But perhaps, most importantly:

Lyme arthritis can develop because the Borrelia burgdorferi bacterium has an unusual chemical composition (Jutras BL, 2019).

Components from the Borrelia bacteria may persist after initial infection and act like immunogens. An immunogen triggers an immune response from the immune system. This may contribute to or cause the excessive inflammation seen in Lyme arthritis. It can occur even after the Lyme bacteria have been killed off (Jutras BL, 2019).

Borrelia burgdorferi bacteria dies during the early stages of Lyme Disease transmission (Donta ST, 2021). It is thought that Borrelia is no longer present in the synovial fluid of the joints after antibiotics. But a component of the Borrelia bacteria, called the peptidoglycan (PG), may persist and cause a continued immune response (Lochhead RB, 2021). PG prompts pro-inflammatory responses during the infection and even post-Lyme infection (Donta ST, 2021).

A peptidoglycan is part of the cell wall, found in all bacteria including Borrelia burgdorferi. The peptidoglycan or PG forms a mesh around the cell membrane and provides resistance against intracellular pressure to prevent the flow of fluids across the cell membrane.

The Borrelia bacteria is different from other bacteria. Borrelia burgdorferi does not have a PG recycling pathway. Other bacteria do. In normal bacteria, 40–50% of their PG is degraded in the normal remodeling and recycling process (Jutras BL, 2019). In gram-negative bacteria, the majority of PG is recycled (Jutras BL, 2019).

But the peptidoglycan of Borrelia burgdorferi has a different structure and the bacteria is unable to reuse it. Instead, Borrelia dumps the PG into its immediate surroundings. So large amounts of PG fragments are released into the immediate location of the Borrelia bacteria (Donta ST, 2021).

PG then collects in the joints where Borrelia is found (Jutras BL, 2019). In fact, Lyme arthritis patients have peptidoglycan in their joint fluid (Jutras BL, 2019). They also typically have specific antibodies to peptidoglycan in the joint fluid, suggesting that the peptidoglycan is driving the inflammatory process (Jutras BL, 2019).

PG stimulates immune pathways and causes inflammation. PG from gram-positive bacteria can induce acute arthritis in mice and rats. PG stimulates pro-inflammatory cytokines to be produced in mice with Lyme Disease (Jutras BL, 2019).

In humans, PG from the Borrelia burgdorferi bacteria stimulates interleukin 1 (IL-1) to be produced (Jutras BL, 2019). This causes skin reactions characteristic of inflammation.

One study looked at patients with Lyme arthritis who did not get better with antibiotics. They found these patients still had peptidoglycan and IgG antibodies against Borrelia burgdorferi peptidoglycan in their joint fluid (Donta ST, 2021). But the joint fluid no longer had detectable Borrelia DNA (Donta ST, 2021).

PG is also found in Lyme arthritis synovial fluid samples from Lyme arthritis patients both before and after oral and IV antibiotics. This means the PG material remains in these patients long after the Borrelia burgdorferi bacteria has been killed (Jutras BL, 2019).

All major pro-inflammatory markers are significantly up-regulated in the synovial fluid of Lyme arthritis patients. PG may cause inflammation without the normal anti-inflammatory response that usually compensates for the inflammation (Jutras BL, 2019). Control samples of synovial fluid from patients with other forms of arthritis (rheumatoid, osteoarthritis, fibromyalgia and gout), or a torn ACL, did not have these antibodies against PG. This tells us that the immune system’s IgG response was specific to PG from the Borreli bacteria (Jutras BL, 2019).

Is Post-infectious Lyme Arthritis an Autoimmune Issue?

Autoimmunity is suspected. PG is elevated in the synovial tissue of post-infectious Lyme arthritis patients for months to years after antibiotics. So even after Borrelia and the infection itself has been cleared, there is still an immune response to PG and autoantigens that may contribute to autoimmunity. Furthermore, differences in PG-specific immune responses among different people with Lyme arthritis may contribute to variability in the severity of the arthritis symptoms (Jutras BL, 2019).

Certain features that confirm the autoimmunity process have been seen in post-infectious Lyme arthritis. For example, Interferon gamma (IFN-gamma) is upregulated (Lochhead RB, 2021). IFN-gamma is a pro-inflammatory cytokine involved in inflammation and autoimmunity, thought to be a regulator of immune responses and inflammation. It activates and stimulates macrophages, natural killer cells and neutrophils.

At the same time that pro-inflammatory IFN-gamma is upregulated, IL-10, an anti-inflammatory cytokine, is downregulated (Lochhead RB, 2021). IL-10 has a critical role in limiting the immune response to pathogens. Dysregulation of IL-10 is linked to immune system issues in response to infection and an increased risk for autoimmune disease (Iyer SS, 2012).  This combination contributes to on-going inflammation and the potential for autoimmunity seen in post-infectious Lyme arthritis (Lochhead RB, 2021).

This may explain why people with Lyme arthritis who do not respond to antibiotics often improve with medications used in autoimmunity treatment (Donta ST, 2021).

Treatment in Conventional Medicine

In conventional medicine, treatment for long-lasting post-infectious Lyme arthritis is either drugs, or an operation, or both.

The first port of call is to try antibiotics as the standard treatment. Treatment is typically 30 days of antibiotics. If there is still a little residual joint swelling after 30 days of oral antibiotics, then 30 more days of oral antibiotics is recommended (Arvikar SL, 2015). For patients who have moderate-to-severe joint swelling after 30 days of oral antibiotics, the next step is an IV antibiotic (Arvikar SL, 2015).

A small percentage of patients may continue to have persistent arthritis for months or years after both oral and IV antibiotics (Arvikar SL, 2015), meaning the antibiotics did not work. In these cases, the standard treatment in conventional medicine is to take immunosuppressive drugs commonly used for autoimmune conditions and/or a synovectomy (Miller JB, 2021):

Antibiotics: If antibiotics are not successful, a patient with post-infectious Lyme arthritis can try DMARDs, a category of anti-inflammatory drugs that dampen immune responses. DMARDS are used with rheumatoid arthritis, and other autoimmune conditions such as ankylosing spondylitis, psoriatic arthritis, and systemic lupus erythematosus. They decrease pain and inflammation, reduce or prevent joint damage and preserve the structure and function of the joints (Cohen S, 2022).

Immunosuppressive drugs: Almost all patients with persistent Lyme arthritis get better when treated with immunosuppressive drugs, including non-steroidal anti-inflammatory drugs, corticosteroids, and other antirheumatic drugs, such as methotrexate or tumor necrosis factor-alpha inhibitors (Donta ST, 2021). These are types of drugs used in autoimmune conditions to damp down the immune system response.

Surgery: Synovectomy is a procedure in which the synovial tissue surrounding a joint is removed. The goal is to provide pain relief when the synovial membrane or the joint lining becomes inflamed and irritated and cannot be controlled by medication. It is used in conditions like Lyme arthritis. The knee is the joint most often selected for synovectomy as it is the joint most often affected by chronic inflammation.

How does Functional Medicine Treat Lyme-related Joint Pain and Arthritis?

While these treatment approaches may help, there are always side effects from long term pharmaceutical use and risks with surgery. In our clinic, we always look for natural treatment approaches. We use medications too but always look to less-invasive solutions with the least side effects first.

There are various things we do when treating Lyme Disease, chronic Lyme symptoms and Lyme arthritis:

Co-infections: We test and check for Lyme co-infections. Ehrlichia, Anaplasma, Bartonella and others are co-infections that may be transmitted through the same tick bite. These possible infections need to be addressed for any Lyme treatment to be complete. 

Herbs: We use various herbs with Lyme Disease. Lyme is a complex microbe so working with and trying out different herbs gives the best chances of success. Japanese knotweed is antimicrobial and anti-inflammatory. Cat’s claw is anti-inflammatory and antimicrobial, stimulates white blood cells and supports immune function. Andrographis, Cistus and turmeric reduce inflammation. Adaptogenic herbs combat stress and regulate the HPA axis.

Supplements: It is important to cover possible nutrient deficiencies with a multi-vitamin /mineral formula. Medicinal Reishi mushrooms have beta-glucans that boost the immune system. Omega 3 reduces inflammation. Monolaurin is antibacterial, antiviral and antifungal, helping to fight pathogens that cause Lyme and common Lyme co-infections. It is important to use a biofilm buster to ensure all of the Lyme, or other, bacteria are treated and eliminated. Bacteria can burrow into tissue and hide from the antimicrobials. With something to break down the biofilm, the bacteria are exposed to the antimicrobials and can be eliminated.

Anti-inflammatory diet: Inflammation can be reduced though a better diet. We like the Paleo or the gluten-free Mediterranean diet best to decrease inflammation, pain and autoimmune-type flare-ups.

Exercise: Exercise is always beneficial but in cases of illness, it needs to be at an appropriate level. Start with physical therapy as supervision to make sure you don’t overdo it. Bike riding is very good for the knees. Being too sedentary is actually associated with immune dysfunction and toxin build-up, which are two things that can worsen Lyme symptoms.

Stress reduction and management: We want to maintain proper hormonal balance and regulate cortisol and keep it at healthy levels. To cope with stress, we recommend meditation, yoga, tai chi, guided mediations, apps and other resources. Each person needs to find a stress management method that works best for them.

Sleep: Good sleep is critical to maintain strong immune function and general good health.

Gut heath: Gut health is the foundation of overall health. 70-80% of immune function is based on good gut health. At a minimum, try prebiotics and probiotics.

Toxins: Reducing toxin exposure and possibly detoxing toxins help the immune system to function well.

In the end, healing Lyme Disease and its various symptoms is an on-going process. It is not based on one specific drug, supplement, herb or therapy. We employ a range of different immune-boosting, health-promoting strategies to strengthen the immune system and keep pathogens under control.

In our clinic, we treat Lyme Disease, any post-Lyme chronic symptoms and Lyme-relayed arthritis or post-infectious Lyme arthritis. We are experts at diagnosing and treating Lyme Disease and its multiple symptoms. We use both natural and pharmaceutical approaches, depending on the individual case.

** Please stay tuned for our next Blog!  **

If you are a clinician wanting to learn more about treatment of Lyme Disease, please check out our clinician training programs here.