Steffen Schubert

Georg-August-Universität Göttingen | GAUG · Information Network of Departments of Dermatology

Background: Hydroperoxides of limonene (Lim-OOHs) and linalool (Lin-OOHs) are potent contact sensitizers. Objectives: To investigate the prevalence of positive patch test (PT) reactions to Lim-OOHs and Lin-OOHs in consecutive patients, their demographic factors and concomitant reactions. Methods: Between 7/2018 and 12/2020, Lim-OOHs 0.3% pet....

Background: Benzisothiazolinone (BIT; CAS No. 2634-33-5) is used as a biocide in various products, including water-based paints, metalworking fluids, and household products. In recent years, increasing sensitization rates have been observed in Europe. Objective: To describe a time trend of sensitization to BIT, analyse concomitant reactions, and...

We outline constituents of tattoo and permanent make-up ink with regard to inflammatory tattoo reactions and population-based confounders. The comprehensive review of patch tested tattoo patients between 1997-2022 shows that tattoo allergy cannot be reliably diagnosed via patch testing with today's knowledge. Weak penetration and slow haptenization...

Beim Tätowieren oder beim Anfertigen eines Permanent Make-ups werden Kontaktallergene direkt in die Haut verabreicht, und Pigmente verbleiben für Jahrzehnte an Ort und Stelle. Diese Pigmente werden im Laufe der Zeit chemisch verändert, dabei kann es auch zu Unverträglichkeitsreaktionen kommen. Die Typ-IV-Allergie bezeichnet kontaktallergische Reakt...

Background: Continual analyses of patch test results with the European baseline series (EBS) serve both contact allergy surveillance and auditing the value of included allergens. Objectives: To present results of current EBS patch testing, obtained in 53 departments in 13 European countries during 2019 and 2020. Methods: Anonymised or pseudony...

Background: Essential oils (EOs) are widely used in cosmetics, perfumes, massage fluids, aroma therapy, and natural medicine. Some essential oils contain contact sensitizers. Objectives: To describe the frequency of sensitization to EOs in dermatitis patients presenting in skin clinics including concomitant reactions, to evaluate the EO patch te...

Background: In 2019, a number of allergens (haptens), henceforth, 'the audit allergens,' were considered as potential additions to the European baseline series (EBS), namely, sodium metabisulfite, 2-bromo-2-nitropropane-1,3-diol, diazolidinyl urea, imidazolidinyl urea, Compositae mix II (2.5 or 5% pet), linalool hydroperoxides (lin-OOH), limonene...

Background: Benzyl alcohol is a widely used preservative, solvent, and fragrance material. According to published data, it is a rare sensitizer in humans. Objectives: To identify characteristics and sensitization patterns of patients with positive patch test reactions to benzyl alcohol and to check the reliability of the patch test preparation b...

Background: Patch test (PT) readings are recommended after 48h and 72h (D3). An additional day 7 (D7) reading has been suggested by some, although data on efficient patient selection is scarce. Objective: Investigation of positive D7 reactions regarding (i) allergens in the baseline series and additional PT series of the German Contact Dermatiti...

Introduction Painters and varnishers (“painters”) are exposed to various contact allergens and skin irritants, and therefore, at risk to develop occupational dermatitis (OD). Objective To describe the spectrum of occupational sensitizations in painters and revise corresponding current patch test recommendations. Patients and Methods Retrospective...

Background: In about half of the patients reacting positive to fragrance mix I (FM I), breakdown testing remains negative. This raises the question whether the reaction to FM I is false-positive, or the breakdown test is false-negative. Objectives: To identify characteristics and sensitization patterns of patients positive to FM I, but not to it...

Background Metalworkers are exposed to a variety of contact allergens by handling tools, metals, metalworking fluids (MWFs), oils and greases, rubber materials etc. Most large‐scale reports on contact allergy due to MWFs are more than 10 years old, and there are only few studies on contact allergy in mechanics and other metal workers not exposed to...

Background Studies on patch testing with workplace materials and evaluation of current occupational relevance of positive patch test (PT) reactions are scarce in patients with occupational dermatitis (OD). Objectives To identify frequent sensitizations with occupational relevance and to determine the value of patch testing with workplace materials...

Background: Metalworkers occupationally exposed to metals, tools, metalworking fluids (MWFs), technical oils, gloves, skin care products etc. frequently suffer from occupational dermatitis (OD). Objectives: To investigate occupational exposure and to identify relevant occupational sensitizers in metalworkers with OD, and to evaluate suitability...

Nucleotide excision repair (NER) is the most versatile DNA repair system in humans. NER can repair a variety of bulky DNA damage including ultraviolet light‐induced DNA damage. The consequences of defective NER factors are demonstrated by the three most common but still rare autosomal recessive NER defective syndromes: xeroderma pigmentosum (XP), C...

Background: Sensitization to methylisothiazolinone (MI) has seen an exceptional epidemic, mainly attributed to its use in cosmetics. Objectives: To trace the epidemic of MI allergy 2009-2018), and to analyse a possible change of patients' characteristics. Methods: IVDK-data of patients patch tested between 2009 and 2018 with MI (0.05 % aq.) we...

Background Contact sensitization in children is increasing. The offending allergens differ depending on patient age and sex. We aimed to determine the sensitization profiles in children (aged 6‐12) and adolescents (aged 13‐18), compare these to a control group of adults (aged 60‐66), and to evaluate differences in sensitization patterns between wor...

The preservative methyldibromo glutaronitrile (MDBGN) (CAS 35691‐65‐7) is known since long as an important contact allergen mainly used in cosmetics (Review: [1]). MDBGN was banned EU‐wide from being used in leave‐on products in 2005, for rinse‐off products in 2008, and further restricted for non‐cosmetic (technical) applications in 2010. However,...

近期研究表明,患有银屑病这种皮肤病的人发生接触性皮炎的风险较低,接触性皮炎是在皮肤接触某种刺激物(刺激性接触性皮炎)或过敏原(过敏性接触性皮炎,或称 ACD)后作出的湿疹样反应。本研究专门调查了 ACD 的发病率,接受贴片试验的银屑病患者有 2387 人,相比之下,接受贴片试验的非银屑病人群为 161981 人。贴片试验用来确定哪种潜在过敏原引起某人发生皮肤反应。总的来说,25.2% 的银屑病患者和 38.9% 的非银屑病者对贴片试验使用的过敏原至少发生过一次反应。这些发现表明,银屑病患者发生 ACD 的总体风险显著更低。综上所述,银屑病和接触性皮炎都涉及机体免疫系统的复杂过程,因此在两者同时出现时,很难了解体内具体发生了哪些变化。本研究有助于加深我们对这一主题的认识。 Linked Art...

Recent research suggests that people with the skin disease psoriasis may be at less risk of developing contact dermatitis, which is an eczema‐like reaction in response to the skin coming into contact with an irritant (irritant contact dermatitis) or allergen (allergic contact dermatitis, or ACD). This study looked at the prevalence of ACD specifica...

Background Professional musicians have prolonged and intense physical contact with their instruments. This can lead to occupational skin diseases, particularly irritant and allergic contact dermatitis. Objectives To assess the skin diseases and sensitization patterns common among professional musicians. Methods A retrospective analysis of the dat...

Background The Compositae plant family includes many thousands of species, making it one of the most widespread group of plants worldwide. Sensitization to Compositae allergens may occur in private or in occupational settings. Objectives To monitor the current sensitization spectrum to Compositae allergens, especially in cooks and florists. Metho...

Background Earlier studies suggested an inverse association between contact allergy and psoriasis, although the results of clinical studies have been inconsistent. Gene‐expression studies in human contact allergy focusing on immune responses revealed nickel being an inducer of Th1/Th17 and some Th22 immune polarization, whereas fragrances were foun...

Tattoos and Permanent Make-up are two ways of everlasting beautification of the human body and these days gain rising popularity. Allergologists all over the World are confronted with increased numbers of intolerance tattoo reactions. This article comprises an overview about ingredients of tattoo inks, clinical appearances and diagnostic possibilit...

In this chapter allergic reactions related to body art procedures will be discussed.

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 sum...

Background: Dental technicians (DTs) are at increased risk for allergic contact sensitization. Objectives: To assess the current spectrum of occupational sensitization in DTs with occupational contact dermatitis (OCD). Methods: A retrospective analysis of Information Network of Departments of Dermatology patch test data from the years 2001-201...

Background: Risk factors for p-phenylenediamine (PPD) sensitization include the use of hair dyes, the application of temporary black henna tattoos, working as a hairdresser, and, possibly, exposure to hair dye pretests. Objectives: To quantify the impact of these (putative) risk factors on PPD sensitization. Methods: Six items related to PPD e...

Tattoos and Permanent Make-up are two ways of everlasting beautification of the human body and these days gain rising popularity. Allergologists all over the World are confronted with increased numbers of intolerance tattoo reactions. This article comprises an overview about ingredients of tattoo inks, clinical appearances and diagnostic possibilit...

The two endonucleases XPF and XPG are essentially involved in nucleotide excision repair (NER) and interstrand crosslink (ICL) repair. Defects in these two proteins result in severe diseases like xeroderma pigmentosum (XP). We applied our newly CRISPR/Cas9 generated human XPF knockout cell line with complete loss of XPF and primary fibroblasts from...

The XPF/ERCC1 heterodimeric complex is essentially involved in nucleotide excision repair (NER), interstrand crosslink (ICL), and double-strand break repair. Defects in XPF lead to severe diseases like xeroderma pigmentosum (XP). Up until now, XP-F patient cells have been utilized for functional analyses. Due to the multiple roles of the XPF/ERCC1...

The increasing application of gene panels for familial cancer susceptibility disorders will probably lead to an increased proposal of susceptibility gene candidates. Using ERCC2 DNA repair gene as an example, we show that proof of a possible role in cancer susceptibility requires a detailed dissection and characterization of the underlying mutation...

Distribution of PhyloP and CADD scores for 1000G, ClinVar and the mutations identified in this study in the ERCC2 gene. A) Evolutionary conservations (PhyloP) and Combined Annotation Dependent Depletion (CADD) scores are represented for all non-synonymous ERCC2 variants found in BC/OC patients. Blue: Variants with no significant functional effect;...

Effect prediction of ERCC2 missense variants. The probability of effect of non-synonymous mutations in ERCC2 was predicted by the computer programs: SIFT, Sorting Invariant from Tolerated (Score under 0,05: not tolerated; Range 0–1); PolyPhen-2, Classification following PSIC scores (HumVar, "benign"- "possibly damaging“—"probably damaging ", Range:...

Genes covered by the TruSight-Cancer gene panel. (DOCX)

ERCC2/XPD primers for Sanger-validation of NGS derived mutations and analysis of familial segregation. All sequences shown in 5’ → 3’ direction. XPD = alternate name of ERCC2. (DOCX)

Primer pairs used for PCR amplification, Sanger sequencing, and site directed mutagenesis of ERCC2 variants. All primers (de-salted and deprotected) were synthesized by Sigma-Aldrich (Taufkirchen, Germany). (DOCX)

ERCC2 amino acid (AA) sequence alignment. Multiple sequence alignment of protein regions from various species surrounding the identified human ERCC2 missense variants (S4 Table). Affected residues are indicated in red letters. The dotted lines correspond to sequence gaps or sequence regions not yet available. Except Glu167, all affected residues sh...

ERCC2 domain structure and overlay of ERCC2 missense mutations Arg478Trp and Asp423Asn. A) Schematic showing the domain structure and canonical motifs of human ERCC2. Helicase motor domains HD1 (blue) and HD2 (green) form the DNA ATP-binding interface. The FeS (orange) and the Arch (purple) domains are inserted into HD1. The boundaries of the FeS c...

Background: Geriatric nurses (GN) have a high risk of occupational contact dermatitis (OCD), with chronic irritant contact dermatitis predominating. However, allergic contact dermatitis is an important issue as well. Little is known whether the relevant occupational allergen spectrum reported in the 1990s, including fragrances, preservatives, rubb...

Background: The nucleotide excision repair (NER) pathway, defective in xeroderma pigmentosum (XP) patients, removes DNA photolesions in order to prevent carcinogenesis. Complementation group C (XP-C) is the most frequent group of XP patients worldwide. Methods: We analyzed seven XP-C patients clinically and molecular-genetically applying: post-U...

The term trichothiodystrophy (TTD) was introduced by Price et al in 1980(1) to describe a group of rare autosomal recessive disorders characterized by sulfur-deficient brittle hair and other neuroectodermal symptoms. An eight weeks-old boy was referred to our clinic with dry, scaly skin on the trunk and dorsal extremities sparing the flexures (Fig....

A major challenge in gene library generation is to guarantee a large functional size and diversity that significantly increases the chances of selecting different functional protein variants. The use of trinucleotides mixtures for controlled randomization results in superior library diversity and offers the ability to specify the type and distribut...

Introduction: Breast and ovarian cancer (BC/OC) predisposition is associated with a number of high- and low-penetrance susceptibility genes. Despite comprehensive testing there is still a large portion of high risk cases without mutation in any of the known susceptibility loci. Therefore novel candidate genes need to be identified. Here we report o...

Background: The nucleotide excision repair (NER) pathway repairs UV-induced DNA lesions in an accurate fashion and prevents UV-irradiated areas of the skin from tumour formation. The XPA protein plays a major role in DNA damage demarcation as well as stabilization of other NER factors and was found to be defective in xeroderma pigmentosum (XP) com...

Xeroderma pigmentosum (XP) is an autosomal recessive disease, caused by a gene defect in the nucleotide-excision-repair (NER) pathway or in translesional DNA synthesis. At the age of eight, patients already develop their first skin cancers due to this DNA repair defect. In contrast, in the Caucasian population the first tumor formation in UV expose...

Zusammenfassung Xeroderma pigmentosum (XP) ist eine autosomal‐rezessiv vererbte Erkrankung, welche durch einen Defekt in der Nukleotid‐Exzisions‐Reparatur oder der transläsionalen DNA‐Synthese gekennzeichnet ist. Bereits mit acht Jahren entwickeln Patienten, die an XP leiden, aufgrund ihres DNA‐Reparaturdefekts den ersten Hautkrebs. Dies steht im G...

The nucleotide excision repair (NER) pathway repairs UV-induced photoproducts1. Seven xeroderma pigmentosum (XP) complementation groups (XP-A to XP-G) according to the respective mutated genes (XPA-XPG) and a variant form with a defect in translesion synthesis (Pol H gene) have been identified2. Patients belonging to XP complementation groups B, D,...

The European Journal of Human Genetics is the official Journal of the European Society of Human Genetics, publishing high-quality, original research papers, short reports, News and Commentary articles and reviews in the rapidly expanding field of human genetics and genomics.

The xeroderma pigmentosum (XP) group D protein is involved in nucleotide excision repair (NER) as well as in basal transcription. Determined by the type of XPD mutation, six different clinical entities have been distinguished: XP, XP with neurological symptoms, trichothiodystrophy (TTD), XP⁄TTD complex, XP⁄Cockayne syndrome (CS) complex or the cere...

Only 16 XPG-defective patients with 20 different mutations have been described. The current hypothesis is that missense mutations impair repair (XP symptoms) whereas truncating mutations impair repair and transcription (XP and CS symptoms). We identified three cell lines of XPG-defective patients (XP40GO, XP72MA, XP165MA). Patients' fibroblasts sho...

Patients belonging to xeroderma pigmentosum (XP) complementation group C comprise one-third of all XP patients. Only four major reports compiled larger groups of XP-C patients from southern Europe (12 pts), North America (16 pts) and Africa (14 and 56 pts) as well as their genetic background (46 XPC mutations). We identified 16 XP-C patients from G...

Only 16 XPG-defective patients with 20 different mutations have been described. The current hypothesis is that missense mutations impair repair (xeroderma pigmentosum (XP) symptoms), whereas truncating mutations impair both repair and transcription (XP and Cockayne syndrome (CS) symptoms). We identified three cell lines of XPG-defective patients (X...

Melanoma is one of the most aggressive human cancers. The vitamin D system contributes to the pathogenesis and prognosis of malignancies including cutaneous melanoma. An expression of the vitamin D receptor (VDR) and an anti-proliferative effect of vitamin D in melanocytes and melanoma cells have been shown in vitro. Studies examining associations...

UV-induced skin cancers comprise a major problem in organ transplant recipients (OTRs). Cyclosporin A, a calcineurin inhibitor, is used as a standard immunosuppressant and clearly increases the skin cancer risk. Azathioprine does not appear to result in such an increase in skin cancer risk, and mTOR inhibitors are associated with an even lesser ski...