Clinical Reference / Therapeutic Strategies / Borreliosis (Lyme Disease)

Borreliosis (Lyme Disease)

Key Points

  • Infection with various Borrelia species causes borreliosis, which may have cutaneous and systemic manifestations. This infection is transmitted through bites of the Ixodes species of ticks.
  • Early Lyme disease (erythema chronicum migrans) and late Lyme disease (acrodermatitis chronicum atrophicans) are the classic cutaneous complications of these infections.
  • Disseminated borreliosis may involve joints, heart, skin, eyes, and the nervous system.
  • Serologic testing is essential for diagnosis, especially in cases of systemic involvement.
  • Avoidance of tick bites is the primary prevention of Lyme disease.
  • Many late complications of Lyme disease may be prevented by systemic antibiotic therapy early in the course of infection.


Borreliosis results from the infection of the spirochete, Borrelia species. Many different Borrelia species exist with relevance to human disease. Borrelia burgdorferi is the most common cause of borreliosis in North America, and is most commonly associated with joint disease. In Europe, several Borrelia species are implicated in human disease; Borrelia afzelii and B. garinii are the most common causes of borreliosis in Europe and are typically associated with skin (B. afzelii) and neurologic (B. garinii) symptoms.

Infection typically begins as a localized skin lesion, with later dissemination to joints, heart, eyes, and the nervous system. Erythema chronicum migrans is the cutaneous eruption of early borreliosis and is the most common manifestation of Lyme disease, affecting 89% of patients in one European case series. The same European study revealed that systemic involvement is fairly uncommon, with arthritis affecting 5% of patients, early neurologic involvement in 3%, lymphocytoma in 2%, acrodermatitis chronicum atrophicans in 1%, and <1% with cardiac manifestations. Similar complication rates have been reported in American case series, with the key exception of late cutaneous presentations of borreliosis (lymphocytoma, acrodermatitis chronicum atrophicans) occurring exclusively in European individuals.

A solitary lesion of erythema chronicum migrans represents localized infection. The presence of multiple lesions of erythema chronicum migrans indicates early disseminated disease, and affected patients require systemic diagnostic evaluation. Patients with multiple erythema chronicum migrans lesions in particular require complete neurologic evaluation and lumbar puncture prior to treatment, or they should be treated as if they have neuroborreliosis. Neurologic symptoms present across a broad clinical spectrum, including facial palsy, meningitis, or meningo-radiculitis; encephalitis, myelitis and cerebral vasculitis are rare presentations. Widespread systemic involvement may occur in immunosuppressed or immunocompromised individuals.

Further diagnostic evaluation is often warranted to determine whether an individual has disseminated disease. Serologic testing involves initial testing with ELISA (for antibodies) with secondary determination of specific IgM and IgG levels. It is important to note that serologic markers may be absent when a solitary lesion of erythema chronicum migrans initially presents, and may remain negative for up to 6 weeks. In endemic areas, seropositivity may exist in four to as high as 50% of residents.

The therapeutic strategy is to eradicate the pathogenic organism. Systemic antibiotic therapy early in the course of infection may prevent disseminated infection. Prevention is possible only through avoidance of tick bites; in cases of B. burgdorferi, infection may be prevented through early removal of the tick, including the mouthparts (less than 36 hours after tick bite). No vaccines are currently available for humans.

Initial Evaluation

Erythema chronicum migrans

Acrodermatitis chronica atrophicans

These lesions may occur at the sites of prior erythema chronicum migrans. Atrophic epidermis is the hallmark. Sclerodermatous changes, with thickening and dermal induration, may also occur. Single or multiple blue-to-violaceous fibrotic nodules may arise from within lesions of acrodermatitis chronica atrophicans.


Lymphocytoma typically presents as a solitary lesion. The earlobe, nipple, scrotum, and axillary folds are common sites of involvement.

Differential diagnosis




First-line therapy: Systemic antibiotics is first-line treatment. Borreliosis will respond to tetracyclines, penicillins, most second or third generation cephalosporins, and macrolides. Therapy for two to four weeks is required. There is limited evidence to support a longer duration of treatment. Although skin lesions of erythema chronicum migrans may resolve without therapy, antibiotic treatment is still required to prevent further complications of disseminated infection. It is important to note that symptoms of fatigue and arthralgia may persist for up to three months despite appropriate treatment with systemic antibiotics.

  • Doxycycline 100 mg orally twice daily for 10-21 days. In one comparative trial, 10 days of doxycycline was equivalent to 20 days, although rare treatment failures can occur with any duration of oral therapy.
  • Amoxicillin, 500 mg three times daily for 14-21 days; this is the preferred medication in pregnancy. For children, give amoxicillin 250 mg 3 times daily or 50 mg/kg/day in 3 divided doses.
  • Patients with first-degree heart block or facial palsy as their only manifestation should be treated for 14-21 days with the aforementioned oral antibiotic regimens.
  • Patients with arthritis should receive 30 days of an oral systemic antibiotic. This 30-day course can be repeated once if symptoms do not improve. Parenteral treatment is indicated if the patient fails to respond to two courses of oral systemic antibiotic therapy.
  • Ceftriaxone is the parenteral treatment of choice, and is indicated for neurologic involvement or severe cardiac involvement. Severe cardiac involvement is defined as second-degree heart block (or more severe) or if the patient has symptomatic first-degree heart block. For both conditions, the treatment should involve ceftriaxone 2g IV daily for 14 days. Patients with severe cardiac involvement should be admitted to hospital for ongoing cardiac monitoring in addition to their antibiotic treatment.

Alternative treatment

  • In patients allergic to or intolerant of doxycycline and amoxicillin, use cefuroxime 125 mg twice daily or 30 mg/kg per day in two divided doses for 14-21 days.
  • Only in patients unable to take all three of the above medications, erythromycin 250 mg 3 times daily or 30 mg/kg/day in 3 divided doses for 14-21 days.
  • Alternative parenteral treatment for neurologic or cardiac involvement includes: cefotaxime 2 g IV every 8 hours for 14-21 days, or penicillin G sodium 3.3 million units IV every 4 hours (20 million U/day) for 14-28 days.

Subsequent steps

Regular follow-up of these patients for potential cardiac, neurologic, or arthritic sequelae is important.

Ancillary treatment

  • A single dose of doxycycline 200 mg is effective (87%) prophylaxis after a tick bite occurring in an endemic region.
  • Protective clothing and insect repellents containing DEET should be worn in endemic areas.
  • Careful skin examination after potential exposures to tick bites in an endemic region may enable early tick removal and potential avoidance of borrelial transmission.


Erythema chronicum migrans is a clinical diagnosis, as serologic testing may be negative at this stage. Treatment should not be withheld if the diagnosis is uncertain. Seek consultation or treat presumptively.

When to consult a dermatologist

  • If the diagnosis of borreliosis is not clear or if a skin biopsy is needed to confirm the diagnosis
  • For the evaluation of lesions in which acrodermatitis chronicum atrophicans or lymphocytoma are suspected

Clinical Cases

Case 1

  • 14-year-old teenage girl with a rash on the right lateral cheek present for four days
  • Skin lesion developed three days after a hike through the woods
  • No known history of tick bites
  • Otherwise healthy, feeling well

Initial evaluation

  • Exam reveals a 7 cm annular erythematous, urticarial plaque consistent with erythema chronicum migrans
  • No tick bites noted
  • Review of systems does not indicate any ocular, joint, cardiac, or neurologic symptoms
  • Recommend doxycycline 100 mg p.o. b.i.d. for 10 days
  • Follow-up in one month

One-month follow-up evaluation

  • Skin lesion now resolved
  • Review of systems does not indicate any ocular, joint, cardiac, or neurologic symptoms
  • Follow-up in three months as part of ongoing monitoring for development of symptoms and signs of disseminated infection

Three-month follow-up evaluation

  • No evidence of disseminated infection noted

Case 2

  • 18-year-old male presents with new onset unilateral facial palsy
  • History of a tick bite that occurred while camping several months prior to presentation, with development of an annular, erythematous, urticarial plaque at the site of the tick bite (suggestive of erythema chronicum migrans)
  • Otherwise healthy
  • Denies joint, cardiac, ocular, or additional neurologic symptoms

Initial evaluation

  • Reveals no skin lesions
  • Neurologic exam notable only for unilateral facial palsy
  • Electrocardiography performed in clinic is normal
  • Blood testing notable for (+) Lyme antibodies by ELISA
  • Diagnosis of Lyme-related facial palsy
  • Doxycycline 100 mg p.o. b.i.d. for 21 days

One-month follow-up evaluation

  • Denies joint, cardiac, ocular, or new neurologic symptoms
  • Facial palsy improving
  • Repeat neurologic exam is otherwise normal
  • Follow-up in one month


Marques A (2010). Lyme disease: a review, Curr All Asthma Rep, 10: 13-20.

Mullegger RR (2004). Dermatological manifestations of Lyme borreliosis, Eur J Derm, 14: 296-309.

Stanek G, Wormser GP, Gray J, Strle F (2011). Lyme borreliosis, Lancet, September e-Pub ahead of print.