Lyme Disease

What is Lyme Disease?

Lyme disease (LD) is an infection caused by Borrelia burgdorferi, a type of bacterium called a spirochete (pronounced spy-ro-keet) that is carried by deer ticks (Click here for pictures of deer ticks). An infected tick can transmit the spirochete to the humans and animals it bites. Untreated, the bacterium travels through the bloodstream, establishes itself in various body tissues, and can cause a number of symptoms, some of which are severe. Often, an erythema migrans (EM) rash appears within 7-14 days at the site of a tick bite (click to see picture of a typical EM rash). LD manifests itself as a multisystem inflammatory disease that affects the skin in its early, localized stage, and spreads to the joints, nervous system and, to a lesser extent, other organ systems in its later, disseminated stages. If diagnosed and treated early with antibiotics, LD is almost always readily cured. Generally, LD in its later stages can also be treated effectively, but because the rate of disease progression and individual response to treatment varies from one patient to the next, some patients may have symptoms that linger for months or even years following treatment. In rare instances, LD may cause permanent damage.

Although LD is now the most common arthropod-borne illness in the U.S. (more than 150,000 cases have been reported to the Centers for Disease Control and Prevention [CDC] since 1982), its diagnosis and treatment can be challenging for clinicians due to its diverse manifestations and the limitations of currently available serological (blood) tests. The prevalence of LD in the northeast and upper mid-west is due to the presence of large numbers of the deer tick’s preferred hosts – white-footed mice and deer – and their proximity to humans. White-footed mice serve as the principal “reservoirs of infection” on which many larval and nymphal (juvenile) ticks feed and become infected with the LD spirochete. An infected tick can then transmit infection the next time it feeds on another host (e.g., an unsuspecting human).

Borrelia burdgorferi

The LD spirochete, Borrelia burgdorferi, infects other species of ticks but is known to be transmitted to humans and other animals only by the deer tick (also known as the black-legged tick) and the related Western black-legged tick. Studies have shown that an infected tick normally cannot begin transmitting the spirochete until it has been attached to its host about 36-48 hours; the best line of defense against LD, therefore, is to examine yourself at least once daily and remove any ticks before they become engorged (swollen) with blood. Generally, if you discover a deer tick attached to your skin that has not yet become engorged, it has not been there long enough to transmit the LD spirochete. Nevertheless, it is advisable to be alert in case any symptoms do appear; a red rash (especially surrounding the tick bite), flu-like symptoms, or joint pains in the first month following any deer tick bite could signal the onset of LD. Manifestations of what we now call Lyme disease were first reported in medical literature in Europe in 1883. Over the years, various clinical signs of this illness have been noted as separate medical conditions: acrodermatitis, chronica atrophicans (ACA), lymphadenosis benigna cutis (LABC), erythema migrans (EM), and lymphocytic meningradiculitis (Bannwarth’s syndrome). However, these diverse manifestations were not recognized as indicators of a single infectious illness until 1975, when LD was described following an outbreak of apparent juvenile arthritis, preceded by a rash, among residents of Lyme, Connecticut.

Where is Lyme Disease Prevalent?

LD is spreading slowly along and inland from the upper east coast, as well as in the upper midwest. The mode of spread is not entirely clear and is probably due to a number of factors such as bird migration, mobility of deer and other large mammals, and infected ticks dropping off of pets as people travel around the country. It is also prevalent in northern California and Oregon coast, but there is little evidence of spread. In order to assess LD risk you should know whether infected deer ticks are active in your area or in places you may visit. The population density and percentage of infected ticks that may transmit LD vary markedly from one region of the country to another. There is even great variation from county to county within a state and from area to area within a county. For example, less than 5% of adult ticks south of Maryland are infected with B. burgdorferi, while up to 50% are infected in hyperendemic areas (areas with a high tick infection rate) of the northeast. The tick infection rate in Pacific coastal states is between 2% and 4%.

Recent Tick Surveillance Data

Lyme Disease Incidence Rates for 2002-2019, Global, United States, and Canada (Johns Hopkins Bloomberg School of Public Health)

Symptoms of Lyme Disease

The spirochetal agent of Lyme disease, Borrelia burgdoferi, is transmitted to humans through a bite of a nymphal stage deer tick Ixodes scapularis (or Ixodes pacificus on the West Coast). The duration of tick attachment and feeding is a key factor in transmission. Proper identification of tick species and feeding duration aids in determining the probability of infection and the risk of developing Lyme disease. Spirochete transmission poster: how long has that tick been feeding on you? The early symptoms of LD can be mild and easily overlooked. People who are aware of the risk of LD in their communities and who do not ignore the sometimes subtle early symptoms are most likely to seek medical attention and treatment early enough to be assured of a full recovery.

The first symptom is usually an expanding rash (called erythema migrans, or EM, in medical terms) which is thought to occur in 80% to 90% of all LD cases. An EM rash generally has the following characteristics:

• Usually (but not always) radiates from the site of the tickbite
• Appears either as a solid red expanding rash or blotch, OR a central spot surrounded by clear skin that is in turn ringed by an expanding red rash (looks like a bull’s-eye)
• Appears an average of 1 to 2 weeks (range = 3 to 30 days) after disease transmission
• Has an average diameter of 5 to 6 inches (range = 2 inches to 2 feet)
• Persists for about 3 to 5 weeks
• May or may not be warm to the touch
• Is usually not painful or itchy

EM rashes appearing on brown-skinned or sun-tanned patients may be more difficult to identify because of decreased contrast between light-skinned tones and the red rash. A dark, bruise-like appearance is more common on dark-skinned patients. Ticks will attach anywhere on the body, but prefer body creases such as the armpit, groin, back of the knee, and nape of the neck; rashes will therefore often appear in (but are not restricted to) these areas. Please note that multiple rashes may, in some cases, appear elsewhere on the body sometime after the initial rash, or, in a few cases, in the absence of an initial rash. Around the time the rash appears, other symptoms such as joint pains, chills, fever, and fatigue are common, but they may not seem serious enough to require medical attention. These symptoms may be brief, only to recur as a broader spectrum of symptoms as the disease progresses. As the LD spirochete continues spreading through the body, a number of other symptoms including severe fatigue, a stiff, aching neck, and peripheral nervous system (PNS) involvement such as tingling or numbness in the extremities or facial palsy (paralysis) can occur. The more severe, potentially debilitating symptoms of later-stage LD may occur weeks, months, or, in a few cases, years after a tick bite. These can include severe headaches, painful arthritis and swelling of joints, cardiac abnormalities, and central nervous system (CNS) involvement leading to cognitive (mental) disorders. The following is a checklist of common symptoms seen in various stages of LD: Localized Early (Acute) Stage:

• Solid red or bull’s-eye rash, usually at site of bite
• Swelling of lymph glands near tick bite
• Generalized achiness
• Headache

Early Disseminated Stage:

• Two or more rashes not at site of bite
• Migrating pains in joints/tendons
• Headache
• Stiff, aching neck
• Facial palsy (facial paralysis similar to Bell’s palsy)
• Tingling or numbness in extremities
• Multiple enlarged lymph glands
• Abnormal pulse
• Sore throat
• Changes in vision
• Fever of 100 to 102 F
• Severe fatigue

Late Stage:

• Arthritis (pain/swelling) of one or two large joints
• Disabling neurological disorders (disorientation; confusion; dizziness; short-term memory loss; inability to concentrate, finish sentences or follow conversations; mental “fog”)
• Numbness in arms/hands or legs/feet

Diagnosis of Lyme Disease

If you think you have LD symptoms you should see your physician immediately. The EM rash, which may occur in up to 90% of the reported cases, is a specific feature of LD, and treatment should begin immediately. Even in the absence of an EM rash, diagnosis of early LD should be made on the basis of symptoms and evidence of a tick bite, not blood tests, which can often give false results if performed in the first month after initial infection (later on, the tests are more reliable). If you live in an endemic area, have symptoms consistent with early LD and suspect recent exposure to a tick, present your suspicion to your doctor so that he or she may make a more informed diagnosis. If early symptoms are undetected or ignored, you may develop more severe symptoms weeks, months or perhaps years after you were infected. In this case, the CDC recommends using the ELISA and Western-blot blood tests to determine whether you are infected. These tests, as noted above, are considered more reliable and accurate when performed at least a month after initial infection, although no test is 100% accurate. If you have neurological symptoms or swollen joints your doctor may, in addition, recommend a PCR (Polymerase Chain Reaction) test via a spinal tap or withdrawal of synovial fluid from an affected joint. This test amplifies the DNA of the spirochete and will usually indicate its presence. Issues and Insights Related to the Diagnosis of Lyme Disease:

• Use of Host Lipids by the Lyme Disease Spirochete May Lead to Biomarkers
• Antiphospholipid Autoantibodies in Lyme Disease Arise After Scavenging of Host Phospholipids by Borrelia burgdorferi
• Misdiagnosis of Lyme Disease: When not to Order Serologic Tests
• Executive Summary: 2nd Banbury Conference on the Laboratory Diagnosis of Lyme Disease
• Straight Talk About the Diagnosis of Lyme Disease
• Natural Killer Cell Counts are not Different Between Patients with Post-Lyme Disease Syndrome and Controls
• Comprehensive Seroprofiling of 16 B. burgdoreferi OspCs: Implications for Lyme Disease Diagnostics Design
• The Laboratory Diagnosis of Lyme Borreliosis: Guidelines from the Canadian Public Health Laboratory Network
• Two-tiered Antibody Testing for Early and Late Lyme Disease, Using an Immunoglobulin G Blot with the Addition of a VlsE Band in the Second Tier: a Rapid, Simple, Quantitative and Highly Sensitive Serological Test for Lyme Disease
• CDC Issues Cautions Regarding Testing for Lyme Disease —
• BBK07 Immunodominant Peptides as Serodiagnostic Markers of Lyme Disease
• Misdiagnosis of Late Lyme Arthritis by Inappropriate Use of Synovial Fluid in Borrelia burgdorferi Immunoblot Testing
• Single-tier Testing with the C6 Peptide ELISA Kit Compared with Two-tier Testing for Lyme Disease
• High Frequency of False Positive IgM Immunoblots for Borrelia burgdoreferi in Clinical Practice
• CXCL13 May Improve Diagnosis of Early Neuroborreliosis with Atypical Laboratory Findings: a Case Report
• The Nervous System as an Ectopic Germinal Center: CXCL13 and IgG in Lyme Neuroborreliosis
• An Outer Surface Protein C (OspC) Peptide Derived from Borrelia burgdorferi sensu stricto as a Target for the Serodiagnosis of Early Lyme Disease
• Laboratory Diagnostic Testing for Borrelia burgdorferi Infection
• Performance of United States Serologic Assays in the Diagnosis of Lyme Borreliosis Acquired from Europe
• Identification of OppA2 Linear Epitopes as Serodiagnostic Markers for Lyme Disease
• U.S. Healthcare Providers’ Experience with Lyme Disease and Other Tick-borne Diseases
• A Concise Critical Analysis of Serologic Testing for the Diagnosis of Lyme Disease
• Development of a Metabolic Biosignature for the Detection of Early Lyme Disease
• Lyme Disease Diagnosed by Alternative Methods: a Common Phenotype with Chronic Fatigue Syndrome
• Understanding Antibody-based Diagnostic Tests for Lyme Disease
• Testing Patients with Nonspecific Symptoms for Antibodies against Borelia burgdorferi sensu lato does not Provide Useful Clinical Information About Their Etiology
• Poor Positive Predictive Value of Lyme Disease Serologic Testing in an Area of Low Disease Incidence.
• The Positive Predictive Value of Lyme ELISA for the Diagnosis of Lyme Disease in Children
• Lyme Disease Diagnosed by Alternative Methods: a Phenotype Similar to that of Chronic Fatigue Syndrome
• Development of a Multi-antigen Panel for Improved Detection of Borrelia burgdorferi Infection in Early Lyme Disease
• Testing Practices and Volume of Non-Lyme Tickborne Diseases in the United States
• Lyme Disease Diagnosis and Serology
• New Serological Test Proposed for the Diagnosis of Infection caused by Borrelia myomotoi
• False Positive Lyme Disease IgM Immunoblots in Children
• Current Guidelines, Common Clinical Pitfalls, and Future Directions for the Laboratory Diagnosis of Lyme Disease, United States.
• Comparison of Males versus Females with Culture-confirmed Early Lyme Disease at Presentation and at 11-20 Years after Diagnosis
• Detection of Borrelia burgdorferi Nucleic Acids after Antibiotic Therapy does not Confirm Viability
• Evaluation of Modified 2-tiered Serodiagnostic Testing Algorithms for Early Lyme Disease
• Metabolic Differentiation of Early Lyme Disease from Southern Tick-associated Rash Illness (STARI)
• High Volume of Lyme Disease Laboratory Reporting in a Low-incidence State- Arkansas, 2015-2016
• Seroreactivity to the C6 Peptide in Borrelia miyamotoi Infections Occurring in the Northeastern United States
• Diagnosis of Lyme Disease
• Evaluation of Modified Two-Tiered Algorithms for Lyme Disease Laboratory Diagnosis Using Well-Characterized Serum Samples
• Limitation and Confusing Aspects of Diagnostic Testing for Neurologic Lyme Disease in the United States.
• Is it Possible to Make a Correct Diagnosis of Lyme Disease on Symptoms Alone? Review of Key Issues and Public Health Implications
• FDA clears new indications for existing Lyme disease tests that may help streamline diagnosis
• Misdiagnosis of Lyme Disease with Unnecessary Antimicrobial Treatment Characterizes Patients Referred to an Academic Infectious Diseases Clinic
• Evaluation of the modified two-tiered testing (MTTT) method in children
• The Lyme Disease Polymerase Chain Reaction Test Has Low Sensitivity