Lyme Disease


Borrelia burgdorferi, B. mayonii

Lyme disease blood smear

Where Found

Lyme disease is most frequently reported from the Upper Midwestern and northeastern United States. Some cases are also reported in northern California, Oregon, and Washington. In 2015, 95% of Lyme disease cases were reported from 14 states: Connecticut, Delaware, Maine, Maryland, Massachusetts, Minnesota, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, Vermont, Virginia, and Wisconsin.

Incubation Period

3-30 days

Signs and Symptoms

Localized Stage*

  • Erythema migrans (EM)—red ring-like or homogenous expanding rash; classic rash not present in all cases. See examples on following pages.
  • Flu-like symptoms—malaise, headache, fever, myalgia, arthralgia
  • Lymphadenopathy

*During the localized (early) stage of illness, Lyme disease may be diagnosed clinically in patients who present with an EM rash. Serologic tests may be insensitive at this stage. During disseminated disease, however, serologic tests should be positive.

Disseminated Stage

  • Multiple secondary annular rashes
  • Flu-like symptoms
  • Lymphadenopathy

Rheumatologic Manifestations

  • Transient, migratory arthritis and effusion in one or multiple joints
  • Migratory pain in tendons, bursae, muscle, and bones
  • Baker’s cyst
  • If untreated, arthritis may recur in same or different joints

Cardiac Manifestations

  • Conduction abnormalities, e.g. atrioventricular node block
  • Myocarditis, pericarditis

Neurologic Manifestations

  • Bell’s palsy or other cranial neuropathy
  • Meningitis
  • Motor and sensory radiculoneuropathy, mononeuritis multiplex
  • Subtle cognitive difficulties
  • Encephalitis, encephalomyelitis, subtle encephalopathy, pseudotumor cerebri (all rare)

Additional Manifestations

  • Conjunctivitis, keratitis, uveitis
  • Mild hepatitis
  • Splenomegaly

Lyme Disease or STARI?

An erythema migrans-like rash has also been described in humans following bites of the lone star tick, Amblyomma americanum. This  condition has been named Southern Tick-Associated Rash Illness (STARI). Although the rash may be accompanied by flu-like symptoms, long-term sequelae have not been reported. Because the cause of STARI is unknown, diagnostic blood tests are not available.

Lone star ticks can be found from central Texas and Oklahoma eastward across the southern states and along the Atlantic Coast as far north as Maine.

It is not known whether antibiotic treatment is necessary or beneficial for patients with STARI. Nevertheless, because STARI resembles early Lyme disease, physicians often treat patients with the same antibiotics recommended for Lyme disease.

General Laboratory Findings

  • Elevated erythrocyte sedimentation rate
  • Mildly elevated hepatic transaminases
  • Microscopic hematuria or proteinuria
  • In Lyme meningitis, CSF typically shows lymphocytic pleocytosis, slightly elevated protein, and normal glucose.

Laboratory Diagnosis

  • Demonstration of diagnostic IgM or IgG antibodies in serum. A two-step testing protocol is recommended. If the first step is negative, no further testing is recommended. If the first step is positive or indeterminate (sometimes called “equivocal”), the second step should be performed. The overall result is positive only when the first step is positive (or equivocal) and the second step is positive (or for some tests, equivocal).
  • Isolation of organism from a clinical specimen

Notes on Serologic Tests for Lyme Disease

  • Serologic tests are insensitive during the first few weeks of infection. During this stage, patients with an EM rash may be diagnosed clinically. While not necessary, acute and convalescent titers may be helpful in some cases.
  • In persons with illness duration of more than 1 month, only IgG or combined IgG/IgM testing should be performed (not IgM alone). A positive IgM test alone in a patient with illness duration of more than 1 month is not reliable for diagnosing current disease.
  • Due to antibody persistence, single positive serologic test results cannot distinguish between active and past infection.
  • Serologic tests cannot be used to measure treatment response.
  • Infection with other diseases, including some tickborne diseases, or some viral, bacterial, or autoimmune diseases, can result in false positive test results.

NOTE: Coinfection with B. microti and/or A. phagocytophilum should be considered in patients who present with initial symptoms that are more severe than are commonly observed with Lyme disease alone, especially in those who have high-grade fever for more than 48 hours despite appropriate antibiotic therapy or who have unexplained leukopenia, thrombocytopenia, or anemia. Coinfection should also be considered in patients whose erythema migrans skin lesion has resolved but have persistent flu-like symptoms.


Treatment regimens listed in the following table are for localized (early) Lyme disease. See references for treatment of patients with disseminated (late) Lyme disease. These regimens may need to be adjusted depending on a person’s age, medical history, underlying health conditions, pregnancy status, or allergies. Consult an infectious disease specialist regarding individual patient treatment decisions.


Lyme disease treamtnet regimen
Age Category Drug Dosage Maximum Duration, Days
Adults Doxycycline 100 mg twice per day, orally N/A 10-21*
Cefuroxime axetil 500 mg twice per day, orally N/A 14-21
Amoxicillin 500 mg three times per day, orally N/A 14-21
Children Amoxicillin 50 mg/kg per day orally, divided into 3 doses 500 mg per dose 14-21
Doxycycline 4 mg/kg per day orally, divided into 2 doses 100 mg per dose 10-21*
Cefuroxime axetil 30 mg/kg per day orally, divided into 2 doses 500 mg per dose 14-21

*Recent publications suggest the efficacy of shorter courses of treatment for early Lyme disease.

NOTE: For patients intolerant of amoxicillin, doxycycline, and cefuroxime axetil, the macrolides azithromycin, clarithromycin, or erythromycin may be used, although they have a lower efficacy. Patients treated with macrolides should be closely observed to ensure resolution of clinical manifestations.


Aguero-Rosenfeld ME, Wang G, Schwartz I, et al. Diagnosis of Lyme borreliosis. Clin Microbiol Rev 2005;18(3):484-509.

American Academy of Pediatrics. Lyme disease (Lyme borreliosis, Borrelia burgdorferi infection). In: Pickering LK, Red Book: 2012 Report of the Committee on Infectious Diseases. 29th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2012:474–479.

Centers for Disease Control and Prevention. Updated CDC Recommendation for Serologic Diagnosis of Lyme Disease. MMWR 2019;68(32);703.

Centers for Disease Control and Prevention. Notice to readers: caution regarding testing for Lyme disease. MMWR 2005;54:125–126.

Centers for Disease Control and Prevention. Recommendations for test performance and interpretation from the second national conference on serologic diagnosis of Lyme disease. MMWR 1995;44:590–591.

Halperin JJ, Baker P, Wormser GP. Common misconceptions about Lyme disease. Am J Med 2013;126(3):264.

Hu LT. Lyme Disease. Ann Intern Med 2016 Nov 1;165(9):677.

Kowalski TJ, Tata S, Berth W, et al. Antibiotic treatment duration and long-term outcomes of patients with early Lyme disease from a Lyme disease-hyperendemic area. Clin Infect Dis 2010;50(4):512-520.

Marques A. Lyme Disease: A Review. Curr Allergy Asthma Resp 2010, 10:13-20.

Sanchez E, Vannier E, Wormser GP, Hu LT. Diagnosis, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: A review. JAMA. 2016 Apr 26;315(16):1767-77.

Smith RP, Schoen RT, Rahn DW, et al. Clinical characteristics and treatment outcome of early Lyme disease in patients with microbiologically confirmed erythema migrans. Ann Intern Med 2002;136:421–8.

Stanek G, Wormser GP, Gray J, et al. Lyme borreliosis. Lancet 2012;379(9814):461-73.

Steere AC. Borrelia burgdorferi (Lyme disease, Lyme borreliosis). In: Mandell GL, Bennett JE, Dolin R, editors. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 6th ed. Philadelphia, PA: Churchill Livingstone; 2005;2798–2809.

Stupica D, Lusa L, Ruzi´c-Sablji´c E, et al. Treatment of erythema migrans with doxycycline for 10 days versus 15 days. Clin Infect Dis. 2012;55(3):343-350.

Erythema Migrans Rashes

The erythema migrans (EM) rash occurs in 70–80% of patients with Lyme disease. EM rashes expand slowly over a few days after which they may develop a “bull’s-eye” appearance consisting of a red ring with central clearing. However, EM may take alternate forms—solid lesions, blue-purple hues, and crusted or blistering lesions have all been documented. The rash is not painful or pruritic, but it may be warm to the touch. If early localized Lyme disease is not treated, patients may develop multiple secondary circular rashes as spirochetes disseminate throughout the body.

Classic EM—Circular red rash with central clearing that slowly expands




Photo courtesy of Taryn Holman.

Bluish hue without central clearing




Photo courtesy of Yevgeniy Balagula.

Red, expanding lesion with central crust




Photo courtesy of Bernard Cohen.

Red, oval-shaped plaque on trunk




Photo courtesy of Alison Young.

Purple lesion on back of knee




Photo courtesy of New York State Department of Health.

multiple red lesions with dusky centers




Photo courtesy of Bernard Cohen.

Embedded tick in person's skin with mild allergic reaction




Not an erythema migrans. Allergic reactions typically appear within the first 48 hours of tick attachment and are usually <5 cm in diameter.


Special thanks to DermAtlas for providing many photographs.