Lyme Disease

Lyme disease results from infection of a tick-borne spirochete, Borrelia burgdorferi. It usually presents with a characteristic rash (“erythema migrans”) at the site of the tick bite. Often, symptoms are limited to headache, fever, muscle aches, and joint pain, though some patients may develop cranial nerve palsies, meningitis, or myocarditis/pericarditis. A late manifestation of Lyme disease is arthritis, typically affecting the knee. Lyme disease is named for the town in Connecticut where it was first diagnosed.

Structure and Function

Lyme disease is a multisystem inflammatory disease caused by infection of Borrelia burgdorferi or some other spirochete within the Borrelia genus (Figure 1). It is transmitted to humans through the bite of an infected deer tick, most commonly Ixodes scapularis.

Figure 1: Photomicrograph of Borrelia burgdorferi. The corkscrew shape gives rise to the designation of this bacterium as a spirochete.

Lyme disease is a multisystem inflammatory disease caused by infection of Borrelia burgdorferi or some other spirochete within the Borrelia genus (Figure 1). It is transmitted to humans through the bite of an infected deer tick, most commonly Ixodes scapularis.

Patient Presentation

The first presenting sign of Lyme disease is a rash that appears one to two weeks after a tick bite. This rash, known as erythema migrans, is found in ~75% of cases. The prototypical appearance is a “bull’s eye” target, with a red macule or papule at least 5 cm in diameter with an area of central clearing (Figure 2), though a diffuse rash without central clearing is frequently seen as well. The rash itself typically produces no symptoms beyond mild warmth.

Figure 2: The classic appearance of erythema migrans: a bull's eye pattern. (Reproduced from

The course of Lyme disease follows three stages. Stage 1, which occurs within the first month of infection, is characterized by nonspecific symptoms such as fever, headaches, and fatigue. Muscle aches and neck stiffness may be present.

Stage 2, which occurs weeks to months after the original tick bite, is caused by disseminated infection. Stage 2 findings occur in about 20% of untreated patients. The stage 2 findings that prompt medical attention include facial palsy or joint pain–at times with the patient unaware of a tick bite, rash or even exposure, for that matter. Lymphocytic meningitis and cardiac are possible, but rare.

Stage 3 of Lyme disease is characterized by arthritis and recurrent effusions of a single large joint such as the knee or shoulder.

Objective Evidence

The presence of a characteristic rash following recent tick exposure is sufficient evidence to diagnose Lyme disease.

In the absence of a rash or history of tick exposure, the diagnosis of Lyme disease can be made by detecting antibodies according to a two-stage protocol. First, a sensitive enzyme-linked immunosorbent assay (ELISA) test is performed. A negative ELISA effectively rules out the diagnosis, but because 20% of the normal population have antibodies against Lyme, a positive test does not definitively establish the diagnosis. Thus, a more specific Western blot is needed for confirmation. The Western blot looks for both immunoglobulin M (IgM) and IgG antibodies. IgM antibodies usually are detected first at 2–4 weeks post-infection, while IgG antibodies appear later at the 4–6 week point.

Notably, all patients with Lyme arthritis can be expected to have positive IgG serology as arthritis is a late manifestation of the infection.

In the case of suspected Lyme arthritis, joint effusions can be aspirated to help exclude other diagnoses such as gout and septic arthritis. The synovial fluid in Lyme arthritis typically shows an elevated white blood cell (WBC) count in the range of about 10,000 WBC/mm3. This cell count is lower than what is seen in gout (~20,000-50,000 WBC/mm3) and septic arthritis (>50,000 WBC/mm3).

Culture of the synovial fluid is not sensitive, as the joint fluid itself may impede the growth of Borrelia burgdorferi. Polymerase chain reaction (PCR) testing is sensitive for detecting Borrelia burgdorferi DNA but may be nonspecific, especially for active infections.

Peripheral WBC counts are usually in the normal range, though the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels may be elevated.

Imaging studies are not diagnostic and only performed to exclude alternative diagnoses.


There are approximately 25,000 confirmed cases of Lyme disease reported in the United States each year, though this number is thought to understate the true incidence by a factor of ten (i.e., there are 250,000 cases annually).

In the United States, Lyme disease is most prevalent in the northeast (e.g., places like Lyme, CT), though any area with a high deer population can be affected; indeed, Lyme has been reported in every state in the continental United States. Outside the northeast, the upper midwest (Minnesota and Wisconsin) and the west coast (northern California and Oregon) are the areas that are most affected.

Lyme disease is more common in children ages 5 to 15, and in adults older than 50 years. There is a slight (approximately 3:2) female-to-male predominance.

Lyme disease is more common in children ages 5 to 15, and inadults older than 50 years. There is a slight (approximately 3:2) female-to-male predominance.

Notably, fewer than 1% of tick bites result in Lyme disease.

Having Lyme disease does not generate enduring protective immunity; reinfection may occur.

Differential Diagnosis

Lyme arthritis can be distinguished from ordinary bacterial septic arthritis in that most cases of septic arthritis are characterized by an inability to bear weight, elevated serum WBC count, and a considerably higher synovial fluid WBC count (>50,000 versus ~10,000 for Lyme).

Lyme arthritis can also be distinguished from other forms of arthritis on clinical grounds. For example, unlike osteoarthritis, Lyme arthritis typically causes minimal pain with motion and, unlike rheumatoid arthritis, usually involves only a single large joint. Furthermore, unlike the chronic and progressive nature of both osteoarthritis and rheumatoid arthritis, Lyme disease is more likely to have intermittent symptoms.

Fibromyalgia generally causes more diffuse pain and lacks objective evidence of inflammation.

Lyme disease affecting the nervous system can create radiating arm or leg pain similar to that seen with a disc herniation, though there is no preceding history of a traumatic event as might be reported in the case of a disc herniation.

Red Flags

Lyme disease can cause enduring problems if not treated, and thus an appropriate index of suspicion must be applied to all patients presenting with a history or findings suggestive of the condition.

Treatment Options and Outcomes

The recommended treatment of Lyme arthritis is a 28-day course of antibiotics. A typical regimen would be oral doxycycline 100 mg twice daily or amoxicillin 500 mg 3 times daily. Doxycycline should be avoided in children.

If detected early, treatment with antibiotics is usually curative. According to the Centers for Disease Control, a second course of the same oral antibiotic can be considered for patients with improving but persistent symptoms after an initial course of oral antibiotics.

In addition to antibiotics, nonsteroidal anti-inflammatory drugs such as ibuprofen may be used. Intraarticular corticosteroid injections should be avoided until antibiotic treatment is completed.

Physical therapy should be provided especially if prolonged activity modification is needed to control the effusions.

About 5% of patients develop so-called post-treatment Lyme disease syndrome, with lingering musculoskeletal symptoms despite treatment. More powerful medications such as hydroxychloroquine or methotrexate or arthroscopic synovectomy can be employed in cases not responsive to first line therapies.

Risk Factors and Prevention

The risk of Lyme disease can be reduced by minimizing contact with ticks and avoiding wooded areas, especially during warmer months. If such exposure cannot be avoided, treating clothing and gear with an insecticide such as permethrin can help decrease the risk of tick bites.

People in high-risk areas should wear long-sleeved shirts tucked into pants and pants tucked into socks to decrease exposed skin. Once inside, a full body skin and clothing exam should be performed to check for any attached ticks or tick bites (Figure 3). Showering can also help wash off unattached ticks.

Figure 3: Sites for a full body skin exam upon return from potentially tick-infested areas. (Reproduced from

Attached ticks should be removed as soon as possible, ideally within 36 hours. If ticks are found on the skin, they should be removed using tweezers(Figure 4).

Figure 4: Tick removal per CDC recommendations: “Use clean, fine-tipped tweezers to grasp the tick as close to the skin’s surface as possible, Pull upward with steady, even pressure. Don’t twist or jerk the tick, this can cause the mouth-parts to break off and remain in the skin. After removing the tick, thoroughly clean the bite area and your hands with rubbing alcohol or soap and water. Never crush a tick with your fingers.” (Figure and legend from

Currently, there is no available human vaccine against Borrelia burgdorferi.


The bacteria that causes Lyme disease was named Borrelia burgdorferi in honor of Wilhelm Burgdorfer who discovered it.

Key Terms

Borrelia burgdorferi, erythema migrans


Recognize the presenting signs and symptoms of Lyme disease. Perform an inspection for ticks.

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