Erythema Migrans /Lyme Disease (Erythema Chronicum Migrans)

Are You Confident of the Diagnosis?

What you should be alert for in the history

Erythema migrans (EM) is the skin finding that characterizes early Lyme disease. It is the most common objective manifestation of Lyme disease and occurs in approximately 90% of cases. This lesion is so characteristic that it allowed for the accurate description of the clinical manifestations of Lyme disease many years before the causative organism was identified and serological tests were developed.

Patients may have no other symptoms at the time the rash appears, or they may experience systemic symptoms of early Lyme disease which include fever, fatigue, headache and myalgias. There may be a history of significant outdoor exposure in an endemic area, but most patients will not remember a tick bite due to the very small size of the deer tick that is the vector.

The diagnosis of Lyme disease should be considered in those who present with nonspecific illnesses in the late spring and summer in endemic areas. A complete exam of the skin should be performed to assess body areas that patients cannot see.

Characteristic findings on physical examination

EM begins as a small macule or papule at the site of the bite and enlarges slowly over days (Figure 1). The usual appearance is a circular or ovoid lesion that expands. Initially, the area is uniformly red. Later, central clearing may be observed around the initial tick bite site giving an annular appearance, which may remain erythematous. Central clearing is a function of duration of EM. The center of the lesion may become vesicular or develop necrosis. The annular appearance was very commonly described in older literature; most cases described in the U.S. in recent years have been diagnosed and treated within a week or two of onset and most have lacked central clearing on presentation. The border of the lesion remains bright red. The area may feel warm and patients may describe it as painful, burning or pruritic.

The size of an EM lesion is a function of its duration. Centers for Disease Control (CDC) criteria designate the diameter to be greater than 5 cm, so that other noninfectious manifestations of tick or insect bites are excluded, however, the size alone should not be used to exclude the diagnosis in those with consistent clinical and epidemiologic features. Some patients will present with multiple lesions (Figure 2) beyond the initial bite site, indicating early dissemination of the causative organism (Borrelia burgdorferi).

EM-like lesions are not pathognomonic for Lyme disease. An EM-like lesion has been identified in patients who live in areas that are not endemic for Lyme disease such as the southern US, but Borrelia burgdorferi has not be isolated from these lesions and serology is negative. It has been concluded that these lesions do not represent Lyme disease and it has come to be known as southern tick-associated rash illness (STARI) or Masters disease. Treatment is the same as for EM.

There is no reliable and easily available test to confirm Lyme disease at the time of the appearance of EM. The characteristic appearance makes the diagnosis and treatment should be initiated. Commercially available serologic tests that detect IgM and IgG to Borrelia burgdorferi are unreliable in early disease. Treatment at this time, which is recommended, will often block the antibody response so that later testing for antibodies to confirm the diagnosis may also be unsuccessful.

Diagnosis confirmation

The differential diagnosis includes bacterial cellulitis, contact dermatitis, arthropod bite, herpes simplex or varicella zoster infection if the lesion is vesicular, tinea infection, urticaria, fixed drug eruption and a spider bite.

Who is at Risk for Developing this Disease?

Individuals who live in areas where the common tick vector (ticks of the Ixodes, or deer tick, family) are present are at risk. In the US, these areas are throughout the Northeast from Maine to Virginia, in the Midwest (Wisconsin, Michigan and Minnesota) and the West (mostly Northern California). The geographic areas where these ticks are endemic have been reported to spread annually.

Individuals with greater outdoor exposure are more at risk, although most patients will not remember a specific tick bite. Those without exposure to wooded or grassy areas may still be at risk if they have pets that go outdoors and bring ticks into the home.

What is the Cause of the Disease?

Lyme disease is the most common tick-borne illness in the US. It is caused by B burgdorferi, a spirochetal organism that is inoculated into a human through the bite of an infected deer tick (Ixodes scapularis or Ixodes pacificus in the United States) (Figure 3). The tick needs to be attached and feeding for several hours before causing infection. The small size of this tick may prevent detection even after feeding. After inoculation of the organism, there is an incubation period of 3-30 days.

The organism replicates locally, leading to the appearance of the erythema migrans lesion. The bacteria then disseminate to multiple sites, multiple EM lesions can appear at the time of this dissemination. Local symptoms involving joints and the central nervous system may then occur.

Systemic Implications and Complications

If Lyme disease is not detected and treated at the time of appearance of erythema migrans, patients can develop clinical manifestations of early disseminated infection. These include malaise, fatigue, headache, fever and chills, generalized aches and occasionally regional lymphadenopathy. Patients may develop signs of meningeal irritation which include more severe headaches and neck pain. Some will develop signs of mild encephalopathy which include problems with memory and thinking. Hepatitis, sore throat, generalized lymphadenopathy and splenomegaly have been reported. Symptoms are usually intermittent and changing, although fatigue is commonly constant.

After several weeks to months, 15% of untreated patients will develop neurologic disease that includes meningitis, encephalitis, cranial neuritis (including bilateral facial palsy), radiculopathy, and myelitis. The cerebrospinal fluid (CSF) of patients with meningitis will usually show a lymphocytic pleocytosis and elevated protein; glucose is normal. B burgdorferi antibody can be detected in the CSF.

Five percent of patients may develop cardiac involvement, usually atrioventricular block including complete heart block. Involvement is usually temporary, and a permanent pacemaker is unnecessary. Symptomatic patients who experience palpitations, fatigue, or shortness of breath should have an EKG performed. Acute myocarditis has also been reported. Conjunctivitis is the most common ocular finding, but iritis has also been reported.

Later, (months after illness was acquired) 60% of untreated patients will experience recurring attacks of joint swelling and pain, usually in large joints, most commonly the knee and usually one or two joints. Synovial fluid will have elevated white blood cell counts, predominantly polymorphonuclear cells. Diagnosis can be confirmed by synovial fluid Borrelia polymerase chain reaction (PCR) testing, or B burgdorferi serum antibody testing.

Treatment during early Lyme disease will effectively terminate the infection and prevent later manifestations.

Treatment Options

EM, EARLY LYME (including EM and early disseminated disease)



doxycycline: 100mg orally twice a day for 14 days

amoxicillin: 500mg orally three times a day for 14-21 days

cefuroxime axetil: 500mg orally twice a day for 14-21 days

Alternatives (for patients with intolerance or allergy to all preferred agents)

azithromycin: 500mg orally daily for 7-10 days

clarithromycin: 500mg orally twice a day for 14-21 days

erythromycin: 500mg orally four times a day for 14-21 days

Children (< 8 years old)


amoxicillin: 50 mg/kg daily divided in 3 doses (maximum 500mg per dose)

cefuroxime axetil: 30 mg/kg daily divided in 2 doses (maximum 500mg per dose)


azithromycin: 10 mg/kg/day (maximum 500mg daily)

clarithromycin: 7.5 mg/kg twice a day (maximum 500mg per dose)

erythromycin: 12.5 mg/kg four times a day (maximum 500 mg per dose)

*Macrolides have lesser efficacy.

Optimal Therapeutic Approach for this Disease

Patients with ECM who may have other systemic symptoms of early Lyme disease can be treated with oral agents, without serologic testing to confirm the diagnosis. Because doxycycline has activity against other tickborne agents that can cause illness, it is often the drug of first choice. Patients that have manifestations of early Lyme disease such as cranial nerve palsy without meningitis but do not have ECM can be treated for Lyme disease in the appropriate clinical setting, with serologic testing for confirmation.

Patient Management

Patients treated for EM generally have excellent long-term outcomes after treatment. EM lesions usually resolve within 3 weeks. Ninety percent of patients are asymptomatic within 3 months. Approximately 10% of appropriately treated patients have residual vague subjective symptoms that do not require additional courses of therapy.

Patients may sustain additional episodes of Lyme disease after the first episode has resolved. Reinfection from a repeat tick bite is the most likely cause of recurrent EM. Patients should be instructed on tick avoidance including use of repellants (permethrin is best, followed by DEET), covering the skin, skin inspection, and removal of attached ticks.The tick should be removed.

The head of the tick is grabbed with a hemostat as close to the attachment to the skin as possible. Next one gently pulls back at an angle that the tick pierces the skin. Typically this is 90 degrees to the skin surface. If any parts remain after removal, a small punch biopsy can remove any remaining parts. Clean the skin afterwards with an alcohol swab or similar agent.

Prophylaxis with doxycycline can decrease the chance of developing Lyme disease if given within 3 days of a bite from an I scapularis tick. A single dose (200mg) may be used for preventing Lyme disease in specific settings: removal of an attached I scapularis tick after period of feeding, in an area of high endemicity infection in ticks and if given within 3 days of attachment.

Relapse has occurred in patients treated with cephalexin and in those treated with second-line agents such as macrolides.

Unusual Clinical Scenarios to Consider in Patient Management

I scapularis can also transmit Babesia microti causing concurrent babesiosis, a malaria-like infection, and Anaplasma phagocytophilum causing concurrent human granulocytic anaplasmosis (HGA, ehrlichiosis). Concurrent infection may confuse the clinical presentation of Lyme disease. The presence of cytopenias or persistent fever while on therapy suggests that consideration be given to concurrent infection.

Immunocompromised hosts with Lyme disease may have more frequent early dissemination.

An early report of adverse fetal outcomes in pregnant women has not been confirmed in subesquent reports. Treatment is the same for pregnant women, except that doxycycline should be avoided.

Acrodermatitis chronica atrophicans is seen in Europe as a potential late stage (stage III) lyme disease. It is caused by active infection with the European strain of Borrelia. B afzeli is felt to produce this rare fibrosing dermatitis. Atrophic skin lesions may first appear and later sclerosis develops, predominately in acral regions. This is most often seen in Europe, but with the amount of travel back and forth between Europe and the rest of the world may be seen anywhere.

Borrelial lymphocytoma is rarely reported in European nations, and it has been seen erratically in the United States. The clinical appearance is of a red dermal papule or plaque. Histology mimics lymphocytoma cutis. Many Borrelia species have been implicated and these skin lesions respond to antibiotic therapy.

What is the Evidence?

Dandache, P, Nadelman, RB. “Erythema Migrans”. Infect Dis ClinNorth Am. vol. 22. 2008. pp. 235-60. (Excellent review of clinical features and treatment.)

Wormser, GP, Dattwyler, RJ, Shapiro, ED, Halperin, JJ, Steere, AC. “The clinical assessment, treatment and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis:Clinical practice guidelines by the Infectious Diseases Society of America”. Clin Infect Dis. vol. 43. 2006. pp. 1089-1134. (Evidence-based guidelines for diagnosis and treatment of erythema migrans and other stages of Lyme disease.)

Mullegger, Robert, R. “Dermatological manifestations of Lyme borreliosis”. Eur J Dermatol. vol. 14. 2004. pp. 296-309. (Review of erythema migrans plus additional skin manifestations reported only in Europe.)

Steere, A, Mandell, GL, Bennett, JE, Dolin, R. “Borrelia burgdorferi”. Mandell, Douglas and Bennett's principles and practice of infectious diseases. 2010. pp. 3071-5. (Thorough review of pathogenesis as well as clinical manifestations and treatment of Lyme disease.)

Masters, EJ, Grigery, CN, Masters, RW. “STARI, or Masters disease: Lone star tick- vectored Lyme-like illness”. Infect Dis ClinN Am. vol. 22. 2008. pp. 361-76. (Review of current knowledge of STARI.)