S3 Guidelines: Epicutaneous patch testing with contact allergens and drugs - Short version, Part 2.

Epicutaneous patch testing is the diagnostic standard for the detection of allergic contact dermatitis. The present guidelines are aimed at residents and board-certified physicians in the fields of dermatology and allergology as well as other medical specialties involved in establishing the indication for patch testing and its execution in patients with contact dermatitis and other forms of delayed-type hypersensitivity. The target audience also includes other health care providers and insurance funds. Based on a systematic literature search and a formal consensus process (S3), the guidelines were developed by dermatologists in collaboration with pediatricians, occupational medicine physicians, nursing staff as well as patient representatives. The systematic methodological approach and appraisal of evidence upon which the recommendations are based are outlined in a separate method report that also contains evidence tables. The guidelines address general aspects of patch testing as well as medicolegal issues. The recommendations given relate to topics such as the indication for patch testing, informed patient consent, as well as the choice of test substances, test chambers and test site, duration of exposure, reading times and interpretation of test reactions. Furthermore, recommendations are provided with respect to endogenous and exogenous factors, specific patient groups (children, pregnant women, immunosuppressed individuals) as well as possible risks and adverse events associated with patch testing using contact allergens.

S3 guidelines: Epicutaneous patch testing with contact allergens and drugs - Short version, Part 1.

Epicutaneous patch testing is the diagnostic standard for the detection of allergic contact dermatitis. The present guidelines are aimed at residents and board-certified physicians in the fields of dermatology and allergology as well as other medical specialties involved in establishing the indication for patch testing and its execution in patients with contact dermatitis and other forms of delayed-type hypersensitivity. The target audience also includes other health care providers and insurance funds. Based on a systematic literature search and a formal consensus process (S3), the guidelines were developed by dermatologists in collaboration with pediatricians, occupational medicine physicians, nursing staff as well as patient representatives. The systematic methodological approach and appraisal of evidence upon which the recommendations are based are outlined in a separate method report that also contains evidence tables. The guidelines address general aspects of patch testing as well as medicolegal issues. The recommendations given relate to topics such as the indication for patch testing, informed patient consent, as well as the choice of test substances, test chambers and test site, duration of exposure, reading times and interpretation of test reactions. Furthermore, recommendations are provided with respect to endogenous and exogenous factors, specific patient groups (children, pregnant women, immunosuppressed individuals) as well as possible risks and adverse events associated with patch testing using contact allergens. Note: This publication is part 1 of the short version of the S3 guidelines for "Epicutaneous patch testing using contact allergens and drugs" (registry no. 013 - 018; date: March 20, 2019; valid until December 31, 2021). Part 2 of the short version will be published in the next issue. The long version of these guidelines can be accessed at www.awmf.org. The method report is available as online publication (https://www.awmf.org/leitlinien/detail/ll/013-018.html) and contains the evidence tables in its appendix.

Histomorphology and Immunophenotype of Eczematous Skin Lesions Revisited-Skin Biopsies Are Not Reliable in Differentiating Allergic Contact Dermatitis, Irritant Contact Dermatitis, and Atopic Dermatitis.

Lesions of allergic contact dermatitis (ACD), irritant contact dermatitis (ICD), and atopic dermatitis (AD) share similar clinical features and thus, their diagnosis can be challenging. The aim of this study was to reassess histopathology and immunophenotyping properties to distinguish between ACD, ICD, and AD. Charts of patients with eczema, who had undergone complete routine diagnostic workup (skin biopsies, patch tests, skin prick tests, and respectively or serum IgE levels), were reviewed. Thirty-five skin biopsy specimens of 28 patients (mean age 64 ± 15 years; ♀ = 13 ♂ = 15) with clear diagnosis of ACD (n = 15), ICD (n = 6), or AD (n = 14) were analyzed. Histomorphological and immunohistochemical (CD3, CD4, CD8, CD11c, CD34, CD123, S100, and IL-17) parameters were evaluated using Kruskal-Wallis test, Wilcoxon test, Fisher exact test, and decision tree analysis. Eosinophils were statistically significant (P = 0.0184), more often observed in AD than in ACD or ICD. No other statistically significant differences were found with regard to epidermal patterns, patterns of dermal infiltrates, or immunophenotyping. Using predictive modeling approaches, dermal eosinophils were found to be associated with AD, necrotic epidermal keratinocytes with ICD, and a focal type of parakeratosis with ACD. As an additional finding, pseudo-Pautrier microabscesses, which were present in the skin of 2 AD and 2 ACD patients, contained myeloid dendritic cells (CD11c). Differentiation of ACD, ICD, and AD should be based on clinical features and results of allergy tests. Histopathology does not reliably differentiate between ACD, ICD, and AD, but helps to exclude psoriasis, tinea, or T-cell lymphoma.

Effects of structured patient education in adults with atopic dermatitis: Multicenter randomized controlled trial.

BACKGROUND: Atopic dermatitis (AD) is a chronic relapsing skin disease prevalent in 1% to 3% of adults in Western industrialized countries. OBJECTIVE: We sought to investigate the effectiveness of educational training in an outpatient setting on coping with the disease, quality of life, symptoms, and severity in adults with AD. METHODS: In this German prospective, randomized controlled multicenter study, adult patients with moderate-to-severe AD were educated by referring to a comprehensive 12-hour training manual consented by a multiprofessional study group from different centers (Arbeitsgemeinschaft Neurodermitisschulung für Erwachsene [ARNE]). Patients were randomly allocated to the intervention or waiting control groups. Study visits were performed at baseline and after 1 year (1 year of follow-up). Primary outcomes were defined as a decrease in (1) "catastrophizing cognitions" with respect to itching (Juckreiz-Kognitions-Fragebogen questionnaire), (2) "social anxiety" (Marburger Hautfragebogen questionnaire), (3) subjective burden by symptoms of the disease (Skindex-29 questionnaire), and (4) improvement of disease signs and symptoms assessed by using the SCORAD index at 1 year of follow-up. Data were analyzed on an intention-to-treat basis. RESULTS: At 1 year of follow-up, patients from the intervention group (n = 168) showed a significantly better improvement compared with the waiting group (n = 147) in the following defined primary study outcomes: coping behavior with respect to itching (P < .001), quality of life assessed by using the Skindex-29 questionnaire (P < .001), and the SCORAD index (P < .001). CONCLUSIONS: This is the first randomized, controlled multicenter study on patient education in adult AD. The ARNE training program shows significant beneficial effects on a variety of psychosocial parameters, as well as AD severity.

A variant of the CXCL11 gene may influence susceptibility to contact allergy, particularly in polysensitized patients.

BACKGROUND: Hereditary factors may influence individual susceptibility to contact allergy. OBJECTIVES: To investigate genetic variants with impacts on early inflammatory reactions and T cell functions that possibly increase the risk of contact allergy. PATIENTS AND METHODS: Three hundred and seventy two patients undergoing patch testing were recruited from the Information Network of Departments of Dermatology (IVDK). Of these, 133 were monosensitized and 239 were polysensitized, defined as reacting to three or more unrelated sensitizers. Within the polysensitized individuals, a subgroup with at least one particularly strong patch test reaction (strong reactors; n = 194) was considered. Three hundred and forty-seven blood bank donors served as controls. Fifteen genetic variants in 13 genes were analysed. RESULTS: The homozygous variant CXCL11 AA genotype (rs6817952) was significantly more frequent among polysensitized patients (10 of 239 = 4.2%; p = 0.0048; odds ratio 7.49; 95%CI: 1.7-36.1) than among monosensitized patients (2.2%) and in the control group (0.6%). None of the remaining genetic variants investigated were characterized by similarly strong associations. However, the significance was lost after correction for multiple comparisons. CONCLUSIONS: The homozygous variant CXCL11 genotype is associated with an increased risk of contact allergy. To confirm this exploratory finding, further independent studies are needed.

Epidemiological data on airborne contact dermatitis - results of the IVDK.

BACKGROUND: Airborne contact dermatitis (AirbCD) is not uncommon, according to a large number of published case reports and review articles. Epidemiological data on AirbCD based on larger clinical samples have not yet been published. OBJECTIVES: To investigate demographic characteristics and patch test reactivity in patients diagnosed with both occupational and non-occupational AirbCD. METHODS: A retrospective analysis of data from the Information Network of Departments of Dermatology (IVDK), 1994-2013, including 201 344 consecutively patch tested patients, was performed. RESULTS: One thousand two hundred and three patients (0.6%) were diagnosed with AirbCD, 421 (35.0%) of these with an occupational background. Occupational dermatitis and face involvement were more prevalent than in patients without AirbCD (n = 200 141). Sensitization to epoxy resin and sensitization to methylchloroisothiazolinone (MCI)/methylisothiazolinone (MI) were significantly associated with AirbCD, and there was a trend for sensitization to Compositae mix and/or sesquiterpene lactone mix to be associated with AirbCD. Adhesives, plastics, construction materials, paints and varnishes in occupational cases, and plants in non-occupational cases, were the most commonly documented culprit product categories. CONCLUSIONS: AirbCD is more common in patients with occupational dermatitis than in patients with non-occupational dermatitis. In our clinical sample, components of epoxy resin systems, MCI/MI and Compositae allergens were the most important contact allergens associated with AirbCD. Patch testing with additional allergens is important.

Predictors of benefit from an atopic dermatitis education programme.

BACKGROUND: Multidisciplinary, age-related, structured, group educational programmes for children with atopic dermatitis (AD) and their parents have shown positive long-term outcomes with respect to quality of life and coping behaviour of the participants. We aimed to identify predictors of favourable long-term outcome of an education measure for parents of children with AD aged 3 months to 7 years in the framework of The German Atopic Dermatitis Intervention Study (GADIS). METHODS: In an exploratory approach, the data of 274 child-parent pairs were analysed with respect to the influence of various somatic and psychological variables as possible predictors of treatment success. Changes in parents' QoL, SCORAD (Scoring Atopic Dermatitis), topical corticosteroid use and parents' knowledge about AD between baseline and 12-months' follow-up were chosen as measures of long-term treatment success (outcome). RESULTS: Psychological rather than somatic parameters were identified as predictors of treatment success. Parents who had negative treatment experiences in the past and possessed only poor coping abilities with regard to scratch control benefitted the most from the training programme. The outcome of the education measure was independent of parents' schooling, vocational level and income. CONCLUSIONS: Parents of children with AD who lack adequate coping abilities should be particularly encouraged to take part in such an education programme.

Anxiety, depression and impaired health-related quality of life in patients with occupational hand eczema.

BACKGROUND: Occupational hand eczema is one of the most frequent occupational diseases. Few data about the prevalence of mental comorbidities are available. Objectives. We aimed to investigate the prevalence of anxiety, depression symptoms, the impairment of health-related quality of life (HRQoL) and their correlates in patients with occupational hand eczema. PATIENTS AND METHODS: A test battery consisting of the German versions of the Hospital Anxiety and Depression Scale, the Dermatology Life Quality Index (DLQI) as a specific instrument and the Short Form Health Survey-36 (SF-36) as a generic instrument for HRQoL was applied in 122 patients. The severity of hand eczema was assessed with the Osnabrueck Hand Eczema Severity Index (OHSI). RESULTS: Twenty per cent of patients had a positive anxiety score, and 14% had a positive depression score. Higher anxiety levels, a greater impairment in the SF-36 mental component summary score and a higher DLQI category score for symptoms and feelings was detected in females than in males. The OHSI correlated with the impairment in HRQoL, and an association of severe hand eczema with symptoms of anxiety and depression was found in males. CONCLUSIONS: We found a high prevalence of anxiety and depression in our study population of patients with occupational hand eczema. Preventive measures should consider the psychosocial implications of occupational hand eczema.

Dermatological rehabilitation.

Chronic and chronically recurring diseases often cannot be treated causally and usually lead to a considerable impairment in social and occupational participation. In order to deal appropriately with such restrictions, a more comprehensive therapeutic approach is required in the sense of a bio-psychosocial model of disease and health which serves as the basis for modern dermatological rehabilitation. Multimodal, quality-controlled dermatological rehabilitation gives patients with chronic skin diseases a treatment option that goes beyond the primarily symptom-oriented outpatient care provided by office-based physicians and the acute care of inpatient facilities. This paper presents the complex opportunities offered by dermatological rehabilitation. The aim of this paper is to put dermatologists working in the practical field in a position to help their patients with chronic skin diseases to realize their statutory right to participate in society. For this purpose, it will impart the understanding of medical rehabilitation that is necessary so that the dermatologist in charge can advise his or her patient competently, in order to successfully arrange for the corresponding care appropriate to the indication and taking into account personal circumstances and insurance-related requirements.

Occupational airborne contact allergy to tetrazepam in a geriatric nurse.

A 52-year-old geriatric nurse presented with recurrent eczema localized in uncovered skin areas. Patch testing produced an eczematous skin reaction with type IV sensitization totetrazepam. A relapse of contact dermatitis was successfully prevented by using occupational skin protection measures and organizational measures.Our case indicates that a sensitization to drugs should be considered when allergic contact dermatitisis suspected in nursing personnel.

Staphylococcus aureus-derived enterotoxins enhance house dust mite-induced patch test reactions in atopic dermatitis.

BACKGROUND: Up to 65% of Staphylococcus aureus strains isolated from the skin of patients with atopic dermatitis (AD) produce exotoxins with superantigenic properties that may also act as allergens leading to an induction of exotoxin-specific IgE antibodies. Staphylococcal enterotoxin B (SEB) applied epicutaneously in a concentration of 10 micro g/cm(2), i.e. 200 micro g/ml, under occlusion induces cutaneous inflammation in patients with AD and healthy individuals. METHODS: We performed patch tests in 32 adult patients with AD using different concentrations (i.e. 2-200 micro g/ml) of SEA, SEB and house dust mite (HDM) extract (500 micro g/ml). Furthermore, the respective enterotoxins and HDM extract were applied simultaneously to the same patch test site. Specific IgE levels to SEA, SEB and HDM were measured with the CAP FEIA. RESULTS: The rates of patch test reactions to SEA and SEB increased with rising enterotoxin concentrations. There were no differences in the rates of patch test reactions to SEA and SEB between patients sensitized to the corresponding enterotoxin and non-IgE-sensitized patients. The number of patch test reactions to the mixture of enterotoxin and HDM extract was higher than the number of patch test reactions to either the enterotoxins or HDM extract. We identified 11 patients with AD who reacted neither to the enterotoxins nor to HDM extract, but who showed patch test reactions to the mixture. These reactions were not predicted by the presence of enterotoxin- or HDM-specific IgE. CONCLUSIONS: Colonization with exotoxin-producing S. aureus may influence the outcome of patch tests in patients with AD.

Allergic manifestations of skin diseases--atopic dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease which often becomes manifest in early infancy and is characterized by itchy eczematous lesions with characteristic localization. The cellular infiltrate of allergic eczematous skin diseases (i.e. AD, allergic contact dermatitis) is mainly composed of mononuclear cells. Whereas allergic contact dermatitis is always triggered by allergen-specific T cells, a number of allergic and nonallergic trigger factors appear to be relevant in AD. This article discusses data coming from immunological studies focusing on T-cell responses in AD. The concept of a switch from a T helper type 1 (Th1) to a Th2 cytokine profile in lesional skin of AD is well accepted. Besides CD4+ T lymphocytes, CD8+ cells are likely to play an important role in the pathogenesis of AD. Recent studies point to the induction of apoptosis in keratinocytes by interferon-gamma derived from skin-homing T cells as a further important mechanism for the induction and maintenance of the eczema. Recent clinical studies have confirmed the major role of food allergy and infectious microorganisms as trigger factors of AD. New therapeutic strategies for AD include topical calcineurin inhibitors which were introduced as a new therapeutic principle at the beginning of this decade.

Safety and efficacy of topical calcineurin inhibitors in the treatment of childhood atopic dermatitis.

Approximately 10-20% of infants in industrialized countries experience atopic dermatitis. In recent decades topical corticosteroids have been the first-choice therapy for treatment of flares. However, this form of therapy may induce skin atrophy, especially after application to facial lesions or with long-term use. Thus, development of new anti-inflammatory topical agents for the treatment of childhood atopic dermatitis was needed. The topical calcineurin inhibitors tacrolimus and pimecrolimus have an effect on various cells of the cutaneous immune system, specifically on T cells, by inhibiting the phosphatase calcineurin and preventing the transcription of proinflammatory cytokines. In several clinical studies of children and adults with atopic dermatitis, topical calcineurin inhibitors were found to be effective both on the face and the trunk and extremities, in both short- and long-term treatment regimens. Tachyphylaxis or rebound were not observed. In most patients an improvement of their eczema occurred during the first week of treatment, as measured by subjective and objective clinical signs of atopic dermatitis. Treatment significantly reduced the incidence of flares and the need for corticosteroids in children and adults. Treatment success, commonly defined as 'excellent improvement' or 'clearing of all lesions', was observed in more than one-third of all children treated with 0.03% or 0.1% tacrolimus or 1% pimecrolimus. Topical application of pimecrolimus and tacrolimus does not lead to significant blood concentrations of these agents in the majority of children with atopic dermatitis, and any increase in blood concentrations decreases after a few days of therapy. No changes in laboratory parameters were observed in short- and long-term studies in patients with atopic dermatitis. The most common adverse effect following the application of topical calcineurin inhibitors is mild to moderate symptoms of irritation such as burning, erythema and pruritus, which occurred in up to 20% of all children treated with tacrolimus and 10% of children treated with pimecrolimus, and usually faded after a few days. In contrast to topical corticosteroids, calcineurin inhibitors do not induce skin atrophy, even after long-term use. Topical calcineurin inhibitors have been proven to be effective and have a good safety profile during short-term and long-term use for up to 1 year with pimecrolimus and up to 4 years with tacrolimus. Given the lack of extensive experience with use of topical calcineurin inhibitors over longer periods, regular use of these agents, particularly in children, should be undertaken only after careful consideration of individual cases. Sun protection should also be advised.