Lyme disease

Definition

Lyme disease, which is also known as Lyme borreliosis, is an infection transmitted by the bite of deer ticks carrying the spirochete (spiral-shaped bacterium) Borrelia burgdorferi. The disease was named for Lyme, Connecticut, the town where it was first diagnosed in 1975 after a puzzling outbreak of juvenile arthritis. The organism that causes the disease was identified in 1982 and named for its discoverer, Willy Burgdorfer.

Description

Lyme disease is classified as a zoonosis, which means that it is a disease of animals that can be transmitted to humans under natural conditions; it cannot be transmitted person-to-person. B. burgdorferi is carried by infected deer ticks (more precisely known as black-legged ticks) and passed to humans or household pets when they are bitten by the ticks. In the United States, the white-footed mouse is the usual host of immature (nymphal and larval) ticks, while deer are the most common hosts of the adult ticks. In Europe, sheep are the usual hosts of adult infected ticks. Adult black-legged ticks are hard to detect because of their small size; an adult male tick, for example, is about 0.039 in (1 mm) long. An adult female is slightly larger, about 0.051 in (1.3 mm) long.

Ticks feed on their hosts by piercing the skin and slowly sucking blood through the broken tissue. The spiro-chete enters the host as the tick fills itself with blood. After the spirochete has been introduced into the person's skin, it may be destroyed by the body's defense mechanisms. If it is not eliminated, it may either remain in the skin or spread throughout the body through the lymphatic system or the bloodstream. B. burgdorferi can spread to the heart, joints, or central nervous system once it has gained access to the person's circulation. Studies show that B. burgdorferi can penetrate the central nervous system relatively early in the course of the infection without causing any neurologic symptoms. It can also remain in the person's skin for years without causing symptoms.

Lyme disease is a systemic illness, which means that it affects all parts of the body. The most commonly affected areas and organs, however, are the skin, nervous system, heart, joints, and eye. The symptoms of Lyme disease typically emerge in three stages.

It is possible for a person to contract Lyme disease more than once; having the disease does not lead to immunity.

Demographics

The risk of getting Lyme disease depends more on geographical location and the amount of time spent outdoors in tick-infested areas than on age, sex, or race per se, although about 25% of cases in the United States are reported in children younger than 14. Cases of Lyme disease have been reported in 49 of the 50 states; however, 92% of the 17,730 cases reported to the Centers for Disease Control and Prevention (CDC) in 2000 were from only nine states (Connecticut, Rhode Island, New York, Pennsylvania, Delaware, New Jersey, Maryland, Massachusetts, and Wisconsin). The disease is also found in Scandinavia, continental Europe, the countries of the former Soviet Union, Japan, and China; in addition, it is possible that it has spread to Australia.

Lyme disease is seasonal in occurrence. In the United States, humans are most likely to be infected from May through August, when the ticks are most active and people are spending more time outdoors.

The number of cases reported in the United States continues to increase each year; the CDC attributes this increase to the growing size of the deer herd and the geographical spread of infected ticks rather than to improved diagnosis. In addition, some epidemiologists believe that the actual incidence of Lyme disease in the United States may be five to ten times greater than that reported by the CDC. The reasons for this difference include the narrowness of the CDC's case definition as well as frequent misdiagnoses of the disease.

Causes and symptoms

Lyme disease itself is caused by a bacterium known as Borrelia burgdorferi, which enters the skin through the bite of an infected tick belonging to the genus Ixodes. In Europe, the disease is caused by related species known as B. afzinii and B. garinii.

Currently, scientists do not completely understand exactly how B. burgdorferi produces the variety of symptoms that characterize Lyme disease. Some symptoms are

directly caused by the spirochete, but others may result from the body's immune response to the organism.

The symptoms of Lyme disease are typically divided into three stages: early localized, early disseminated, and late. Neurologic complications are most common in disseminated and late-stage Lyme disease.

EARLY LOCALIZED DISEASE Early symptoms of Lyme disease include low-grade fever and erythema migrans, or EM, a red spot or patch on the skin that is found in about 75% of patients with Lyme disease. The initial spot is usually found on the arms, legs, armpits, or trunk within 3–32 days after the tick bite. Erythema migrans often has a ring-like or "bull's-eye" appearance, with the bite itself in the center of the affected area, surrounded by a ring of reddened and inflamed skin. The ring grows outward around the central lesion, sometimes growing as large as 27 in (70 cm) in diameter. Secondary EM lesions appear in about 20% of patients. The rash does not usually itch or burn, and typically fades in a few weeks even if untreated.

Other symptoms of early-stage Lyme disease include flu-like muscular aches and pains, headache, a stiff neck, and fatigue. Nausea and vomiting or sore throat occur in some patients, but are less common symptoms.

EARLY DISSEMINATED DISEASE Early disseminated Lyme disease is characterized by ongoing fatigue; arthritis-like pains in the joints; a headache that comes and goes; inflammation of the tendons and their protective sheaths (synovitis); and red or itchy eyes (conjunctivitis). It is common for the aches and pains in muscles and joints to move from one part of the person's body to another. About 8% of people with Lyme disease develop cardiac complications, which may include heart block and inflammation of the walls of the heart (myocarditis).

Neurologic symptoms in early disseminated Lyme disease affect about 15% of people, usually within a few weeks to months after the onset of EM. The following may be the first symptoms in people who did not develop EM, however:

Bell's palsy. This refers to weakness or paralysis of the facial muscles caused by inflammation or swelling of the seventh cranial nerve. People with facial palsy caused by Lyme disease may be affected on both sides of the face. This symptom may be important in diagnosis, as Bell's palsy caused by other disorders typically affects only one side of the face.

Radiculoneuropathy. This is the medical term for disease affecting nerves and nerve roots. In Lyme disease, neuropathy often takes the form of abnormal sensations (paresthesias) in the hands or feet.

Meningoencephalitis. This refers to inflammation of the brain tissue and the protective membranes that cover it (the meninges). This complication of Lyme disease often causes sleep disturbances, memory problems, difficulty concentrating, mood swings, headache, ataxia (loss of muscular coordination), paresis (mild paralysis), and disturbances in the person's deep tendon reflexes. To test these reflexes, or involuntary responses of certain muscles to a stimulus, the physician gently taps with a small hammer below the person's kneecap, behind the elbow, over the Achilles tendon at the back of the heel, and over the biceps and triceps muscles in the upper arm. The deep tendon reflexes are often weakened or asymmetrical in people with meningoencephalitis related to Lyme disease.

LATE DISEASE The most common symptom of late disseminated Lyme disease is swelling and pain in a few large weight-bearing joints, most often the knee. The affected joints are typically much more swollen than painful, but the arthritis may be accompanied by low-grade fever and fatigue. Lyme-related arthritis develops within weeks to months after the initial eruption of erythema migrans. About 10% of people diagnosed with Lyme disease develop chronic arthritis of the knee.

A late-stage complication of Lyme disease that affects the skin is acrodermatitis chronica atrophicans, a disorder in which the skin on the person's lower legs or hands becomes inflamed and paper-thin. This disorder is seen more frequently in Europe than in the United States.

People with late-stage Lyme disease may develop a neurologic disorder characterized by personality changes and problems with thinking or memory that persist in spite of antibiotic treatment. This syndrome has been called persistent Lyme disease, or PLD. One study of 33 patients diagnosed with PLD found that the most common symptoms were headache (36.4% of patients); memory problems (27.3%); insomnia (33.3%); problems with gait and coordination (36.4%); and impaired deep tendon reflexes (9%). Children with PLD have difficulty getting along with classmates in school as well as making academic progress, and are at increased risk of developing long-term psychiatric disturbances.

Diagnosis

Early diagnosis and prompt treatment are critical to preventing the neurologic complications of Lyme disease.

Patient history and symptoms

The diagnosis of Lyme disease is complicated by the fact that about 25% of patients do not develop the characteristic rash. It is important for the doctor to determine the likelihood of Lyme disease by taking a careful history of exposure to ticks, as only about 25% of patients recall being bitten. In addition to the history, the doctor will examine the patient for the following symptoms:

Erythema migrans. When present, EM has a characteristic "bull's-eye" pattern. In addition, the bite location is often significant; tick bites are more frequently found in such body folds as the armpits or on areas on the trunk near elastic bands in bra straps or underwear.
Fever. The fever that accompanies early Lyme disease is usually low; a high fever indicates either concurrent infection with babesiosis or a different diagnosis altogether.
Absence of digestive or respiratory symptoms.
Presence of fatigue, headache, and muscle or joint pains.

Laboratory tests

Blood testing is not considered necessary if the patient has EM, a history of exposure to ticks, and other indications of a high likelihood of Lyme disease. Moreover, it is difficult to culture B. burgdorferi from human tissues and body fluids. Timing is another important factor in interpreting blood tests for Lyme disease; patients in the early stages of the disease may continue to test negative for several weeks after being infected. Blood testing is, however, recommended for patients with Bell's palsy or myocarditis. The CDC advises doctors to perform a two-step blood test: a screening ELISA test, followed by a Western blot test for confirmation.

Polymerase chain reaction (PCR) testing may not be available in all hospitals, but can be used to detect the DNA of B. burgdorferi in fluid drawn from the joints of untreated patients with late-stage symptoms.

Imaging studies

Imaging studies are rarely used to diagnose Lyme disease with the exception of late-stage arthritis. X rays of patients with Lyme-related arthritis usually show considerable swelling of soft tissue; erosion of bone or cartilage also appears in a small minority of these patients.

Treatment team

Patients are usually treated initially by an emergency physician (if they have gone to an emergency room to have the tick removed) or by a primary care physician (PCP).

The PCP may consult a neurologist, dermatologist, or infectious disease specialist to confirm the diagnosis or advise about medications, particularly in cases of chronic or late-stage disease.

Treatment

Initial treatment

Immediate removal of an attached tick is the first step in treatment for people who know they have been bitten. Because black-legged ticks are slow feeders, it takes about 36 hours for B. burgdorferi to make its way into the body; infection is unlikely if the tick is removed within 24 hours of attachment. People who find ticks on themselves should not use a hot match, petroleum jelly, nail polish, or similar items to remove the tick. They should use fine-tipped tweezers, grasp the tick as close to the skin as possible, and pull the tick away from the skin with a steady motion. The area should then be cleansed with an antiseptic.

If the person has been bitten in an area with a high percentage of infected ticks, the doctor will usually prescribe a prophylactic (disease-preventing) course of antibiotics. The usual dosage is 10 days of oral amoxicillin, doxycycline, or cefuroxime, although a study published in 2001 reported that a single 200-mg dose of doxycycline is also effective.

Aspirin or NSAIDs may be given to relieve fever, aching muscles, and other flu-like symptoms of early Lyme disease.

Treatment of disseminated disease and neurologic complications

Patients who have developed heart block as a complication of disseminated Lyme disease may require a temporary pacemaker. Those with swollen knee joints may need to have excess fluid removed by aspiration, a procedure in which the doctor withdraws the fluid through a fine needle.

Patients with Bell's palsy may be given oral antibiotics for 21–30 days. Patients who have neurologic symptoms together with Lyme-related arthritis are usually treated with intravenous ceftriaxone.

Recovery and rehabilitation

Most patients with neurologic complications of Lyme disease recover completely following treatment with antibiotics. Those who do not respond are usually given an additional course of antibiotics. As of 2003, however, treatment recommendations for central nervous system (CNS) complications of Lyme disease are still evolving, and there is ongoing disagreement among specialists regarding the effectiveness of various treatments for PLD.

Clinical trials

As of October 2003, the National Institute of Neurological Disorders and Stroke (NINDS) is recruiting patients for a 24-week treatment study of persistent Lyme disease (PLD). The investigators will be using brain imaging (MRI and PET scans) to study the effects of intra-venous antibiotic treatment on the neurologic symptoms of PLD. Two other trials are recruiting patients with Lyme disease in order to study the immune system's response to the disorder and to evaluate various treatment regimens.

Prognosis

Patients who are treated early with antibiotics and take their medications on schedule should recover completely from Lyme disease. Most long-term effects of the infection result from misdiagnosis or delayed treatment. Co-infection with such other tick-borne diseases as babesiosis and ehrlichiosis may lead to treatment failures or more severe symptoms. The few fatalities reported with Lyme disease occurred in patients who had also contracted babesiosis.

Neurologic symptoms of early disseminated Lyme disease may last for several months but usually resolve completely. Late neurologic complications of Lyme disease, however, may not respond to antibiotic therapy, particularly if diagnosis and treatment were delayed.

Special concerns

A vaccine for Lyme disease known as LYMErix was available from 1998 to 2002, when it was removed from the United States market. The decision was influenced by reports that LYMErix may be responsible for neurologic complications in vaccinated patients. Researchers from Cornell-New York Hospital presented a paper at the annual meeting of the American Neurological Association in October 2002 that identified nine patients with neuropathies linked to vaccination with LYMErix. In April 2003, the National Institute of Allergy and Infectious Diseases (NIAID) awarded a federal grant to researchers at Yale University School of Medicine to develop a new vaccine against Lyme disease.