Skip to main content

Lyme Disease

Lyme disease is the result of a bite by a tick and is associated with three different species of ticks. The clinical manifestations associated with Lyme disease are described as variable in severity as well as result in a diverse number of characteristics that affect a multitude of body systems. The manifestations are divided into three key phases: 1) Early Localized Disease 2) Early Disseminated Disease 3) Late Lyme Disease 

  • Early localized disease is notable for the distinct skin lesion, erythema migrans which is typically apparent within a month from the initial bite. It is important to note that not all erythema migrans are the characteristic "bullseye" lesion but all have a notable amount of erythema and often vesicular lesions in the central portion of the lesion. The classic "bullseye" rash is notable for central clearing with a distinct spot of necrosis in the center of the lesion. Data shows that up to 80% of patients present with this integumentary system manifestation. During this phase, there may be associated symptoms that are similar to viremia. 
  • Early disseminated disease characteristics include multiple erythema migrans lesions and cardiac and/or neurological findings. Cardiac findings are rare but may include heart block, cardiomyopathy, or pericarditis. Neurological findings are predominant and range from mild findings like headache to meningitis or nerve palsies. The highest reported manifestation involves the musculoskeletal system and include migratory arthralgias. Essentially any body system can be involved at this stage so the clinician should also be aware for involvement in the lymphatic system, liver, kidneys, as well as ocular findings. 
  • Late Lyme disease highlights the persistent arthralgias which can involve the large joints, particularly the knee joint, and other neurological findings such as encephalopathy or polyneuropathy. The timeline for the development of late Lyme disease is variable and can precipitate months to years following the acute infection. 

Of note is the long-standing clinical symptoms that can persist following primary treatment for Lyme disease. Symptoms of fatigue, headache, cognitive strain, and arthritic pain may be reported for months following treatment and is called post-Lyme disease syndrome. This phenomenon can last for 6-12 months and the criteria for this syndrome includes confirmed diagnosis of Lyme disease, treatment with a recommended regimen, as well as persistent subjective symptoms (>6 months) despite therapy. Referral to a Lyme disease specialist is recommended to assess for complications like synovitis or neurological symptoms that interfere with quality of life or functionality. Additionally, it is not recommended to continue long-term antibiotic therapy in patients with post-Lyme disease syndrome and has been linked to increased mortality in some cases.


The CDC has recently published new guidelines for diagnostic testing for Lyme disease and can be found by clicking here. Prior to testing the clinician should assess for the following to guide the need for diagnostic investigation: 1) Risk of exposure 2) Clinical manifestations as previously described that may indicate that the patient is experiencing symptoms from one of the three phases of disease. Testing is not recommended for patients that present with nonspecific symptoms or those that live in an endemic area which remain asymptomatic


Of note, the clinician should not perform serologic testing during the early localized disease stage or following treatment during the early phase when only erythema migrans is present. The clinical application regarding this guidance is related to the fact that antibodies have not likely developed and could lead to a false-negative result and halt or delay treatment. Two algorithms are available and are dependent on the availability of the testing within each clinical setting. 1) Traditional: EIA or IFA followed by a Western blot if the first result is positive (recommended for suspected late disease) 2) Two sequential EIA (recommended for early disease detection). Caution: The IgM Western blot testing is susceptible to false-positive and the progression of disease is an important component to interpretation of this diagnostic study. It is not recommended to interpret the IgM but rather the IgG when interpreting these results. It is important to note that not all patients seroconvert but several do; therefore, it is not recommended to repeat antibody testing due to the lack of knowledge of how long antibodies persist. Reinfection can occur and should be suspected if a patient with prior history of Lyme disease presents with a new onset of erythema migrans within a new calendar year. However, data shows that reinfection with Lyme disease is less likely for those patients that developed Lyme arthritis and thought to be connected to the higher antibody titer which holds longer immunity.

Differential Diagnosis

  • Chronic fatigue syndrome
  • Fibromyalgia
  • Myofascial pain syndrome
  • Polymyalgia rheumatica
  • Hypothyroidism
  • Inflammatory myopathies
  • Chronic traumatic encephalopathy