Chronic Lyme arthritis: A mystery solved?

In 1975, researchers from Yale investigated an epidemic of 51 patients with arthritis who lived near the woodsy town of Lyme, Connecticut. The most common symptom was recurrent attacks of knee swelling. A few had pain in other joints, such as the wrist or ankle. Many had fever, fatigue, and headache. Some remembered a round skin rash before the onset of knee swelling.

We now know that Lyme disease is an infection acquired from tick bites, caused by a spiral bacterium named Borrelia burgdorferi. After a tick bite, Borrelia bacteria wriggle through the skin away from the bite site. This leads to a circular red rash, known as erythema migrans. In its more advanced stages, erythema migrans may take on a bullseye appearance. Many people are unaware of the rash, as it is usually painless, and ticks may bite in less visible locations, such as a buttock or shoulder blade.

Lyme disease is diagnosed with blood tests that detect antibodies to B. burgdorferi. Two-step testing is traditionally performed. A rapid enzyme immunoassay is performed first. If this is positive, a more time-consuming Western blot test is sent for confirmation. The FDA recently approved two rapid tests for Lyme disease that are performed simultaneously, reducing the turnaround time.

Lyme disease often leads to Lyme arthritis

Although Lyme disease may affect many organs, such as the heart and nervous system, joint involvement tends to be the most common and persistent manifestation, resulting in joint swelling and pain. About 60% of people who are infected with Lyme develop arthritis unless they receive antibiotics.

In most, Lyme arthritis resolves after 30 days of treatment with an oral antibiotic, such as doxycycline or amoxicillin. Individuals with persistent symptoms despite an oral antibiotic usually respond to treatment with an intravenous antibiotic for 30 days. However, about 10% of those with Lyme arthritis fail to respond to antibiotic treatment, for reasons that have long been unclear.

Fragments from Lyme bacteria persist in joints, even after the bacteria are killed off

A new study published in Proceedings of the National Academy of Sciences sheds light on this medical mystery. To keep from spilling open, bacteria have rigid cell walls made of a matrix of protein and sugars, called peptidoglycan. Most bacteria recycle their peptidoglycan when they grow and divide, but the peptidoglycan of B. burgdorferi has a peculiar structure, and the bacteria is unable to reuse it. Instead, it dumps it into its immediate surroundings, like a microbial litterbug.

This peptidoglycan collects in the joints where B. burgdorferi is found. Almost all patients in the PNAS study with Lyme arthritis had peptidoglycan in their joint fluid. Most of them also had specific antibodies to peptidoglycan in the joint fluid, suggesting that the peptidoglycan was driving the inflammatory process. These antibodies were not found in fluid from people with other joint conditions, such as rheumatoid arthritis, osteoarthritis, or gout.

Patients with Lyme arthritis who did not get better with antibiotics still had peptidoglycan in their joint fluid. However, their joint fluid did not contain detectable B. burgdorferi DNA. This suggests that even after the bacteria were killed off, the peptidoglycan stayed behind, and stimulated further inflammation. This may explain why people with Lyme arthritis who do not respond to antibiotics may improve with medications that damp down the immune system, such as methotrexate or TNF inhibitors.

How to prevent tick-borne illness

High-risk regions for infection include the Atlantic coast from Maine to Virginia, as well as Minnesota, Wisconsin, and Michigan. Lyme disease was once rare in Canada, but has been steadily ratcheting its range northward as a result of climate change.

If you live in an area where Lyme disease is common, some simple steps can minimize the risk of tick bites:

• Avoid scrubby areas with bushes, high grass, and leaf litter, where ticks abound.
• When walking in the woods, stick to the center of trails.
• Tick repellents containing picaridin, IR3535, or 20% DEET will provide several hours of protection to exposed skin.
• Clothing and camping gear can be treated with sprays containing 0.5% permethrin.
• Looking at your body in a full-length mirror will help you to identify and remove ticks.
• When checking children for ticks, pay special attention to the scalp and ears, the shoulder blades, the waist, belly button, behind the knees, and between the legs.
• Ticks are vulnerable to heat and dehydration. Washing your clothes in hot water, or putting them in the dryer on high heat, should kill ticks hiding in them.
• If you find ticks attached to your body, use fine-tipped (jeweler's) tweezers to remove them. Grasp them next to the skin and apply steady, gentle pressure. Do not yank or twist the tick, as this may cause its mouth parts to break off and stay embedded in your skin.
• Do not apply nail polish or petroleum jelly to the tick, or try to burn it off.
• Clean the bite site with soap and water, iodine, or rubbing alcohol.
• If you develop a rash at the bite site or feel ill, see your doctor.