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Die spezifische Immuntherapie ist bei einer Hymenopterengiftallergie eine sehr wirksame und sehr gut vertragliche Therapieoption. Zahlreiche Patienten konnen mit oft nur geringen Nebenwirkungen erfolgreich behandelt werden. Meist treten bei Therapieeinleitung lediglich Schwellungen im Bereich der Injektionen auf, systemische Reaktionen sind selten. Fur die Kontrolle des Therapieansprechens sind bisher keine zuverlassigen Laborparameter bekannt. Eine Identifikation von Therapieversagern kann durch die Durchfuhrung einer Stichprovokation mit einem lebenden Insekt uberpruft werden, bei fehlendem Schutz erfolgen eine Erhohung der Behandlungsdosis und im Verlauf eine erneute Stichprovokation. Dies ist fur die Mehrzahl der Patienten ein bewahrtes Therapiekonzept. In einzelnen Fallen jedoch kann es u. a. aufgrund von individuellen Risikofaktoren zum Auftreten von schweren Anaphylaxien bereits wahrend der Einleitungsphase kommen. In der Vergangenheit fuhrte dies nicht selten zum Therapieabbruch. Durch Verfugbarkeit des fur andere Indikationen zugelassenen Omalizumab steht hier eine zusatzliche Therapieoption zur Verfugung, die seit 2005 auch in unserer Universitats-Hautklinik erfolgreich eingesetzt wird. In dem vorliegenden Beitrag soll neben den eigenen Erfahrungen auch auf aktuelle Daten eingegangen werden, um fur die Zukunft ein mogliches Vorgehen bei Durchfuhrung einer spezifischen Immuntherapie der Hymenopterengiftallergie bei besonderen Risikopatienten zu diskutieren.

ZusammenfassungHintergrund Organtransplantierte Patienten entwickeln vermehrt nicht-melanozytare Hauttumoren. Aufgrund des multiplen Auftretens und aggressiven Wachstumsverhaltens stellt die chirurgische Therapie oftmals eine Herausforderung dar. Die Umstellung der immunsuppressiven Therapie auf einen mTOR-Inhibitor kann eine antitumorale Wirkung haben. Patienten und Methodik In einer monozentrischen retrospektiven Erhebung wurden im Zeitraum von 2008 bis 2010 organtransplantierte Patienten erfasst, die sich aufgrund von nicht-melanozytaren Hauttumoren vorgestellt hatten. Erfahrungen mit Patienten, die aufgrund von nicht-melanozytaren Hauttumoren auf eine Therapie mit einem mTOR-Inhibitor umgestellt wurden, werden detailliert dargestellt und aktuelle Studiendaten dazu zusammengefasst. Ergebnisse Insgesamt wurden 60 organtransplantierte Patienten mit nicht-melanozytaren Hauttumoren erfasst. Aufgrund der Entwicklung von vielen nicht-melanozytaren Hauttumoren innerhalb weniger Jahre wurde die systemische immunsuppressive Therapie bei 7 Patienten auf Everolimus und bei 5 Patienten auf Sirolimus umgestellt. Acht Patienten konnten hinsichtlich der Anzahl neu entstehender nicht-melanozytarer Hauttumoren nach Umstellung ausgewertet werden, 4 Patienten mussten die neue immunsuppressive Therapie aufgrund verschiedener Nebenwirkungen wieder absetzen. In den 12 Monaten vor Umstellung der Immunsuppression entwickelten die 8 Patienten histologisch gesichert 16 Plattenepithelkarzinome, 3 Basalzellkarzinome und 22 Morbus Bowen. In den 12 Monaten nach Umstellung auf einen mTOR-Inhibitor war die Zahl der Plattenepithelkarzinome (n = 2) und der Morbus Bowen (n = 3), nicht jedoch die der Basalzellkarzinome (n = 2) signifikant reduziert. Auch 5 kurzlich publizierte prospektiv-randomisierte Studien konnten ein vermindertes Auftreten nicht-melanozytarer Hauttumoren nach Umstellung der immunsuppressiven Therapie auf einen mTOR-Inhibitor bei organtransplantierten Patienten zeigen. Schlussfolgerung Eine Umstellung der immunsuppressiven Therapie auf einen mTOR-Inhibitor sollte bei organtransplantierten Patienten mit nicht-melanozytaren Hauttumoren diskutiert werden.

SummaryBackground Organ transplant recipients are prone to the development of non-melanoma skin cancer. Organ transplant recipients often develop multiple non-melanoma skin cancers and the tumors show an aggressive growth pattern, therefore surgical therapy can be difficult. Switch of the immunosuppressive regimen to mTOR-inhibitors such as everolimus or sirolimus can have an antitumor effect. Patients and Methods In a monocentric retrospective study we evaluated organ transplant recipients who presented with non-melanoma skin cancer in the years 2008–2010. Experience with patients who were switched to an mTOR-inhibitor due to non-melanoma skin cancer are reported in detail, and recent clinical studies are reviewed. Results 60 organ transplant recipients with non-melanoma skin cancer were evaluated. Due to the development of multiple non-melanoma skin cancer within a few years, the immunosuppressive regimen was switched to everolimus in 7 patients and to sirolimus in 5 patients. Eight patients were evaluable for the effect of mTOR-inhibitors on the development of non-melanoma skin cancer; 4 patients had to discontinue the medication with mTOR-inhibitors early due to various side effects. In the year before the switch to mTOR-inhibitors, 8 patients developed 16 squamous cell carcinomas, 3 Basal cell carcinomas and 22 cases of Bowen's disease. All tumors were histologically confirmed. In the year after switch of immunosuppression, the rate of squamous cell carcinomas (n = 2) and Bowen's disease (n = 3), but not of basal cell carcinomas (n = 2) was significantly reduced. Moreover, 5 prospective randomized trials recently have demonstrated a reduced number of non-melanoma skin cancers in organ transplant recipients after switch of the immunosuppressive regimen to mTOR-inhibitors. Conclusion Switch of the immunosuppressive regimen to mTOR-inhibitors should be considered for organ transplant recipients suffering from multiple non-melanoma skin cancers.

This guideline is the result of a systematic literature review using the 'Grading of Recommendations Assessment, Development and Evaluation' (GRADE) methodology and a structured consensus conference held on 28 and 29 November 2012, in Berlin. It is a joint initiative of the Dermatology Section of the European Academy of Allergy and Clinical Immunology (EAACI), the EU-funded network of excellence, the Global Allergy and Asthma European Network (GA(2)LEN), the European Dermatology Forum (EDF), and the World Allergy Organization (WAO) with the participation of delegates of 21 national and international societies. Urticaria is a frequent, mast cell-driven disease, presenting with wheals, angioedema, or both. the life-time prevalence for acute urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic forms of urticaria do not only cause a decrease in quality of life, but also affect performance at work and school and, as such, are members of the group of severe allergic diseases. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors and pathomechanisms. in addition, it outlines evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Charite, Allergy Ctr Charite, Dept Dermatol & Allergy, D-10117 Berlin, Germany Med Univ Graz, Dept Dermatol, Graz, Austria Clin San Carlo, Allergy Clin, Paderno Dugnano, MI, Italy Univ Southern Denmark, Odense Univ Hosp, Dept Dermatol & Allergy Ctr, Odense, Denmark Med Univ Silesia, Allergol & Clin Immunol Katowice, Dept Internal Dis, Zabrze, Poland Univ Genoa, IRCCS AOU SanMartino, Genoa, Italy Universidade Federal de São Paulo, Dept Clin Immunol & Allergy, São Paulo, Brazil Univ Autonoma Barcelona, Hosp Mar Parc Salut Mar, E-08193 Barcelona, Spain Dr DY Patil Med Coll & Hosp, Dept Dermatol, Navi Mumbai, India Fac Med, Dermatol Clin, Coimbra, Portugal Univ Hosp, Coimbra, Portugal Guys & St Thomas Hosp NHS Fdn Trust, St Johns Inst Dermatol, London, England Ctr Appl Res Allergy Quebec, Quebec City, PQ, Canada Hiroshima Univ, Inst Biomed & Hlth Sci, Dept Dermatol, Hiroshima, Japan Med Univ S Carolina, Dept Med, Div Pulm & Crit Care Med, Charleston, SC USA Hannover Med Sch, Dept Dermatol & Allergy, Hannover, Germany Pantai Hosp Kuala Lumpur, Dept Paediat, Kuala Lumpur, Malaysia Univ Hosp Tenon, Dept Dermatol & Allergy, Paris, France Johns Hopkins Asthma & Allergy Ctr, Baltimore, MD USA Ctr Medicodocente Trinidad, Allergy & Clin Immunol Dept, Caracas, Venezuela Univ Hosp, Dept Dermatol, Allergy Unit, Zurich, Switzerland Univ Manitoba, Dept Pediat & Child Hlth, Winnipeg, MB R3T 2N2, Canada Univ Manitoba, Dept Immunol, Winnipeg, MB, Canada Univ Med Ctr Mainz, Dept Dermatol, Mainz, Germany Univ Toronto, Div Allergy & Clin Immunol, Toronto, ON, Canada Technion, Fac Med, Bnai Zion Med Ctr, Haifa, Israel Univ Bari, Dept Biomed Sci & Human Oncol, Unit Dermatol & Venereol, Bari, Italy Peking Univ, Hosp 1, Dept Dermatol, Beijing 100871, Peoples R China Universidade Federal de São Paulo, Dept Clin Immunol & Allergy, São Paulo, Brazil Web of Science

Head or neck location of primary cutaneous melanomas has been described as an adverse prognostic factor, but this has to be reassessed after the introduction of sentinel lymph node (SLN) excision (SLNE). Descriptive statistics, Kaplan–Meier estimates and Cox proportional hazard models were used to study retrospectively a population of 2302 consecutive melanoma patients from three German melanoma centres undergoing SLNE. Approximately 10% of the patients (N=237) had a primary melanoma located at the head or neck (HNM). In both the SLN-positive and SLN-negative subpopulation, patients with HNM were significantly older, more frequently men and had thicker primaries compared with patients with tumours in other locations. The proportion of positive SLNs was lower in HNM compared with other locations of the primary (20 vs. 26%, P=0.048). The false-negative rate was higher in HNM (17.5 vs. 8.4%, P=0.05). In patients with HNM, the SLN status was a significant factor for recurrence-free survival but not for overall survival. SLN-negative HNM patients had a significantly worse overall survival than the SLN negatives with primaries at other sites, whereas the prognosis of the SLN-positive patients was similar in both groups. The prevalence of lymph node metastases after SLNE is lower in patients with HNM compared with other melanoma locations. As a result, the prognostic information provided by the SLN for HNM seems less important. Decision making for SLNE in HNM should be carefully balanced considering the potential morbidity of the procedure. Melanoma Res 00:000–000 c 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins. Melanoma Research 2013, 00:000–000

Background Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal pulmonary disease with an estimated 5-year survival of approximately 20%. Pirfenidone is a novel orally available antifibrotic agent that reduces disease progression and improves survival of patients with IPF. The most common adverse effects of pirfenidone include gastrointestinal symptoms, hepatic dysfunction or skin photosensitivity and rash. A 64-year-old male patient presented in our clinic with a strong generalized exfoliative erythema and intense itching accompanied by fatigue and mild fever after a mild sun exposure for 5 days during holidays in Turkey. The patient had been diagnosed with IPF 2 months ago and 1 month later he started a therapy with pirfenidone with good tolerability. Objective In this report, we noted a severe phototoxic reaction under treatment with pirfenidone which underlies the potential phototoxic effect of this drug besides the already reported photosensitivity. Methods Routine laboratory tests and a skin biopsy were performed. Results Laboratory tests indicated increased markers of inflammation. The skin biopsy showed a perivascular lymphocytic inflammatory infiltrate, ballooning of keratinocytes with increased apoptosis. These findings were most consistent with a severe phototoxic reaction to pirfenidone which had been directly discontinued. The patient was started on oral methylprednisolone 100 mg/day which was gradually tapered off along with topical corticosteroids (mometasone furoate 0.1% cream) and oral antihistamines. This treatment led to a slow but complete resolution of the skin lesions within 20 days. Conclusion To our knowledge, this is the first reported case of a severe phototoxic reaction during treatment with pirfenidone. Our aim by presenting this case is to increase the awareness of clinicians for severe phototoxic effects of oral pirfenidone.

Bei der chronischen spontanen Urtikaria, den physikalischen Urtikariaformen und den Urtikariasonderformen ist ein gezieltes diagnostisches Vorgehen empfehlenswert. Dabei liegt der Schwerpunkt auf subklinischen bakteriellen und viralen Foci. Hierbei wird besonders haufig eine Infektion mit Helicobacter pylori nachgewiesen. Nicht selten kann eine Autoimmunurtikaria mittels autologem Serumtest diagnostiziert werden. Als unspezifische Werte sind bei der akuten Urtikaria die Zahl der Leukozyten im Blutbild und C-reaktives Protein manchmal hilfreich (hinweisend auf subklinische Infekte). In der Regel ist keine weitere Diagnostik indiziert. Besonders bei langjahrigen Verlaufen, ohne dass ein Triggerfaktor identifiziert werden kann, sowie bei entsprechenden anamnestischen Hinweisen bei intermittierend auftretenden Urtikariaschuben kann eine erweiterte Diagnostik mit Berucksichtigung von moglichen IgE-vermittelten Reaktionen (α-Gal und ω-5-Gliadin) wegweisend sein. Das seit einigen Jahren in unserer Sprechstunde an einer Universitats-Hautklinik erfolgreich eingesetzte Vorgehen kann aktuell individuell durch rezent identifizierte Einzelallergene bzw. Allergenkomponenten komplettiert werden. Der vorliegende Beitrag soll unser Vorgehen exemplarisch darstellen.

According to the guidelines the treatment goal for all types of urticaria is to achieve complete symptom relief. Therefore the available literature for urticaria treatment was reviewed regarding this aim and treatment failure, respectively. Systematic studies are not available. Standard doses of H1-antihistamines are the only approved therapy. Review of the limited data where statements are made about complete alleviation of symptoms shows that standard doses of H1-antihistamines rarely achieve this. Even when the dosage is increased up to four-fold, the failure rate is high. Additional therapy with montelukast, dapsone, and cyclosporine A also often fails to produce complete control. For severe chronic spontaneous urticaria, controlled studies using omalizumab have shown low failure rates over long time periods. It has not been investigated whether up-dosing or reduced injection intervals could further improve this rate. Taken together, the small amount of available data on complete symptom relief in urticaria treatment is astonishing. Moreover, the studies can not be compared due to different inclusion criteria (severity of urticaria, allowed basic treatment) and evaluated parameters. Further controlled studies are vitally needed to achieve the goal of complete symptom relief in urticaria.

Bullous pemphigoid (BP) is an autoimmune blistering skin disease that is more common in elderly individuals. The aim of this study was to determine the functional activity of eosinophils in patients with BP compared with healthy donors. Blood, skin and blister-derived eosinophils were strongly activated in patients with BP, seen by increased surface expression of CD69 compared with controls. CD11b was also increased in BP blood eosinophils, which may explain the striking accumulation of eosinophils in BP (1×106 per ml blister fluid). Furthermore, CCL26 was expressed by activated eosinophils in BP skin and in blister fluid. BP eosinophils also released IL-6, IL-8 and IL-1α in BP blister fluids. Apoptosis in cultivated BP eosinophils was increased and accompanied by enhanced surface externalization of CD95. Caspase 3 positive eosinophils in lesional BP skin and blister fluid also showed the initiation of apoptosis. These results reveal novel pathophysiological aspects of BP, with a strong activation pattern and increased apoptosis of eosinophils in the peripheral blood, skin and blister fluids.

A 42-year-old woman with ulcerative colitis previously well controlled on mesalazine presented with blistering, crusts and severe itching on her upper body and legs together with painful erosions on her conjunctivae and oral mucous membranes in addition to active bowel symptoms for two weeks. Clinical examination revealed multiple lesions consisting of vesiculopustules with circinate distribution and central crusts in sunflower-like configuration on her flanks and legs, a typical characteristic of intraepidermal neutrophilic dermatosis (IEN)-type of IgA pemphigus (Figure 1A and 1C) [1]. Lips, nasolabial folds and eyelids were affected by yellow crusts and erosions on erythematous base (Figure 1B). This article is protected by copyright. All rights reserved.

Contact allergies at the oral mucosa are associated with diverse symptoms. In this article we focus on the contact allergy of delayed type. Oral mucosa changes including stomatitis or lichenoid inflammation can give first evidence for such a contact allergy. Subjective symptoms including pain, burning or dryness of the oral mucosa can be associated with a contact allergy but may also occur in other diseases which need to be excluded. The first step in the diagnosis of a contact allergy is the complete examination of the oral mucosa. Additionally, a careful history of the patient's oral care products, drugs and dental materials is important. If mucosal changes are present, a patch test is recommended for the diagnostic work up for contact allergy of delayed type. In case of a positive patch test reaction, a careful check for the clinical relevance is needed in order to have a clear recommendation for both patient and dentist e.g. if replacement of prosthetic materials is needed.

Overexpression of microRNA-21 (miR-21) has been observed in various cancer types, but little is known about the role of miR-21 in melanoma. In this study, we demonstrate that levels of miR-21 are significantly increased in primary melanoma tissues as compared to benign nevi and in human melanoma cell lines as compared to melanocytic cell preparations. We show that downregulation of miR-21 in melanoma cell lines with high endogenous miR-21 expression induced apoptosis, whereas proliferation was not significantly altered. Upregulation of miR-21 in melanocytes resulted in increased proliferation and decreased apoptosis. However, in the MEWO melanoma cells with low endogenous miR-21 expression, upregulation of miR-21 had no functional effects. These findings indicate a potential pathogenetic role of miR-21 upregulation in a subgroup of melanomas.

Pruritus ist eines der lastigsten Symptome, das bei vielen Haut- und auch internistischen Erkrankungen, aber auch ohne erkennbar zugrunde liegende Ursache auftreten kann. Es ist bekannt, dass der chronische Pruritus einen schwerwiegenden Einfluss auf die Lebensqualitat von Patienten hat. Die Therapie des schweren chronischen Pruritus ist oftmals eine Herausforderung, insbesondere wenn eine zugrunde liegende Ursache nicht gefunden werden kann. Neben der erhohten Dosierung von nicht sedierenden Antihistaminika, die therapeutisch bei schwerem Pruritus oftmals nicht hilfreich ist, wird eine Therapie mittels Psychopharmaka, wie beispielweise tri- oder tetrazyklischen Antidepressiva und selektiven Serotoninwiederaufnahmehemmern, empfohlen, die wir in diesem Beitrag erortern.

Zusammenfassung Die Mundschleimhaut wird konstant einer Reihe von potenziell irritierenden und sensibilisierenden Dentalmaterialien ausgesetzt. Dentalmaterialien, die bei Fullungen, festsitzendem oder herausnehmbarem Zahnersatz und Implantaten eingesetzt werden, mussen eine zufriedenstellende Biokompatibilitat vorweisen. Daher werden bei der Herstellung von Kronen beispielsweise Metalllegierungen verwendet, die als Kern zusammen mit Keramik das Konstrukt des artifiziellen Zahnes bilden, gegen den Patienten eine Kontaktallergie entwickeln konnen. Die klinische Manifestation der Kontaktallergie gegenuber Dentalmaterialien ist nicht einheitlich. Objektivierbare Symptome einer kontaktallergischen Reaktion beinhalten die Stomatitis und lichenoide Reaktionen an der Mundschleimhaut. Bei Patienten, die von subjektiven Symptomen wie Brennen, Schmerzen und Trockenheit an der Mundschleimhaut berichten, mussen diese Symptome von einer echten kontaktallergischen Reaktion differenziert werden. In diesem Artikel prasentieren wir eine Ubersicht uber das Management von Kontaktallergien gegenuber Dentalmaterialien.

Ein 43-jahriger Patient mit kutaner und pulmonaler Sarkoidose wurde aufgrund der Hautbeteiligung systemisch uber insgesamt 11 Monate mit Fumarsaureestern (Fumaderm®) behandelt. Hierunter kam es sowohl zu einer Ruckbildung der Hautinfiltrate als auch der pulmonalen Veranderungen. Auch laborchemisch zeigte sich eine Normalisierung des Angiotensin-converting-Enzyms (ACE) nach Therapieende. Diese Kasuistik ist ein weiteres von bisher nur wenigen Beispielen der erfolgreichen Therapie einer kutanen und pulmonalen Sarkoidose mit Fumarsaureestern.

To cite this article: Raap U, Weismantel S, Gehring M, Eisenberg AM, Kapp A, Folster-Holst R. IL-31 significantly correlates with disease activity and Th2 cytokine levels in children with atopic dermatitis. Pediatr Allergy Immunol 2012: 23: 285–288. Abstract Recently, we could show that IL-31 serum levels are significantly increased in adult patients with atopic dermatitis compared with skin healthy controls. However, the regulation of IL-31 in children with atopic dermatitis so far is not clear. Thus, we analyzed IL-31 serum levels together with IL-4, IL-13, ECP, and total IgE levels in 60 children with extrinsic, in five children with intrinsic atopic dermatitis, and 20 non-atopic healthy children. Further, we determined the SCORAD score, sleeplessness, and pruritus severity in all children with atopic dermatitis. IL-31 was significantly increased in children with the intrinsic and extrinsic type of atopic dermatitis compared with non-atopic healthy children (p

The oral mucosa is constantly exposed to a large number of potentially irritating and sensitizing dental materials. Dental materials used for fillings and fixed or removable replacements must have a good biocompatibility. Metals including palladium are used in alloys for the production of the core of crowns, onto which porcelain is bonded for the generation of an artificial tooth to which the patient can develop an allergic contact dermatitis. The clinical manifestations of contact allergy to dental materials are not uniform. Objective symptoms of a contact allergy include a stomatitis and lichenoid reactions. However, patients may present with more subjective affections of the oral mucosa including burning, pain and dryness which need to be differentiated from a real contact allergic reaction. In this article we focus on the management of contact allergy to dental materials.

Background Little is known about the effect of neuropeptides on basophils, which are important effector cells in immune and allergic responses. Objective This study aimed at revealing the role of α-melanocyte–stimulating hormone (α-MSH) on basophil function. Methods Expression of melanocortin receptors and proopiomelanocortin (POMC) was analyzed by means of RT-PCR, Western immunoblotting, fluorescence-activated cell sorting, and double-immunofluorescence analysis. Signal transduction studies included cyclic AMP and Ca 2+ mobilization assays. Basophil activity was assessed based on CD63 surface expression and cytokine release. Results MC-1R expression was detectable in basophils isolated from human peripheral blood, as well as in basophils within nasal tissue. In isolated basophils from human blood, truncated POMC transcripts were present, but there was no POMC protein. Treatment of basophils with α-MSH increased intracellular Ca 2+ but not cyclic AMP levels. α-MSH at physiologic doses potently suppressed basophil activation induced by N-formyl-methionyl-leucyl-phenylalanine, phorbol 12-myristate 13-acetate, or grass pollen allergen in whole blood of healthy or allergic subjects, respectively. The effect of α-MSH on basophil activation was MC-1R mediated (as shown by blockade with a peptide analogue of agouti-signaling protein) and imitated by adrenocorticotropic hormone but not elicited by the tripeptides KPV and KdPT, both of which lack the central pharmacophore of α-MSH. Moreover, α-MSH at physiologic doses significantly suppressed secretion of 3 proallergic cytokines, IL-4, IL-6, and IL-13, in basophils stimulated with anti-IgE, N-formyl-methionyl-leucyl-phenylalanine, or phorbol 12-myristate 13-acetate. Conclusion Our findings highlight a novel functional activity of α-MSH, which acts as a natural antiallergic basophil-response modifier. These findings might point to novel therapeutic strategies in treating allergic diseases.

Iatrogene Kaposi-Sarkome (KS) bei Organtransplantierten werden haufig mit einer Umstellung der Immunsuppression auf einen mTOR-Inhibitor wie Everolimus oder Sirolimus behandelt, da so immunsuppressive und antitumorale Effekte erzielt werden. Wir berichten uber einen 80-jahrigen Patienten, der aufgrund einer Myasthenia gravis mit Azathioprin und Prednisolon therapiert wurde und darunter ein disseminiertes kutanes KS entwickelte. Nach Absetzen des Azathioprins kam es trotz fortlaufender Kortisontherapie zu einem Progress des KS und einem Anstieg des Autoantikorperspiegels gegen den nikotinischen Acetylcholinrezeptor. Unter der Gabe von Everolimus kam es zu einer langfristigen, fast vollstandigen Remission des KS und einem Ruckgang der Autoantikorper. Dieser Fall zeigt, dass auch bei Nichtorgantransplantierten mit iatrogenem KS eine Umstellung der Immunsuppression auf einen mTOR-Inhibitor sinnvoll sein kann.

Summary Background: No consistent data are available on the currently employed diagnostic tools for autoimmune bullous diseases in Germany. The aim of this survey was to describe currently performed diagnostic methods for bullous autoimmune diseases in German dermatology departments. Methods: A standardized questionnaire evaluated the available diagnostic methods i. e. direct immunofluorescence microscopy (IFM), indirect IFM, commercial ELISA systems, and non-commercial serological tests as well as the number of samples per year in all 34 university and 39 non-university dermatology departments. Results: The overall return rate was 89 %, 100 % and 79 % for the university and non-university departments, respectively. Direct IFM was the most frequently used method and was applied in 98 % of the responding departments. In 74 % of the responding departments, indirect IFM was used mainly on monkey esophagus and human salt-split skin. Commercial ELISA systems were employed in 58 % of the clinics; all of them used anti-desmoglein ELISA, while anti-BP180 and anti-BP230 ELISA were established in 49 % and 48 % of departments, respectively. Non-commercial analytic methods were only performed in 22 % of the departments. Conclusions: The high return rate of this survey allows a relatively precise description of the current diagnostic methods used in German dermatology departments. Standard diagnostic tests are available nationwide and in bullous pemphigoid and pemphigus, the antigen-specific detection of autoantibodies is routinely performed in half of the departments. Rare disorders may be diagnosed by cooperation with some specialized centers.

Grosere retrospektive Studien zeigen, dass epikutane Sensibilisierungen bei atopischen und nichtatopischen Patienten ahnlich haufig vorkommen. Auch bei Kindern und Jugendlichen scheint die Wahrscheinlichkeit fur eine epikutane Sensibilisierung unabhangig von der Diagnose einer atopischen Dermatitis (AD) zu sein. Hingegen sind Patienten mit einer AD nach einer neueren Untersuchung in der Gruppe der polysensibilisierten Patienten uberreprasentiert. Als mogliche Risikofaktoren fur eine epikutane Sensibilisierung bei AD wurden das Vorliegen IgE-vermittelter Sensibilisierungen und die Krankheitsdauer bzw. ein fruher Krankheitsbeginn bei AD identifiziert. Ferner fordert eine gestorte Hautbarriere bei AD die Penetration von Kontaktallergenen und Irritanzien in die Epidermis und stellt einen wichtigen Kofaktor fur die Sensibilisierung dar. Es konnte eine Assoziation zwischen dem Vorliegen von Mutationen im Filaggrin-Gen bei AD und einer klinisch relevanten Sensibilisierung gegenuber Nickel, nicht jedoch gegenuber anderen Kontaktallergenen nachgewiesen werden. Weitere prospektive Studien an grosen Patientenkohorten sind notwendig, um den Zusammenhang zwischen gestorter Hautbarriere bei AD und dem Risiko der Entstehung einer Kontaktallergie naher zu untersuchen.

Schlusselworter • Retinoide • Vitamin-A-Derivate • Fettstoffwechsel • Hyperlipidamie Zusammenfassung Retinoide und Vitamin-A-Derivate zahlen seit uber 30 Jahren zum dermatologisch therapeutischen Standard bei der Behandlung hyperund parakeratotischer Dermatosen, Genodermatosen, schwerer Akne, Autoimmunerkrankungen (u. a. Lupus erythematodes) sowie kutaner T-Zell-Lymphome. Neben den therapeutisch gewunschten proliferationshemmenden, die Zelldifferenzierung induzierenden, antiinflammatorischen oder sebosuppressiven Effekten konnen systemisch eingesetzte Vitamin-A-Derivate pathophysiologisch zudem den Fettstoffwechsel beeinflussen. Dies ausert sich primar durch einen moglichen Anstieg der Transaminasen, Triglyceride und Cholesterinwerte in unterschiedlicher Auspragung. Der Grad der Beeinflussung einzelner Fettstoffwechselparameter ist bei den einzelnen Vitamin-A-Derivaten unterschiedlich stark ausgepragt und begrundet sich einerseits durch die differenten rezeptorselektiven Bindungsinteraktionen (RAR/RXR), andererseits spielen aber auch posttranslationale Vorgange eine gewichtige Rolle. Diese Ubersichtsarbeit vermittelt in komprimierter Form einen, fur den Dermatologen relevanten, Uberblick uber die einzelnen Vitamin-A-Derivate und der zu erwartenden Beeinflussung von Fettstoffwechselparametern. Zudem enthalt die Arbeit eine Konsensusempfehlung zum Umgang mit und Management von Laborwertveranderungen vor, wahrend und nach einer systemischen Vitamin-A-Derivat-Therapie, die es dem Dermatologen im Praxisalltag erleichtern soll, fur den einzelnen Patienten ein individuelles Therapiemanagement zu formulieren. Die Konsensusempfehlung ist eine gemeinsam erarbeitete Stellungnahme der „Deutschen Dermatologischen Gesellschaft“ (DDG) in Kooperation mit der „Deutschen Gesellschaft zur Bekampfung von Fettstoffwechselstorungen und ihren Folgeerkrankungen“ (DGFF [Lipid-Liga] e. V.). Beeinflussung des Fettstoffwechsels durch systemische Vitamin-A-Derivate – Welche Empfehlungen leiten sich daraus fur die dermatologische Praxis ab?

Fur die Therapie der chronischen spontanen Urtikaria stehen neben Antihistaminika einige weitere Optionen zur Verfugung, die gemas dem Stufenschema der aktuellen Leitlinie angewandt bei den meisten Patienten zu guten Therapieerfolgen fuhren. In einigen Fallen kann mithilfe der etablierten Wirkstoffe jedoch keine ausreichende Symptomkontrolle erreicht werden. Daruber hinaus besteht in schweren Fallen bei der chronischen spontanen Urtikaria und anderen Subtypen eine deutliche Einschrankung der Lebensqualitat, besonders wenn die Beschwerden uber mehrere Jahre auftreten. Im folgenden Beitrag wird der Einsatz von Omalizumab in der Behandlung besonders betroffener Patienten im Rahmen individueller Heilversuche aus der Urtikariasprechstunde einer Universitatshautklinik prasentiert.

Summary Background Chronic spontaneous urticaria is triggered by many direct and indirect aggravating factors including autoreactive/autoimmune mechanisms, infections, non-allergic and pseudoallergic intolerance reactions. However, the role of neuroimmune mechanisms in chronic spontaneous urticaria so far is unclear. Objective Thus, we wanted to address the regulation of the neurotrophin brain-derived neurotrophic factor (BDNF) in serum and inflammatory skin of patients with chronic spontaneous urticaria in comparison to subjects with healthy skin. Methods Fifty adult patients with chronic spontaneous urticaria and 23 skin-healthy subjects were studied. Chronic spontaneous urticaria was defined as recurrent weals for more than 6 weeks. Autologous serum skin test was performed in all patients with chronic spontaneous urticaria and BDNF serum levels were analysed by enzyme immunoassay in all subjects. Furthermore, skin biopsies were taken from weals of eight patients with chronic spontaneous urticaria as well as from healthy skin of eight controls to evaluate the expression of BDNF and its receptors including tyrosine kinase (trk) B and pan-neurotrophin receptor p75NTR by immunohistochemistry. Results BDNF serum levels were detectable in all subjects studied. However, BDNF levels were significantly higher in patients with chronic spontaneous urticaria compared to non-atopic skin-healthy controls (P

Substanzen, die zur medikamentosen Tumortherapie eingesetzt werden, konnen kutane Nebenwirkungen mit einem relativ typischen klinischen Bild hervorrufen. Vor allem die neuen zielgerichteten Therapien sind haufig mit spezifischen kutanen Nebenwirkungen assoziiert, wie z. B. papulopustulose Exantheme unter EGFR-Blockern und Hauttumoren unter BRAF-Blockern. In dieser Ubersicht werden das klinische Bild sowie pathogenetische und therapeutische Aspekte dieser kutanen Nebenwirkungen zusammengefasst, insbesondere des Hand-Fus-Syndroms, des papulopustulosen Exanthems, der epithelialen Hauttumoren, der Paronychien sowie der Veranderungen von Nageln und Haaren. Um Pausierungen oder ein vorzeitiges Absetzen der medikamentosen Tumortherapie zu vermeiden, sind die Kenntnis der spezifischen Nebenwirkungen sowie des Nebenwirkungsmanagements wichtig, insbesondere da bei einigen Substanzen ein Zusammenhang zwischen kutanen Reaktionen und dem Ansprechen der Therapie beobachtet wurde.

Retinoids and vitamin A derivatives have been widely used topically and systemically in the treatment of hyper- and parakeratotic skin diseases, genodermatoses, severe acne, autoimmune diseases (i. e. lupus erythematosus) or cutaneous T-cell lymphoma for more than 30 years. In addition to the desired proliferation-inhibiting, differentiation-inducing and antiinflammatory or sebo-suppressive effects, vitamin A derivatives also affect lipid metabolism. This is shown primarily by an increase of transaminases, triglycerides or cholesterol levels which vary in intensity from patient to patient. The degree of impact on the different parameters of lipid metabolism depends on the nature of the vitamin A derivative on the one hand due to different receptor specific binding interactions (RAR/RXR), while on the other hand posttranslational processes also play a major role. This review paper gives a brief, concise overview of the vitamin A derivatives and possible effects on lipid metabolism that can be expected. Additionally it contains a recommendation for secure handling of abnormal laboratory values before, during and after oral therapy with vitamin A derivatives. The aim of this article is to provide practical help and confidence in dealing with vitamin A derivatives in daily clinical practice. The publication was created in cooperation with the Deutsche Dermatologische Gesellschaft (DDG) and Deutsche Gesellschaft zur Bekampfung von Fettstoffwechselstorungen und ihren Folgeerkrankungen (DGFF [Lipid-Liga] e. V.).

Die Entfernung des Schildwachterlymphknotens (SLNE), haufig auch als Schildwachterlymphknotenbiopsie oder Sentinel-Node-Biopsie bezeichnet, beinhaltet die gezielte Entfernung des tumordrainierenden Lymphknotens nach vorheriger Markierung mittels Lymphabflussszintigraphie. Seit der ersten Beschreibung von Morton im Jahr 1990 hat sich die SLNE in vielen Zentren zur operativen Standardversorgung bei der Erstdiagnose fortgeschrittener Primarmelanome entwickelt. Durch die SLNE werden fruhzeitig klinisch okkulte regionare Lymphknotenmetastasen (Mikrometastasen) erkannt. Die histopathologische und immunhistochemische Detektion regionarer Mikrometastasen gibt wichtige Informationen uber die Prognose der Patienten und kann bei der Entscheidung fur eine weitere operative Versorgung und adjuvante Therapie hilfreich sein. Gleichzeitig wird die SLNE aber auch kritisch hinterfragt, da es bislang keinen Beweis dafur gibt, dass dadurch die Prognose der Melanompatienten verbessert wird. Dennoch wird die Durchfuhrung einer SLNE in den aktuellen Leitlinien ab einer Primarmelanom-Tumordicke von 1 mm empfohlen, und der Status des Schildwachterlymphknotens wurde in die Klassifikation des Melanoms integriert.

Mithilfe der zellularen In-vitro-Allergiediagnostik ist eine Erfassung antigenabhangiger zellularer Vorgange ohne Risiko fur den Patienten moglich. Der zellulare Antigenstimulationstest mit der Bestimmung der Sulfidoleukotrienproduktion in Leukozytensuspensionen sowie die durchflusszytometrischen Basophilenaktivierungstests mit der Analyse von Oberflachenaktivierungsmarkern (CD63, CD203c) stellen nach Antigenstimulation gute Modelle fur die In-vivo-Mastzellstimulation im Rahmen von v. a. IgE-vermittelten Soforttypreaktionen dar. Ihre Wertigkeit sollte stets bezogen auf das Antigen sowie die weiteren diagnostischen Moglichkeiten beurteilt werden. Problematisch in der Bewertung der bisher publizierten Evidenz sind die in den einzelnen Studien haufig nicht vergleichbaren Allergenkonzentrationen, Stimulationsbedingungen, Testdurchfuhrung und ermittelte Grenzwerte. Im klinischen Alltag hat die aufgrund des logistischen Aufwands meist nur in spezialisierten Laboren verfugbare zellulare In-vitro-Allergiediagnostik v. a. bei klarer Anamnese, aber fehlendem oder diskrepantem Sensibilisierungsnachweis mithilfe der konventionellen Allergiediagnostik, bei seltenen Allergenen (Arzneimittel, exotische Nahrungsmittel) sowie bei Kontraindikationen fur den Hauttest und/oder Provokationstest (Insektengiftallergie, Anaphylaxie) Bedeutung.

A 19-year-old patient presented with epidermodysplasia verruciformis (EV). In this genodermatosis, pathogenetic factors such as infection by human papilloma viruses as well as sun exposure are considered responsible for the malignant transformation of EV lesions to skin cancer within decades. So far, several therapeutic strategies have been unsatisfactory. In our case HPV 5b was detected and the associated skin lesions were successfully treated with imiquimod 5% cream.

Eine Urtikaria kann als Reaktion auf unterschiedliche Triggerfaktoren auftreten. Infektionen werden seit vielen Jahren diskutiert, ihre exakte Bedeutung und der zur Mastzellaktivierung fuhrende Mechanismus bleiben unklar. Bei der akuten spontanen Urtikaria ist ein kausaler Zusammenhang zu Infektionen unbestritten, und jede chronische Urtikaria hat per definitionem als akute Urtikaria begonnen. Auch bei der chronischen spontanen Urtikaria sind Remissionen nach Beseitigung zugrunde liegender chronisch persistierender Infekte beschrieben. Eine Zusammenfassung publizierter Studien zeigt statistisch signifikant haufiger eine komplette oder partielle Remission nach Helicobacter-Eradikation im Vergleich zu Nicht-Eradizierten oder Helicobacter-Negativen. Da mit der einzig zugelassenen Therapie, der Standarddosis eines H1-Antihistaminikums, nur ein Bruchteil der Patienten mit chronischer Urtikaria symptomfrei ist und Infektionen leicht zu behandeln sind, sollte eine entsprechende Infektdiagnostik zum Routinemanagement gehoren.

Urticaria is a frequent dermatological skin disease characterized by the occurrence of transient pruritic wheals. The sensation of pruritus has been described to be stinging, tickling and burning in patients with chronic urticaria. Because of the unpredictable attacks of pruritus and swelling, urticaria strongly affects the quality of life in patients. In this review we focus on clinical characteristics, therapeutic options and new pathophysiological mechanisms including the novel T-cell cytokine IL-31 in pruritus of patients with chronic urticaria.

Previously an increased frequency of KIT aberrations in mucosal melanomas was reported, whereas c-KIT in most types of cutaneous melanomas does not appear to be of pathogenetic importance. Imatinib has become the standard of care in other cancers with KIT mutations such as gastrointestinal stromal tumors. Recently 12 cases of metastatic melanoma and KIT-activating mutations have been published to be successfully treated with c-KIT blockers such as imatinib, sunitinib, dasatinib or sorafenib. We report here on one of our patients with KIT-activating mutation in metastatic anal mucosal melanoma, who showed a response to imatinib therapy and summarize the available literature regarding this new therapeutic option.

This guideline, together with its sister guideline on the classification of urticaria (Zuberbier T, Asero R, Bindslev-Jensen C, Canonica GW, Church MK, Gimenez-Arnau AM et al. EAACI/GA(2)LEN/EDF/WAO Guideline: definition, classification and diagnosis of urticaria. Allergy 2009;64: 1417-1426), is the result of a consensus reached during a panel discussion at the Third International Consensus Meeting on Urticaria, Urticaria 2008, a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the EU-funded network of excellence, the Global Allergy and Asthma European Network (GA(2)LEN), the European Dermatology Forum (EDF) and the World Allergy Organization (WAO). As members of the panel, the authors had prepared their suggestions regarding management of urticaria before the meeting. The draft of the guideline took into account all available evidence in the literature (including Medline and Embase searches and hand searches of abstracts at international allergy congresses in 2004-2008) and was based on the existing consensus reports of the first and the second symposia in 2000 and 2004. These suggestions were then discussed in detail among the panel members and with the over 200 international specialists of the meeting to achieve a consensus using a simple voting system where appropriate. Urticaria has a profound impact on the quality of life and effective treatment is, therefore, required. The recommended first line treatment is new generation, nonsedating H(1)-antihistamines. If standard dosing is not effective, increasing the dosage up to four-fold is recommended. For patients who do not respond to a four-fold increase in dosage of nonsedating H(1)-antihistamines, it is recommended that second-line therapies should be added to the antihistamine treatment. In the choice of second-line treatment, both their costs and risk/benefit profiles are most important to consider. Corticosteroids are not recommended for long-term treatment due to their unavoidable severe adverse effects. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS).

Background: Nonsedating H1-antihistamines are recommended for the treatment of urticaria by the recent EAACI/GA2LEN/EDF guidelines. The aim of this study was to compare the efficacy, after 4 weeks of treatment, with levocetirizine 5 mg and desloratadine 5 mg, both once daily in the morning, in symptomatic chronic idiopathic urticaria (CIU) patients. Methods: This multi-center, randomized, double-blind study involved 886 patients (438 on levocetirizine and 448 on desloratadine). The primary objective was to compare their efficacy on the mean pruritus severity score after 1 week of treatment. Mean pruritus severity score over 4 weeks and pruritus duration score, number and size of wheals, mean CIU composite score (sum of the scores for pruritus severity and numbers of wheals), quality of life, and the patient’s and investigator’s global satisfaction with treatment, were secondary efficacy measures. Results: Levocetirizine led to a significantly greater decrease in pruritus severity than desloratadine over the first treatment week; mean pruritus severity scores of 1.02 and 1.18 for levocetirizine and desloratadine, respectively (P

We report about a 51-year-old man presented to our outpatient department with infiltrated, oozing and crusting erythema, papulovesicles and tiny scattering eczematous lesions on his buttocks that had begun a few days ago. In the course of treatment he developed similar skin lesions on his thigh and his chest. After a few weeks of treatment he told us that skin lesions started a few days after he had become a new black leather purse and a matching key case. Patch testing revealed strong positive reactions to nickel and to the patients purse and key case (leather inside and outside and the metal label). The dimethylglyxim test showed nickel in the metal label and in other metal components of the purse and the key case. However, no nickel was detected in the leather. After allergen avoidance and transient treatment with local steroids our patient resolved quickly. Due to the severe contact dermatitis in spite of no direct skin contact (the patient wore clothes) the possibility of an additional sensitization to ingredients of the black purse, e.g. leather dyes or tannins that were not included in the commercially available patch test series should be considered.

Chronic skin ulcers, such as leg ulcers, pressure sores and diabetic foot ulcers, are a challenge to physicians and medical personnel and a cause of tremendous discomfort and ensuing loss of quality of life to the patients. Wound healing involves production and action of various growth factors. A novel approach, distinct from the application of single growth factors, is the administration of the macrophage stimulator macrophage-activating lipopeptide-2 (MALP-2). The rationale is based on the finding that macrophages are the main source of several growth factors required for wound healing, which are sequentially released during this process. MALP-2 has previously been shown to be effective in an established animal model with diabetic mice. The purpose of the present phase I study was to establish tolerability of MALP-2 when applied into small cutaneous wounds in human beings. Twelve patients (six females and six males; mean age 66.8 years; range 52-87 years) with different diagnoses were enrolled into the study. An artificial wound was created with a 2-mm diameter skin biopsy punch and a volume of 30 microl MALP-2 (0.125-1 microg) or vehicle control, respectively, was injected intracutaneously into the wound and closed with a water-resistant transparent adhesive. Photos were taken daily from every patient up to 6 days, and skin biopsies were performed after 1 week from six patients. We could show in the present study for the first time that MALP-2 caused a transient erythema and was tolerated without any systemic side effects up to a dose of 1 microg per wound in human beings. In healthy as well as in diabetic patients, MALP-2 induced local inflammation that faded after 48 h. The effectiveness of MALP-2 in the healing of chronic wounds in humans, e.g. in chronic skin ulcers, such as leg ulcers, pressure sores and diabetic foot ulcers, could now be addressed in further studies.