The diagnosis, management, and prevention of Lyme disease

Author: Margaret Trexler Hessen, MD, FACP, FSHEA, Medical Editor, Point of Care Content at Elsevier

Summer is (finally) here, and with it comes a rise in insect and arthropod populations and the diseases they transmit. Lyme disease is the most commonly reported tick-borne infection in the United States; it also occurs in some parts of Europe and Asia. Diagnosis and management can both be challenging, so as “tick season” begins, we offer a refresher on the disease, and discuss some of the dilemmas and pitfalls it presents to clinicians.

The disease is caused by various species of Borrelia, is transmitted by Ixodes ticks, and may become clinically evident after an incubation period of 3 to 32 days. In many (but not all) cases, the initial presentation includes the characteristic erythema migrans rash, an expanding red macule (usually at the site of the tick bite) that reaches a diameter of 5 cm or more, with or without a central clearing or necrosis; several of these lesions may occur if the patient has multiple bites or is bacteremic. After a period of several weeks to months, untreated patients may experience cardiac involvement characterized by conduction disturbances (including heart block) or neurologic conditions including aseptic meningitis, cranial nerve palsies, or radiculopathy. Late manifestations may develop months to years later, most commonly arthritis (usually mono- or oligoarticular and accompanied by painless effusion) or neurologic abnormalities (cranial or peripheral neuropathy, radiculopathy, encephalomyelitis). Some patients may not experience clinical manifestations at each stage; there is a continuum of disease, and stages may overlap.

Diagnostic strategy depends on the stage at which the disease is suspected. In endemic areas, the appearance of a typical erythema migrans rash can be considered diagnostic. In later stages, appropriate studies include serologic testing (ELISA followed by confirmatory Western blot) or polymerase chain reaction for the organism in infected body fluids (eg, synovial fluid).

Recommended antibiotics include doxycycline, amoxicillin, macrolides, and second- and third-generation cephalosporins; specific antibiotic doses and duration depend on the stage of disease and organ system(s) involved.

Prevention revolves around use of tick repellant and full clothing coverage. Daily body inspection to detect and remove ticks avoids the prolonged (36 hours) attachment required for transmission of infection. A postexposure dose of doxycycline 200 mg is effective in preventing disease if administered within 72 hours.


Erythema migrans: erythematous target-like plaque of Lyme disease.
The primary skin lesion of Borrelia infection is noted for centrifugal expansion, sometimes leaving a central clearing.

 

Pitfall #1: Beware the geography

If the patient does not live in or has not visited an endemic area, the diagnosis is unlikely. Neither testing nor empiric treatment is advised. In this context, the pretest probability is low, and a positive result would likely represent a false-positive. Areas of transmission are listed here: https://wwwnc.cdc.gov/travel/yellowbook/2018/infectious-diseases-related-to-travel/lyme-disease

Be aware of regional differences in the causative Borrelia species, and the need to consider alternate means of testing. Specifically, US practitioners who are evaluating patients for disease acquired in Europe or Asia should consider using a C6-based ELISA, rather than the standard ELISA for Borrelia burgdorferi.

 

Pitfall #2: Interpreting the rash

A typical-appearing rash acquired in an endemic area is sufficient for diagnosis; laboratory confirmation is unnecessary and blood tests may be negative early in the illness.

It is not unusual for an inflammatory reaction at the site of the tick bite to develop, occurring as an expanding area of erythema often associated with pruritus or burning. It can be differentiated from erythema migrans by its early appearance (1-2 days) and prompt spontaneous resolution.

 

Pitfall #3: Timeline of antibody development

IgM antibody develops within several weeks of infection, followed by the appearance of IgG antibody. Western blot results must be interpreted in light of this progression. Following a positive (or equivocal) ELISA result, Western blot criteria for confirmation are:

  • During the first month of infection, 2 of 3 IgM bands
  • After the first month, 5 of 10 IgG bands

By 8 weeks, most patients have detectable IgG antibodies; at that point, detection of IgM antibodies alone likely represents a false-positive.

 

Pitfall #4: Persistent symptoms after treatment

Some patients, particularly those who present with later stages of infection, do not achieve full recovery to baseline after antibiotics. Some patients have refractory joint pain; others have more systemic symptoms including fatigue, anorexia, muscular pain, and insomnia. The reasons are not fully understood, but several factors may play a role, including permanent damage (eg, synovial destruction) or an ongoing inflammatory response that is not defused by eradicating the organism.

Optimal management of these patients has been a topic of debate. Thorough review of the literature by the Infectious Diseases Society of America revealed little evidence of either antibiotic failure or sustained improvement following longer treatment courses; this conclusion (along with concerns about the adverse effects of prolonged antibiotics) has led both the CDC and the Infectious Diseases Society of America to recommend against such measures.

In cases in which symptoms are limited to persistent joint pain, retreatment with IV antibiotics may be considered if oral agents were used initially. Synovectomy or use of disease-modifying agents may be helpful. Symptomatic treatment is recommended for other symptoms of post–Lyme disease syndrome, but efficacy is limited and the chronicity and profound debility associated with this unexplained syndrome are a source of great frustration to patients, their families, and health care providers.

For detailed information on the diagnosis, management, and prevention of Lyme disease, see the complete Clinical Overview in ClinicalKey.

Clinical Overviews, produced by Elsevier’s team of experienced physicians and reviewed by authoritative subject matter experts, synthesize the most current, evidence-based literature. They are regularly updated to provide relevant and reliable point-of-care information for practicing clinicians.

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