With the peak period for Lyme disease approaching, new guidelines help clinicians understand when to consider the ailment in patients who present to the ED, how to properly diagnose a case, and how to treat.

  • Recently, Lyme disease has spread into new regions, reaching as far south as the Shenandoah Mountains of Virginia, and north into regions of the upper Midwest and even southern Canada.
  • Patients with Lyme disease often present with erythema migrans, often called a bull's-eye rash. About two-thirds will exhibit fever, headache, or systemic symptoms. Some present with neurologic symptoms like a facial nerve palsy or radiculitis, or with arthritis.
  • Usually, a defined course of antibiotics is sufficient to microbiologically eradicate the bacteria that cause Lyme disease, but some patients report lingering symptoms.
  • Doxycycline now is recommended for children younger than age 8 years diagnosed with Lyme disease. A modified two-tier algorithm for serology produces faster results than older methods.

Recognizing potential cases of Lyme disease can be tricky, particularly for frontline providers who are not accustomed to seeing patients present with the tick-borne illness. But understanding the peculiarities of this disease has grown increasingly important in recent years. The incidence of Lyme disease has spread rapidly into regions beyond the traditional areas of the Mid-Atlantic and upper Midwest where the ailment is most common.

Paul Auwaerter, MBA, MD, clinical director of the division of infectious diseases at Johns Hopkins Medicine, says Lyme disease has been reported in New England, southern Canada, parts of the Rust Belt and Midwest, and in parts of West Virginia and Virginia. “These are all new areas that 10 or 15 years ago did not have [Lyme disease] very commonly. People practicing in these areas need be aware [of possible cases].”

To that end, new guidelines sponsored by the Infectious Diseases Society of America, the American Academy of Neurology, and the American College of Rheumatology have been established to help providers with diagnosis and treatment decisions related to Lyme disease, along with coinfections involving Lyme disease and another tick-borne illness.1

Auwaerter, a co-author of the guidelines, says by focusing specifically on Lyme disease, the authors believed they could produce simpler recommendations than previous guidelines, which addressed multiple tick-borne illnesses. Auwaerter and colleagues also applied the GRADE approach (Grading of Recommendations Assessment, Development and Evaluation) so practitioners could assess the strength of each recommendation.

Recognize the Signs

Typically, patients with Lyme disease in North America present with erythema migrans, often called a bull's-eye rash. It is a tell-tale symptom, but one patients do not always recognize.

“About two-thirds of those people will have fever, headache, or systemic symptoms, but many times they are unaware of a tick bite or unaware that they have a rash,” Auwaerter observes. “Those people might present with neurologic symptoms like a facial nerve palsy or radiculitis [pain that results from pressure on a spinal nerve], or they may present with arthritis.”

Patients with Lyme disease who present to the ED may have aseptic meningitis or endocarditis. “Any of those symptoms in someone who could have a potential tick exposure should prompt [clinicians] to think about tick-borne diseases,” Auwaerter says. “Ask about whether there is a history that might suggest there is a compatible rash recently, if it is not present, or trigger consideration of ordering Lyme serology tests.”

Auwaerter cautions there are some challenges with serology tests because they can be negative early in a Lyme infection. In fact, he says serology tests deliver negative results 60% to 70% of the time in the first week or two of a Lyme infection because it takes time for the immune system to respond.

“However, if someone has had symptoms for six weeks or longer, I think a negative Lyme serological test is sufficient and accurate to rule out concerns that the patient has Lyme disease,” Auwaerter notes.

On top of serological testing complications, Borrelia burgdorferi or Borrelia mayonii, which cause Lyme disease, are difficult to culture. Clinicians usually identify the disease when they see signs or symptoms comparable to Lyme. The incidence of Lyme disease tends to peak in children between the ages of 5 and 8 years and in adults older than age 50 years. There are some differences in presentation between these age groups.

“Particularly in children under the age of 10, they may present with an arthritis that appears more like an affected joint, especially in the hip,” Auwaerter says. “This is especially true in the New England area where there may be more erythrogenic strains of the Borrelia bacteria.” Auwaerter adds clinicians often do not see the rash, neurologic complaints, or even carditis in young children, but these symptoms may be present in teenagers and in young adults. “Carditis might affect more people in older age groups, but it is the least common manifestation [of Lyme disease],” he says.

Consider Coinfections

After making a diagnosis, treat Lyme disease with a short course of antibiotics, generally doxycycline. “Usually, a defined course of antibiotics, generally between 10 to 28 days, depending on disease presentation, is sufficient to microbiologically eradicate the bacteria,” Auwaerter explains.

Following antibiotic treatment, Auwaerter notes there are some patients who seem to experience lingering symptoms, a condition sometimes referred to as post-treatment Lyme disease syndrome. “This particular circumstance, which usually [involves symptoms of] pain and fatigue, does not [typically] respond to additional antibiotic therapy, and it is generally not advocated,” he observes. “There are some rare cases where re-treatment might be necessary.”

While some patients report symptoms even six months following antibiotic treatment, it is unclear what causes these symptoms, notes Auwaerter, although this is a focus of research. However, he says rather than diagnosing a patient with chronic fatigue syndrome or fibromyalgia, some practitioners will say the patient has “chronic Lyme disease,” a term with vague diagnostic criteria and no definition.

“You need to have symptoms compatible with Lyme disease, either early or late disease, and supportive evidence, either through an erythema migrans rash, if early, or positive serology tests,” Auwaerter says.

A small percentage of patients present with coinfections, Lyme disease and another tick-borne illness. Treatment with doxycycline should effectively treat Lyme disease as well as anaplasmosis, which also spreads by ticks. However, if a patient does not show some improvement within 48 hours of treatment, clinicians should consider other tick-borne illnesses. “Lyme disease with babesiosis is the most common [coinfection],” Auwaerter observes.

Clinicians usually identify babesiosis in contaminated blood viewed through a microscope. Generally, clinicians prescribe two medicines: atovaquone plus azithromycin or clindamycin plus quinine. The latter combination usually goes to severely ill patients.2

Experts note babesiosis can be particularly serious in patients without a spleen, who are immunocompromised, or who present with other serious health problems. There should be heightened awareness of potential coinfections in these patients.

While the new guidelines do not present any wholesale changes regarding the diagnosis and treatment of Lyme disease, there are some updates of importance to clinicians. “First, doxycycline, which is part of the tetracycline class, is now recommended for children under the age of 8,” he explains. “The FDA used to have dental enamel staining as a warning on the package information, but that seems to be very unlikely with short-course therapy.”

Auwaerter notes the American Academy of Pediatrics and the CDC also recommend short-course doxycycline for children younger than age 8 years. “Previously, pediatricians and emergency rooms prescribed amoxicillin for Lyme disease [in this group],” he says.

Another updated recommendation concerns the use of a new two-tier testing algorithm for the serologic diagnosis of Lyme disease. “The FDA has optimized what is called a modified two-tier system that includes two different enzyme immunoassays [EIA],” Auwaerter explains.

Previously, serology testing typically involved using a two-tier testing algorithm that included a first-tier test, either an EIA or an immunofluorescence assay, and then a supplemental immunoblot assay in cases in which the first test results in either a positive or equivocal result. The modified two-tier testing process replaces the immunoblot assay with a second EIA.

“A number of labs have adopted this [newer testing algorithm],” Auwaerter observes. “It works just about as well as the traditional two-tier serology [algorithm], which has been around since 1995, but there is generally a quicker turnaround and it is less expensive to perform. That is something practitioners may see, depending on the lab that the hospital uses.”

Frontline clinicians, especially those in areas where there is a higher prevalence of Lyme disease, could see an increase in cases in late spring or early summer. These are the periods when young ticks, called nymphs, are active and biting. “However, we see [Lyme disease] year-round with adult ticks biting, especially in more temperate areas where there are no hard frosts or freezes,” Auwaerter says.

Further, Auwaerter stresses signs of late disease, such as a swollen knee, can happen year-round because it take months or even a year (or longer) for these signs or symptoms to manifest.


  1. Lantos PM, Rumbaugh J, Bockenstedt LK, et al. Clinical practice guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 guidelines for the prevention, diagnosis and treatment of Lyme Disease. Clin Infect Dis 2020; Nov 30;ciaa1215. doi: 10.1093/cid/ciaa1215. [Online ahead of print].
  2. Centers for Disease Control and Prevention. Parasites - babesiosis. Treatment.