Hae-Hyuk Lee

Cutaneous side-effects in patients with rheumatic diseases during application of tumour necrosis factor-α antagonists

Background  Patients with rheumatic diseases receiving antitumour necrosis factor (TNF)‐α‐based treatment may develop cutaneous reactions.

Development and preliminary clinical evaluation of a peptide immunotherapy vaccine for cat allergy

BACKGROUND Allergic sensitization to cat allergens is common and represents a major risk factor for asthma. Specific immunotherapy (SIT) is effective but cumbersome and associated with IgE-dependent adverse events. Immunotherapy targeting allergen-specific T cells, with synthetic peptides representing T-cell epitopes, might improve safety and reduce the duration of treatment. OBJECTIVE We sought to define major T-cell epitopes of Fel d 1 for peptide immunotherapy, generate a peptide vaccine, and evaluate its safety and tolerability in subjects with cat allergy. METHODS We determined the binding affinities of Fel d 1 peptides for 10 commonly expressed HLA-DR molecules. Functionally immunodominant peptides were identified by means of proliferation and cytokine secretion. Histamine-releasing activity was assessed, and a peptide vaccine was formulated. Safety and tolerability were evaluated in a dose-ranging phase IIa clinical trial. RESULTS MHC-binding sequences were identified throughout Fel d 1. Some regions contained multiple overlapping T-cell epitopes that bound multiple MHC molecules. Immunodominant sequences were identified on the basis of proliferative and cytokine (IFN-γ, IL-10, and IL-13) responses. Cat allergen extract, but not peptides, induced histamine release in blood basophils. A single administration of peptide vaccine was safe and well tolerated. The dose of vaccine resulting in the greatest inhibition of the late-phase skin response to intradermal whole allergen challenge was 3 nmol. CONCLUSIONS Fel d 1 contains multiple overlapping MHC-binding motifs. A peptide vaccine comprising the immunodominant regions of the allergen was safe and well tolerated when given to subjects with cat allergy as a single dose. The dose of vaccine resulting in the greatest reduction in late-phase skin response was defined for future clinical development.

Evidence for a restricted rather than generalized stimulatory response of skin-derived human mast cells to substance P

To resolve the controversy regarding substance P (SP) mediated stimulation of mast cells (MC), we demonstrate that SP triggers histamine release from purified human skin MC (sMC), but contrast to stimulation via FcepsilonRI, does not effect the production of TNF-alpha or IL-8. Conversely, both anti-IgE and SP are suppressive in terms of IL-6. By quantitative RT-PCR, the amount of templates at baseline (per 25 ng total RNA) is 2178 (IL-6), 2,665 (IL-8) and 94 (TNF-alpha), and remains unaltered by SP. Contrast to sMC, LAD2 MC respond to SP with stronger histamine release and robust TNF-alpha production in an only partially neurokinin-1R mediated manner, while histamine release of sMC is chiefly mediated by this receptor. We conclude that human sMC are responsive to SP in a selective manner by eliciting degranulation without the induction of cytokines and that SP-triggered cytokine production varies among MC subtypes, likely through differences in signaling mechanisms.

Frequency of atopic dermatitis and relevance of food allergy in adults in Germany.

Many factors may aggravate atopic dermatitis. The aim of this study was to determine the frequency of atopic dermatitis in an unselected population sample and to evaluate the role of food allergy. Patients with atopic dermatitis were recruited from the population in Berlin, Germany, using a postal questionnaire. Skin prick tests for allergens were performed, followed by food challenges. A total of 1739 questionnaires was returned. In all, 23.5% of patients stated that they had atopic dermatitis, and 146 persons (8.4%) fulfilled our atopic dermatitis criteria after a detailed telephone interview. Of these, 111 were examined, and 28 (1.6%) were identified as currently suffering from atopic dermatitis. Twenty-seven patients were further evaluated: 9/27 were found to be skin prick test negative, 19/27 were skin prick test positive either to pollen and/or food allergens. Nine of 27 were challenged with the suspected food allergen: 1/9 showed a worsening of the eczema, 3/9 had oral symptoms, and 5/9 were negative. In conclusion, only 20% of adults with a positive history of atopic dermatitis show active eczema lesions at a given time point. The data indicate that most individuals with atopic dermatitis were sensitized against pollen allergens and according to that, pollen-associated food allergens. A non-selected AD patient cohort does not frequently suffer from clinically relevant pollen-associated food allergy.

Prevalence and treatment profile of patients with grass pollen and house dust mite allergy.

In Europe, grass pollen and house dust mites are the most common allergens responsible for IgE‐mediated allergies. The aim of our study was to examine the data provided by various medical practices specialized in allergic diseases in Germany regarding patients with rhinoconjunctivitis in terms of demographic data and the prescribed treatment by different medical specialists.

Prospective safety analysis of an ultrarush specific immunotherapy in adults with wasp venom allergy

Sublingual immunotherapy for allergic rhinitis: systematic review and metaanalysis. Allergy 2005;60:4–12. 4. Gidaro GB, Marcucci F, Sensi L, Incorvaia C, Frati F, Ciprandi G. The safety of sublingual-swallow immunotherapy: an analysis of published studies. Clin Exp Allergy 2005;35:1407– 1408. 5. Bousquet J. Sublingual immunotherapy: from proven prevention to putative rapid relief of allergic symptoms. Allergy 2005;60:1–3. 6. Rolinck-Werninghaus C, Wolf H, Liebke C, Baars JC, Lange J, Kopp MV et al. A prospective, randomized, double-blind, placebo-controlled multi-centre study on the efficacy and safety of sublingual immunotherapy (SLIT) in children with seasonal allergic rhinoconjuntivitis to grass pollen. Allergy 2004;59:1285–1293.

Sicherheit der spezifischen Immuntherapie

ZusammenfassungDie Erfassung unerwünschter Wirkungen im Rahmen der spezifischen Immuntherapie ist ein wichtiger Aspekt zum Schutz der Patienten. Die Identifizierung möglicher Risikofaktoren oder eines Patientenkollektivs mit erhöhtem Risiko sorgt für eine verbesserte Sicherheit und dient der ständigen Aktualisierung von Leitlinien. Vorliegende Daten zur Sicherheit der spezifischen Immuntherapie zeigen, dass bei der subkutanen Immuntherapie die Rate von schweren oder tödlichen Nebenwirkungen in den letzten 20 Jahren stetig zurückgegangen ist. Die sublinguale Immuntherapie ist mit einem geringeren Risiko von systemischen Reaktionen behaftet, die aber auch hier nicht vollständig auszuschließen sind, wie erste Einzelfallberichte zeigen. Weitere Daten zur Sicherheit der spezifischen Immuntherapie sind auch zukünftig für eine angemessene Nutzen-Risiko-Abwägung wichtig und notwendig.SummaryPharmacovigilance is important for the safety of patients. The identification of risk factors for severe adverse reactions or of patient groups at substantial risk of experiencing side effects allows an improvement of treatment modalities and the continuous update of guidelines. Data on the safety of subcutaneous immunotherapy shows a reduction of the rate of serious or life-threatening side effects over the last 20 years. In case of sublingual immunotherapy, life-threatening systemic side effects are generally not expected. However, recently published case reports demonstrate the possibility of anaphylactic reactions also during sublingual immunotherapy. Further data on the safety of specific immunotherapy is still needed to perform an optimal risk-benefit assessment.

Aktuelle Empfehlungen zur praktischen Durchführung von SCIT und SLIT

ZusammenfassungDie spezifische Immuntherapie mit Allergenen (SIT) gilt als wichtigste kausale Behandlungsform Typ-1-allergischer Erkrankungen. Für ihren erfolgreichen Einsatz müssen vor und während der Therapie zahlreiche Voraussetzungen geprüft werden. Die Aufklärung der Patienten sollte vor Beginn der Therapie unter Berücksichtigung sämtlicher Indikationen und Kontraindikationen schriftlich dokumentiert werden. Die SIT wird von erfahrenen Allergologen indiziert und von Ärzten mit Erfahrung in dieser Therapie durchgeführt, die zur Notfallbehandlung befähigt sind. Die Applikationsform der Allergene, die Allergenextrakte und die Behandlungsdauer werden von den klinischen Symptomen und dem Alter der Patienten bestimmt. Aufgrund zahlreicher verfügbarer Produkte und verschiedener Applikationsprotokolle ist eine patientenadaptierte Therapie möglich.AbstractAllergen specific immunotherapy (SIT) is the only potentially curative treatment of IgE mediated allergic diseases. To ensure its effective use, many requirements must be met before and during therapy. Before starting immunotherapy, informed consent should be obtained, along with the consideration of the indications and contraindications. SIT should be prescribed and administered only by physicians with experience in allergic disease who are qualified to manage severe anaphylactic reactions. The clinical symptoms and the age of the patients determine the route of application, choice of allergen extracts and the duration of treatment. Numerous products and protocols facilitate an individualised therapy.

Current recommendations for the use of SCIT and SLIT

ZusammenfassungDie spezifische Immuntherapie mit Allergenen (SIT) gilt als wichtigste kausale Behandlungsform Typ-1-allergischer Erkrankungen. Für ihren erfolgreichen Einsatz müssen vor und während der Therapie zahlreiche Voraussetzungen geprüft werden. Die Aufklärung der Patienten sollte vor Beginn der Therapie unter Berücksichtigung sämtlicher Indikationen und Kontraindikationen schriftlich dokumentiert werden. Die SIT wird von erfahrenen Allergologen indiziert und von Ärzten mit Erfahrung in dieser Therapie durchgeführt, die zur Notfallbehandlung befähigt sind. Die Applikationsform der Allergene, die Allergenextrakte und die Behandlungsdauer werden von den klinischen Symptomen und dem Alter der Patienten bestimmt. Aufgrund zahlreicher verfügbarer Produkte und verschiedener Applikationsprotokolle ist eine patientenadaptierte Therapie möglich.AbstractAllergen specific immunotherapy (SIT) is the only potentially curative treatment of IgE mediated allergic diseases. To ensure its effective use, many requirements must be met before and during therapy. Before starting immunotherapy, informed consent should be obtained, along with the consideration of the indications and contraindications. SIT should be prescribed and administered only by physicians with experience in allergic disease who are qualified to manage severe anaphylactic reactions. The clinical symptoms and the age of the patients determine the route of application, choice of allergen extracts and the duration of treatment. Numerous products and protocols facilitate an individualised therapy.

Wirksamkeit von Tacrolimus-0,1-%-Salbe bei Prurigoerkrankungen. Efficacy of tacrolimus 0.1 % ointment in prurigo

Hintergrund: Hochpotente topische Steroide werden zur Behandlung des quälenden Juckreizes bei Prurigoerkrankungen eingesetzt. Dies führt bei langfristiger Anwendungsdauer zum Auftreten von lokalen Nebenwirkungen an der Haut wie Atrophie und Teleangiektasien.