The Challenge of ‘Chronic Lyme’

From the moment I saw the chief complaint—“target-shaped rash”—pop up on my clinic schedule, I had expected this conversation would be difficult. A sweet three-year-old girl was sitting in her Little Mermaid underwear on my exam table, finding turtles in an I Spy book while her mother and I talked. I had checked the rash on the kid’s leg. It was target-shaped, but small—about a centimeter across.

“Did you see a tick or a bug on her skin?” I asked her mother.

“No,” she said. “But she wears shorts, and she runs in the grass. She plays outside all day.”

“That sounds like a wonderful childhood,” I said. “Has the rash been bothering her? Itching or hurting?”

“No,” she said.

“Have you put anything on it?”

“No. I came straight here when I saw it.”

“Are there any other spots you’ve noticed?”

“Just that one,” she said.

It was time to address the worry she hadn’t voiced. “I bet you’re worried about Lyme disease,” I said, and she nodded. “I can see why,” I said. “This rash does have the shape of erythema migrans, the rash that Lyme disease causes. But it’s very small. Erythema migrans—erythema means ‘red’ and migrans means it moves. It gets bigger, slowly. So I would worry about Lyme disease if this rash got gradually bigger over the next few days. If this red border spread out, and it was wider than five centimeters, then I would think about treating for Lyme.”

“But can’t we just treat her now?” the woman asked.

“Well, the rash I see today could be caused by a lot of things. It could be any random bug bite, or a fungus, or a bite from a different kind of tick. It’s not until the rash really shows itself to be erythema migrans that we think of Lyme disease.”

She was not convinced.

In the state of Idaho, where I cared for this child, there were nine confirmed cases of Lyme disease in 2016. The year before, there were three. I’d bet most of these cases were documented in-state but contracted elsewhere—people who had traveled to the East Coast or the Upper Midwest, where Ixodes scapularis lives. Although known as the “deer tick,” Ixodes usually feeds on mice, and it is mice that transmit Borrelia burgdorferi—the spiral-shaped bacteria that cause Lyme disease in people—to Ixodes. Borrelia goes from mice to ticks to humans after a bite from infected Ixodes ticks, but only about 5 percent of people bitten by infected ticks will contract Lyme disease. I shared these data with the mother.

“Well,” she said, “I got it. I got chronic Lyme here in the 1970s.”

My heartbeat quickened a notch when she said “chronic Lyme.” Physicians are able to identify several stages of Lyme disease: early localized disease (the rash of erythema migrans), early disseminated disease (which may include joint pain and fevers), and late disseminated Lyme disease. Post-treatment Lyme Disease Syndrome (PTLDS) describes persistent symptoms in a person who had Lyme disease but has been fully treated.

And then, there’s chronic Lyme. Chronic Lyme is as nebulous as gender, an identity as much as a biological category. It describes a constellation of enduring symptoms—joint pain, fatigue, muscle pain, brain fog, fevers, blurry vision, and much more—occurring in a person who attributes these symptoms to an infection with Borrelia burgdorferi, but who may have no plausible laboratory, clinical, or epidemiological evidence of exposure to the bacterium. Thousands of Australians identify as chronic Lyme patients, for example, despite the fact that Ixodes does not live in Australia and there has never been a laboratory-verified case of Lyme contracted there. 

I did not want to debate the biological reality of chronic Lyme, so I nodded toward the child and said, “It’s true there are some cases in Idaho. And if this rash looked like erythema migrans, I would treat it. I’d do fourteen days of amoxicillin or cefuroxime.” And this is true—if Lyme disease is caught in the early stages, the diagnosis is clinical: you see the rash, and you know you live in an area with endemic Lyme, so you treat. (In areas where the disease is not endemic but the fear of it is, physicians are advised not to test unless the patient’s symptoms are highly consistent with Lyme.) In cases where symptoms have been present for more than four weeks, physicians perform a two-tier blood test to confirm the diagnosis: an enzyme assay, followed by a Western Blot, which looks for antibodies to Borrelia. If performed alone (without the preceding enzyme assay), or performed on people who are unlikely to have actual Lyme disease (Australians, for example), the Western Blot produces some false positives. False negatives are rare.

“I had to go to California to get treated,” she said. “My Western Blot was a false negative, so I went to—” and she named a clinic. “You’ve probably heard of the clinic?” she asked. I had not. She raised her eyebrows, apparently surprised at my ignorance. “Well. My levels were above the CDC standard, so even regular doctors would have said that I was positive. I had suffered for so long. Awful pain. My stomach got burned because of the high fever when I had the Lyme disease—you know, the acid—and I’ve had three surgeries on my intestines now.”

My jaw tightened, and I found it hard to meet her eyes. Something about her use of that clinical language—the CDC standard, Western Blot, false negative—in a tale so medically implausible irked me. When patients meet my own attempts at using straightforward words with medical jargon, there is often a power issue in the room: my patient feels threatened. She has come into this room bearing a history I don’t yet know, and she needs to assert some power in this space.

I believed that this woman had been told she had chronic Lyme, and maybe even that her surgical problems were linked to it. I believed she had suffered, and been taken advantage of by unscrupulous providers who promised an answer when, really, things are so gray—often people suffer, and medicine cannot explain why.

She went on. “For the Lyme, I got treated the natural way,” she said. “Otherwise, it’s two years of antibiotics. As you know.” 

I did not know. I know that even late-stage Lyme disease is treated with only three to four weeks of antibiotics. The only patients I’ve had who needed years of antibiotics were kids with HIV or cancer or immune deficiency, plus one with neurocysticercosis—pig tapeworm cysts in his brain—and these were always at lower, prophylactic doses. The “natural way” of treating chronic Lyme could mean anything from homeopathy to bee-sting therapy to plasmapheresis (a process by which your blood is drained mechanically from your body, passed along a filter, and then returned).

So I turned back to the kid, and started making faces with her—the beginning of a pediatric neurological exam. Her facial muscles were moving well, with none of the nerve palsies that Lyme can cause. She was strong and bright and agile. Everything looked normal, and I explained this to her mother.

“If the rash gets bigger, or if it starts to flake or itch, bring her back,” I said.

The woman nodded. “I will,” she said, surprising me. “I would just never want her to go through what I went through.”

We both looked at the child, who was pulling on her purple jelly-sandals. We agreed.

*

It is often tempting, as a pediatrician, just to give parents what they want—to get blood tests on a kid with a stomach ache, or a Computerized Tomography (CT) scan for a girl who stood up quickly and fainted, or to give antibiotics for colds. Aware of the excesses of American medicine, many parents expect not to be arguing for more intervention, but rather, defending their kids from overzealous doctors. When parents find the opposite to be true, they’re unnerved.

If my usual tactics of reassurance—listening, taking parents’ concerns seriously, doing a thorough physical exam, explaining why I am not worried and what signs would mean I need to see their child again—don’t work, it feels so easy to capitulate. After all, I won’t be the one holding their screaming kid down while we draw their blood.

The problem is, of course, that parents are not the ones who would actually be subjected to my interventions. The children, my patients, don’t get to choose. And it isn’t fair to treat parents’ worry through the vulnerable bodies of their children.

I am too cognizant of the ones we’ve hurt: kids doubled over in pain from the awful cramps of Clostridium difficile diarrhea, which was brought on in part by antibiotics; kids whose seizure medicines turn on them, creating a side-effect called Toxic Epidermal Necrolysis, which causes them to lose so much skin that they have to go to burn units, their lips to bubble, and their corneas to blister to such an extent they risk going blind. Then there is the subtler stuff. New evidence suggests that repeated sedation can cause cognitive delay, so am I really going to sedate this two-year-old child for an unnecessary CT? What if my unnecessary blood test finds an incidental, unimportant abnormality—then the kid gets poked again, and maybe again, for yet more tests? Experience has taught me that any test, any medicine, can do harm as well as good.

Accordingly, I am cautious. And if there is something that offends me about the practitioners—both naturopaths and allopathic doctors like myself—who treat chronic Lyme disease with years of antibiotics, it is their hubris: Do they even know how much harm they might be doing?

*

I recently cared for a teenager who had been on antibiotics and antimalarials for months for chronic Lyme. She had belly pain, and had also been through the hospital-medicine wringer: she’d had CT scans and MRIs and a colonoscopy and a Barium swallow and a procedure known as an esophagogastroduodenoscopy—none of which found anything that could explain her symptoms. Finally, a naturopath diagnosed chronic Lyme and prescribed a startling array of medicines: antibiotics, antiparasitics, antimalarials, and more. In Washington State, where I work, naturopaths are licensed to prescribe the same medicines I prescribe, despite our very different training. The only exceptions are controlled substances such as opiates and amphetamines.

The diagnosis of Lyme disease is frequently described as tricky and unreliable. In his 2013 New Yorker article “The Lyme Wars,” Michael Specter writes that “Diagnostic failures cause much of the confusion associated with Lyme disease… many people who become infected will test negative in error, while others who aren’t infected will test positive.” Few physicians would agree either that there is a war going on or that the test is so unreliable. When used as it should be (on patients with classic symptoms, four or more weeks after a plausible exposure), the classic two-tier test detects 99 percent of cases, and the false-positive rate is vanishingly small.

If, on the other hand, you test a hundred healthy people who live in an area with a low rate of Lyme, then you will get between two and five false positives. (These will mostly be cases of people who have another spirochete infection such as syphilis, or a virus like Epstein-Barr.) False negatives are largely due to the test being ordered too early—it takes a few weeks for the body to build up antibodies against Borrelia.

When used as it should be, the two-tier test for Lyme disease is more accurate than many tests we use and trust: it has fewer false negatives than the rapid strep test for detecting strep throat or the urinalysis for detecting a urinary tract infection (UTI). If I suspect strep throat but a kid’s rapid strep test is negative, I send the sample for a culture; the same is true with urinalysis. The combination of a primary test and follow-up culture works similarly to the two-tier test for Lyme: the first phase may require a second phase, for backup. As with all tests, discretion on the part of the person ordering and interpreting the test is critical. If I tested every kid who walked into my office for strep throat, I’d get more false positives than true positives. To preclude that, in general I only test school-age kids who have sore throats and a fever but no cough. Just as in testing for Lyme disease, that kind of discretion keeps what scientists call my “pre-test probability”—the likelihood that the disease I’m looking for is present—high, and false positives low.

I scanned down my teenage patient’s medicine list. There was levofloxacin, which can cause Achilles tendon rupture, particularly with prolonged use. There was clindamycin at twice the appropriate dose for her weight. There was doxycycline, which can erode the esophagus and stomach. There was mefloquine, an antimalarial that can cause long-term, even permanent, psychosis. There was another antimalarial, and drugs for high blood pressure, and an herb I would have to look up, and melatonin. The doses were random, and she had been on them all for far, far too long.

“What’s the mefloquine for?” I asked her father.

“For the malaria that goes along with chronic Lyme,” he said.

“Has she ever been to Sub-Saharan Africa or Southeast Asia?” I asked. “Or anywhere with malaria?”

She hadn’t, and this dad was shocked to find that I didn’t know that malaria can also be transmitted by Ixodes. (It cannot.) “Oh,” he said, “there are tons of co-infections.”

“How did they diagnose the malaria?” I asked.

“They did a blood test,” he said.

I ended up sitting and talking with this father for a long time. I was surprised to find that, like the mother with chronic Lyme, he really wanted to hear my perspective on his daughter’s health. I was reminded of the data on what we pediatricians call “vaccine hesitant” parents: even though they aren’t sure about vaccination, most of them say that their pediatrician is the person they trust the most for information about vaccines. When we engage with these parents, we often do have an effect on the choices they make.

*

In 2003, a group of researchers from the University of Connecticut published a study on the use of antibiotics to treat cognitive dysfunction in patients with Post-Treatment Lyme Disease Syndrome (PTLDS). This syndrome describes patients who have been diagnosed with Lyme disease, treated appropriately, and still have some symptoms such as fatigue and brain fog. As the CDC acknowledges, “the cause of PTLDS is not known.” The difference between PTLDS and chronic Lyme is that people with PTLDS had clinically- or laboratory-verified Lyme disease at some point.

This study enrolled 129 people with PTLDS. Half of these people were given four weeks of IV antibiotics followed by eight weeks of oral antibiotics. The other half were given four weeks of IV placebo followed by eight weeks of oral placebo—essentially, saline injections and sugar pills.

Both groups got better. The antibiotics didn’t work any better than the placebos, though. Placebos are highly effective for many conditions, and have been shown to enact neurophysiological change in patients exposed to them. That is, placebos can change your brain. The reason that new drugs are tested against a placebo is precisely because placebos work so well—if a drug is more effective than a placebo, it’s pretty good.

When I read this study, it made me think of the mother who brought her daughter in for the leg rash: the mother’s treating her chronic Lyme “the natural way” must have helped her. Perhaps the only downside was lost time and money, but clearly it had been worth it. I wish chronic Lyme were always treated with safe, gentle interventions such as acupuncture, massage, and biofeedback (all of which have been shown to work better than placebo for certain conditions). But long-term, high-dose antibiotics should not be used in cases where they work only as well as placebo. For one thing, they are too dangerous; several people have died from complications of antibiotic treatment for chronic Lyme. Antibiotics are also too important to be used that way. As Jerome Groopman has argued in the Review, antibiotics are life-saving drugs whose overuse and misuse puts us all at risk of drug-resistant infections.

In the 2003 study, despite the fact that people who enrolled were experiencing brain fog, depression, and fatigue, their initial neuro-cognitive and psychological testing was normal. The tests didn’t detect clinical depression, loss of function, or cognitive deficits—they couldn’t show evidence of what the people were experiencing. But at the end of the study, subjects’ scores had improved: the “feeling better” that they experienced could be demonstrated on a test. Does this make the reported improvement in their condition more real, more objective?

To me, the phenomenon suggests not that objective demonstrations of subjective feelings make those feelings more real, but rather that the subjective is real, and always was. People treated with intravenous injections and pills see improvements in a condition that exists entirely, so far as we know, in the realm of experience.

That chronic Lyme exists in the realm of experience doesn’t mean it isn’t real: sorrow is real, tingling is real, tension headaches are real—and I can’t know if my patients have those things unless I ask them. When medicine does not acknowledge the reality of the subjective—the thick reality of lived experience—we fall laughably short in our efforts to serve patients. What is a life but experience, and why does illness matter except insofar as it affects the way we feel and the experiences we have or are denied?

Lidija Haas began her review for The New Yorker of Porochista Khakpour’s Sick, a memoir of chronic Lyme, by asking “Is Lyme disease a feminist issue?” Haas describes how disease in women is painfully under-studied and how physician bias affects women’s health. The most famous case of this is multiple sclerosis (MS), an often-debilitating autoimmune disease that is more common in women. As Haas mentions, MS was essentially chalked up to hysteria until the invention of Magnetic Resonance Imaging (MRI), which allowed doctors to see the characteristic lesions in the brains and spines of patients with MS. When doctors could see it, we designated it as real.

But MS was real before the MRI, and chronic Lyme is also real. It comprises a constellation of symptoms and a community of sufferers, too often attended to by unscrupulous providers. Insofar as the history of chronic Lyme is a history of physicians’ ignoring, downplaying, or refusing to investigate the symptoms of women, chronic Lyme is also a feminist issue.

Should women’s suffering be listened to, attended to, and investigated? Yes. Does our suffering deserve heroic efforts to develop and provide evidence-based therapies? Absolutely. But is our suffering caused by tick bites? Usually not.

Even that most ardent feminist critic of science, Donna Haraway, acknowledged the importance of standards of objectivity existing alongside the thick reality of the subjective. In her essay on “The Science Question in Feminism,” Haraway argued that bringing together multiple voices speaking of their “situated knowledges” might create an objective viewpoint.

In medicine, this situated knowledge must include the experience of the patient, and it must include a doctor who is aware of her own biases. But it must also include physical exams, lab tests, double-blind randomized trials, and the cumulative knowledge of biomedicine. These are the situated knowledges that have created our medicines, which can be so fantastically effective, but also so dangerous.

It is tempting to say that if allopathic physicians would just listen more attentively to our women patients, we wouldn’t be driving them into the arms of unscrupulous naturopaths. In her piece, Haas suggests as much. But I don’t agree: not only men but also women, not only doctors but also patients, prize the trappings of scientific objectivity. The mother with chronic Lyme insisted that her “levels” were “above the CDC standard.” The father whose daughter had been diagnosed with malaria on top of chronic Lyme—despite the fact that she had never traveled to a malarial environment—believed the diagnosis because it came from “a blood test.” Although many of the parents whose children I care for can trust a thorough and well-explained physical exam, others crave the CT scan or the lab report: something they can see.

The providers who treat chronic Lyme are very aware of this craving. They have adorned their messages with the trappings of objectivity despite the utter lack of scientific evidence behind most of the therapies they offer for chronic Lyme. Clinics specializing in chronic Lyme use the language of “co-infection,” “biofilms,” and “therapeutic apheresis.” Some such clinics also prescribe antibiotics: dangerous doses of them, for dangerously extended periods. Some of their patients get ports surgically implanted into their chests so they can receive long-term intravenous antibiotics without a daily poke; some have died from the blood infections that are a risk for patients making frequent use of IV treatment. So-called “natural” medicine often makes my low-intervention style seem painfully old-fashioned.

I’m not sure there is a clear way out of this bind. In his research on Australians who report suffering from chronic Lyme, the researcher Miles Beaman proposed a new name for the condition: Australian Multisystem Disorder. Which is reasonable: name it, study it, separate it from Borrelia infection. But if physicians can keep track of, and distinguish between, early localized Lyme disease and early disseminated Lyme disease and late-disseminated Lyme disease and Post-Treatment Lyme Disease Syndrome, why can we not also understand chronic Lyme as a condition that is not related to Borrelia, and may respond to intensive treatment with placebos?

To do so would require a kind of epistemological gentleness from physicians, an acknowledgement that experiences we cannot pin to biological variance are nevertheless real. But even if we do this—even if we listen carefully and openly for as long as it takes—I fear we may not meet the needs of these patients. I fear it is insulting to both physicians and chronic Lyme patients to suggest that these patients just need to be heard. Presumably, they want more than that. Like everybody else, they want to be cured.

And cure is tricky; sometimes I have seen it, but often it eludes. I have frequently been able to listen to families for whom cures are not forthcoming (parents of children with relentless neurodegenerative disorders, for example, or of kids whose cancers progressed despite the best available therapies). They appreciated good communication and the healing power of having their realities acknowledged, but also they wanted their children to survive. Presumably, Porochista Khakpour would like to have her reality affirmed, but would also prefer to walk without a cane.

As it stands, allopathic medicine and biomedical research are ill-equipped to develop effective therapies for conditions whose manifestations are as variegated and as particular to each patient as chronic Lyme, and which so far lack a clear biological aberration—an infection, a protein, an imbalance of electrolytes, a change in the structure of nerves—for our therapies to target. Such things fall into the category of suffering we cannot explain. The danger of proceeding with therapeutic attempts in the absence of a biological understanding of disease is illustrated precisely by chronic Lyme: unscrupulous providers seem to just be making stuff up, and the longer and riskier their treatments are, the more they profit. As things stand, listening—and frequent follow-up with a good primary-care physician—may be the best we can offer.

When it comes to Ixodes-borne Lyme disease itself, we all need to expand our horizons. So many kinds of suffering cannot be identified with lab tests or treated reliably with specific medicines. That suffering is real. It must be attended to. But to insist beyond all plausibility that one’s suffering is related to a tick bite is not feminist; it’s absurd. And to prey on suffering people who crave that certainty, offering them expensive, intensive, and dangerous treatments is worse than absurd; it’s cruel.

Some patient details have been altered or omitted to protect confidentiality.