Early localized disease: Erythema migrans occurs in approximately 80% of infected patients.  Patients, after exposure, can develop erythema at the site of a bite due to localized immune reaction to tick antigens.  Usually, within several days the lesion begins to expand into the classical erythema migrans rash. EM may reach 20 cm in diameter.  EM lesions are usually

found in the axilla, popliteal fossa, inguinal area, and beltline.  Multiple lesions are indicative of spirochetemia, not multiple tick bites. Lesions typically are painless but may itch or have slight burning.  Lesions feel warm to the touch.  

Initially, the lesion is uniform, but a central clearing can develop as the rash expands.  One study found in infected patients confirmed by PCR, the lesions were homogenous in 59%, had central erythema in 32%, and central clearing in 9%.  In a prospective study of 79 patients with culture-confirmed Lyme disease, other early clinical manifestations included: fatigue 54%, anorexia 26%, headache 42%, neck stiffness 35%, myalgias 44%, arthralgias 44%, regional lymphadenopathy 23%, and fever 16%.15

Early disseminated disease

Neurological findings of early disseminated disease include lymphocytic meningitis, cranial nerve palsies (especially bilateral bell’s palsy), radiculopathy, poly/mononeuropathy, cerebellar ataxia, and encephalomyelitis., Cardiac manifestations include AV heart block, myopericarditis, and sudden cardiac death.,  Ocular symptoms may be present and consist of conjunctivitis, iridocyclitis, optic neuropathy, keratitis, retinal vasculitis, choroiditis, and uveitis., 

Late Lyme disease

Intermittent or persistent arthritis, principally involving the knee, is a hallmark of late Lyme disease.  Fibromyalgia may also occur months after infection.  Late neurologic manifestations of Lyme disease are different than those seen in early disease.   Lyme encephalopathy characterized by subtle cognitive impairment and axonal polyneuropathy, which presents as spinal radicular pain or paresthesias, are the late manifestations seen in the US.,

Post-Lyme disease syndrome

Constitutional symptoms such as headache, arthralgias, and fatigue may linger after treatment.  These symptoms gradually lessen in intensity and usually resolve within 6-12 months., The IDSA has developed detailed inclusion and exclusion criteria for Post-Lyme syndrome. 5-15% of patients with Lyme disease may develop Post-Lyme syndrome.  An expert panel of 3 societies does not support the theory that persistent spirochete infection, post adequate treatment, is the cause of post Lyme syndrome.18,31,  Patients who have persistent arthritis where B. Burgdorferi has been cleared do not benefit from further antibiotic treatment.  Symptoms usually resolve within 5 years.

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