Lyme Disease

Article Author:
Gwenn Skar
Article Editor:
Kari Simonsen
10/27/2018 12:31:42 PM
PubMed Link:
Lyme Disease


Lyme disease or Lyme borreliosis is the most commonly transmitted tick-borne infection in the United States and among the most frequently diagnosed tick-borne infections worldwide. Lyme disease is divided into three stages: early localized, early disseminated, and late. The early localized disease is distinguished by the red ring-like expanding rash of Erythema migrans at the site of a recent tick bite. Other symptoms experienced at this stage may be flu-like symptoms, malaise, headache, fever, myalgia, and arthralgia. Most patients only experience the symptoms of early, localized disease. About 20% of patients develop the early disseminated disease, with the most common symptoms being multiple erythema migrans lesions. Other symptoms of the disseminated stage are flu-like symptoms, lymphadenopathy, arthralgia, myalgia, palsies of the cranial nerves (especially CN-VII), ophthalmic conditions, and lymphocytic meningitis. Additionally, cardiac manifestations such as conduction abnormalities, myocarditis, or pericarditis may occur. The most common manifestation of the late disease is arthritis that is usually pauciarticular and affects large joints, especially the knees.[1][2]


In the United States, Lyme disease is caused by the bacterial spirochete Borrelia burgdorferi and is transmitted by the bite of an Ixodes genus tick, mostly commonly Ixodes scapularis. In Eurasia, the predominant causes are B. burgdorferiBorrelia afzelii, and Borrelia garinii.[3][4]


Lyme disease is most commonly reported in the  Northeastern and upper Midwestern United States. The primary states with endemic Lyme disease are Connecticut, Delaware, Maine, Maryland, Massachusetts, Minnesota, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, Vermont, Virginia, and Wisconsin. Sporadic cases have been reported in northern California, Oregon, and Washington.[5][6]


The most common and first presenting sign of Lyme disease is the erythema migrans rash, which is found in 70% to 80% of cases and appears at the site of the tick bite as an expanding, erythematous skin lesion, measuring 5 cm in diameter or larger. The lesion may present as homogeneous erythema or display a targetoid appearance. The appearance of the rash occurs one to two weeks after the initial tick bite. If untreated, disease progression may lead to other relatively common findings including early arthritis in up to 30% in some series; neurologic manifestations, 10% to 15%; or cardiac involvement, 1% to 2%.[7]


Erythema migrans histologic findings are nonspecific, usually showing a perivascular cellular infiltrate which consists of histiocytes, lymphocytes, and plasma cells. Rarely, mast cells and neutrophils are identified. A biopsy may show eosinophilic infiltrates which consist of a local reaction to the bite. Spirochetes may be identified using antibody-labeled or silver stains. Usually, a paucity of spirochetes is found in the tissues of those infected with Lyme disease.

Acrodermatitis Chronica Atrophicans

In acrodermatitis chronica atrophicans, an early biopsy may show a lymphocytic dermal infiltrate, often perivascular in location, with some vascular lymphedema and telangiectasia. Plasma cells may be seen in the cellular infiltrate. Late lesions may demonstrate epidermal thinning with loss of skin appendages. In the later stages, plasma cells may be the only feature to distinguish morphea from acrodermatitis chronica atrophicans.

Fibrotic nodules may show fibrosis of the deeper dermis and hyalinization of collagen bundles. B. burgdorferi can sometimes be cultivated from the lesions.

Borrelial Lymphocytoma

Histologic examination is performed in patients with suspected borrelial lymphocytoma when the history is not clear enough to support a diagnosis. Borrelial lymphocytoma biopsy shows a dense dermal lymphocytic infiltrate with lymphoid follicles and pseudoterminal centers. Lymphocytes with both B- and T-cell markers, occasional macrophages, plasma cells, and eosinophils are seen.

History and Physical

Localized Lyme disease is characterized by erythema migrans occurring 1 to 2 weeks after tick exposure in an endemic area. The differential diagnosis for early Lyme disease with erythema migrans includes other skin conditions such as tinea and nummular eczema. If not treated in the localized stage, patients may go on to develop early disseminated or late disease manifestations. Early neurologic Lyme disease manifestations include facial nerve (CN-VII) palsy, lymphocytic meningitis, or radiculopathy. Cardiac involvement includes myopericarditis and typically presents with heart block. Lyme arthritis is mono- or pauciarticular, generally involving large joints, most commonly the knee, and occurring months removed from the initial tick bite.


Serologic testing is insensitive during the first few weeks of infection, and patients presenting with erythema migrans rash and history of residing in or traveling to an endemic region may be treated based on clinical findings. In later stages of the disease, a 2-step approach is recommended for the serologic diagnosis of Lyme disease. The first step is to perform a quantitative screening test for serum antibodies to B. burgdorferi using a sensitive enzyme immunoassay (EIA) or immunofluorescent antibody assay (IFA). A Western blot should follow specimens with positive or equivocal results. Serologic diagnosis is sensitive (greater than 80%) for patients presenting with neurologic or cardiac manifestations.[8][9][10]

Treatment / Management

Specific treatment is dependent upon the age of the patient and stage of the disease. For patients older than 8 years of age with early, localized disease, doxycycline is recommended for 10 days. Patients under the age of 8 should receive amoxicillin or cefuroxime for 14 days to avoid the potential for tooth staining caused by tetracycline use in young children. Longer courses and parenteral antibiotics may be required for more severe manifestations such as arthritis, atrioventricular heart block, carditis, meningitis or encephalitis, although European data and newer studies demonstrate that oral treatment regimens or transitioning to oral therapy at hospital discharge may be appropriate for some patients.[11][12][13]

Differential Diagnosis

In patients with erythema migrans, a careful history and physical examination are all that is required to establish the diagnosis of Lyme disease. However, many patients with Lyme disease present with erythema migrans or extracutaneous symptoms where diagnosis becomes a challenge. In those cases, erythema migrans may never have occurred, may not have been recognized, or may not have been correctly diagnosed by the clinician.

Other problems include the following:

  • Acute memory disorders
  • Ankylosing spondylitis and rheumatoid arthritis
  • Atrioventricular nodal block
  • Cellulitis
  • Contact dermatitis
  • Gout and pseudogout
  • Granuloma annulare
  • Prion-related diseases


Stages of Lyme Disease

  1. Stage 1: Localized disease associated with erythema migrans and flu-like symptoms; Duration 1 to 30 days
  2. Stage 2: Early disseminated disease with malaise, pain, and flu-like symptoms; May affect the neurological, ocular, and musculoskeletal organs; Duration 3 to 10 weeks
  3. Stage 3: Late or chronic disease chiefly affects the joints, muscles, and nerves, May last months or years, Lyme arthritis is a hallmark of this stage.
  4. The occurrence of post-treatment Lyme syndrome is debatable.


For early cases, treatment is usually curative. However, treatment may be complicated due to late diagnosis, antibiotic treatment failure, and concomitant infection with other tick-borne diseases such as ehrlichiosis, babesiosis, and immune suppression.

Approximately 5% of patients will have lingering symptoms of fatigue, pain, or joint and muscle aches after treatment. These symptoms can last for 6 or more months. This is called post-treatment Lyme disease syndrome. Chronic Lyme disease is generally managed similarly to fibromyalgia or chronic fatigue syndrome.



  • Infectious disease expert
  • Dermatologist
  • Neurologist

Pearls and Other Issues

Based on the geographic distribution of the shared vector Ixodes scapularis, co-infections with Lyme disease and human granulocytic anaplasmosis and/or babesiosis can occur. Co-infected patients may be more severely ill at presentation, have a persistent fever longer than 48 hours after initiating antibiotic therapy for Lyme disease, or present with anemia, leukopenia, and/or thrombocytopenia. When co-infection is suspected or confirmed, treatment with an appropriate antimicrobial regimen for each infection is necessary for resolution of illness.

Enhancing Healthcare Team Outcomes

The key to Lyme disease is prevention. All healthcare workers should provide patient education on measures to prevent tick bites while hiking or working outdoors. In areas where ticks are common, cleaning up of the environment by removing the underbrush and spraying an insecticide may reduce the tick burden in the area. The nurse should educate the patient on how to remove the tick from the skin and when to seek medical assistance. The pharmacist should educate the patient on medication compliance for those who have been confirmed to have acquired Lyme disease. Even though there is a Lyme vaccine the public should be educated that the effects of the vaccine are not consistent or long-lasting; hence one should not rely on the vaccine to prevent Lyme disease.[14][15] (Level V)


The prognosis for patients who are treated for Lyme disease is excellent with no residual deficits. However, a few individuals may develop a recurrent infection if an infected tick bites them. Individuals who receive late treatment may develop neurological and musculoskeletal symptoms. Lyme arthritis is not uncommon. Some patients may develop Lyme carditis that results in a heart block and requires temporary pacing of the heart. Despite the large numbers of people affected, Lyme disease is not fatal. There continues to be a debate about the existence of post-treatment Lyme disease, but so far, this diagnosis has been promoted by the lay public and media as there is no good evidence that such a condition exists.[16][17] (Level V)

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      Contributed by James Gathany, Center for Disease Control and Prevention (CDC PHIL)


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