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.

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.

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.

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.

Variant of TYR and autoimmunity susceptibility loci in generalized vitiligo.

BACKGROUND: Generalized vitiligo is an autoimmune disease characterized by melanocyte loss, which results in patchy depigmentation of skin and hair, and is associated with an elevated risk of other autoimmune diseases. METHODS: To identify generalized vitiligo susceptibility loci, we conducted a genomewide association study. We genotyped 579,146 single-nucleotide polymorphisms (SNPs) in 1514 patients with generalized vitiligo who were of European-derived white (CEU) ancestry and compared the genotypes with publicly available control genotypes from 2813 CEU persons. We then tested 50 SNPs in two replication sets, one comprising 677 independent CEU patients and 1106 CEU controls and the other comprising 183 CEU simplex trios with generalized vitiligo and 332 CEU multiplex families. RESULTS: We detected significant associations between generalized vitiligo and SNPs at several loci previously associated with other autoimmune diseases. These included genes encoding major-histocompatibility-complex class I molecules (P=9.05x10(-23)) and class II molecules (P=4.50x10(-34)), PTPN22 (P=1.31x10(-7)), LPP (P=1.01x10(-11)), IL2RA (P=2.78x10(-9)), UBASH3A (P=1.26x10(-9)), and C1QTNF6 (P=2.21x10(-16)). We also detected associations between generalized vitiligo and SNPs in two additional immune-related loci, RERE (P=7.07x10(-15)) and GZMB (P=3.44x10(-8)), and in a locus containing TYR (P=1.60x10(-18)), encoding tyrosinase. CONCLUSIONS: We observed associations between generalized vitiligo and markers implicating multiple genes, some associated with other autoimmune diseases and one (TYR) that may mediate target-cell specificity and indicate a mutually exclusive relationship between susceptibility to vitiligo and susceptibility to melanoma.

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.

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.

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.

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.

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.

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.

Vitiligo: concise evidence based guidelines on diagnosis and management.

Vitiligo is a common disease that causes a great degree of psychological distress. In its classical forms it is easily recognised and diagnosed. This review provides an evidence based outline of the management of vitiligo, particularly with the non-specialist in mind. Treatments for vitiligo are generally unsatisfactory. The initial approach to a patient who is thought to have vitiligo is to make a definite diagnosis, offer psychological support, and suggest supportive treatments such as the use of camouflage cosmetics and sunscreens, or in some cases after discussion the option of no treatment. Active therapies open to the non-specialist, after an explanation of potential side effects, include the topical use of potent or highly potent steroids or calcineurin inhibitors for a defined period of time (usually 2 months), following which an assessment is made to establish whether or not there has been a response. Patients whose condition is difficult to diagnose, unresponsive to straightforward treatments, or is causing psychological distress, are usually referred to a dermatologist. Specialist dermatology units have at their disposal phototherapy, either narrow band ultraviolet B or in some cases photochemotherapy, which is the most effective treatment presently available and can be considered for symmetrical types of vitiligo. Depigmenting treatments and possibly surgical approaches may be appropriate for vitiligo in selected cases. There is no evidence that presently available systemic treatments are helpful and safe in vitiligo. There is a need for further research into the causes of vitiligo, and into discovering better treatments.

Mapping of melanin-concentrating hormone receptor 1 B cell epitopes predicts two major binding sites for vitiligo patient autoantibodies.

The melanin-concentrating hormone receptor 1 (MCHR1) has been identified as a B cell autoantigen in vitiligo with antibodies to the receptor detectable in binding and function-blocking assays. Two epitope domains (amino acids 1-138 and 139-298) have been previously identified. In this study, we aimed to further define the epitope specificity of MCHR1 antibodies using phage-display technology and to identify the epitopes recognised by receptor antibodies detected in MCHR1 function-blocking assays. Antibody reactivity to MCHR1 peptides 51-80, 85-98, 154-158 and 254-260 was identified by phage-display and subsequently confirmed in phage ELISA in 2/12, 5/12, 3/12 and 6/12 of vitiligo patients, respectively. The results suggest that major autoantibody epitopes are localised in the 85-98 and 254-260 amino acid regions of MCHR1 with minor epitopes in amino acid sequences 51-80 and 154-158. Antibodies with MCHR1 function-blocking activity were determined to recognise epitope 254-260, this being the first epitope to be reported as a target site for antibodies that block the function of the receptor.

The importance of propolis in patch testing--a multicentre survey.

BACKGROUND: Propolis is widely used in 'natural' cosmetics, remedies, and over-the-counter products. The incidence of propolis allergy is increasing, and cross-reaction with fragrance mix I (FMII), colophonium, and Myroxylon pereirae can occur. OBJECTIVES: To find out the prevalence and clinical relevance of positive patch tests to propolis and assess cross-reactions with Myroxylon pereirae, colophonium, FMI, and beeswax. METHODS: Two thousand eight hundred and twenty-eight subjects in 10 UK centres were patch tested with propolis and beeswax. Generic data were acquired from British Contact Dermatology Society (BCDS) database and further relevant information was requested by survey of participating centres. RESULTS: The prevalence of propolis allergy was 1.9% (55/2828). Out of these 55 subjects, only 4 (7.2%) were allergic to beeswax, 22 (40%) to Myroxylon pereirae, 15 (27.2%) to colophonium, and 6 (10.9%) to FMI. Additional data for 41 propolis allergic subjects were collected by questionnaire. Hands were the most common sites of involvement, and cosmetics were the most common source of contact. Eight out of 12 subjects reported improvement in eczema following avoidance of propolis. CONCLUSIONS: Propolis is an important allergen of increasing frequency and its inclusion in BCDS baseline series is appropriate. Cross-sensitivity to beeswax is rare.

The European baseline series in 10 European Countries, 2005/2006--results of the European Surveillance System on Contact Allergies (ESSCA).

BACKGROUND: Continual surveillance based on patch test results has proved useful for the identification of contact allergy. OBJECTIVES: To provide a current view on the spectrum of contact allergy to important sensitizers across Europe. PATIENTS/METHODS: Clinical and patch test data of 19 793 patients patch tested in 2005/2006 in the 31 participating departments from 10 European countries (the European Surveillance System on Contact Allergies' (ESSCA) www.essca-dc.org) were descriptively analysed, aggregated to four European regions. RESULTS: Nickel sulfate remains the most common allergen with standardized prevalences ranging from 19.7% (central Europe) to 24.4% (southern Europe). While a number of allergens shows limited variation across the four regions, such as Myroxylon pereirae (5.3-6.8%), cobalt chloride (6.2-8.8%) or thiuram mix (1.7-2.4%), the differences observed with other allergens may hint on underlying differences in exposures, for example: dichromate 2.4% in the UK (west) versus 4.5-5.9% in the remaining EU regions, methylchloroisothiazolinone/methylisothiazolinone 4.1% in the South versus 2.1-2.7% in the remaining regions. CONCLUSIONS: Notwithstanding residual methodological variation (affecting at least some 'difficult' allergens) tackled by ongoing efforts for standardization, a comparative analysis as presented provides (i) a broad overview on contact allergy frequencies and (ii) interesting starting points for further, in-depth investigation.

Update on contact dermatitis 2007: Medical pearls from the annual meeting of the British Contact Dermatitis Society at the annual meeting of the British Association of Dermatologists.

Contact dermatitis is an integral part of dermatology. Many patients affected by contact dermatitis suffer significant morbidity and require prompt diagnosis and treatment. Here we give an overview of contact dermatitis related presentations made during the British Contact Dermatitis Society at 87th annual meeting of the British Association of Dermatologists, which took place on 10-13 July 2007 in Birmingham, UK.