Figure. Erythema migrans of the posterior right shoulder in a patient with Lyme disease. Image courtesy of the CDC Public Health Library.
Early Disseminated Disease
The early disseminated stage of Lyme disease is characterized by symptoms from 2 weeks to months after the tick bite. Annular skin lesions smaller than those of erythema migrans may be the first sign of early disseminated disease; however, some individuals with Lyme disease do not develop these additional lesions.2,9 Nonspecific symptoms include severe headaches and neck stiffness, facial palsy, arthritis, malaise, fatigue, and migratory pain in joints, bones, and muscles.9 Atrioventricular heart block, sometimes with myopericarditis, can occur.2,9
Late-Stage Disease
Late-stage disease is defined as symptoms occurring from months to years after the tick bite. Fatigue and prolonged chronic arthritis are common nonspecific symptoms. Severe complications include encephalopathy, polyneuropathy, lymphocytic meningitis, and lymphocytoma.2,9
Recognized Complications of Lyme Disease
Recognized complications of late-stage disease include Lyme carditis,11 neurologic Lyme disease,12 and Lyme arthritis.13
Lyme carditis occurs when B burgdorferi infects the heart.11,14 The condition manifests as myocarditis and/or atrioventricular nodal conduction abnormalities.11,14 Carditis can occur any time after the early localized stage and can be fatal. Symptoms include light-headedness, fainting, shortness of breath, heart palpitations, and chest pain.11 The condition is treated with oral or intravenous antibiotics, with the choice of antibiotic and dosage based on the degree of heart block.11 Importantly, the CDC recommends that patients with suspected Lyme carditis should be hospitalized for cardiac monitoring and treated with antibiotics prior to laboratory confirmation of Lyme disease.2,11
Neurologic Lyme disease occurs when B burgdorferi infects the peripheral or central nervous system (CNS).12,14 Cranial nerve involvement can result in unilateral or bilateral facial palsy, and peripheral nerve involvement can cause radiculoneuropathy that can manifest as numbness, tingling, shooting pain, or weakness in the arms or legs.12 Though not common in the United States, CNS involvement can result in meningitis or encephalitis with associated cognitive dysfunction and memory loss.14 The condition is treated with antibiotics based on the degree of neurological involvement.12
Lyme arthritis, which occurs when B burgdorferi infects the joints, is a common complication; more than 1 in 4 Lyme disease cases reported to the CDC include Lyme arthritis as a clinical manifestation.13 The condition typically develops 1 to a few months after infection and is characterized by the swelling of 1 or more joints.13 The knee is the most commonly affected, but other large joints such as the shoulder can be involved. If untreated, Lyme arthritis can lead to permanent joint damage.13,14 Although most patients respond to a course of oral antibiotic treatment of 28 days, some patients are less responsive.2 Patients with no or minimal response may require a 2- to 4- week course of intravenous antibiotics, with referral to a rheumatologist if treatment failure persists.2
Diagnosis of Lyme Disease
Diagnosis of early localized Lyme disease may be made based on the presence of erythema migrans alone, if there is a history of exposure in an area where Lyme disease is endemic.2 If lesions are atypical and a diagnosis is not clear, laboratory testing should be performed.2,15
Serological testing for Lyme disease primarily uses US Food and Drug Administration (FDA)–cleared tests for immunoglobulin M (IgM) or immunoglobulin G (IgG) antibodies to B burgdorferi, guided by symptoms and the timeline of exposure.2,15,16 Two to 4 weeks following the tick bite, positive antibody results for IgM and negative results for IgG indicate early infection. Testing performed >1 month after infection will typically be positive for IgG and negative for IgM.2,15,16 However, this result does not differentiate between active or past infection.2,15,16 Positive IgM results >1 month are unlikely to reflect active disease unless IgG is also positive.2 Although IgM and IgG antibodies to B burgdorferi may persist for 10 years or more after infection, these responses do not indicate active infection.17 False-positive results can occur as a result of infection with other tick-borne diseases, some viral or bacterial infections, or autoimmune diseases.16
The CDC recommends testing for IgM or IgG using a standard (STTT) or modified (MTTT) 2-tiered test.2,15,16 An STTT uses a sensitive enzyme immunoassay (EIA) or immunofluorescence assay (IFA) as a first test, followed by a Western immunoblot assay for specimens yielding positive or equivocal results.2,15,16 An MTTT uses a second EIA in place of the Western immunoblot assay. FDA-cleared MTTTs became available in 20192,15,16 and may detect up to 30% more cases as compared to an STTT in patients with early Lyme disease.2
PCR-based testing (molecular testing) is not recommended for a primary diagnosis of Lyme disease because the organism is typically found in the peripheral circulation for a relatively brief period of time.2 However, testing for B burgdorferi DNA may be useful under certain circumstances. When Lyme arthritis is suspected, treatment decisions may require more definitive evidence of active infection than serology. 2 PCR detection of Borrelia DNA in synovial fluid, commonly from the knee, supports the diagnosis of Lyme arthritis (sensitivity, 78%; specificity, 100%).18