Skin testing with a suspected drug has been reported to be helpful in determining the cause of cutaneous adverse drug reactions (CADR). Many isolated reports of positive drug skin tests are published, but without detailed information concerning the clinical features of the CADR and the method used in performing drug skin tests, such data are not very informative. A working party of the European Society of Contact Dermatitis (ESCD) for the study of skin testing in investigating cutaneous adverse drug reactions, has proposed the herein-reported guidelines for performing skin testing in CADR in order to standardize these procedures. In each reported case, the imputability of each drug taken at the onset of the CADR and a highly detailed description and characterization of the dermatitis need to be given. Drug skin tests are performed 6 weeks to 6 months after complete healing of the CADR. Drug patch tests are performed according to the methods used in patch testing in studying contact dermatitis. The commercialized form of the drug used by the patient is tested diluted at 30% pet. (pet.) and/or water (aq.). The pure drug is tested diluted at 10% in pet. or aq. In severe CADR, drug patch tests are performed at lower concentrations. It is also of value to test on the most affected site of the initial CADR. Drug prick tests are performed on the volar forearm skin with the commercialized form of the drug, but with sequential dilutions in cases of urticaria. Intradermal tests (IDT) are performed with sterile sequential dilutions (10-4, 10-3, 10-2, 10-1) of a pure sterile or an injectable form of the suspected drug with a small volume of 0.04 ml. Drug skin tests need to be read at 20 min and also later at D2 and D4 for patch tests, at D1 for prick tests and IDT. All these tests also need to be read at 1 week. The success of skin tests varies with the drug tested, with a high % of positive results, for example, with betalactam antibiotics, pristinamycin, carbamazepine and tetrazepam on patch testing, or with betalactam antibiotics and heparins on delayed readings of IDT. The results of drug skin tests also depend on the clinical features of the CADR. The use of appropriate control patients is necessary to avoid false-positive results.

Background and Objectives: Hand eczema is a chronic disease with negative impact on quality of life (QoL). In this study, QoL in hand eczema patients is assessed and related to age, sex, severity, and diagnostic subgroups.

It is suggested that this classification be used in clinical work and in clinical trials.

A 10-year multicentre analysis of the frequency of sensitivity to common preservatives collected in 16 centres in 11 countries has shown stable but persisting high levels of sensitivity to formaldehyde and 5-chloro-2-methyl-4-isothiazolin-3-one + 2-methyl-4-isothiazolin-3-one (MCI/MI). It has also revealed a significant increase in the level of reactivity to methyldibromoglutaronitrile (MDBGN) from 0.7% in 1991 to 3.5% in 2000. The current high level of sensitivity to MDBGN requires an urgent safety re-evaluation and risk assessment update along with consideration of immediate lowering of use concentrations, especially in leave-on products.

The initial step in Langerhans cell (LC) migration from the epidermis to the lymph node involves migration of maturing LC into the dermis. Here, we investigated the migration of LC out of the epidermis after exposure of the skin to contact allergens. Ex vivo intact human skin, epidermal sheets, and LC derived from the MUTZ-3 cell line (MUTZ-LC) were used to determine whether dermal fibroblasts play a role in mediating LC migration towards the dermis. Exposure of epidermal sheets or MUTZ-LC to allergens (nickel sulphate, 2,4-dinitrochlorobenzene, and cinnamaldehyde) or a cytokine maturation cocktail resulted in LC migration towards dermal fibroblasts. This was due to upregulation of CXCR4 on maturing LC and secretion of CXCL12/stromal derived factor-1 chemokine by fibroblasts. Neutralizing antibodies to either CXCL12 or CXCR4 completely blocked migration. Injection of CXCL12 neutralizing antibodies into intact human skin totally inhibited LC migration into the dermis. In contrast, neutralizing antibodies to CCL19/ CCL21 did not inhibit migration into the dermis. We describe a novel and essential role of dermis-derived CXCL12 in initiating migration of maturing human LC to the dermis thus permitting their further journey to the draining lymph nodes.Key words: Allergy . Chemotaxis . Cytokines . DC . Skin See accompanying commentary by Villablanca and Rodrigo IntroductionHuman skin is the external barrier to harmful environmental factors. Upon environmental assault (e.g. exposure to pathogens or allergens), Langerhans cells (LC) residing in the epidermis start to mature and migrate through the dermis [1,2]. Pathogenor allergen-exposed LC then migrate further into the afferent lymphatics towards the local lymph node where they are able to initiate a T-cell-mediated response [3]. LC migration is regulated by the sequential and differential expression of chemokines and their receptors [4,5]. Although migration to the lymph node is well documented, the chemokine ligands/receptors involved in the initial step of human LC migration out of the epidermis and into the dermis are as yet unknown.Several studies describe an essential role of CCR7 in mediating migration of mature LC towards the lymphatics [6][7][8][9][10]. CCR7 is highly expressed on fully mature, but not on immature LC, and is the chemokine receptor for the ligands CCL19 (MIP-3b) and CCL21 (6Ckine) [11][12][13]. Both of these chemokines are upregulated by lymphatic endothelial cells in response to allergen exposure [14]. Simultaneously, the chemokine receptor CCR6 on LC is downregulated upon maturation [15]. CCR6 is the receptor for CCL20 , which is mainly produced by keratinocytes (KC) in clinically normal human skin. CCR6/CCL20 is thought to 3050be of importance for epidermal homeostasis and homing of immature LC [16][17][18][19]. Taken together these reports show that loss of CCR6 and gain of CCR7 play important roles in the migration of mature LC out of the epidermis and into the lymphatic vessels. However, it is probable that other as yet unidentified sig...

A group of interested European Contact Dermatologists/Photobiologists met to produce a consensus statement on methodology, test materials and interpretation of photopatch testing. While it is recognized that a range of local variables operate throughout Europe, the underlying purpose of the work is to act as an essential preamble to a Pan European Photopatch Test Study focusing particularly on sunscreen chemicals.

In order to establish a consensus recommendation for performing photopatch testing, a photopatch test taskforce group was established under the joint umbrella of the European Society for Contact Dermatitis and the European Society for Photodermatology in 2000. After proposing the most adequate methodology in 2004 and completing a European multicentre photopatch test study in 2011, this taskforce is recommending a list of photoallergens that should form part of a baseline series for photopatch testing in Europe. It contains mainly ultraviolet filters and drugs, mostly non-steroidal anti-inflammatory drugs. The choice of chemicals was based on the results of a recent multicentre study, previous published cases of photoallergy, and use of the substances in the European market. It is suggested that an extended list of photoallergens should be photopatch tested in selected cases, along with patients' own products. Two contact allergens, cinnamyl alcohol and decyl glucoside, should be simultaneously patch tested in order to clarify photopatch and patch test reactions, respectively, to ketoprofen and methylene bis-benzotriazolyl tetramethylbutylphenol (Tinosorb M™).

Differentiation between allergic and irritant contact dermatitis reactions is difficult, as both inflammatory diseases are clinically, histologically, and immunohistologically very similar. Previous studies in mice revealed that the chemokine IP-10 is exclusively expressed in allergic contact dermatitis reactions. In the present study, we investigated whether the mRNA expression of IP-10 and the related CXCR3 activating chemokines, Mig and IP-9 are also differentially expressed in human allergic contact dermatitis and irritant contact dermatitis reactions. Skin biopsies from allergic (13 cases) and sodium lauryl sulfate-induced irritant patch test reactions (13 cases), obtained 1-72 h after patch testing, were studied by means of an in situ hybridization technique. Results of chemokine mRNA expression were correlated with clinical scoring, histology, and immunohistochemical data including the proportion of inflammatory cells expressing CXCR3, the receptor for IP-10, Mig, and IP-9, and ICAM-1 and HLA-DR expression on keratinocytes. IP-10, Mig, and IP-9 mRNA were detected in seven of nine allergic contact dermatitis reactions after 24-72 h, but not in sodium lauryl sulfate-induced irritant contact dermatitis reactions. ICAM-1 expression by keratinocytes was only found in allergic contact dermatitis reactions and correlated with chemokine expression. Moreover, up to 50% of the infiltrating cells in allergic contact dermatitis expressed CXCR3, in contrast to only 20% in irritant contact dermatitis reactions. In conclusion, we have demonstrated differences in chemokine expression between allergic contact dermatitis and irritant contact dermatitis reactions, which might reflect different regulatory mechanisms operating in these diseases and may be an important clue for differentiation between allergic contact dermatitis and irritant contact dermatitis reactions.