approaches for the different subtypes of urticaria.     

EAACI/GA2LEN/EDF guideline: definition, classification and diagnosis of urticaria

This guideline is the result of a consensus reached during a panel discussion at the 2nd International Consensus Meeting on Urticaria, Urticaria 2004, a joint initiative of the European Academy of Allergology and Clinical Immunology Dermatology Section and the European Union (EU)-funded network of excellence, GA2LEN. It covers the definition and classification of urticaria, taking into account the recent progress in identifying causes, eliciting factors and pathomechanisms of this disease. We have outlined useful diagnostic approaches for different subtypes of urticaria. This guideline was, in addition, accepted by the European Dermatology Forum (EDF) and was formally approved by the European Union of Medical Specialists (UEMS).     

Effect of Azelastine Nasal Spray on Histamine-and Allergen-Induced Skin Wheal Response in Patients with Allergic Rhinitis

Effect of azelastine nasal spray on histamine-and allergen-induced skin test response in patients suffering with allergic rhinitis was evaluated. Baseline cutaneous response to histamine and 18 common allergen extracts were recorded by skin prick tests on 10 patients. The patients were then advised to take azelastine nasal spray (1 spray per nostril, twice daily; 0.28 mg/dose). This pediatric dose is reported to be effective also in adults (age ≥ 12 years) with improved tolerability as compared with usually recommended adult dose of 2 sprays per nostril twice daily. Skin tests were repeated 2 and 6 hours after single dose, as well as after 6 days of continuous treatment. We did not find any significant difference in skin wheal response with single dose and 6 days' treatment of azelastine nasal spray (p > 0.05). It is concluded that diagnostic allergen skin tests may be performed on patients undergoing azelastine nasal spray treatment (0.28 mg/dose, twice a day) during their symptomatic period.     

Attenuation of cutaneous reactivity to histamine by cetirizine and dexchlorpheniramine

Summary A double-blind cross-over study was performed in 12 healthy female volunteers comparing cetirizine di-HCl (10 mg) and sustained release dexchlorpheniramine maleate (6 mg) with respect to attentuation of histamine-induced skin wheals and subjective central nervous system (CNS) effects. Cetirizine was significantly more effective than dexchlorpheniramine in suppressing the size of wheals from 2 to 24 h after drug administration. In fact, at 24 h cetirizine was still as affective as 2 h after ingestion. Ten subjects receiving dexchlorpheniramine reported subjective symptoms relating to CNS depression, in contrast to only one subject given cetirizine.     

Antihistaminic effect of terfenadine: A new piperidine-type antihistamine

The antihistaminic effect of terfenadine was studied in the isolated guinea pig ileum, histamine skin wheals in guinea pigs and monkeys, and i.v. histamine-induced death in guinea pigs. In the guinea pig ileum, terfenadine, 1 × 10^?7 M, shifted the histamine dose-response curve to the right in a parallel fashion without affecting the dose-response curve of acetylcholine and barium chloride. However, as the dose of terfenadine was increased (3.16 × 10^?7 and 1 × 10^?6 M) the histamine dose-response curves were displaced to the right with a depression of the maximum response and a reduction of the slope. Thus an unsurmountable type of antagonism was observed. Acetylcholine was also antagonized in a similar fashion by these two concentrations. In contrast, terfenadine appeared to displace the barium chloride dose-response curve to the right in a parallel fashion. At 0.4 and 0.8 mg/kg p.o., terfenadine shifted the histamine skin wheal dose-response curves to the right in a parallel fashion, but at 1.6 to 6.4 mg/kg, terfenadine antagonized the histamine wheal dose-response curves with a depression of the maximum and the slope of the curve. These results were also similar to those of cyproheptadine but were different from those of chlorpheniramine, which produced parallel shifts. In monkeys, terfenadine produced a substantially greater effect on the histamine wheal than did chlorpheniramine (both administered at 30 mg/kg p.o.). Terfenadine also completely protected against i.v. histamine-induced death in guinea pigs. Terfenadine produced no atropine-like effect against pilocarpine-induced salivation in rabbits, no demonstrable histamine H₂ antagonism, no antiserotonin activity, no α or β antagonism, and no untoward cardiovascular effects. Most significantly, terfenadine had no overt central nervous system (CNS) effects in mice, rats, guinea pigs, or monkeys; whereas chlorpheniramine produced tremors and convulsions in mice and monkeys when tested at much lower doses than those used for terfenadine. It is concluded that terfenadine is an effective and specific antihistaminic compound with the potential advantage of a lack of CNS sedative effects.     

Prick test: evolution towards automated reading

The prick test is one of the most common medical methods for diagnosing allergies, and it has been carried out in a similar and laborious manner over many decades. In an attempt to standardize the reading of the test, many researchers have tried to automate the process of measuring the allergic reactions found by developing systems and algorithms based on multiple technologies. This work reviews the techniques for automatic wheal measurement with the aim of pointing out their advantages and disadvantages and the progress in the field. Furthermore, it provides a classification scheme for the different technologies applied. The works discussed herein provide evidence that significant challenges still exist for the development of an automatic wheal measurement system that not only helps allergists in their medical practice but also allows for the standardization of the reading and data exchange. As such, the aim of the work was to serve as guideline for the development of a proper and feasible system.     

EAACI/GA2LEN/EDF/WAO guideline: definition,classification and diagnosis of urticaria

This guideline, together with its sister guideline on the management of urticaria [Zuberbier T, Asero R, Bindslev‐Jensen C, Canonica GW, Church MK, Giménez‐Arnau AM et al. EAACI/GA²LEN/EDF/WAO Guideline: Management of urticaria. Allergy, 2009; 64 :1427–1443] is the result of a consensus reached during a panel discussion at the 3rd International Consensus Meeting on Urticaria, Urticaria 2008, a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the EU‐funded network of excellence, the Global Allergy and Asthma European Network (GA²LEN), the European Dermatology Forum (EDF) and the World Allergy Organization (WAO). Urticaria is a frequent disease. The life‐time prevalence for any subtype of urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic forms of urticaria do not only cause a decrease in quality of life, but also affect performance at work and school and, as such, are members of the group of severe allergic diseases. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors, and pathomechanisms. In addition, it outlines evidence‐based diagnostic approaches for different subtypes of urticaria. The correct management of urticaria, which is of paramount importance for patients, is very complex and is consequently covered in a separate guideline developed during the same consensus meeting. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS).     

Double-blind, crossover comparison of olopatadine and cetirizine versus placebo: suppressive effects on skin response to histamine iontophoresis

Olopathadine, a newly developed histamine H1-receptor antagonist, was compared with cetirizine in its suppressive effects on histamine-induced wheal and flare reaction using an iontophoresis technique in a double-blind, crossover, placebo-controlled fashion. As a result, olopathadine was found to have effects comparable to cetirizine. This finding may predict the efficacy of this new H1-antagonist in treating pruritic skin diseases.     

Comparison of on-site and photographic evaluations of the suppressive effects of cetirizine, loratadine, and fexofenadine on skin response to histamine lontophoresis: A double-blind, crossover study in healthy volunteers

Background:

The standard method used to determine the potency of antihistaminesis to assess the degree of suppression of skin response to histamine challenge.

Objectives:

The aims of this study were to compare the efficacy of 3 antihistaminesusing a histamine challenge test and the usefulness of on-site evaluation with that of photographic evaluation of skin-test reactions.

Methods:

In this prospective, double-blind, crossover study, healthy volunteerswere given cetirizine 5 mg (CTZ-5) and 10 mg (CTZ-10), loratadine 10 mg (LOR), fexofenadine 60 mg BID (FEX), and placebo (PLC), in a randomly assigned order, with an interval of at least 1 week between treatments. Before and 0.5 to 24 hours after administration, the areas of flare and wheal induced by histamine iontophoresis were measured directly (on site) by 1 evaluator and by another evaluator using photographic images on a computer monitor.

Results:

Ten healthy volunteers (6 men, 4 women; mean age, 28.2 years[range, 20-39 years]; mean weight, 60.7 kg [range, 41-81 kg]) were enrolled. The data from 9 subjects were analyzed; the data from 1 subject were omitted because the subject used an over-the-counter cold medication containing diphenhydramine several times during the study. By both methods, all antihistamines were shown to suppress flare significantly from 4 to 24 hours after administration. CTZ was most potent in suppressing both flare and wheal. For flare, the areas as measured using on-site evaluation were larger overall than those measured using photographic evaluation, but the shapes of the time-course graphs were similar for both. Overall, the flare area measurements started to decrease significantly from baseline values 4 hours after drug administration, reached a nadir at 10.5 hours, and remained significantly lower compared with baseline values at 24 hours. Comparisons between antihistamines showed significant differences in mean flare areas between the 2 doses of CTZ and LOR from 8 to 12 hours after administration in both evaluation methods. The wheal areas were significantly reduced from baseline values by most of the antihistamines 4 to 12 hours after drug administration, reached their lowest values at 10.5 hours, and returned to near-baseline values at 24 hours. Comparisons with PLC values at each time point, however, showed significant differences only for CTZ-5 and CTZ-10 from 4 to 12 hours after administration. Comparison between antihistamines showed significant differences in mean flare areas between the 2 doses of CTZ and LOR from 8 to 12 hours after administration in both evaluation methods. Although the flare areas measured by both methods correlated linearly (r = 0.90; P < 0.001), the correlation for wheal areas was weaker (r = 0.76; P < 0.001).

Conclusions:

In this study in healthy volunteers, single doses of CTZ 5 mg and CTZ 10 mg were more potent compared with single-dose LOR 10 mg and FEX 60 mg BID in suppressing skin response. Although linear correlations were found between skin-response areas, as measured by on-site and photographic evaluation, it was difficult to differentiate between wheal and flare by photographic evaluation, especially when a typical wheal was suppressed to slightly edematous erythema by antihistamines.     

Starvation reduces allergen-induced skin wheal responses and plasma substance P and vasoactive intestinal peptide in patients with atopic eczema/dermatitis syndrome

The effect of starvation on allergen-induced skin wheal responses and plasma neuropeptide levels was not previously reported. Starvation for 24 h reduces allergen-induced skin wheal responses and plasma levels of substance P and vasoactive intestinal peptide in patients with atopic eczema/dermatitis syndrome, but not in control subjects. These results may have implications for the pathophysiology of the atopic eczema/dermatitis syndrome.