D J Gawkrodger

Edinburgh Napier University, Edinburgh, Scotland, United Kingdom

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Publications (280)

  • [Show abstract] [Hide abstract] ABSTRACT: Vitiligo is an autoimmune disease in which depigmented skin results from the destruction of melanocytes, with epidemiological association with other autoimmune diseases. In previous linkage and genome-wide association studies (GWAS1 and GWAS2), we identified 27 vitiligo susceptibility loci in patients of European ancestry. We carried out a third GWAS (GWAS3) in European-ancestry subjects, with augmented GWAS1 and GWAS2 controls, genome-wide imputation, and meta-analysis of all three GWAS, followed by an independent replication. The combined analyses, with 4,680 cases and 39,586 controls, identified 23 new significantly associated loci and 7 suggestive loci. Most encode immune and apoptotic regulators, with some also associated with other autoimmune diseases, as well as several melanocyte regulators. Bioinformatic analyses indicate a predominance of causal regulatory variation, some of which corresponds to expression quantitative trait loci (eQTLs) at these loci. Together, the identified genes provide a framework for the genetic architecture and pathobiology of vitiligo, highlight relationships with other autoimmune diseases and melanoma, and offer potential targets for treatment.
    Article · Oct 2016 · Nature Genetics
  • D. J. Gawkrodger · C. W. McLeod · K. Dobson
    Conference Paper · Oct 2016
  • [Show abstract] [Hide abstract] ABSTRACT: Vitiligo is an autoimmune disease in which depigmented skin results from destruction of skin melanocytes, with strong epidemiologic association with several other autoimmune diseases. In previous linkage and genome-wide association studies (GWAS1, GWAS2), we identified 27 vitiligo susceptibility loci in patients of European (EUR) ancestry. We carried out a third GWAS (GWAS3) of vitiligo in EUR subjects, with augmentation of GWAS1 and GWAS2 controls, genome-wide imputation, and meta-analysis of all three vitiligo GWAS, followed by an independent replication study. The combined analyses, with 4,680 vitiligo cases and 39,586 controls, identified 23 novel replicated loci, as well as 7 new suggestive loci, most encoding immune regulators, apoptotic regulators, and melanocyte regulators, several of which are also associated with other autoimmune diseases. Functional analyses indicate a predominance of causal regulatory variation, in some cases corresponding to eQTL at these loci. Together, the identified genes provide a framework for vitiligo genetic architecture and pathobiology, highlight genetic relationships to other autoimmune diseases and melanoma, and offer potential targets for vitiligo treatment.
    Article · Aug 2016
  • Ruth A Sabroe · Catherine R Holden · David J Gawkrodger
    [Show abstract] [Hide abstract] ABSTRACT: Background: Essential oils are fragrance substances that are labelled on cosmetic products by their INCI names, potentially confusing consumers. Objectives: To establish whether contact allergy to essential oils might be missed if not specifically tested for. Methods: We tested 471 patients with 14 essential oils and 2104 patients with Melaleuca alternifolia oil between January 2008 and June 2014. All patients were tested with fragrance mix I, fragrance mix II, hydroxyisohexyl 3-cyclohexene carboxaldehyde, and Myroxylon pereirae. Three hundred and twenty-six patients were tested with hydroperoxides of limonene and linalool. Results: Thirty-four patients had a +/++/+++ reaction to at least one essential oil. Eleven had no reaction to any of the six marker fragrance substances. Thus, 4 of 11 positive reactions to M. alternifolia oil, 2 of 7 reactions to Cymbopogon flexuosus oil, 1 of 5 reactions to Cananga odorata oil, 3 of 4 reactions to Santalum album oil and 2 of 3 reactions to Mentha piperita oil would have been missed without individual testing. Conclusion: A small number of patients who are allergic to essential oils could be missed if these are not specifically tested. Labelling by INCI names means that exposure may not be obvious. Careful inspection of so-called 'natural' products and targeted testing is recommended.
    Article · Jan 2016 · Contact Dermatitis
  • S. Garg · J.P. Thyssen · W. Uter · [...] · D.J. Gawkrodger
    [Show abstract] [Hide abstract] ABSTRACT: Background Nickel allergy is common worldwide. It is associated with hand dermatitis, and sensitization is often induced by nickel-releasing jewellery. The European Union (EU) introduced legislation to control nickel content and release from jewellery and other consumer items through the EU Nickel Directive 1994, which came into force in 2001 and is now part of the REACH regulation. Objectives To examine the effects of the EU nickel regulations on the prevalence of nickel allergy in four European countries. Methods Nickel patch-test data from 180 390 patients were collected from national databases in Denmark, Germany, Italy and the U.K. from between 1985 and 2002 to 2010. Patients with suspected allergic contact dermatitis who had been patch tested with nickel sulfate 5% in petrolatum were included in the analysis. The main outcomes studied were the percentage of positive results to nickel patch tests, and changes in trends with time in an age- and sex-stratified analysis. ResultsA statistically significant decrease in nickel allergy was observed in Danish, German and Italian women aged below 30 years. In female patients in the U.K. this was observed between 2004 and 2010. In young men, a statistically significant decrease in nickel allergy was observed in Germany and the U.K., whereas a nonsignificant increase was observed in Italy. Conclusions There has been a reduction in the prevalence of nickel allergy in young women, contemporaneous with the introduction of the nickel regulation. A reduction is also suggested in men in Germany and the U.K. A causative effect of the regulatory intervention is the most likely explanation.
    Article · Oct 2013 · British Journal of Dermatology
  • David J Gawkrodger
    Article · Jun 2013 · Contact Dermatitis
  • [Show abstract] [Hide abstract] ABSTRACT: Background:  Vitiligo is a common, acquired, idiopathic depigmenting skin disorder. Although the exact pathogenesis remains unknown, genetic susceptibility and autoimmune responses play a role in vitiligo development. Previous studies have suggested that the D allele of the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene is associated with vitiligo in Indians and Koreans. Furthermore, significantly higher serum ACE levels have been demonstrated in patients with some autoimmune and autoinflammatory disorders. Objectives:  The objectives were to investigate any association between the ACE I/D polymorphism and vitiligo susceptibility in an Indian population, and to compare serum ACE levels in vitiligo patients and healthy subjects. Methods:  The ACE I/D genotypes of 79 vitiligo patients and 100 normal individuals were determined by PCR amplification. A meta-analysis compared the distribution of the ACE I/D alleles and genotypes in the current and three previous studies. Serum ACE levels were evaluated by ELISA. Results:  A significant increase in the frequency of the ACE I/D D allele was evident in vitiligo patients in both the case-control study (P = 0.005; odds ratio (OR): 1.87; 95% confidence intervals (CI): 1.22-2.85) and the meta-analysis (P = 0.044; OR: 1.44; 95% CI: 1.01-2.06). Serum ACE levels were significantly increased in vitiligo patients compared to healthy subjects (P < 0.0001). Conclusion:  In agreement with earlier reports, the ACE I/D D allele is associated with vitiligo susceptibility in the Indian population. The significantly elevated serum ACE levels in our cohort of vitiligo patients concur with those previously found in patients with some other autoimmune diseases.
    Article · Dec 2012 · British Journal of Dermatology
  • A Taieb · A Alomar · M Böhm · [...] · M Picardo
    [Show abstract] [Hide abstract] ABSTRACT: The etiopathogenic mechanisms of vitiligo are still poorly understood, and this has held back progress in diagnosis and treatment. Up until now, treatment guidelines have existed at national levels, but no common European viewpoint has emerged. This guideline for the treatment of segmental (SV) and non segmental (NSV) vitiligo has been developed by the members of the Vitiligo European Task Force (VETF) and other colleagues. It summarizes evidence-based and expert-based recommendations (S1 level).
    Article · Aug 2012 · British Journal of Dermatology
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    Jacob P Thyssen · David J Gawkrodger · Ian R White · [...] · Carola Lidén
    [Show abstract] [Hide abstract] ABSTRACT: Nickel is used in coins because the metal has beneficial properties, including price, colour, weight, and corrosion resistance, and also because it is easy to stamp. It has often been claimed that the duration of skin contact with coins is too short to cause nickel release and dermatitis. However, it is well known by dermatologists specialized in occupational skin diseases, and by their nickel-allergic patients, that hand eczema in cashiers and other professionals who handle coins may be caused or aggravated by nickel release from coins. In this review, we present evidence from past studies showing that nickel-containing coins can indeed pose a risk for those who handle them. For protection of the health of consumers, cashiers, and other workers who handle coins, it is suggested that coins without nickel release should be used as a substitute for the high nickel-releasing coins currently in widespread use. The key risk factor in this situation is the ability of metal alloys in coins to release nickel and contaminate the skin after repeated contact from coin handling.
    Full-text available · Article · Jul 2012 · Contact Dermatitis
  • [Show abstract] [Hide abstract] ABSTRACT: We previously reported a genome-wide association study (GWAS) identifying 14 susceptibility loci for generalized vitiligo. We report here a second GWAS (450 individuals with vitiligo (cases) and 3,182 controls), an independent replication study (1,440 cases and 1,316 controls) and a meta-analysis (3,187 cases and 6,723 controls) identifying 13 additional vitiligo-associated loci. These include OCA2-HERC2 (combined P = 3.80 × 10(-8)), MC1R (P = 1.82 × 10(-13)), a region near TYR (P = 1.57 × 10(-13)), IFIH1 (P = 4.91 × 10(-15)), CD80 (P = 3.78 × 10(-10)), CLNK (P = 1.56 × 10(-8)), BACH2 (P = 2.53 × 10(-8)), SLA (P = 1.58 × 10(-8)), CASP7 (P = 3.56 × 10(-8)), CD44 (P = 1.78 × 10(-9)), IKZF4 (P = 2.75 × 10(-14)), SH2B3 (P = 3.54 × 10(-18)) and TOB2 (P = 6.81 × 10(-10)). Most vitiligo susceptibility loci encode immunoregulatory proteins or melanocyte components that likely mediate immune targeting and the relationships among vitiligo, melanoma, and eye, skin and hair coloration.
    Article · May 2012 · Nature Genetics
  • Danielle T Greenblatt · David J Gawkrodger · Ian R White
    Article · Apr 2012 · BMJ (online)
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    [Show abstract] [Hide abstract] ABSTRACT: The pattern of contact sensitization to the supposedly most important allergens assembled in the baseline series differs between countries, presumably at least partly because of exposure differences. Objectives. To describe the prevalence of contact sensitization to allergens tested in consecutive patients in the years 2007 and 2008, and to discuss possible differences. Data from the 39 departments in 11 European countries comprising the European Surveillance System on Contact Allergy network (www.essca-dc.org) in this period have been pooled and analysed according to common standards. Patch test results with the European baseline series, and country-specific or department-specific additions to it, obtained in 25 181 patients, showed marked international variation. Metals and fragrances are still the most frequent allergens across Europe. Some allergens tested nationally may be useful future additions to the European baseline series, for example methylisothiazolinone, whereas a few long-term components of the European baseline series, namely primin and clioquinol, no longer warrant routine testing. The present analysis points to 'excess' prevalences of specific contact sensitization in some countries, although interpretation must be cautious if only few, and possibly specialized, centres are representing one country. A comparison as presented may help to target in-depth research into possible causes of 'excess' exposure, and/or consideration of methodological issues, including modifications to the baseline series.
    Full-text available · Article · Apr 2012 · Contact Dermatitis
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    File available · Data · Apr 2012
  • Conference Paper · Apr 2012
  • P J Cousen · H M Ramsay · D J Gawkrodger
    Article · Mar 2012 · Clinical and Experimental Dermatology
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    [Show abstract] [Hide abstract] ABSTRACT: Background Objective parameters to assess disease activity in non-segmental vitiligo are lacking. Melanocyte antigen-specific antibodies are frequently found in the sera of patients with vitiligo and the presence of these antibodies may correlate with disease activity. Objective To investigate the relationship between melanocyte antigen-specific antibodies and recent disease activity in patients with vitiligo and to evaluate the potential usefulness of this objective parameter in daily clinical practice. Methods The prevalence of tyrosinase, melanoma antigen recognized by T-cells-1 (MART1), melanin-concentrating hormone receptor-1 (MCHR1), gp100 and tyrosine hydroxylase (TH) antibodies was evaluated in 21 patients with non-segmental vitiligo and in 20 healthy controls. Results In 21 patients, nine (42.8%) showed antibody responses against tyrosinase, MART1, MCHR1, gp100 or TH. No antibody responses were found in the 20 controls. No correlation was found between the presence of antibodies and recent disease activity or other clinical characteristics such as age, gender, extension and duration of vitiligo. Conclusions In this study, 42.8% of the vitiligo patients showed an antibody response to melanocyte antigen-specific antigens. However, the presence of antibodies against melanocytes did not correlate with recent disease activity or other relevant disease parameters, and for the moment screening for these antibodies in individual patients does not appear to be clinically relevant.
    Full-text available · Article · Mar 2012 · Journal of the European Academy of Dermatology and Venereology
  • [Show abstract] [Hide abstract] ABSTRACT: We previously detected antibodies against tyrosine hydroxylase (TH) in 23% of patients with nonsegmental vitiligo and in 19% of patients with alopecia areata (AA). To identify TH epitopes recognized by TH antibodies in patients with vitiligo and AA. Recombinant plasmids containing defined fragments of TH cDNA were constructed. The cloned TH cDNA fragments were subsequently translated in vitro to produce a series of [(35) S]-labelled TH protein fragments which were then used in radioimmunoassays to analyse the immunoreactivity of sera from 18 TH antibody-positive patients with vitiligo and so initially define TH epitope domains. Further localization of TH epitopes was investigated by antibody absorption experiments using synthetic TH peptides and nonradiolabelled, in vitro-expressed TH protein fragments. Antibody binding to identified epitopes was confirmed in TH peptide enzyme-linked immunosorbent assays. Analysis of the results obtained indicated the presence of two major antibody-binding sites on TH between amino acids 1 and 14 (epitope 1-14) and between amino acids 61 and 80 (epitope 61-80). Of 18 patients with vitiligo and six with AA, 17 (94%) and five (83%), respectively, had antibodies against epitope 1-14. In addition, 11/18 (61%) vitiligo and 2/6 (33%) AA patient sera displayed immunoreactivity against epitope 61-80. Two major binding sites for human TH antibodies are located at the N-terminus of the protein. The humoral immune response to TH in vitiligo and AA is heterogeneous in nature in that patients may have antibodies to more than one TH epitope. TH antibodies from patients with vitiligo or AA can recognize identical epitopes.
    Article · Feb 2012 · British Journal of Dermatology
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    [Show abstract] [Hide abstract] ABSTRACT: Background The two most common agent groups currently responsible for photoallergic contact dermatitis (PACD) are organic ultraviolet (UV) absorbers in sunscreens and topical nonsteroidal anti-inflammatory drugs (NSAIDs). However, availability of information on the photoallergenic potential of these agents is scarce. Objectives To obtain current information on the frequency of PACD to 19 organic UV absorbers and five topical NSAIDs, including newer agents, in common usage in Europe. Methods A prospective, multicentre photopatch test study was conducted with 1031 patients attending for investigation of suspected PACD in 30 centres across 12 European countries. Results A total of 346 PACD reactions in 200 (19·4%) subjects occurred. PACD was most commonly caused by the topical NSAIDs, ketoprofen (128 subjects) and etofenamate (59 subjects). Of the organic UV absorbers, octocrylene, benzophenone-3 and butyl methoxydibenzoylmethane most frequently elicited PACD. The ‘newer’ organic sunscreen absorbers rarely led to PACD. There appeared to be an association between the agents ketoprofen, octocrylene and benzophenone-3, with several subjects developing PACD to two or all three agents concomitantly. Allergic contact dermatitis (ACD) was less commonly observed than PACD, comprising 55 reactions in 47 (5%) subjects. Irritant reactions and photoaugmentation and photoinhibition of ACD occurred infrequently. Conclusions The European multicentre photopatch test study has provided current information on the relative frequency of PACD to common photoallergens. Such data will be of value when deciding on which agents to include in a future European ‘baseline’ photopatch test series.
    Full-text available · Article · Jan 2012 · British Journal of Dermatology
  • Mili Shah · David J. Gawkrodger
    [Show abstract] [Hide abstract] ABSTRACT: Air hammer (handheld power tools) operators encounter a variety of irritants as well-recognized contact allergens due to the labor-intensive nature of occupation in industries such as forestry, construction, and, less commonly, the dental professionals. Laborers are known to develop hand-arm vibration syndrome (HAVS) which is characterized by vascular, neurological, and musculoskeletal symptoms. Vibrations emitted between 30 and 300 Hz are strongly associated with the development of HAVS. Numerous other variables influence the development of HAVS, including type of vibration, ambient temperature, and smoking status, hence the latency period varies considerably. The neurological component of HAVS is significantly debilitating and can interfere in daily activities resulting in a reduced quality of life. Prevention is the focus of management of HAVS with avoidance of further vibration exposure being crucial.
    Chapter · Jan 2012
  • [Show abstract] [Hide abstract] ABSTRACT: Background  Vitiligo is a common, idiopathic skin disorder characterized by depigmented skin due to the loss of cutaneous melanocytes. Several studies have reported the clinical and demographic characteristics of Indian vitiligo patients, however, none has characterized their antibody profiles. Objective  To establish the clinical, demographic and serological details of a population of vitiligo patients from Mumbai, India, and to evaluate the data for any associations between clinical presentations and the occurrence of antibody responses. Methods  Vitiligo patients (n = 79) were recruited to the study and their clinical and demographic details recorded. Serum antibodies, including those against melanocyte-specific antigens, thyroid antigens and keratinocytes, were evaluated. Results  The prevalence of vitiligo was independent of sex, and non-segmental vitiligo was the most common form of the disease occurring in 65% of the patients. Patients with segmental vitiligo (mean age = 14.4 ± 4.6 years) presented at a younger age than those with non-segmental disease (mean age = 32.5 ± 17.8 years). Personal and family histories of other autoimmune diseases occurred in 3% and 8% of patients, respectively. Antibodies were detected against tyrosinase, tyrosine hydroxylase, thyroid peroxidase, thyroglobulin and keratinocytes at frequencies of 11%, 22%, 18%, 24% and 27%, respectively. Overall, antibodies were more common in patients with non-segmental vitiligo (50-67%) than in those with segmental disease (0-17%), and were detected more frequently in patients with shorter disease durations (<10 years). Conclusion  Our study provides novel information relative to the clinical details, demographic features and serological parameters of a population of vitiligo patients from Mumbai, India. Important distinctions from similar surveys conducted in European patients were evident such as an infrequency of family history, a low prevalence of clinical autoimmune disease, and an absence of particular antibody specificities. These differences may have a bearing on the pathogenesis and course of the disease in Indian patients.
    Article · Nov 2011 · Journal of the European Academy of Dermatology and Venereology

Publication Stats

7k Citations

Institutions

  • 2008
    • Edinburgh Napier University
      Edinburgh, Scotland, United Kingdom
  • 1992-2007
    • The University of Sheffield
      Sheffield, England, United Kingdom
  • 2006
    • The University of Manchester
      Manchester, England, United Kingdom
  • 1998-2001
    • Royal Berkshire NHS Foundation Trust
      Reading, England, United Kingdom
  • 1988
    • The University of Edinburgh
      • Department of Dermatology
      Edinburgh, SCT, United Kingdom