Chronic Lyme: Genetic susceptibility

Lyme disease affects ~476,000 people a year in the US, mostly in the Northeast and upper Midwest, but is now found in almost all states. It is also a disease that is controversial, causing heated online arguments, misunderstood patients, and sometimes wacky cures.[ref][ref]

Genetic variants impact how Lyme disease affects you and how well antibiotics work to cure Lyme. I’ll explain how genes interact with chronic Lyme and possible solutions.

Members will see their genotype report below, plus additional solutions in the Lifehacks section. Consider joining today 

Background on Lyme Disease:

In North America, Lyme disease is caused by Borrelia burgdorferi, a bacteria carried by black-legged (deer) ticks.

Symptoms of Lyme include:

  • fever
  • headache
  • fatigue
  • skin bull’s-eye rash – erythema migrans

The CDC’s data on Lyme disease dates back to 1991, but reports of Lyme disease go back to the mid-1970s. The number of cases has grown steadily since the early ’90s, and the areas where the disease is found have spread across the country.[ref]

In Europe, Lyme is also present and sometimes called Borreliosis. Cases can involve genospecies of Borrelia, including B. afzeliiB. garinii, and B. valaisiana.[ref][ref]

The Borrelia species are a type of bacteria known as a spirochete. Our immune system has difficulty recognizing this bacterial spirochete because the surface proteins continually change, which keeps the pathogen one step ahead of the acquired immune response.[ref]

An excellent overview of the history of Lyme disease can be found in PMC7946767.

Can Lyme disease be completely cured?

Several weeks of antibiotic treatment will cure Lyme disease for most people.[ref]

Unfortunately, not everyone reacts the same way to Lyme disease. Genetic variants can cause some people’s immune systems to act differently towards the Borrelia species, and other genetic variants can influence how well antibiotics work within your cells.

Screenshot from PMC8046170, another great overview of Lyme.

What is chronic Lyme disease?

People use the term chronic Lyme to indicate they still have symptoms such as fatigue and brain fog after undergoing antibiotic treatment for Lyme disease.

There seems to be a lot of swirling controversy regarding the diagnosis of chronic Lyme because it was initially dismissed by some physicians or thought to be a made-up illness. Even recent articles, such as this one, use terminology such as “supposed symptoms” and claim that the “medical establishment maintains that there is no such thing as chronic Lyme”.

The term chronic Lyme is also often applied to people who don’t feel well (fatigue, brain fog) but also haven’t ever had blood tests that show up positive for Borrelia burgdorferi. The vague usage and alternative medical diagnoses have caused a big backlash from mainstream medical people.

Chronic Lyme seems to be a fairly polarizing topic that leaves patients getting the short end of the stick.

Encouragingly, research is now catching up on chronic Lyme symptoms and treatments.

Researchers and doctors now use the term Post Treatment Lyme Disease (PTLD). There are now hundreds of solid studies on PTLD syndrome showing the physiological and cellular changes in people with PTLD.

What is Post Treatment Lyme Disease Syndrome (PTLD)?

PTLD syndrome is much easier to define than chronic Lyme. After receiving standard treatment for Lyme (several weeks of antibiotics), some people continue to have ‘clinically relevant’ pain, fatigue, sleep disturbance, depression, and lower quality of life. Usually, the blood tests for these people are normal. This has been well documented in several studies.[ref]

PTLD affects between 10 and 20% of people treated for Lyme, according to official estimates. Other studies show that mild symptoms, whether ‘clinically relevant’ or not, remain for half or more of patients after treatment.[ref][ref]

Symptoms used in research studies to identify PTLD include:[ref]

  • muscle pain
  • joint pain
  • fatigue
  • memory problems
  • difficulties concentrating and problems finding words
  • impact on daily activities

While these symptoms can also be due to other underlying causes, a recent study found that people with a history of Lyme disease were five times more likely to meet the criteria for PTLD than those with no prior Lyme diagnosis.[ref]

A recent study found that the long-term cognitive problems in PTLD continued without improvement for 12+ months after completing treatment. More encouragingly, the fatigue scores did improve a little over the course of a year.[ref]

What causes PTLD? There are several possibilities.

  • Bacteria (B.burgdorferi) remain even after aggressive antibiotics.[ref]
  • The inability of some antibiotics to kill Borrelia burgdorferi in biofilm-like structures.[ref]
  • Inflammatory Borrelia burgdorferi components remain after the bacteria are killed.[ref]

The question then becomes: Why do 10 -20% of people treated for Lyme not recover completely?

With over 400,000 Lyme cases per year just in the US, that could leave 60,000 people per year who deal with chronic, long-lasting symptoms. One study estimates that by 2020 the cumulative number of people dealing with PTLD could be as high as 1.9 million.[ref]

One study found that patients with the bull’s-eye rash (erythema migrans) were 3-times less likely to end up with chronic Lyme when compared to patients with disseminated Lyme (later symptoms).[ref] Perhaps a stronger initial immune reaction determines who gets PTLD.

A recent study showed that non-viable components of B. burgdorferi stimulated a higher immune response in brain cells than the total bacteria.[ref] Components of the bacteria wouldn’t be affected by antibiotics, which may explain why taking more rounds of antibiotics doesn’t knock out the infection.

What is different in people with persistent Lyme?

Genetics can play a role in how well treatments for Lyme disease work and help us understand what is happening. A 2019 study found that genetically based hyperinflammation may play a role. The chronic Lyme patients had imbalanced IL-6 along with elevated IL-1β and IL-8 (inflammatory cytokines).[ref]

Proteomics studies look at the differences in the blood proteins of people with chronic Lyme compared with people who had Lyme and recovered and those who never had Lyme. The research shows a clear difference in people with PTLD.

A new study found that 35 gene biomarkers could be used to identify chronic Lyme. Several immune system pathways are involved. Interestingly, a couple of the genes are also related to epilepsy (CACNB4, ALDH7A1, SCN3A) which could be a molecular reason for the neurological symptoms of PTLD.[ref]


Chronic Lyme Genotype Report

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Not a member? Join here. Membership lets you see your data right in each article and also gives you access to the member’s only information in the Lifehacks sections.

 

Genetic variants that impact how well treatments work:

ABCB1 gene: controls how the cells export medications (like antibiotics) back out of the cell.

Check your genetic data for rs1128503 (23andMe v4, v5; AncestryDNA):

  • A/A: typical risk of PTLD
  • A/G: increased risk of post-treatment Lyme disease syndrome[ref]
  • G/G: typical risk of PTLD

Members: Your genotype for rs1128503 is .

Genetic variants that impact your body’s immune response to Lyme:

TLR1 gene: part of the body’s immune response system

Check your genetic data for rs5743618 (23andMe v4 only):

  • C/C: 1.9x more likely to have antibiotic-refractory Lyme arthritis[ref]
  • A/C: typical Lyme risk
  • A/A: typical Lyme risk

Members: Your genotype for rs5743618 is .

HLA-DRB1: part of the body’s immune response system

Check your genetic data for rs660895 (23andMe v4, v5; AncestryDNA):

  • G/G: increased risk of Lyme arthritis, rheumatoid arthritis[ref]
  • A/G: increased risk of rheumatoid arthritis
  • A/A: typical risk

Members: Your genotype for rs660895 is .

TLR2 gene: codes for a part of the immune system response to pathogens

Check your genetic data for rs5743708 (AncestryDNA only):

  • A/A: probably less likely to have Lyme (rare genotype)
  • A/G: much less likely to have advanced-stage Lyme[ref]
  • G/G: typical

Members: Your genotype for rs5743708 is .

ANO10 gene: codes for a protein involved in macrophages and cellular volume in the immune response

Check your genetic data for rs41289586 (23andMe v5 only):

  • C/C: typical
  • C/T: increased risk of Lyme[ref]
  • T/T: increased risk of Lyme

Members: Your genotype for rs41289586 is .


Lifehacks

If you find a tick and have symptoms of Lyme, the earlier you get treated, the better the odds are of a complete recovery.[ref][ref]

There are several ongoing clinical trials for different protocols to determine the best treatments for Lyme, so hopefully, more answers will be available soon.[ref]

Medication options:

Antibiotics:

Regarding chronic Lyme, research shows that more antibiotics after the initial course aren’t likely to help.[ref][ref]
Pulse dosing with ceftriaxone after other antibiotics doesn’t seem to work very well either.[ref]

A randomized controlled trial found that amoxicillin (20-day course) was a little more effective than azithromycin (7-day course).[ref] If you have a choice of antibiotics and no allergies to either, amoxicillin might be your better option — but this is definitely one of those things to talk with your doctor about.

Steroids:

In a trial of steroids along with antibiotics for Lyme disease associated with facial palsy, the results showed worse outcomes for patients with steroids.[ref]

Disulfiram:

The anti-alcohol abuse drug disulfiram was identified as a highly active compound against Borrelia. Three case studies of people with PTLD treated with disulfiram showed positive results. Disulfiram also is a drug candidate for treating parasites and viruses.[ref] The case studies are open access, so you may want to read them and talk with your doctor (especially about the side effects, which include psychiatric disturbances).[ref]

Research on natural treatments for chronic Lyme:

There are a lot of websites that sell natural cures for chronic Lyme disease, but it can be hard to tell if they really work or not. I’ll cover the research-backed options here.

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About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering and also an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.