One day, Meghan O’Rourke started experiencing “electrical shocks” throughout her legs and arms - a spasming and itchiness that left doctors confused. Like many other patients, the doctors all sent her home with simple hypotheses and a “wait-and-see” treatment plan. But more symptoms piled on over the years, forcing her to continue seeking answers, only to still be shrugged at by practitioners.
Her joint pain was treated as “arthritis;” her other symptoms - vertigo, fatigue, and night sweats, were not investigated beyond a (negative) test for Lupus. Eventually she was diagnosed with Hashimoto’s thyroiditis, but even with lifestyle changes, her cognition and basic functioning was still in decline.
Lyme disease came into public view forty years ago, when a surge of children in Lyme, Connecticut began complaining of what looked to be rheumatoid arthritis. As the climate and land has changed, reported cases have increased almost five times in the last 25 years. It is spread by ticks, originally thought to be restricted to the forests of the Northeast, but has spread through the entire USA. Experts consider it an “unparalleled threat to regular American life" - anyone brushing by some grass could contract a diseased tick.
Lyme and its co-infections are so misunderstood that practitioners argue over who truly has the disease, whether it can become chronic, why it might become chronic. These arguments have resulted in massive conflicts within scientific communities.
As of today, there is still no preventable vaccine, no reliable test, and no treatments - let alone cures.
“Infectious diseases are the kind of clear-cut illness that our medical system generally excels at handling,” O'Rourke explains. But Lyme manages to elude both a common symptom profile as well as effective testing. Most infectious diseases have similar symptoms, reliable tests, and successful antibiotic treatments. However, with Lyme, a significant portion of patients never develop a rash, can receive negative or inconclusive results, or show no improvements after taking the prescribed antibiotics.
Physicians in Lyme-endemic areas were desperate to help their patients. They tested out long-term antibiotics, IV antibiotics, testing for co-infections, and rotating drugs. In 1999, these doctors joined together to form the International Lyme and Associated Diseases Society (ILADS).
ILADS decided that Lyme disease tests were too inconclusive, the bacteria could persist in hosts even after treatment, and that there needed to be a different care standard for patients - one that more broadly defined the illness and allowed options for more extensive treatment.
Despite their work and intentions, they were met with resistance from the medical industry and research communities, specifically the Infectious Diseases Society of America or IDSA. “Chronic Lyme disease, in the Infectious Diseases Society of America’s view, was a pseudoscientific diagnosis—an ideology rather than a biological reality.” The IDSA felt that chronic Lyme was an impossibility. and that prolonged antibiotic treatment for it was dangerous and irresponsible.
"In the midst of the current debate over Lyme," O'Rourke writes, "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...'" In fact, when a researcher in 1983 suggested that most ulcers were caused by a bacteria, he was nearly laughed out of a room of experts, "who swore by the medical tenet that the stomach was a sterile environment." Even though the researchers were able to culture H. pylori bacteria from the gastric biopsies of patients with ulcers, the medical community still refused to acknowledge ulcers could be caused by anything other than stress. Frustrated, one of the researchers underwent gastric biopsy in 1985 to have evidence that he didn't carry the bacterium, "then deliberately infected himself to show that it in fact caused acute gastric illness."
- Susan Sontag, Illness as Metaphor, quoted in Why Is Lyme Disease So Hard to Understand? - The Atlantic by Meghan O'Rourke
The IDSA even implied that the patients were actually delusional and mentally ill - a frequent dismissal used on chronic illness patients in general.
When things like hysteria, delusion, or hysterical conversion reaction are used "as a 'wastebasket' diagnosis for unexplained symptoms, patients with treatable medical conditions may go unrecognized." Patients with rare diseases suffer for on average seven years before being correctly diagnosed, despite seeking help from an average of four primary care doctors and four specialists, all while receiving multiple misdiagnoses.
From Mislabelling Absolute Neurological Illnesses as Conversion Disorder, Saeed Shoja Shafti (M.D)
One patient was told by researchers "Your symptoms have nothing to do with Lyme. You have chronic fatigue syndrome, or fibromyalgia, or depression." Brian Fallon, director of the Lyme and Tick-Borne Diseases Research Center at Columbia University, saw the side of the patient: "that didn’t make sense to these patients, who were well until they got Lyme, and then were sick... the evidence that something more complex is going on is tantalizing and substantial."
One patient, David Roth, had suffered for years without answers despite seeing doctors and getting scans. “Here is what I don’t understand,” he said. “Somebody can get ill and not know what it is and the symptoms get worse and worse. Two years or more later, they can learn that they have Lyme. They take antibiotics for a month. And then, according to their doctors and insurance companies, they are done. Cured. Sometimes that is enough. But many people continue to be sick, and the government’s position, in a world where there are ten times as many bacterial cells as human cells in our body, is that this particular bacteria has been removed forever and the problem must be due to something else.”
Another reason why we have unanswered questions is a simple lack of funding for Lyme disease.
The only funding available is largely going to prevention. In fact, the NIH spends $768 for every new Lyme case, while $36,063 is spent on each new case of hepatitis C. Private funding is one of the only ways PTLDS has been investigated.
We know that Lyme is caused by ticks that carry the bacterium Borrelia burgdorferi, a spirochete shaped like a corkscrew that is covered in a “biofilm” that prevents detection by the immune system. It moves from the blood to tissue, making it even more elusive as it is not present enough in body fluids to then culture. Untreated, the bacteria move into joints, spinal cord, brain, and also the heart- causing Lyme carditis, which is often fatal.
However, the current Lyme tests are looking only for antibodies - not the B. burgdorferi spirochete. This indirect testing misses early infection and cannot determine if the infection has been wiped out or even if a new one has occurred. Additionally, antibodies to autoimmune and viral diseases can look like the ones the body makes in response to Lyme.
In addition to this, the test does not look for common co-infections associated with a bite. More accurate tests exist for Lyme and its co-infections but are not typically covered by insurance and can cost thousands of dollars.
O'Rourke had mixed results. “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.”
Around the time O’Rourke finished treatment, a study at Johns Hopkins showed “the presence of persistent brain fog, joint pain, and related issues” in those who took the prescribed treatment. Other studies found symptoms in as many as 20% of patients.
This phenomenon was finally named “post-treatment Lyme disease syndrome,” or PTLDS, and it is recognized by the CDC. The CDC’s associate director for policy in the Division of Vector-Borne Diseases stated: “many are very rightfully frustrated that it’s been decades and we still don’t have answers for some patients.”
Allen Steere, the rheumatologist who discovered Lyme disease, suspects that varied factors are at play. Joint inflammation can persist in Lyme patients long after treatment, or other illnesses could be causing the symptoms. His research on Lyme patients with continuing arthritis symptoms showed a genetic predisposition to inflammation responses, which has since led to effective Lyme arthritis treatments using anti-rheumatic agents.
- Ying Zhang, Johns Hopkins Bloomberg School of Public Health
We now know that Lyme bacteria can remain in many mammals even after antibiotic treatment - a 2012 study of rhesus macaques had intact B. burgdorferi even months after treatment. The IDSA scrutinized this study for not proving whether the bacteria were biologically active, but the research was still a revelation. The same team of researchers has since managed to actually culture B. burgdorferi, proving it was viable in mice even after a course of doxycycline. Human studies on this are currently underway.
This leads into one of the emerging theories on Lyme disease: the presence of “persister bacteria,” similar to those found in staph infections. In the mice, these bacteria caused severe symptoms and the current Lyme antibiotic protocol did not eradicate them.
This makes sense: doxycycline does not directly kill the bacteria, it only inhibits their replication. This means it would only affect actively dividing bacteria and not dormant ones, which relies on a functioning immune system to kill any B. burgdorferi that remain.
An enlightening result came from the study when Zhang’s team applied staph treatment methods to the mice: using 3 antibiotics, including a drug known to affect persistent staph infections, the mice were able to clear out the persistent B. burgdorferi infection.
This means we now have a plausible explanation as well as a potential treatment plan. It is still possible that active bacteria may still not be the cause of the symptoms, but Kim Lewis, a specialist in persister bacteria at Northeastern University, will be continuing on this theory to see. Her research aims to determine whether a compound that targets persister cells could help PTLDS patients.
Ramzi Asfour, a physician and member of the Infectious Diseases Society of America, explained that even the best minds are still not sure what's going on. He uses personalized medicine, diagnostic testing, and treatment plans to help each patient personally. He explains that concierge medicine is one of the only ways to treat patients with rare, chronic diseases like Lyme: because abnormal immune system responses to diseases are incredibly complex, unique to each individual, and not yet understood, they require the custom-tailored approach of personalized medicine.
One example is how autoimmune diseases can be caused by trauma or infection. Lab reports also cannot reliably show evidence of diseases at their early onset - a patient would need to continue following up for testing.
The key is to listen to and treat each patient as a unique case, because immune system responses are unique.
O'Rourke had 8 months of severe suffering on antibiotics and an anti-malaria drug under the supervision of a Lyme specialist before finally recovering. She still keeps in contact with her practitioner and undergoes additional treatment during intense periods of her life, such as pregnancy, but has since been in much better shape.
Other patients who do not respond as well as O'Rourke to the current antibiotic protocol will hopefully be able to try the treatments coming from the persister bacteria research.
"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."
- Meghan O'Rourke