by Lisa Sanders
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.
These kinds of consistent results from three separate, rigorous experiments, published in high-quality, peer-reviewed journals, would normally be considered a slam dunk in the medical world. The results clearly showed that antibiotics were not helpful for patients with persistent symptoms after being treated for Lyme disease, which strongly suggested that whatever was wrong with these people, it was not because they were harboring some “super burgdorferi” in their bodies. Leading medical groups involved in the study of Lyme disease published guidelines recommending against the use of multiple courses of antibiotics to treat the persistent symptoms. Normally, this would settle the matter and medical science would move on to a new mystery.
But that’s not what happened here. Instead a small but vocal group of doctors and patients refused to accept these results, refused even to accept the designation of Post–Lyme Disease syndrome. They clung, instead, to “chronic Lyme disease” and insisted that these symptoms did reflect an ongoing infection that warranted continuing treatment with antibiotics. They countered the randomized controlled trials with research of their own, which often showed improvement in patients given antibiotics. But none of these studies compared the antibiotics against a placebo. The randomized controlled trials showed that while patients getting antibiotics did improve, so did those getting the saltwater placebo. Studies done without the placebo had no way of telling whether the antibiotics were really effective or if the improvement was due to something in the normal ebbs and flows of any human condition.
Advocates of the “chronic Lyme disease” model of understanding also seized on the complexities of Lyme tests and argued that because of their limitations, they should simply be disregarded. According to the International Lyme and Associated Diseases Society (ILADS), a group founded in 1999 to promote the dissemination of information on “chronic Lyme disease,” diagnosis should be based only on the patient’s symptoms. They don’t trust either physical exams or the two tests for Lyme disease.
“Available data suggest that objective evidence alone is inadequate to make treatment decisions,” say the ILADS guidelines, “because a significant number of Chronic Lyme Disease cases may occur in symptomatic patients without objective features on examination or confirmatory laboratory testing.”
The same guidelines assert that when the two-step testing for Lyme is used as recommended by the CDC, up to 90 percent of cases are missed. But this is misleading at best. The “research” offered in the guidelines to support this “fact” consists of a single unpublished study. And if you use the test on everyone with the common symptoms of fatigue, insomnia, and muscle pains, 90 percent of them probably will have a negative test because they don’t really have Lyme disease.
In fact, when used as recommended, the tests accurately diagnose Lyme correctly more than 90 percent of the time.
Instead of testing or the physical examination, ILADS and “Lyme literate” doctors suggest that diagnosis be made on symptoms alone. The problem here is that the symptoms these doctors have chosen to rely on are hopelessly broad and over-inclusive. They include fatigue, sore throat, muscle pain, joint pain, insomnia, chest pain, abdominal pain, dizziness, nausea, poor concentration, headaches, irritability, depression, back pain. These are some of the most common symptoms of patients presenting to a primary care office. As an internist who sees patients regularly, most of the patients I see complain of these symptoms—and they certainly don’t all have Lyme disease. Because I have an urban practice, I see only a few cases of Lyme disease a year.
And yet this is the diagnostic strategy that allows doctors like Davidson and Gaito to maintain that patients like Carol Ann or Will have “chronic Lyme disease” and that they should be continually treated with antibiotics because of a lingering infection with the Lyme bacteria.
But there is probably an additional factor at work in the stubborn refusal of the “Lyme literate” doctors and patients to accept evidence that most other doctors find compelling. It’s an unavoidable aspect of all medical practice and is particularly related to the limitations of diagnostic testing—limitations that are particularly acute with Lyme disease. I’m talking about a discomfort with uncertainty, with ambiguity, with not knowing. And the doctors most uncomfortable in this way are the ones most likely to seize upon a diagnosis or diagnostic label and distort their own thinking in an attempt to prove to themselves and their patients that they know what’s going on.
The fact is that, more often than doctors like to admit, they cannot find a cause for a patient’s symptoms. This was powerfully illustrated in a 1998 study of two hundred patients diagnosed with Lyme disease. It turned out that more than half of the patients had no evidence of ever being infected with Lyme disease. As we’ve seen, it could be that some of these patients were treated for Lyme so quickly that they never developed the antibodies that would prove their infection. Maybe. But that surely could not account for such a huge fraction of these patients who tested negative for Lyme.
Only 44 of the 200 patients (20 percent) were found to have active Lyme disease—with symptoms, physical exam findings, and blood tests consistent with Lyme disease. Another 40 (19 percent) were found to have Post–Lyme Disease syndrome—with a clear history of Lyme infection, adequate treatment, and persistent symptoms. The other 116 patients in the study—60 percent of those enrolled—had no evidence of either current or past Lyme disease, even though all had been diagnosed with the disease
. Clearly these results show that Lyme disease is being seriously over-diagnosed. But the results also shed light on the issue of uncertainty in medicine.
If the 116 patients who thought they had Lyme didn’t, then what did they have? A lot of things, it turns out. Fourteen had rheumatoid arthritis. Fifteen had osteoarthritis. Eight were diagnosed with another infection, and another dozen had some kind of neurological disorder such as multiple sclerosis or amyotrophic lateral sclerosis (ALS), often referred to as Lou Gehrig’s disease. Several were diagnosed with depression.
These diagnoses covered about half of the 116—and clearly demonstrate how the phantom diagnosis of “chronic Lyme disease” is concealing a great many real diseases that patients should be getting help with. But the other half of the participants are also interesting. These people were obviously suffering from real ailments—real symptoms—but neither the study doctors nor their own physicians could determine a cause. These patients had what doctors call “medically unexplained symptoms.”
Nobody likes not knowing, but doctors, perhaps, find this state of being even more intolerable because it utterly thwarts their ability to alleviate suffering, which is often the fundamental motivation for their entire career. But a doctor’s discomfort in the face of the unexplained can lead them astray. Rather than accepting a patient’s symptoms as real, but unexplained, physicians all too often either dismiss the symptoms as unreal (“all in your head”) or, alternatively, read too much into scanty evidence in an effort to banish uncertainty with a crisp diagnosis. Neither response serves patients.
We can see the results of both types of responses in Will Hammer’s experience.