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BACKGROUND Polyethylene glycol (PEG) may elicit anaphylaxis to COVID-19 mRNA vaccines, and guidance for patients at risk is needed. METHODS In retrospective patients with PEG allergy collected from 2006 till 2019, clinical, skin, and basophil activation test (BAT) characteristics discriminative for PEG allergy were analyzed and compared with the literature. In 421 prospective real-life patients asking for allergy workup for COVID-19 vaccine hypersensitivity in 2020/2021, risk assessment was performed and tolerance of the recommended vaccination approach was assessed. RESULTS Ten patients with PEG allergy were found in the retrospective cohort. Patients reacted with immediate anaphylaxis (100%) not only to PEG-based laxatives/bowel preparations or injections, but also to cold medication, antiseptics, analgetics, or antibiotics. Skin tests ± BAT with PEG ± elicitors were positive in 10/10. Provocation tests were positive in 7/9 patients. From the prospective cohort, 370/421 patients self-reporting increased risk for vaccine allergy lacked criteria necessitating allergy workup and were recommended for routine vaccination. A total of 51/421 patients were tested, and three (6%) with PEG allergy were identified, whereas 48 patients remained negative in skin tests. Vaccination was recommended in all those patients. No hypersensitivity reactions were reported to vaccination including six PEG-allergic patients tolerating COVID-19 vaccination. CONCLUSIONS Taking a detailed history excluded PEG allergy in most referred patients and enabled direct safe vaccination. Immediate urticaria/anaphylaxis to typical elicitors identified patients requiring PEG allergy workup. Skin tests ± BAT identified PEG allergy and helped to select the vaccine and the vaccination approach. Even PEG-allergic patients can tolerate COVID-19 vaccines.

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Background: The alpha-gal syndrome (AGS) describes a new type I allergy entity to the carbohydrate epitope galactose-α-1,3-galactose (alpha-gal), which is mainly found in mammalian food products (e.g., beef, pork, and venison). Apart from meat products, alpha-gal can also be found in products containing gelatin of bovine or porcine origin. Recent case reports pointed to severe anaphylaxis in patients suffering from AGS after vaccination with vaccines containing hydrolyzed gelatin. It was the objective of this study to evaluate if basophil activation tests (BATs) performed with such vaccines were positive in patients with AGS. Methods: BAT was performed with different dilutions of a gelatin-containing measles, mumps, and rubella (MMR) live vaccine; an attenuated varicella (V) vaccine; an attenuated V-zoster (VZ) vaccine; a MMR live vaccine not containing gelatin (non-gelatin MMR vaccine) in 2 patients with confirmed AGS, 2 patients highly suspicious for AGS, and 2 healthy individuals without any previous medical history for allergies. Results: All patients showed strongly positive results for all gelatin-containing vaccines (MMR vaccine, V vaccine, and VZ vaccine). Non-gelatin MMR vaccine was negative. The 2 healthy controls did not show any basophil activation. Conclusions: Gelatin-containing vaccines should be administered with caution or avoided in patients with AGS because of their high potential to activate basophils indicating a risk for anaphylaxis. Also, BAT is a useful additional tool when it comes to screening for potentially high-risk alpha-gal-containing drugs.

This study aimed to provide long-term clinical data about an innovative epidermal radioisotope therapy called Rhenium-SCT52 NMSC patients with a mean age of 71.7 years were treated with rhenium-188 skin cancer therapy between the years 2005 and 2014. An acryl matrix containing rhenium-188 was applied on a plastic foil covering the tumor. The treatment time for reaching a radiation dose of 50 Gy was calculated by a software program. Patients' characteristics and clinical follow-up data were collected and retrospectively analyzed.Overall 55 lesions (32 BCC, 19 SCC, 2 M. Bowen and 2 extramammary Paget's disease (EMPD)) mainly in the head and neck region (72.3%) were treated. The average size of the irradiation area was 9.79 cmRhenium-SCT

Purpose: The innate tumor homing potential of mesenchymal stem cells (MSCs) has been used for a targeted delivery of the theranostic sodium iodide symporter (NIS) transgene into solid tumors. We have previously shown that external beam radiotherapy (EBRT) results in the enhanced recruitment of NIS-expressing MSCs into human hepatocellular carcinoma (HuH7). In parallel, the tumor-associated cytokine TGFB1 becomes strongly upregulated in HuH7 tumors in response to EBRT. Experimental Design: We therefore evaluated the effects of combining focused EBRT (5 Gy) with MSC-mediated systemic delivery of the theranostic NIS transgene under control of a synthetic TGFB1-inducible SMAD-responsive promoter (SMAD-NIS-MSCs) using 123I-scintigraphy followed by 131I therapy in CD1 nu/nu mice harboring subcutaneous human hepatocellular carcinoma (HuH7). Results: Following tumor irradiation and SMAD-NIS-MSC application, tumoral iodide uptake monitored in vivo by 123I-scintigraphy was enhanced as compared with nonirradiated tumors. Combination of EBRT and SMAD-NIS-MSC–mediated 131I therapy resulted in a significantly improved delay in tumor growth and prolonged survival in therapy mice as compared with the combined therapy using CMV-NIS-MSCs or to control groups receiving EBRT or saline only, or EBRT together with SMAD-NIS-MSCs and saline applications. Conclusions: MSC-based NIS-mediated 131I therapy after EBRT treatment dramatically enhanced therapeutic efficacy when a TGFB1-inducible SMAD-responsive promoter was used to drive NIS expression in adoptively applied MSCs. The remarkable therapeutic effect seen is thought to be linked in large part to the enhanced TGFB1 produced in this context, which leads to a highly selective and focused amplification of MSC-based NIS expression within the tumor milieu.

For some years now the basophil activation test (BAT) using flow cytometry has emerged as a powerful tool and sensitive marker that can be used to detect clinically relevant allergies, provide information on the severity of an allergic reaction, and monitor therapies. Compared to other in vitro diagnostic tests, BAT seems to have a better informative value in terms of clinical relevance. In general, the BAT can be used for the diagnosis of the most common forms of IgE-mediated allergy such as hymenoptera venom allergy, inhalant allergy, food allergy, and drug allergy. Various basophil markers and parameters have been established which, depending on the trigger of the respective allergy, can provide information on the clinical relevance of sensitization, on the development of natural tolerance, on trigger thresholds, and on the severity of the allergic reaction. The BAT also serves as a suitable follow-up instrument for various therapeutic approaches such as specific immunotherapy, desensitization protocols, or use of anti-IgE-antibodies for the various diseases. Quality controls for routine use, standardization, and automatization are expected to expand the range of applications for the above-mentioned indications.

Background: Galactose-alpha-1,3-galactose (alpha-gal) syndrome is characterized by the presence of serum specific IgE antibodies to alpha-gal and delayed type I allergic reactions to the carbohydrate alpha-gal after consumption of mammalian (red) meat products and drugs of mammalian origin. Diagnostics currently rely on patient history, skin tests, determination of serum specific IgE antibodies, and oral food or drug challenges.Objective: We sought to assess the utility of different basophil parameters (basophil reactivity and sensitivity, the ratio of the percentage of CD63(+) basophils induced by the alpha-gal-containing allergen to the percentage of CD63(+) basophils after stimulation with anti-Fc epsilon RI antibody [%CD63(+)/anti-Fc epsilon RI], and area under the dose-response curve [AUC]) as biomarkers for the clinical outcome of patients with alpha-gal syndrome compared with subjects with asymptomatic alpha-gal sensitization.Methods: In addition to routine diagnostics, a basophil activation test (Flow CAST) with different concentrations of alpha-gal-containing allergens (eg, commercially available alpha-gal-carrying proteins and pork kidney extracts) was performed in 21 patients with alpha-gal syndrome, 12 alphagal-sensitized subjects, and 18 control subjects.Results: Alpha-gal-containing allergens induced strong basophil activation in a dose-dependent manner in patients. Basophil reactivity at distinct allergen concentrations, the % CD63(+)/anti-FceRI ratio across most allergen concentrations, the AUC of dose-response curves, and basophil allergen threshold sensitivity (CD-sens) with pork kidney extract were significantly higher in patients with alpha-gal syndrome compared with those in sensitized subjects. All parameters were negative in control subjects.Conclusion: The basophil activation test should be considered as an additional diagnostic test before performing time-consuming and potentially risky oral provocation tests. The % CD63(+)/anti-Fc epsilon RI ratio for all allergens and AUCs for pork kidney were the best parameters for distinguishing patients with alpha-gal syndrome from subjects with asymptomatic alpha-gal sensitization.

Die mobile Teledermatoskopie ist eine vielversprechende Technik zur Erganzung oder Substitution einer dermatologischen Untersuchung. In dieser Pilotstudie wurde das Ergebnis teledermatoskopischer Konsultationen mit den Ergebnissen aus klinischen Konsultationen sowie histologischen Resultaten verglichen. Konventionelle und dermatoskopische Fotos von Einzellasionen wurden mithilfe eines auf ein Mobiltelefon aufgesetzten Handyscopes bei 26 Patienten aufgenommen. Funf Arzte/innen fuhrten die klassische klinische Untersuchung einschlieslich Dermatoskopie durch, eine erfahrene Oberarztin beurteilte die teledermatologischen und teledermatoskopischen Bilder. Die Ergebnisse wurden bezuglich der gestellten Diagnose, der genannten Differenzialdiagnosen, des empfohlenen weiteren Vorgehens und der subjektiven und objektiven Diagnosesicherheit verglichen. Daruber hinaus wurden 23 % der Lasionen exzidiert und histologisch befundet. Die am haufigsten gestellte Diagnose war „Navuszellnavus“, gefolgt von „subungualem Hamatom“ und „Basalzellkarzinom“. Die Ergebnisse der klinischen Konsultation und der Teledermatoskopie stimmten hinsichtlich der Diagnose in 92,3 % der Falle uberein. Die Therapieempfehlungen deckten sich zu 76,9 %. Von den 6 histologisch gestellten Diagnosen waren 66,7 % gleichermasen mittels Teledermatoskopie bzw. konventionell klinisch-dermatoskopisch gestellt worden. Bezuglich der Diagnosesicherheit ergab sich kein Nachteil zulasten der Teledermatoskopie. Teledermatologische Aufnahmen von Einzellasionen, die mit teledermatoskopischen Aufnahmen kombiniert werden, lassen sich gut und sicher beurteilen. Bei eingeschranktem Zugang zu facharztlicher Beratung ist die mobile Dermatoskopie eine belastbare Alternative zur klassischen dermatologischen Konsultation.

Zusammenfassung Eine Allergiediagnostik beruht auf einer gründlichen Anamnese, Sensibilisierungstests und Provokationstests zur objektiven Bestätigung des verursachenden Allergenes unter kontrollierten Bedingungen. In dieser Übersicht werden die verfügbaren molekularen und zellulären Tests zur Allergensuche beschrieben. Seit der Identifikation, Klonierung und Expression des Hauptallergens der Birkenpollen, Bet v 1, haben sich die molekularen Einsatzmöglichkeiten in der Allergiediagnostik enorm gesteigert. In einer frei verfügbaren Monographie der European Academy of Allergy and Clinical Immunology (EAACI), dem „Molecular Allergy Users Guide 2016“, werden die Möglichkeiten einer modernen molekularen serologischen Diagnostik detailliert beschrieben. Auch die zelluläre Diagnostik hat sich in den letzten Jahren rasch weiterentwickelt mit der Möglichkeit molekulare Allergene einzusetzen und dem Ziel eine wiederholte Exposition des Patienten mit dem Allergen zu vermeiden. Exakte Messungen sind von externer Qualitätssicherung abhängig, die für die Serumdiagnostik bereits vorhanden ist und in der zellulären Diagnostik derzeit entwickelt wird. Mit der europäischen Standardisierung der diagnostischen Tests im Labor erweitert sich die Palette der Möglichkeiten zur persönlichen Allergiediagnostik.

Allergen-specific immunotherapy is the only curative treatment of honeybee venom (HBV) allergy, which is able to protect against further anaphylactic sting reactions. Recent analyses on a molecular level have demonstrated that HBV represents a complex allergen source that contains more relevant major allergens than formerly anticipated. Moreover, allergic patients show very diverse sensitization profiles with the different allergens. HBV-specific immunotherapy is conducted with HBV extracts which are derived from pure venom. The allergen content of these therapeutic extracts might differ due to natural variations of the source material or different down-stream processing strategies of the manufacturers. Since variations of the allergen content of therapeutic HBV extracts might be associated with therapeutic failure, we adressed the component-resolved allergen composition of different therapeutic grade HBV extracts which are approved for immunotherapy in numerous countries. The extracts were analyzed for their content of the major allergens Api m 1, Api m 2, Api m 3, Api m 5 and Api m 10. Using allergen-specific antibodies we were able to demonstrate the underrepresentation of relevant major allergens such as Api m 3, Api m 5 and Api m 10 in particular therapeutic extracts. Taken together, standardization of therapeutic extracts by determination of the total allergenic potency might imply the intrinsic pitfall of losing information about particular major allergens. Moreover, the variable allergen composition of different therapeutic HBV extracts might have an impact on therapy outcome and the clinical management of HBV-allergic patients with specific IgE to particular allergens.

Phototesting is used to assess individual sensitivity to ultraviolet (UV) radiation in order to determine adequate UV dosage for phototherapy1 . In the standard procedure, small skin areas are exposed to increasing doses of UV radiation. The lowest UV dose that induces a delineated erythema at 24±2 h after UV exposure defines the minimal erythema dose (MED)2 . Visual assessment is the gold standard for MED determination; however, it is prone to observer variability3 . Optical methods have been considered to quantify the magnitude of erythema response. However, they are limited by light scattering therefore high-resolution is restricted to depths of

The pandemic outbreak of coronavirus disease 2019 (COVID-19) affects health care systems globally and leads to other challenges besides infection and its direct medical consequences. The aim of this study was to investigate the impact of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic on the university dermatology outpatient clinic (UDOC) of the Technical University of Munich, Germany. We analyzed datasets from 2015 until 2020 extracted from the hospital information system database and our documented outpatient files regarding patient numbers, gender, age, and diagnoses. In 2020, case numbers of outpatient care declined significantly (p = 0.021) compared to previous years and was related to the timing of political announcements answering SARS-CoV-2 pandemic. Additionally, during calendar week 10 to 15&mdash, the peak time of the spread of COVID-19 in Germany&mdash, the proportion of patients missing their consultation was significantly higher in 2020 than in 2019 (22.4% vs. 12.4%, p &lt, 0.001). Gender-associated differences regarding absences were not detected, but patients aged 85 years or older were significantly more likely to miss their consultation compared to all other age groups (p = 0.002). Regarding different disease clusters, patients with chronic inflammatory skin diseases and infectious and malignant diseases were more likely to miss their consultation (p = 0.006). Noticeably, less patients with malignant diseases, and particularly malignant melanoma, were registered during this pandemic. Our data support the hypothesis that medically constructive prioritization might not be implemented properly by patients themselves. Identifying missed patients and catching up on their medical care apart from COVID-19 will pose an enormous challenge for health care systems globally.

Increased photosensitivity is a common cutaneous adverse effect associated with the BRAF inhibitor vemurafenib. Clinically, it presents as an immediate sensation of heat and edematous erythema during sun exposure, as well as a sunburn reaction in terms of a late reaction. Phototesting has shown that the UVA range (320 nm to 400 nm), triggers both the immediate and the late reaction. In terms of pathogenesis, photochemical studies have suggested that exposure of vemurafenib to UVA radiation produces an UVA-absorbing photoproduct. In vitro studies on various cell models have also demonstrated that the phototoxic effects of vemurafenib are exclusively caused by UVA irradiation. This latter mechanism is probably responsible for the photosensitivity clinically observed in patients receiving vemurafenib. In addition, vemurafenib is able to inhibit ferrochelatase. The resulting increase in protoporphyrin IX has also been observed in some human studies involving the drug. However, it is yet unproven whether porphyrins actually contribute to the immediate skin reactions seen in individuals on vemurafenib, even though the clinical presentation is similar to that found in erythropoietic protoporphyria with a comparable pathomechanism. Other BRAF inhibitors, such as dabrafenib and encorafenib, are associated with significantly lower photosensitivity. It is essential that patients treated with vemurafenib are informed about immediate and delayed reactions potentially caused even by low doses of UVA. This includes counseling on photoprotective measures.

BACKGROUND: Hymenoptera stings can cause severe anaphylaxis in untreated venom-allergic patients. A correct diagnosis regarding the relevant species for immunotherapy is often hampered by clinically irrelevant cross-reactivity. In vespid venom allergy, cross-reactivity between venoms of different species can be a diagnostic challenge. To address immunological IgE cross-reactivity on molecular level, seven recombinant antigens 5 of the most important Vespoidea groups were assessed by different diagnostic setups.METHODS: The antigens 5 of yellow jackets, hornets, European and American paper wasps, fire ants, white-faced hornets, and Polybia wasps were recombinantly produced in insect cells, immunologically and structurally characterized, and their sIgE reactivity assessed by ImmunoCAP, ELISA, cross-inhibition, and basophil activation test (BAT) in patients with yellow jacket or Polistes venom allergy of two European geographical areas.RESULTS: All recombinant allergens were correctly folded and structural models and patient reactivity profiles suggested the presence of conserved and unique B-cell epitopes. All antigens 5 showed extensive cross-reactivity in sIgE analyses, inhibition assays, and BAT. This cross-reactivity was more pronounced in ImmunoCAP measurements with venom extracts than in sIgE analyses with recombinant antigens 5. Dose-response curves with the allergens in BAT allowed a differentiated individual dissection of relevant sensitization.CONCLUSIONS: Due to extensive cross-reactivity in various diagnostic settings, antigens 5 are inappropriate markers for differential sIgE diagnostics in vespid venom allergy. However, the newly available antigens 5 from further vespid species and the combination of recombinant allergen-based sIgE measurements with BAT represents a practicable way to diagnose clinically relevant sensitization in vespid venom allergy.

The nature of basophil activation as an ex vivo challenge makes it a multifaceted and promising tool for the allergist. Through the development of flow cytometry, discovery of activation markers such as CD63 and markers identifying basophil granulocytes, the basophil activation test ( BAT) has become a pervasive test. BAT measures basophil response to allergen crosslinking IgE on between 150 and 2,000 basophil granulocytes with remarkable analytical sensitivity in < 0.1 ml fresh blood. Dichotomous activation is assessed as the fraction of reacting basophils. In patients with food-, insect venom-, and drug allergy and patients with chronic urticaria BAT can be part of the diagnostic evaluation in addition to history, skin prick testing, and specific IgE determination. BAT may also be helpful in determining the clinically relevant allergen. Basophil sensitivity may be used to monitor patients on allergen immunotherapy, anti-IgE treatment, or in the natural resolution of allergy. The test may use fewer resources and be more reproducible than oral, sting, nasal or bronchial challenge testing. BAT may be useful before challenge testing as it is less stressful for the patient and avoids severe allergic reactions. It may be useful before challenge testing. An important next step is to standardize BAT and make it available in diagnostic laboratories. This article provides an overview of the practical and technical details as well as the utility of BAT in diagnosis and management of allergic diseases.

The strawberry fruit proteins Fra a 1.01E-1.08 are homologues of the major birch pollen allergen Bet v 1. Three of the proteins are known to have essential biological functions in pigment formation during fruit ripening and seem to be responsible for allergic reactions to strawberry fruit. We evaluated the cross-reactive allergenic potential of these putative strawberry allergens in patients allergic to birch pollen. Activation of basophils of eight atopic patients was studied using different concentrations of Fra a 1 isoforms. Bet v 1a was used as control and as atopic patient selection criterion. Although Fra a 1.01E-1.08 have amino acid sequence identities of 74.5-97.5% with Fra a 1.02, the basophil activation mediated by the eight Fra a 1 proteins differed substantially. Fra a 1.03 and Fra a 1.02 showed the highest activation of basophils, 73 and 66% of total basophils, respectively. On the basis of the high relative expression of the gene Fra a 1.02 in ripe strawberry fruits of allergenic varieties, Fra a 1.02 was identified as the main strawberry allergen of the Bet v 1 superfamily. Knowledge of the allergenic potential of Fra a 1.02/1.03 will help to improve food safety and can serve as a valuable marker for the development of red-fruited hypoallergenic strawberry cultivars.

Background The phenomenon of allergy transfer from an allergic donor to a non-allergic recipient via hematopoietic cell transplantation has been described by several reports. However, it could not yet been conclusively shown that allergic reaction of the recipient is elicited by the donor's cells. Objectives In the case of a 46-year-old male patient who – for the first time in his life – had two episodes of oral allergic syndrome upon kiwi consumption after having received myeloablative hematopoietic stem cell transplantation (HCT) from his kiwi-allergic sister, we aimed to clarify the origin of allergen reactive cells in the donor. We not only intended to demonstrate if allergy was transferred by HCT but also to present an experimental workup for the analysis of allergy transfer by HCT. Methods Allergic sensitization to kiwi in recipient and donor was proven by ImmunoCAP. Furthermore, origin of peripheral blood mononuclear cells (PBMCs) was analyzed by chromosomal fluorescence in situ hybridization (FISH). To confirm allergic reaction and activation of hematopoietic cells by customized kiwi extract, we performed basophil activation test from whole blood as well as T cell proliferation assays from purified PBMCs of both recipient and donor. Results Basophil activation upon kiwi extract was demonstrated in both recipient and donor. Besides, we showed proliferation of CD4+ T cells after incubation with kiwi extract. FISH analysis proved that hematopoietic cells of the male recipient completely originated from the female donor. Conclusion Exemplified in this patient, we show for the first time that allergy transfer is mediated by the donor's cells. Moreover, our experimental approach using customized kiwi extract to prove contribution of kiwi-specific T and B cells in both kiwi-allergic recipient and donor could serve as a model approach for future studies.

Honeybee (Apis mellifera) venom (HBV) represents an ideal model to study the role of particular venom components in allergic reactions in sensitized individuals as well as in the eusociality of Hymenoptera species. The aim of this study was to further characterize the HBV components C1q-like protein (C1q) and PDGF/VEGF-like factor 1 (PVF1). C1q and PVF1 were produced as recombinant proteins in insect cells. Their allergenic properties were examined by determining the level of specific IgE antibodies in the sera of HBV-allergic patients (n = 26) as well as by their capacity to activate patients' basophils (n = 11). Moreover, the transcript heterogeneity of PVF1 was analyzed. It could be demonstrated that at least three PVF1 variants are present in the venom gland, which all result from alternative splicing of one transcript. Additionally, recombinant C1q and PVF1 from Spodoptera frugiperda insect cells exhibited specific IgE reactivity with approximately 38.5% of sera of HBV-allergic patients. Interestingly, both proteins were unable to activate basophils of the patients, questioning their role in the context of clinically relevant sensitization. Recombinant C1q and PVF1 can build the basis for a deeper understanding of the molecular mechanisms of Hymenoptera venoms. Moreover, the conflicting results between IgE sensitization and lack of basophil activation, might in the future contribute to the identification of factors that determine the allergenic potential of proteins.

Vitiligo ist eine erworbene Hauterkrankung, an der weltweit 0,5 % der Bevolkerung erkranken und die eine grose Herausforderung in der dermatologischen Versorgung darstellt. Die Erkrankung geht fur Betroffene oftmals aufgrund der fleckigen Depigmentierung mit einer kosmetischen Entstellung und grosem Leidensdruck einher. Pathophysiologisch werden als Hauptursachen fur den Verlust funktionierender Melanozyten eine genetische Pradisposition, autoimmune Mechanismen und oxidativer Stress angesehen. Vorgestellt werden die Therapieempfehlungen der europaischen Leitlinie in Erganzung mit Empfehlungen aus aktuellen Ubersichtsarbeiten zu Vitiligo. Bisherige therapeutische Optionen greifen auf drei Wegen: (1.) Regulation der Autoimmunantwort mit topischen und systemischen immunmodulierenden Pharmaka (Kortikosteroide und Calcineurininhibitoren), (2.) Reduktion des melanozytaren, oxidativen Stress mittels topischer und systemischer Antioxidantien sowie (3.) Aktivierung der Melanozytenregeneration durch Phototherapie (v. a. UVB) und Transplantation von pigmentierten Zellen. Daruber hinaus sollten dem Patienten Techniken zur Camouflage angeboten werden. Nach erfolgreicher Repigmentierung ist eine Rezidivprophylaxe mit Calcineurininhibitoren sinnvoll. Kombinationstherapien oben genannter Therapieansatze werden generell als erfolgreicher angesehen als Monotherapien. Auch ist ein moglichst fruher Therapiebeginn prognostisch gunstig. Mit Hilfe der genannten Therapieansatze kann es gelingen das Fortschreiten der Erkrankung aufzuhalten, depigmentierte Herde zu stabilisieren und eine Repigmentierung zu erreichen. Nur in Ausnahmefallen kommt eine dauerhafte Depigmentierung in Frage. Weiterreichende Erkenntnisse zur Pathogenese der Erkrankung lassen auf neue Therapieansatze hoffen.

Hymenoptera venom allergy can cause severe anaphylaxis in untreated patients. Polistes dominula is an important elicitor of venom allergy in Southern Europe as well as in the United States. Due to its increased spreading to more moderate climate zones, Polistes venom allergy is likely to gain importance also in these areas. So far, only few allergens of Polistes dominula venom were identified as basis for component-resolved diagnostics. Therefore, this study aimed to broaden the available panel of important Polistes venom allergens. The 100 kDa allergen Pol d 3 was identified by mass spectrometry and found to be a dipeptidyl peptidase IV. Recombinantly produced Pol d 3 exhibited sIgE-reactivity with approximately 66% of Polistes venom-sensitized patients. Moreover, its clinical relevance was supported by the potent activation of basophils from allergic patients. Cross-reactivity with the dipeptidyl peptidases IV from honeybee and yellow jacket venom suggests the presence of exclusive as well as conserved IgE epitopes. The obtained data suggest a pivotal role of Pol d 3 as sensitizing component of Polistes venom, thus supporting its status as a major allergen of clinical relevance. Therefore, Pol d 3 might become a key element for proper diagnosis of Polistes venom allergy.

Purpose: This study aimed to assess the safety, efficacy, and patient satisfaction of superficial radiation therapy in the treatment of Peyronie's disease (PD) in a retrospective analysis. Methods and materials: We performed a retrospective analysis of 83 patients who underwent radiation therapy between 1999 and 2008 with 8 fractions of 4 Gy over a period of 6 months. With a mean follow-up time of 52 months, patients responded to a comprehensive questionnaire that covered patient characteristics, disease duration before radiation therapy, course of disease, treatment response, side effects, and patient satisfaction. Results: After a mean follow-up time of 52 months, 78% of the treated patients reported that PD progression had stopped. Furthermore 47% of patients had a symptom regression. Only 7% of patients reported PD progression. The penile curvature was improved in 49% of patients, and plaque induration could be reduced in 42% of patients. Moreover, 71% of patients reported substantial pain relief, as measured by a visual analogue scale (1 = not satisfied; 10 = very satisfied). Treatment satisfaction was rated with a median of 8 in a visual analogue scale out of 10. Side effects included transient erythema in 38.6% of patients and 9.6% reported of transient or chronic dryness. No severe side effects were observed. Conclusions: Radiation therapy for PD in the disease's early stages proved to be a safe and well-tolerated method with good results in pain relief, especially in patients aged

The strawberry fruit Fra a 1-proteins are homologues of the major birch pollen allergen Bet v 1 and have essential biological functions in pigment formation during fruit ripening. Patients affected by allergy against birch pollen tolerated fruits of a naturally occurring white-fruited F.×ananassa genotype, which showed reduced levels of Fra a 1 proteins along with enzymes of the anthocyanin pigment pathway. We evaluated the cross-reactive allergenic potential of a number of naturally occurring white- and red-fruited strawberry varieties to detect genotypes with low allergenic reactivity, whose fruit might be tolerated by patients with mild allergy. Protein extracts of 51 different strawberry varieties (Fragaria×ananassa, F. vesca, and F. nilgerensis) were screened by Western blot analysis with a polyclonal Fra a 1.02 antibody. Besides, activation of basophils of eight atopic patients allergic to birch pollen were studied using Bet v 1a and different concentrations of 15 selected strawberry protein extracts out of the 51 strawberry genotypes. Median percentages of activated basophils stimulated by extracts from white- and red-fruited genotypes ranged from 36 to 84% and 44 to 76%, respectively indicating that white-fruited strawberry are not per se hypoallergenic. Protein extracts from white-fruited F. vesca cv. Yellow Wonder showed the lowest cross-reactivity but high biological variability. The knowledge about the allergenic potential of different strawberry genotypes may help to improve food safety and can serve as starting point for the development of red-fruited hypoallergenic strawberry cultivars.

Up to present no curative treatment is known for Dupuytren's disease (DD). Surgery remains the most common treatment but lack of long-term efficacy and complications limit this therapeutic option.In a retrospective analysis, the results of radiotherapy with soft X-rays in the treatment of DD were evaluated.A total of 206 patients (297 affected hands) with DD were included. Radiation therapy was carried out with soft X-rays. A structured questionnaire considering patient and disease characteristics and effects of radiotherapy was evaluated after a median follow-up time of 40 months.Ninety-three (45%) of the 206 treated patients were reported on a regression of symptoms after radiation. No further disease progression (including patients with regression) was present in 165 patients (80%). Satisfaction with the therapy was expressed with an average score of 7.9 points (visual analogue scale, 0 = not satisfied, 10 = extremely satisfied). Subjective therapeutic effects for 426 nodules and/or cords showed a reduction of 92 nodules and/or cords.In 206 DD patients further disease progression was stopped in most patients. Radiotherapy proved to be well-tolerated, successful and satisfying for the patients.

BACKGROUND: Allergy to food is a hypersensitivity disorder of the immune system to normally harmless food ingredients. A promising solution for allergenic patients is the development of hypoallergenic food. OBJECTIVE: Selection and breeding of low-allergenic variety is the conventional strategy to produce hypoallergenic food. The strawberry fruit proteins Fra a 1.01E, Fra a 1.02 and Fra a 1.03 are homologous of the major birch pollen allergen Bet v1 but their individual allergenic potentials are unknown. METHOD: We produced the recombinant Fra a allergens and evaluated their cross allergenic potential in birch pollen allergic patients by a basophil activation test. Anti-Fra a 1.02 antibodies were also used to screen for allergen deficient strawberry lines. RESULTS: Although Fra a 1.01E, Fra a 1.02 and Fra a 1.03 have sequence similarities of 70, 71 and 74% with Bet v 1 Fra a 1.02 showed the highest allergenic potential. The data support the role of Fra a 1.02 as the major allergen for individuals affected by a strawberry allergy. The screening of strawberry varieties detected genotypes with significantly reduced levels of the allergen. CONCLUSION: Genotypes with reduced Fra a 1.02 proteins might serve as starting material for the breeding of hypoallergenic strawberry varieties.

Purpose of Review: We review basophil testing by flow cytometry with an emphasis on advantages and disadvantages. Recent Findings: There are many tools available to assess the presence and severity of allergic diseases in patients. For 50 years, peripheral blood basophils have been used as tools to study these diseases. It is a very accessible cell that binds IgE antibody and secretes the classical mediators responsible for the symptoms of allergic reactions. In the last decade, an even more accessible methodology, using flow cytometry, has been developed to enhance the ability to use basophils for both mechanistic and clinical diagnostics. Basophil testing has been included in diagnostics for different forms of allergies as well as to monitor disease status. Summary: A variety of studies have begun to establish both precise methods and their clinical relevance for disease diagnosis, but there remain some important questions on how to take optimal advantage of the behaviours of basophils.

Background Polymorphous light eruption (PLE) is the most common chronic and idiopathic photodermatosis. PLE is assumed to represent an immunological hypersensitivity reaction to a radiation-induced cutaneous antigen involving reactive oxygen species (ROS) on the basis of a genetic predisposition. Among others, cellular protection against ROS is provided by glutathione S-transferases (GSTs). Different variants of the GST enzymes may influence the activity and efficiency of detoxification and biotransformation of unknown UV-induced skin-antigens and other factors that may play an important role in the pathogenesis of PLE. Methods In this study the relationship between isoenzymes of the GST genes GSTM1, GSTT1 and GSTP1 and possible protective or predisposing effects on PLE was examined in 29 patients and 144 controls. Diagnosis of PLE was based on the presence of characteristic clinical features. Results No association between the functional polymorphisms of the GST gene family and PLE was found. Prevalence of certain GST isoenzymes or polymorphisms in patients with PLE did not differ from healthy controls. Conclusion Our data do not support prevalence of GST isoenzymes or polymorphisms as a protective effect against PLE. Especially a higher carrier frequency of GSTP1 Val105 as a protective factor against PLE which has been published before could not be proved. The GST genotypes GSTM1, GSTT1 and GSTP1 (including SNPs) seem to have no relevant association with PLE.

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Background: Hymenoptera venom sensitization in highly exposed individuals frequently requires risk assessment for future severe sting reactions. In this study, we determined the prevalence of Hymenoptera venom sensitization in individuals who hunt and fish and analyzed possible correlations between the severity of sting reactions and the IgE sensitization profile. Methods: In this cross-sectional study, paper-based, self-filled questionnaires about previous insect stings and sting reactions were obtained from individuals who hunt and fish in Bavaria, Germany. Blood samples were taken and analyzed for the levels of tryptase, total IgE and IgE to honey bee (i1) and wasp (13) venom, the recombinant allergens rApi m 1, rApi m 2, rApi m 3, rApi m 5, rApi m 10, rVes v 1, rVes v 5, and the CCD marker molecule MUXF3. Odd ratios (ORs) for sensitization and anaphylaxis and Pearson's correlations for the different allergens were calculated. Results: Of 257 participants, 50.2% showed a sensitization to honey bee venom (i1), and 58.4% showed sensitization to wasp venom (i3). A total of 98.4% of participants claimed to have been stung at least once. Anaphylaxis was reported in 18.7%, and a local sting reaction was reported in 18.3%. The highest sensitization rates were found for whole venom extracts, sensitization to any of the available recombinant allergens exceeded sIgE levels to honeybee venom (i1) in 28.5% and to wasp venom (i3) in 52.9% of participants. Participants with a history of more than 5 stings showed a higher risk for anaphylaxis. Conclusions: Sensitization to Hymenoptera venom and their recombinant allergens are present in the majority of individuals who hunt and fish. Sensitization to distinct recombinant allergens does not necessarily affect the severity of sting reactions including anaphylaxis. A meticulous medical history of the number of previous stings as well as systemic reactions remains essential. Keywords: Anaphylaxis, Hymenoptera venom sensitization, Outdoor population, Recombinant allergens, Sting reaction

In approximately 20% of patients with suspected allergies, no organic symptom explanation can be found. Limited knowledge about patients with "medically unexplained symptoms (MUS)" contributes to them being perceived as "difficult" and being treated inadequately. This study examined the psychobehavioural characteristics of patients presenting for a diagnostic allergy work-up. Patients were interviewed and completed various self-rating questionnaires. Patient-Doctor interaction was evaluated, and the organic explicability of the patients' symptoms was rated by allergists. Patients with vs. those without MUS differed in several respects. Mental comorbidity, female sex, dissatisfaction with care, and a problematic countertransference (the interviewer's feelings towards the patient) independently predicted MUS. Patients whose symptoms could be explained organically reported more psychobeha-vioural problems than a control group of immuno-therapy patients. There were no differences in patient-doctor interaction. In patients with suspected allergies, recognition of psychological burden and concurrent mental disorders is important. Mental comorbidity and a difficult patient-doctor interaction may predict MUS.

Andre Franke and colleagues report a genome-wide association study for psoriasis vulgaris in a German cohort with replication in German and North American psoriasis cohorts. They identify variants in TRAF3IP2, encoding a protein involved in IL-17 mediated T-cell immune response, associated with psoriasis. Psoriasis is a multifactorial skin disease characterized by epidermal hyperproliferation and chronic inflammation, the most common form of which is psoriasis vulgaris (PsV). We present a genome-wide association analysis of 2,339,118 SNPs in 472 PsV cases and 1,146 controls from Germany, with follow-up of the 147 most significant SNPs in 2,746 PsV cases and 4,140 controls from three independent replication panels. We identified an association at TRAF3IP2 on 6q21 and genotyped two SNPs at this locus in two additional replication panels (the combined discovery and replication panels consisted of 6,487 cases and 8,037 controls; combined P = 2.36 × 10−10 for rs13210247 and combined P = 1.24 × 10−16 for rs33980500). About 15% of psoriasis cases develop psoriatic arthritis (PsA). A stratified analysis of our datasets including only PsA cases (1,922 cases compared to 8,037 controls, P = 4.57 × 10−12 for rs33980500) suggested that TRAF3IP2 represents a shared susceptibility for PsV and PsA. TRAF3IP2 encodes a protein involved in IL-17 signaling and which interacts with members of the Rel/NF-κB transcription factor family.

We carried out a meta-analysis of two recent psoriasis genome-wide association studies with a combined discovery sample of 1,831 affected individuals (cases) and 2,546 controls. One hundred and two loci selected based on P value rankings were followed up in a three-stage replication study including 4,064 cases and 4,685 controls from Michigan, Toronto, Newfoundland and Germany. In the combined meta-analysis, we identified three new susceptibility loci, including one at NOS2 (rs4795067, combined P = 4 × 10⁻¹¹), one at FBXL19 (rs10782001, combined P = 9 × 10⁻¹⁰) and one near PSMA6-NFKBIA (rs12586317, combined P = 2 × 10⁻⁸). All three loci were also associated with psoriatic arthritis (rs4795067, combined P = 1 × 10⁻⁵; rs10782001, combined P = 4 × 10⁻⁸; and rs12586317, combined P = 6 × 1⁻⁵) and purely cutaneous psoriasis (rs4795067, combined P = 1 × 10⁻⁸; rs10782001, combined P = 2 × 10⁻⁶; and rs12586317, combined P = 1 × 10⁻⁶). We also replicated a recently identified association signal near RNF114 (rs495337, combined P = 2 × 10⁻⁷).

Objective Psychobehavioral characteristics of patients with somatoform disorders (SFDs), are increasingly discussed as possible positive criteria for this diagnostic group. However, little is known about psychobehavioral differences, or similarities, between the different SFD presentations, i.e., polysymptomatic [multisomatoform/somatization disorders (MSD)] versus mono- or oligosymptomatic courses [pain disorder (PD), undifferentiated somatoform disorder (USD)]. Methods This is a cross-sectional study including 268 consecutive allergology inpatients. After an Structured Clinical Interview for DSM-IV , patients completed several self-rating questionnaires. Results were compared within the different SFD presentations as well as between patients with versus without SFDs. Results We identified 72 patients with an SFD. There were fewer and smaller psychobehavioral differences within patients with the different SFD presentations (MSD, USDs, PDs) than between patients with undifferentiated versus no SFD. Patients with one of the three different SFD subdiagnoses scored similarly on many measures referring to psychosocial distress (e.g., psychological distress, mental health-related quality of life, dissatisfaction with care). The number of reported symptoms, somatic symptom severity, a self-concept of bodily weakness, the degree of disease conviction, and physical health-related quality of life discriminated the different SFD presentations not only from patients without SFDs but also from each other. Conclusions Patients diagnosed with one of the different SFD subtypes share many psychobehavioral characteristics, mostly regarding the reporting of psychosocial distress. Perceived somatic symptom severity and physical impairment as indicators of bodily distress could either further define categorical subdivisions of SFD or dimensionally graduate one general SFD category defined by bothering bodily symptoms and disproportionate psychosocial distress.

Summary Background Flow cytometric basophil activation tests (BAT) have been developed as cellular tests for in vitro diagnosis of IgE-mediated reactions. Different markers and techniques have been used after stimulation with various allergens. Objective It was the aim of the present study to compare an established BAT (Flow-CAST®) with a newly developed basophil activation protocol using CD63 and CCR3 (Flow2 CAST®) in patients with type-I allergy to antibiotics. Materials and methods Twenty-four patients with a history of type-I allergy to antibiotics were examined. A careful allergy history was taken, and skin tests and determination of specific IgE antibodies were performed. Two different BAT using CD63 expression but different protocols were carried out after stimulation with different concentrations of antibiotics. Fifteen healthy subjects without a history of antibiotic allergy were studied as controls. Results The Flow2 CAST® showed a higher sensitivity than the Flow-CAST® (55% vs. 53%) with regard to patients' history. Specificity was 80% both for the Flow2 CAST® and for the Flow-CAST® with regard to controls with negative history and negative RAST. Conclusion These results show the value of two different BAT as cellular tests in the in vitro diagnosis of patients with antibiotic allergy with equal specificity and a slightly higher sensitivity for the Flow2 CAST®. Cite this as: B. Eberlein, I. Leon Suarez, U. Darsow, F. Rueff, H. Behrendt and J. Ring, Clinical & Experimental Allergy, 2010 (40) 411–418.

OBJECTIVE: To explore a combination of health-related psychobehavioral features as potential positive criteria for somatoform disorders (SFD). Currently, SFD can only be diagnosed in the absence of sufficient organic symptom explanation, resulting in low criterion validity and delay of appropriate therapy. METHODS: Cross sectionally, we studied various psychobehavioral characteristics of 197 inpatients with suspected allergies. At the beginning of the medical work-up, patients were interviewed and completed a set of self-rating questionnaires (Illness Perception Questionnaire-Revised, Whiteley Index-7, Cognitions About Body And Health Questionnaire, Scale for the Assessment of Illness Questionnaire, Health Attitude Survey, Reassurance Questionnaire, and Patient Health Questionnaire). Organic explicability of the presenting symptoms was assessed by allergists at the end of the work-up. Forty-eight patients with SFD were compared with 149 patients without SFD, and predictive models were set up. To control for effects of the work-up situation, we also investigated 47 patients with an established diagnosis of hymenoptera venom allergy. RESULTS: In the work-up group, various self-reported psychobehavioral features discriminated patients with SFD from patients without SFD. In logistic regression analysis, self-reported dissatisfaction with medical care, disease conviction, reduced symptom controllability, and reduced body scanning independently predicted SFD. A predictive model based on these psychobehavioral characteristics had high sensitivity and specificity (area under the curve = 0.86, 95% Confidence Interval = 0.79-0.93; p < .001), which was comparable to the Patient Health Questionnaire-15, an established SFD screening tool assessing somatization. CONCLUSIONS: Psychobehavioral characteristics in patients with SFD cannot solely be attributed to the uncertainty of a work-up situation. Their predictive value is comparable to that of the traditional measuring of symptom number and severity; hence, they should be considered as SFD positive criteria in Diagnostic and Statistic Manual of Mental Disorders, 5th Edition.