Retrospective Evaluation of Patch Testing Before or After Metal Device Implantation FREE

Implanted devices, such as orthopedic prostheses and pacemakers, are being used increasingly. A source of concern to patients and their physicians and surgeons is whether an “allergy” to these devices, particularly implanted metals, might cause loosening, pain, skin eruptions, or other problems. Over the past decade, evidence has accumulated to support this concern.^{1 - 7}

Patch testing is one possible method for detecting an allergy to an implanted device. The efficacy of such testing in the case of metal sensitivity and implantable devices is a matter of considerable debate.^{8 - 9} Recently, Granchi et al² concluded that patch testing may be a suitable method for the detection of sensitization to implant components.

Because patch testing might be a means of detecting an allergy to an implanted device, dermatologists are asked occasionally to patch test patients with implanted devices (such as orthopedic prostheses and pacemakers). Because data describing how to approach patch testing in this context are limited, we developed a protocol for patch testing patients who are about to undergo or who have undergone device implantation. Herein, we review our experience with this patch testing protocol.

Patients who underwent patch testing for evaluation of suspected allergic contact dermatitis in the context of an implanted device at Mayo Clinic, Rochester, Minnesota, from January 1999 through March 2006, were identified from an existing clinical database. In general, patients were not patch tested if they applied topical corticosteroids to potential patch test sites; took immunosuppressive drugs, including oral corticosteroids; or had medical conditions that could compromise the evaluation of skin responsiveness.^{10 - 11} Information on patient demographics, characteristics of the devices, reasons for patch testing, and patch test results was extracted from the clinical database and clinical records. This study was approved by the Mayo Clinic institutional review board.

Patients who had undergone patch testing were excluded if they had fewer than 90 days of follow-up or poor documentation by the referring surgeon, dermatologist, or both, which did not allow an accurate assessment of the relevance of the patch test results to the proposed device. Patients who declined research authorization were excluded from the analysis.

The implanted devices considered in this study were orthopedic devices and pacemakers. For the group of patients evaluated before surgery, change in management was defined as a documented change in the choice of metal implant to be used, for any reason. In the group of patients evaluated with patch testing after device implantation, if device revision was performed (including surgically changing the device or removing it completely), the reason for revision was extracted from the prerevision surgeon's note.

For the sensitivity disk patch test, we request that the orthopedic surgeon or cardiologist obtain the sensitivity disks for the exact device that has been implanted or is to be implanted. These are obtained from the device manufacturers, who readily supply the various disks to be used. Generally, only 1 or 2 sensitivity disks are provided; these are usually metals. These disks are then placed on the patient's back. This procedure approximates a use test in this context. Examples of specific sensitivity disks used are listed in Table 1.

Allergens commonly found in prostheses were assembled in a prosthesis series (Table 1) and include typical metals, acrylates, and other allergens peculiar to prostheses.

Patients also commonly had a metal series placed (Table 1). The most common concern in implanted devices is the metal used; performing the metal series provides information if an alternative device containing metal needs to be used by the orthopedic surgeon or cardiologist.

Many patients were also tested with a standard series of allergens (Table 1). This practice provided more information about a possible contact dermatitis if the results of the metal and prosthesis series and sensitivity disk patch testing were unrevealing.

The methods for patch test application, chambers used, and reading times were the same as those used by the North American Contact Dermatitis Group (NACDG).^{10 ,12} Testing was conducted with aluminum chambers (Finn Chambers, Tuusula, Finland) on porous surgical paper tape (Scanpor; Norgesplaster Aksjeselskap, Vennesia, Norway), and patches were applied to patients' upper backs and removed after 48 hours. Metals were applied directly to the back. Most of the allergens for the metal series were purchased from Chemotechnique Diagnostics AB (Malmö, Sweden). Other allergens were compounded by the Mayo Clinic pharmacy. Sensitivity disks were obtained directly from the device manufacturers. Any antihistamine regimens were not discontinued before patch testing.

Allergens were placed on day 1. Reactions were evaluated initially on the day of removal of the allergens from the back (day 3), then again 2 to 3 days later (day 5 or 6), and then again the following week (days 11-14). The additional reading in the second week was performed because patch test reactions to metals may occur late, beyond day 5.

Patch test reactions were interpreted by using criteria similar to the NACDG criteria: negative reaction, macular erythema, weak reaction (nonvesicular erythema, infiltration, and possibly papules), strong reaction (edematous or vesicular), extreme reaction (spreading, bullous, ulcerative lesions), and irritant reaction.^{10 ,12} All reactions were further interpreted as relevant or irrelevant on the basis of a history of known contact of the affected skin areas with substances containing the allergen or a history of circumstances of likely contact with substances containing the allergen. For the purposes of this study, a positive allergic patch test result was defined as a weak, strong, or extreme reaction or as a macular erythematous reaction if the result was relevant. In general, we wait 15 to 20 minutes after removing the patch tests before performing the reading to minimize the possibility of positive results from pressure.

Our review identified 59 patients who were referred for patch testing. Sufficient follow-up information was available for 44 patients: 22 who underwent patching before surgery and 22 whose patch sites were evaluated after surgery. The clinical details of the 2 groups are summarized in Table 2.

Patients evaluated with patch testing before device implantation were referred by the orthopedic surgery (21 patients) and cardiology (1 patient) departments. Nineteen patients received dynamic orthopedic devices, 2 received static devices, and 1 received a cardiac pacemaker.

Twelve patients underwent patch testing with sensitivity disks before device implantation. None of these patients had positive test results to a manufacturer-supplied sensitivity disk. Five patients had positive patch test results to a component of the proposed prosthesis (Table 3).

All 22 patients referred for patch testing before surgical implantation of a metallic device had a personal history of metal allergy, most commonly evident when wearing jewelry. Nineteen patients had positive patch test results to any metal, most commonly nickel sulfate (12 patients), but also cobalt chloride (7), palladium chloride (4), beryllium sulfate tetrahydrate (3), and chromium chloride (2). Two of the 19 patients who had positive patch test results to any metal were newly positive after day 11 of the patch test. The 2 metals to which these patients had positive test results during the second week of testing were cobalt chloride and gold sodium thiosulfate.

On the basis of the patch test results, 4 of the 5 patients with positive patch test results to a component of the proposed device had a documented change in the choice of implanted device. The surgeon for the fifth patient chose not to change the device. Although the patient was proven to have a delayed-type hypersensitivity to nickel sulfate, the nickel used in the device was in the form of stainless steel, and therefore the surgeon believed there was little chance of an adverse reaction. This individual had not reported any postoperative complications at 390 days of follow-up.

Seventeen patients had negative patch test results to the components of the proposed prosthetic devices. One patient did choose a different device (one that was free of nickel) on the basis of clinical history alone, despite negative patch test results to nickel. In the long-term, none of the patients who had negative patch test results developed postoperative dermatitis over the site of the implant or over the whole body. Two of these patients later underwent device revision—1 because of a dislodged left ventricular lead in a pacemaker and 1 because of joint loosening after a fall.

There were 3 referral sources for patients who underwent patch testing after device implantation: orthopedic surgeons (15 patients), cardiologists (4), and patient self-referral (3). Ten patients received dynamic orthopedic devices, 8 received static devices, and 4 received cardiac pacemakers. Thirteen patients had an unexplained skin eruption postoperatively over the site of the device in temporal association with implantation of the device. The skin eruptions were most commonly described by a dermatologist as consistent with dermatitis, although 1 was thought to be a cellulitis. The skin eruptions in these patients lasted anywhere from a few weeks to 14 months. The skin eruption was localized either over the implanted device or over the implanted device as well as distal sites (Table 4). All patients received topical corticosteroids and over-the-counter lotions. Nine patients were referred for reasons other than a skin eruption: chronic pain (8) and joint loosening of unknown etiology (1).

Eleven patients underwent testing with sensitivity disks. None of these patients was reactive to a manufacturer-provided sensitivity disk. None of the 22 referred patients had positive patch test results to any component of their previously implanted metal-containing device.

Ten patients had positive patch test results to at least 1 metal. Seven of these patients were among the 13 who presented with a skin eruption. Each of these 10 patients was found to have positive patch test results to a metal on test day 5 or earlier. Six of these patients underwent device revision for reasons other than the positive patch test reaction: chronic pain at the implant site (2 patients), joint loosening (2), persistent overlying skin eruption (1), and device end of life (1).

Twelve patients had negative patch test results to both the prosthesis series as well as the metal series. Of these, 7 underwent joint revision: 4 for infection, 2 for joint loosening, and 1 because of radius nonunion.

In this article, we present our clinical experience with patients referred for patch testing because a device (orthopedic prosthesis or pacemaker) was to be implanted or had been implanted. This is an approach to evaluate the suitability of the device used in these patients and does not answer the more fundamental questions as to whether patch testing can truly detect allergic reactions to implanted devices or indeed whether supposed allergies to implanted devices really cause problems such as loosening or dermatitis.

To summarize the clinical experience presented, in general, patch testing was performed before device implantation because a patient reported a history of metal allergy, and the results helped guide the choice of the device implanted. The value of patch testing after device implantation was less clear; no cases of relevant positive patch testing were found in our series.

Several lines of evidence suggest that allergy to implanted metals may cause problems such as device failure and dermatitis.

In sum, it seems logical that the components of implanted devices may play a role in both device failure and dermatitis. However, how does one prove this or demonstrate an allergy? The causality of allergy in these events is still in question.

We found that among the 22 patients who were referred by a surgical service to the department of dermatology before implantation of a metal device and who had a clinical history of metal allergy, 19 had positive patch test results to any metal. Other investigators^{2 ,14} have reported similar rates. Our group of patients included predominantly women, which is consistent with other studies¹⁴ in which patients underwent patch testing before receiving a metal implant because they had a clinical history of metal allergy. Women have more opportunity both to be sensitized to metals and also to be aware of a sensitivity because they typically wear costume jewelry more frequently than men.¹⁵

The results of patch testing seemed to influence the choice of device in all cases. In our experience, then, patch testing may play a role in the selection of implantable devices by surgical colleagues. Whether the change in device is necessary is still a matter of open debate. Most patients with an allergy to a specific component in an implantable device do not have any problems. Carlsson and Möller¹⁷ identified 18 patients who had undergone patch testing and were verified to have contact allergy to a component of a metallic orthopedic device before undergoing implantation of that device. These patients were followed up for a mean duration of 6.3 years with clinical and radiologic examination. None of the patients had dermatologic or orthopedic complications owing to the contact allergy.

One patient was found to have a positive patch test result to nickel sulfate, a component of the total knee prosthesis the patient was scheduled to receive. The surgeon and patient elected to proceed with implantation of the nickel-containing device despite these results because the device was made of stainless steel. At 390 days of follow-up, there were no reported problems associated with this device. Although patch testing did prove the presence of metal sensitivity to a component of the patient's device, it is impossible to draw a conclusion about the usefulness of such testing based solely on a single case.

The most common reason for referral of a patient to the dermatology department concerning a possible allergic reaction to a previously implanted metal device was the presence of an unexplained skin eruption over the device or involving more of the patient's body surface shortly after undergoing implantation. Less common reasons included chronic pain localized to the implant site and aseptic joint loosening of unknown etiology. Cutaneous reactions to metal implants have been documented.^{3 - 4 ,13 ,16} Although allergic contact dermatitis can clearly be caused by metal implants, whether sensitization can affect device outcome is still under discussion.^{2 ,6 ,9 ,16} In our experience, patch testing after device implantation seems to have little bearing on management.

None of the 22 referred patients had a positive patch test result to a component of the implanted device. Other studies reported similar rates of 6.1%,¹⁸ 8.4%,¹⁹ and 10.0%.¹⁶ The present study found that among the patients tested retrospectively, 47.8% had a positive patch test result to any metal. A study¹⁴ of patients undergoing total hip arthroplasty found a sensitization rate of 47.1%. It is interesting to note that this rate is consistent with our results, given that the mean implant time in situ was 1.3 years in our study and 13.6 years in the comparable study.

First, can allergies to devices such as orthopedic prostheses and pacemakers really lead to problems with the device? Second, is patch testing the best way of detecting allergy to an implanted device? Patch testing is a means of detecting delayed-type hypersensitivity on the skin; does it have value in detecting allergy to devices implanted deep in the body? Negative patch test results are reassuring, but might a reaction to the device still occur? If a patch test result is positive, should a device be avoided or removed if already implanted? If allergy to a component of an implanted device is playing a role, is patch testing (which is designed specifically to detect allergic contact dermatitis) the best way of detecting that allergy? Data are limited in answer to all these questions.

The results reported herein should be viewed in light of the limitations of the study. This is a retrospective case review of our experience with patch testing and metal implants. The sample size is small and represents a clinical experience. Also, it is possible that negative patch test readings are falsely negative. The study design did not permit us to address the fundamental question of whether patch testing is truly predictive or reflective of device failure or sensitization to components of the device.

In this clinical experience with patch testing in patients with an implanted device (orthopedic device or pacemaker), half the requests for patch testing were made before implantation, and half occurred after implantation. Patch testing was performed at the request of orthopedic surgeons, cardiologists, and patients themselves. In general, patch testing before device implantation was performed because a patient reported a history of metal allergy; the result helped guide the choice of device to be implanted. The value of patch testing after device implantation was less clear; patch testing was not positive and relevant in that circumstance. This is a clinical experience; the problem of whether patch testing is truly relevant to implanted devices remains unresolved. Further studies are needed to address the many unanswered questions.

Correspondence: Mark D. P. Davis, MD, Department of Dermatology, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (davis.mark2@mayo.edu).

Accepted for Publication: October 7, 2007.

Author Contributions: Dr Davis had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Reed, Davis, Nakamura, and Hanson. Acquisition of data: Reed, Nakamura, Hanson, and Richardson. Analysis and interpretation of data: Reed and Davis. Drafting of the manuscript: Reed, Davis, and Hanson. Critical revision of the manuscript for important intellectual content: Davis and Richardson. Obtained funding: Davis. Administrative, technical, and material support: Davis, Hanson, and Richardson. Study supervision: Davis.

Financial Disclosure: None reported.

Additional Contributions: The Section of Scientific Publications at Mayo Clinic provided editing, proofreading, and reference verification.