Patch testing in children – recommendations of the German Contact Dermatitis Research Group (DKG)

Allergic contact dermatitis occurs frequently in children. Patch testing is needed to identify the responsible allergens and should be performed in children. We recommend a panel of 12 contact allergens as a standard series in children from 6–12 years. Four additional contact allergens should be tested in case of a positive history or suggestive clinical picture. For patch testing in children, the allergens should be applied for 24 hours and the readings should be performed at 48 and 72 hours. Standardized patch testing makes it possible to systematically investigate allergic contact dermatitis and identify relevant allergens in children.     

Immunological,chemical and clinical aspects of exposure to mixtures of contact allergens

Allergic contact dermatitis is one of the most frequent forms of skin inflammation. Very often, we are exposed to mixtures of allergens with varying potencies, doses/areas, and exposure times. Therefore, improved knowledge about immune responses to combinations of contact allergens is highly relevant. In this article, we provide a general introduction to immune responses to contact allergens, and discuss the literature concerning immune responses to mixtures of allergens. According to the existing evidence, increased responses are induced following sensitization with combinations of allergens as compared with single allergens. The response to a mixture of allergens can be both additive and synergistic, depending on the dose and combination of allergens. Importantly, sensitization with combinations of either fragrance allergens or metal salts can result in increased challenge responses to specific allergens within the mixture. Taken together, the immune responses to mixtures of allergens are complex, and further studies are required to obtain the necessary knowledge to improve consumer safety.     

Immunologie der Kontaktallergie

Contact allergy is a skin disease that is caused by the reaction of the immune system to low molecular weight chemicals. A hallmark of contact allergens is their chemical reactivity, which is not exhibited by toxic irritants. Covalent binding of contact allergens to or complex formation with proteins is essential for the activation of the immune system. As a consequence antigenic epitopes are formed, which are recognized by contact allergen-specific T cells. The generation of effector and memory T cells causes the high antigen specificity and the repeated antigen-specific skin reaction of contact allergy. New findings reveal that the less specific reaction of the innate immune system to contact allergens closely resembles the reaction to an infection. Therefore, contact allergy can be viewed as an immunologic misunderstanding since the skin contact with chemical allergens is interpreted as an infection. The growing understanding of the molecular and cellular pathologic mechanisms of contact allergy can aid the development of specific therapies and of in vitro alternatives to animal testing for the identification of contact allergens.     

Oral tolerance to contact allergens: a common occurrence? A review

Experimental and clinical oral tolerance to contact allergens has been reported sporadically, most notably in respect of nickel, and is generally assumed to be an uncommon phenomenon. There has recently been increased understanding of the immunological mechanisms inducing and maintaining oral tolerance. There are several contact allergens, including fragrance, antioxidant, and preservative chemicals, to which subjects are exposed through both cutaneous and oral routes. We examine the possibility that oral tolerance to contact allergens may be more common than previously thought. Animal models of oral tolerance to contact allergens indicate that cutaneous exposure to small, subsensitizing doses of contact allergens might negate any subsequent attempts to induce tolerance by oral administration. Extrapolating these observations to common human practises raises the possibility that application of contact allergens (fragrances, preservatives and antioxidants) in consumer products used by children could prevent or inhibit the later acquisition of specific tolerance resulting from 'natural' dietary exposure after weaning. Existing data on formaldehyde may conflict with this theory, though this could be explained by allergen specificity. We propose that further work in this area is needed.     

Patch testing with the European baseline series fragrance markers: a 2016 update

Fragrance contact allergy is a common cause of allergic skin reactions that can cause eczema. Contact allergy can develop by repeated skin exposure to allergens over time. Fragrance contact allergy is diagnosed by patch testing (applying known allergens to the skin to assess for reactions). In the EU, cosmetic products are regulated to limit the exposure to known allergens. Furthermore, there is a requirement to label cosmetic products that contain any of 26 known individual fragrance allergens to help consumers avoid those allergens to which they are allergic. In most dermatology departments in the UK, instead of patch testing to all 26 individual fragrance allergens, fragrance contact allergy is diagnosed by patch testing to 4 screening markers: Fragrance Mix I, Fragrance Mix II, Myroxylon pereirae and hydroxyisohexyl 3‐cyclohexane carboxaldehyde. In this study, the authors reviewed 2084 records of patients with eczema who underwent patch testing to all the individual fragrance allergens, as well as the screening markers of fragrance allergy, to find out the proportion of actual fragrance contact allergy detected by testing only to the screening markers. They found that patch testing only to the screening markers detected 40.8% of patients with actual fragrance contact allergy (patients who were diagnosed with fragrance allergy when additionally tested with individual fragrance allergens). They also found that the majority of patients with fragrance contact allergy were not aware that they developed skin reactions upon exposure to fragrances. The authors concluded that the current screening markers used are not sufficient for the diagnosis of fragrance contact allergy.     

呼和浩特地区1036例可疑皮肤过敏者斑贴试验分析

目的探讨呼和浩特地区常见化学过敏原的种类及其与变应性接触性皮炎之间的关系。方法对内蒙古医科大学附属医院皮肤科2013年3月—2016年3月1 036例过敏性皮肤病患者进行斑贴试验,并对性别、年龄和患病情况进行分析。结果斑贴试验总阳性率为54.8%,变应原阳性率列前5位的过敏原分别为硫酸镍、硫柳汞、异噻唑、溴硝丙醇、氯化钴。结论斑贴试验能帮助大多数变应性接触性皮炎患者查找到过敏原,为了解呼和浩特地区常见过敏原提供相关参考。     

Epikutantestung mit der DKG-Standardreihe 2001–2004

Patch testing is the standard procedure to detect contact sensitivity. The most frequent contact allergens are included in the standard series. We report on current trends regarding results obtained with the standard series from 2001-2004 in Germany, Austria (Graz, Vienna) and Switzerland (Basel). This analysis includes the frequency of the most common contact allergens and other aspects such as age and gender distribution and parameters of diagnostic quality such as reaction index and positivity ratio. Information on the most common contact allergens is updated.     

Kontaktallergie bei Kindern

Although the prevalence of contact allergy in children is largely unknown, the most frequent contact allergens in childhood are nickel, fragrances, p-phenylenediamine, thimerosal, preservatives and components of skin care and hygiene products. Children with persistent eczema or otherwise suspected contact allergy should be patch tested. For children, the same preparations of allergens and test techniques can be used as for adults. Patch tests should be done with allergens suggested by history and with a shortened standard series, at best with small Finn-Chambers that are attached for 1 day only. Positive readings need to be assessed with regard to clinical relevance. In children, the treatment of allergic contact dermatitis follows the same principles as in adults. Topical corticosteroids are agents of well proven efficiency whereas non-steroidal anti-inflammatory drugs should not be applied to the skin because there is of a risk of contact sensitization. For reasons of prophylaxis it is important to avoid potential contact allergens in childhood.     

Shoe contact dermatitis

The incidence of contact allergy was studied in a series of 165 patients with eczematous dermatitis of the feet correlated clinically with shoe contact. Positive reactions to one or more substances were recorded in 108 patients (65.4%). Among the relevant sensitizers were chromium, paraphenylenediamine, paratertiary butylphenolformaldehyde resin and nickel, while the other allergens were benzocaine, neomycin, balsam of Peru, ethylenediamine and parabens. Allergic contact dermatitis of the feel can he prevented by recognition of the allergens responsible, control of hyperhidrosis and avoidance of topical allergens.     

New concepts in cutaneous allergy

Allergic contact dermatitis affects a worrying proportion of the general population. The mechanisms underlying this chemical‐triggered delayed‐type hypersensitivity are still not fully understood. In recent years, basic research has shown that the immune system reacts to contact allergens by activation of signalling pathways that are usually used to fight infections. Ongoing work is aimed at the elucidation of the path that leads from the chemistry of contact allergens to the inflammatory skin disease. The cellular players and their complex interactions are being characterized. Proteins are being identified whose chemical modification by contact allergens results in the activation of signalling pathways involved in pathogenesis. Pathway identification is supported by genomic and proteomic techniques. All of these efforts will yield a cellular and molecular understanding of the orchestration of the innate and adaptive immune response to contact allergens. This knowledge will help in the identification of gene and protein signatures for improved diagnostics, the identification of novel drug targets for targeted treatments, as well the development of in vitro assays for contact allergen identification.     

Categorization of fragrance contact allergens for prioritization of preventive measures: clinical and experimental data and consideration of structure–activity relationships

Contact allergy to fragrances is still relatively common, affecting ～ 16% of patients patch tested for suspected allergic contact dermatitis, considering all current screening allergens. The objective of the review is to systematically retrieve, evaluate and classify evidence on contact allergy to fragrances, in order to arrive at recommendations for targeting of primary and secondary prevention. Besides published evidence on contact allergy in humans, animal data (local lymph node assay), annual use volumes and structure–activity relationships (SARs) were considered for an algorithmic categorization of substances as contact allergens. A total of 54 individual chemicals and 28 natural extracts (essential oils) can be categorized as established contact allergens in humans, including all 26 substances previously identified as contact allergens (SCCNFP/0017/98). Twelve of the 54 individual chemicals are considered to be of special concern, owing to the high absolute number of reported cases of contact allergy (> 100). Additionally, 18 single substances and one natural mixture are categorized as established contact allergens in animals. SARs, combined with limited human evidence, contributed to the categorization of a further 26 substances as likely contact allergens. In conclusion, the presence of 127 single fragrance substances and natural mixtures should, owing to their skin sensitizing properties, be disclosed, for example on the label. As an additional preventive measure, the maximum use concentration of 11 substances of special concern should be limited to 100 ppm. The substance hydroxyisohexyl 3‐cyclohexene carboxaldehyde and the two ingredients chloroatranol and atranol in the natural extracts Evernia prunastri and Evernia furfuracea should not be present in cosmetic products.     

A new patient education approach in contact allergic dermatitis: the Contact Allergen Replacement Database (CARD)

BACKGROUND: When a patient is identified by patch testing as being sensitive to a specific contact allergen, he or she is generally advised to read the product labels and avoid products that contain the specific allergen. Patients are often confronted with difficult chemical names, synonyms, and cross-reactants for individual allergens. At the same time, dermatologists may spend a considerable amount of time trying to educate their patients about the avoidance of these allergens and explaining which products may contain them. METHODS: We applied a new educational approach to inform patients about products that are free of their allergens. RESULTS: We present a patient with multiple contact allergens in whom the Contact Allergen Replacement Database was used to educate about specific allergens. This approach has proved to be an invaluable tool for both physicians and their patients in contact allergy counseling.     

Intrinsic characteristics of contact and respiratory allergens influence production of polarizing cytokines by dendritic cells

Type 1 and type 2 cytokines are primary mediators in contact allergy and aeroallergen-mediated disorders, respectively. For both types of disease, dendritic cells (DCs) are pivotal in initiating immune hyperresponsiveness. We studied whether contact and respiratory allergens possess intrinsic capacities to polarize DC towards DC1 and DC2 functions, independent of environmental factors. Human monocyte-derived DCs were exposed to the positive controls [type 1: lipopolysaccharide (LPS) + interferon-gamma; type 2: LPS + prostaglandin E(2)], contact allergens [2,4-dinitrochlorobenzene (DNCB), oxazolone (OXA), and nickel sulfate (NiSO(4))], and respiratory allergens [trimellitic anhydride (TMA) and the protein allergen derived from Dermatophagoides pteronyssinus (Der p1)]. The polarizing potentials of the allergens on DCs were determined by the secretion of type 1 [tumour necrosis factor-alpha (TNF-alpha), CXCL10, and interleukin (IL)-12p70] and type 2 (IL-10) cytokines. The contact allergens, DNCB and OXA, induced strict type 1 DC polarization, whereas the respiratory allergens, TMA and Der p1, showed strict type 2 DC polarization. The contact allergen, NiSO(4), induced both DC1 (TNF-alpha and CXCL10 production) and DC2 (decreased IL-12p70/IL-10 ratio) features. These results support the view that allergens have an intrinsic capacity to skew immune responses at the DC level, irrespective of local factors such as those determined by cutaneous or mucosal epithelial microenvironments.     

Patch test results in a Turkish paediatric population

Allergic contact dermatitis is increasing in childhood. In children, population-based patch test studies point to different contact sensitizers and reflect the variations in the exposure to certain allergens among different countries. Our aim is to show common contact allergens in a paediatric population in Turkey. Contact dermatitis and identifying the suspected allergen in children are important as sensitization occurring during childhood may cause a susceptibility to the contact dermatitis later in their life.     

Positive patch tests with a dermatophagoides mix relate to an increased responsiveness to standard patch test allergens

The diagnostic meaningfulness of patch tests with house dust mite allergens is still questionable. Our own impression has been that positive results with a dermatophagoides mix may occur preferentially in patients with a generally enhanced responsiveness to contact allergens. To check this, all of our patients allocated to patch testing with the standard series were additionally patch tested with a dermatophagoides mix by the same technique that was used for standard contact allergens. Out of 571 patients tested, 188 showed delayed responses to this mix that were indistinguishable from typical allergic patch test reactions but of no apparent clinical relevance. No relationship was found between positive dermatophagoides patch tests and an atopic disposition of the patients or characteristics of their eczema. However, 64.4% of the patients with a positive dermatophagoides patch test showed a response to at least 1 contact allergen of the standard series, compared to only 56.4% of the patients without a positive dermatophagoides reaction (p < 0.05). The reactivity to the mite mix was not related to the responsiveness towards any particular contact allergens. We suppose that some unidentified factors may contribute to positive reactions to the dermatophagoides mix that may also favour an enhanced general responsiveness to contact allergens.     

The detection of clinically relevant contact allergens with a standard screening tray of 28 allergens

Background. A standard method for diagnosing allergic contact dermatitis in the United States is the Thin‐layer Rapid Use Epicutaneous (TRUE) test (TRUE Test?), which consists of three panels containing 20 individual allergens and eight allergen mixes. Previous studies had raised concern regarding the adequacy of the initial two‐panel TRUE Test? system (16 individual allergens and seven allergen mixes) in fully assessing patients with possible allergic contact dermatitis. Objectives. We sought to investigate the effectiveness of the current three‐panel TRUE Test? as the sole diagnostic tool for detecting allergic contact dermatitis. Patients/materials/methods. This study was a retrospective analysis of 2088 patients who underwent patch testing between 1995 and 2010. Study groups were analysed to determine whether positive reactions were to allergens and/or mixes present in the TRUE Test? panels. Results. Of the 2088 patch‐tested patients, 1385 had at least one positive reaction. Among these 1385 patients, 27.6% were fully evaluated by use of only the TRUE Test? series, 49.9% were partially evaluated, and 22.5% did not have any of their allergens detected. On assessment for clinical relevance, similar percentages were observed. Conclusion. In our study, the current TRUE Test? series of 28 allergens would have completely identified allergens in only 27.6% of patients. Broadening the standard panel to include common allergens causing >50% of allergic contact dermatitis cases in a given geographical location and aim testing allergens on the basis of the patient's history will increase the test's sensitivity.     

系统性接触性皮炎8例分析

系统性接触性皮炎（SCD）是一种特殊类型的接触性皮炎，是已经接触致敏的个体系统摄入相同致敏原后发生的皮肤炎症性疾病。本文报道了8例金属镍所致SCD，并结合文献简要介绍了SCD的定义、临床表现、发病机制、诊断、治疗及常见致病原因。     

化妆品变应性接触性皮炎变应原检测分析

目的 调查化妆品变应原种类,为化妆品过敏提供流行病学资料和临床依据.方法 对89例门诊疑诊化妆品变应性接触性皮炎患者采用49种欧洲化妆品系列变应原及5种中国筛查系列化妆品变应原进行斑贴试验,按国际接触性皮炎研究组推荐标准判读结果.结果 89例患者中,61例对1种或1种以上化妆品变应原过敏,阳性反应率68.5%.其中阳性率较高的有香料33.7%,防腐剂30.3%,对苯二胺25.8%,阿莫醇10.1%.结论 香料、防腐剂、对苯二胺、阿莫醇等是化妆品变应性接触性皮炎患者的主要致敏原.

Abstract：

Objective To make a survey on common cosmetic allergens, and to provide epidemiological data and clinical evidence for cosmetic allergy. Methods Patch test was performed by using 49cosmetic allergens from a European cosmetic series and 5 Chinese standard screening allergens on 89patients with suspected cosmetic allergic contact dermatitis. Test results were determined according to the International Contact Dermatitis Research Group (ICDRG) recommendation. Results Of the 89 patients, 61(68.5%) showed positive reactions to one or more cosmetic allergens. The most common allergens were fragrances (33.7%), followed by preservatives (30.3%), para-phenylenediamine (25.8%) and amerchol L 101(10.1%). Conclusion Fragrances, preservatives, para-phenylenediamine and amerchol L 101 are dominant causative allergens in patients with cosmetic allergic contact dermatitis.     

Contact sensitization in the elderly

Contact dermatitis from irritant and allergic sources is the reason for 6% to 10% of all dermatologic visits with considerable morbidity and economic impact. Allergic contact dermatitis is a T-cell-mediated inflammatory reaction and develops in predisposed individuals as a consequence of environmental exposure to allergens. Aging is correlated with the rate and type of contact sensitization because of “immunosenescence.” The number of old people is growing around the world. This contribution reviews the main findings from published epidemiologic studies on contact allergy in elderly populations. In all examined studies, patch testing was performed in patients with cutaneous manifestations possibly related to contact dermatitis; the prevalence of contact dermatitis in the elderly was from 33% to 64%. Establishing the most frequent allergens responsible for allergic contact dermatitis in the elderly is a hard task. The commonest allergens reported were nickel sulfate, fragrance mix, diamino diphenylmethane, lanolin alcohols, paraben mix, Euxyl K400, quinoline mix, and balsam of Peru. We emphasize that allergens surveillance is needed to realize an “elderly series” for having a useful adjunct to contact allergy that may help the treatment of each patient.