What is Lyme disease?

Lyme disease is an infectious disease caused by Borrelia burgdorferi spread by ticks. Typical symptoms include fever, headache, fatigue and a characteristic skin rash called erythema migrans. When the infection is left untreated it can spread to joints, the heart and the central nervous system.

Discovery of Lyme disease

Lyme disease is named after the town Old Lyme in Connecticut. The Connecticut Department of Health asked the CDC to investigate a mysterious outbreak of juvenile arthritis back in the 1970’s. Researchers noticed that some of the patients also presented with a red circular rash with central clearing. This rash was later referred to as erythema chronicum migrans.

In Europe a similar disease was reported. After a tick bite European scientists described the same chronic skin rash that was accompanied by a long list of strange symptoms involving the heart, skin, joints and central nervous system. In Europe they suspected that this disease was caused by a spirochete because the early stage of this disease responded to treatment with antibiotics.

In 1981, microbiologist Willy Burgdorfer discover that there were spirochetes in the gut of a collection of ticks he was studying in a search to find another tick borne infection called Rocky Mountain spotted fever. While observing the spirochetes he knew he had just discovered the elusive cause of erythema chronicum migrans in Europe and Lyme disease in the United States. The spirochetes were named after its discoverer: Borrelia burgdorferi.

It took a few extra days for Willy Burgdorfer to find the presence of similar spirochetes in the intestines of the European tick, Ixodes ricinus. The related Borrelia species that he found were eventually called Borrelia garinii and Borrelia afzelii and would be known as the causative agents of the European variant of Lyme disease.

Borrelia burgdorferi

The bacteria that cause Lyme disease are from the genus Borrelia. Borrelia bacteria are spirochetes. Spirochetes have a corkscrew shaped appearance by which they can be recognized under the microscope.

Borrelia are divided in two groups: Lyme disease causing Borrelia and relapsing fever causing Borrelia. Lyme disease is transmitted by black legged ticks of the  Ixodes species and relapsing fever causing Borrelia are spread by soft body ticks (tick borne relapsing fever) and lice (louse borne relapsing fever).

Lyme disease is caused by Borrelia burgdorferi in the United States and Borrelia afzelii or Borrelia garinii in Europe. Read more about the presence of Lyme disease throughout the world in the next chapter Lyme disease worldwide.

Lyme disease symptoms

Lyme disease is divided into 3 stages: stage 1: localized infection, stage 2: disseminated infection and stage 3: chronic and neurological infection.

Stage 1: localized infection

In the early stage of Lyme disease the skin at the site of the tick bite becomes infected with Borrelia burgdorferi bacteria which usually causes a typical round or oval skin rash that expands slowly around the bite. This skin rash is called erythema chronicum migrans. This means chronic migrating redness. It can appear from one day to one month after the tick bite.

This can be accompanied with flu-like symptoms such as achiness, chills, fever, sweats, fatigue, malaise, headache, stiff neck, sore muscles, joint pain, swollen lymph nodes and sore throat. The combination of the erythema chronicum migrans and the flu-like symptoms are the primary manifestations of the early stage of Lyme disease.

Stage 2: early disseminated infection

The symptoms of the second stage of infection can be difficult to attribute. Symptoms include severe fatigue, fever, pain, intermittent weakness and achiness of muscles and joints, numbness in arms and legs, vision changes, cognitive difficulties, short term memory problems and problems with multitasking. Because most of these symptoms are very subjective, can’t be observed by the doctor and are not specific for Lyme disease and can also happen in other conditions, the diagnosis of second stage Lyme disease can be challenging.

More objective symptoms of early disseminated neurological infection include Bell’s Palsy, meningitis with severe headache and stiff neck. Cardiac symptoms include passing out and feeling faint. Infection of the heart can cause an abnormally slow heart rate, irregular heart palpitations or unexplained difficulty tolerating exercise. Meningitis and carditis are potentially serious and deadly conditions of Lyme disease and warrant immediate medical attention.

Stage 3: chronic and late stage Lyme disease

Late stage Lyme disease can result when treatment was unsuccessful or delayed because due to unrecognized symptoms or misdiagnosis. The late disseminated stage of Lyme disease occurs months to years after the initial infection and have a big impact on the health and quality of life of a patient.

When the Lyme spirochete infects the joint this causes a monoarthritis of one or multiple major joints. Often it affects the knees. This condition is called Lyme arthritis. Fluid accumulates in affected joints which is accompanied by pain and swelling.

Neurological Lyme disease is another late stage condition that can also be debilitating and difficult to diagnose. When the brain is affected this can result in a chronic, sometimes subtle encephalopathy that causes symptoms such as concentration difficulties, fatigue, mood disturbances such as anxiety and depression, memory loss and impairment of cognition, confusion and word finding problems. Other neurological symptoms that include the peripheral nervous system are numbness and tingling, burning and pain in extremities, shooting and stabbing pains. Psychiatric manifestations include but are not limited to paranoia, depression, anxiety and hallucinations.

Table of symptoms 

Erythema migrans

  • 70% gets a skin rash 7-14 days after the infection (some say only 30% get a skin rash)
  • May be accompanied with flu-like symptoms (but it’s not a requirement)
  • Skin rash can differ from the bull’s-eye shape or doesn’t appear at all

Heart problems

Joint problems

  • Monoarthritis of major joints (preference for the knee)

Neurological problems

Late neurologic

  • Encephalitis (subtle)
  • Chronic encephalopathy
  • Encephalomyelitis (mimics MS and movement disorders like Parkinson’s) (Will be coded under 8A45.0Y in the upcoming ICD11 revision)
  • Dementia (Will be coded under 6D85.Y in the upcoming ICD11 revision)

Lyme disease diagnosis

According to the CDC, Lyme disease is a clinical diagnosis – based on your medical history, symptoms and exposure to ticks. The diagnosis is supported by laboratory testing.

ELISA and WesternBlot blood tests are used to detect antibodies against Borrelia burgdorferi. These tests are very insensitive in the early phase of the disease and a negative test result cannot rule out the infection. In later stages these tests are thought to perform much better but are still not 100% accurate.  When a tests returns negative it can still be Lyme disease.

In Germany, some laboratories work with an LTT-test or Elispot. This is a blood test that detects a cellular immune response to Borrelia. A recent study from the Netherlands concluded that this test cannot differentiate between active- and passed infection and specialists advise against its use. The test isn’t validated for Lyme disease. Currently no test can fully rule out the infection or confirm a cure.

Case surveillance criteria

For the CDC to recognize a Lyme disease case for surveillance purposes there must be ‘objective’ symptoms such as Bell’s Palsy, monoarthritis, and positive blood tests. These symptoms don’t have to be present for someone to have a late stage chronic Lyme infection. The absence of abnormalities does not rule out the infection and the patient might have debilitating symptoms while tests come back normal.

Co-infections

Ticks can carry many different pathogens – bacteria, protozoa, viruses and nematodes and transmit all these infections during a bite at the same time.

Tickborne infections in the United States include Lyme disease, Babesiosis, Anaplasmosis, Ehrlichiosis, Relapsing Fever, Tularemia, Rocky Mountain Spotted Fever (RMSF) and possibly Bartonellosis.

Diagnosis of these co-infections might be difficult. Babesia and Bartonella infections in particular can be difficult to diagnose and might resist or persist the treatments that are given for Lyme disease. Since the discovery of Lyme disease in 1981, researchers found over 15 tick-borne infections that were unknown before.

Lyme disease treatment

Treatment depends on the stage of the disease and the manifestations. In the early stage of the infection antibiotics for a duration of 14-21 days is usually sufficient to cure the infection.

Treatment of late stage Lyme disease can be a little bit more complicated. When Lyme disease causes Lyme arthritis it is usually treated with a 4 week course of antibiotics which might be repeated or given intravenously when a patient does not fully respond.

Neurological Lyme disease is treated with intravenous antibiotics for 2-4 weeks because intravenous antibiotics are thought to have a better penetration into the central nervous system.

Jarisch-Herxheimer reaction

After starting antibiotic therapy for Lyme disease you can experience a Jarisch-Herxheimer reaction. This is a reaction to endotoxin-like products released by the death of harmful bacteria during antibiotic treatment. The release of these bacterial toxins results in a systemic inflammatory response. A Jarisch Herxheimer reaction is usually not life-threatening

A Jarisch-Herxheimer reaction usually starts between 24-72 hours after the start of antibiotic therapy for Lyme disease and can cause fever, chills, stiffness/rigor, muscle pain, hypotension, headache, heart palpitations, hyperventilation and anxiety. The intensity of the reaction indicates the severity of the inflammation.

The reaction is associated with the treatment of syphilis, leptospirosis, Lyme disease and relapsing fever. There have been reports of a Jarisch-Herxheimer reaction accompanying treatment of infections such as Q-fever, bartonellosis and brucellosis.

Ibuprofen, aspirin or acetaminophen can be taken to minimize the reaction. Drinking enough fluids and taking rest are also recommended.

Prognosis

The prognosis of Lyme disease patients is usually good when the disease is diagnosed and treated in the early stage of the infection. Unfortunately still 10-20% of patients have persistent symptoms of fatigue, headache, muscle aches and fogginess of the brain. What causes these ongoing symptoms is not understood. Because there is no test that can tell your doctor whether all bacteria are killed some doctors prescribe the antibiotics for a little longer or repeat the course of antibiotics when these symptoms persist.

In a small group of patients that developed Lyme arthritis, the swelling of the joints persists after oral and intravenous antibiotics apparently eliminated the bacteria. The complication is thought to result from the development of autoimmunity in affected joints. This condition is called antibiotic refractory Lyme arthritis and is treated by most doctors with anti inflammatory medications or disease-modifying antirheumatic drugs.

Patients that develop late stage neurological Lyme disease are most at risk of developing severe and chronic symptoms that persist after treatment. This condition can be severe and debilitating and is called post treatment Lyme disease syndrome (PTLDS). The cause of these persistent symptoms is currently unknown. A minority of scientists believe that the Borrelia burgdorferi bacteria persisted antibiotic treatment and think this condition needs to be treated with long-term antibiotic therapy. A larger group of scientists believe that this condition is the result of a yet unknown autoimmune process.