D J Gawkrodger

Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, England, United Kingdom

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Publications (238)1047.15 Total impact

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    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.
    British Journal of Dermatology 10/2013; 169(4). DOI:10.1111/bjd.12556 · 4.28 Impact Factor
  • David J Gawkrodger ·

    Contact Dermatitis 06/2013; 68(6):321-2. DOI:10.1111/cod.12106 · 3.75 Impact Factor
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    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.
    British Journal of Dermatology 12/2012; 168(6). DOI:10.1111/bjd.12177 · 4.28 Impact Factor
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    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).
    British Journal of Dermatology 08/2012; 168(1). DOI:10.1111/j.1365-2133.2012.11197.x · 4.28 Impact Factor
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    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.
    Contact Dermatitis 07/2012; 68(1). DOI:10.1111/j.1600-0536.2012.02127.x · 3.75 Impact Factor
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    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.
    Nature Genetics 05/2012; 44(6):676-80. DOI:10.1038/ng.2272 · 29.35 Impact Factor
  • Danielle T Greenblatt · David J Gawkrodger · Ian R White ·

    BMJ (online) 04/2012; 344(apr19 1):e2730. DOI:10.1136/bmj.e2730 · 17.45 Impact Factor
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    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.
    Contact Dermatitis 04/2012; 67(1):9-19. DOI:10.1111/j.1600-0536.2012.02070.x · 3.75 Impact Factor
  • S. Emhemad · H. Sandhu · A. McDonagh · D. Gawkrodger · A. Weetman · H. Kemp ·

    Meeting of the British-Society-for-Investigative-Dermatology; 04/2012
  • P J Cousen · H M Ramsay · D J Gawkrodger ·

    Clinical and Experimental Dermatology 03/2012; 37(5):589-90. DOI:10.1111/j.1365-2230.2011.04290.x · 1.09 Impact Factor
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    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.
    Journal of the European Academy of Dermatology and Venereology 03/2012; 27(9). DOI:10.1111/j.1468-3083.2012.04501.x · 2.83 Impact Factor
  • S F E Rahoma · H K Sandhu · A J G McDonagh · D J Gawkrodger · A.P. Weetman · E H Kemp ·
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    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.
    British Journal of Dermatology 02/2012; 167(1):17-28. DOI:10.1111/j.1365-2133.2012.10889.x · 4.28 Impact Factor
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    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 5 topical NSAIDs, including newer agents, in common usage in Europe. Methods:  A prospective, multi-centre photopatch test study of 1,031 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 (4.6%) subjects. Irritant reactions and photoaugmentation and photoinhibition of ACD occurred infrequently. Conclusions:  The EMCPPTS 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 future European "baseline" photopatch test series.
    British Journal of Dermatology 01/2012; 166(5). DOI:10.1111/j.1365-2133.2012.10857.x · 4.28 Impact Factor
  • V Pradhan · M Patwardhan · V Thakkar · V Kharkar · U Khopkar · K Ghosh · A.P. Weetman · D.J. Gawkrodger · E.H. Kemp ·
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    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.
    Journal of the European Academy of Dermatology and Venereology 11/2011; 27(3). DOI:10.1111/j.1468-3083.2011.04367.x · 2.83 Impact Factor
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    E. Helen Kemp · Sherif Emhemad · David J. Gawkrodger · Anthony P. Weetman ·

    Autoimmune Disorders - Pathogenetic Aspects, 10/2011; , ISBN: 978-953-307-643-0
  • Philippa J Cousen · David J Gawkrodger ·
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    ABSTRACT: There are concerns about the induction of metal allergy with second-generation metal-on-metal prostheses, and the role that this may play in the development of complications such as 'pseudotumours' or failure of the implant. In this review, we attempt to set out the current knowledge on this subject. From a review of the literature, it is apparent that the first-generation metal-on-metal replacement hips did cause metal sensitization, and that joint failure was associated with this, although it is still not clear which one led to the other. Highly engineered second-generation metal-on-metal arthroplasties used in joint resurfacings are now increasingly employed. Several studies have recently shown an association between metal sensitization and peri-implant hypersensitivity reactions and implant loosening and failure, although the overall risk appears to be low. The pragmatic approach adopted by most contact dermatologists for patients known to be allergic to nickel, cobalt or chromium and who require joint replacement is to recommend prostheses made of titanium-based alloys. Patch testing continues to be a useful tool as laboratory investigations for metal hypersensitivity continue to emerge. The development of guidelines on the management of patients receiving metal-on-metal arthroplasties suspected of being metal-allergic is desirable.
    Contact Dermatitis 09/2011; 66(2):55-62. DOI:10.1111/j.1600-0536.2011.01970.x · 3.75 Impact Factor
  • D.J. Gawkrodger · C.W. McLeod · K Dobson ·
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    ABSTRACT: Nickel is a frequent allergen throughout the world. However, the extent to which nickel is relevant as an occupational contact allergen as opposed to being simply a reflection of jewellery exposure has been unclear. Some thresholds for cutaneous nickel exposure to induce a dermatitis reaction in nickel-allergic individuals have been defined. Over recent years it has become possible to measure accurately the quantity of nickel on the skin of individuals in a number of occupations. To measure the quantities of nickel on the skin of the fingers in workers employed in occupations for which nickel has been suspected as a contact allergen. To define the threshold for a dermatitis reaction after the single application of a quantity of nickel to the skin of nickel-allergic individuals when read at 2days. We employed the 'finger immersion' technique for sample collection and induction coupled plasma mass spectrometry for the nickel measurement. Nickel platers, cashiers, sales assistants, caterers, healthcare assistants, office workers, dental nurses and hairdressers were studied (five in each group except for seven cashiers). A correction was made for the fact that the finger immersion method underestimates the amount of nickel on the fingertip. The threshold for reactivity to a single application of nickel was studied by the application of various concentrations of nickel (μgcm(-2) ) [0·05 (two subjects), 0·5 (two subjects), 2·5 (three subjects), 5·0 (21 subjects), 15 (19 subjects), 30 (19 subjects) and 45 (18 subjects)] in 21 subjects overall using Finn chambers on forearm skin. The reading was made at 2days and reactions were graded using the International Contact Dermatitis Research Group classification. Nickel levels on the fingers of platers, cashiers, sales assistants, caterers, and even office staff, were at or above the 0·035μgcm(-2) level at which 22% of nickel-allergic subjects will react (after applying a correction). The single open application of nickel study demonstrated a dose-response relationship, with no subjects reacting to ≤ 2·5μgcm(-2) , but increasing numbers reacting at the higher concentrations as follows: six of 21 (28%) at 5·0μgcm(-2) , six of 19 (31%) at 15μgcm(-2) , seven of 19 (37%) at 30μgcm(-2) and 11 of 18 (61%) at 45μgcm(-2) . This study confirms that nickel levels on the skin in coin handling occupations and some others are sufficient to induce an allergic contact dermatitis in some nickel-allergic subjects. A single application of 5μgcm(-2) when read at 2days induced a dermatitis reaction in six of 21 nickel-allergic subjects.
    British Journal of Dermatology 09/2011; 166(1):82-7. DOI:10.1111/j.1365-2133.2011.10644.x · 4.28 Impact Factor
  • T Patel · D J Gawkrodger ·
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    ABSTRACT: Food intolerance is a popular notion in the general population but limited data are available on the presence of food allergy in adult patients with eczema. We wanted to characterize food hypersensitivity in this group of patients. A retrospective study was carried out on all patients with food related symptoms attending a cutaneous allergy clinic. Our study showed that while the reported prevalence of food allergy in adult patients with eczema is low (10%), more than half of these will show immunological evidence of a food allergy which support the clinical history. Immediate symptoms are usual, with nuts and tomatoes the major allergens. Demographic factors such as age, gender and duration of eczema did not significantly correlate with number of foods or an allergen-specific IgE of ≥grade 2. Food-related symptoms were associated with significant anxiety in all our patients leading to a profound effect on their behaviour.
    Journal of the European Academy of Dermatology and Venereology 07/2011; 25(7):865-7. DOI:10.1111/j.1468-3083.2010.03858.x · 2.83 Impact Factor
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    ABSTRACT: Allergic contact dermatitis in children is less recognized than in adults. However, recently, allergic contact dermatitis has started to attract more interest as a cause of or contributor to eczema in children, and patch testing has been gaining in recognition as a useful diagnostic tool in this group. The aim of this analysis was to investigate the results of patch testing of selected children with eczema of various types (mostly atopic dermatitis) attending the Sheffield Children's Hospital, and to assess potential allergens that might elicit allergic contact dermatitis. We analysed retrospectively the patch test results in 110 children aged between 2 and 18 years, referred to a contact dermatitis clinic between April 2002 and December 2008. We looked at the percentages of relevant positive reactions in boys and girls, by age groups, and recorded the outcome of treatment following patch testing. One or more positive allergic reactions of current or past relevance was found in 48/110 children (44%; 29 females and 19 males). There were 94 allergy-positive patch test reactions in 110 patients: 81 had a reaction of current or past relevance, 12 had a reaction of unknown relevance, and 1 had reaction that was a cross-reaction. The commonest allergens with present or past relevance were medicaments, plant allergens, house dust mite, nickel, Amerchol® L101 (a lanolin derivative), and 2-bromo-2-nitropropane-1,3-diol. However, finding a positive allergen was not associated with a better clinical outcome. We have shown that patch testing can identify relevant allergens in 44% of children with eczema. The commonest relevant allergens were medicament allergens, plant allergens, house dust mite, nickel, Amerchol® L101, and 2-bromo-2-nitropropane-1,3-diol. Patch testing can be performed in children as young as 2 years with the proper preparation.
    Contact Dermatitis 04/2011; 65(4):208-12. DOI:10.1111/j.1600-0536.2011.01900.x · 3.75 Impact Factor
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    ABSTRACT: Koebner’s phenomenon (KP) has been observed in a number of skin diseases, including vitiligo. Its clinical significance in vitiligo with respect to disease activity and course is still debatable, while its relevance for surgical techniques has been demonstrated in some reports. We present a literature review on the currently known facts about KP in vitiligo, including details of clinical, experimental, and histopathological changes. The consensus view is that there are still no methods to define and assess KP in vitiligo. A new classification is proposed to allow an evaluation of KP in daily practice or in experimental studies. However, many unanswered questions still remain after redefining KP in patients with vitiligo. Active research focusing on KP in vitiligo may not only provide unexpected clues in the pathogenesis of vitiligo but also help to tailor novel therapies against this chronic and often psychologically devastating skin disease.
    Pigment Cell & Melanoma Research 03/2011; 24(3):564 - 573. DOI:10.1111/j.1755-148X.2011.00838.x · 4.62 Impact Factor

Publication Stats

6k Citations
1,047.15 Total Impact Points


  • 2011-2012
    • Sheffield Teaching Hospitals NHS Foundation Trust
      Sheffield, England, United Kingdom
  • 1989-2012
    • Royal Berkshire NHS Foundation Trust
      Reading, England, United Kingdom
    • Western General Hospital
      Edinburgh, Scotland, United Kingdom
  • 1991-2009
    • The University of Sheffield
      • • Department of Biomedical Science
      • • Department of Chemistry
      • • Medical School
      Sheffield, England, United Kingdom
  • 2008
    • Edinburgh Napier University
      Edinburgh, Scotland, United Kingdom
  • 2004
    • The University of Manchester
      • Centre for Occupational and Environmental Health
      Manchester, England, United Kingdom
  • 1989-1998
    • WWF United Kingdom
      Londinium, England, United Kingdom
  • 1984-1991
    • The University of Edinburgh
      • Department of Dermatology
      Edinburgh, Scotland, United Kingdom