Every Patient Tells a Story (28 page)

The earliest and most common symptom of Lyme disease is an expanding circular rash, which usually appears around the site of the tick bite within a few weeks. The rash often presents in a “bull’s-eye” pattern: a red ring circling a central clearing. However, some studies suggest that the most common presentation is a completely red, somewhat round patch that expands over the course of several days.

Left untreated, the
burgdorferi
bacteria migrate to other parts of the body
and the immune system responds with inflammation, fever, muscle aches, and other symptoms as it tries to fight the infection.

Until Willy Burgdorfer’s discovery of the bacterial cause of Lyme disease, no test existed for it—for the simple reason that nobody knew what to look for. Even after the identification of the bacteria, testing for the disease remained difficult. Many types of bacterial infections can be diagnosed by culture—taking a sample (a throat swab, for example), rubbing it on a material that fosters bacterial growth, incubating the sample for a period of days, and then identifying the colonies of bacteria that form. But the Lyme bacteria don’t grow well in culture.

Instead, doctors seeking to diagnose Lyme disease must depend on the body’s response to the infection. To do this, doctors use two separate tests, neither of which is good enough to use alone but which, used together, can reliably identify those who have been exposed to the bacteria. It’s an old strategy and while once commonplace, it has been replaced by better, more specific tests in many diseases. It’s still used for a couple of diseases such as HIV and hepatitis C—other diseases that cannot be easily grown in culture.

The first of the two tests is known as an ELISA (enzyme-linked immuno-sorbent assay) and it detects antibodies to the invading bacteria or virus in a person’s blood. Antibodies are part of the body’s defense system and help kill invaders. This ELISA looks for antibodies to the Lyme bacteria. And it’s a pretty good test but cannot distinguish between
Borrelia burgdorferi
and many of its look-alike brothers, nephews, or distant cousins. Some types of normal flora can cause a positive reaction on the ELISA.

That’s why a second test is needed. If a person tests positive or equivocal on the ELISA, then a second test is conducted called the Western blot test. Again, this test is looking at antibodies, not actual bacteria. This test looks for antibodies not to the whole organism but to the basic building blocks of the Lyme bacteria—individual proteins. It’s a complicated process because many types of bacteria use the same building blocks. So it’s not enough to identify, for example, two or three of the proteins known to be part of
burgdorferi
bacteria. Those same proteins are also found in many other species.

The CDC has determined a standard for interpreting results from the
Western blot test series. The standards say that Lyme disease should be suspected only if a person’s blood is found to have antibodies to five out of the ten proteins that are commonly tested for. If a patient tests positive on ELISA
and
is positive on at least five out of the ten relevant Western blot tests, then it is very likely he has been exposed to Lyme disease.

If this were the end of the story, it wouldn’t be so bad. The tests for Lyme disease would be indirect and require two steps, but the end result would be about as clear as we get in medicine. Unfortunately, it’s more complicated than that.

First, it usually takes the body several weeks to develop enough antibodies against the bacteria to be measured by either of the two tests. In the earliest days of the infection, therefore, even though you may have the rash or other symptoms of early Lyme disease, neither of the two tests is likely to be positive. And if treatment is started early enough, the bacteria will be killed so quickly that the antibodies may
never
get created. That means there’s no way to definitely prove, years later, that a person did
not
have Lyme disease at some point in the past. But an even more important complication in testing for Lyme disease is that once the body does make antibodies, they stick around—for months or years—as protection against future infections. That means that the tests for Lyme will remain positive long after the bacteria that originally caused the symptoms are eradicated. It will look for all the world as though you still harbor the bacteria even though you don’t, because the tests don’t measure bacteria—they measure antibodies.

The Phantom Epidemic

Carol Ann, of course, did not understand these layers of complexity about testing for Lyme disease when she consulted with Dr. Davidson. All she knew was that when she had left Davidson’s office on her initial visit, he said he would send off a sample of her blood for a confirmatory test—which certainly seemed to Carol Ann like responsible medical practice. Two weeks later, the results came back: they were negative. This struck Carol Ann as
odd, but didn’t seem to bother Dr. Davidson at all. He told her that testing was notoriously unreliable in making this diagnosis. He sent off more blood and started her on an antibiotic despite the negative test.

Several weeks later Davidson told Carol Ann the results of the second test were positive. He did not tell her that he wasn’t following the guidelines for interpreting the results set by the CDC. Rather than the standard of five out of ten antibodies that the CDC regards as evidence of Lyme disease, her test had been positive in only three—which Davidson interpreted as “positive.”

Like his “Lyme literate” colleagues, Davidson justifies his more lenient testing standards as necessary for not missing anyone who may have the disease. But this is a poor argument. It’s like saying that all patients who have a sore throat, runny nose, and a fever have the dreaded avian flu. You probably won’t miss any cases of avian flu with such a vague set of criteria, but most of the time your diagnosis will be wrong. Instead most of the patients you identify this way will have other, far more common illnesses—a cold, maybe bronchitis, or maybe the usual flu.

But all this was invisible to Carol Ann, who took some comfort in the apparent confirmation of her illness. In any case, she was feeling a little better since starting the latest round of antibiotics. Her shoulder didn’t hurt quite as much and she was sleeping better. But the medication was taking a toll on her stomach. She lost a few pounds because she felt nauseated—especially in the hours right after taking the medication. Davidson thought it was important to continue the antibiotic, especially in light of the “positive” Lyme test, and encouraged her to soldier on. The hope of a complete recovery and of being her old self again made Carol Ann determined to continue taking the medication despite how ill it made her feel.

At about the same time that Carol Ann was forging ahead with her prescribed regimen of antibiotics, forty-four-year-old Will Hammer was negotiating slippery November roads to see his own “Lyme literate” physician. He had been diagnosed with Lyme disease over a decade earlier but, when I spoke with him, he said he’d suffered from the disease for more than half his
life. A tall man with short-cropped red hair and a quiet manner, he told me proudly that he hadn’t missed a day of work because of his “chronic Lyme disease” in over five years. He attributed his success to Dr. Andrea Gaito, a rheumatologist and leader in the “Lyme literate” movement who had had him on daily antibiotics for nearly thirteen years.

Hammer said he first developed symptoms in high school following a camping trip. He never had the fever, muscle pain, and headache typical of Lyme, but felt tired and run-down. “Occasionally I’d feel not quite right and I’d wonder about it,” he told me, “but it wasn’t overwhelming.” The symptoms worsened in his twenties. He would have periods of insomnia, body pains, and fatigue. He went to doctor after doctor. No one even had a name for the illness he suffered, much less a cure.

Eventually he heard about Lyme disease and wondered if that could be causing his symptoms. He’d been tested for it in the past and been told the test was negative, but now he was hearing that the test wasn’t very reliable. That’s when he ended up in Gaito’s office, who quickly diagnosed him with “chronic Lyme disease” and started him on a six-week course of antibiotics.

The effect was immediate and life-altering, Hammer said. “The first time I was treated here I felt better than I had in my entire adult life. I felt great.” But, he told me, that good feeling didn’t last long.

A couple of months after completing his treatment, he started having trouble sleeping again. Then the fatigue and body aches reappeared. Then he began to have problems with his memory. “At first it was little things. Then one day, I was driving my son to soccer as I had every weekend for months and suddenly I couldn’t remember where to go. I couldn’t quite remember where I was.” He pulled off the road into a parking lot. His heart was racing. Slowly and carefully, he figured out how to get where he needed to go. His young son, confused by his uncharacteristic behavior, asked what was the matter. Nothing was wrong, he reassured his son, but inwardly he wondered what the hell was happening to him.

He went back to Gaito and started back on antibiotics. He’s been on them with only a couple of short breaks ever since. At several points over the years since starting these medications, Hammer found himself as sick as he’d
been to start with despite the daily antibiotics. He’d go back to his doctor—discouraged, frustrated, and depressed. Gaito would help him get through it, increasing the dose of the antibiotics or changing him to a new one and eventually he’d start to feel a bit better. When I last spoke to Hammer, he was going to Dr. Gaito every three to four months, but he worried that he might never be well enough to stop taking the antibiotics.

Both Carol Ann and Will tell versions of a common story in Lyme country: a diagnosis of Lyme disease, followed by antibiotic treatment, an initial improvement, and then a return of symptoms. This pattern emerged early in the history of the disease. Allen Steere noticed that while most of his patients got well after a two-to-four-week course of antibiotics, between 10 and 20 percent took months and occasionally even years to feel completely better. Like Will Hammer and Carol Ann DeVries, these patients often noticed a lingering fatigue and body aches. Some complained that they had trouble sleeping or problems with their memory. Still others would have recurrences of the joint pain and swelling that brought them to the rheumatologist in the first place. Steere dubbed this phenomenon Post–Lyme Disease syndrome.

In the early 1990s, Steere and researcher Nancy Shadick set out to determine how common the syndrome really was. They recruited one hundred residents from Ipswich, Massachusetts, an area that had been hard hit by Lyme disease. Half the patients had a documented history of Lyme disease, which had been treated; the other half had never had the disease. Nearly one in three of the treated patients continued to have residual pain and other symptoms more than five years after getting Lyme disease. These symptoms were seen far more frequently in those with Lyme than in those who’d never had it. Other studies too have found that those with a history of Lyme disease report more joint pain, fatigue, and memory problems than those who have never had the disease.

Initially there was concern that these symptoms represented an ongoing infection, which persisted despite a full course of antibiotics. Patients themselves
said that it
felt
like an infection, and so Steere, Shadick, and many other doctors responded initially by treating these symptoms with a second or third course of antibiotics.

But it soon became obvious to Steere and others that while many of those with these persistent symptoms got better after multiple courses of antibiotics, so did people who only got the one round of antibiotics—those prescribed at the time of their original diagnosis. Ultimately, most people got better and it wasn’t at all clear whether the repeated courses of antibiotics made any difference at all, once the disease had been treated initially.

To better understand what was going on, researchers in the field did what researchers do—they set up experiments to study in a very careful, controlled way whether antibiotics really helped people with Post–Lyme Disease syndrome recover faster.

The
New England Journal of Medicine
published the first experimental results in 2001. Researchers at Tufts Medical Center in Boston and Yale–New Haven Hospital looked at 129 patients who had documented proof of a previous infection with Lyme disease and persistent symptoms even after being given the recommended regimen of antibiotics. Most had some degree of musculoskeletal pain. Half were treated with ninety days of antibiotics and half were treated with an identical-looking placebo. Neither doctor nor patient knew who was getting which. Each participant was evaluated for physical and psychological health before, during, and after treatment with the drug or placebo.

Just over 40 percent of the patients treated with the antibiotics felt better after the first month. And almost that many felt better, overall, after the full course of antibiotics and three months later. What about those on the placebo? The response was almost identical: 35 percent of the patients getting a completely inert substance felt better after the first month and 40 percent felt better by the end of the study. The antibiotics had made no difference at all.

Two other rigorous trials investigated the same issue. One showed a small improvement in symptoms of fatigue in those getting the antibiotics, but nothing else. The third study was done by psychologist Brian Fallon,
a “Lyme literate” researcher and the head of a research center at Columbia University that is funded in part by a “chronic Lyme disease” advocacy group. But even Fallon failed to find any significant difference between the group on antibiotics and the group getting the placebo. Moreover, in each of these studies a significant number of participants had complications stemming from antibiotic treatment. Many experienced the kinds of adverse reactions felt by Carol Ann, and sometimes the complications were serious enough that the study participants had to be hospitalized.