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Biomedical subjects

D J Gawkrodger

Publications and source records attributed to D J Gawkrodger.

At least 37 records · Page 2Linked to original sources
PubMed2003

Occupational contact dermatitis to nickel: experience of the British dermatologists (EPIDERM) and occupational physicians (OPRA) surveillance schemes.

AIMS: To examine, from occupational surveillance reporting data, whether scheme reporters considered nickel exposure to play a role in occupational contact dermatitis (OCD) in the UK. METHODS: Data on occupational skin disease in the UK are collected by two occupational disease surveillance schemes, EPIDERM and OPRA. Cases of OCD believed to have relevant nickel exposure reported to EPIDERM or OPRA from February 1993 to January 1999 were studied. RESULTS: An estimate of 1190 cases of occupational contact dermatitis thought to have relevant nickel exposure (12% of total estimated OCD) was derived from reports by dermatologists, an average of 198 per year. The highest incidence rates were seen in hairdressers (23.9/100 000 workers/year), bar staff (4.7), chefs and cooks (4.4), retail cash and checkout operators (2.8), and catering assistants (2.5). From May 1994 to January 1999, 158 cases of nickel associated dermatitis (1.9% of total OCD cases) were estimated; the most frequently reported occupations were electronic assemblers, nurses, sales assistants, and general assemblers. From July 1997 to January 1999, 547 positive patch tests to nickel were reported; in 195 cases (36%), nickel was felt to be a relevant occupational allergen (for example, coin handling). In hairdressers, nurses, cooks, and beauticians, nickel was usually considered, if relevant at all, to be only one of several causes of dermatitis. CONCLUSIONS: Up to 12% of total estimated cases of OCD were thought to be due in part to nickel. Results suggest that nickel hypersensitivity is one of several contributors to OCD in subjects with multiple occupational exposures. Coin handling may be a source of OCD to nickel.

Adolescent↗
PubMed2002

Role of the autoimmune regulator (AIRE) gene in alopecia areata: strong association of a potentially functional AIRE polymorphism with alopecia universalis.

Alopecia areata is characterized by a reversible form of patchy or complete hair loss associated with T-cell infiltration of hair follicles. The lifetime disease risk of approximately 1.4% in the general population is increased to more than 30% in autoimmune polyendocrinopathy candidiasis ectodermal dysplasia syndrome (APECED), a recessive condition resulting from a mutation of the autoimmune regulator (AIRE) gene on chromosome 21q22.3. Aire protein is thought to have transcriptional regulatory activity but its role is not well defined at present. In this study, we have examined the possible involvement of AIRE in the pathogenesis of alopecia areata. On screening the AIRE coding sequence, we identified 20 variants. Two of these at positions, G961C and T1029C, give rise to amino acid changes, S278R and V301A, located in the DNA-binding segment (SAND) and PHD1 zinc finger motif, respectively. We found no difference in the frequency of the AIRE T1029C polymorphism between the control and patient groups. We genotyped 202 alopecia areata patients and 175 matched Caucasian controls for the AIRE G961C alleles. The frequency of the rare allele (961G) was 0.08 in the controls and there was a significant increase to 0.13 in alopecia areata overall and 0.20 in severe disease (alopecia universalis). We found no association between the AIRE G961G variant and mild (patchy) alopecia areata or alopecia totalis. However, the AIRE 961G allele is a potent risk factor (> 3) for the severest form of alopecia areata, and for disease of early age at onset (at 30 years). The change from serine to arginine in the SAND domain of AIRE protein may have a significant effect on AIRE DNA-binding activity. Moreover, our results could provide a rational explanation of the unusually high frequency of AA in APECED patients, supporting the concept of AA as an autoimmune disease.

Adolescent↗
PubMed2002

Type IV hypersensitivity reactions to natural rubber latex: results of a multicentre study.

BACKGROUND: Positive patch test reactions to natural rubber latex (NRL) have been interpreted as allergic or irritant by different groups. Additives to the NRL test solution have also caused positive reactions in previous studies. OBJECTIVES: Five centres of the British Contact Dermatitis Group conducted a prospective study on the prevalence of type IV hypersensitivity to NRL, using ammonia-preserved NRL solution for testing. PATIENTS AND METHODS: A total of 2738 consecutive patients were patch tested. Where clinically indicated, specific IgE was measured or a prick test done. RESULTS: Twenty-seven patients (1%) had a positive patch test reaction to NRL, which was considered to be allergic and of current relevance in 19 (70%) patients. Fourteen of these also had a positive prick test or specific IgE. Thirteen patients (48%) were male, 19 (70%) atopic and 13 (48%) had eczema on their hands. CONCLUSIONS: We conclude that delayed-type hypersensitivity to NRL is a problem for a proportion of patients with eczema, particularly on their hands, and that patch testing with ammonia-preserved NRL can be recommended to identify these patients. Patients with a positive patch test should be investigated for contact urticaria to NRL.

Adult↗
PubMed2002

Type-IV hypersensitivity to betamethasone valerate and clobetasol propionate: results of a multicentre study.

BACKGROUND: Most studies investigating steroid allergy have been performed with tixocortol pivalate, hydrocortisone butyrate and budesonide. Betnovate and Dermovate are widely prescribed in the U.K. but little is known about the frequency of sensitization to them. OBJECTIVES: To determine the optimum method to detect contact allergy to betamethasone valerate (BV) and clobetasol propionate (CP). METHODS: Seven centres tested consecutive patients attending for investigation of suspected allergic contact dermatitis to these steroids at a range of concentrations in different vehicles. RESULTS: Of 1562 patients tested, 16 (1%) reacted to either BV or CP. Ten patients (0.7%) reacted to BV and 13 (0.8%) to CP. Two patients of a further centre were included in analysis of dilutions and vehicles. Sixteen of a total of 25 reactions (64%) were identified with a 1% dilution in ethanol. CONCLUSIONS: Consideration should be given to adding BV and CP to a standard allergy series, given that both are frequently used in the treatment of eczema and that most patients sensitized to them are not identified with currently used markers of steroid allergy. If patch tests to BV and CP are initially negative, but an allergy is suspected, the patient should be further investigated. Further studies are required to identify the ideal patch test material.

Adult↗
PubMed2002

Autoantibodies in vitiligo patients are not directed to the melanocyte differentiation antigen MelanA/MART1.

Recent studies have demonstrated the presence of circulating MelanA (MART1)-specific cytotoxic T lymphocytes in a significant number of vitiligo patients when compared to control subjects. High levels of the skin-homing receptor cutaneous lymphocyte-associated antigen were expressed on the T cells and their frequency correlated with the extent of depigmentation and disease activity in the vitiligo patients. The present study was designed to examine vitiligo patient sera for the presence of autoantibodies to MelanA. The incidence of autoantibodies to MelanA in patients with vitiligo (n = 51) and in healthy individuals (n = 20) was examined using a radiobinding assay with 35S]-labelled MelanA and using Western blot analysis with a glutathione S-transferase (GST)-MelanA fusion protein. Autoantibodies to MelanA could not be detected in any of the vitiligo patient sera or control sera analysed using either of these detection systems. It is therefore possible that MelanA only induces cellular rather than humoral autoreactivity in vitiligo.

Adolescent↗
PubMed2001

Occupational contact dermatitis has an appreciable impact on quality of life.

In this study, we examined the impact of occupational contact dermatitis on quality of life. 181 patients, diagnosed with occupational contact dermatitis over a period of 3 years (1996-1999 inclusive), were sent a questionnaire based on the Dermatology Life Quality Index (DLQI) and the Short Form-36 (SF-36). 60 (32%) patients were in industrial occupations and 27 (14%) in health care. An overall response rate of 39% (n=70) was obtained. The median DLQI score was 5, with a mean score 6.6 (SD 6.4), which is similar to that seen in Behçet's syndrome and urticaria. There was no statistically-significant difference between male and female median scores (p=0.98) and no significant correlation between age and DLQI score nor between DLQI score and time from diagnosis. The most problematic quality of life areas were symptoms and feelings. Males scored highest in problems associated with work, relationships and treatment, whereas females scored highest in problems associated with symptoms and feelings, daily activities and leisure. The SF-36 scores showed an association between physical problems and emotional problems affecting work. From this study, it can be seen that occupational contact dermatitis has an appreciable impact on quality of life.

Adolescent↗
PubMed2001

Occupational contact dermatitis in nurses with hand eczema.

Occupationally related dermatitis is a common problem in nurses, who are exposed to a wide variety of allergenic and irritant substances. In a group of 44 nurses with hand dermatitis (40 female, 4 male), 18 were thought to have a predominantly allergic contact dermatitis, 15 an irritant dermatitis, 7 other form of eczema, 3 atopic dermatitis and one pompholyx. 10 of the 15 irritant cases were diagnosed as occupational. Of the 18 patients with allergic contact dermatitis, the allergens were thought to be occupationally relevant in 8 cases. In 6 of these 8 the dermatitis was due to natural rubber latex (3) or other rubber chemicals (3). 2 had additional evidence of immediate-type hypersensitivity to natural rubber latex (one was patch test allergic to latex, the other to thiuram mix). Natural rubber latex allergy, both delayed and immediate, is a significant problem, and nurses at risk should be tested for both types of hypersensitivity, as well as being patch tested to standard, rubber and medicaments series.

Adult↗
PubMed2001

Keratinocytes suppress TRP-1 expression and reduce cell number of co-cultured melanocytes - implications for grafting of patients with vitiligo.

A pilot study for grafting of patients with vitiligo using cultured epithelial autografts containing melanocytes gave disappointing clinical results, with pigmentation achieved in only one out of five patients. Irrespective of the fate of melanocytes grafted back onto the patients, we experienced problems in identifying melanocytes within these well-integrated keratinocyte sheets. This led us to explore the fate of these cells within these sheets in vitro and to seek to improve their number and function within the sheets. We report that the introduction of a fibroblast feeder layer can improve melanocyte number within melanocyte/keratinocyte co-cultures initially, but at very high keratinocyte density, there is a marked loss of melanocytes (as detected by staining for S100). Additionally, we found that keratinocytes not only down-regulate melanocyte number, but also pigmentary function; thus, it was possible to identify melanocytes that were S100 positive but tyrosinase-related protein-1 (TRP-1) negative in confluent well-integrated keratinocyte sheets. In summary, our data suggest that keratinocytes at high density initially suppress melanocyte pigmentation (as evidenced by a lack of TRP-1 expression) and then cause a physical loss of melanocytes. The introduction of a fibroblast feeder layer can help maintain melanocyte number while keratinocytes are subconfluent, but fails to oppose the inhibitory influence of the keratinocytes on melanocyte TRP-1 expression.

Adult↗
PubMed2001

Molecular mapping of epitopes on melanocyte-specific protein Pmel17 which are recognized by autoantibodies in patients with vitiligo.

Previously, we reported the identification of Pmel17 autoantibodies in some patients with vitiligo. Here, we have determined the B cell epitopes on Pmel17 which are recognized by these autoantibodies. Deletion derivatives of Pmel17 cDNA were constructed using either subcloning of specific cDNA fragments or polymerase chain reaction amplification. Full-length Pmel17 cDNA and its truncated derivatives were then translated in vitro to produce [(35)S]-labelled proteins. The radiolabelled ligands were used subsequently in radiobinding assays to investigate the reactivity of sera from vitiligo patients. Two epitope regions were identified: one located at the C-terminal end of Pmel17 between amino acids 634--644 and one in a central region of the protein between amino acids 326--341. Computer analysis of the potential B cell epitopes on Pmel17 revealed that the epitope domain encompassing amino acids 326--341 was located in an area of the protein which was predicted to be highly antigenic. In contrast, the epitope identified at the C-terminal of Pmel17 (amino acids 634--644) was located in a region of the protein predicted to have low antigenicity. The amino acid sequences of the identified Pmel17 epitopes were compared to the amino acid sequences of the related melanogenic enzymes tyrosinase, tyrosinase-related protein-1 and tyrosinase-related protein-2. However, no sequence homology was found between either of the Pmel17 epitopes and the aforementioned proteins. This finding is consistent with our previous study in which we were unable to show the presence of Pmel17 antibodies which were cross-reactive with either tyrosinase, tyrosinase-related protein-1 or tyrosinase-related protein-2. It also suggests that the IgG response to Pmel17 is distinct from the antibody response to the other melanocyte-specific antigens.

Adult↗
PubMed2000

Angry back syndrome is often due to marginal irritants: a study of 17 cases seen over 4 years.

17 patients with angry back syndrome were identified over a 4-year period (1994-97). 10 such patients were classified as multiple reactors and 7 as exacerbations of atopic eczema. The 10 multiple reactors reacted most commonly to medicaments, rubber chemicals, fragrances, methylchloroisothiazolinone/methylisothiazolinone, colophonium and nickel. A final diagnosis of relevant allergic contact dermatitis was made in 8 of the 10 patients with multiple reactions. Relevant contact allergens were rubber chemicals, plants, metals and preservatives, all of which can be marginal irritants. None of the reactions in the patients with exacerbation of dermatitis were thought to be relevant or helpful in the further management of the patient. Reactions in the angry back syndrome appear to be due most commonly to marginal irritants. In multiple reactors, marginal irritants were also the most common allergens finally identified.

Dermatitis, Allergic Contact↗
PubMed2000

Contact sensitivity to nickel and other metals in jewelry reactors.

BACKGROUND: Many patients who give a history of a dermatitis reaction to jewelry or metal contact with skin are negative to metals on standard patch testing. Some may be showing false-negative reactions. OBJECTIVE: Our purpose was to determine whether patients with a history of jewelry reactions but whose standard patch tests were negative have a false-negative reaction or are allergic to metals other than nickel, cobalt, or chromium. METHODS: Four hundred forty-nine patients were studied who gave a history of reacting to jewelry or metal. Of these, 210 were tested to the metals in the European standard series (ie, nickel, cobalt, and chromate), and 239 were tested to the metals in the standard series and to an extended metal series of palladium, gold, platinum, a second nickel salt, and a nickel/cobalt mixture. These were compared with 752 patients who did not give a history of jewelry or metal reactions, of which 50, besides the standard series, were also treated with the additional metal series. RESULTS: A higher proportion of jewelry-reactive patients tested with the extended series reacted to nickel (and to other metals) than those who were tested only with the European standard series: (61% vs 38%; P <.0001 ). The use of the extended series showed that palladium allergy was common, present in 34% of nickel-allergic patients, but it always occurred with nickel sensitivity. Gold allergy coexisted with nickel sensitivity in 10% of cases. Testing simultaneously with separate patches containing 5% nickel sulfate and 5% nickel chloride showed a concordance of 71% in identified nickel-sensitive patients. Nickel sulfate was more likely than nickel chloride to detect nickel sensitivity. The use of a combined preparation of 2.5% nickel sulfate and 0.5% cobalt chloride in petrolatum revealed only 3 jewelry-reactive patients who were negative to other metals. There was a slightly higher proportion of atopic patients in the patch test-negative jewelry reactors group than in the positive group; however, the difference was not significant and it was not sufficient to account for the negative findings. CONCLUSION: Some jewelry reactors who had negative patch tests are likely to be subclinically allergic to nickel. We suggest that the higher number of antigens, or perhaps the larger nickel load, in the extended metal series, resulted in a larger proportion of patients reacting. To better demonstrate nickel allergy in jewelry reactors, patients should be patch tested to a metal series that contains palladium and gold salts and perhaps a second nickel patch because these may reveal the presence of nickel sensitivity when standard patch tests would otherwise have been negative.

Chromium↗
PubMed2000

Alpha-melanocyte stimulating hormone can reduce T-cell interaction with melanoma cells in vitro.

This study was undertaken to investigate whether alpha-melanocyte stimulating hormone (alphaMSH) influences the interaction of melanoma cells with T-lymphocytes in the light of previous work from our laboratories showing that alphaMSH can reduce tumour necrosis factor-alpha (TNFalpha) stimulated ICAM-1 upregulation in both normal and transformed melanocytes. Two cutaneous melanoma cell lines--A375-SM and HBL--were examined initially. A375-SM cells gave only a two-fold increase in T-cell proliferation, which was not much improved by the pretreatment of the melanoma cells with cytokines. HBL cells induced a three-fold increase in T-cell proliferation, which was slightly enhanced by the addition of cytokines. Neither cell line expressed B7(1), HBL cells expressed a low level of B7(2), whereas A375-SM cells had little, if any, B7(2) expression. Addition of alphaMSH reduced the interaction between these cutaneous melanoma cells and T-lymphocytes in some, but not all, conditions. An ocular melanoma cell line transfected with B7 showed a modest interaction with T-cells (in two out of three donors) and this response was reduced by the addition of alphaMSH. Pretreatment of the transfected line with cytokines markedly enhanced stimulation of T-cell proliferation by these tumour cells, and alphaMSH reduced the interaction between melanoma cells and T-cells for two out of three donors. In summary, under experimental conditions where melanoma cell stimulation of T-cells occurred (generally pretreatment of the cells with interferon-gamma gave the most convincing response), alphaMSH reduced this response in the majority of experiments, providing preliminary evidence to confirm the hypothesis that MSH may assist melanoma cells to evade interaction with immune cells.

Antibodies, Monoclonal↗