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Alexander Kapp

Publications and source records attributed to Alexander Kapp.

At least 19 recordsLinked to original sources
PubMed2007

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

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

Adolescent↗
PubMed2006

Proceedings of the 4th Georg Rajka International Symposium on Atopic Dermatitis, Arcachon, France, September 15-17, 2005.

The 4th Georg Rajka International Symposium on Atopic Dermatitis presented a comprehensive view of our current understanding and management of atopic dermatitis (AD). These proceedings highlight contributions related to the history of AD doctrines; genetic and epigenetic background; epidemiology; maturation of the immune system; infection and innate-adaptive immunity; epidermal inflammation, including neurogenic inflammation and pruritus; animal models; skin barrier; evidence-based therapy and education programs; prognostic and severity markers; and allergy testing. Several studies in animal models and human subjects point to impaired skin barrier function as a primary defect that facilitates the effect of environmental factors and immune dysregulation found in AD. The new frontier in AD therapy should, in the near future, reflect our better understanding of the skin barrier. The influence of environmental factors on the skin and other epithelial barriers in the perinatal period needs to be better understood to implement appropriate prevention programs.

Animals↗
PubMed2006

Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/American Academy of Allergy, Asthma and Immunology/PRACTALL Consensus Report.

There are remarkable differences in the diagnostic and therapeutic management of atopic dermatitis practiced by dermatologists and pediatricians in different countries. Therefore, the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology nominated expert teams who were given the task of finding a consensus to serve as a guideline for clinical practice in Europe as well as in North America. The consensus report is part of the PRACTALL initiative, which is endorsed by both academies.

Adult↗
PubMed2006

Efficacy and safety of sublingual immunotherapy with grass allergen tablets for seasonal allergic rhinoconjunctivitis.

BACKGROUND: Allergen immunotherapy (desensitization) by injection is effective for seasonal allergic rhinitis and has been shown to induce long-term disease remission. The sublingual route also has potential, although definitive evidence from large randomized controlled trials has been lacking. OBJECTIVE: The aim was to confirm the efficacy of a rapidly dissolving grass allergen tablet (GRAZAX, ALK-Abelló, Hørsholm, Denmark) compared with placebo in patients with seasonal rhinoconjunctivitis. METHODS: A longitudinal, double-blind, placebo-controlled, parallel-group study that included 51 centers from 8 countries. Subjects were randomized (1:1) to receive a grass allergen tablet or placebo once daily. A total of 634 subjects with a history of grass pollen-induced rhinoconjunctivitis for at least 2 years and confirmation of IgE sensitivity (positive skin prick test and serum-specific IgE) were included in the study. Subjects commenced treatment at least 16 weeks before the grass pollen season, and treatment was continued throughout the entire season. RESULTS: The primary efficacy analysis showed a reduction of 30% in rhinoconjunctivitis symptom score (P < .0001) and a reduction of 38% in rhinoconjunctivitis medication score (P < .0001) compared with placebo. Side effects mainly comprised mild itching and swelling in the mouth that was in general well tolerated and led to treatment withdrawal in less than 4% of participants. There were no serious local side effects and no severe systemic adverse events. CONCLUSION: Sublingual immunotherapy with grass allergen tablets was effective in grass pollen-induced rhinoconjunctivitis. The tablet was well tolerated with minor local side effects. CLINICAL IMPLICATIONS: The grass allergen tablet represents a safe alternative to injection immunotherapy suitable for home use.

Administration, Sublingual↗
PubMed2006

Levocetirizine is an effective treatment in patients suffering from chronic idiopathic urticaria: a randomized, double-blind, placebo-controlled, parallel, multicenter study.

BACKGROUND: Chronic idiopathic urticaria (CIU) is defined by the almost daily presence of urticaria for at least 6 weeks without an identifiable cause. Symptoms include short-lived wheals, itching, and erythema. CIU impedes significantly a patient's quality of life (QoL). Levocetirizine is an antihistamine from the latest generation approved for CIU. AIM: To investigate the efficacy of levocetirizine, 5 mg, and placebo for the symptoms and signs of CIU, as well as for the QoL and productivity. METHODS: The primary criteria of evaluation were the pruritus severity scores over 1 week of treatment and over 4 weeks. The QoL was assessed via the Dermatology Life Quality Index (DLQI). RESULTS: Baseline pruritus severity scores were comparable in the two treatment groups (2.06+/-0.58). After 1 week, levocetirizine was superior to placebo and demonstrated a considerable efficacy (difference=0.78, P<0.001). This efficacy was maintained over the entire study period (4 weeks, P<0.001). The number and size of wheals were considerably reduced compared with placebo over 1 week and over the total treatment period (P <or= 0.001). This was paralleled by an improvement in the QoL (DLQI: 7.3 units in the levocetirizine group and 2.4 units in the placebo group) and a higher productivity at work in the levocetirizine group (3.0 workdays lost per patient per month in the placebo group, 0.3 in the levocetirizine group). No unexpected adverse events occurred. CONCLUSIONS: Levocetirizine, 5 mg once daily, is an effective treatment for CIU, characterized not only by a rapid and sustained response, but also by an important improvement in QoL.

Adult↗
PubMed2006

Allergic manifestations of skin diseases--atopic dermatitis.

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

Allergens↗
PubMed2006

Cost effectiveness of levocetirizine in chronic idiopathic urticaria : a pooled analysis of two randomised controlled trials.

BACKGROUND: Chronic idiopathic urticaria is a distressing condition that severely affects patients' quality of life. The overall costs associated with this disease, both for the healthcare payer and society, are unknown. The objective of this study was to evaluate the cost effectiveness of levocetirizine, a first-line treatment for urticaria. METHODS: Data were collected from two placebo-controlled trials and from official French databases. The effectiveness of the treatment was assessed by the mean number of pruritus-free days experienced by the patient within a 30-day period (PFD30). Direct cost parameters were medications used, medical procedures and hospitalisations for urticaria or treatment of adverse events. Productivity cost parameters were the workdays lost, defined as absenteeism and/or presenteeism, resulting from urticaria. The costing was performed using a French societal perspective. Costs were reported in euro (2002 values) and were standardised to a 30-day month. Whenever possible, incremental cost-effectiveness ratios (ICERs) were derived from these data. RESULTS: The pooled sample contained 294 patients. Compared with placebo, patients in the levocetirizine group experienced an additional mean 6.5 (95% CI 3.8, 9.3) pruritus-free days per month (p < 0.001). Considering only direct medical costs, the incremental cost of treatment with levocetirizine was totally offset by the reduction in other medical costs (i.e. reduced cost of additional medications, medical procedures and hospitalisations). From the perspective of society, treatment with levocetirizine was cost saving, with a net gain of Euro 91.93 per patient per month. CONCLUSION: Treating chronic idiopathic urticaria with levocetirizine is a dominant strategy for society since it is more effective (in terms of pruritus-free days gained) and less costly than placebo.

Adult↗
PubMed2005

Cloning, expression, and functional characterization of cynomolgus monkey (Macaca fascicularis) CC chemokine receptor 1.

The CC chemokine receptor 1 (CCR1) has emerged as a relevant factor contributing to inflammatory diseases such as allergic asthma. Commonly used animal models of allergic airway inflammation, especially murine models, have certain limitations. The elaborate, nonhuman, primate models of asthma display the highest comparability with the situation in humans. These models play an important role in the understanding of the pathogenesis of asthma. To improve the understanding in cynomolgus monkey models, we identified and characterized CCR1 in this nonhuman primate. Initially, we cloned the cynomolgus monkey CCR1 (cCCR1) gene, and the sequence analysis revealed high homology at the nucleotide (92%) and amino acid (88.4%) levels with its human counterpart. Human embryonic kidney 293 cells were stably transfected with cCCR1 and used in functional assays. Among those CCR1 ligands tested, CCL14(9-74) was most potent in the induction of intracellular Ca2+ fluxes as observed for human CCR1 (hCCR1). Complete cross-desensitization could be achieved between CCL14(9-74) and CCL15. However, CCL3 could not fully abrogate the response to the potent ligand CCL14(9-74). Competition-binding studies with radiolabeled CCL3 concordantly showed that CCL14(9-74) has a higher affinity to cCCR1 than hCCL3. Moreover, differential tissue-specific expression of cCCR1 was investigated by real-time quantitative polymerase chain reaction, displaying the highest levels in spleen. This study adds basic information needed for the evaluation of the role of CCR1 in the pathophysiology of asthma using the highly relevant cynomolgus monkey model and in addition, aids in the preclinical evaluation of potential novel drugs targeting CCR1.

Amino Acid Sequence↗
PubMed2005

Brain-derived neurotrophic factor is increased in atopic dermatitis and modulates eosinophil functions compared with that seen in nonatopic subjects.

BACKGROUND: Recently, the pivotal role of brain-derived neurotrophic factor (BDNF) has been described in allergic asthma. However, the role of this neurotrophin in atopic dermatitis (AD) still remains unknown. OBJECTIVE: The aim of this study was to investigate the functional role of BDNF on eosinophils and to assess BDNF levels in patients with AD and nonatopic control subjects. Methods p75 Neurotrophin receptor and tyrosine kinase B receptor expression was demonstrated by using FACS analysis and immunohistochemistry. BDNF levels were assessed with ELISA and FACS analysis. Chemotactic activity (modified Boyden chamber assay), eosinophil cationic protein release (fluoroenzyme immunoassay), respiratory burst (lucigenin-dependent chemiluminescence), and apoptosis (Nicoletti protocol and Annexin-V method) assays were used to assess BDNF functional activity. RESULTS: BDNF levels were increased in serum, plasma, eosinophils, and supernatants of stimulated eosinophils from patients with AD compared with levels seen in nonatopic control subjects ( P < .05-.001). In addition, p75 neurotrophin receptor and tyrosine kinase B expression was higher on eosinophils from patients with AD compared with that seen on eosinophils from nonatopic control subjects ( P < .05-.001). Eosinophil apoptosis was inhibited by BDNF ( P < .05-.01) and chemotactic index was increased ( P < .001) in BDNF-stimulated eosinophils from patients with AD, whereas this effect was not shown in eosinophils from nonatopic control subjects. However, no response of BDNF through the release of eosinophil cationic protein or reactive oxygen species was found. CONCLUSION: This study provides the first evidence for a functional role of BDNF on eosinophils from patients with AD, probably mediated by an increased expression of BDNF receptors compared with that seen in nonatopic control subjects. In addition, higher intracellular, serum, and plasma BDNF levels, as well as the release of BDNF by eosinophils, underline the particular importance of BDNF in patients with AD, pointing to new pathophysiologic aspects of this chronic inflammatory skin disease.

Apoptosis↗
PubMed2005

Neuroimmunological findings in allergic skin diseases.

PURPOSE OF REVIEW: Recent studies have gained widespread information about the complex regulation of genetic, environmental, immunologic, and pharmacologic factors that contribute to the development of allergic inflammatory skin diseases such as atopic dermatitis. Neuroimmune mechanisms, however, still remain to be elucidated. This review will focus on the interaction between the cutaneous immune and peripheral nervous system in allergic inflammatory skin such as atopic dermatitis. RECENT FINDINGS: Neuropeptides and neuropeptide-positive nerve fibres are prominently increased in lesions of atopic dermatitis. The density of nerve fibres is increased while peripheral nerve endings are in an active state of excitation. In this regard, neurotrophins particularly described for their functional role on nerve cells are also expressed in atopic dermatitis skin. In addition, neurotrophins modulate the functional role of eosinophils as main target effector cells in atopic dermatitis, as described recently. Interestingly, eosinophils are capable of neurotrophin as well as neuropeptide production itself, pointing to a bidirectional communication between neuronal cell populations and main target effector cells. SUMMARY: Neurotrophins and neuropeptides modulate both the functional activity of sensory neurons and immune cells. We have therefore developed the concept of a neuroimmune network between target effector cells and sensory nerves that links pathogenic events to dysfunctions of the cutaneous immune and peripheral nervous system in allergic inflammatory skin diseases.

Humans↗
PubMed2005

Immunomodulation and safety of topical calcineurin inhibitors for the treatment of atopic dermatitis.

Atopic dermatitis (AD) is a chronic or chronically relapsing inflammatory skin condition that primarily affects children. Topical corticosteroids have been the mainstay of treatment since the late 1950s. While providing excellent short-term efficacy, topical corticosteroid usage is limited by potential adverse effects, including impairment of the function and viability of Langerhans cells/dendritic cells. The recently introduced topical calcineurin inhibitors pimecrolimus cream 1% (Elidel) and tacrolimus ointment 0.03 and 0.1% (Protopic) exhibit a more selective mechanism of action and do not affect Langerhans cells/dendritic cells. For the immune system of young children 'learning' to mount a balanced Th1/Th2 response, this selective effect has particular benefits. In clinical experience, topical calcineurin inhibitors have been shown to be a safe and effective alternative to topical corticosteroids in almost 7 million patients (>5 million on pimecrolimus; >1.7 million on tacrolimus). Topical pimecrolimus is primarily used in children with mild and moderate AD, whereas tacrolimus is used preferentially in more severe cases. None of the topical calcineurin inhibitors have been associated with systemic immunosuppression-related malignancies known to occur following long-term sustained systemic immunosuppression with oral immunosuppressants (e.g., tacrolimus, cyclosporine A, and corticosteroids) in transplant patients. Preclinical and clinical data suggest a greater skin selectivity and larger safety margin for topical pimecrolimus.

Administration, Topical↗
PubMed2005

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

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

Administration, Topical↗
PubMed2004

Cell-to-cell contact between activated CD4+ T lymphocytes and unprimed monocytes interferes with a TH1 response.

BACKGROUND: The production of IL-12 by monocytes and dendritic cells is tightly regulated and critically dependent on signals from surrounding cells in the micromilieu. OBJECTIVE: We studied the capacity of T cells to regulate directly the production of IL-12 by human monocytes. METHODS: Human isolated CD4 + T cells from peripheral blood and T cells from acute patch test lesions were cocultured with autologous monocytes. IL-12 expression and production were measured, and intracellular signal transduction pathways were studied. Monocytes, which had been cocultured with activated T cells, were further investigated for their capacity to induce TH1-directed responses. RESULTS: A marked inhibition of IL-12 production was observable on coculture of monocytes with isolated CD4 + activated autologous T lymphocytes derived from blood or from acute eczematous skin lesions. The inhibiting effect of activated T lymphocytes on IL-12 production was dependent on cell-to-cell contact to monocytes but not on their ability to secrete soluble mediators. Experiments performed in the presence of mitogen-activated protein kinase kinase 1/2 inhibitors provided evidence that activation of the p44/42 pathway plays an important role for the inhibition of IL-12 production in monocytes (here referred to as IL-12 low monocytes). In addition, T cells cocultured with IL-12 low monocytes showed a markedly lower expression of the TH1 specific transcription factor T-bet, IFN-gamma, and IL-12Rbeta2 cell surface expression. CONCLUSION: Activated T lymphocytes may directly contribute to the TH2-like cytokine milieu found at sites of allergic inflammation (eg, in acute eczematous skin lesions) by inhibiting IL-12 production of unprimed antigen-presenting cells.

Antigen-Presenting Cells↗
PubMed2004

Comparison of localized high-dose UVA1 irradiation versus topical cream psoralen-UVA for treatment of chronic vesicular dyshidrotic eczema.

BACKGROUND: Vesicular dyshidrotic palmoplantar eczema is a common disorder but treatment is difficult. Localized photochemotherapy (cream psoralen-UVA [PUVA]) has widely been used for therapy. Although the efficacy of cream PUVA therapy is well known, potential side effects may occur. Therefore, a more standardized safe and effective UV therapy should be carried out. OBJECTIVE: This study compared the effects of localized high-dose UVA1 irradiation versus topical cream PUVA for treatment of chronic vesicular dyshidrotic eczema. METHODS: On the basis of the assessment of the Dyshidrotic Area and Severity Index, the decrease of score points on the UVA1-treated side was compared with the decrease on the cream PUVA-treated side in 27 patients. In addition, analysis of serum markers was performed. RESULTS: Of 27 patients, 24 showed a good response to localized UVA1 irradiation or cream PUVA. Dyshidrotic Area and Severity Index scores significantly decreased on both sides and were reduced to half of the pretreatment values. No statistically significant differences between localized UVA1 irradiation or cream PUVA could be detected. CONCLUSION: This study demonstrates that localized UVA1 phototherapy is easy to perform and appears to be an effective and safe treatment for vesicular dyshidrotic eczema.

Administration, Topical↗