Human AZFb deletions cause distinct testicular pathologies depending on their extensions in Yq11 and the Y haplogroup: new cases and review of literature - Vogt, P. H.; Bender, U.; Deibel, B.; Kiesewetter, Franklin; Zimmer, J.; Strowitzki, T. (Cell & Bioscience, 2021)
Genomic AZFb deletions in Yq11 coined “classical” (i.e. length of Y DNA deletion: 6.23 Mb) are associated with meiotic arrest (MA) of patient spermatogenesis, i.e., absence of any postmeiotic germ cells. These AZFb deletions are caused by non-allelic homologous recombination (NAHR) events between identical sequence blocks located in the proximal arm of the P5 palindrome and within P1.2, a 92 kb long sequence block located in the P1 palindrome structure of AZFc in Yq11. This large genomic Y region includes deletion of 6 protein encoding Y genes, EIFA1Y, HSFY, PRY, RBMY1, RPS4Y, SMCY. Additionally, one copy of CDY2 and XKRY located in the proximal P5 palindrome and one copy of BPY1, two copies of DAZ located in the P2 palindrome, and one copy of CDY1 located proximal to P1.2 are included within this AZFb microdeletion. It overlaps thus distally along 2.3 Mb with the proximal part of the genomic AZFc deletion. However, AZFb deletions have been also reported with distinct break sites in the proximal and/or distal AZFb breakpoint intervals on the Y chromosome of infertile men. These so called “non-classical” AZFb deletions are associated with variable testicular pathologies, including meiotic arrest, cryptozoospermia, severe oligozoospermia, or oligoasthenoteratozoospermia (OAT syndrome), respectively. This raised the question whether there are any specific length(s) of the AZFb deletion interval along Yq11 required to cause meiotic arrest of the patient’s spermatogenesis, respectively, whether there is any single AZFb Y gene deletion also able to cause this “classical” AZFb testicular pathology? Review of the literature and more cases with “classical” and “non-classical” AZFb deletions analysed in our lab since the last 20 years suggests that the composition of the genomic Y sequence in AZFb is variable in men with distinct Y haplogroups especially in the distal AZFb region overlapping with the proximal AZFc deletion interval and that its extension can be “polymorphic” in the P3 palindrome. That means this AZFb subinterval can be rearranged or deleted also on the Y chromosome of fertile men. Any AZFb deletion observed in infertile men with azoospermia should therefore be confirmed as “de novo” mutation event, i.e., not present on the Y chromosome of the patient’s father or fertile brother before it is considered as causative agent for man’s infertility. Moreover, its molecular length in Yq11 should be comparable to that of the “classical” AZFb deletion, before meiotic arrest is prognosed as the patient’s testicular pathology.
CRIS-Team Scopus Importer:2021-05-14
Keywords: AZFb Y genes; AZFb “de novo” and “polymorphic” deletions; AZFb-c amplicons; Meiotic arrest; OAT syndrome; Y-haplogroups; “Classical” and “non-classical” AZFb deletions

Identification of Sola l 4 as Bet v 1 homologous pathogenesis related-10 allergen in tomato fruits - Wangorsch, Andrea; Jamin, Annette; Foetisch, Kay; Malczyk, Anna; Reuter, Andreas; Vierecke, Sabine; Schuelke, Stefan; Bartel, Detlef; Mahler, Vera; Lidholm, Jonas; Vieths, Stefan; Scheurer, Stephan (Molecular Nutrition & Food Research, 2015)
The aim was to investigate the potential contribution of a major birch pollen Bet v 1-homologous allergen to birch pollen-associated tomato fruit allergy.Two isoforms of a Bet v 1-homologous protein (designated Sola l 4) from tomato fruit were identified by cDNA-cloning and produced as recombinant proteins. Allergen-specific IgE levels to tomato, birch pollen, Bet v 1, and Sola l 4 were determined in birch pollen allergic patients with allergy or tolerance to tomato. Sola l 4 was recognized in 76% of birch/tomato allergic patients, while tomato- and Bet v 1-specific IgE was detectable in 64% and 81% of sera. Almost all patients sensitized to Bet v 1 reacted with Sola l 4. Both Sola l 4 isoforms displayed allergenic potency and IgE-cross-reactivity with Bet v 1 as investigated by competitive ELISA and in vitro mediator release assay. Nevertheless, the reactivity pattern of patients' sera was diverse.Sola l 4, a novel pathogenesis related-10 protein, qualifies as major allergen in tomato fruits. Data suggest Sola l 4 as class II allergen. IgE-testing using Sola l 4 showed low clinical specificity, but high sensitivity in tomato allergic patients and will further improve component-resolved allergy diagnosis.
EVALuna2:19548

Nickel and cobalt release from metal alloys of tools - a current analysis in Germany - Kickinger-Lörsch, Anja; Bruckner, Thomas; Mahler, Vera (Contact Dermatitis, 2015)
The former 'EU Nickel Directive' and, since 2009, the REACH Regulation (item 27 of Annex XVII) do not include all metallic objects. The nickel content of tools is not regulated by the REACH Regulation, even if they may come into in prolonged contact with the skin. Tools might be possible sources of nickel and cobalt sensitization, and may contribute to elicitation and maintenance of hand eczema.To perform a current analysis of the frequency of nickel or cobalt release from new handheld tools purchased in Germany.Six hundred unused handheld tools from the German market were investigated with the dimethylglyoxime test for nickel release and with disodium-1-nitroso-2-naphthol-3,6-disulfonate solution for cobalt release.Nickel release was detected in 195 of 600 (32.5%) items, and cobalt in only six (1%) of them. Positive nickel results were nearly twice as frequent in tools 'made in Germany' than in tools without a mark of origin. Tools made in other European countries did not release nickel. Cobalt release was only found in pliers and a saw. A correlation was found between price level and nickel release. Among toolkits, 34.2% were inhomogeneous concerning nickel release.The German market currently provides a large number of handheld tools that release nickel, especially tools 'made in Germany'. For consumer protection, it seems appropriate to include handheld tools in the REACH Regulation on nickel.
EVALuna2:19554

Non-celiac gluten/wheat sensitivity (NCGS)—a currently undefined disorder without validated diagnostic criteria and of unknown prevalence - Reese, Imke; Schaefer, Christiane; Kleine-Tebbe, Joerg; Ahrens, Birgit; Bachmann, Oliver; Ballmer-Weber, Barbara; Beyer, Kirsten; Bischoff, Stephan C.; Bluemchen, Katharina; Doelle, Sabine; Enck, Paul; Enninger, Axel; et al. (Allergo Journal, 2018)
Within the last decade, non-celiac gluten/wheat sensitivity (NCGS) has been increasingly discussed not only in the media but also among medical specialties. The existence and the possible triggers of NCGS are controversial. Three international expert meetings which proposed recommendations for NCGS were not independently organized and only partially transparent regarding potential conflicts of interest of the participants. The present position statement reflects the following aspects about NCGS from an allergist's and nutritionist's point of view: (A) Validated diagnostic criteria and/or reliable biomarkers are still required. Currently, this condition is frequently self-diagnosed, of unknown prevalence and non-validated etiology. (B) Gluten has not been reliably identified as an elicitor of NCGS because of high nocebo and placebo effects. Double-blind, placebo-controlled provocation tests are of limited value for the diagnosis of NCGS and should be performed in a modified manner (changed relation of placebo and active substance). (C) Several confounders hamper the assessment of subjective symptoms during gluten-reduced or gluten-free diets. Depending on the selection of food items, e.g., an increased vegetable intake with soluble fibers, diets may induce physiological digestive effects and can modify gastrointestinal transit times independent from the avoidance of gluten. (D) A gluten-free diet is mandatory in celiac disease based on scientific evidence. However, a medically unjustified avoidance of gluten may bear potential disadvantages and risks. (E) Due to a lack of diagnostic criteria, a thorough differential diagnostic work-up is recommended when NCGS is suspected. This includes a careful patient history together with a food-intake and symptom diary, if necessary an allergy diagnostic workup and a reliable exclusion of celiac disease. We recommend such a structured procedure since a medically proven diagnosis is required before considering the avoidance of gluten.
EVALuna2:50606

Non-Celiac Gluten-/Wheat Sensitivity (NCGS) - A previously undefined Symptoms with lack of Diagnostic Criteria and unknown Frequency Position Paper of the Working Group Food Allergy of the German Society of Allergology and clinical Immunology (DGAKI) - Reese, Imke; Schaefer, Christiane; Kleine-Tebbe, Joerg; Ahrens, Birgit; Bachmann, Oliver; Ballmer-Weber, Barbara; Beyer, Kirsten; Bischoff, Stephan C.; Bluemchen, Katharina; Doelle, Sabine; Enck, Paul; Enninger, Axel; et al. (Ernährungsumschau, 2018)
EVALuna2:51598

Omalizumab treatment in patients with chronic inducible urticaria: A systematic review of published evidence - Maurer, Marcus; Metz, Martin; Brehler, Randolf; Hillen, Uwe; Jakob, Thilo; Mahler, Vera; Pfohler, Claudia; Staubach, Petra; Treudler, Regina; Wedi, Bettina; Magerl, Markus (Journal of Allergy and Clinical Immunology, 2018)
BACKGROUND: Omalizumab, a recombinant anti-IgE antibody, effectively treats chronic spontaneous urticaria. Evidence is lacking in patients with chronic inducible urticarias (CIndUs), which are frequently H1-antihistamine resistant. OBJECTIVE: From the current published literature, we aimed to determine the strength of evidence for omalizumab efficacy and safety in the treatment of CIndUs. METHODS: We performed a PubMed search to identify evidence on omalizumab use in the following 9 CIndU subtypes: symptomatic dermographism, cold urticaria, delayed-pressure urticaria, solar urticaria, heat urticaria, vibratory angioedema, cholinergic urticaria, contact urticaria, and aquagenic urticaria. RESULTS: Forty-three trials, case studies, case reports, and analyses were identified. Our review indicates that omalizumab has substantial benefits in patients with various CIndUs. The evidence is strongest for symptomatic dermographism, cold urticaria, and solar urticaria. Little/no evidence was available on vibratory angioedema and aquagenic and contact urticaria. Our review supports rapid onset of action demonstrated through early symptom control in most cases, sometimes within 24 hours. Many patients gained complete/partial symptom relief and substantially improved quality of life. Adverse events were generally low, with omalizumab being well tolerated by most patients, including children. CONCLUSIONS: A strong body of evidence supports the use of omalizumab in the treatment of patients with therapy-refractory CIndU. More data from randomized controlled studies are warranted.
EVALuna2:34800

Patch test results with the European baseline series and additions thereof in the ESSCA network, 2015-2018 - Uter, Wolfgang; Bauer, Andrea; Belloni Fortina, Anna; Bircher, Andreas J.; Brans, Richard; Buhl, Timo; Cooper, Susan M.; Czarnecka-Operacz, Magdalena; Dickel, Heinrich; Dugonik, Aleksandra; Geier, Johannes; Gimenez-Arnau, Ana M.; et al. (Contact Dermatitis, 2020)
Background Clinical surveillance of the prevalence of contact allergy in consecutively patch tested patients is a proven instrument to continually assess the importance of contact allergens (haptens) assembled in a baseline series. Objectives To present current results from the European Surveillance System on Contact Allergies, including 13 countries represented by 1 to 11 departments. Methods Anonymized or pseudonymized patch test and clinical data from various data capture systems used locally or nationally as transferred to the Erlangen data centre were pooled and descriptively analysed after quality control. Results In the 4 years (2015-2018), data from 51 914 patients patch tested with the European baseline series (EBS) of contact allergens were analysed. Contact allergy to nickel was most frequent (17.6% positive), followed by contact allergy to fragrance mix I (6.9%), methylisothiazolinone (MI; 6.2%), andMyroxylon pereiraeresin (balsam of Peru; 5.8%). Conclusions While the prevalence of MI contact allergy decreased substantially following regulatory intervention, the persistently high levels of allergy to metals, fragrances, other preservatives, and rubber chemicals point to problems needing further research and, potentially, preventive efforts. Results with national additions to the baseline series provide important information on substances possibly to be considered for inclusion in the EBS.
CRIS-Team WoS Importer:2020-10-23

Patterns of chronic hand eczema: a semantic map analysis of the CARPE registry data - Cazzaniga, Simone; Apfelbacher, C.; Diepgen, T.; Ofenloch, R. F.; Weisshaar, E.; Molin, S.; Bauer, A.; Mahler, Vera; Elsner, P.; Schmitt, J.; Ballmer-Weber, B. K.; Spring, P.; et al. (British Journal of Dermatology, 2018)
BACKGROUND: Hand eczema has a high incidence and prevalence and has a negative impact on both physical and psychological well-being, with the risk of persistence as a chronic condition. Epidemiological studies on hand eczema provided mainly descriptive and risk analyses, but pattern analyses of variables associated with hand eczema, in particular chronic hand eczema, have not been explored to date. OBJECTIVES: To investigate and display the semantics of associations between variables of hand eczema obtained from the Swiss and German registries of chronic hand eczema (CARPE) to dissect patterns and novel links. METHODS: This was a cross-sectional study on selected variables from the CARPE registries. Associations between variables were analysed by means of an autoassociative system. A semantic connectivity map was generated by using a maximum spanning tree algorithm. RESULTS: Baseline datasets of 1466 patients with chronic hand eczema (Switzerland: 199; Germany: 1267) were analysed. Occupational exposure had the highest impact in the total and country cohorts. We identified two areas of exposure linked to corresponding occupations that clearly demarcated the sexes. CONCLUSIONS: This study, using semantic connectivity as a novel method of data analysis, reveals the complexity of features characterizing chronic hand eczema as well as novel association patterns that deserve further investigation.
EVALuna2:34803

Quality of life and disease severity in dermatitis patients with fragrance allergy—A cross-sectional European questionnaire study - Bennike, Niels H.; Heisterberg, Maria S.; White, Ian R.; Mahler, Vera; Silvestre-Salvador, Juan F.; Giménez-Arnau, Ana; Johansen, Jeanne D. (Contact Dermatitis, 2019)
Background: Fragrance contact allergy is common, but few studies on quality of life (QoL) in affected patients exist. Recently, the disease-specific Fragrance Quality of Life Index (FQLI) was developed. Objectives: To characterize QoL in European dermatitis patients with fragrance contact allergy at the time of diagnosis. Methods: This was a cross-sectional study, in which 2011 Danish, British, Spanish and German adult consecutive dermatitis patients were invited to complete a questionnaire on self-reported disease severity, the Dermatology Life Quality Index (DLQI), and the FQLI immediately prior to being patch tested. Results: One thousand seven hundred and fifty-eight patients responded, and 259 (14.7%; country range 11.7%-18.5%) were fragrance-positive. Among these, the total (SD) DLQI score was 6.2 (5.6) and the total (SD) FQLI score was 60 (25), with both estimates being comparable to those in fragrance-negative patients. Adjusting the total FQLI score for age, sex and self-rated disease severity showed a higher (ie, worse) score in fragrance-positive patients (3.6-point increase; 95% confidence interval: 0.30-6.8 points; P = 0.03). Specifically, contact allergy to oxidized linalool was associated with greater impairment in QoL. Conclusions: QoL in patients with fragrance contact allergy is impaired at a level comparable to that in other patch tested dermatitis patients, at the time of diagnosis, across several European countries.
CRIS-Team Scopus Importer:2019-06-07
Keywords: allergic contact dermatitis; contact allergy; cross-sectional questionnaire; European; fragrance allergy; patch testing; patient-reported outcomes; quality of life

S2k-Leitlinie zum Gebrauch von Präparationen zur lokalen Anwendung auf der Haut (Topika) - Wohlrab, Johannes; Staubach, Petra; Augustin, Matthias; Eisert, Lisa; Huenerbein, Andreas; Nast, Alexander; Reimann, Holger; Stroemer, Klaus; Mahler, Vera (Journal der Deutschen Dermatologischen Gesellschaft, 2018)
Diese Leitlinie richtet sich an Assistenz- und Fachärzte der Dermatologie sowie an Kostenträger und politische Entscheidungsgremien. Die Leitlinie wurde im formellen Konsensusverfahren (S2k) von Dermatologen unter Einbindung von Apothekern erstellt. Die Leitlinie stellt allgemeine Aspekte der Pharmakokinetik sowie der regulatorischen Begrifflichkeiten dar. Es werden Empfehlungen zur Indikation von Magistralrezepturen sowie deren Qualitätssicherung gegeben. Die Bedeutung der galenischen Grundlagen und die Problematik bei einer Substitution gegeneinander verschiedener Grundlagen werden dargestellt. Die Leitlinie umfasst Kriterien zur Auswahl einer adäquaten Grundlage sowie spezifische Aspekte zur Therapieplanung. Die Leitlinie gibt Empfehlungen zum Management bei Unverträglichkeiten gegenüber Bestandteilen der Grundlagen oder Hilfsstoffe.
EVALuna2:34799

Severity and functional disability of patients with occupational contact dermatitis: validation of the German version of the Occupational Contact Dermatitis Disease Severity Index - Ofenloch, Robert F.; Diepgen, Thomas L.; Popielnicki, Ana; Weisshaar, Elke; Molin, Sonja; Bauer, Andrea; Mahler, Vera; Elsner, Peter; Schmitt, Jochen; Apfelbacher, Christian (Contact Dermatitis, 2015)
The Occupational Contact Dermatitis Disease Severity Index (ODDI) was designed in Australia to measure severity and functional disability in patients with occupational contact dermatitis (OCD) of the hands. The ODDI was translated into the German language with a linguistic validation process. The psychometric properties of the German version of the ODDI are still unclear.To report the linguistic validation procedure and to perform a psychometric validation by investigating the validity and reliability of the German ODDI version in a sample of patients with OCD.Data were drawn from the baseline assessment (T0) and first follow-up (T1) of the German chronic hand eczema (CHE) registry (CARPE). Spearman correlations of the ODDI with reference measures were computed to assess validity. Cronbach's alpha was calculated as a measure of internal consistency, and the intraclass correlation coefficient (ICC) was calculated to assess retest reliability. The smallest real difference (SRD) and minimal clinically important difference (MCID) were calculated to assess sensitivity to change. Physician Global Assessment (PGA) was used as an anchor for the MCID.Four hundred and twenty-two patients (54.5% female, mean age 45.1 years) were included for analysis. Cronbach's alpha was found to be 0.73. The ICC was 0.79. Correlations between the ODDI total and the Dermatology Life Quality Index (rho = 0.36), and between PGA (rho = 0.48) and patient-assessed disease severity (rho = 0.40), were of moderate strength. The MCID (1.29) was found to be smaller than the SRD (1.87).The German ODDI version is reliable and valid for the measurement of functional impairment and disease severity in patients suffering from OCD.
EVALuna2:19560

Statement of the German Contact Dermatitis Research Group (DKG) and the German Dermatological Society (DDG) on liability issues associated with patch testing using a patient's own materials - Mahler, Vera; Dickel, Heinrich; Diepgen, Thomas Ludwig; Hillen, Uwe; Geier, Johannes; Kaufmann, Roland; Kreft, Burkhard; Schnuch, Axel; Szliska, Christiane; Bender, Albrecht (Journal der Deutschen Dermatologischen Gesellschaft, 2017)
EVALuna2:35415

Topical delgocitinib is an efficacious and well tolerated treatment for patients with chronic hand eczema - Worm, Margitta; Bauer, Andrea; Elsner, Peter; Mahler, Vera; Molin, Sonja; Nielsen, Thor Schutt Svane (JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY, 2019)
CRIS-Team WoS Importer:2019-09-17

Type IV contact allergies in the food processing industry: an update - Bauer, A.; Schubert, S.; Geier, J.; Mahler, Vera (Hautarzt, 2018)
BACKGROUND: The food sector is one of the high-risk areas for occupational irritative and allergic contact eczema. OBJECTIVES: The present work provides an overview of the main allergens as well as sensitization frequencies and risk in various food industry occupations. METHODS: The literature on type IV sensitization in the food sector is summarized. RESULTS: The relative risk of developing a work-related eczema in food processing is increased by more than 3 times. The comparison group was calculated on the basis of the proportion of documented cases in the IVDK (Informationsverbund Dermatologischer Kliniken) network per 100,000 working persons in relation to the average of the years 2005 and 2010. For this purpose, the average risk of all patients was set as reference to 1. Bakers, pastry chefs, cooks and meat and fish processors are mainly affected. In addition to irritant contact eczema, allergic contact eczema and protein contact dermatitis often occur. Leading haptens (main allergens) are rubber ingredients, but also disinfectants and compositae. CONCLUSION: Only a few contact allergens are responsible for the majority of job-relevant sensitizations in the food industry.
EVALuna2:34791

Which factors are associated with the use of systemic antihistamines in patients with chronic hand eczema? Results from the CARPE registry - Apfelbacher, Christian; Weiss, M.; Molin, S.; Bauer, A.; Mahler, Vera; Schmitt, J.; Elsner, P.; Diepgen, T. L.; Weisshaar, E. (Journal of the European Academy of Dermatology and Venereology, 2016)
Antihistamines (AH) are often used to treat chronic skin diseases related to allergy and/or pruritus. Data on the use of AH in patients with chronic hand eczema (CHE) is scarce.The objective of this study was to investigate prevalence and determinants of AH use in patients with CHE.Data were drawn from the German CARPE registry. The relationship of clinical, demographic and treatment-related variables with AH use in the past 12 months was analysed by means of logistic regression. Odds ratios (OR) with corresponding 95% confidence intervals (CIs) were computed.A total of 1255 patients with CHE were eligible for analysis (54.1% female; mean age: 47.1 years, standard deviation (SD) 13.6 years). Mean subjective disease severity was 5.0 (SD 2.5). 25% of the sample reported to have used AH in the past 12 months. Significant positive associations with AH use were identified for moderate (OR = 3.05, 95% CI 1.81-5.15) or severe (OR = 4.27, 95% CI 2.40-7.59) pruritus, a history of systemic treatment (e.g. alitretinoin) (OR = 2.85, 95% CI: 2.06-3.96), UV phototherapy (OR = 1.78, 95% CI 1.28-2.46), flexural eczema (OR = 1.89, 95% CI 1.32-2.71), allergic rhinitis/conjunctivitis (OR = 2.41, 95% CI 1.71-3.39) and female gender (OR = 1.58, 95% CI 1.16-2.14) in multivariate analyses (N = 1184). Significant inverse associations were found for an eczema localization besides the hands (OR = 0.66, 95% CI 0.46-0.94) and for patients being recruited in hospital (vs. dermatological practice; OR = 0.47, 95% CI 0.33-0.67).This study suggests that AH use is frequent in patients with CHE and mainly related to female gender, disease severity, pruritus, comorbid atopic disease and treatment centre.
EVALuna2:19546

Year-round treatment initiation for a 6-grasses pollen allergoid in specific immunotherapy of allergic rhinoconjunctivitis and asthma - Mahler, Vera; Zielen, Stefan; Rosewich, Martin (Immunotherapy, 2019)
Aim: Allergen immunotherapy (AIT) is an effective treatment for allergic diseases. We investigate whether treatment-initiation during the pollen season is safe. Methods: RCT-IIIb-trial of 6-grass-pollen-allergoid (Allergovit (R)) in grass pollen-allergic patients (18-65 years) with moderate-severe rhinitis/rhinoconjunctivitis (+/- controlled asthma), randomized 2:1 to treatment-initiation during (Group-A) versus outside the pollen season (Group-B). Results: Of 240 patients (32.8 +/- 9.9 years, 19.5% asthma) treated, 84.9% (Group-A) and 86.6% (Group-B) reached maintenance dose without delay. Treatment-emergent adverse events occurred in 108 (68.4%/Group-A) and 41 patients (56.2%/Group-B) leading to premature trial-termination in 11 patients (7%/A) versus 3 (4.1%/B). Across groups, physicians (for 190 patients; 85.2%) and patients (192; 86.1%) rated the tolerability as 'very good'-'good'. Phleum pratense-specific IgG4 increased in both groups (p < 0.0001). Conclusion: Year-round allergen immunotherapy-initiation with this preparation is safe.
CRIS-Team WoS Importer:2020-02-04