H.F. Merk

EAACI/GA 2 LEN/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).

EAACI/GA(2)LEN/EDF/WAO guideline: management of urticaria.

This guideline, together with its sister guideline on the classification of urticaria (Zuberbier T, Asero R, Bindslev‐Jensen C, Canonica GW, Church MK, Giménez‐Arnau AM et al. EAACI/GA²LEN/EDF/WAO Guideline: definition, classification and diagnosis of urticaria. Allergy 2009;64: 1417–1426), is the result of a consensus reached during a panel discussion at the Third 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). As members of the panel, the authors had prepared their suggestions regarding management of urticaria before the meeting. The draft of the guideline took into account all available evidence in the literature (including Medline and Embase searches and hand searches of abstracts at international allergy congresses in 2004–2008) and was based on the existing consensus reports of the first and the second symposia in 2000 and 2004. These suggestions were then discussed in detail among the panel members and with the over 200 international specialists of the meeting to achieve a consensus using a simple voting system where appropriate. Urticaria has a profound impact on the quality of life and effective treatment is, therefore, required. The recommended first line treatment is new generation, nonsedating H1‐antihistamines. If standard dosing is not effective, increasing the dosage up to four‐fold is recommended. For patients who do not respond to a four‐fold increase in dosage of nonsedating H1‐antihistamines, it is recommended that second‐line therapies should be added to the antihistamine treatment. In the choice of second‐line treatment, both their costs and risk/benefit profiles are most important to consider. Corticosteroids are not recommended for long‐term treatment due to their unavoidable severe adverse effects. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS).

GA2LEN/EAACI pocket guide for allergen-specific immunotherapy for allergic rhinitis and asthma

To cite this article: Zuberbier T, Bachert C, Bousquet PJ, Passalacqua G, Walter Canonica G, Merk H, Worm M, Wahn U, Bousquet J. GA2LEN/EAACI pocket guide for allergen‐specific immunotherapy for allergic rhinitis and asthma. Allergy 2010; 65: 1525–1530.

Clinical usefulness of microarray-based IgE detection in children with suspected food allergy

Background:  Component‐resolved diagnostics using microarray technology has recently been introduced into clinical allergology, but its applicability in children with food allergy has hardly been investigated so far. The aim of this study was to evaluate the utility of microarray‐based IgE detection in the diagnostic workup of food allergy and to compare this new diagnostic tool with established methods of allergen‐specific IgE detection.

The basophil activation test in wasp venom allergy: sensitivity, specificity and monitoring specific immunotherapy

Background:  As in vitro diagnosis of wasp venom sensitization by specific serum IgE has a sensitivity of only 60–80%, additional in vitro tests are desirable. Basophil activation is associated with the expression of CD63 and its measurement has been proposed as a novel in vitro test for immediate‐type allergy. Furthermore, to date, no in vitro test exists to monitor successful specific immunotherapy (SIT) with wasp venom. Therefore, the potentially harmful sting challenge is still recommended.

Penetration of normal, damaged and diseased skin — An in vitro study on dendritic core–multishell nanotransporters

A growing intended or accidental exposure to nanoparticles asks for the elucidation of potential toxicity linked to the penetration of normal and lesional skin. We studied the skin penetration of dye-tagged dendritic core-multishell (CMS) nanotransporters and of Nile red loaded CMS nanotransporters using fluorescence microscopy. Normal and stripped human skin ex vivo as well as normal reconstructed human skin and in vitro skin disease models served as test platforms. Nile red was delivered rapidly into the viable epidermis and dermis of normal skin, whereas the highly flexible CMS nanotransporters remained solely in the stratum corneum after 6h but penetrated into deeper skin layers after 24h exposure. Fluorescence lifetime imaging microscopy proved a stable dye-tag and revealed striking nanotransporter-skin interactions. The viable layers of stripped skin were penetrated more efficiently by dye-tagged CMS nanotransporters and the cargo compared to normal skin. Normal reconstructed human skin reflected the penetration of Nile red and CMS nanotransporters in human skin and both, the non-hyperkeratotic non-melanoma skin cancer and hyperkeratotic peeling skin disease models come along with altered absorption in the skin diseases.

Total Serum IgE as a Parameter to Differentiate Between Intrinsic and Extrinsic Atopic Dermatitis in Children

Atopic dermatitis (AD) has been sub-classified into extrinsic and intrinsic types according to the presence or not of allergen-specific IgE antibodies. Although total serum IgE levels are frequently elevated in AD, their potential to predict allergen-specific IgE (asIgE) has rare ly been studied. We investigated 103 children with AD and suspected allergen-specific sensitization. A thorough clinical examination, a structured medical history and total serum IgE and asIgE measurements were performed. Fifty-three male and 50 female patients, median age 35 months (range 3 months to 17 years), were recruited. Sixty-three percent of patients were asIgE positive, while 37% did not reveal such IgE antibodies; median total serum IgE levels were 224.0 kU/l (14-12,013 kU/l) and 25.2 kU/l (0-4352 kU/l), respectively. Associations of asIgE status with atopic co-morbidity and total serum IgE levels were statistically significant. At a cut-off total serum IgE level of 106 kU/l (sensitivity 68.7%; specificity 92.3%), positive and negative predicted values (93.6% and 64.3%, respectively) were determined. Clinical decision points predictive of positive asIgE results were identified in 90%, 95% and 99% of patients, respectively. Total serum IgE values were significantly associated with the asIgE status of investigated patients. However, these preliminary data warrant further large-scale investigations before total serum IgE levels can be regarded as a clinically useful parameter between patients with extrinsic atopic dermatitis and intrinsic atopic dermatitis.

Expression and Induction of Cytochrome P450 Isoenzymes in Human Skin Equivalents

Organotypic skin models are frequently used for a wide range of applications and latterly also for dermatotoxicological studies. To evaluate their practicability for the investigation of xenobiotic metabolism in human skin we compared three types of organotypic skin models, acquired by purchase from different manufacturers, to a self-constructed in-house model with regard to cytochrome P450 (CYP) isoenzyme expression on mRNA and protein level and the inducibility of these enzymes by aryl hydrocarbon receptor ligands. To induce enzyme activity, models were treated with benzanthracene, liquor carbonis detergens, pix lithanthracis or dimethyl sulfoxide as a solvent control. RNA was isolated by phenol-chloroform extraction and purified. Gene expression patterns were studied by cDNA microarray analysis. Microarray data were confirmed by real-time PCR. For quality control of the models and to detect and localize enzyme expression, immunofluorescence staining was performed with antibodies against CYPs and structure proteins. The immunofluorescence staining demonstrated the regular structure of our models. We could provide evidence for the expression of CYP types 1A1, 1B1, 2E1, 2C and 3A5 in organotypic skin models. The expression of CYP1A1 and CYP1B1 was highly inducible by treatment with liquor carbonis detergens. The proof of the expression and inducibility of CYP enzymes in organotypic skin models suggests that skin equivalents are a valuable tool that can emulate CYP-dependent metabolism of drugs and other xenobiotics in human skin.

In vitro detection and characterization of drug hypersensitivity using flow cytometry

Background:  The lymphocyte transformation test (LTT) is the only in vitro test for detecting drug sensitization at the cellular level irrespective of the reaction’s phenotype. However, the LTT includes working with radioactive substances and is considered impracticable for routine laboratory investigation.

Association between TNFA-308 G/A polymorphism and sensitization to para-phenylenediamine: a case–control study

Background:  Para‐phenylenediamine (PPD) and related chemicals are common contact sensitizers, frequently causing allergic contact dermatitis (ACD). The cytokine tumor necrosis factor‐alpha (TNF‐α) plays a key role in contact sensitization.