Atopy patch testing with aeroallergens in a large clinical population of dermatitis patients in Germany and Switzerland, 2000-2015: a retrospective multicentre study.

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.

Ethylene oxide as an occupational contact allergen - an underestimated problem?

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.

Hyperresponsiveness to antihistamines in spontaneous urticaria and heat urticaria.

. 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.

[Cutaneous granulomatous reactions at botulinum neurotoxin A injection sites: First manifestation of systemic sarcoidosis]. / Granulomatöse Hautveränderungen an Botulinumtoxin-A-Injektionsstellen : Erstmanifestation einer systemischen Sarkoidose.

CASE REPORT: We report a case of granulomatous skin reaction after injection of an unknown botulinum neurotoxin (BoNT) A preparation. Four years after occurrence of skin lesions, systemic sarcoidosis became manifest. CONCLUSION: In addition to injection trauma, the BoNT A preparation may have acted as an immunogenic stimulus leading to cutaneous manifestation of sarcoidosis.

Chronic stress experience and burnout syndrome have appreciable influence on health-related quality of life in patients with psoriasis.

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 <75% at discharge from the rehabilitation measure had lower baseline QoL and showed more symptoms of depression, chronic stress and burnout than patients who achieved a PASI improvement of ≥75. CONCLUSION: Chronic stress and burnout have appreciable influence on HRQoL and may adversely affect treatment success in psoriasis patients. Our data underscore the importance of a multidimensional approach in the management of psoriasis.

Tertiary individual prevention improves mental health in patients with severe occupational hand eczema.

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.

Contact allergy induced by bisphenol A diglycidyl ether leachables from aluminium tubes for pharmaceutical use.

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.

Severe occupational hand eczema, job stress and cumulative sickness absence.

BACKGROUND: Stress is known to activate or exacerbate dermatoses, but the relationships between chronic stress, job-related stress and sickness absence among occupational hand eczema (OHE) patients are inadequately understood. AIMS: To see whether chronic stress or burnout symptoms were associated with cumulative sickness absence in patients with OHE and to determine which factors predicted sickness absence in a model including measures of job-related and chronic stress. METHODS: We investigated correlations of these factors in employed adult inpatients with a history of sickness absence due to OHE in a retrospective cross-sectional explorative study, which assessed chronic stress (Trier Inventory for the Assessment of Chronic Stress), burnout (Shirom Melamed Burnout Measure), clinical symptom severity (Osnabrück Hand Eczema Severity Index), perceived symptom severity, demographic characteristics and cumulative days of sickness absence. RESULTS: The study group consisted of 122 patients. OHE symptoms were not more severe among patients experiencing greater stress and burnout. Women reported higher levels of chronic stress on some measures. Cumulative days of sickness absence correlated with individual dimensions of job-related stress and, in multiple regression analysis, with an overall measure of chronic stress. CONCLUSIONS: Chronic stress is an additional factor predicting cumulative sickness absence among severely affected OHE patients. Other relevant factors for this study sample included the 'cognitive weariness' subscale of the Shirom Melamed Burnout Measure and the physical component summary score of the SF-36, a measure of health-related life quality. Prevention and rehabilitation should take job stress into consideration in multidisciplinary treatment strategies for severely affected OHE patients.

Membrane muscle function in the compliant wings of bats.

Unlike flapping birds and insects, bats possess membrane wings that are more similar to many gliding mammals. The vast majority of the wing is composed of a thin compliant skin membrane stretched between the limbs, hand, and body. Membrane wings are of particular interest because they may offer many advantages to micro air vehicles. One critical feature of membrane wings is that they camber passively in response to aerodynamic load, potentially allowing for simplified wing control. However, for maximum membrane wing performance, tuning of the membrane structure to aerodynamic conditions is necessary. Bats possess an array of muscles, the plagiopatagiales proprii, embedded within the wing membrane that could serve to tune membrane stiffness, or may have alternative functions. We recorded the electromyogram from the plagiopatagiales proprii muscles of Artibeus jamaicensis, the Jamaican fruit bat, in flight at two different speeds and found that these muscles were active during downstroke. For both low- and high-speed flight, muscle activity increased between late upstroke and early downstroke and decreased at late downstroke. Thus, the array of plagiopatagiales may provide a mechanism for bats to increase wing stiffness and thereby reduce passive membrane deformation. These muscles also activate in synchrony, presumably as a means to maximize force generation, because each muscle is small and, by estimation, weak. Small differences in activation timing were observed when comparing low- and high-speed flight, which may indicate that bats modulate membrane stiffness differently depending on flight speed.

Biomechanics of smart wings in a bat robot: morphing wings using SMA actuators.

This paper presents the design of a bat-like micro aerial vehicle with actuated morphing wings. NiTi shape memory alloys (SMAs) acting as artificial biceps and triceps muscles are used for mimicking the morphing wing mechanism of the bat flight apparatus. Our objective is twofold. Firstly, we have implemented a control architecture that allows an accurate and fast SMA actuation. This control makes use of the electrical resistance measurements of SMAs to adjust morphing wing motions. Secondly, the feasibility of using SMA actuation technology is evaluated for the application at hand. To this purpose, experiments are conducted to analyze the control performance in terms of nominal and overloaded operation modes of the SMAs. This analysis includes: (i) inertial forces regarding the stretchable wing membrane and aerodynamic loads, and (ii) uncertainties due to impact of airflow conditions over the resistance-motion relationship of SMAs. With the proposed control, morphing actuation speed can be increased up to 2.5 Hz, being sufficient to generate lift forces at a cruising speed of 5 m s(-1).

[Applications for medical rehabilitation in the field of dermatology]. / Beantragung medizinischer Rehabilitation in der Dermatologie.

New rehabilitation guidelines and laws have been introduced to promote competition. As a result, the application procedures for rehabilitation measures have been reformed. Since 2007, the application procedure depends on the type of benefit (e.g. secondary or tertiary prevention) and the insurance provider (statutory health or pension insurance company). Thus in order to prescribe rehabilitation as a form of tertiary prevention payable by a statutory health insurance company, accredited doctors have to demonstrate that they have the necessary qualifications as stipulated by the rehabilitation guidelines. As before 2007, any accredited doctor may however apply for rehabilitation in the sense of tertiary prevention payable by a statutory pension insurance company, and for benefits associated with primary and secondary prevention payable by a statutory health insurance company, without providing corresponding proof of qualification. In addition, dermatologists should report occupational skin diseases to the statutory accident insurance using the "optimized dermatologist's report" which also allows them to recommend secondary and tertiary preventative measures. Every insurance-accredited dermatologist should understand the application process and the contents of preventative and rehabilitation measures to ensure their patients' right to participate.

[Cooperation among clinics and practices. Integrated medical care in occupational dermatology]. / Neue Formen der Zusammenarbeit zwischen Praxis und Klinik. Integrierte Versorgung in der Berufsdermatologie.

Preventive measures in occupational dermatology have proven to be very effective in recent years, especially measures of primary and secondary prevention as components of a complex hierarchical prevention concept. For those cases of occupational dermatoses in which these outpatient prevention measures are not successful, interdisciplinary inpatient rehabilitation measures have been developed ("tertiary individual prevention" [TIP]). TIP comprises 3 weeks inpatient treatment including intensive disease-oriented teaching and psychological counseling, followed by outpatient treatment by the local dermatologist. In 2005, a German prospective cohort multicenter study ("Medizinisch-Berufliches Rehabilitationsverfahren Haut--Optimierung und Qualitätssicherung des Heilverfahrens" [ROQ]) started which will further standardize TIP and evaluate long-term success and scientific sustainability in depth. This integrated concept of an inpatient/outpatient disease management reveals remarkable pertinent options for patients with severe occupational dermatoses in all high-risk professions.

Isolation of alpha-toxin-producing Staphylococcus aureus from the skin of highly sensitized adult patients with severe atopic dermatitis.

BACKGROUND: Staphylococcus aureus (S. aureus) is a well-known trigger factor of atopic dermatitis (AD). Besides staphylococcal superantigens, alpha-toxin may influence cutaneous inflammation via induction of T-cell proliferation and cytokine secretion. OBJECTIVES: To investigate the association between sensitization to inhalant allergens and skin colonization with alpha-toxin-producing S. aureus in AD. PATIENTS AND METHODS: We investigated 127 patients with AD, aged 14-65 years, who were on standard anti-inflammatory and antiseptic treatment before investigation. We evaluated skin colonization, medical history, severity of AD and sensitization to inhalant allergens. RESULTS: Forty-eight of 127 patients were colonized with S. aureus, suffered from more severe AD, had asthma more often and showed higher sensitization levels to inhalant allergens. Thirty of 48 patients with S. aureus skin-colonizing strains produced alpha-toxin and had higher total IgE and specific IgE to birch pollen and timothy grass pollen. CONCLUSIONS: Under topical treatment with antiseptic and anti-inflammatory agents the colonization of lesional skin with S. aureus was clearly lower than commonly found in untreated patients with AD. Colonization with S. aureus was associated with a higher severity of AD, higher degree of sensitization, and a higher frequency of asthma. The proportion of patients whose skin was colonized with alpha-toxin-producing S. aureus was higher than expected from a former study. Cutaneous colonization with alpha-toxin-producing S. aureus was associated with a higher sensitization level to birch pollen allergen in AD. This may point to a higher susceptibility of patients with higher T-helper 2 polarization towards alpha-toxin-producing S. aureus.

[Optimal care of patients with occupational hand dermatitis: considerations of German occupational health insurance]. / Optimierte Versorgung von Patienten mit berufsbedingten Handekzemen: Hautarztverfahren und Stufenverfahren Haut der gesetzlichen Unfallversicherung.

Occupational dermatoses (OD) have been at the top of all occupational diseases in Germany for years (>25% of all occupational diseases officially reported annually to the public statutory employers' liability insurance bodies). More than 90% of OD-cases are hand eczema. Several pilot initiatives to improve prevention of occupational skin diseases have been developed and funded since 2005 by the statutory employers' liability insurance schemes. The concept underpinning these initiatives is a nationwide multi-step intervention approach recently implemented by the public statutory insurance system administration ("step- wise procedure") which aims at offering quick and specific preventive help at all levels of severity of OD. The dermatologist has a pivotal function in this concept; for early secondary prevention, the so-called dermatologist's procedure was recently updated in order to provide more rapid and concise dermatological consultations and care. Additionally, combined outpatient dermatological and educational intervention seminars ("secondary individual prevention", SIP) and interdisciplinary inpatient prevention measures have been developed ("tertiary individual prevention", [TIP]) and are currently being further evaluated in multicenter studies.

The role of lubricin in the mechanical behavior of synovial fluid.

Synovial fluid is a semidilute hyaluronate (HA) polymer solution, the rheology of which depends on HA-protein interactions, and lubricin is a HA-binding protein found in synovial fluid and at cartilage surfaces, where it contributes to boundary lubrication under load. Individuals with genetic deficiency of lubricin develop precocious joint failure. The role of lubricin in synovial fluid rheology is not known. We used a multiple-particle-tracking microrheology technique to study the molecular interactions between lubricin and HA in synovial fluid. Particles (200 nm mean diameter) embedded in normal and lubricin-deficient synovial fluid samples were tracked separately by using multiple-particle-tracking microrheology. The time-dependent ensemble-averaged mean-squared displacements of all of the particles were measured over a range of physiologically relevant frequencies. The mean-squared displacement correlation with time lag had slopes with values of unity for simple HA solutions and for synovial fluid from an individual who genetically lacked lubricin, in contrast to slopes with values less than unity (alpha approximately 0.6) for normal synovial fluid. These data correlated with bulk rheology studies of the same samples. We found that the subdiffusive and elastic behavior of synovial fluid, at physiological shear rates, was absent in fluid from a patient who lacks lubricin. We conclude that lubricin provides synovial fluid with an ability to dissipate strain energy induced by mammalian locomotion, which is a chondroprotective feature that is distinct from boundary lubrication.

Material odor-odoractive compounds identified in different materials--the surprising similarities with certain foods, possible sources and hypotheses on their formation.

UNLABELLED: Increased efforts have been undertaken by manufacturers to reveal the secrets of material odors, the structure of the odorants responsible, with regard to finding out the source(s) of odor and possible starting points for odor reduction, and therewith product improvement, increased consumer satisfaction and improved indoor air quality. The identification of odor-active compounds in materials by means of gas chromatography-olfactometry (GC-O, also called GC-sniffing), performed at the Fraunhofer Institute for Building Physics (IBP) during the previous years, showed surprising similarities between certain odorants found in materials and those previously identified in certain kinds of food. Examples of important odorants found in different material samples and similarities with food odorants were analyzed. Odorant sources are indicated as regards materials, and possible conditions and mechanisms of formation suggested to show starting points for odor reduction and odor improvement in material development. PRACTICAL IMPLICATIONS: If technical materials are planned to be used indoors and if they spread a distinct odor, the analysis of the compounds contained and emitted by this material using gas chromatography-olfactometry is a means to help reveal the compounds being responsible for that odor. The exact knowledge of the structure of the odorants is the prerequisite for drawing conclusions on possible sources and formation mechanisms and to reveal starting points for odor reduction and product improvement, e.g. by changing ingredients or production conditions. This contributes to an improvement of indoor air quality. Furthermore, quite often the concentrations of certain single odorants found in materials can be very low and the same odorants can be part of other well-known food flavors. This information might be useful to reduce consumers' fears of a possible impairment of their health in the future.

[Inpatient rehabilitation of adults with atopic dermatitis]. / Stationäre medizinische Rehabilitation bei erwachsenen Patienten mit atopischer Dermatitis.

Atopic dermatitis is a chronic inflammatory skin disease which often persists until adulthood. In severe cases, eczematous lesions and pruritus are resistant to therapy and result in depression, impairment of professional activities and social withdrawal. The goal of inpatient rehabilitation measures is to keep the patient involved and active in professional and social activities. Rehabilitative measures include diagnostics and medical therapy according to current guidelines, instruction in basic medical information, psychological intervention (relaxation techniques, improvement of self-confidence), dietetic measures, exercise, and social advice. Patients with atopic dermatitis often have work-related problems which should be identified as early as possible during rehabilitation.

Influence of short-term exposure to airborne Der p 1 and volatile organic compounds on skin barrier function and dermal blood flow in patients with atopic eczema and healthy individuals.

BACKGROUND: Epidemiological studies indicate environmental pollutants to be involved in the increase in the prevalence of allergic diseases. In human exposure studies, volatile organic compounds (VOCs) have been shown to cause exacerbations of allergic asthma whereas, no data concerning atopic eczema (AE) are available. OBJECTIVE: We investigated the effect of airborne VOCs on the skin of patients with AE and controls in the presence or absence of house dust mite allergen, Der p 1. METHODS: In a double-blind crossover study, 12 adults with AE and 12 matched healthy volunteers were exposed on their forearms to Der p 1 and subsequently to a mixture of 22 VOCs (M22, 5 mg/m(3)) in a total body exposure chamber for 4 h. Transepidermal water loss (TEWL) and skin blood flow were measured in all subjects before, during and after exposure. Additionally, an atopy patch test (APT) with Der p 1 was applied to the skin after exposure. RESULTS: A significant increase in transepidermal water loss was observed 48 h after exposure to VOCs as compared with exposure with filtered air in all individuals (mean difference: +34%; 95% Confidence Interval: 7-69%). Prior Der p 1 exposure resulted in a significant rise of dermal blood flow after 48 h in patients with AE but not in controls. Six out of seven patients showed enhanced atopy patch test (APT) reactions to HDM allergen after previous exposure to VOCs. CONCLUSION: Our results show that exposure to VOCs - at concentrations commonly found in indoor environments - can damage the epidermal barrier and enhance the adverse effect of Der p 1 on sensitized subjects with AE. These findings may contribute to a better understanding of the mechanisms underlying the increase in prevalence and exacerbation of AE.

Usefulness of specific immunotherapy in patients with atopic dermatitis and allergic sensitization to house dust mites: a multi-centre, randomized, dose-response study.

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 >or=40 and allergic sensitization to house dust mites [CAP-FEIA >or=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, 2,000 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 (2,000, 20,000 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.

Alpha-toxin is produced by skin colonizing Staphylococcus aureus and induces a T helper type 1 response in atopic dermatitis.

BACKGROUND: Staphylococcus aureus is a well known trigger factor of atopic dermatitis (AD). Besides the superantigens, further exotoxins are produced by S. aureus and may have an influence on the eczema. OBJECTIVE: To explore the impact of staphylococcal alpha-toxin on human T cells, as those represent the majority of skin infiltrating cells in AD. METHODS: Adult patients with AD were screened for cutaneous colonization with alpha-toxin producing S. aureus. As alpha-toxin may induce necrosis, CD4(+) T cells were incubated with sublytic alpha-toxin concentrations. Proliferation and up-regulation of IFN-gamma on the mRNA and the protein level were assessed. The induction of t-bet translocation in CD4(+) T cells was detected with the Electrophoretic Mobility Shift Assay. RESULTS: Thirty-four percent of the patients were colonized with alpha-toxin producing S. aureus and alpha-toxin was detected in lesional skin of these patients by immunohistochemistry. Sublytic alpha-toxin concentrations induced a marked proliferation of isolated CD4(+) T cells. Microarray analysis indicated that alpha-toxin induced particularly high amounts of IFN-gamma transcripts. Up-regulation of IFN-gamma was confirmed both on the mRNA and the protein level. Stimulation of CD4(+) T cells with alpha-toxin resulted in DNA binding of t-bet, known as a key transcription factor involved into primary T helper type 1 (Th1) commitment. CONCLUSION: alpha-toxin is produced by S. aureus isolated from patients with AD. We show here for the first time that sublytic alpha-toxin concentrations activate T cells in the absence of antigen-presenting cells. Our results indicate that alpha-toxin is relevant for the induction of a Th1 like cytokine response. In AD, this facilitates the development of Th1 cell dominated chronic eczema.