Metal patch test positive with rash and knee replacement

Your question was shared with Dr. Luz Fonacier, chief of allergy/immunology at Winthrop University and chair of the work group that produced the practice parameter on contact dermatitis (1). I have summarized her observations and suggestions below.

I would have a few questions about this case

1. A positive to 14 metals is very unusual. You may be dealing with ‘angry back syndrome’ from the start. I usually suspect ‘angry back’ if you have more than 5 positive patch tests.

2. A quote from Fisher’s textbook on contact dermatitis is the following: “if metal salts were tested close to each other a strong positive to nickel would be accompanied by false positive patch test reactions to adjacent metal salts, particularly cobalt and copper” (2). Apparently, a strong positive reaction to nickel creates a nonspecific hypersensitivity of the surrounding skin and induces a false positive reaction. This may be the situation you are facing.

3. If all of the positive tests are metals, you may be dealing with irritant reactions, usually pustules and follicular lesions, more common to metals and more likely in atopic individuals, perhaps due to skin barrier issues. In most irritant reactions, intensity usually wanes between the time of patch removal and the final reading.

4. A 72- and 96-hour reading is provided. Was the patch test removed at 48 hours and what was the reading at that time? If the patches were removed and read at 72 hours, the response was most likely an irritant reaction

5. Responses at 7-10 days after removal may help distinguish a true from false positive result. True positive responses tend to persist for 7-10 days, false positives do not.

6. The lymphocyte transformation test has several issues:
a. viable lymphocytes are required therefore logistical issues of shipping often complicate testing;
b. in vitro testing is only available for a limited number of metals;
c. most 3rd party payers do not cover this testing which is not FDA approved and has limited validation data other than from a single European site (3);
d. most literature continue to recommend patch testing as the standard, possibly with the exception of titanium due to potential occurrence of false negative patch skin test results.
Fisher’s textbook on contact dermatitis provides a summary of the ‘state of the art’ for in vitro lymphocyte proliferation (2):
i. Even if a patient has a positive delayed type hypersensitivity skin test response, reactions to an orthopedic implant are rare and cannot be predicted
ii. The most likely adverse effect of an allergy to an orthopedic implant is dermatitis, often at the site of the implant but can become generalized and affect the hands;
iii. Failure of the implant and delayed or poor wound or surgical site healing hav occurred;
iv. Preoperative testing may identify preexisting sensitivity but does not predict likelihood of joint failure and may help with selection of type of implant;
v. Postoperative testing may help in determining if metal allergy is responsible;
vi. Documented titanium allergy is very rare, if other metals are test positive then titanium would be an alternative;
vii. In cases of documented delayed type metal hypersensitivity or when an individual has a strong belief related to this possibility, legal concerns may outweigh medical concerns;
viii. The additional cost of titanium implant may be judged reasonable in light of the financial and personal cost in a knee or hip implant.
ix. The criteria for postimplant metal hypersensitivity are:
a. Major
i. Dermatitis overlying the implant
ii. Positive patch test to metal used in the implant
iii. Complete recovery after removal of the offending implant
iv. Chronic dermatitis beginning weeks to months after the transplant
b. Minor
i. Therapy resistant dermatitis
ii. Morphology consistent with acute eczema
iii. Systemic allergic skin symptoms or signs
iv. Histology consistent with eczema
v. Positive in vitro test to metals

The criteria are a bit confusing as the recommendation is not to use the in vitro test but a minor criteria is a positive in vitro test.

In summary, there is no official recommendation to use in vitro methodology as the testing has not been validated by multiple investigators and the FDA has not approved the testing. The use of viable lymphocytes and the absence of 3rd payer coverage also limit the utility of the testing. I would repeat the patch tests with the chamber more than 6 inches apart, take pictures before and at 48 hours, 72 hour, and possibly 4, 5 and 6 days. I would share this information with the patient and the orthopedist and recommend a titanium implant without nickel unless the repeat tests do not show sensitivity. I would emphasize that the in vitro testing is an option but currently not recommended. I am skeptical that the in vitro testing would facilitate a better alloy than titanium. If a non-metal option is a consideration, then I would recommend if multiple patch tests are positive.
1.  https://www.aaaai.org/Aaaai/media/MediaLibrary/PDF%20Documents/Practice%20and%20Parameters/Contact-dermatitis-2015.pdf
Fonacier L, Bernstein D, Pacheco K et al. Contact dermatitis: A practice update—Update 2015. J Allergy Clin Immunol Pract 2015;3:S1-S39.
2. Fowler, Joseph F., and Matthew J. Zirwas. Fisher's Contact Dermatitis. 2019. Chapter 8, Medical devices, implants and equipment.
3. Wood MW, Warshaw EM. Hypersensitivity to titanium: diagnosis and management. Dermatitis 26;2015:1-25.

I hope this information is of help to you and your practice.

All my best.
Dennis K. Ledford, MD, FAAAAI