What’s In a Name? A Look at Post-Treatment Lyme Disease Syndrome

“Pop icon Justin Timberlake’s recent disclosure that he has Lyme disease is drawing new attention to a common but often misunderstood illness—and may open the door to conversations between physicians and their patients.”

Joedy McCreary, Enterprise & Investigative Writer, MedPage Today

“I have yet to see any problem, however complicated, which, when looked at in the right way did not become still more complicated.”

Poul Anderson, American author

Tickborne infections are capturing more and more attention due to the expansion of tick populations fostered by climate change (global warming). (See, “More Reasons to Hate Ticks,” Germ Gems, May 14, 2025). Two tickborne diseases that are becoming increasingly problematic in the U.S. are alpha-gal syndrome and Lyme disease (LD). In today’s post, I return to LD for a more thorough look at of one of its most troubling complications, Post-treatment Lyme Disease Syndrome (PTLDS), an entity that’s in the news because it recently sidelined the 44-year-old pop-musician, Justin Timberlake.

What is LD? To understand PTLDS, a brief recap of LD is necessary. LD was first described in 1975 following the investigation of a cluster of cases of acute arthritis in Old Lyme, Connecticut. In 1981, microbiologist Willy Burgdorfer discovered the etiologic agent, the bacterium Borrelia burgdorferi carried by the blacklegged (deer) tick, Ixodes scapularis.           

Both the tick and the disease rapidly spread throughout the U.S., in particular across New England and the upper Midwest. LD soon became the most common vector-borne disease in North America. The Centers for Disease Control and Prevention (CDC) now estimates approximately 476,000 Americans are diagnosed and treated for LD each year.

Early diagnosis and treatment of LD are crucial for a full recovery. The classic symptoms and signs of the disease are: a characteristic skin rash called erythema migrans (which often appears as a red expanding rash with a bullseye or target-like appearance), fever, fatigue, headache, and muscle and joint pains. Doxycycline, a safe and inexpensive antibiotic, is usually highly effective in treating acute LD.  

There are, however, challenges to early diagnosis of LD. First, a number of patients with LD do not manifest the classic symptoms or signs of the disease. Second, the current LD laboratory tests are not always sensitive, meaning they can produce false negative results, especially in early LD. (Note: A new LD assay looks promising, and if the results of early studies—91.7% sensitivity, 90.7% specificity—hold up, this could represent a major breakthrough in the management of acute LD. See, Hicks, L. “New Lyme Blood Test Bests Standard Diagnostics in Detecting Early Disease,” Medscape, August 4, 2025). Therefore the disease goes untreated enabling it to progress to affect the joints, heart, and nervous system.

What about PTLDS? Even with early diagnosis and treatment, some LD patients do not fully recover and go on to develop PTLDS. The symptoms of PTLDS include lingering fatigue, muscle or joint pain, cognitive issues (“brain fog”), and other neurological or pain-related symptoms. These symptoms persist for at least 6 months after standard antibiotic therapy and significantly impair daily functioning.

A modeling study estimated the total number of Americans living with PTLDS to be between approximately 69,000 and 1.52 million in 2016, increasing to nearly 2 million by 2020. While the exact number of cases of PTLDS is unknown, it appears that tens of thousands of new PTLDS cases occur per year in the U.S. Current estimates suggest about 10–20% of Americans treated for LD go on to develop PTLDS—meaning roughly 10,000 to 40,000 cases per year.

There is no diagnostic test or standard biomarker for PTLDS. Long-term antibiotics have been shown to be ineffective. Therefore, treatment approaches focus on symptom management akin to those used for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) or Long COVID.

Management of PTLDS. The CDC provides a toolkit to help clinicians care for patients with PTLDS. Developed in partnership with the American Medical Association (AMA), this toolkit includes resources for both clinicians and patients and can be accessed through the AMA website or the CDC website. The goal of the toolkit is to improve the lives of patients experiencing prolonged symptoms related to PTLDS like fatigue, body aches, or difficulty thinking. All patients with PTLDS should be encouraged to access this toolkit.

Many, if not most, PTLDS patients, however, remain in urgent need of treatment that addresses their disabling symptoms. Justin Timberlake’s recent disclosure may reduce the stigma of this chronic illness and open the door to conversations between physicians and their patients about their health struggles. In addition to reassurance that researchers are searching for an effective treatment, all PTLDS patients need a physician who listens and cares because caring is always an important medicine (Rule 10). (Peterson, P., Get Inside Your Doctor’s Head, 10 Commonsense Rules for Making Better Decisions about Medical Care, Johns Hopkins University Press, 2013). 

Bewildering pathogenesis of PTLDS—what’s in a name? All the features of the pathogenesis of PTLDS, that is the mechanisms involved in its development, are not established. One thing, however, is increasingly clear: PTLDS shares the same or a similar symptom complex with a number of other chronic disabling illnesses many of which are precipitated by known infectious agents. These include Long COVID (SARS-CoV-2), chronic brucellosis (Brucella), and Q fever (Coxiella burnetii), and last, but far from least, ME/CFS, which has been linked by some studies to Epstein-Barr virus.

Fortunately, the National Academy of Sciences Engineering and Medicine is helping coordinate research efforts that ultimately will benefit patients suffering with many of these complex medical disorders. As Brian A. Fallon, MD, MPH, professor of clinical psychiatry and director of the Lyme and Tick-Borne Diseases Research Center at the Columbia University Irving Medical Center, New York City, said,  “This vision [for research] is terrific because basically it’s saying that we need to view Lyme disease similarly to the way we view other illnesses that have chronic persistent symptoms…and that we can learn a lot from sharing knowledge…The time is now.”