Biomedical subjects

U Darsow

Publications and source records attributed to U Darsow.

At least 19 recordsLinked to original sources

PubMed2006

No effect of anti-interleukin-5 therapy (mepolizumab) on the atopy patch test in atopic dermatitis patients.

BACKGROUND: The atopy patch test (APT) is an in vivo model to study the induction of eczema by inhalant allergens in atopic dermatitis (AD) patients. Mepolizumab is a monoclonal antibody to interleukin-5, which reduces peripheral blood eosinophils. Previously, we reported that mepolizumab treatment did not result in clinical improvement in AD. The current study investigates the effect of mepolizumab therapy on the APT in the same patients. METHODS: Mepolizumab treatment was given at days 0 and 7 in a double-blind placebo-controlled design. The APT was applied at days -2, 0, 14 and 28. Clinical evaluation of each APT was conducted 48 h after application at days 0, 2, 16 and 30. Skin biopsies were taken at days 0, 2 and 16 for eosinophil counts. RESULTS: The mepolizumab-treated group showed no significant reduction in macroscopic outcome of the APT. Tissue eosinophils were reduced in the mepolizumab-treated group at day 16 compared with placebo; however, this was not significant. CONCLUSION: Mepolizumab therapy cannot prevent the eczematous reaction induced by the APT. Furthermore, the influx of tissue eosinophil numbers in the APT is not significantly inhibited after mepolizumab treatment compared with placebo, despite a significant reduction in peripheral blood eosinophils.

Adult↗

PubMed2006

[Clinical classification of chronic pruritus. Interdisciplinary consensus proposal for a diagnostic algorithm].

Chronic pruritus is a frequent symptom in dermatology caused by a variety of dermatologic, neurologic and other systemic diseases. For adequate, economically-appropriate medical care of patients with chronic pruritus, a clinical classification of pruritus which also serves as a diagnostic algorithm is necessary. Currently suggested classifications are etiologic and not helpful in daily clinical routine. The proposed clinical classification is oriented at the clinical appearance of the patients and differentiates between disorders with or without primary or secondary skin lesions.

Algorithms↗

PubMed2006

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.

Adult↗

PubMed2006

Comparison of basophil activation tests using CD63 or CD203c expression in patients with insect venom allergy.

BACKGROUND: Flow cytometric basophil activation tests have been developed as cellular tests for in vitro diagnosis of IgE-mediated reactions. Different activation markers (CD63 or CD203c) with distinct ways of regulation have been used after stimulation with various allergens. OBJECTIVE: It was the aim of the present study to compare basophil activation tests by measuring both CD63 and CD203c upregulation in patients with insect venom allergy. MATERIALS AND METHODS: 43 patients with a history of insect venom anaphylaxis were examined. A careful allergy history was taken, and skin tests and determination of specific IgE-antibodies were performed. Basophil activation tests (BAT) using CD63 or CD203c expression were done after stimulation with different concentrations of bee and wasp venom extracts. 25 healthy subjects with negative history of insect venom allergy were studied as controls. RESULTS: The CD203c protocol showed a slightly higher sensitivity than the CD63 protocol (97% vs. 89%) with regard to patients' history. The magnitude of basophil response was higher with CD203c in comparison to CD63 for both insect venoms. Specificity was 100% for the CD63 protocol and 89% for the CD203c protocol with regard to controls with negative history and negative RAST. CONCLUSION: These results support the reliability of basophil activation tests using either CD63 or CD203c as cellular tests in the in vitro diagnosis of patients with bee or wasp venom allergy with a slightly higher sensitivity for the CD203c protocol.

Allergens↗

PubMed2006

EAACI/GA2LEN position paper: present status of the atopy patch test.

A number of scientific reports have been published on patch tests with protein allergens performed on patients with atopic eczema (AE). Evaluation of eczematous skin lesions with an atopy patch test (APT) can be used as a diagnostic tool in characterizing patients with aeroallergen- and food-triggered AE. Indications for testing with APT, choice of allergens (aeroallergens and foods), test materials and technique, including present knowledge on sensitivity and specificity, are reviewed on the basis of available literature. This position paper also points out the need for future research on the clinical use of the APT.

Allergy and Immunology↗

PubMed2006

Atopic eczema: what's new?

Atopic eczema (AE) is a chronic inflammatory skin disease characterized by recurrent intense pruritus and a typical age-related distribution of skin lesions. Several new aspects with regard to the pathogenetic background as well as strategies for prevention, diagnosis and treatment of AE have emerged. There are ongoing studies on genetic susceptibility loci, as well as environmental and nutritional factors associated with an increase or a decrease of AE lesions. The atopy patch test is now available for identification of allergens in aeroallergen-triggered AE. New topical therapies, such as the calcineurin inhibitors, have broadened the therapeutic armamentarium substantially. In order to increase knowledge and coping strategies, patient education programs have been launched. Learning objective Upon completing this paper, the reader should be aware of new developments in AE, especially on nomenclature, prevention strategies, diagnostic tests, as well as therapeutic options.

Animals↗

PubMed2005

[Atopy patch testing with aeroallergens and food].

The atopy patch test (APT), a patch test employing allergens known to elicit IgE-mediated reactions which is assessed by evaluating eczematous skin lesions after 24 h to 72 h, was developed as a diagnostic tool for characterizing patients with aeroallergen-triggered atopic eczema (AE, atopic dermatitis). Positive APT reactions are associated with allergen-specific T-cell responses. The specificity of APT is higher than the specificity of skin prick tests or RAST. More studies for the standardization of APT methods are necessary, especially with regard to food APT.

Adult↗

PubMed2005

Association of CARD15 polymorphisms with atopy-related traits in a population-based cohort of Caucasian adults.

BACKGROUND: Influences of microbial pathogens are crucial for the maturation of the immune system. Caspase-recruitment domain containing protein 15 (CARD15) is a cytosolic receptor involved in bacterial recognition by antigen-presenting cells. CARD15 polymorphisms have been associated with Crohn's disease. Recently, associations with atopic phenotypes have been reported in children. OBJECTIVE: Within a large population of German adults (n=1875), we evaluated eight CARD15 polymorphisms for associations with atopic phenotypes. METHODS: Subjects were phenotyped by standardized questionnaires and interviews as well as total and allergen-specific IgE measurements. Genotyping was performed using matrix-assisted laser desorption ionization--time of flight mass spectrometry. Haplotypes were estimated using the SAS/Genetics module. RESULTS: Subjects with a T allele at rs1077861 had a decreased risk of developing asthma (odds ratio OR=0.648, P=0.013), whereas the presence of an A allele at rs3135500 was significantly associated with an increased risk (OR=1.374, P=0.023). In addition, a CARD15 haplotype revealed to be protective against the development of asthma (OR=0.326, P=0.003). Subjects with an A allele at position rs5743266 or a T allele at rs2066842 had a significantly decreased risk of developing allergic rhinoconjunctivitis with ORs of 0.820 (P=0.049) and 0.801 (P=0.025). Polymorphism rs2066845 showed a significant association with increased total serum IgE (OR=2.155, P=0.006). CONCLUSION: Genetic variants of CARD15 that might result in inappropriate immunomodulation are not only associated with autoimmune diseases but also with atopic disorders.

Alleles↗

PubMed2005

Anti-IL-5 recombinant humanized monoclonal antibody (mepolizumab) for the treatment of atopic dermatitis.

BACKGROUND: Eosinophils may play an important role in the pathogenesis of atopic dermatitis (AD). Interleukin-5 is essential for eosinophil growth, differentiation and migration. A monoclonal antibody to human interleukin-5 (mepolizumab) was developed for atopic diseases. This study was designed to study the effect of mepolizumab in AD. METHODS: Two single doses of 750 mg mepolizumab, given 1 week apart, were studied in patients with moderate to severe AD using a randomized, placebo-controlled parallel group design. The primary endpoint of 'success' to treatment was defined as the percentage of patients with at least 'marked improvement' after 2 weeks as assessed by the Physician's Global Assessment of Improvement (PGA). Furthermore, SCORing AD (SCORAD), pruritus scoring, number of blood eosinophils and serum thymus and activation-regulated chemokine (TARC) values served as secondary endpoints. Fluticasone propionate cream 0.05%, once daily could be used as rescue medication from day 16 if no improvement was recorded. RESULTS: Eighteen patients received mepolizumab and 22 placebo treatment. Peripheral blood eosinophil numbers were significantly reduced in the treatment group compared with placebo (P < 0.05). No clinical success was reached by PGA assessment (P = 0.115), SCORAD (P = 0.293), pruritus scoring and TARC values in the mepolizumab-treated group compared with placebo. However, modest improvement (<50% improvement) assessed by PGA was scored significantly more in the mepolizumab-treated group compared with placebo (P < 0.05). CONCLUSION: Two single doses of 750 mg mepolizumab did not result in clinical success in patients with AD, despite a significant decrease in peripheral blood eosinophils.

Adult↗

PubMed2005

Standard skin prick testing and sensitization to inhalant allergens across Europe--a survey from the GALEN network.

Skin prick testing (SPT) is the standard method for diagnosing allergic sensitization but is to some extent performed differently in clinical centres across Europe. There would be advantages in harmonizing the standard panels of allergens used in different European countries, both for clinical purposes and for research, especially with increasing mobility within Europe and current trends in botany and agriculture. As well as improving diagnostic accuracy, this would allow better comparison of research findings in European allergy centres. We have compared the different SPT procedures operating in 29 allergy centres within the Global Allergy and Asthma European Network (GA(2)LEN). Standard SPT is performed similarly in all centres, e.g. using commercial extracts, evaluation after 15-20 min exposure with positive results defined as a wheal >3 mm diameter. The perennial allergens included in the standard SPT panel of inhalant allergens are largely similar (e.g. cat: pricked in all centres; dog: 26 of 29 centres and Dermatophagoides pteronyssinus: 28 of 29 centres) but the choice of pollen allergens vary considerably, reflecting different exposure and sensitization rates for regional inhalant allergens. This overview may serve as reference for the practising doctor and suggests a GA(2)LEN Pan-European core SPT panel.

Administration, Inhalation↗

PubMed2005

Position paper on diagnosis and treatment of atopic dermatitis.

The diagnosis of atopic dermatitis (AD) is made using evaluated clinical criteria. Management of AD must consider the symptomatic variability of the disease. It is based on hydrating topical treatment, and avoidance of specific and unspecific provocation factors. Anti-inflammatory treatment is used for exacerbation management. Topical corticosteroids remain the first choice. Systemic anti-inflammatory treatment should be kept to a minimum, but may be necessary in rare refractory cases. The new topical calcineurin inhibitors (tacrolimus and pimecrolimus) expand the available choices of topical anti-inflammatory treatment. Microbial colonization and superinfection (e.g. with Staphylococcus aureus, Malassezia furfur) can have a role in disease exacerbation and can justify the use of antimicrobials in addition to the anti-inflammatory treatment. Evidence for the efficacy of systemic antihistamines in relieving pruritus is still insufficient, but some patients seem to benefit. Adjuvant therapy includes ultraviolet (UV) irradiation preferably of UVA wavelength; UVB 311 nm has also been used successfully. Dietary recommendations should be specific and only given in diagnosed individual food allergy. Stress-induced exacerbations may make psychosomatic counselling recommendable. 'Eczema school' educational programmes have proved to be helpful.

Anti-Bacterial Agents↗

PubMed2005

Review of the potential photo-cocarcinogenicity of topical calcineurin inhibitors: position statement of the European Dermatology Forum.

Topical Calcineurin Inhibitors (TCIs) used for the treatment of atopic eczema modify the immune regulatory function of the skin and may have the potential to enhance immunosuppressive ultraviolet (UV) effects. Current recommendations on UV protection in eczema patients treated with PCIs are inconsistent and have given rise to uncertainty and anxiety in patients. Therefore, the European Dermatology Forum (EDF) developed a position statement which reviews critically the available data with regard to the problem, especially analysing and commenting the limitations of rodent models for the human situation. There is no conclusive evidence from rodent trials to indicate that long-term application of TCIs is photococarcinogenic. There is a need for further studies to investigate the validity of mouse models as well as long-term cohort studies in patients using TCIs. Available data suggest that long-term application of TCIs is safe, that there is no evidence of increased skin cancer risk and that it is ethical to treat patients with TCIs when indicated.

Administration, Topical↗

PubMed2004

The prevalence of positive reactions in the atopy patch test with aeroallergens and food allergens in subjects with atopic eczema: a European multicenter study.

BACKGROUND: The atopy patch test (APT) was proposed to evaluate IgE-mediated sensitizations in patients with atopic eczema (AE). OBJECTIVE: The prevalence and agreement with clinical history and specific IgE (sIgE) of positive APT reactions was investigated in six European countries using a standardized method. METHODS: A total of 314 patients with AE in remission were tested in 12 study centers on clinically uninvolved, non-abraded back skin with 200 index of reactivity (IR)/g of house dust mite Dermatophagoides pteronyssinus, cat dander, grass, and birch pollen allergen extracts with defined major allergen contents in petrolatum. Extracts of egg white, celery and wheat flour with defined protein content were also patch tested. APT values were evaluated at 24, 48, and 72 h according to the European Task Force on Atopic Dermatitis (ETFAD) guidelines. In addition, skin-prick test (SPT) and sIgE and a detailed history on allergen-induced eczema flares were obtained. RESULTS: Previous eczema flares, after contact with specific allergens, were reported in 1% (celery) to 34% (D. pteronyssinus) of patients. The frequency of clear-cut positive APT reactions ranged from 39% with D. pteronyssinus to 9% with celery. All ETFAD intensities occured after 48 and 72 h. Positive SPT (16-57%) and elevated sIgE (19-59%) results were more frequent. Clear-cut positive APT with all SPT and sIgE testing negative was seen in 7% of the patients, whereas a positive APT without SPT or sIgE for the respective allergen was seen in 17% of the patients. APT, SPT and sIgE results showed significant agreement with history for grass pollen and egg white (two-sided Pr > /Z/ < or = 0.01). In addition, SPT and sIgE showed significant agreement with history for the other aeroallergens. With regard to clinical history, the APT had a higher specificity (64-91% depending on the allergen) than SPT (50-85%) or sIgE (52-85%). Positive APT were associated with longer duration of eczema flares and showed regional differences. In 10 non-atopic controls, no positive APT reaction was seen. CONCLUSION: Aeroallergens and food allergens are able to elicit eczematous skin reactions after epicutaneous application. As no gold standard for aeroallergen provocation in AE exists, the relevance of aeroallergens for AE flares may be evaluated by APT in addition to SPT and sIgE. The data may contribute to the international standardization of the APT.

Adolescent↗

PubMed2004

Association of a STAT 6 haplotype with elevated serum IgE levels in a population based cohort of white adults.

BACKGROUND: Several studies have shown linkage of chromosome 12q 13-24 with atopy related phenotypes. Among candidate genes in this region is STAT6 (signal transducer and activator of transcription), which is essential for Th2 cell differentiation, recruitment, and effector function. METHODS: We evaluated six polymorphisms of STAT6 for evidence of associations with serum IgE levels and atopic diseases in a population based cross sectional cohort of 1407 German adults. Genotyping was performed using the matrix assisted laser desorption ionisation-time of flight mass spectrometry method. Haplotypes were estimated using the SAS/Genetics module, and population-derived IgE percentiles (50% IgE>53 kU/l, 66% IgE>99 kU/l and 90% IgE>307 kU/l) were modelled as outcome variables in haplotype trend regression analysis. RESULTS: All polymorphisms were genotyped successfully. Haplotype reconstruction revealed 8/64 possible haplotypes, reaching estimated frequencies of 1% or more. One polymorphism in intron 2 (rs324011) showed a significant association with total serum IgE (p = 0.015). A STAT6 risk haplotype for elevated IgE showing odds ratios of 1.7 (p = 0.015) for IgE cut-off 100 kU/l, and 1.54 (p = 0.032), 1.6 (p = 0.025), and 2.54 (p = 0.007) for IgE percentiles 50%, 66%, and 90%, respectively was detected. The increased risk of this haplotype was confirmed by linear haplotype trend regression on log transformed IgE values (p = 0.007). Analysis further revealed a risk haplotype for specific sensitisation and a risk haplotype for asthma. CONCLUSION: The data indicate that genetic variants within STAT6 contribute significantly to IgE regulation and manifestation of atopic diseases.

Adult↗

PubMed2003

[Atopic patch test. Atopic eczema and allergy].

The role of IgE-mediated allergic reactions in atopic eczema remains controversial. Using the atopy patch test, aeroallergens such as house dust mites, animal dander or pollen can be identified as relevant trigger factors in a subgroup of patients with atopic eczema. The atopy patch test is an epicutaneous patch test employing allergens known to elicit IgE-mediated reactions and used to evaluate eczematous skin reactions. In a series of single- and multicenter studies, a method was developed, standardized and compared to other diagnostic techniques (specific serum-IgE, skin prick test) in atopic eczema patients. With regard to clinical history, the most specific results were obtained with the atopy patch test (allergen-dependent 69-92%), while sensitivity was higher for skin prick test (69-82%) and specific IgE (65-94%). The characterization of a patient subgroup with relevant IgE-mediated allergy may lead to more efficient avoidance and perhaps even specific immunotherapy strategies in the management of atopic eczema.

Adolescent↗

PubMed2003

[MRI of prostate cancer using three different coil systems: image quality, tumor detection, and staging].

PURPOSE: To compare three MRI coil systems in terms of image quality, delineation of prostate cancer, and tumor staging. MATERIALS AND METHODS: 49 patients with prostate cancer underwent MRI at 1.5 Tesla using a combination of an endorectal coil with a phased-array body coil (combination coil) prior to radical prostatectomy. Images were reconstructed from the data sets acquired with the endorectal coil alone and from those acquired with the combined coil. In addition, 19 patients of the study patients were examined with the body phased-array coil alone without the endorectal coil. The prostate was imaged at a slice thickness of 3 mm using axial and coronal T 2 -weighted sequences and an axial T 1 -weighted sequence. Preoperative analysis of all images acquired was done to determine the accuracy of MRI in local staging of prostate cancer. An additional retrospective analysis served to compare the different coil systems in terms of overall image quality, delineation and localization of the tumor, and criteria for local staging of prostate cancer. RESULTS: Preoperative analysis showed MRI to have an accuracy of 59 % in local tumor staging. Retrospective coil-by-coil analysis demonstrated image quality and tumor delineation to be best for the combination coil and the endorectal coil. Regarding the staging criteria for transcapsular tumor extension and infiltration of adjacent organs, a significant advantage of the combination coil compared to the endorectal coil was identified only for the criterion of smooth bulging. In addition, the endorectal coil and the combination coil were found to be superior to the body phased-array coil in assessing 15 of 17 criteria for local tumor staging but the differences were not significant. CONCLUSION: In view of the achieved superior image quality, the combination coil or the endorectal coil is the preferred method for staging prostate cancer.

Aged↗

PubMed2001

Atopic eczema and allergy.

Although the pathomechanisms of respiratory atopy are well established, the role of IgE-mediated hypersensitivity in the elicitation and maintenance of eczematous skin lesions in atopic eczema (AE) is still controversial. There is, however, evidence for exogenous elicitation of AE by contact with aero- or food allergens (house dust mite, cat, and so forth). Recent investigations show that epidermal Langerhans' cells bind IgE via different receptors, especially the high-affinity receptor (Fc epsilon RI), which is significantly more strongly expressed in lesional skin of AE compared with other inflammatory skin diseases including allergic contact dermatitis. The clinical relevance of IgE-mediated sensitization in AE has been evaluated by the so-called atopy patch test (APT). The APT shows a much higher specificity compared with the skin prick test and radioallergosorbent test. However, allergic reactions do not play a decisive role in every case of AE. Other factors, such as nonspecific skin irritability or psychosomatic interactions, have to be considered. The concept of "extrinsic" versus "intrinsic" types of AE seems attractive. The concept of AE starting with TH2 inflammation, becoming TH1 inflammation in chronicity, and finally progressing to an autoimmune disease with IgE antibodies against autologous epidermal proteins is very attractive. Based on new knowledge, new methods in diagnosis, treatment, and prevention will develop, including more effective avoidance strategies, more potent anti-inflammatory treatment (e.g., immunomodulation or topical immunophyllins), and new ultraviolet modalities. The new findings have given rise to a possible new classification of eczema/dermatitis. The concept of "patient management," including all aspects from avoidance to therapy, has gained acceptance.

Animals↗

PubMed2001

Central activation by histamine-induced itch: analogies to pain processing: a correlational analysis of O-15 H2O positron emission tomography studies.

The aim of this study was to identify the functional cerebral network involved in the central processing of itch and to detect analogies and differences to previously identified cerebral activation patterns triggered by painful noxious stimuli. Repeated positron emission tomography regional cerebral blood flow (rCBF) measurements using O15-labeled water were performed in six healthy right-handed male subjects (mean age 32 +/- 2 years). Each subject underwent 12 sequential rCBF measurements. In all subjects a standardized skin prick test was performed on the right forearm 2 min before each rCBF measurement. For activation, histamine was applied in nine tests in logarithmically increasing concentrations from 0.03 to 8%. Three tests were performed with isotonic saline solution serving as a control condition. Itch intensity and unpleasantness were registered with a visual analogue scale during each test. Subtraction analysis between activation and control conditions as well as correlation analysis with covariates were performed. Itch induced a significant activation in the predominantly contralateral somatosensory cortex and in the ipsilateral and contralateral motor areas (supplementary motor area (SMA), premotor cortex, primary motor cortex). Additional significant activations were found in the prefrontal cortex and the cingulate gyrus, but not in subcortical structures nor in the secondary somatosensory cortex. In correlation analyses, several cortical areas showed a graded increase in rCBF with the logarithm of the histamine concentration (bilateral sensorimotor areas and cingulate cortex; contralateral insula, superior temporal cortex and prefrontal cortex) and with itch unpleasantness (contralateral sensorimotor cortex, prefrontal cortex and posterior insula; ipsilateral SMA). Induction of itch results in the activation of a distributed cerebral network. Itch and pain seem to share common pathways (a medial and a lateral processing pathway and a strong projection to the motor system). In contrast to pain activation studies, no subcortical (i.e. thalamic) activations were detected and correlation analyses suggest differences in subjective processing of the two sensations.

Adult↗