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.     

Nickel sensitivity and the implantation of orthopaedic prostheses

There is no evidence that nickel-sensitive patients, when given a modern plastic-to-steel hip replacement, develop cutaneous reactions or loosening of their prostheses. However, eczema I occasionally seen with static metal prostheses and eruptions sometimes accompanied the use of the older types of joint prosthesis. Modern plastic-to metal joint replacements rarely cause sensitization to the composite metals. In the rare instances when this has been detetcted by patch testing, the affected patients have not developed eczema or loosening of their prostheses.     

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.     

Pragmatic approach to the clinical work-up of patients with putative allergic disease to metallic orthopaedic implants before and after surgery

Allergic complications following insertion of metallic orthopaedic implants include allergic dermatitis reactions but also extracutaneous complications. As metal-allergic patients and/or surgeons may ask dermatologists and allergologists for advice prior to planned orthopaedic implant surgery, and as surgeons may refer patients with complications following total joint arthroplasty for diagnostic work-up, there is a continuous need for updated guidelines. This review presents published evidence for patch testing prior to surgery and proposes tentative diagnostic criteria which clinicians can rely on in the work-up of patients with putative allergic complications following surgery. Few studies have investigated whether subjects with metal contact allergy have increased risk of developing complications following orthopaedic implant insertion. Metal allergy might in a minority increase the risk of complications caused by a delayed-type hypersensitivity reaction. At present, we do not know how to identify the subgroups of metal contact allergic patients with a potentially increased risk of complications following insertion of a metal implant. We recommend that clinicians should refrain from routine patch testing prior to surgery unless the patient has already had implant surgery with complications suspected to be allergic or has a history of clinical metal intolerance of sufficient magnitude to be of concern to the patient or a health provider. The clinical work-up of a patient suspected of having an allergic reaction to a metal implant should include patch testing and possibly in vitro testing. We propose diagnostic criteria for allergic dermatitis reactions as well as noneczematous complications caused by metal implants.     

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.     

Unverträglichkeit von Implantaten – Herausforderung für die Allergologie

Summary: With increasing distribution and use of various metal implants in modern medicine, there has been an aggravation of reported allergic reactions against metal implant materials in the last decades. For patients who received metal implants both localized and generalized eczema, urticaria, delayed wound healing, vasculitis, bullous disease and erythema exudativum like rashes have been described. Since metal implants are usually made of alloys containing nickel, cobalt and chromium these metals are presumed to be the deciding aetiologic factors as all of them are well known contact sensitizers. However, it is important to note that very often specific individual factors play a role in the pathology of these reactions as well. In accordance with aseptic loosening of metal implants cell infiltration around these implants are characterized by delayed type hypersensitivity. On the other hand, the complexity of all enrolled pathophysiological mechanisms makes it very difficult to determine and further characterize this reaction. Furthermore preoperatively performed epicutanous tests do not allow a reliable prediction of preexisting sensitisation against metals. For this reason more and more in vitro‐testing will be used in the future to assess metal allergy.     

Rejection of metal to metal prosthesis and skin sensitivity to cobalt

Metal to metal prostheses give satisfactory results in 90% of patients. About half of the failure rate may be due to allergic reaction to the metals involved, particularly cobalt. A total of 35 patients in this unsatisfactory group have been patch-tested; 16 were positive to metals, 13 to cobalt, 4 to nickel, and 2 to chromate. Only two patients showed any skin lesions - one a localized dermatitis round the knee joint from nickel sensitivity, and one to cobalt who had a widespread scattered circular erythematous lesion suggestive of a generalized allergic vasculitis. Patients requiring a metal/metal prosthesis should have a careful history taken for metal sensitivity and be patch-tested with the metals. All the patients in this investigation had metal/metal prostheses and no reaction was seen after metal/high density polyethylene implants. Titanium 318 may be a satisfactory substitute for cobalt chrome alloy if reactions are encountered.     

Metal-induced generalized pruriginous dermatitis and endovascular surgery

Metal contact allergy is a common problem in the general population. Diagnostic and therapeutic medical-surgical procedures in which metals can be responsible for eczema are diverse. Endovascular aortic surgery is still an experimental but less invasive technique. A generalized eczematous dermatitis elicited by metal of an endovascular prosthesis is presented. An abdominal aortic aneurysm was diagnosed in a 79-year-old woman. Endoluminal repair with a straight Vanguard endograft was successful. 3 weeks later, she suffered a severe episode of erythema and eczema on the legs. Since then, she complained of continuous pruritus with eczema and excoriated papules. The dermatitis and also the patch test pathology showed eczema. Patch testing was positive to nickel sulfate and cobalt chloride. An endograft semi-quantitative metal analysis was performed with plasma-induction joint mass-spectrometry. The self-expanding metal stent was mainly composed of nickel (approximately 55%) and titanium (21%) with reinforcing thread of platinum. Antimony was detected only in the polyester textile. These results are consistent with Nitinol composition. The need for preoperative patch testing for metals is controversial. Enquiry about metal allergy is recommended before endoluminal surgical procedures. In the near future, the design of endografts must take into account the possibility of this sort of reaction.     

Allergy in hip arthroplasty

A prospective study was made in 85 patients of the relationship between implantation of metal-to-polyethylene hip prostheses and the incidence of delayed-type allergy to components of the prostheses. It shows that sensitization to cobalt, nickel and chromate, and to methacrylate, can develop as a result of such implantation. Loosening did not occur in any of the cases of possible sensitization. Evidence of allergy to prosthetic components was not found in any of the 10 cases of loosening.     

Benzoyl peroxide: is it a relevant bone cement allergen in patients with orthopaedic implants?

Contact allergies to orthopaedic implant material are discussed to be relevant for postoperative complaints. We aimed at determining the prevalence of sensitizations to implant metals and to bone cements in patients with implants. We investigated 13 consecutive patients with suspicion of contact allergy to implant material. Epicutaneous patch testing was performed with metals and bone cement components including benzoyl peroxide (BPO). The chief complaints were skin disorders (n = 3), loosening of implant (n = 2), swelling (n = 6), and pain (n = 2). 6 patients had a sensitization to at least 1 allergen. 3 patients reacted to BPO, being of possible relevance in 1 of these patients suffering from dermatitis. Other sensitizations, such as those to nickel, fragrance, and balsam of Peru, were observed, with no clinical relevance (n = 1, respectively). BPO in bone cements may lead to type 4 sensitizations of which the relevance, however, remains questionable. Nevertheless we recommend this allergen to be tested in patients with complicated cemented orthopaedic implants.     

Metal sensitivity in patients with orthopaedic implants: a prospective study

Background. Sensitization to orthopaedic implant materials is an unpredictable event that might affect implant performance. Objectives. In candidates for hip or knee joint prosthesis implantation, to evaluate preoperative assessments for identifying patients with metal sensitivity, to determine the percentage of patients who developed metal sensitivity at 1 year after prosthesis implantation, and to examine the clinical relevance of patch tests and lymphocyte transformation tests (LTT‐MELISA®) for the evaluation of metal sensitization. Patients and methods. A total of 100 patients referred for total hip or total knee arthroplasty were assessed preoperatively and then at 1 year post‐implantation by means of patch tests with the metals present in the implant alloys. In a pilot study, 20 patients also underwent both patch testing and a lymphocyte transformation test (LTT‐MELISA®) for the same metals. Results. Only 72 of 100 patients were patch tested both before and after surgery, and 12 of 20 also underwent LTT‐MELISA® before and after surgery. Of 31/100 patients with an apparent history of nickel sensitivity determined during preoperative assessment of subjects, 12 tested negative on both tests, and 4 with a negative history of nickel sensitivity tested positive. One year post‐implantation (72 patients), 5 patients who had initially tested negative for a metal allergy became positive for at least one or more metal constituents of the prosthesis on at least one or the other test. Conclusions. Given the discrepancies between the information obtained while taking patient histories and test results, preoperative history‐taking alone appears to be insufficient for identifying patients with metal sensitivity. Moreover, the increase in the percentage of patients who tested positive for metal sensitivity 1 year post‐implantation suggests the possibility of prosthesis‐induced sensitization. Therefore, objective determination of metal sensitivity at preoperative assessment should be considered in planning arthroplasty intervention, as it would help the surgeon in selecting the most appropriate prosthesis for the patient and could benefit implant performance.     

Implantation of orthopaedic devices in patients with metal allergy

Patients with a contact allergy to chromium, cobalt and/or nickel, patch test verified before implantation of a metallic orthopaedic device, were followed up years later by clinical and radiographic examination as well as with epicutaneous and intracutaneous tests. Eighteen patients had been exposed to an orthopaedic implant for several years (mean 6.3 years) containing a metal to which they were allergic. None had suffered any dermatologic or orthopaedic complications attributable to the contact allergy.     

Is nickel allergy an occupational disease? Discussion of the occupational relevance of a type IV allergy to nickel (II) sulfate using case reports

Type IV sensitization to nickel (II) sulfate is common in the general population. Nickel can be found in different metals leading to occupational exposition in industrial professions.The individual clinical relevance of nickel allergy can easily be identified but it can be difficult to assess if nickel allergy was acquired privately or occupationally. The problem if nickel allergy fulfills the criteria of an occupational skin disease is presented in three case reports. The occupational relevance of a type IV sensitization to nickel in a chemical laboratory assistant, a flight attendant and a cashier are discussed. Important conditions for acquiring nickel allergy are contact with nickel‐plated and nickel‐releasing materials, the kind of skin contact, the status of the epidermal barrier, and the individual working conditions with an increased bioavailability of nickel. In cases of type IV sensitization to nickel, the affected person cannot continue to work in metal plating or with contact to nickel‐plated metals.The causal relationship between the type IV sensitization to nickel and the occupation needs to be clarified in each individual case. In general, occupationally caused nickel allergy is rare and the occupational relevance of nickel allergy is often overestimated.     

Difficulties in medico-legal diagnosis of occupational dermatoses in women sensitive to nickel

The frequency of positive results of patch tests with nickel was analysed in 1044 patients with positive results of patch tests examined because of suspected occupational diseases in the years 1977-1988. More frequent presence of allergy to nickel was demonstrated in women (21.8%) than men (6.9%), and it was found that the allergy to this metal has increased sixfold in women in the period 1985-1988 in relation to the period 1977-1980. A particularly high increase of the allergy to nickel in women was observed in the last year (69.4%). This increase of allergy was noted not only in young women but also in middle-aged ones. In women monovalent allergy to nickel and bivalent allergy to nickel and cobalt prevailed, while in men bivalent allergy to nickel and chromium was most frequent. The problems of diagnosis and expertise in occupational diseases in women with allergy to nickel present in metal jewelry and working in contact with metals in occupation are discussed.     

Role of body piercing in the induction of metal allergies.

BACKGROUND: Metal allergies have been linked to body piercing in women, but few studies have explored this phenomenon in men. It has been postulated that nickel/cobalt and nickel/palladium exhibit coreactivity in patients allergic to metals. OBJECTIVES: (1) Determine the incidence rate and the source for the induction of metal allergy in 3 groups of men: unpierced, one site-pierced, and multiple sites-pierced; and (2) evaluate the degree of coreactivity between nickel/cobalt and nickel/palladium. METHODS: Men aged 18 to 43 years (n = 118) were patch-tested using the North American Contact Dermatitis Group's protocol to nickel sulfate 2.5%, gold sodium thiosulfate 0.5%, cobalt chloride 1%, and palladium chloride 1%. RESULTS: Eleven (9.3%) subjects had at least 1 positive reaction. When characterized by the number of pierced sites, positive reactions were seen in 2 of 50 (4.0%) unpierced, 3 of 27 (11.1%) one site-pierced, and 6 of 41 (14.6%) multiply pierced men. The number of piercings was a statistically significant predictor of metal allergy (P = .04). Four (66.7%) cobalt and no palladium reactions occurred in nickel-positive subjects. The source for the induction of the allergic response was primarily jewelry, which accounted for 5 of 6 nickel allergies and 2 of 3 gold allergies. Silver jewelry was a significant predictor of an allergic response. CONCLUSION: This study represents the first report that the number of body piercings has positive bearing on the incidence of metal allergy in men. The data also support the theory of coreactivity for nickel/cobalt, but not for nickel/palladium.     

Prevalence of nickel allergy among Finnish university students in 1995

Nickel allergy was studied in a sample of 1st-year university students starting their studies in 1995. A total of 296 subjects (72%) of 413 invited participated in the clinical examination, and 284, 96 male and 188 female, were patch tested (69%). A history of nickel sensitization was enquired for. Prick tests and serum specific IgE levels were determined. Occurrence of atopic dermatitis, hand eczema, and current exposure to metals were recorded. Nickel allergy was encountered in 39% of all female students, in 42% of females with pierced skin, and in 14% of females without pierced skin. The corresponding figures for males were 3%, 7% and 3%. In the multiple regression analysis, the risk factors for nickel allergy were female sex (OR 8.1, p<0.01), current metal exposure at examination (OR 4.1, p<0.01) and skin piercing (OR 3.6, p<0.05). Positive prick tests or elevated IgE levels to common allergens were not significantly associated with nickel allergy. In female students, the prevalence of nickel allergy has increased from 13% in 1986 to 39%. The prevalence among males has remained low at 3%. The results indicate that, in addition to skin piercing, current metal contacts are important risk factors for nickel allergy. This finding gives support to the EU Nickel Directive.     

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.     

Metal contact sites: a hidden localization for nail varnish allergy?

It is thought that many people with nickel dermatitis use nail varnish as a barrier coat on nickel‐containing metals; however, nail varnish allergy at sites in contact with such coated has only been documented once previously, to our knowledge. The aim of this study was to search for a possible link between nail varnish and metal allergy. In total, 1607 consecutively patch‐tested patients were enrolled; 16 (1%) of these had nail varnish allergy, located mainly on the eyelids. Eight also had nickel allergy. Six of these eight had successfully used protective nail varnish on metals until subsequent development of ‘failure of protection’ even before the eyelid eczema developed. Sites in contact with metal might be a hidden and even initial localization for nail varnish allergy. ‘Failure of protection’ after a successful protective period despite renewing nail varnish coatings should raise suspicion of sensitization to the nail varnish itself. Future studies should focus on the incidence of allergic contact dermatitis and primary sensitization from nail varnish used as a barrier against nickel dermatitis.     

Metal allergy in north Norwegian schoolchildren and its relationship with ear piercing and atopy

In 424 schoolchildren (223 boys and 201 girls) aged 7–12 years undergoing routine patch tests, 21.0% (89 children), 38.8% (78/201) of girls and 4.9% (11/223) of boys, had had their ears pierced. 18.6% (79 children, 55 girls and 24 boys) gave a history of cutaneous reactions to metallic jewellery, and in 17.2% (73 children, 49 girls and 24 boys), sensitivity to one or more metals was confirmed. Metal allergy was confirmed by patch testing in only 34.2% of the children with a history of metal dermatitis, and 13.3% of those without a history of metal reactions had, in fact, positive patch tests to 1 or more metals. The low sensitivity (37.0%) and low positive predictive value (34.2%), together with high specificity (85.2%) and high negative predictive value (86.7%), seem to justify dermatological examination of individuals with a positive symptom-based diagnosis only. Nickel sensitivity was found in 14.9% (63 children, 44 girls and 19 boys). There is clearly a relationship between ear piercing and induction of nickel allergy in girls, as nickel sensitivity in girls with pierced ears was 2 × (30.8%) that found in those without (16.3%) pierced ears. In boys, nickel sensitivity was much less frequent and few cases were related to ear piercing. Atopy appeared to influence the propensity for developing metal sensitivity in girls, as atopic girls showed positive metal tests 2xas frequently (30.8%) as non-atopic (17.0%). No such differences were found in boys. Girls with a combination of atopy and ear piercing showed the highest frequency of positive metal tests (45.5%). The frequency of metal allergy increased with increasing number of holes in the ear lobes. Symptoms of nickel allergy were reported in 30.2% (19/63) of mothers whose children had nickel allergy, compared to 16.3% (59/361) of mothers whose children had negative nickel tests. Only 4 children reported symptoms of nickel allergy in their father. The high frequency of nickel sensitivity in all children tested may indicate an influence of sources other than ear piercing.