Lyme Disease Is Baffling, Even to Experts
But new insights are at last accumulating.
In the fall of 1997, after I graduated from college, I began experiencing what I called “electric shocks”—tiny stabbing sensations that flickered over my legs and arms every morning. They were so extreme that as I walked to work from my East Village basement apartment, I often had to stop on Ninth Street and rub my legs against a parking meter, or else my muscles would begin twitching and spasming. My doctor couldn’t figure out what was wrong—dry skin, he proposed—and eventually the shocks went away. A year later, they returned for a few months, only to go away again just when I couldn’t bear it anymore.
Over the years, the shocks and other strange symptoms—vertigo, fatigue, joint pain, memory problems, tremors—came and went. In 2002, I began waking up every night drenched in sweat, with hives covering my legs. A doctor I consulted thought, based on a test result, that I might have lupus, but I had few other markers of the autoimmune disease. In 2008, when I was 32, doctors identified arthritis in my hips and neck, for which I had surgery and physical therapy. I was also bizarrely exhausted. Nothing was really wrong, the doctors I visited told me; my tests looked fine.
In 2012, I was diagnosed with a relatively mild autoimmune disease, Hashimoto’s thyroiditis. Yet despite eating carefully and sleeping well, I was having difficulty functioning, which didn’t make sense to my doctor—or to me. Recalling basic words was often challenging. Teaching a poetry class at Princeton, I found myself talking to the students about “the season that comes after winter, when flowers grow.” I was in near-constant pain, as I wrote in an essay for The New Yorker at the time about living with chronic illness. Yet some part of me thought that perhaps this was what everyone in her mid-30s felt. Pain, exhaustion, a leaden mind.
One chilly December night in 2012, I drove a few colleagues back to Brooklyn after our department holiday party in New Jersey. I looked over at the man sitting next to me—a novelist I’d known for years—and realized that I had no idea who he was. I pondered the problem. I knew I knew him, but who was he? It took an hour to recover the information that he was a friend. At home, I asked my partner, Jim, whether he had ever experienced anything like this. He shook his head. Something was wrong.
By the following fall, any outing—to teach my class, or to attend a friend’s birthday dinner—could mean days in bed afterward. I hid matters as best I could. Debt piled up as I sought out top-tier physicians (many of whom didn’t take insurance)—a neurologist who diagnosed neuropathy of unclear origin, a rheumatologist who diagnosed “unspecified connective-tissue disease” and gave me steroids and intravenous immunoglobulin infusions. I visited acupuncturists and nutritionists. I saw expensive out-of-network “integrative” doctors (M.D.s who take a holistic approach to health) and was diagnosed with overexhaustion and given IV vitamin drips. Many doctors, I could tell, weren’t sure what to think. Is this all in her head? I felt them wondering. One suggested I see a therapist. “We’re all tired,” another chided me.
I was a patient of relative privilege who had access to excellent medical care. Even so, I felt terrifyingly alone—until, in the fall of 2013, I found my way to yet another doctor, who had an interest in infectious diseases, and tested me for Lyme. I had grown up on the East Coast, camping and hiking. Over the years, I had pulled many engorged deer ticks off myself. I’d never gotten the classic bull’s-eye rash, but this doctor ordered several Lyme-disease tests anyway; though indeterminate, the results led her to think I might have the infection.
I began to do research, and discovered other patients like me, with troubling joint pain and neurological problems. To keep symptoms at bay, some of them had been taking oral and intravenous antibiotics for years, which can be dangerous; one acquaintance of mine was on her fifth or sixth course of IV drugs, because that was the only treatment she’d found that kept her cognitive faculties functioning. I read posts by people who experienced debilitating exhaustion and memory impairment. Some were so disoriented that they had trouble finding their own home. Others were severely depressed. Along the way, nearly all had navigated a medical system that had discredited their testimony and struggled to give them a diagnosis. Many had been shunted by internists to psychiatrists. The stories were not encouraging.
After a decade and a half in the dark, I at last had a possible name for my problems. Yet instead of feeling relief, I felt I had woken into a nightmare. I wasn’t sure whether the disease I had really was untreated Lyme. Even if I did have Lyme, there was little agreement about how to treat a patient like me—whose test results were equivocal and who had been diagnosed very late in the course of the disease—and no guarantee that I would get better if I tried antibiotics.
It was a scary path to walk down. My own doctor cautioned that the label Lyme disease was easy to pin on one’s symptoms, because the tests can be inaccurate. I understood. I’d gotten my hopes up before. My experience of medicine had led me to conclude that specialists often saw my troubles through their particular lens—an autoimmune disease! a viral issue! your mind! And I worried that if I were to go see a Lyme specialist—an internist with a focus on the disease—he would say I had it no matter what.
In the absence of medical clarity, I had to decide what to do. Was I going to become a Lyme patient? If so, whom was I to trust, and how far would I go? Then one night, in my rabbit-hole searching, I stumbled on a thread of Lyme patients describing the same electric shocks that had bedeviled me for years. The back of my neck went cold. For nearly 20 years I had tried to find a doctor who would think the problem was something other than dry skin. I had asked friends if they had any idea what I was talking about. No one ever did. I had thought I was imagining it, or being oversensitive—or was somehow at fault. To see my ordeal described in familiar, torturous detail jolted me to attention.
I knew then that I needed to learn more about the complex reality of Lyme disease and tackle the near-impossible task of sorting out what was understood and what wasn’t. I didn’t yet know that simply by exploring whether untreated Lyme disease could be the cause of my illness, I risked being labeled one of the “Lyme loonies”—patients who believed that a long-ago bite from a tick was the cause of their years of suffering. They’d been called that in a 2007 email sent by the program officer overseeing Lyme grants at the National Institutes of Health. The now-infamous phrase betrayed just how fiercely contested the disease is—“one of the biggest controversies that medicine has seen,” as John Aucott, a physician and the director of the Johns Hopkins Lyme Disease Clinical Research Center, later described it to me.
Lyme Disease was discovered in Connecticut in the mid-1970s. Today it is a major, and growing, health threat, whose reach extends well beyond its initial East Coast locus. Reported cases increased almost fivefold from 1992 to 2017, and the Centers for Disease Control and Prevention estimates that annual incidences have risen to more than 300,000, and may even range above 400,000. Step into parks in coastal Maine or Paris, and you’ll see ominous signs in black and red type warning of the presence of ticks causing Lyme disease. In the summer in the eastern United States, many parents I know cover their children from head to toe—never mind the heat—for a hike in the woods or a jaunt to a grassy playground. On a recent trip to my brother’s new country house in Vermont, a few weeks before his partner woke up one morning with a dramatic bull’s-eye rash, I chased my toddler sons around, spraying them so often with tick repellent that they thought we were playing a special outdoor game.
By now, just about everyone knows someone who’s been diagnosed with Lyme disease, and most of us know to look for the telltale rash (often described as a bull’s-eye, many Lyme rashes are solid-colored lesions) and to ask for a prompt dose of antibiotics. For most of those who get swiftly diagnosed and treated, that will be the end of the story. But lots of Americans have also heard secondhand reports of people who stayed sick after that course of antibiotics. And lots know of cases in which no rash appeared and a diagnosis came late, when damage had already been wrought. Plenty of others, upon discovering an attached deer tick, have encountered doctors who balk at prescribing antibiotics to treat a possible Lyme infection, wary of overdiagnosis.
The degree of alarm and confusion about such a long-standing public-health issue is extraordinary. The consequences can’t be overestimated, now that Lyme disease has become an almost “unparalleled threat to regular American life,” as Bennett Nemser, a former Columbia University epidemiologist who manages the Cohen Lyme and Tickborne Disease Initiative at the Steven & Alexandra Cohen Foundation, characterized it to me. “Really anyone—regardless of age, gender, political interest, affluence—can touch a piece of grass and get a tick on them.”
Even as changes in the climate and in land use are causing a dramatic rise in Lyme and other tick-borne diseases, the American medical establishment remains entrenched in a struggle over who can be said to have Lyme disease and whether it can become chronic—and if so, why. The standoff has impeded research that could help break the logjam and clarify how a wily bacterium, and the co-infections that can come with it, can affect human bodies. After 40 years in the public-health spotlight, Lyme disease still can’t be prevented by a vaccine; eludes reliable testing; and continues to pit patients against doctors, and researchers against one another. When I got my inconclusive diagnosis, I knew better than to dream of a quick cure. But I didn’t know how extreme the roller coaster of uncertainty would be.
Lyme Disease came into public view when an epidemic of what appeared to be rheumatoid arthritis began afflicting children in Lyme, Connecticut. A young rheumatologist at Yale named Allen Steere, who now conducts research at Massachusetts General Hospital, in Boston, studied the children. In 1976 he named the mysterious illness after its locale and described its main symptoms more fully: a bull’s-eye rash; fevers and aches; Bell’s palsy, or partial paralysis of the face, and other neurological issues; and rheumatological manifestations such as swelling of the knees. After much study, Steere realized that the black-legged ticks that live on mice and deer (among other mammals) might be harboring a pathogen responsible for the outbreak. In 1981, the medical entomologist Willy Burgdorfer finally identified the bacterium that causes Lyme, and it was named after him: Borrelia burgdorferi.
B. burgdorferi is a corkscrew-shaped bacterium known as a spirochete that can burrow deep into its host’s tissue, causing damage as it goes and, in laboratory conditions at least, morphing as needed from corkscrew to cystlike blob to, potentially, slimy “biofilm” forms. Because of this ability, researchers describe it as an “immune evader.” Once it hits the human bloodstream, it changes its outer surface to elude an immune response, and then quickly moves from the blood into tissue, which poses problems for early detection. (Hard to find in the bloodstream and other body fluids, the B. burgdorferi spirochete is hard to culture, which is how bacterial infections are definitively diagnosed.) If it goes untreated, B. burgdorferi can make its way into fluid in the joints, into the spinal cord, and even into the brain and the heart, where it can cause the sometimes deadly Lyme carditis.
By the mid-’90s, a mainstream consensus emerged that Lyme disease was relatively easy to diagnose—thanks to the telltale rash and flulike symptoms—and to treat. Infectious diseases are the kind of clear-cut illness that our medical system generally excels at handling. Evidence indicated that the prescribed treatment protocol—a few weeks of oral antibiotics, typically doxycycline—would take care of most cases that were caught early, while late-stage cases of Lyme disease might require intravenous antibiotics for up to a month. That assessment, made by the Infectious Diseases Society of America, formed the basis of the IDSA’s treatment guidelines from 2006 until recently. (In late June, a revised draft called for, among other things, a shorter course—10 days—of doxycycline for patients with early Lyme.)
Yet the picture on the ground looked far murkier. A significant percentage of people who had Lyme symptoms and later tested positive for the disease had never gotten the rash. Others had many characteristic symptoms but tested negative for the infection, and entered treatment anyway. Most startling, a portion of patients who had been promptly and conclusively diagnosed with Lyme disease and treated with the standard course of doxycycline didn’t really get better. When people from each of these groups failed to recover fully, they began referring to their condition as “chronic Lyme disease,” believing in some cases that the bacterium was still lurking deep in their bodies.
Frustrated with the medical system’s seeming inability to help them, patients emerged as an activist force, arguing that Lyme disease was harder to cure than the establishment acknowledged. Family physicians in Lyme-endemic areas, confronted with patients who weren’t getting better, tried out other treatment protocols, including long-term oral and intravenous antibiotics, sometimes administered for months or years. They also started testing assiduously for tick-borne co-infections, which were appearing in some of the sickest patients. Many of these doctors rotated drugs in the hope of finding a more effective regimen. Some patients responded well. Others didn’t get better. In 1999, these doctors banded together to form the International Lyme and Associated Diseases Society. Highlighting the problems with Lyme-disease tests and citing early evidence that bacteria could persist in animals and humans with Lyme disease even after they’d been treated, ILADS proposed an alternative standard of care that defined the illness more broadly and allowed for more extensive treatment.
But some prominent Lyme-disease researchers were skeptical that the infection could persist after treatment—that bacteria could remain in the body. They argued that many chronic Lyme-disease patients were being treated for an infection they no longer had, while others had never had Lyme disease in the first place but had appropriated the diagnosis for symptoms that could easily have other causes. Chronic Lyme disease, in the Infectious Diseases Society of America’s view, was a pseudoscientific diagnosis—an ideology rather than a biological reality. Under the sway of that ideology, it contended, credulous patients were needlessly being treated with dangerous IV antibiotics by irresponsible physicians. (It didn’t help when a Lyme patient in her 30s died from an IV-related infection.)
To make its case, the IDSA cited a handful of studies indicating that long-term antibiotic treatment of patients with ongoing symptoms was no more effective than a placebo—proof, in its view, that the bacterium wasn’t causing the symptoms. The IDSA also highlighted statistics suggesting that the commonly cited chronic Lyme symptoms—ongoing fatigue, brain fog, joint pain—occurred no more frequently in Lyme patients than in the general population. In the press, experts in this camp implied that patients who believed they had been sick with Lyme disease for years were deluded or mentally ill.
The antagonism was “fierce and alienating for the patients,” Brian Fallon, the director of the Lyme and Tick-Borne Diseases Research Center at Columbia University Irving Medical Center, told me. Hostilities continued to intensify, not just between patients and experts, but between community doctors and academic doctors. In 2006, the IDSA guidelines for patients and physicians argued that “in many patients, posttreatment symptoms appear to be more related to the aches and pains of daily living rather than to either Lyme disease or a tick-borne co-infection.” This message rang hollow for many. “Researchers were saying, ‘Your symptoms have nothing to do with Lyme. You have chronic fatigue syndrome, or fibromyalgia, or depression,’ ” Fallon told me. “And that didn’t make sense to these patients, who were well until they got Lyme, and then were sick.”
By the time the doctor first floated the possibility, in 2013, that I might have Lyme, my headaches, brain fog, and joint pain had gotten much worse, and tiny bruises had bloomed all over my legs and arms. I was so dizzy that I began fainting. A black ocean, it seemed, kept crashing over me, so that I couldn’t catch my breath. I could no more touch the old delights of my life than a firefly could touch the world beyond the jar in which it had been caught.
When I returned to the doctor’s office two weeks later to go over the test results, I didn’t know what I was in for. Imperfect diagnostics lie at the core of the whole debate over Lyme disease. Standard Lyme tests—structured in two tiers, to minimize false positives—can’t reliably identify an infection early on or determine whether an infection has been eradicated. That’s because the tests are not looking for the “immune evader” itself—the B. burgdorferi spirochete—in your blood. Instead, they assess indirectly: They look for the antibodies (the small proteins our bodies create to fight infection) produced in response to the bacteria. But antibody production takes time, which means early detection can be hard. And once produced, antibodies can last for years, which makes it difficult to see whether an infection is resolved, or even whether a new one has occurred. What’s more, antibodies to autoimmune and viral diseases can look like the ones the body makes in response to Lyme.
For a thorough interpretive reading, some doctors will send blood to several different labs, which can deliver results that don’t always agree with one another. And the CDC—which recommends that only a specific pattern of antibodies, agreed on by experts in 1994, be considered indicative of a positive test—suggests that, when needed, doctors should use their judgment to make what’s called a “clinical diagnosis,” based on symptoms and likelihood of exposure, along with the lab tests.
I was confused. My doctor showed me mixed results from three labs. Two had a positive response on one part of the test but not the other, while the third had a negative response on both parts. Because of my medical history as well as particular findings on my tests, she concluded that I probably did have Lyme disease. But she also noted that I had a few nasty viruses, including Epstein-Barr. In addition, the test may have been picking up on autoimmune antibodies, given my earlier diagnosis.
At the recommendation of a science-writer friend, I finally went to see Richard Horowitz, a doctor in upstate New York who specializes in Lyme disease and had earned a reputation as a brilliant diagnostician. Horowitz, who goes by “Dr. H” with many of his patients, is a practicing Buddhist, with bright-blue eyes and an air of brimming eagerness. He recently served as a member of the Tick-Borne Disease Working Group convened by the Department of Health and Human Services, which in 2018 issued a report to Congress outlining problems with the diagnosis and treatment of Lyme patients.
I told him that I wasn’t sure I had Lyme disease. I had brought along a stack of lab results nearly half a foot tall—a paper trail that would scare off many doctors. He perused every page, asking questions and making notes. Finally, he looked up.
“Based on your labs, your symptoms, and your various results over the years, I highly suspect you have Lyme,” he said. “See these?”—he bent over a set of results from Stony Brook laboratory—“these bands are specific for Lyme.”
In his waiting room, I had completed an elaborate questionnaire designed to single out Lyme patients from a pool of patients with other illnesses that affect multiple biological systems. (It has since been empirically validated as a screening tool.) Now Dr. H did a physical exam and ordered a range of tests to rule out further thyroid problems, diabetes, and other possible causes of my symptoms. Because I had night sweats and the sensation that I couldn’t get enough air into my lungs—a symptom known as “air hunger”—he proposed that I might have a co-infection of babesia, a malaria-like parasite also transmitted by ticks. Curious, I told him that I had always thought of Lyme as a primarily arthritic disease, whereas I had many neurological and cognitive symptoms. He explained that B. burgdorferi is now known to come in different strains, which are thought to produce different kinds of disease.
“The funny thing is, I think you’re actually a very strong and healthy person, and that’s why you did okay for so long,” he continued. “Now your body needs help.”
Dr. H prescribed a month of doxycycline, and warned me about something I’d read online. When I began the antibiotic, I might at first feel worse: As the bacteria die, they release toxins that create what’s known as a Jarisch-Herxheimer reaction—a flulike response that Lyme patients commonly refer to as “herxing.” But over time, he said, I should feel better. If not, we were on the wrong track.
Over dinner that night, back in Brooklyn, I told Jim that despite what Horowitz had urged, I wasn’t sure I wanted to take the antibiotics. I didn’t have a cut-and-dried positive test for Lyme, and I knew how damaging antibiotics are to the microbiome. “What do you really have to lose?” he asked, in disbelief. “You’re sick, you’re suffering, and you’ve tried everything else.”
The next morning, I took a dose of the doxycycline, along with Plaquenil, which is thought to help the antibiotics penetrate cells better. I took another dose that night with dinner. I went to bed and woke up feeling like hell. My throat was sore and my head was foggy. My neck was a fiery rebar.
Two days later, we went out to get lunch. I was still groggy and unwell. It was a heavy, gray day, with low clouds. Returning home, I felt rain all over my bare arms. I told Jim we should hurry.
“Why?” he said.
“It’s not raining,” he said. “It’s just cloudy.” I raised my hands to show him the raindrops. A dozen pips of cold popped along my arm. But there was no rain. As we walked home, cold drops rushed all over my body, my skin crawling as if a strange, violent water were cleansing it.
Several days later, though, I felt excited to fly to a conference in Chicago, rather than exhausted by the prospect. For three more weeks, I took the drugs and supplements Dr. H had prescribed. The doxycycline made me allergic to the sun. One late-spring morning, I forgot to put sunblock on my right hand before taking a walk with a friend, holding a coffee cup. It was 9 o’clock and cloudy. By the time I got home, my hand felt tender. Over the next few days a second-degree burn developed, blistering into an open wound.
After a month of antibiotic treatment, I took the train back up to Dr. H’s office. On his questionnaire, I rated my symptoms as less severe than I had a month earlier, but my total score still fell in the high range. Dr. H changed the protocol, adding an antimalarial drug. He was concerned about my continued night sweats and air hunger.
When I started taking the new drugs, in June 2014, I was nearly as sick as I had ever been. I flew to Paris to teach at NYU’s summer writing program. Within two days of arriving, I could barely walk down the street. Violent electric shocks lacerated my skin, and patches of burning pain and numbness spread up my neck. I shook and shivered. The reaction lasted five days, during which panic mixed with the pain. How was I to know whether this was herxing and a positive reaction to the drugs as they killed bacteria and parasites, or a manifestation of the disease itself? Or were weeks of antibiotics themselves causing problems for me?
“I know you think you’re doing the right thing,” a concerned colleague said, “but aren’t you just making yourself sicker?”
On the sixth day, I was sitting on the couch in my rented apartment and the shocks were so violent, racing across my forearms and thighs and calves, that when I looked up at the tall open windows, the sun streaming through them, it occurred to me that I could jump out of them and find relief.
The next morning I woke up to the same bright sun, feeling better than I had in ages. Stunned by my energy, I went out for a run. I wasn’t exactly racing down the sidewalk, but 40 minutes later, for the first time in years, I had run three miles. As the weeks passed, I felt better and better. My drenching night sweats vanished. The air hunger was gone. I had loads of energy. I took antibiotics for several more months, and each month I had fewer symptoms. After eight months of treatment, Dr. H decided that I could stop. It was the spring of 2015.
That fall I got pregnant, at the age of 39. At Dr. H’s urging, I took antibiotics on and off during my pregnancy. In the summer of 2016, I delivered a healthy baby boy.
By the time I started treatment, the fact that Lyme disease causes ongoing symptoms in some patients could no longer be viewed as the product of their imaginations. A well-designed longitudinal study by John Aucott at Johns Hopkins showed the presence of persistent brain fog, joint pain, and related issues in approximately 10 percent of even an ideally treated population—patients who got the Lyme rash and took the recommended antibiotics. Other studies found these symptoms in up to 20 percent of patients. The condition, christened “post-treatment Lyme disease syndrome,” or PTLDS, is now recognized by the CDC. (Of course, the term doesn’t apply to patients like me, who never had a rash or a clearly positive test.) Even so, the condition is hotly contested, and plenty of high-level people in the field—as well as the Infectious Diseases Society of America itself—still don’t recognize it as an official diagnosis. Perhaps most important, crucial questions about the cause of ongoing symptoms remain unanswered, due in part to the decades-long standoff over whether and how the disease can become chronic. As Sue Visser, the CDC’s associate director for policy in the Division of Vector-Borne Diseases, acknowledges, “Many are very rightfully frustrated that it’s been decades and we still don’t have answers for some patients.”
Recently, though, a host of new studies has freshly tackled a lot of those questions: Why do Lyme symptoms persist in only some patients? What don’t we know about the behavior of the B. burgdorferi bacteria that might help explain the variation in patients’ responses to it?
There isn’t much federal funding to study Lyme disease, and what there is often goes to research on prevention and transmission. (The NIH spends only $768 on each new confirmed case of Lyme, compared with $36,063 on each new case of hepatitis C.) Much of the money to investigate PTLDS has come from private foundations, including the Steven & Alexandra Cohen Foundation, the Global Lyme Alliance, and the Bay Area Lyme Foundation. The CDC and the NIH recently reached out to these groups, officials told me, spurred on in part by the 2018 Tick-Borne Disease Working Group report to Congress outlining major holes in the scientific understanding of Lyme disease.
In a conversation I had with him, Bennett Nemser of the Cohen Foundation laid out some of the hypotheses that are currently being explored. The complexity is daunting. A patient with ongoing symptoms may actually still have a Lyme infection, and/or a lingering infection from some other tick-borne disease. Or the original infection might have caused systemic damage, leaving a patient with recurring symptoms such as nerve pain and chronic inflammation. Or the Lyme infection might have triggered an autoimmune response, in which the immune system starts attacking the body’s own tissues and organs. Or a patient might be suffering from some combination of all three, complicated by triggers that researchers have not yet identified.
One way or another, an intricate interplay of the infection and the immune system, new research suggests, is at work in patients who don’t get better. The immune response to the Lyme infection, it turns out, is “highly variable,” John Aucott told me. For example, some research has suggested that ongoing symptoms are a result of an overactive immune response triggered by Lyme disease. Recently, though, a study co-authored by Aucott with scientists at Stanford found that, in patients who developed PTLDS, the Lyme bacteria had actually inhibited the immune response.
By now, accumulating evidence suggests that in many mammals, Lyme bacteria can persist after treatment with antibiotics—leading more scientists to wonder if the bacteria can do the same in humans. In 2012, a team led by the microbiologist Monica Embers of the Tulane National Primate Research Center found intact B. burgdorferi lingering for months in rhesus macaques after treatment. Embers also reported that the macaques had varying immune responses to the infection, possibly explaining why active bacteria remained in some. The study drew criticism from figures in the IDSA establishment; in their view it failed to prove that the bacteria remained biologically active. But Embers told me that this year, in their work with mice, she and her team have managed the feat of culturing B. burgdorferi, showing that it was viable after a course of doxycycline. New studies looking into possible bacterial persistence in humans—conducted by the National Institute of Allergy and Infectious Diseases, part of the NIH—are under way.
Meanwhile, several researchers, including Ying Zhang at the Johns Hopkins Bloomberg School of Public Health, have proposed another explanation for how B. burgdorferi can remain after treatment: the presence of what are called “persister bacteria,” similar to those found in certain hard-to-treat staph infections but long thought not to exist in Lyme. In the case of Lyme disease, persister bacteria are a subpopulation that enters a dormant state, allowing them to survive a normally lethal siege of antibiotics. These persister bacteria, Zhang’s team found, caused severe symptoms in mice, and the current single-antibiotic Lyme protocols didn’t eradicate them—which makes sense: Doxycycline functions not by directly killing bacteria, but by inhibiting their replication. Thus it affects only actively dividing bacteria, not dormant ones, relying on a healthy immune system to dispatch any B. burgdorferi that remain.
The big outcome, though, was that when Zhang’s team treated the mice with a three-antibiotic cocktail, including a drug known to work on persistent staph infections, the mice cleared the persistent B. burgdorferi infection. “We now have not only a plausible explanation but also a potential solution for patients who suffer from persistent Lyme-disease symptoms despite standard single-antibiotic treatment,” Zhang said. Taking the next step, Kim Lewis at Northeastern University, who has had a distinguished career studying persister bacteria, is about to conduct a study, in collaboration with Brian Fallon, looking at whether a compound that specifically targets persister cells can help patients with PTLDS.
Of course, even if active bacteria do remain in some Lyme patients, they may well not be the cause of the symptoms, as many in the IDSA have long contended. Paul Auwaerter, the clinical director of infectious diseases at Johns Hopkins School of Medicine and a former president of the IDSA, points out that Lyme bacteria can leave behind DNA “debris” that may trigger ongoing “low-grade inflammatory responses.” Lewis told me that the overarching question—“whether the pathogen is there and is slowly causing damage, or has already left the body and has wrecked the immune system”—has yet to be settled, in his view. But, he said, “I’m optimistic that we and others are going to find a cure for PTLDS.”
When my son was seven months old, my interlude of feeling energetic and mostly symptom-free abruptly ended. He was not a good sleeper, and months of waking at night had worn me down. In early April 2017, we both got sick, and I didn’t recover. My body ached. My brain got foggy. My primary-care doctor noted that the Epstein-Barr virus was active in my system again. Dr. H suggested that the Lyme infection had recurred, and that I needed another course of antibiotics, but I hesitated. I wasn’t sure whether to believe that the Lyme infection could persist, and I attributed my ill health to an autoimmune flare or postviral fatigue. For months I stalled, but soon the electric shocks were back, zapping my arms and legs, and life became a slog. I started antibiotics. Within five days, my energy returned and I felt almost completely well again. A month later, feeling better than I had in almost 20 years, I got pregnant with my second son.
Could this recovery be attributed to the placebo effect?, I wondered. If so, it was the only placebo that had ever worked for me.
Meanwhile, my father, who lived in Connecticut, had begun to suffer drenching night sweats, fatigue, and aches and pains. His tests were negative for Lyme but suggestive of ehrlichiosis, another tick-borne infection, and his doctor—in the heart of Lyme country—decided to treat what seemed like a plausible culprit and its co-infection. My father was put on doxycycline for five months. He didn’t improve, which surprised me, given that I had seen immediate results. Then one day my brother found him at home, on the verge of collapse, and took him to an ER, where batteries of tests revealed that he had a different problem. He was suffering from Stage 4 Hodgkin’s lymphoma.
In 2018, my father died of complications from pneumonia, after recovering from the cancer. I couldn’t help wondering how much those lost months had perhaps cost him, as the cancer advanced and weakened him—all because Lyme had seemed like an obvious enough explanation, and the testing was sufficiently murky, that his doctor did not pursue other diagnoses. Though promising new diagnostic technologies are on the horizon, we still can’t reliably sort out who has a tick-borne disease and who doesn’t.
On a brisk March day this year, the kind of day that can’t decide whether it’s warm or cold, I visited a research laboratory at Massachusetts General Hospital directed by Allen Steere, the rheumatologist who discovered Lyme disease and helped establish the testing parameters for it. A slim, gray-haired man with an intense gaze, he has become, in the eyes of many Lyme patients, an embodiment of the medical system’s indifference, because he has long suggested that some chronic Lyme patients were incorrectly diagnosed in the first place. He has been shouted down at conferences and ambushed by people purporting to be journalistic interviewers. Scientists who disagree with him had nonetheless singled him out to me for his commitment to studying Lyme. I wanted to hear his perspective on the disease and on the debate after four decades of immersion in both.
While underscoring that medicine can be humbling, and that Lyme disease is complex, Steere spoke with the calm air of someone setting a child straight. Emphasizing that in many people Lyme disease can resolve on its own without antibiotics, he carefully described a disease that in the United States frequently follows a specific progression of stages if untreated, beginning with an early rash and fever, then neurological symptoms, and culminating later in inflammatory arthritis. The joint inflammation can continue for months or even years after antibiotic treatment, but not, he believes, because the bacteria persist. His research on patients who have these continuing arthritis symptoms has revealed one cause to be a genetic susceptibility to an ongoing inflammatory response. This discovery has led to effective treatment for the longer-term challenges of Lyme arthritis, using what are called disease-modifying anti-rheumatic agents.
After I told him a little about my case, he struck a note of similarly solicitous firmness. He told me that in his view, late-stage Lyme (which is what I had been diagnosed with) usually does not cause a lot of “systemic symptoms,” such as the fatigue and brain fog I had experienced. “I want you to free yourself from the Lyme ideology,” he said. “You clearly were helped by antibiotic therapy. But I don’t favor the idea that it was spirochetal infection. Of course, there are other infectious agents,” he continued, noting that some of them trigger complex immune responses.
I left Steere’s office unnerved, thinking that if I had met a doctor with some version of this view in 2014, I would never have started doxycycline and gotten better. Could it really be that I had some condition other than Lyme that turned out to respond to antibiotics? He was an expert who had devoted his entire career to studying the mechanics of the disease; I was a patient who happens to be temperamentally both exacting and excitable, and scientifically curious—a layperson craving evidence.
That night I curled up with my computer in my hotel room and reread a 1976 New York Times article about the discovery of Lyme. New things struck me, in particular Steere’s growing suspicion back then that bacteria couldn’t be the cause, because this microorganism wasn’t acting like a bacterium:
The bacterial infections that are known to cause arthritis leave permanent joint damage, and bacteria are easy to see in body fluids and easy to grow in test tubes. Every effort to culture bacteria from fluids and tissues from the patients has failed.
Steere had moved on to a new possibility: “A virus is the most likely candidate,” he told the Times. “Just because we haven’t found one yet doesn’t mean it isn’t there. We’ll keep looking.” When I recently wrote to ask him if he had been “fooled” by Lyme disease back in the 1970s, he reminded me of how much he and others had learned, in just a few years, about this then-new infection. He went on to remind me that science can “lead to one ‘dead end’ after another. One needs to learn from these dead ends and continue trying.”
“Anyone who says they really understand the pathophysiology of what’s going on is oversimplifying to some degree,” said Ramzi Asfour, a physician and member of the Infectious Diseases Society of America with notably open views on Lyme disease, when I reached him on the phone in his Bay Area office. Asfour has found that a one-size-fits-all approach to Lyme diagnosis and treatment is inadequate for most patients in his medical practice. We don’t know enough yet about diseases that are characterized by abnormal activity of the immune system, he emphasized. But, alongside the usual standardized protocols, they clearly call for the tactics of personalized medicine, because the immune system is so complex—and so individualized. For example, autoimmune diseases can be triggered by stressors that include trauma or infection. And standard lab reports don’t always capture early stages of disease. Listening to patients is crucial.
“Being an infectious-disease doctor is usually pretty rewarding in the conventional sense,” Asfour said. “The patient is in the ICU; you grow a bacteria, and you see it; then you give them a magic pill. They get better and walk home. It’s very satisfying.” The experience of Lyme patients challenges that model. As the surgeon Atul Gawande once wrote of the medical profession, “Nothing is more threatening to who you think you are than a patient with a problem you cannot solve.”
The less we understand about a disease, as Susan Sontag argued years ago in Illness as Metaphor, the more we tend to psychologize or stigmatize it. In the midst of the current debate over Lyme, I can’t help thinking about other illnesses that modern medicine misunderstood for years. Multiple sclerosis was once called hysterical paralysis, and ulcers were considered “a disease of tense, nervous persons who live a strenuous and worrisome life,” as one mid-century medical manual put it, outlining a notion that remained common until the 1980s. In fact, ulcers are caused by bacteria—though when a researcher proposed as much in 1983, he was almost literally laughed out of a room of experts, who swore by the medical tenet that the stomach was a sterile environment. Doctors now also know that not everyone with the bacteria gets an ulcer—it’s caused by a complex interplay of pathogen and host, of soil and seed, perhaps like post-treatment Lyme disease syndrome.
It is true that Lyme disease has become a term that stands for more than itself. If not an ideology, it is a metonym for all tick-borne illness, for embattled suffering, for the ways that medicine has fallen short of its promised goal of doing no harm—in this case by dismissing and mocking suffering patients. As Wendy Adams of the Bay Area Lyme Foundation put it to me, “We now have incontrovertible data that says these people are legitimately sick.” Just because a symptom is common and subjective—as fatigue is—doesn’t mean that a patient can’t tell the difference between a normal version of it and a pathological one. After all, we’re able to distinguish between the common cold and a case of the flu. When I was very ill, I felt like a zombie—more important, I felt categorically different from myself. By contrast, today I have aches and pains, and I’m tired, but I am more or less “me.”
Recently, I called Richard Horowitz and several other Lyme experts to ask them, once again, if they really thought it was likely that I had Lyme. “Meghan. You have Lyme disease,” Dr. H said. “You have had multiple Lyme-specific antibodies show up on your tests. You had all the symptoms that led to a clinical diagnosis. And you got better when you took antibiotics.” Others echoed his conclusion.
I live in uncertainties, as the poet John Keats put it while he was dying of an infection then thought to be a disease of sensitive souls, which we now know is tuberculosis. But I am fairly sure of one thing. In a week, or a month, or six months, I will start feeling less well. My head will get foggier, my energy level will sink. When I wake in the morning, I will have a severe headache. Sharp electric shocks will start running along my legs and arms, for minutes, then hours, then days. My older son will stop eating his breakfast as I twitch in pain, and say, “What’s wrong, Mommy?” And once again I will ask Dr. H for antibiotics.
While writing this article, it happened. I took the antibiotics. I felt worse, and then I felt dramatically better. In a few months, when I have stopped nursing my younger son, I will try Dr. H’s new anti-persister regimen. Consisting of three different drugs, including antibiotics used to treat persister bacteria found in diseases like TB and leprosy, it has put some of his most challenging patients into remission for nearly two years now.
I can’t know for sure that I have Lyme disease. But to imagine that I might never have found the treatment that has saved my life in every sense—restoring its joy—terrifies me. I think often about patients who are less fortunate, whose disease, whatever it may be, has gone unrecognized. One of the bitterest aspects of my illness has been this: Not only did I suffer from a disease, but I suffered at the hands of a medical establishment that discredited my testimony and—simply because of my search for answers, and my own lived experiences—wrote me off as a loon. In the throes of illness, cut off from the life you once lived, fearing that your future has been filched, what do you have but the act of witness? This is what it is like. Please listen, so that one day you might be able to help.
This article appears in the September 2019 print edition with the headline “Life With Lyme.”