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Der diagnostische Standard zum Nachweis einer bestehenden allergischen Kontaktdermatitis ist der Epikutantest. Die vorliegende Leitlinie richtet sich an Assistenz- und Facharzte der Dermatologie, Allergologie und Arzte weiterer Fachgruppen in Klinik und Praxis, die an der Indikationsstellung oder Durchfuhrung von Epikutantests bei Patienten mit Kontaktekzemen und weiteren Spattypallergien beteiligt sind, sowie Kooperationspartner der Arzteschaft (Fachberufe im Gesundheitswesen, Kostentrager). Die Leitlinie zur Durchfuhrung des Epikutantests mit Kontaktallergenen wurde auf der Basis einer systematischen Literatursuche zu definierten Schlusselfragen evidenzbasiert und im formellen Konsensusverfahren (S3) von Dermatologen unter Einbindung von Padiatern, Arbeitsmedizinern, Assistenzpersonal und Patientenvertretern erstellt. Bezuglich der methodischen und inhaltlichen Arbeit, auf denen die Empfehlungen basieren, wird auf Methodenbericht und Evidenztabellen verwiesen. Die Leitlinie stellt allgemeine Aspekte der Epikutantestung sowie medizinrechtliche Aspekte dar. Es werden Empfehlungen gegeben zur Indikationsstellung, Patientenaufklarung, Auswahl von Testsubstanzen und Kammersystemen, Expositionsort, -dauer und Ablesezeitpunkten, Interpretation von Testreaktionen, endogenen und exogenen Einflussfaktoren, Testung besonderer Personengruppen (Kinder, Schwangere, Immunsupprimierte) sowie Risiken und unerwunschten Nebenwirkungen bei der Durchfuhrung des Epikutantests mit Kontaktallergenen.

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.

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.

Der diagnostische Standard zum Nachweis einer bestehenden allergischen Kontaktdermatitis ist der Epikutantest. Die vorliegende Leitlinie richtet sich an Assistenz- und Facharzte der Dermatologie, Allergologie und Arzte weiterer Fachgruppen in Klinik und Praxis, die an der Indikationsstellung oder Durchfuhrung von Epikutantests bei Patienten mit Kontaktekzemen und weiteren Spattypallergien beteiligt sind, sowie Kooperationspartner der Arzteschaft (Fachberufe im Gesundheitswesen, Kostentrager). Die Leitlinie zur Durchfuhrung des Epikutantests mit Kontaktallergenen wurde auf der Basis einer systematischen Literatursuche zu definierten Schlusselfragen evidenzbasiert und im formellen Konsensusverfahren (S3) von Dermatologen unter Einbindung von Padiatern, Arbeitsmedizinern, Assistenzpersonal und Patientenvertretern erstellt. Bezuglich der methodischen und inhaltlichen Arbeit, auf denen die Empfehlungen basieren, wird auf Methodenbericht und Evidenztabellen verwiesen. Die Leitlinie stellt allgemeine Aspekte der Epikutantestung sowie medizinrechtlicher Aspekte dar. Es werden Empfehlungen gegeben zur Indikationsstellung, Patientenaufklarung, Auswahl von Testsubstanzen und Kammersystemen, Expositionsort, -dauer und Ablesezeitpunkten, Interpretation von Testreaktionen, endogenen und exogenen Einflussfaktoren, Testung besonderer Personengruppen (Kinder, Schwangere, Immunsupprimierte) sowie Risiken und unerwunschten Nebenwirkungen bei der Durchfuhrung des Epikutantests mit Kontaktallergenen.

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.

Background: H1 antihistamines are important drugs for the treatment of urticaria and are commonly well tolerated. Cases of hypersensitivity reactions to antihistamines have rarely been reported, the underlying pathomechanism is unknown yet. Case report: We report the case of a 28-year-old female patient suffering from chronic spontaneous urticaria who experienced severe episodes of wheals and flares induced by different H1 antihistamines. Methods: We performed skin prick tests (SPT) with a diversity of H1 antihistamines and CAST and FlowCAST analyses. Moreover, a placebo controlled oral challenge test to mizolastin was done. Results: We saw positive SPT reactions to nearly all H1 antihistamines tested with the exception of mizolastin. We observed neither a release of sulfidoleukotrienes nor an upregulation of basophil activation markers in the CAST and FlowCAST analyses. The oral challenge test with mizolastine resulted in the development of generalized wheals and flares. Conclusion: H1 antihistamines are effective drugs for the treatment of urticaria, but they may lead to hypersensitivity reactions in rare cases. Because of the negative CAST and FlowCAST results, an IgE-mediated pathomechanism is improbable. We propose that hypersensitivity reactions to H1 antihistamines may be induced by a paradox H1 receptor activation.

BACKGROUND The diagnostic significance of the atopy patch test for the management of dermatitis possibly triggered by aeroallergens is still controversial. However, sufficiently large studies with routinely tested standardized aeroallergen patch test preparations in dermatitis patients are lacking. OBJECTIVE To evaluate the reaction frequency and the reaction profiles of 10 until mid-2015 commercially available, standardized aeroallergen patch test preparations of the 'Stallerpatch' test series (Stallergenes, Antony Cedex, France) in a large multicentre patient cohort. METHODS A retrospective data analysis of patients with suspected aeroallergen-dependent eczematous skin lesions was performed, who were patch tested in 15 Information Network of Departments of Dermatology-associated clinics between 2000 and 2015. Patients were stratified according to their atopic dermatitis (AD) status. RESULTS The study group included 3676 patients (median age 41 years, 34.8% males, 54.5% AD). The most common aeroallergens causing positive patch test reactions were Dermatophagoides pteronyssinus (19.6%), Dermatophagoides farinae (16.9%), birch (6.2%), timothy grass (6.0%), cat dander (5.4%), mugwort (4.9%) and dog dander (4.6%). Reactions to other pollen allergen preparations, that is 5 grasses (3.2%), cocksfoot (2.1%) and plantain (1.6%), were less common. Positive patch test reactions to aeroallergens were consistently more frequent in patients with AD. These patients showed proportionally less dubious, follicular, irritant and weak positive reactions. Independent of AD status, a patient history of past or present allergic rhinitis was associated with an increased chance of a positive aeroallergen patch test reaction to pollen allergens. CONCLUSION The aeroallergen patch test is a useful add-on tool in clinical routine, especially in patients with AD and/or respiratory allergy. A patch test series comprising Dermatophagoides pteronyssinus, Dermatophagoides farinae, birch, timothy grass, cat dander and mugwort seems to be suitable. Controlled studies with specific provocation and elimination procedures are required to further evaluate the diagnostic significance of the proposed screening series.

Background Ethylene oxide (EtO) is a volatile epoxy compound which is used to sterilize medical devices. EtO may cause irritant contact dermatitis, but only few cases of allergic contact dermatitis have been reported yet. Objectives About 20 employees of a department for surgery developed eczematous skin reactions at the contact areas to wrist bands of surgical gowns which had been sterilized with EtO. Patch tests were performed to exclude contact allergy. Methods Due to the volatility of EtO, patch tests were done with epichlorohydrin (0.1% pet., 1% pet.) which is an epoxy compound chemically related to EtO. Results 7/8 patients and 4 healthy control persons showed non-allergic irritant reactions to 1.0% epichlorohydrin. 1.0% epichlorohydrin may have induced an iatrogenic sensitization in one of the control persons. None of the control persons reacted to 0.1% epichlorohydrin. Allergic contact dermatitis to EtO and a cross sensitization to epichlorohydrin was diagnosed in a nurse who showed an allergic crescendo patch test reaction to 0.1% epichlorohydrin. Conclusions EtO can act as an occupational contact allergen in health personnel, a problem that may have been underestimated in the past due to methodological difficulties in patch testing. When allergic contact dermatitis to EtO is suspected, a patch test to 0.1% epichlorohydrin should be performed.

Summary Background Hereditary factors may influence individual susceptibility to contact allergy (CA). Objectives To investigate genetic variants with impacts on early inflammatory reactions and T cell functions that possibly increase the risk of CA. 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 CA. To confirm this exploratory finding, further independent studies are needed.

Summary 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.

Wir berichten uber den Fall einer granulomatosen Hautreaktion im Bereich der Injektionsstellen eines unbekannten Botulinumneurotoxin (BoNT)-A-Praparates. Vier Jahre nach Auftreten der Hautveranderungen manifestierte sich eine systemische Sarkoidose. Moglicherweise hat das verwendete BoNT-A-Praparat uber das Injektionstrauma hinaus durch seine immunogene Wirkung zur kutanen Manifestation der Sarkoidose gefuhrt.

Background Occupational hand eczema (OHE) is associated with impaired health-related quality of life (QoL) and mental distress. Interdisciplinary inpatient rehabilitation measures in the framework of tertiary individual prevention (TIP) offered by the German employers' liability insurance associations include dermatological treatment, education and psychological interventions. Objective To investigate the effects of interdisciplinary inpatient rehabilitation in the framework of TIP on mental health in patients with severe OHE and the relationships between recovery of OHE and improvement of mental health and QoL. Methods A total of 122 patients participated in the study. A test battery consisting of the German versions of the Hospital Anxiety and Depression Scale (HADS-D), the Dermatology Life Quality Index (DLQI), the Short Form Health Survey-36 (SF-36) and the Trier Inventory for the Assessment of Chronic Stress (TICS) was applied at the time of admission (T1) and 3 weeks after dismissal (T2). Severity of hand eczema was assessed with the Osnabrueck Hand Eczema Severity Index (OHSI). Results All parameters improved significantly from T1 to T2. A relationship was established between the improvement of QoL and recovery of OHE, while there was no such relationship between the improvement of mental distress and improvement of OHE. Nonresponders had significantly more cumulative days of sickness at T1. Conclusions Our data underscore the importance of psychological interventions in addition to dermatological treatment in the framework of prevention measures for OHE. These measures should be applied at an early stage of OHE prior to the occurrence of sick leave.

Background Aluminium tubes for pharmaceutical use are internally lacquered with epoxy resins (ER) based on bisphenol A diglycidyl ether (BADGE). Recently, it was shown that remnants of ER polymerization like BADGE are extractable from epoxy-based coatings of commercially available tubes and may leach into semi-solid drug preparations. We aimed to evaluate the safety of BADGE-contaminated macrogol ointments in individuals sensitized to ER based on BADGE by use tests. Methods Repeated open application testing (ROAT) in 11 patients sensitized to ER based on BADGE with BADGE in macrogol ointments (3 mg/kg; 30 mg/kg, equivalent to BADGE concentration determined in macrogol ointment after storage in a commercially available tube; 300 mg/kg). Results The 30 mg/kg BADGE ointment elicited reactions in three patients, and another three patients reacted to 300 mg/kg BADGE ointment. No reactions to the vehicle control and 3 mg/kg BADGE were observed. Conclusions Elevated BADGE concentrations in ER-coated aluminium tubes pose a risk of developing contact dermatitis to patients sensitized to ER based on BADGE. Quality standards are deemed necessary for the production of ER-coated aluminium tubes intended for pharmaceutical use and should consider the results of the present ROAT study.

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.

Die besondere Bedeutung von Praventionsangeboten in der Berufsdermatologie konnte in den letzten Jahren speziell fur Masnahmen auf der Ebene der primaren und sekundaren Pravention als Bestandteil eines komplexen hierarchischen Praventionskonzeptes belegt werden. Fur die Falle von Berufsdermatosen, in denen diese ambulanten Praventionsmasnahmen nicht erfolgreich sind, wurden interdisziplinare stationare Rehabilitationsmasnahmen entwickelt [“Tertiare Individual-Pravention“ (TIP)]. TIP umfasst eine 3-wochige stationare Behandlung einschlieslich intensivierter gesundheitspadagogischer und gesundheitspsychologischer Interventionen mit anschliesender 3-wochiger Arbeitsunfahigkeit zur Stabilisierung des Hautbefundes unter Weiterbehandlung durch den Dermatologen am Heimatort. Im Jahr 2005 wurde in Deutschland eine prospektive Kohorten-Multicenterstudie [“Medizinisch-Berufliches Rehabilitationsverfahren Haut – Optimierung und Qualitatssicherung des Heilverfahrens“ (ROQ)] initiiert, mit der TIP weiter standardisiert und im Hinblick auf die Nachhaltigkeit detailliert wissenschaftlich evaluiert werden wird. Das integrierte Konzept einer ambulant/stationaren Versorgung zeichnet sich bereits jetzt durch eine hohe Effektivitat fur Patienten mit Berufsdermatosen aus allen Risikoberufen aus.

Berufsbedingte Hauterkrankungen manifestieren sich in mehr als 90% der Falle in Form von Handekzemen und nehmen seit Jahren mit mehr als ein Viertel aller gemeldeten Berufskrankheitenverdachtsfalle die Spitzenposition im Berufskrankheitengeschehen in Deutschland ein. Zur Optimierung der Versorgung von Patienten mit berufsbedingten Handekzemen wurde ab 2005 innerhalb der gesetzlichen Unfallversicherung das „Stufenverfahren Haut“ eingefuhrt. Dieses stellt sicher, dass Betroffene mit berufsbedingten Hauterkrankungen den jeweils indizierten verschiedenen Praventionsangeboten rasch und stadienadaptiert zugefuhrt werden konnen. Voraussetzung hierfur ist, dass die Erkrankungsfalle den zustandigen Tragern der gesetzlichen Unfallversicherung moglichst fruhzeitig gemeldet werden. Diese zentrale Aufgabe kommt dem Hautarzt zu, dem hierfur der 2006 eingefuhrte optimierte Hautarztbericht zur Verfugung steht. Mit dem optimierten Hautarztbericht wurde eine Plattform geschaffen, die eine fruhzeitige ambulante interdisziplinare Pravention und einen Informationsfluss zwischen den beteiligten Akteuren ermoglicht. Der optimierte Hautarztbericht ist komplementar zu den im Stufenverfahren Haut vorgesehenen Praventionsmoglichkeiten aufgebaut und berucksichtigt somit insbesondere die in den letzten Jahren weiterentwickelten und vernetzten interdisziplinaren (ambulanten und stationaren) Versorgungsstrukturen der sekundaren und tertiaren Individualpravention in der Berufsdermatologie.

Hereditary factors may influence individual susceptibility to contact allergy.To investigate genetic variants with impacts on early inflammatory reactions and T cell functions that possibly increase the risk of contact allergy.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.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.The homozygous variant CXCL11 genotype is associated with an increased risk of contact allergy. To confirm this exploratory finding, further independent studies are needed.

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.To investigate demographic characteristics and patch test reactivity in patients diagnosed with both occupational and non-occupational AirbCD.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.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.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.

Background: Staphylococcal enterotoxins have been shown to contribute to cutaneous inflammation in atopic dermatitis. Enterotoxins may both act as superantigens leading to polyclonal T cell activation and as allergens inducing an enterotoxin specific IgE response. The presence of skin-infiltrating enterotoxin-specific T cells in atopic dermatitis has not been shown yet. Since enterotoxins lead to unspecific T cell activation in their function as superantigens, it is not possible to clearly differentiate enterotoxin-(superantigen-) reactive and enterotoxin-specific T cell responses in vitro. Therefore, we have investigated the T cell response to 30 octapeptides spanning the whole amino acid sequence of staphylococcal enterotoxin B (SEB). Due to their structure, a response to those peptides reflects an SEB-specific T cell response. Methods: PBMC derived from patients with atopic dermatitis sensitized to SEB as determined by CAP FEIA and healthy controls were incubated with SEB peptides. The proliferative response was determined using the Vibrant CFDA SE Cell Tracer Assay. Using limiting dilution cultures, peptide-reactive T cell clones were generated from skin and blood of patients who showed a proliferative response to at least one octapeptide. Results: 70% of the patients sensitized to SEB exhibited a proliferative response to at least one peptide. We could identify two peptides which preferentially induced T cell activation. Frequencies of peptide-reactive T cells in the peripheral blood and the skin were rather low compared to classical allergens and ranged between 0.1 and 0.5% of all T cells. Peptide-specific T cell clones were generated from peripheral blood and lesional skin. Stimulation of these T cell clones resulted in only weak proliferation. The T cell clones were mostly CD4-positive and exhibited a THO- or THI-like cytokine profile. Conclusions: These data suggest that an enterotoxin-specific T cell response is present in the skin and blood of patients with atopic dermatitis sensitized to SEB, but this response is rather weak and probably of minor clinical importance in relation to the superantigen-reactive T cell response.

Background: The effect of specific immunotherapy (SIT) on eczema in atopic dermatitis is not known. Therefore, a multi-centre, randomized dose–response trial, double-blind with respect to the efficacy of a biologically standardized depot house dust mite preparation was performed. Methods: Eighty-nine adults with a chronic course of atopic dermatitis, SCORAD ≥40 and allergic sensitization to house dust mites [CAP-FEIA ≥3] were included, of whom 51 completed the study. Subcutaneous SIT with a house dust mite preparation (Dermatophagoides pteronyssinus/D. farinae) applying maintenance doses of 20, 2000 and 20 000 SQ-U in weekly intervals for 1 year. The main outcome measures addressed the change of the SCORAD as average of the values after 9 and 12 months of SIT in comparison with the value at baseline. Results: The SCORAD declined in the three dose groups in a dose-dependent manner (P = 0.0368, Jonckheere–Terpstra test) and was significantly lower in the two high-dose groups (2000, 20000 SQ-U) compared with the low-dose group of 20 SQ-U (P = 0.0379, U-test) after 1 year of SIT. The use of topical corticosteroids was significantly reduced with higher doses (P = 0.0007, Mantel–Haenszel chi-square test). Conclusions: Allergen-SIT for 1 year with a house dust mite preparation is able to improve the eczema in patients with atopic dermatitis who are sensitized to house dust mite allergens and reduces the need for topical corticosteroids. SIT may be valuable in the treatment of this chronic skin disease.

Summary Background Noninfectious granulomatous skin diseases are inflammatory disorders of unknown aetiology which are often recalcitrant to common anti-inflammatory treatment regimens. Recently, in several case reports, fumaric acid esters (FAE) have proved beneficial in granulomatous skin diseases, but studies on a larger collection of consecutive patients have not yet been performed. Objectives To investigate the therapeutic efficacy of FAE for the treatment of granulomatous skin diseases. Patients and methods The therapeutic efficacy and side-effects of FAE were analysed retrospectively in 32 patients with disseminated granuloma annulare (n = 13), annular elastolytic giant cell granuloma (n = 3), sarcoidosis (n = 11), necrobiosis lipoidica (n = 4), or granulomatous cheilitis (n = 1). Results Three patients discontinued treatment within 4 weeks because of side-effects. Of the remaining 29 patients, 18 patients responded to treatment with FAE. Marked improvement or complete clearance was seen in seven patients. We observed a slight to moderate improvement in 11 patients, and 11 patients did not respond. In patients showing a complete remission, the maximum effect was observed after 8·5 months (SD ±6 months, range 3–20 months). In two patients with systemic sarcoidosis, the pulmonary changes improved in parallel with the skin. Side-effects were usually mild and resolved spontaneously upon dose reduction or discontinuation of the therapy. Conclusions The data presented here indicate that FAE may be considered for the treatment of recalcitrant granulomatous skin disease.

Atopic dermatitis is a chronic inflammatory skin disease which runs periods of exacerbations and remissions. The calcineurin inhibitor pimecrolimus – an immunomodulatory macrolactam – is a cell-selective inhibitor of inflammatory cytokines specifically developed to treat inflammatory skin diseases. In this article the currently available data on pharmacology, clinical efficacy and safety are reviewed. In several short and long-term studies on children and adults with AD, most patients showed an improvement of their eczema, paralleled by a rapid relief of pruritus. Moreover, pimecrolimus reduced the incidence of flares and the need for corticosteroids in children and adults. Pimecrolimus has a favourable safety profile. In several pharmacokinetic studies, the topical application of pimecrolimus did not lead to significant blood levels in children and adults. Symptoms of irritation such as burning, erythema and pruritus may occur in the first days. A significant increase of skin infections or systemic infections was not observed, though the incidence of viral skin infections tended to increase slightly. Thus, pimecrolimus may represent an alternative compound to the topical corticosteroids for the treatment of atopic dermatitis.

Food allergy is a common problem in patients with atopic dermatitis, particularly in children. Cow's milk, hen's egg, soy and wheat have been identified as frequent food allergens in this age group. While immediate reactions to food are well characterized, the importance of food as a provocation factor for late eczematous reactions has been a subject of debate for several decades. We have investigated the importance of food for the induction of late eczematous reactions in children with atopic dermatitis aged 1 - 10 years. This article shows the results of our study and discusses the previous literature. 46% of our challenges were related to a clinical reaction. 43% of these reactions were associated with an isolated immediate reaction. An exacerbation of atopic dermatitis (late eczematous reaction) commonly occured 24 hours after the ingestion of food. Isolated late eczematous reactions were seen in 12% of all positive challenges. 45% of the positive challenges were associated with late eczematous responses, which followed immediate-type reactions. We correlated the clinical outcome to the results of specific IgE determinations and atopy patch tests, which resulted in poor predictive values for both in-vitro and skin tests particularly for the late eczematous reactions. Therefore, food challenges have still to be regarded as the gold standard for the appropriate diagnosis of food responsive eczema in children with atopic dermatitis.

Background: Food allergy to cow's milk or hen's egg is a common problem in children with atopic eczema/dermatitis syndrome (AEDS) but the role of birch pollen-related food for the induction of allergic symptoms is still not clear. Patients/methods: Twelve children (median age 5 years) with AEDS underwent an oral challenge with those birch pollen-related foods which were reported to induce no immediate symptoms, but were consumed on a regular basis. Total IgE and specific IgE to birch pollen, Bet v 1/2 and various birch pollen-related foods were determined. Results: Seven of 12 children showed immediate and/or late eczematous reactions upon ingestion of birch pollen-related foodstuff. Four children showed a worsening of eczema 24 h upon oral challenge with a significant difference in SCORAD before and after challenge. There were no differences in terms of total IgE or birch pollen-specific IgE between children with a late eczematous response and non-reacting children. Conclusions: Birch pollen-related food may induce allergic symptoms in children with AEDS who exhibit a sensitization to birch pollen. Oral challenge tests should be performed in those children who suffer from severe AEDS and who are highly sensitized to birch pollen allergens even in the absence of a history suggestive of food allergy.

Two in vitro assays for the detection of allergen-specific IgE (sIgE) were compared reestimating sera with sIgE to common inhalants (birch t3, timothy g6, mugwort w6, cat dander el, dog dander e5, housdust mite D. pter. dl) and food allergens (FA) (hen's egg fl, cow's milk f2, wheat flour f4, soy bean f14, hazelnut f17, apple f49). Quantitative values (kU/l) of both systems were associated to different degrees depending on the allergen: allergen/n t3/48, g6/47, w6/39, e1/40, e5/42, d1/39. Spearman's rho 0.95***, 0.9***, 0.82***, 0.9***, 0.82***, 0.85***, allergen/n f1/37 f2/38 f4/68 f14/52f17/40 f49/40. Spearman's rho 0.84***, 0.6***, 0.6***, 0.31*, 0.68***, 0.82***, *** p < 0.001; * p < 0.05. Values to inhalants (t3, g6, el, e5) were scattered moderately around an ideal regression line (diagonal between x-and y-axis). In contrast, sIgE-levels to FA (f2, f4, f14, fl7) showed stronger discrepancies between both systems. Similarly, different degrees of association and spreading, depending on the individual allergen, were found comparing semiquantitative classes (0 - 6) of both systems. Taken together, values of sIgE to inhalants detected by different in vitro methods are stronger associated than sIgE to FA; IgE-values to allergens with one dominant major allergen (i.e. t3, el) seem to be more concordant than complex allergen mixtures (i.e. dl); identical units (kU/l) can not garantee equivalent IgE results. The data presented do not allow estimates of the real IgE concentrations or judgement on superiority of one of the tests over the other. The study is restricted to compare both methods analytically, since the diagnostic concordance could not be calculated due to a lack of corresponding clinical data. Despite these limitations, comparative sIgE studies are necessary and helpful to define the concordance of IgE values detected by different immunoassays. They also set the basis for subsequent improvement of allergens used in test systems detecting specific IgE.

Background: In the published studies on the efficacy of the topical immunomodulator pimecrolimus, different eczema scores were used, and the impact on morphological key signs of eczema was not analysed. Objective: To compare the influence of pimecrolimus cream 1% on different standard eczema scores in infants with atopic dermatitis and to analyse the impact of treatment on the individual morphological key signs of eczema. Methods: Pimecrolimus cream 1% (n = 129) or double-blind vehicle control (n = 66) was administered for 4 weeks. The Eczema Area and Severity Index (EASI), Investigators’ Global Assessment (IGA) and Scoring Atopic Dermatitis Index (SCORAD) were determined and were correlated with each other. Results: Following treatment with pimecrolimus, the EASI, IGA and SCORAD were significantly reduced on day 29 as compared with the vehicle group (p < 0.001, p < 0.001, p = 0.002, respectively). There was a close correlation between EASI, IGA and SCORAD. The single parameters of the EASI were already significantly decreased by day 4 in the pimecrolimus group as compared to vehicle (each p < 0.001). Conclusion: Treatment with pimecrolimus 1% cream leads to a rapid improvement of all morphological signs of eczema. The close correlation of different scores was shown for the first time.

A number of constitutive cutaneous cells and cells which infiltrate the skin from the circulation contribute to allergic inflammatory skin reactions. The knowledge about the roles of different cell types in allergic skin reactions has been considerably grown during the last years. This review describes functions both of keratinocytes, dermal endothelial cells and antigen-presenting cells of the skin and of skin-infiltrating T-lymphocytes. A focus is laid on skin-infiltrating T-cells since allergic eczematous skin diseases are associated with an infiltration of this cell type into the inflamed organ. The work also contains some thoughts about futural perspectives in the treatment of allergic skin diseases using immunomodulatory principles.

Background Psoriasis has a negative impact on health-related quality of life (HRQoL) and may favour mental comorbidity. Objective To investigate the contribution of chronic stress and burnout experience to HRQoL and how mental health influences the efficacy of an inpatient rehabilitation measure in psoriasis patients. Methods Eighty-four psoriasis patients taking part in a 3-week inpatient rehabilitation measure participated in the study. Severity of psoriasis was assessed with the Psoriasis Area and Severity Index (PASI) and by patients' self-evaluation at the beginning and end of treatment. The following aspects of mental health were explored using validated questionnaires. Symptoms of chronic stress and burnout experience: Trier Inventory for the Assessment of Chronic Stress (TICS) and Shirom Melamed Burnout Measure (SMBM). Symptoms of depression: depression scale of the Patient Health Questionnaire in the German version (PHQ-D). HRQoL: Dermatology Life Quality Index (DLQI) and Short Form Health Survey-8 (SF-8). Results Linear regression analyses revealed that chronic stress, burnout experience and perceived symptom severity but not clinician-assessed severity of psoriasis had independent negative effects on HRQoL. Patients who achieved a PASI reduction of

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.

Background:Staphylococcus aureus has been identified as a possible trigger factor in atopic dermatitis (AD). Some 30–60% of S. aureus strains isolated from patients with AD are able to produce exotoxins with superantigenic properties, mostly staphylococcal enterotoxins A, B, C, and D (SEA–D) and toxic shock syndrome toxin-1 (TSST-1). Recently, it was demonstrated that the presence of IgE antibodies to SEA and SEB is correlated with the severity of skin lesions in children with AD. To determine the relevance of staphylococcal enterotoxins in adult patients with AD, we investigated the relationship between the severity of skin lesions and sensitization to SEA and SEB. Methods: Clinical severity was determined by the SCORAD index. Circulating IgE antibodies to SEA and SEB, serum eosinophil cationic protein (ECP) levels, and urine eosinophil protein X (EPX) levels were measured. Results: The skin condition was significantly worse in patients sensitized to SEB than in unsensitized patients. Serum ECP and urine EPX levels were found to be significantly higher in SEB-sensitized patients, confirming the higher degree of cutaneous inflammation. Conclusions: Our results demonstrate a relationship between severity of skin lesions and sensitization to SEB in adult patients with AD, but a relationship between disease activity and sensitization to SEA could not be shown.