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, myalgia, and arthralgia, 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 (see Figure 1) or with other spirochetes of the Borrelia genus. It is transmitted to humans through the bite of an infected deer tick, most commonly Ixodes scapularis.

Figure 1: Photomicrograph of the Borrelia burgdorferi. The “corkscrew-shape” gives rise to the designation of this bacterium as a spirochete.
Ixodes ticks have a two-year life cycle consisting of four distinct developmental stages: egg, larva, nymph, and adult. The lifecycle begins when an adult tick lays eggs in the spring. In the summer, the eggs emerge as larva, which feed on small invertebrates such as mice and squirrels. The larvae emerge as nymphs the following spring, and also feed on small invertebrates such as mice and squirrels. The nymphs then mold into adult ticks in the fall and feed on larger animals, such as deer. Ixodes ticks acquire the Borrelia burgdorferi spirochete by feeding on infested animals during the larva, nymph, and adult stages. Mice and deer are able to carry the spirochete, however they do not become infected. Only ticks in the nymph and adult stages are able to transmit Borrelia burgdorferi. Most humans become infected through nymph bites, as the nymphs are small (less than 2 mm) and often hard to see. Adult ticks tend to be seen and removed before they can transmit the bacteria.
During an Ixodes tick bite, the tick saliva disrupts the local immune system, which creates a protective environment for spirochete replication. Replication of the spirochetes within the dermis leads to a localized post inflammatory response, which causes a bull's-eye rash termed erythema chronicum migrans. Over a period of days, the spirochetes spread via the bloodstream to the joints, nervous system, and cardiac tissue. Once present in the joint, the spirochete leads to an inflammatory response, which ultimately results in synovial hypertrophy and accumulation of immune complexes in the synovial fluid.
Lyme disease signs and symptoms are thought to be a consequence of the immune response, and thus may persist after the spirochetes have been eliminated from the body.


Patient Presentation

The first presenting sign of Lyme disease is a rash, one to two weeks after a tick bite. This rash, known as erythema migrans, is found in approximately 75% of cases. The classic configuration is a “bullseye” target (Figure 2), with red macule or papule at least 5 cm in diameter, with an area of central clearing. More commonly there is simply diffuse erythema without central clearing.The rash itself typically produces no symptoms beyond mild warmth.

Figure 2: The classic appearance of erythema migrans: a bulls eye pattern. (Reproduced from
The course of Lyme disease follows three stages. Stage 1, within the first month of infection, is characterized by non-specific symptoms such as fever, headaches and fatigue. Muscle aches and neck stiffness may be present.
Stage 2 findings, caused by disseminated infection, appears weeks to months after the tick bite, 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 Lyme disease is characterized by arthritis and recurrent effusions of a single large joint, e.g., 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 a history of tick exposure, the diagnosis 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, yet because 20% of the normal population have antibodies against Lyme, a positive test is not definitive. Thus, a more specific Western blot is needed for confirmation, looking for both immunoglobulin M (IgM) and IgG antibodies. IgM antibodies usually are detected first, at 2–4 weeks post infection, with IgG appearing at the 4–6 week point, and possibly persisting for years.

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 typically shows elevated white blood cell (WBC) counts, though only about 10,000 WBC/mm3 – lower than what is seen with gout and septic arthritis.


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


Peripheral white blood cell counts are usually normal range, but the erythrocyte sedimentation rate and C-reactive protein levels may be elevated.


Imaging studies are not diagnostic and are performed if at all to excluded 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 heavy deer population can be affected; indeed Lyme has been reported in every state in the continental US but beyond the northeast, the upper Midwest (Minnesota and Wisconsin), and the west (northern California and Oregon) are most affected.


Lyme disease is more common in the months of May to September, owing to both the life cycle of the tick responsible for most cases as well as the increased likelihood of people going into the woods with exposed skin.


Lyme disease is more common in children ages 5 to 15, and in adults older than 50 years. There is a slight (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 counts and a considerably higher synovial fluid WBC count (>50,000, as opposed to ~10,000 for Lyme).


Serologic testing can distinguish Lyme arthritis from other forms of arthritis on clinical grounds. Lyme arthritis typically causes minimal pain with motion, and usually involves only one joint. Also, 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 a radiculopathy similar to what is seem with a disk herniation, often in conjunction with a cranial neuropathy and meningitis.



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. Lyme arthritis, per se, is a late manifestation but many young, healthy patients may seek musculoskeletal care early in the course of the disease, simply for their muscle or joint symptoms.



Treatment Options and Outcomes

The treatment of Lyme arthritis is a short course of antibiotics. A typical regimen would be a 28-day course of 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 are to be avoided until antibiotic treatment is completed.


Especially if prolonged activity modification is needed to control the effusions, some physical therapy should be provided.


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 by avoiding wooded areas, especially during warmer months. If such exposure cannot be avoided, treating clothing and gear with an insecticide such as permethrin is helpful.


People in high-risk areas should wear long sleeved shirts tucked into pants, and pants tucked into socks, to decrease exposed skin. Skin and clothing can be checked for ticks once inside. Insect repellant can also be used to decrease the risk of tick bites.


Showering soon after being potentially tick-infested areas may help wash off unattached ticks, and it is a good opportunity for a full examination for ticks that may be attached (Figure 3).


Figure 3: Sites for a full body check 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 (see Figure 4).


Figure 4: Tick removal as 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 pathogen 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.