Courtesy National Jewish HealthA PET scan shows inflammation in Paula Spurlocks right hip. Doctors at National Jewish Health in Denver were able to identify that she was allergic to the cobalt in her new implant. A titanium implant in her left hip, however, caused her no problems.

More than a million artificial knee and hip joints are implanted in the U.S. each year, and the vast majority of patients recover with greater mobility and less pain. But with the numbers of implants expected to explode in the next decade as baby boomers age, orthopedic surgeons have yet to resolve a key issue: the extent to which patients might be allergic to the metal in their new hips and knees.

“It’s really been a concern since the advent of joint replacement in the early ’60s and ’70s,” said Dr. Joshua Jacobs, chairman of the orthopedics department at Rush University in Chicago and a former president of the American Academy of Orthopedic Surgeons. “Unfortunately, here we are 50 years later and we still have more questions than answers.”

Studies suggest about 17 percent of women and about 3 percent of men have experienced sensitivity to metals, most commonly to nickel, chromium and cobalt. (Women are thought to experience reactions more often because they have greater exposure to such metals in jewelry.) But nowhere near that many joint-replacement patients experience allergic reactions to their implants.

According to the Centers for Disease Control and Prevention, fewer than 10 percent of total joint replacements end up failing within five years, mainly due to infection or mechanical failure. Some small percentage of the rest may be due to metal allergies, but nobody is sure how many. And some surgeons wonder if it happens at all.

“If you talk to high-volume joint-replacement surgeons, some of them do question whether it does exist. They have a hard time identifying a case,” Jacobs said. “There are some fairly well-documented case reports in the literature that suggest this is a real entity. But at least for the typical total knee replacement, it is extremely rare.”

Those published case studies describe symptoms such as pain, swelling, itching and stiffness that arise after a knee or hip implant and then resolve after the offending metal is replaced with one made from alternative materials.

Paula Spurlock, 51, of Denver, for example, experienced itching and pain throughout her entire body after a hip replacement in 2011. Her right hip “lit up” on a PET scan, she said. More than a year after it was implanted, tests showed she was allergic to the cobalt in the implant and the cement used to hold it in place.

“That’s the one thing that never occurred to any of us,” she said. “No wonder I was miserable.”

Spurlock had the troublesome metal hip removed and replaced with a ceramic implant and her symptoms resolved.

“It was a very long and miserable year and a half,” she said.

Spurlock had previously had her left hip replaced with a titanium implant, and experienced no problems.

“If we find a patient is allergic after the fact, unfortunately, the only option right now is to take the joint out and replace it with something to which they’re not allergic,” said Dr. Karin Pacheco, who developed the blood test that diagnosed Spurlock’s condition. “It would be nice to get it right the first time.”

Unreliable results

Allergists are perhaps more likely to accept the metal allergy scenario than orthopedic surgeons, because patients routinely test positive for metal allergies on skin-patch or blood tests, while surgeons see few unexplained implant failures.

Allergists typically rely on skin-patch testing, where a potential allergen is applied to a spot on the patient’s back. After two to three days, the allergist can examine the area for signs of an allergic reaction. It’s a highly subjective process, with the allergists gauging the degree of reactivity.

Surgeons question how well that reflects what’s happening deep inside the body. The skin serves as the first line of defense for the immune system, and as such, has different types of cells and protections to ward off foreign invaders.

Lymphocyte Transformation Testing, or LTT, attempts to more accurately re-create the reactions that go on inside the body. The test isolates certain immune cells, the lymphocytes, and exposes them to different metal particles or ions over a period of a week. In patients with a hypersensitivity, the lymphocytes will multiply, providing an objective, quantifiable way to measure the reaction.

But it’s also unclear how well those numbers reflect the situation with implants. A metal bound tightly with other metals in an alloy used to make an implant will not trigger the same sort of reaction. It is only when the metal degrades and releases individual particles or ions that an allergic response arises.

“All implants degrade once you put them in. It’s a nice salty environment,” said Nadim Hallab, a metal allergy researcher at Rush who also runs the lymphocyte testing firm Orthopedic Analysis. “The metals we do use are chosen because they are so corrosion-resistant. They resist this tendency to degrade the most, but they still do, and especially when they are articulating and there are parts rubbing on parts.”

Hallab said it was only with the metal-on-metal hip implant debacle in recent years that physicians really began to take notice of the metal allergy issue. Hip joints in which both the ball and socket are made of metal could release metal shavings into the bloodstream, sometimes leading to an aggregation of metal particles, dying tissue and immune cells into a pseudo-tumor around the joint.

How much metal is released in metal-on-plastic hip or knee joints, though, is unclear. To date, no one has done the large-scale studies to determine the extent to which they could trigger an allergic response.

“Over time we expect implants to cause a subtle inflammation over 15 to 20 years, causing enough of a problem that they need a new implant,” Hallab said. “But hypersensitivity is a little bit different. It causes a little more than a subtle reaction and can end that at five years or 10 years or before then.”

One study found that while the average lifespan of a hip implant was 10 years, in those with a positive allergy test or a history of metal allergy, the lifespan dropped to 61/2 years.

Hallab estimates that somewhere between 1 percent to 5 percent of those with failing implants might be experiencing a metal allergy.

“If you go to people who are having implants put in, it’s less than 1 percent that have a failure due to hypersensitivity response,” he said. “That’s just our conservative guess at this point.”

Clinical guidance

With only best guesses and unvalidated testing, surgeons have little hard evidence to guide their decisions.

“Even with the LTT testing, there’s a lack of robust clinical validation,” Jacobs said. “So it leaves the clinician and the patient in a bit of a quandary as to how to know, how to predict who might have such reactions.”

The small studies that have explored using skin-patch testing or LTT as a way to screen for potential metal allergies have shown little predictive value. In one study, the failure rate of knee implants was identical in both the group that was screened with skin-patch testing and the group that wasn’t.

LTT testing has been equally problematic, often providing inconsistent results. At a meeting of the International Conference for Joint Replacement in October, Mayo Clinic surgeon Dr. Henry Clarke showed the test results from two lymphocyte proliferation tests done by separate labs for the same patient. One indicated the patient was allergic to titanium, nickel and chromium, but not cobalt. The other indicated the exact opposite, reactive to cobalt, but not the others.

Post-implantation testing may have even less value. While 60 percent of those with a failing implant will test positive for a metal allergy in an LTT test, so will 25 percent to 50 percent of patients with well-functioning knee implants.

“It’s unclear whether failure, because it’s generating more ions, is going to lead to sensitization, or is this a reflection that they have some kind of allergy to the metal that has led to implant failure,” Clarke said. “We don’t know which is chicken and which is egg.”

Surgeons might be tempted to assume a metal allergy after ruling out things like infection or mechanical failure of the implant, and replace it with a different joint. But studies show that revision surgery without identifying the cause of the pain or swelling tends to have poor results. Surgeons also have their favorite implants, and have more experience and better outcomes with their go-to product than with a less familiar implant.

Clarke has opted to rely only on patient history to guide his decision. If the patient reports a history of a metal allergy, he will avoid implants with that metal.

“I just don’t want to have an argument with them down the road about why I put a nickel-containing implant in them when I know they had a nickel allergy before surgery,” he said. “There are good choices. I take the easy path and use a non-nickel-containing implant in these patients.”

In one survey, 72 percent of orthopedists said they would use a nickel-free implant if they knew the patient had a nickel allergy.

Surgeons can avoid metal altogether and implant ceramic joints. Many orthopedic surgeons believe the smoother ceramic implants will prove to be more wear-resistant over time and so use them more frequently in younger patients who will have to live longer with their implants. But there are concerns that ceramic implants can break inside the body and there is little long-term data on their reliability and longevity. Ceramic joints currently account for about 15 percent of joint implants.

Dr. Mike Caravelli, an orthopedic surgeon with The Center: Orthopedic & Neurosurgical Care & Research in Bend, said he routinely asks patients if they have any history of metal allergies before choosing an implant. If they do, he will refer them to an allergist for skin-patch testing.

“If there is a possibility of a reaction, we do have options,” he said. “There are different implant systems that I can use to try to minimize the risk.”

But over the past four years, he has had only one individual report a metal allergy, and she tested negative for nickel and cobalt on the skin-patch test. Caravelli said he gave the patient the option of using an alternative implant, but she opted to go with his standard choice and has had no problems with the joint.

“She’s done beautifully,” he said.

Dr. Stephanie Trautman, an allergy specialist with Bend Dermatology Clinic, has done skin-patch testing for patients referred by orthopedic surgeons. At times, the surgeon can provide a sample of the metal that will be used in the implant. But local orthopedists say some implant companies have stopped providing the metal disks for that purpose.

Skin-patch testing costs approximately $13 per patch, which can add up as the number of metals tested increases. Most people who are allergic to one metal are also allergic to others. LTT testing can cost $200 to $500, depending on the number of metals tested. The lymphocyte tests are done only in certain labs, so generally require a blood sample to be sent away for analysis. Many surgeons say the questionable value of the tests as well as the costs make it impractical to test every patient before joint replacement. It might be up to the patient to raise the issue with the surgeon.

“Your physician really wants to know the history,” Caravelli said. “That’s really helps tremendously to identify the need for testing.”

—Reporter: 541-617-7814, mhawryluk@bendbulletin.com