Lyme disease is a tick-borne bacterial infection caused by spirochetes in the Borrelia burgdorferi sensu lato group, transmitted to humans by Ixodes ticks during a blood meal lasting more than 36 hours. The Centers for Disease Control estimates roughly 476,000 US cases each year based on insurance claims, with 95% concentrated in the Northeast, upper Midwest, and mid-Atlantic.
Lyme disease (ICD-10: A69.2) is a multisystem inflammatory illness caused by infection with spirochetal bacteria in the Borrelia burgdorferi sensu lato complex. In North America, almost all cases are caused by Borrelia burgdorferi sensu stricto, with rare cases due to Borrelia mayonii (identified in the upper Midwest by Pritt and colleagues in 2016). In Europe and Asia, Borrelia afzelii and Borrelia garinii are the dominant pathogens and produce somewhat different clinical pictures — afzelii is more often linked to chronic skin involvement (acrodermatitis chronica atrophicans) and garinii to neurological disease. The bacteria are transmitted by hard-bodied ticks of the Ixodes genus: Ixodes scapularis (blacklegged tick) in the northeastern and upper midwestern United States, Ixodes pacificus on the West Coast, and Ixodes ricinus across most of Europe.
The key symptoms of Lyme Disease are: Erythema migrans rash — an expanding red or pink area at the tick-bite site appearing 3-30 days after exposure, often with central clearing producing a target appearance, growing larger than 5 cm and present in 70-80% of early cases., Flu-like illness with low-grade fever, chills, headache, muscle aches, joint aches, fatigue, and tender lymph nodes — commonly accompanies the rash and can occur without it., Multiple erythema migrans lesions appearing days to weeks later as the spirochetes disseminate through the bloodstream, often smaller and rounder than the primary lesion., Facial nerve palsy producing drooping of one side of the face, sometimes both sides — bilateral facial palsy in an endemic area is Lyme disease until proven otherwise., Lymphocytic meningitis with severe headache, neck stiffness, and photophobia — typically less acute than bacterial meningitis but persistent over days to weeks., Radiculoneuritis with sharp, shooting, often nocturnal pain in a nerve-root distribution; called Bannwarth syndrome when combined with meningitis and cranial neuropathy in European cases., Lyme carditis with palpitations, lightheadedness, syncope, or chest discomfort — caused by fluctuating atrioventricular conduction block (first-, second-, or third-degree AV block)..
Diagnosis of Lyme disease combines clinical pattern, exposure history, and selective laboratory testing — never serology in isolation. The 2020 IDSA/AAN/ACR guideline (Lantos et al.) is the current US standard. In a patient with erythema migrans who lives in or has visited an endemic area, the diagnosis is clinical and antibiotics should be started without waiting for serology, because the antibody response is often still negative in the first 1-2 weeks of infection. Outside this scenario, serology is the cornerstone: either a standard two-tier protocol (a sensitive enzyme immunoassay followed by IgM and IgG Western blots) or, since the CDC's 2019 update, a modified two-tier protocol using two different EIAs back-to-back. IgM blots are interpretable only within the first 30 days of illness; IgG-positive disease later than that points to true infection, while persistent IgM positivity is a frequent source of overdiagnosis. PCR has a defined role in synovial fluid (sensitivity 70-80% in untreated Lyme arthritis) and in cerebrospinal fluid for some neuroborreliosis cases, but it is not validated on whole blood for routine diagnosis. CSF antibody index (intrathecal antibody production) supports the diagnosis of neuroborreliosis when meningitis or radiculoneuritis is suspected. Routine testing of asymptomatic people, post-treatment 'cure' testing, and screening of non-specific fatigue without exposure or objective findings are explicitly discouraged because false positives outnumber true positives in low-pretest-probability populations.
Outcomes after early antibiotic treatment are excellent. Over 90% of patients with erythema migrans treated with the recommended course are symptom-free at 6 months. Facial palsy resolves in 85-95% over 1-3 months; AV block in Lyme carditis reverses in over 95% within 1-6 weeks of antibiotics. Lyme arthritis responds to first-line oral therapy in 60-70% and to combined oral plus intravenous regimens in over 90% long-term, though a small subgroup develops persistent post-infectious antibiotic-refractory arthritis driven by immune dysregulation rather than ongoing infection. Roughly 10-20% of treated patients report persistent fatigue, pain, or cognitive symptoms lasting more than 6 months — this is post-treatment Lyme disease syndrome (PTLDS). Most PTLDS symptoms improve over 1-2 years; longer antibiotic courses do not accelerate that recovery and carry meaningful harm. Untreated Lyme disease progresses unpredictably: some patients clear the infection spontaneously, but others develop late arthritis, neurological disease, or in Europe acrodermatitis chronica atrophicans years after the bite. Death from Lyme disease is rare and almost always due to fulminant Lyme carditis.
Refer to an infectious disease specialist for Lyme carditis, neurological manifestations (meningitis, encephalitis, severe radiculoneuritis, atypical facial palsy), Lyme arthritis that does not resolve after a 28-day oral course, suspected co-infections with Anaplasma or Babesia, treatment failures, pregnancy with active Lyme disease, and persistent symptoms after recommended antibiotic therapy. Most cases of straightforward erythema migrans are managed safely in primary care or urgent care, especially in endemic areas where clinicians see the rash regularly.
Find specialists →The erythema migrans rash typically begins to fade within 48-72 hours of starting antibiotics and resolves over 1-2 weeks. Fever, headache, and fatigue improve within 3-5 days. Facial palsy begins recovering within weeks but full resolution may take 3 months. Lyme carditis with AV block usually reverses within 1-6 weeks of IV antibiotics. Lyme arthritis improves over weeks to months; the knee may take 3-6 months to return to baseline. Persistent post-treatment symptoms, if they occur, gradually settle over 6-24 months in most patients.
During acute illness and the first 2 weeks of antibiotic therapy, rest and light activity are appropriate; avoid strenuous exercise until fevers, joint swelling, and cardiac symptoms have settled. For Lyme carditis specifically, hold competitive or high-intensity training until conduction has normalized and the cardiologist clears resumption. Once antibiotics are complete and acute symptoms resolve, return to regular exercise gradually over 4-6 weeks. Patients with post-treatment Lyme disease syndrome benefit from graded aerobic activity tailored to symptom tolerance.
Choose an infectious disease physician affiliated with an academic medical center in an endemic region — they see Lyme weekly during summer months and follow the current IDSA/AAN/ACR guideline. Beware clinicians advertising 'chronic Lyme' protocols with prolonged or repeated IV antibiotics outside guideline indications: three randomized trials show those regimens do not work and can cause serious harm. For neurological or cardiac involvement, look for joint management with neurology or cardiology at a center with cardiac monitoring capacity.
Medically reviewed by AIHealz Medical Editorial Board · May 12, 2026
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