The clinical manifestations of Lyme disease can be divided into three separate stages: Stages 1 (localized erythema migrans), Stage 2 (disseminated infection) and Stage 3 (persistent infection).  Some patients with Lyme disease may only go through one of these stages, but others experience all three (Steere, 1989). Most patients do not go through all three stages, and some patients only experience Stage 3 without ever showing symptoms of Stage 1 or 2 (Kraus et. al., 1991).  Stage 1 Lyme disease typically begins with flu-like symptoms, and is often mistaken for meningitis.  The most notable and unique symptom of Lyme disease is erythema migrans, a rash that appears in 60-80% of cases.  This rash begins at the site of the bite as a small red papule, and anywhere from 3-23 days after the bite it spreads.  The rash is erythematous and surrounded by concentric red rings (Re et. al. 2004).  The rash appears as a result of the recruitment of immune cells to the site of infection, which attack the pathogen (Diterich and Hartung, 2001). The erythema migrans rash usually diminishes within 3 to 4 weeks regardless of whether it is treated with antibiotics or not.  The rash can reappear later (Steere, 1989).
 

Stage 2 of Lyme disease begins when the spirochete leaves the initial infection site and enters the blood or lymph. This phase of the disease usually occurs 8-10 weeks after the initial infection (Diterich and Hartung, 2001).  Dissemination of the B. burgdorferi infection can have a wide variety of effects on different systems of the body, but the most bacterium most commonly affects the skin, nervous, and musculoskeletal systems (Steere, 1989). Stage 2 skin lesions are similar to erythema migrans, but they are smaller and spread less. Patients may also experience periodic, severe headaches and periodic musculoskeletal pain in the joints, muscles, tendons, bursae, and bone (Steere, 1989).

Stage 2 cardiac and neurological sequelae appear anywhere from weeks to years after the initial infection (Re et. al., 2004).  Fifteen to twenty percent of patients develop neurological abnormalities such as meningitis, encephalitis, cranial neuropathy, and peripheral neuropathy (Steere, 1989). Cranial neuropathy typically manifests in facial palsies. These neurological abnormalities of Stage 2 Lyme disease typically last for weeks or months, unless the infection becomes chronic (Steere, 1989).   Cardiac abnormalities are less common than neurological abnormalities and occur in 4-8% of Lyme disease patients. The most common cardiac abnormalities include atrioventricular block, myopericarditis, and mild left ventricular dysfunction, but these symptoms are usually short-lived, lasting between three days and six weeks (Steere, 1989). A major musculoskeletal dysfunction associated with second stage Lyme disease is Lyme arthritis, which affects 60% of Lyme disease patients. Typically this symptom does not appear until an average of six months after the onset of disease. Attacks of joint pain are sporadic, usually affecting the knee (Steere, 1989).

Stage 3 infection is defined as chronic or persistent infection.  Lyme arthritis is one of the most common indicators of persistent infection, where arthritic episodes last for long periods of time and may cause permanent joint damage through the wearing down of cartilage and bone.  The knee is the most common joint affected.  By definition, chronic arthritis is joint inflammation that lasts for more than one year without subsiding.  Although Lyme arthritis is often classified as chronic, most patients who experience chronic arthritis only have it for 3-4 years (Steere, 1989).  The exact mechanism through which B. burgdorferi causes Lyme arthritis is not understood with certainty, yet 10% of people infected with Lyme disease develop chronic Lyme arthritis (Philip and Johnson, 1994). Chronic Lyme arthritis is typically associated with chronic infection as well as presence of the bacterium in the synovial tissue and fluid of the joints (Philipp and Johnson, 1994). 

Persistent infection can also affect the peripheral and central nervous system, which have their onset over one year after the initial infection.  Nervous sequelae include encephalomyelitis, encephalitis, dementia, demyelination disorders, and other more subtle neurological abnormalities such as memory loss and behavioral changes (Steere, 1989). Cognitive problems, sleep disturbance, and fatigue are also common (Diterich and Hartung, 2001).  Neuroborreliosis, a nervous disorder that manifests in 20-25% of Lyme disease patients who present with erythema migrans, is possibly the most dangerous side-effect of Lyme disease (Steere, 2001). Neuroborreliosis is chronic in 5% of patients who never receive antibiotic treatment. Lyme encephalopathy may also develop which manifests in minor cognitive abnormalities (Steere, 2001).

Five percent of Lyme disease patients develop cardiac abnormalities during Stage 3.  Similar to Stage 2, the most common cardiac abnormalities of Stage 3 are atrioventricular block, myopericarditis, left ventricular dysfunction, cardiomegaly, and even fatal pancarditis (Steere, 2001).  Stage 3 Lyme disease can also affect the skin through a condition called acrodermititis chronica atrophicans, which is caused by lymphocyte and plasma cell infiltration of the dermal and subcutaneous layers of the skin. This epidermal abnormality is characterized by red coloration, swelling, and atrophy (Diterich and Hartung, 2001).

This page was created for an undergraduate Immunology course, Biology 307, at Davidson College in the Spring semester of 2007 under Dr. Sophia Sarafova (sasarafova@davidson.edu)

Please direct all comments and questions to Meredith Prasse (meprasse@davidson.edu)