What do we really know about Lyme disease? Here’s the latest science.

The hard part is what may follow: Among those who do get antibiotics, anywhere between 10 and 25 percent develop long-term symptoms — such as fatigue, brain fog or dizziness. Scientists refer to these patients as suffering from “post-treatment Lyme disease” or “post-treatment Lyme disease syndrome,” also known as PTLDS. In 2020, it was estimated that nearly 2 million people suffered from PTLDS.

There are evidence-backed treatments that can help. For example, drugs in a class called neuromodulators, such as nortriptyline, can help with brain fog or pain often seen in PTLDS. But these treatments can take time to have an effect and may involve a bit of trial and error.

“The issue is that there’s probably not one, unifying mechanism — it may be a heterogeneous disorder,” said Paul Auwaerter, a professor of medicine at Johns Hopkins University School of Medicine and former president of the Infectious Diseases Society of America. “It’s been devilishly difficult to figure out.”

It’s also important not to miss any important other medical conditions that could account for your symptoms. Auwaerter, who has been studying Lyme disease for two decades, said that people have had delays in diagnosis for cancer, ALS and other conditions that had been misdiagnosed as Lyme.

At the same time, he said, doctors should think more about tick-borne diseases and how they can relate to symptoms years down the line. The key is finding a physician you can develop a long-term relationship with.

“It’s really important to find someone who takes the time, starts from scratch, does a thorough history and exam, and reviews your prior tests,” Auwaerter said. “Then over a series of visits, you work together to find the best diagnosis that can direct care.”

What do we really know about Lyme disease?

We’ve learned so much about Lyme disease over the last five years.

We know that in untreated Lyme disease, the bacteria can spread to other parts of the body, leading to complications like carditis or arthritis. But if the condition is treated, the bacteria generally do not evade antibiotics. For example, in one study of 252 patients, in only two patients, or 0.8 percent, did the antibiotics not work; in another study of 225 patients, antibiotics worked in every single case.

But in some patients, scientists now suspect there may be an autoimmune reaction triggered by the initial infection. (Diseases like inflammatory bowel disease or multiple sclerosis may also be triggered by infection.)

In other patients, inflammation triggered by that initial, even if cleared, infection never quite dampens — perhaps because of antigens left behind by the bacteria.

Recent studies have found that PTLDS patients had elevated levels of certain autoantibodies and inflammatory mediators. Patients who had high levels of these markers after antibiotic treatment had a greater than 12-fold risk of developing PTLDS.

PTLDS also may be associated with other conditions, including postural orthostatic tachycardia syndrome (POTS), which causes your heart to beat faster than normal when you transition from sitting or lying down.

We by no means have PTLDS all figured out, but we’re getting closer to improving our approach to prevention and treatment. I’m optimistic about the Phase 2 results of a new three-dose Lyme disease vaccine that were recently published in the Lancet Infectious Diseases. The Phase 2 study found that the vaccine was safe, had few side effects and effectively helped the body create antibodies against the bacteria. Phase 3 clinical trials are underway, and Auwaerter, who is helping lead the trial, expects those results will be available by 2025 or 2026.

Other researchers are building biorepositories of patients who are infected with Lyme disease, tracking blood and urine over time to help understand the mechanisms of why some people develop long-term consequences.

Why is Lyme disease so controversial?

In the past, the ill-defined constellation of symptoms long after infection was called “chronic Lyme disease.” But the Centers for Disease Control and Prevention and others now discourage using the term. Earlier pushback against the name was based on its definition: a persistent microbial infection after antibiotics — which experts argued didn’t exist. This morphed into the idea that the symptoms “didn’t exist” either — and this is where, in the history of medicine, things got ugly.

We’ve seen a similar pattern in the story of long covid — or, before the pandemic, of Epstein-Barr virus — as validated research races to catch up to what patients are feeling. And as in these other cases, people suffering from PTLDS have been long stigmatized.

So let’s remember this: We may debate the cause of an illness and need more research to understand it — after all, that’s the very basis of good science. But someone’s suffering is not imagined.

What treatments don’t work for Lyme disease?

We have fairly sufficient evidence about many therapies that do not work for PTLDS. For example, repeated courses of antibiotics are no better than a placebo, an important lesson learned from multiple randomized-controlled trials. This data did not surprise many in the medical community as none of these trials found evidence of residual infection in the first place.

Auwaerter also cautioned against alternative therapies that may be potentially harmful — such as hyperbaric oxygen, chelation or coffee enemas.

What I want my patients to know

Cases of Lyme disease continue to rise with climate change and are spreading geographically. Recent studies estimate that around half a million people in the United States are diagnosed and treated for it every year. That number misses the people who don’t get treatment — and delays in treatment are common, especially among Black patients and people of color who do not always get a stereotypical bull’s eye rash.