Dermatitis from a chromium dental plate

Systemic absorption of metal or metallic salts from dental and orthopedic surgical implants can produce a cutaneous allergic dermatitis in susceptible individuals. Mercury, nickel and cobalt are the most common metals to elicit such systemic allergic reactions from chronic internal exposure. A case is presented of a generalized eczematoid dermatitis apparently caused by allergy to chromium liberated from a metal dental plate.     

Nickel allergy and allergic contact dermatitis: A clinical review of immunology,epidemiology, exposure,and treatment

Nickel is the most frequent cause of contact allergy worldwide and has been studied extensively. This clinical review provides an updated overview of the epidemiology, exposure sources, methods for exposure quantification, skin deposition and penetration, immunology, diagnosis, thresholds for sensitization and elicitation, clinical pictures, prevention, and treatment. The implementation of a nickel regulation in Europe led to a decrease in the prevalence of nickel allergy, and changes in the clinical picture and disease severity. Nevertheless, the prevalences of nickel allergy in the European general population are approximately 8% to 19% in adults and 8% to 10% in children and adolescents, with a strong female predominance. Well‐known consumer items such as jewellery and metal in clothing are still the main causes of nickel allergy and dermatitis, although a wide range of items for both private and occupational use may cause dermatitis. Allergic nickel dermatitis may be localized to the nickel exposure site, be more widespread, or present as hand eczema. Today, efficient methods for exposure quantification exist, and new insights regarding associated risk factors and immunological mechanisms underlying the disease have been obtained. Nevertheless, questions remain in relation to the pathogenesis, the persistent high prevalence, and the treatment of severe cases.     

Nickel,cobalt and chromium in consumer products: a role in allergic contact dermatitis?

In spite of the improved awareness of the potential for nickel, cobalt and chromium to en use skin allergy, the incidence of serialization to them is generally on the increase, especially for nickel. We review data from the literature and industry on transition metal contamination of consumer products and assess the hazard to man. Consumer products are defined as personal care items and detergent/cleaning products used regularly in domestic York. The analytical data demonstrate that consumer products are a relatively minor source of contact with nickel, cobalt or chromium. The traces found in consumer products will not be the primary cause of sensitization to these metals: levels will be too low and exposure too brief. A person sensitized to these metals has many other more significant sources of daily contact such as earrings, jewellery and metal objects. It is therefore necessary to focus on decreasing the high exposure to these transition metals from other sources rather than on possible trace amounts found in consumer products. Current good manufacturing practice ensures that trace nickel, cobalt and chromium concentrations in consumer products are less than 5 ppm of each metal, it is recommended that this be accepted as a standard for maximum concentrations and that the target should be to achieve concentrations as low as 1 ppm.     

Sensory, clinical and physiological factors in sensitive skin: a review

Certain individuals experience more intense and frequent adverse sensory effects than the normal population after topical use of personal care products, a phenomenon known in popular usage as sensitive skin. Consumer reports of sensitive skin are self-diagnosed and often not verifiable by objective signs of physical irritation. Companies who manufacture cosmetic and personal care products are challenged to provide safe products to an audience with tremendous differences in skin type, culture and habits. This review examines the still incomplete understanding of this phenomenon with respect to aetiology, diagnosis, appropriate testing methods, possible contributing host factors such as, sex, ethnicity, age, anatomical site, cultural and environmental factors, and the future directions needed for research.     

Copper hypersensitivity

The world production of copper is steadily increasing. Although humans are widely exposed to copper‐containing items on the skin and mucosa, allergic reactions to copper are only infrequently reported. To review the chemistry, biology and accessible data to clarify the implications of copper hypersensitivity, a database search of PubMed was performed with the following terms: copper, dermatitis, allergic contact dermatitis, contact hypersensitivity, contact sensitization, contact allergy, patch test, dental, IUD, epidemiology, clinical, and experimental. Human exposure to copper is relatively common. As a metal, it possesses many of the same qualities as nickel, which is a known strong sensitizer. Cumulative data on subjects with presumed related symptoms and/or suspected exposure showed that a weighted average of 3.8% had a positive patch test reaction to copper. We conclude that copper is a very weak sensitizer as compared with other metal compounds. However, in a few and selected cases, copper can result in clinically relevant allergic reactions.     

Dermatological and environmental toxicological impact of the sunscreen ingredient oxybenzone/benzophenone‐3

Oxybenzone (Benzophenone‐3) is an emerging human and environmental contaminant used in sunscreens and personal care products to help minimize the damaging effects of ultraviolet radiation. The Center for Disease Control fourth national report on human exposure to environmental chemicals demonstrated that approximately 97% of the people tested have oxybenzone present in their urine, and independent scientists have reported various concentrations in waterways and fish worldwide. Oxybenzone can also react with chlorine, producing hazardous by‐products that can concentrate in swimming pools and wastewater treatment plants. Moreover, adverse reactions could very well be increased by the closed loop of ingesting fish contaminated with oxybenzone and/or washing the ingredient off our bodies and having it return in drinking water as treatment plants do not effectively remove the chemical as part of their processing protocols. In humans, oxybenzone has been reported to produce contact and photocontact allergy reactions, implemented as a possible endocrine disruptor and has been linked to Hirschsprung's disease. Environmentally, oxybenzone has been shown to produce a variety of toxic reactions in coral and fish ranging from reef bleaching to mortality. Lastly, with the rise in skin cancer rates and the availability of more effective sunscreen actives such as micronized zinc oxide and titanium dioxide, serious doubts about the relative prevention benefit of personal care products containing oxybenzone must be raised and compared with the potential negative health and environmental effects caused by the accumulation of this and other chemicals in the ecosystem.     

Allergy to peanut oil – clinically relevant?

The increasing prevalence of food allergies (especially allergy to peanuts) has led to a discussion of how safe topical preparations containing peanut oil are with respect to allergy. The major allergens from peanuts are proteins that have been characterized at a molecular level and cloned. Clinical signs of peanut allergy symptoms can be observed on the skin (urticaria), or in the gastrointestinal and/or respiratory tract culminating in cardiovascular symptoms and anaphylactic reactions. In most cases, symptoms are elicited by oral uptake; rarely, a contact urticaria has been described. In vegetable oils, the contents of protein differ depending on the production process: crude oils contain approximately 100 times more proteins than refined oils. This has clear-cut implications for allergic individuals. Quantitative data are available regarding elicitation of symptoms in allergic individuals with a threshold dose of 0.1-1 mg peanut allergen in oral provocation tests. There are anecdotal reports of adverse reactions after topical use of peanut oils. In one epidemiological trial, an association between topical use of skin care products containing peanut oil and the development of peanut allergy was observed; however, the data reflect a retrospective analysis without specifying skin care products containing peanut oil and also without analysing the quantity of topicals used. In contrast, oral tolerance was prevented and allergic sensitization was enhanced in a mouse model using high concentrations of peanut protein. So far, no reliable data are available regarding doses required to induce sensitization against peanut allergen via the epidermal route. A possible induction of sensitization against peanut proteins through contact with the skin via skin care products and the respective protein concentrations is a matter of speculation. Patients with atopic diseases, namely eczema, need appropriate skin care because of the disturbed skin barrier function. The benefit of avoiding damage to skin barrier functions of atopic individuals by the use of peanut protein-containing skin care products seems to outweigh possible risks of sensitization and/or allergy induction against substances contained in those products containing refined peanut oil.     

Platinum and palladium nanoparticle‐containing mixture,PAPLAL, does not induce palladium allergy

Palladium (Pd) is a common metal found in jewellery and dental appliances, but it has been shown to be likely to cause metal allergy. We previously reported that platinum (nPt) and palladium (nPd) nanoparticle‐containing mixture (PAPLAL) has both superoxide dismutase and catalase activities and that the topical application of PAPLAL improved skin atrophy induced by chronic oxidative damage in an ageing mouse model. However, the safety of PAPLAL for preventing Pd allergy remains unclear. In the present study, we investigated whether or not PAPLAL induces Pd allergy. We found that PAPLAL treatment caused no skin inflammation, while nPd administration caused only slight skin inflammation compared to the palladium chloride‐induced severe reaction in an experimental metal allergy model. A gene expression analysis revealed that PAPLAL treatment significantly suppressed the expression of Inf‐γ, Il‐1β and Tnfα genes. Even in human clinical trials using patches containing metal nanoparticles, nPd and PAPLAL failed to induce significant skin inflammation. These results suggest that mixing with nPt in PAPLAL suppresses the inflammation response of nPd. PAPLAL can be expected to be applied to various skin treatments as a safe topical substance.     

Chromium allergy and dermatitis: prevalence and main findings

The history of chromium as an allergen goes back more than a century, and includes an interventional success with national legislation that led to significant changes in the epidemiology of chromium allergy in construction workers. The 2015 EU Leather Regulation once again put a focus on chromium allergy, emphasizing that the investigation of chromium allergy is still far from complete. Our review article on chromium focuses on the allergen's chemical properties, its potential exposure sources, and the allergen's interaction with the skin, and also provides an overview of the regulations, and analyses the epidemiological pattern between nations and across continents. We provide an update on the allergen from a dermatological point of view, and conclude that much still remains to be discovered about the allergen, and that continued surveillance of exposure sources and prevalence rates is necessary.     

Retrospective analysis of the clinical response of palmoplantar pustulosis after dental infection control and dental metal removal

Both metal allergy and dental focal infection have been considered as causative factors for palmoplantar pustulosis, and several case reports described that the skin lesions were ameliorated after dental metal removal or dental infection control. However, limited data are available to evaluate the association of these factors with disease severity of palmoplantar pustulosis. This study is designed to analyze the clinical outcome of 85 palmoplantar pustulosis patients after dental infection control (n = 70), tonsillectomy (n = 6) and dental metal removal (n = 9). More than half of the patients (63%, 44/70) showed positive clinical outcome after dental infection control. The skin lesions of all patients with tonsillitis were improved after tonsillectomy (100%, 6/6). On the other hand, one‐third of patients (33%, 3/9) showed positive response after dental metal removal. These results suggest that focal infection is more closely associated with palmoplantar pustulosis than dental metal allergy. According to our findings, palmoplantar pustulosis patients should be preferentially examined for focal infections.     

Cosmetic Allergy

A recent epidemiologic survey in the UK revealed that 23% of women and 13.8% of men experience some sort of adverse reaction to a personal care product over the course of a year. Although most of these reactions may be due to subjective sensory irritation, various studies reveal that up to 10% of dermatologic patients who are patch tested are allergic to cosmetic products or their constituent ingredients. Causative products include deodorants and perfumes, skin care products, hair care products, and nail cosmetics. Allergic contact dermatitis mainly results from fragrance chemicals and preservatives. Recent work has suggested that additional fragrance chemicals may need to be tested in order to identify those patients 'missed' by the current fragrance mix; in particular, hydroxy-isohexyl-3-cyclohexene carboxaldehyde (HMPPC Lyral) has been singled out as an important sensitizing agent. The increased usage of natural fragrances and botanic extracts can also cause problems in their own right or through co-reactivity. The preservative methyldibromo glutaronitrile has also been recognized as an increasingly important sensitizer in Europe, which has led to the recent recommendation that it should be prohibited from 'leave-on' products until information on 'safe' consumer levels becomes available. Other emerging allergens include UV filters, tosylamide/formaldehyde resin, and nail acrylates. The diagnosis of cosmetic allergy should be confirmed with patch testing, including testing of 'whole' products, when necessary, and repeat open application tests can be used to confirm the relevance of reactions in cases of doubt.     

Contact allergies to nickel sulfate, gold sodium thiosulfate and palladium chloride in patients claiming side-effects from dental alloy components

397 patients claiming various subjective symptoms related to dental restoration materials have been tested for the presence of metal allergy. The resultant data have been com pared with the corresponding allergies of eczematous patients. The frequency difference of metal allergy in the dental group is statistically significant or close to significance for nickel sulfate, potassium dichromate, cobalt chloride, palladium chloride and gold sodium thiosulfate. The findings suggest that the dental patient group represents a subgroup with a high frequency of metal allergy.     

Implantatallergien

An increasing number of patients receive and benefit from osteosynthesis materials or artificial joint replacement. The most common complications are mechanical problems or infection. Metals like nickel, chromium and cobalt as well as bone cement components like acrylates and gentamicin are potential contact allergens which can cause intolerance reactions to implants. Eczema, delayed wound/bone healing, recurrent effusions, pain and implant loosening all have been described as manifestation of implant allergy. In contrast to the high incidence of cutaneous metal allergy, allergies associated with implants are rare. Diagnosis of metal implant allergy is still difficult. Thus differential diagnoses – in particular infection – have to be excluded and a combined approach of allergologic diagnostics by patch test and histopathology of peri-implant tissue is recommended. It is still unknown which conditions induce allergic sensitization to implants or trigger peri-implant allergic reactions in the case of preexisting cutaneous metal allergy. Despite the risk of developing complications being unclear, titanium based osteosynthesis materials are recommended for metal allergic patients and the use of metal-metal couplings in arthroplasty is not recommended for such patients. If the regular CoCr-polyethylene articulation is employed, the patient should give informed written consent.     

Provocative use tests in CAPB-allergic subjects with CAPB-containing product

Cocamidopropyl betaine (CAPB) has been identified as a cause of contact allergy in personal care products. Furthermore, it has been suggested that chemicals responsible are impurities, especially dimethylaminopropylamine (DMAPA). However, skin contact concentrations with these impurities, especially DMAPA, are very low. The aim of the study was to analyse whether subjects with previous positive patch tests to CAPB would react in provocative use tests of a product containing CAPB. 10 individuals with a clinical history of contact allergy to CAPB (by positive patch test and history) took part in a ROAT which used a CAPB-based shower gel at 25% (DMAPA concentration < 1 ppm). None of the subjects showed positive allergic reactions. 1 of the test subjects did experience a flare of atopic dermatitis at the treatment site. Later, all 10 subjects were patch tested to 3 different concentrations of CAPB and DMAPA (0.1%, 0.3%, 1%) to verify the threshold that was capable of inducing a positive test reaction. 5/10 showed clear + reactions to 1% CAPB (typically at D3), whilst a further 3 gave marginal and/or irritant reactions. Only 1 of the subjects showed an allergic reaction to DMAPA. Finally, in uncontrolled use testing with the shower gel, none of the test subjects reported any adverse skin reactions. Thus, the study confirmed that CAPB-sensitive individuals can use a CAPB-based rinse-off product without the risk of experiencing an allergic reaction to CAPB.     

Latex allergy: a health care problem of epidemic proportions

Latex allergy is one of the major health concerns of the decade. The induction of latex allergy commonly occurs after exposure of skin or mucous membrane to natural rubber latex. It is usually a type I, immediate hypersensitivity reaction mediated by IgE which can range from mild skin erythema to anaphylaxis and death. To manage latex allergy appropriately, prompt and correct diagnosis is essential. This depends primarily on clinical history, latex specific IgE RAST (in vitro) and skin prick test (in vivo). It affects people who are frequently exposed to products made of natural rubber latex, such as, health care workers, workers in the rubber industry and those who have had multiple surgical operations. The prevalence in the general population was estimated at 0.7% in a population study in France, but this can be higher in health care workers (up to 17%) and in patients with spina bifida to almost 65%. Prevention strategies should therefore target at risk population, rather than the population as a whole. At present this primarily involves providing non-powdered latex gloves in hospitals and primary health care centres. However, once latex allergy has been established, the situation becomes more complicated. Health care workers either have to be moved to a latex free environment or in extreme circumstances may have to give up their occupation. For patients undergoing operations most hospitals have adopted a latex free protocol. It is important that this is understood and followed by every member of the staff. Those who have had serious adverse reactions should wear Medi-Alert bracelets and in exceptional circumstances may need to keep epinephrine injections on their person. Future strategies focus on the reduction of allergens during latex manufacture, development of suitable non latex gloves and immunotherapy including desensitisation of latex allergic individuals and development of candidate vaccine.     

Quantitative risk assessment for the induction of allergic contact dermatitis: uncertainty factors for mucosal exposures

The quantitative risk assessment (QRA) paradigm has been extended to evaluating the risk of induction of allergic contact dermatitis from consumer products. Sensitization QRA compares product-related, topical exposures to a safe benchmark, the sensitization reference dose. The latter is based on an experimentally or clinically determined 'no observable adverse effect level' (NOAEL) and further refined by incorporating 'sensitization uncertainty factors' (SUFs) that address variables not adequately reflected in the data from which the threshold NOAEL was derived. A critical area of uncertainty for the risk assessment of oral care or feminine hygiene products is the extrapolation from skin to mucosal exposures. Most sensitization data are derived from skin contact, but the permeability of vulvovaginal and oral mucosae is greater than that of keratinized skin. Consequently, the QRA for some personal products that are exposed to mucosal tissue may require the use of more conservative SUFs. This article reviews the scientific basis for SUFs applied to topical exposure to vulvovaginal and oral mucosae. We propose a 20-fold range in the default uncertainty factor used in the contact sensitization QRA when extrapolating from data derived from the skin to situations involving exposure to non-keratinized mucosal tissue.     

Intolerance reactions to knee arthroplasty in patients with nickel/cobalt allergy and disappearance of symptoms after revision surgery with titanium‐based endoprostheses

Intolerance reactions to metal implants may present as dermatitis, impaired wound healing, effusions, pain or loosening. The clinical relevance of metal allergy in the differential diagnosis is often unclear and patients may even tolerate implants containing metals to which they are allergic. We present four patients with knee arthroplasty in whom after exclusion of infection or mechanical causes, a nickel/cobalt allergy led to replacement surgery with titanium‐based prostheses. The subsequent alleviation of symptoms underlined the relevance and usefulness of allergological diagnostics in selected cases of complicated arthroplasty.     

Orthopädisch-chirurgische Implantate und Allergien

Materials used in osteosynthesis or artificial joint replacement are usually well tolerated. Complaints after such operations are mostly related to infection or mechanical problems but may also be caused by allergic reactions. The latter encompass skin changes, e.g., eczema, delayed wound/bone healing, recurrent effusion, pain, or implant loosening. In contrast to the high incidence of cutaneous metal contact allergy, allergies associated with implants are a rare condition. However, epidemiological data on the incidence of implant-related allergic reactions are still missing. Typical elicitors are nickel, chromium, cobalt, and constituents of bone cement (acrylates und additives such as gentamicin or benzoyl peroxide). After exclusion of the most common differential diagnoses, allergy diagnostic procedures are primarily based on patch tests including a metal and bone cement component series. Additional analysis of periimplant tissue is recommended. However, further studies are necessary to show the significance of the histologic findings and the role of the lymphocyte transformation test (LTT). Which combinations of factors will induce allergic sensitization to implants or trigger periimplant allergic reactions in the case of preexisting cutaneous metal allergy is still unknown. Titanium-based osteosynthesis materials are recommended for metal allergic patients. In elective hip replacements, a ceramic/polyethylene (PE) articulation should be used, and in knee replacements "alternative materials". If a regular, potentially applicable CoCr/PE articulation is preferred, the patient must be well informed and must give his/her written consent.     

Vesicles: Potential nano carriers for the delivery of skin cosmetics

In the present scenario, consumers are searching for personal care products that supply multiple benefits with minimal efforts. The outcome has been the introduction of nanotechnology-based cosmetic products that are safe to use and results driven. Some topical cosmetics can act efficaciously when they reach their target sites present in the deeper layers of the skin. The main problem with delivering active ingredients across the skin is the barrier function of the skin. Therefore, to get the maximum benefit from cosmetic products and to overcome the problems associated with their skin penetration, scientists are investigating various strategies to overcome these barrier properties. Vesicular carriers have been claimed to improve the topical delivery of active ingredients. This review offers a brief overview of current approaches in the research and development of vesicular carriers to improve the delivery and performance of active ingredients present in the cosmetics.     

Schleimhauterkrankungen aus allergologischer Sicht

The oral allergy syndrome is one of the most common form of food allergy and manifests as contact urticaria of the oral mucosa after consumption of cross reacting foods. Whereas allergic contact stomatitis often occurs due to dental materials, allergic contact cheilitis is usually a reaction due to topical therapeutics like herpes ointments or lip care products. As late type reactions are more frequent than immediate type reactions in the anogenital mucosa, contact dermatitis in this area should be identified via epicutaneous testing. In case of contact urticaria at the genital mucosa, a semen allergy or a latex allergy should be given due consideration as a possible cause. Angioedemas, which are mostly common histamine mediated, usually prefer skin areas with loose connective tissue such as the oral or genital mucosa. Fixed drug eruption also occurs preferentially in these areas. Bullous drug-induced skin reactions (e.g., SJS and TEN) are characterized by severe hemorrhagic, erosive affections of mucous membranes.