That’s a question I’ve heard more often in recent years—from patients, parents, and even colleagues. Ehlers-Danlos Syndrome (EDS) is already a complex condition with far-reaching effects. But when patients with EDS report a sudden downturn—new neurological symptoms, worsening fatigue, or cognitive decline—it’s worth asking whether something more is going on. And in some cases, that “something more” is Lyme disease.

What Is Ehlers-Danlos Syndrome (EDS)?

EDS refers to a group of genetic connective tissue disorders that affect the body’s ability to produce or process collagen. Collagen is a major structural protein found in skin, ligaments, blood vessels, and internal organs. When collagen is faulty or poorly regulated, it can lead to a wide range of systemic problems.

The most common subtype is hypermobile EDS (hEDS), which does not yet have a confirmed genetic test but is diagnosed based on clinical criteria. Symptoms often include:

1. 1. Joint hypermobility and frequent dislocations or subluxations
   2. Chronic musculoskeletal pain and fatigue
   3. Autonomic dysfunction, such as POTS (Postural Orthostatic Tachycardia Syndrome)
   4. Fragile skin, easy bruising, or delayed wound healing
   5. GI motility issues like IBS or gastroparesis
   6. Headaches, often related to cervical instability or cerebrospinal fluid leaks
   7. Proprioceptive deficits (difficulty sensing joint position, leading to balance problems)
   8. Neurodivergent traits including sensory sensitivity or overlapping ADHD/OCD features

Because EDS affects multiple body systems, patients often see several specialists before receiving a unifying diagnosis. Even then, many feel their symptoms aren’t fully explained by connective tissue dysfunction alone.

How Is EDS Diagnosed—and What Are the Limitations?

Ehlers-Danlos Syndrome (EDS) refers to a group of connective tissue disorders, most of which are genetically distinct and testable. However, the most common form—hypermobile EDS (hEDS)—does not yet have a confirmed genetic marker.

That means hEDS is diagnosed clinically, based on physical findings and personal/family history. The 2017 diagnostic criteria for hEDS include:

1. 1. Generalized joint hypermobility (measured using the Beighton score)
   2. Systemic features of connective tissue laxity (such as skin findings, hernias, or mitral valve prolapse)
   3. Positive family history and exclusion of other heritable connective tissue disorders

There is currently no blood test, scan, or genetic panel that can confirm or rule out hEDS. This can lead to delays in diagnosis—or misdiagnosis—especially when symptoms overlap with other chronic illnesses like Lyme disease or POTS.

Genetic testing is available for other forms of EDS (such as classical, vascular, or kyphoscoliotic types), but these are much rarer and typically have more distinctive features or complications.

✅ Common Misunderstandings to Address

Myth: “My genetic test was negative, so I don’t have EDS.”
Fact: A negative genetic test doesn’t rule out hEDS—because we don’t yet know the gene involved.

Myth: “Men don’t get EDS.”
Fact: EDS occurs in all sexes, though it may be underdiagnosed in men. Males may present differently, or may not seek care until symptoms become severe.

Myth: “You can’t have EDS and another chronic illness.”
Fact: EDS often coexists with other complex conditions—especially Lyme disease, POTS, MCAS, fibromyalgia, and IBS. Recognizing overlapping diagnoses is key to effective treatment.

How Lyme Disease Can Complicate EDS

Lyme disease is caused by the bacterium Borrelia burgdorferi, transmitted by blacklegged ticks. It can affect the joints, nervous system, heart, and brain—and in some people, it persists even after standard treatment, leading to what’s known as Post-Treatment Lyme Disease Syndrome (PTLDS).

When Lyme disease or a co-infection like Babesia, Bartonella, or Anaplasma is layered on top of EDS, it can push the body into deeper dysfunction:

1. Joint and Muscular Pain

EDS already causes joint instability and pain. Lyme disease can trigger migratory arthritis, myalgia, and tendonitis, making pain more unpredictable and harder to manage.

2. Fatigue and Exercise Intolerance

Fatigue is common in EDS due to poor energy regulation and deconditioning. Lyme disease can worsen fatigue dramatically, especially when associated with immune activation, Babesia-related oxygen delivery issues, or sleep disruption.

3. Neurologic and Autonomic Symptoms

Many EDS patients experience symptoms like dizziness, lightheadedness, or fainting due to POTS. Lyme disease can also cause dysautonomia, peripheral neuropathy, and cranial nerve involvement—which may mimic or magnify EDS-related issues.

4. Cognitive Dysfunction (“Brain Fog”)

Cognitive issues in EDS are often subtle but can become debilitating when Lyme disease is involved. Patients may notice word-finding difficulties, memory lapses, or trouble concentrating, which are also seen in Lyme-related encephalopathy.

5. Mood and Sensory Dysregulation

Anxiety, depression, and sensory sensitivity are frequently reported in EDS. Lyme disease can add neuropsychiatric symptoms including panic attacks, insomnia, emotional volatility, and sensory hypersensitivity—especially when the infection involves the central nervous system.

When to Suspect More Than EDS

I don’t assume every EDS patient has Lyme disease. But I do pay attention when symptoms include:

1. 1. A clear shift or downturn after outdoor exposure
   2. Cyclical patterns of worsening and partial improvement
   3. Sudden onset of new neurological or cognitive symptoms
   4. Unexplained anxiety, mood swings, or sleep disturbances
   5. Poor response to EDS-directed therapy

In these cases, it’s reasonable to ask whether Lyme disease—or another co-infection—is complicating the picture.

A Case That Illustrates the Overlap

A patient in her mid-20s with diagnosed hEDS came to me after struggling for over a year with worsening fatigue, dizziness, and word-finding problems. She had already seen a cardiologist, neurologist, geneticist, and rheumatologist. Everything was chalked up to “EDS progression.”

But her symptoms began after a hiking trip in the Northeast, and she described “feeling poisoned” ever since. Her labs showed signs of past tick exposure. We started treatment for Lyme disease and Babesia. Within months, her energy improved, her POTS stabilized, and her cognitive symptoms eased. She still had EDS—but the superimposed infection was finally addressed.

Final Thoughts

Lyme disease doesn’t replace EDS. But it can complicate it—sometimes dramatically.

When EDS patients experience a sharp decline or unexplained new symptoms, it’s worth asking whether a persistent infection is making things worse. Ignoring that possibility can delay meaningful recovery. But exploring it with an open mind can change the trajectory of someone’s life.