30 year-old female who wants evaluation regarding possible sensitivity to a marker that will be used during a breast procedure. Patient has a history of reaction to costume jewelry. She states she gets a rash in area of contact with costume jewelry. Rash described as darkening of skin. She will have a procedure on her breast and the doctors want to use a marker. She has been told the marker is titanium. I have no information from the doctors who will do this procedure. I suggested she get information regarding what metals are in the marker. I also said she should find out what metals are in the costume jewelry she reacted to. Should she have patch testing to metal or if the marker only contains titanium can I assume titanium will not be a problem?


Thank you for your inquiry.

This problem should be approached in a manner similar to the strategy used to approach a patient who has potential metal allergy and is scheduled to receive a metal implant such as an artificial knee, artificial hip, or dental implant.

The titanium breast marker is very small - about the size of a sesame seed. It is implanted in the breast to mark a lesion which, if surgery is indicated, helps the surgeon locate the problem. I have not found any incidence of reactions to titanium markers in the medical literature (although there is some lay literature that carries claims of such reactions), but there are reports of reactions to clips used in breast surgery (see abstract).

We have dealt with this type of issue on our "Ask the Expert" website many times. For your convenience, I have copied one such entry/response below, and you can find other entries by going to our website and typing "contact dermatitis to metal" in the search box.

To approach your patient, you have several options. One simple option would be to obtain the marker and have the patient wear it, taped to the skin, to see if there was a reaction. She should wear it for a minimum of three days. You would read it as you would a standard patch test at 48 hours and again at three and five days. If she did not react, that would be a fairly good indication that the marker would be safe. It should also be noted that many titanium products contain nickel, and if she does react to costume jewelry, the most likely culprit would be nickel since most costume jewelry contains a high quantity of nickel. Thus, you could also consider doing a patch test to nickel, but I would warn the patient to take the patch test off early if she felt any irritation.

Finally, patch tests to titanium are also available. Standardized patch testing to titanium would certainly, if negative, rule out the titanium, but would not rule out a reaction to nickel in the marker. So if you wanted to use the standard patch tests, you should write to the manufacturer of the breast marker to make sure that it did not contain nickel.

Thank you again for your inquiry and we hope this response is helpful to you.

Breast Cancer. 2001;8(1):90-2.
A case of allergic reaction to surgical metal clips inserted for postoperative boost irradiation in a patient undergoing breast-conserving therapy.
Tamai K1, Mitsumori M, Fujishiro S, Kokubo M, Ooya N, Nagata Y, Sasai K, Hiraoka M, Inamoto T.
Author information
1Department of Therapeutic Radiology and Oncology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
We report a case of a 28-year-old woman with right-sided breast cancer. The patient had been treated for atopic dermatitis since her infancy. She underwent breast-conserving surgery (BCS) in July 1998, and three titanium clips were placed at the margin of the excision cavity at the time of surgery. Two months after surgery, the patient exhibited a rapid exacerbation of atopic dermatitis. Various drugs were suspected to be the cause of the allergic reaction, but the results of a bi-digital O-ring test (BDORT) suggested an allergic reaction to titanium clips. In August 1999, the patient underwent a second operation to remove the titanium clips under local anesthesia. Allergy to surgical titanium clips is a rare complication, but in patients with a history of severe allergic diseases, a preoperative immunologic examination should be performed and the patient's history of metal allergy should be investigated.

Testing for contact dermatitis to metals
I have received a referral from an orthopedist regarding testing his patient in advance of placement of a 'titanium plate with nickel alloy'. I want to know if I must test to BOTH nickel (in the TRUE test) AND titanium (obtained by either manufacturer or company in Canada ie. allergeaze.com. I have done a literature search regarding titanium contact dermatitis, but the articles refer to impurities or components in the titanium, not reaction to titanium itself. Do you know of contact dermatitis to titanium itself? If so, I must obtain the titanium for testing.

Also the aforementioned Canadian company offers titanium for patch without any base, as well as titanium oxide in a petrolatum base. Which is recommended? I imagine placing the metal on the skin itself could take weeks to react?

Thank you for your inquiry.

You are correct in that there is controversy as to whether true contact dermatitis to titanium exists, and certainly it is much rarer than contact dermatitis due to other metals such as nickel, chromium, and cobalt (see first three abstracts copied below). However, there are several case reports of possible or documented contact allergy to titanium (see other abstracts and references copied below). Therefore, one cannot say for sure that titanium contact reactions do not occur.

Thus, it would be best to test to both metals if you can.

I would thus suggest the following:

1. I would test to titanium because of the information offered above, and I would test to both the patch test without any base and the titanium oxide in a petroleum base.

2. I would also write the manufacturer of the implant that the orthopedist plans to use and see if a patch test kit to the implant exists. If so, I would definitely order the kit and patch test to its contents. Most manufacturers do offer such kits, and if not, they might be able to supply a sliver of the metal which you can use to perform a patch test. In patch testing to the metal itself, you should leave it on for 48 hours as you would a regular patch test, and then read the day of removal of the patch, and then two days and five days later.

Therefore, in an ideal situation, you would patch test to each metal, using both commercially available preparations, and also patch test to the implant itself (preferably using a kit supplied by the manufacturer).

I would also direct you to several inquiries that have been posted on our "Ask the Expert" website regarding metal contact dermatitis. These may be helpful to you.

Thank you again for your inquiry and we hope this response is helpful to you.


Contact Dermatitis. 2011 Sep 29. doi: 10.1111/j.1600-0536.2011.01970.x. [Epub ahead of print]
Metal allergy and second-generation metal-on-metal arthroplasties.
Cousen PJ, Gawkrodger DJ.
Department of Dermatology, Royal Hallamshire Hospital, Sheffield S10 2JF, UK.
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 contactdermatologists 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.

Chem Res Toxicol. 2010 Feb 15;23(2):309-18.
Metal allergy--a review on exposures, penetration, genetics, prevalence, and clinical implications.
Thyssen JP, Menné T.
National Allergy Research Centre and Department of Dermato-Allergology, Gentofte Hospital, University of Copenhagen, Niels Andersens Vej 65, 2900 Hellerup, Denmark.
The prevalence of metal allergy is high in the general population, and it is estimated that up to 17% of women and 3% of men are allergic to nickel and that 1-3% are allergic to cobalt and chromium. Among dermatitis patients, the prevalence of metal allergy is even higher. Metal allergy is mainly an environmental disorder although null mutations in the filaggrin gene complex were recently found to be associated with nickel allergy and dermatitis. Environmental metal exposures include jewelry, buttons, clothing fasteners, dental restorations, mobile phones, and leather. Although consumer exposure is responsible for most cases of metal allergy, the importance of occupational metal exposure remains present and should always be taken into consideration when one interprets allergic patch test reactions to metals. Traditionally, nickel, cobalt, and chromium have been the most important contact allergens. However, recently, gold and palladium have drawn much attention as the prevalence of contact allergy to these metals is high. Palladium allergy is mainly a result of cross-sensitization to nickel, whereas gold allergy is rarely clinically relevant when one takes its high prevalence into account. The epidemiology of metal allergy has recently changed in Europe as nickel allergy among ear-pierced Danish women has decreased following regulatory intervention on nickel release from consumer products. In the United States, the prevalence of nickel allergy is still increasing, which may be explained by the absence of regulation. The prevalence of chromium allergy is increasing in the United States, Singapore, and Denmark among dermatitis patients. This increase is significantly associated with leather exposure in Denmark. Metal allergy may result in allergic contact dermatitis and systemic allergic (contact)dermatitis. Furthermore, metal allergy has been associated with device failure following insertion of intracoronary stents, hip and knee prostheses, as well as other implants. This area is in need of more research.

Orthopade. 2008 Feb;37(2):136-42.
[Alternative materials and solutions in total knee arthroplasty for patients with metal allergy].
[Article in German]
Bader R, Bergschmidt P, Fritsche A, Ansorge S, Thomas P, Mittelmeier W.
Orthopädische Klinik und Poliklinik, Universität Rostock, Doberaner Strasse 142, 18057, Rostock, Deutschland.
The annual number of total knee replacement implantations is rising continuously. A progressive cutaneous hypersensitivity rate against metallic materials in the population has been registered which can lead to an increase of allergy-induced reactions associated with implant loosening in the future although the correlation with an allergic cutaneous sensitisation has not been proven in all cases. On apparent allergy against metallic implant components different alternative solutions to standard endoprostheses should be taken into account for primary implantation or revision of total knee replacement, for example the application of implant components without metallic elements (e.g. ceramics), the use of non-allergic metallic implants, such as titanium or ZrNb alloys, or potential allergy-inducing metallic materials after masking the implant surface using a suitable coating. In the case of primary or revision surgery most patients with metal allergy are treated with a Ti(Nb)N-coated knee implant made of cobalt-chrome or titanium alloys in our hospital. Within an international multi-centre study we are currently implanting a newly developed knee endoprosthesis system with a ceramic femoral component as an alternative.

Contact Dermatitis. 2006 Oct;55(4):199-202.
Hypersensitivity to titanium osteosynthesis with impaired fracture healing, eczema, and T-cell hyperresponsiveness in vitro: case report and review of the literature.
Thomas P, Bandl WD, Maier S, Summer B, Przybilla B.
Klinik und Poliklinik für Dermatologie und Allergologie der Ludwig-Maximilians-Universität, München, Germany.
There are very few reports on hypersensitivity reactions in association with titanium-based materials so that the existence of allergy to titanium is still put in question. We report on a patient in whom impaired fracture healing and eczema localized to the perioperative area developed upon titanium-based osteosynthesis. Patch testing gave no reactions to titanium nor to nickel, chromium, or cobalt. However, in the lymphocyte transformation test, the patient's lymphocytes showed markedly enhanced proliferation in vitro totitanium. After removal of the titanium material, fracture healing was achieved and the eczema cleared. Parallel to this, in vitro hyperreactivity to titanium disappeared. Although contact allergic reactions to titanium have been very rarely reported, these findings support a diagnosis of titanium allergy in our patient.

Contact Dermatitis. 2001 Oct;45(4):244-5.
Allergic contact dermatitis from "titanium" spectacle frames.
Bircher AJ, Stern WB.

Contact Dermatitis. 2001 Apr;44(4):257-8.
Allergic contact dermatitis caused by palladium on titanium spectacle frames.
Suhonen R, Kanerva L.
Department of Dermatology, Mikkeli Central Hospital, Mikkeli, Finland.

Contact Dermatitis. 2000 May;42(5):310-1.
Possible allergy to complex titanium salt.
Basketter DA, Whittle E, Monk B.

Contact Dermatitis. 2000 Jan;42(1):52-3.
Pacemaker dermatitis from titanium.
Yamauchi R, Morita A, Tsuji T.
Department of Dermatology, Nagoya City University Medical School, Nagoya, Japan,

Contact Dermatitis. 1990 Sep;23(3):193-4.
Contact sensitivity to titanium in a hip prosthesis?
Lalor PA, Gray AB, Wright S, Railton GT, Freeman MA, Revell PA.

ARC Bone and Joint Research Unit, London Hospital, Whitechapel, UK.

Phil Lieberman, M.D.

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