Ulrich Amon

Lebensqualität bei Haut- erkrankungen: Vergleich verschiedener Lebensqualitäts-Fragebögen bei Psoriasis und atopischer Dermatitis

ZusammenfassungZiel der vorliegenden Studie war der Vergleich von 4 Lebensqualitäts-(LQ)- Fragebögen bei 228 Patienten mit Psoriasis (Pso, n=148) und atopischer Dermatitis (AD, n=80) hinsichtlich praktischer Anwendbarkeit, diskriminanter Eigenschaften und Veränderungssensitivität. Untersucht wurden vor und nach stationärer Therapie: 1. Freiburger Lebensqualitätsfragebogen für Hauterkrankungen (FLQA), 2. Dermatology Life Quality Index (DLQI), 3. Marburger Hautfragebogen (MHF) und 4. Fragebogen Alltagsleben (ALLTAG). Alle Fragebögen diskriminierten signifikante Verminderungen der LQ bei Pso und bei AD im Vergleich zu Gesunden oder Vergleichsgruppen. Patienten mit AD waren meist nochmals signifikant stärker in ihrer LQ beinträchtigt. Parallel zur signifikanten Besserung der klinischen Scores fanden sich in allen Fragebögen signifikante Verbesserungen der LQ, d.h. alle Fragebögen waren verlaufssensitiv. Im DLQI und im ALLTAG gilt dies allerdings nur für einen Teil der Skalen. Auch konnten in diesen Fragebögen mehrere Skalen wegen zu vieler fehlender Antworten nicht immer berechnet werden. Ansonsten erwiesen sich alle Fragebögen als valide und einfach zu handhaben. Die LQ von Patienten mit Pso und AD kann somit mittels mehrerer Fragebögen zuverlässig erfaßt werden. Entscheidend für die Auswahl sind Studienziel und Studiendesign.SummaryAim of the present study was a comparison of four quality of life (QoL) questionnaires in 228 patients with psoriasis (PSO, n=148) and atopic dermatitis (AD, n=80) regardings feasibility, discriminant validity and sensitivity to change. Evaluating were performed before and after treatment in clinic. The following questionaires were compared. 1) Freiburg Quality of Life Assessment for Dermatoses (FLQA-d), 2) Dermatology Life Quality Index (DLQI), 3) Chronic Skin Disease Questionnaire (CSDQ) and 4) questionnaire on everyday life (ALLTAG). All questionnaires were able to discriminate significant reductions of QoL in PSO and AD, as compared to controls. In parallel to the clinical improvement, all questionnaires showed QoL improvements as well, i.e. the questionnaires were sensitive to change. However, not all of the DLQI and ALLTAG scales were sensitive to change. Also, in some cases part of the scales of these questionnaires could not be calculated due to missing data. Otherwise, all questionnaires were valid and easy to handle. Thus, QoL of patients with PSO and AD can reliably be assessed by various questionnaires. Decisive for selection are the aim and the design of the study.

German adaptation of the Skindex-29 questionnaire on quality of life in dermatology: validation and clinical results.

Background: Health-related quality of life (HRQOL) has increasingly been recognized as an important aspect of a comprehensive clinical assessment in dermatology. Objective: The aim of the present study was to translate and validate one of the most frequently used and established skin disease-specific HRQOL questionnaires originally developed in English for the German language area: the Skindex-29. Methods: 295 in-patients with psoriasis and atopic dermatitis completed the German translation of the Skindex as well as a number of additional skin disease-specific questionnaires. Data from 2 subsamples were analysed separately to test for the robustness of results. Results: Results from principal component analyses supported the scale structure of the original Skindex. Internal consistency coefficients were high for all scales. Further analyses supported the convergent validity of the German adaptation of the Skindex-29 as well as its sensitivity to change. Conclusion: The study provides evidence for the validity and reliability of the Skindex-29.

Mastocytosis – an update

Mastocytosis (MC) encompasses a range of disorders characterized by a clonal, pathological accumulation of mast cells having a somatic activating mutation of the tyrosine kinase receptor Kit (exon 17, codon 816; D816V) in more than 90 % of adult patients. The mutation is much less common in children. Skin and bone marrow are most often affected. Symptoms and clinical course are very heterogeneous due to a variable degree of local or systemic mediator release or organ dysfunction as a result of mast cell infiltrates. Pruritus, wheals, flushing and gastrointestinal symptoms are often reported. The majority of pediatric patients experience spontaneous remission of MC. Adults usually have chronic disease, rarely transforming into an aggressive or lethal type. Indolent systemic MC with involvement of skin and bone is the most common type. In MC the risk for anaphylactic reactions following an insect sting (and other causes of mast cell activation) is increased significantly. Diagnostic hallmarks are biopsies from skin and bone marrow using tryptase antibodies for staining as well as serum tryptase levels. At present a curative treatment for MC is not available. Systemic histamine H1 receptor antagonists are widely used. Aggressive types of MC respond partially to IFN‐α or cladribine. A variety of receptor tyrosine kinase inhibitors is still under critical evaluation for systemic treatment of MC. After introduction of the WHO classification for MC and the development a German MC guideline, as well as the foundation of national and international competence networks for MC, a significantly improved quality of medical care for MC patients can be expected for the future.

Effekte kombinierter therapeutischer Maßnahmen bei Patienten mit Psoriasis und atopischer Dermatitis

ZusammenfassungDie vorliegende Studie untersuchte Effekte einer kombinierten dermatologisch-verhaltenstherapeutischen stationären Therapie auf den Hautzustand und auf krankheitsspezifische Belastungen von 86 Patienten mit Psoriasis und 58 Patienten mit atopischer Dermatitis der PsoriSol-Klinik Hersbruck. Neben diagnoseorientierten dermatologischen Schulungen wurden Übungen zur Entspannung, zur sozialen Kompetenz, zur Kratzkontrolle sowie psychologische Einzelbetreuung angeboten. Der klinische Verlauf wurde durch den PASI (Psoriasis Area and Severity Index) bzw. SCORAD (Scoring of Atopic Dermatitis Index) erhoben. Als psychomotorische Meßinstrumente kamen der Marburger Hautfragebogen (MHF) und der Fragebogen zu gesundheitsbezogenen Kontrollüberzeugungen (GKÜ-S) zum Einsatz. Die Patienten wiesen im Prä-Post-Vergleich signifikante Verbesserungen hinsichtlich des Hautbefundes und psychosozialer Parameter auf. Soziale Ängste, Vermeidung und erlebte Hilflosigkeit konnten reduziert, das psychische Befinden in beiden Erkrankungsgruppen signifikant verbessert werden. Patienten mit Psoriasis zeigten zudem eine Steigerung der internalen Kontrollattributionen. Schlußfolgernd läßt sich für Patienten mit atopischer Dermatitis und Psoriasis konstatieren, daß neben einer dermatologischen Behandlung die kombinierte Anwendung verhaltenstherapeutischer Maßnahmen somatische und psychosoziale Parameter signifikant verbessert.SummaryThe present study examined the effectiveness of combined dermatological and behavioural medicine therapy on the skin status and disease-specific stress of eighty-six patients with psoriasis and fifty-eight patients with atopic dermatitis who were hospitalized in the PsoriSol Clinic, Hersbruck, Germany. In addition to receiving instruction about their stain disease, the patients were offered, practice in relaxation techniques, social contacts and scratching control as well as individual psychological counselling. The clinical change was assessed by PASI and SCORAD, respectively. The Marburg questionnaire for coping with skin diseases (MHF) and a questionnaire for health-related control attributes (GKÜ-S) served as psychometric measures. Patients showed significant improvement in skin status and psychosocial parameters in pre-post comparison. Social fears, avoidance and helplessness were reduced by significant improvement of the emotional status in both groups. Patients with psoriasis also showed an increase in internal control attributes. Dermatological treatment combined with behavioural medicine therapy can be considered an effective method in patients with atopic dermatitis and psoriasis.

Inhibition of interleukin-4 and interleukin-13 release from immunologically activated human basophils due to the actions of anti-allergic drugs.

Human basophils have recently been shown to rapidly produce and release interleukin (IL-)4 and IL-13 as well as histamine and eicosanoids. Since both IL-4 and IL-13 can initiate and maintain late phase allergic reactions we addressed whether some widely used anti-allergic drugs can inhibit the anti-IgE induced release of these cytokines from enriched human basophils. Basophils were enriched (47–92% purity) by Ficoll density centrifugation followed by elutriation and negative selection of contaminating cells using immunomagnetic beads. Basophils were stimulated with sub-optimal dilutions of anti-IgE in the presence or absence of various drugs and the release of histamine and cytokines were measured after 30 min and 4 h, respectively. The β-2 agonist salmeterol, the H1-receptor antagonist terfenadine and the phosphodiesterase inhibitor theophylline inhibited the release of IL-4 and IL-13 by more than 50% following 4 h of basophil stimulation with anti-IgE. These drugs also inhibited the release of histamine following 30 min stimulation, although with less efficacy than for IL-4 and IL-13. Short preincubation of basophils with salmeterol or terfenadine before stimulation gave rise to significantly greater inhibition of histamine release but had less effect on the inhibition of cytokine release. The effects of theophylline, however, were not significantly affected by preincubation of the cells with the drug. In contrast to the aforementioned drugs, salbutamol and cetirizine were ineffective at inhibiting both histamine and cytokine release from basophils. These results suggest that a number of anti-allergic drugs may mediate their effects, in part, in reducing late phase allergic responses due to their actions on IL-4 and IL-13 secretion from basophils.

In vitro investigations with the histamine H1 receptor antagonist, epinastine (WAL 801 CL), on isolated human allergic effector cells.

Abstract.Objective and Design: Skin mast cells, basophils and eosinophils are effector cells of acute and subacute allergic responses due to their capacity to produce a large number of (pro)inflammatory mediators. Histamine H1 receptor antagonists, such as epinastine (WAL 801 CL), have been described to partially exert antiallergic and anti-inflammatory effects both in vivo and in vitro in addition to their antihistaminergic properties. The aim of the present study was to investigate whether epinastine could influence the in vitro activation of isolated human skin mast cells, basophils and eosinophils induced by different secretagogues.¶Methods: Cells were isolated from healthy women following plastic surgery and healthy blood donors, respectively. Mast cells were isolated by enzymatic digestion of the skin. Blood cells were isolated by gradient centrifugation and negative selection with magnetic beads.¶Results: A wide range of concentrations of the drug (1 nmol/l to 100 mmol/l) did not significantly inhibit histamine release from basophils induced by immunologic (anti-IgE, concanavalin A, priming factors interleukin-3 and interleukin-5) and non immunologic (A23187, ionomycin, 12-o-tetradecanoyl-phorbol-13-acetate, C5a, formyl-methionyl-leucyl-phenylalanine) stimuli. Furthermore, the drug had no effect on A23187-induced release of eosinophil cationic protein from eosinophils. However, at a concentration >0.1nmol/l, IgE-mediated LTC4 production from basophils was significantly suppressed. Histamine release from skin mast cells due to anti-IgE or A23187 was inhibited by epinastine in a dose-dependent fashion, whereas substance P-induced activation as well as stem cell factor priming were not. Epinastine did not inhibit isolated protein kinase C from rat brain.¶Conclusion: The results confirm previous in vivo and in vitro observations obtained from animal models that epinastine exerts antiallergic and antiinflammatory effects. Whether the observed effects are due to non specific membrane interactions or by influencing intracellular signal transduction elements has to be further elucidated.

A THREE-STEP PROCEDURE FOR THE PURIFICATION OF HUMAN BASOPHILS FROM BUFFY COAT BLOOD

Abstract.Objective and Design: We report a method for basophil purification from buffy coats, which avoids positive selection of the cells and gives rise to good purity, yield and functional integrity of the cells.¶Subjects: Buffy coat blood (concentrated leukocyte fraction derived from 450 ml venipuncture donations) obtained from healthy blood donors (n = 51).¶Methods: Basophils were enriched by a three-step process starting with Ficoll density centrifugation (1.6 ± 0.1% basophil purity) followed by counter current centrifugal elutriation (17.7 ± 1.4% basophil purity). The final stage involved negative selection using Dynal immunomagnetic beads directed against CD2, CD14, CD16 and CD19 positive cell contaminants. Functional integrity of which was assessed by comparing the anti-IgE or calcium ionophore A23187 induced histamine release from basophils obtained from each enrichment step. Furthermore, basophil morphology was investigated using light and electron microscopy.¶Results: The final mean basophil purity of 67.3 ± 1.4% with a yield of 3.5 ± 0.5 × 106 basophils and a recovery of 21.8 ± 2.4% was achieved. Net histamine release from basophils stimulated with optimal concentrations of anti-human IgE was 39.1 ± 6.5% after Ficoll centrifugation, 41.6 ± 7.7% following elutriation and 35.7 ± 6.8% from the final purified fraction. Additionally, basophils enriched with our method showed intact morphology by electron microscopy and were functionally active to non-immunological stimulation.¶Conclusions: These results compare favourably with previous studies, which have often required the use of positive selection via the FcRI receptor, which may result in cell degranulation, or cell sorting, which cannot be applied to large cell numbers. Our method provides a reproducible technique for basophil enrichment when large numbers of functionally intact basophils are required.

Enteral histaminosis: Clinical implications

Abstract. There is increasing evidence that enteral histaminosis is a major cause of food intolerance resulting from dysfunctional metabolism of endogenous histamine in certain food stuffs. However, this phenomenon has been poorly characterised and, due to the lack of epidemiological data, the existence of this condition has been underestimated, which may lead to incorrect diagnosis. This short commentary highlights a stricter regimen of diagnostic procedure in order to take into account the many causes of food intolerance. The underlying mechanisms ascribed particularly to non-immunologically food reactions require more rigorous research and further work is vital.

Cutaneous infection with Leishmania infantum in an infant treated successfully with miltefosine

A two‐year‐old girl presented with a 20 month history of a facial nodule which had appeared after a vacation on Mallorca. Various topical treatments at other hospitals for the working diagnosis of mastocytoma failed to prevent a slow increase in size and the onset of systemic signs and symptoms. An indurated crusted nodule evolved. Histology, tissue PCR and serologic analysis proved the presence of Leishmania infantum. She was treated with oral miltefosine 10 mg p.o. t.i.d. for 28 days. Regression was apparent after 8 weeks and complete healing after 6 months.

Relationship between basophil chemotaxis and histamine releasability to immunological stimulation.

A striking feature of allergic and inflammatory diseases is the accumulation of activated basophils in the tissue. Since basophils only make up a small proportion of the total blood leukocyte count, this accumulation is thought to involve selective processes including rolling along the endothelium, attachment to the endothelial cells, cell activation, adhesion and transmigration [1]. Chemotaxis of the cells into the tissue is directed along a concentration gradient of chemoattractants. Several mediators have been described which have a chemotactic effect on basophils. These include NAP-1, GRO-a, -b, -g of the C-X-C subfamily of chemokines, RANTES, MCP-1, -2, -3, MIP-1 a and FIC of the C-C subfamily and other cytokines (IL-3, -5, GM-CSF) as well as non-selective substances such as PAF, C5a and FMLP [1, 2]. RANTES has not only been shown to be an effective chemoattractant for basophils but can also directly induce histamine release from these cells [3]. Since the accumulation of basophils at the site of inflammation is a typical feature of IgE-mediated diseases our aim was to discover whether there is a relationship between basophil migration and their ability to release histamine following Fc eRI crosslinking.