Margarida Gonçalo

Guidelines for performing skin tests with drugs in the investigation of cutaneous adverse drug reactions

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.

European Society of Contact Dermatitis guideline for diagnostic patch testing – recommendations on best practice

The present guideline summarizes all aspects of patch testing for the diagnosis of contact allergy in patients suspected of suffering, or having been suffering, from allergic contact dermatitis or other delayed‐type hypersensitivity skin and mucosal conditions. Sections with brief descriptions and discussions of different pertinent topics are followed by a highlighted short practical recommendation. Topics comprise, after an introduction with important definitions, materials, technique, modifications of epicutaneous testing, individual factors influencing the patch test outcome or necessitating special considerations, children, patients with occupational contact dermatitis and drug eruptions as special groups, patch testing of materials brought in by the patient, adverse effects of patch testing, and the final evaluation and patient counselling based on this judgement. Finally, short reference is made to aspects of (continuing) medical education and to electronic collection of data for epidemiological surveillance.

Hand eczema severity and quality of life: a cross-sectional, multicentre study of hand eczema patients

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.

Hand eczema classification: a cross-sectional, multicentre study of the aetiology and morphology of hand eczema.

Background  Hand eczema is a long‐lasting disease with a high prevalence in the background population. The disease has severe, negative effects on quality of life and sometimes on social status. Epidemiological studies have identified risk factors for onset and prognosis, but treatment of the disease is rarely evidence based, and a classification system for different subdiagnoses of hand eczema is not agreed upon. Randomized controlled trials investigating the treatment of hand eczema are called for. For this, as well as for clinical purposes, a generally accepted classification system for hand eczema is needed.

Photopatch testing: a consensus methodology for Europe

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.

Epicutaneous patch testing in drug hypersensitivity syndrome (DRESS)

Background: In some patterns of cutaneous adverse drug reactions, and depending on the culprit drug, patch testing has been helpful in confirming its cause. Its value in Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) has not been established in a large cohort of patients.

Whilst Rome Burns: The Epidemic of Contact Allergy to Methylisothiazolinone

Preservatives, essential in our daily life, can sensitize and elicit allergic contact dermatitis (ACD). Before introduction in the market their sensitizing risk is assessed based on in vivo studies. However, normal exposures to preservative-containing products in the real world can cause ACD. During recent decades we recall several ‘epidemic’ outbreaks of ACD from newly introduced preservatives. Methyldibromo glutaronitrile was completely banned from cosmetic products as no safe use limits were determined. For methylchloroisothiazolinone/methylisothiazolinone (MCI/MI), risk management measures were introduced and following ‘safe’ limits of this preservative in cosmetics in the EU (15 ppm), contact allergy to MCI/MI significantly decreased to around 2% of patch tested patients after the 90’s and until recently. The sensitizing properties of MCI/MI were attributed to methylchloroisothiazolinone (MCI) whereas methylisothiazolinone (MI) was considered a weaker sensitizer, unable to sensitize individuals in concentrations below 1000 ppm (1, 2). After the year 2000, MI was introduced in industrial products (e.g., paints, inks, glues, lacquers, varnishes and cooling fluids), and due to its weaker biocide effect, using higher concentrations. Despite the first description of ACD in an occupational setting in 2004 (3), the following year MI was also allowed in cosmetics products at a maximum level of 100 ppm (Cosmetic Directive 2005/42/EC). Several cases of occupational ACD from MI were then observed from paints (4, 5) followed by non-occupational cases in 2010 (6), mainly due to wet wipes for hygiene (baby wipes, moist tissues, moist toilet paper), hair cosmetics (shampoos), facial cosmetics (7, 8), deodorants (9) and sunscreens (10). Moreover, airborne exposure to MI caused severe cases of airborne and systemic dermatitis particularly from recently painted walls (11, 12) or from toilet cleaners (13), including a case in a 4-year-old child very probably sensitized to MI through baby wipes (11). Accompanying the increasing number of published cases of ACD from MI, particularly since 2009, in Europe a rise in contact allergy to MCI/MI, the only isothiazolinone patch tested in the baseline series, has been observed. In Germany, with more than 12 000 patients tested/year, positive patch tests to MCI/MI increased from 2.3% in 2009 to 3.9% in 2011 (14), similar to Leeds, UK (increase from 0.9% to 4.9%) (15) and London (from<3% to> 8%) (Orton D & Willis C, Contact Dermatitis, submitted). In Coimbra, Portugal, reactivity to MCI/MI rose from 1.5% (in 2006/7) to 2.9% and 3.6%, respectively in 2011 and 2012 (personal data). Similar figures are being observed all over Europe, with alerts particularly during late 2012 in France and Belgium at the REVIDAL, a system to collect alerts in contact dermatitis. The rise in contact allergy to MCI/MI cannot be explained by a change in exposure to MCI/MI but is due to the increasing exposure to MI, present in concentrations very near 100 ppm both in leave-on and rinse-off cosmetics, as documented in a recent survey from Denmark (8). MI has only recently been tested as a single allergen in the baseline series in several countries. Reactivity was around 1.5% until 2008 in Denmark (8) but values increased from 0.9% in 2006 to 1.8% in 2008 in Finland (16) and very high values were detected in 2011/12 in Leeds (4.6%) (15), London (6%), Coimbra (4.5%) and Leuven, Belgium (5.8%), with a very high percentage of relevant reactions (personal data). In Germany, although in selected patients with suspected cosmetic or occupational exposure, MI reactivity rose from 1.9% in 2009 to 4.4% in 2011, particularly in female patients (188% increase) and in patients with facial dermatitis (200%), suggesting that increase in reactivity is most probably related to cosmetic exposure (14). In the USA a similar situation seems to occur as MI was considered the allergen of the year 2013 (10). The increasing rise in contact allergy to MI recalls the outbreak of contact allergy to methyldibromo glutaronitrile but occurring at a faster rate, particularly if we note that MI by itself has been allowed in cosmetics for only 7 years. MI needs to be included in the European baseline patch test series. Testing with MCI/MI, even if at 200 ppm, has too low a concentration of MI (50 ppm) to properly diagnose contact allergy to MI. There is no agreement on the best concentration to test MI, with commercial allergens varying between 0.02% and 0.2% in water (200–2000 ppm). The concentration of 300 ppm fails to detect almost half of the cases. Increasing to 1000 ppm is not irritating and detects more cases, and relevant ones as all patients reacted in the ROAT

Prevalence of contact allergy in the general population in different European regions.

Population‐based studies about contact allergy are scarce.

Recommendation to include methylisothiazolinone in the European baseline patch test series – on behalf of the European Society of Contact Dermatitis and the European Environmental and Contact Dermatitis Research Group

Methylisothiazolinone (MI) is used as a preservative in occupational and household products, and cosmetics. It is a part of the preparation of methylchloroisothiazolinone (MCI)/MI, which is patch tested in water in the European baseline series. However, this preparation fails to detect a significant percentage of allergic contact reactions to MI.

p-Phenylenediamine sensitization is more prevalent in central and southern European patch test centres than in Scandinavian: results from a multicentre study

Background:  Positive patch test reactions to p‐phenylenediamine (PPD) are common. PPD is used in oxidative hair dyes and is also present in dark henna temporary ‘tattoos’. Cross‐sensitization to other contact allergens may occur. Because subjects sensitized to PPD are at risk of clinically severe reactions upon hair dyeing, there is a need for ‘current’ prevalence data on PPD sensitization.