Trends in work-related respiratory diseases attributed to nickel, chromium and cobalt in the UK: descriptive findings from The Health and Occupation Research (THOR) network 1996-2019.

BACKGROUND: Occupational exposure to metals can be associated with respiratory diseases which can adversely affect the individual's health, finances and employment. Despite this, little is known about the incidence of these respiratory conditions over prolonged periods of time. AIMS: This study aimed to investigate the trends in the incidence of work-related respiratory diseases attributed to nickel, chromium and cobalt in the UK. METHODS: Cases of occupational respiratory diseases caused by nickel, chromium or cobalt reported to Surveillance of Work-related and Occupational Respiratory Disease (SWORD), the UK-based surveillance scheme between 1996 and 2019 (inclusive), were extracted and grouped into six 4-year time periods. Cases were characterised by causative metal exposure, occupational and industrial sector. Incidence rates diseases (adjusted for physician participation and response rate) were calculated using ONS employment data. RESULTS: Of cases reported to SWORD during the study period, 1% (173 actual cases) of respiratory problems were attributed to nickel, chromium or cobalt. Diagnoses of asthma compromised the largest proportion of diagnoses (74.4%), followed by lung cancer (8.9%) and pneumoconiosis (6.7%). Cases had a mean age of 47 years (SD 13); 93% were men. The annual incidence fell from 1.6 per million employed in the first 4-year period, to 0.2 in the most recent period. CONCLUSIONS: Over 24 years, a decline in the incidence of metal-related occupational respiratory diseases was observed in the UK. This could be attributed to improvements in working conditions which resulted in reduced metal exposure but could also be due to closure of industries that might have generated case returns.

Trends in occupational and work-related contact dermatitis attributed to nickel, chromium and cobalt in the UK: findings from The Health and Occupation Research network 1996-2019.

BACKGROUND: Occupational exposure to metals such as nickel, chromium and cobalt can be associated with contact dermatitis, which can adversely affect an individual's health, finances and employment. Despite this, little is known about the incidence of metal-related occupational contact dermatitis over prolonged periods of time. OBJECTIVES: To investigate the medically reported trends in the incidence of work-related contact dermatitis attributed to nickel, chromium and cobalt in the UK. METHODS: Incidence and trends in cases of occupational contact dermatitis caused by nickel, chromium or cobalt between 1996 and 2019 (inclusive), reported to the EPIDERM surveillance scheme, were investigated and compared with trends in the incidence of occupational contact dermatitis attributed to agents other than the aforementioned metals. A sensitivity analysis restricting the study cohort to cases attributed to only one type of metal was also conducted. RESULTS: Of all cases reported to EPIDERM during the study period, 2374 (12%) were attributed to nickel, chromium or cobalt. Cases predominantly comprised females (59%), with a mean (SD) age (males and females) of 38 (13) years. Cases were most frequently reported in manufacturing, construction, and human health and social activity industries. The most frequently reported occupations were hairdressing, and sales and retail (assistants, cashiers and checkout operators). The highest annual incidence rate of contact dermatitis was observed in females (2.60 per 100 000 persons employed per year), with the first and second peak seen in those aged 16-24 and ≥ 65 years, respectively. A statistically significant decrease in the incidence of occupational contact dermatitis attributed to metals over the study period was observed for all occupations (annual average change -6.9%, 95% confidence interval -7.8 to -5.9), with much of the decrease occurring between 1996 and 2007. Similar findings were obtained in the sensitivity analyses. CONCLUSIONS: Over a period of 24 years, there has been a statistically significant decline in the incidence of metal-related occupational contact dermatitis in the UK. This could be attributed not only to improvements in working conditions, which have reduced metal exposure, but could also be due to the closure of industries in the UK that might have generated cases of contact dermatitis owing to metal exposure.

The contribution of metal allergy to the failure of metal alloy implants, with special reference to titanium: Current knowledge and controversies.

After almost three-quarters of a century during which contact dermatologists have often struggled to comprehend the relationship between metal allergy and failure of metal-alloy containing implant, it is possible to say that a relationship does exist, particularly for cobalt and chromium, but also for nickel. There is still debate as to whether allergy develops as a consequent of failure but thenceforth contributes to it, or whether sensitisation starts first and induces failure secondarily-opinion probably favours the first. Metal-on-polypropylene articulations were associated with few metal allergic problems but now are less favoured by orthopaedists due to plastic wear products causing osteolysis and pseudotumour formation through local inflammation. New metal alloys are regularly being introduced such that interested dermatologists need to stay on top of the situation. The jury is still out as to whether the recent favouring of titanium-containing alloys will confirm them to be more inert allergenically. Case reports do show some clinical reactions to titanium-containing implants and patch test series have inferred sometimes quite a high background rate of allergy, but interpretation must be tempered by the awareness that titanium salts on patch testing have a tendency to cause irritant reactions. Blood monitoring of metal ion values is now recommended in certain situations after joint replacement and increasing levels may be an indication that allergy with joint failure can develop, in which case patch testing is indicated, and suggested series are available. Predictive patch testing, whilst generally not recommended in the past, has been introduced into some protocols often by non-dermatologists, such that it is now needed for temporo-mandibular joint and Nuss bar insertion, and it can be anticipated that this may become more commonplace in the future. One of the major current deficits for patch testers is standardised guidance on which preparation or preparations to use for suspected titanium allergy. One suggestion is 0.5% titanium sulphate in petrolatum, though experience in at least one centre suggests the use of a battery of titanium salts might be desirable.

Skin diseases in a 19th century English workhouse: analysis of the admission book for the Wakefield Workhouse Infirmary, 1826-1857.

Infectious diseases in the form of 'typhus' (74.2%) and 'fevers' (17.2%) were the commonest conditions accounting for entry to the Wakefield Workhouse Infirmary between 1826 and 1857, as recorded in the admissions book. Skin diseases were noted for 3.2% of admissions, principally scarlet fever (1.5%) and smallpox (0.8%). The mean age for primary dermatological admissions was 20 years (compared with 24 years for patients overall), with a mortality rate of 0.3%. The low number of smallpox cases may be the result of successful vaccination campaigns. The absence of admissions because of scabies (then known as 'the itch') might be as a result of exclusion of such patients from entry because of the known extreme infectivity of the condition. Workhouses played an important role in medical care in 19th century Britain but, in this example, skin diseases did not feature highly as causes of admission.

Skin disease and military conflicts: Lessons from the Crimean War (1854-56).

In the Crimean War (1854-56), infamous for its high death rate from disease at 212 per thousand British troops annually - one third of which was due to cholera or dysentery - skin disease was common, accounting for 13% of all admissions and 4.2% of all deaths. Excluding typhus, skin disease caused 252 per thousand annual admissions and 8.8 per thousand annual deaths, with an overall case fatality of 3.4%. The commonest skin diseases were: localised cellulitis/abscess, ulcer, venereal disease, frostbite, scurvy, eruptive rashes and scabies. The biggest number of skin disease-related deaths were from frostbite and scurvy. Cutaneous afflictions with the highest case fatality were erysipelas (27%), gangrene (25%), smallpox (21%) and frostbite (19%). Problems from frostbite lessened during the better provisioned second winter. The experience of skin disease in the Crimea highlights the importance of public health and personal sanitation to skin health in the military context, and shows that skin-related infections and nutritional deficiencies easily develop if environmental conditions deteriorate.

Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants.

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.

Contact allergy to essential oils cannot always be predicted from allergy to fragrance markers in the baseline series.

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.

Coin exposure may cause allergic nickel dermatitis: a review.

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.

Genome-wide association analyses identify 13 new susceptibility loci for generalized vitiligo.

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.

Current patch test results with the European baseline series and extensions to it from the 'European Surveillance System on Contact Allergy' network, 2007-2008.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Metal allergy and second-generation metal-on-metal arthroplasties.

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.

Patch testing is a useful investigation in children with eczema.

BACKGROUND: 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. OBJECTIVES: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Koebner's phenomenon in vitiligo: European position paper.

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.

Genome-wide analysis identifies a quantitative trait locus in the MHC class II region associated with generalized vitiligo age of onset.

Generalized vitiligo is a common autoimmune disease in which acquired patchy depigmentation of skin, hair, and mucous membranes results from loss of melanocytes from involved areas. Previous genetic analyses have focused on vitiligo susceptibility, and have identified a number of genes involved in disease risk. Age of onset of generalized vitiligo also involves a substantial genetic component, but has not previously been studied systematically. In this study, we report a genome-wide association study of vitiligo age of onset in 1,339 generalized vitiligo patients, with replication in an independent cohort of 677 cases. We identified a quantitative trait locus for vitiligo age of onset in the major histocompatibility complex (MHC) class II region, located near c6orf10-BTNL2 (rs7758128; P=8.14 × 10(-11)), a region that is also associated with generalized vitiligo susceptibility. In contrast, there was no association of vitiligo age of onset with any other MHC or non-MHC loci that are associated with vitiligo susceptibility. These findings highlight the differing roles played by genes involved in vitiligo susceptibility versus vitiligo age of onset, and illustrate that genome-wide analyses can be used to identify genes involved in quantitative aspects of disease natural history, as well as disease susceptibility per se.

Autoantibodies against tyrosine hydroxylase in patients with non-segmental (generalised) vitiligo.

Vitiligo is an acquired idiopathic hypomelanotic skin disorder characterised by depigmented macules because of loss of cutaneous melanocytes. Although the exact cause of vitiligo remains obscure, evidence suggests that autoimmunity plays a role in the pathogenesis of the disease. Previously, tyrosine hydroxylase (TH) was identified as a putative autoantigen in vitiligo using phage-display technology. In this study, the prevalence of TH antibodies in patients with vitiligo was investigated. A radioimmunoassay (RIA) was used to detect TH antibodies in sera from patients with either non-segmental vitiligo (n=79), segmental vitiligo (n=8) or other autoimmune diseases without concomitant vitiligo (n=91). Sera from healthy individuals (n=28) were also tested. Patients with segmental vitiligo, healthy controls and patients with other autoimmune diseases without concomitant vitiligo were all negative for TH antibody reactivity. Of 79 patients with non-segmental vitiligo, 18 (23%) were positive for TH antibodies in the RIA, and a significant increase in the prevalence of TH antibodies in patients with non-segmental vitiligo was evident when compared with controls (P=0.003). TH antibody prevalence was also significantly elevated in patients with active vitiligo compared to those with stable disease (P=0.009). Overall, the results indicate that TH is an antibody target in non-segmental but not in segmental vitiligo and that TH antibodies appear to be more frequent in patients with active vitiligo.