In the early 1970s, a mysterious clustering of arthritis cases occurred among children in Lyme, Connecticut, and surrounding towns. Medical researchers soon recognized the illness as a distinct disease, which they called Lyme disease. They subsequently described the clinical features of Lyme disease, established the usefulness of antibiotic therapy in its treatment, identified the deer tick as the key to its spread, and isolated the bacterium that caused it.
Lyme disease is still mistaken for other ailments, and it continues to pose many other challenges: It can be difficult to diagnose because of the inadequacies of today's laboratory tests, and it can be troublesome to treat in its later phases.
(GlaxoSmithKline PLC launched LYMErix in 1999, a vaccine intended to prevent Lyme disease. It is approved for people 15 to 70 years old who live or work in grassy or wooded areas where ticks are present.)
How Lyme Disease Became Known
Lyme disease was first recognized in 1975 after researchers investigated why unusually large numbers of children were being diagnosed with juvenile rheumatoid arthritis in Lyme, Connecticut, and two neighboring towns. The investigators discovered that most of the affected children lived near wooded areas that harbored ticks. They also found that the children's first symptoms typically started in the summer months coinciding with the height of the tick season. Several of the patients interviewed reported having a skin rash just before developing their arthritis, and many also recalled being bitten by a tick at the rash site.
Further investigations resulted in the discovery that tiny deer ticks infected with a spiral-shaped bacterium or spirochete (which was later named Borrelia burgdorferi) were responsible for the outbreak of arthritis in Lyme.
In Europe, a skin rash similar to that of Lyme disease had been described in medical literature dating back to the turn of the century. Lyme disease may have spread from Europe to the United States in the early 1900s but only recently was recognized as a distinct illness.
The ticks most commonly infected with B. burgdorferi usually feed and mate on deer during the adult part of their life cycle. The recent resurgence of the deer population in the Northeast and the influx of suburban developments into rural areas where deer ticks are commonly found have probably contributed to the disease's rising prevalence.
The number of reported cases of Lyme disease, as well as the number of geographic areas in which it is found, has been increasing. Lyme disease has been reported in nearly all states in this country, although most cases are concentrated in the coastal Northeast, mid-Atlantic states, Wisconsin and Minnesota, and Northern California. Lyme disease is endemic in large areas of Asia and Europe.
Ticks that Most Commonly Transmit B. Burgdorferi in the U.S.
- Ixodes scapularis: most common in the Northeast and the Midwest, but also found in the South and the Southeast
- Ixodes pacificus: found on the West Coast
Symptoms
Erythema migrans: In most people, the first symptom of Lyme disease is a red rash known as erythema migrans (EM). The telltale rash starts as a small red spot at the site of the tick bite. The spot expands over a period of days or weeks, forming a circular or oval-shaped rash. Sometimes the rash resembles a bull's-eye, appearing as a red ring surrounding a clear area with a red center. The rash, which can range in size from that of a dime to the entire width of a person's back, appears within a few weeks of a tick bite and usually occurs at the site of a bite. As infection spreads, rashes can appear at different sites on the body.
Erythema migrans is often accompanied by symptoms such as fever, headache, stiff neck, body aches and fatigue. Although these flu-like symptoms may resemble those of common viral infections, Lyme disease symptoms tend to persist or may occur intermittently.
Arthritis: After several months of being infected by B. burgdorferi, slightly more than half of those people not treated with antibiotics develop recurrent attacks of painful and swollen joints that last a few days to a few months. The arthritis can shift from one joint to another; the knee is most commonly affected. About 10 percent to 20 percent of untreated patients will go on to develop chronic arthritis.
Neurological symptoms: Lyme disease can also affect the nervous system, causing symptoms such as stiff neck and severe headache (meningitis), temporary paralysis of facial muscles (Bell's palsy), numbness, pain or weakness in the limbs, or poor motor coordination. More subtle changes such as memory loss, difficulty with concentration, and a change in mood or sleeping habits have also been associated with Lyme disease.
Nervous-system abnormalities usually develop several weeks, months, or even years following an untreated infection. These symptoms often last for weeks or months and may recur.
Heart problems: Fewer than one out of ten Lyme disease patients develops heart problems, such as an irregular heartbeat, which can be signalled by dizziness or shortness of breath. These symptoms rarely last more than a few days or weeks. Such heart abnormalities generally surface several weeks after infection.
Other symptoms: Less commonly, Lyme disease can result in eye inflammation, hepatitis and severe fatigue, although none of these problems is likely to appear without other Lyme disease symptoms being present.
How Lyme Disease Is Diagnosed
Lyme disease may be difficult to diagnose because many of its symptoms mimic those of other disorders. In addition, the only distinctive hallmark unique to Lyme disease -- the erythema migrans rash -- is absent in at least one-fourth of the people who become infected. The results of recent studies indicate that an infected tick must be attached to a person's skin for at least two days to transmit the Lyme bacteria. Although a tick bite is an important clue for diagnosis, many patients cannot recall having been bitten recently by a tick. This is not surprising because the tick is tiny, and a tick bite is usually painless.
When a patient with possible Lyme disease symptoms does not develop the distinctive rash, a physician will rely on a detailed medical history and a careful physical examination for essential clues to diagnosis, with laboratory tests playing a supportive role.
Blood tests: The Lyme disease microbe itself is difficult to isolate or culture from body tissues or fluids. Most physicians look for evidence of antibodies against B. burgdorferi in the blood to confirm the bacterium's role as the cause of a patient's symptoms. Antibodies are molecules or small substances tailor-made by the immune system to lock onto and destroy specific microbial invaders.
Some patients experiencing nervous system symptoms may also undergo a spinal tap. Using this procedure, doctors can detect brain and spinal cord inflammation and can look for antibodies or genetic material of B. burgdorferi in the spinal fluid.
The inadequacies of the currently available diagnostic tests may prevent physicians from firmly establishing whether the Lyme disease bacterium is causing a patient's symptoms. In the first few weeks following infection, antibody tests are not reliable because a patient's immune system has not produced enough antibodies to be detected. Antibiotics given to a patient early during infection may also prevent antibodies from reaching detectable levels, even though the Lyme disease bacterium is the cause of the patient's symptoms.
The antibody test used most often is called an ELISA test. When an ELISA is positive, it should be confirmed with a second, more specific test, called a Western blot.
Physicians must rely on their clinical judgment in diagnosing someone with Lyme disease even though the patient does not have the distinctive erythema migrans rash. Such a diagnosis would be based on the time of year, history of a tick bite, the patient's symptoms, and a thorough ruling out of other diseases that might cause those symptoms. Doctors may consider such factors as an initial appearance of symptoms during the summer months when tick bites are most likely to occur, and outdoor exposure in an area where Lyme disease is common.
New tests under development: To improve the accuracy of Lyme disease diagnosis, NIH-supported researchers are developing a number of new tests that promise to be more reliable than currently available procedures.
NIH scientists are developing tests that use the highly sensitive genetic engineering technique, known as polymerase chain reaction (PCR), to detect extremely small quantities of the genetic material of the Lyme disease bacterium in body tissues and fluids.
A bacterial protein, outer surface protein (Osp) C, is proving useful for the early detection of specific antibodies in people with Lyme disease.
How Lyme Disease Is Treated
Nearly all Lyme disease patients can be effectively treated with an appropriate course of antibiotic therapy. In general, the sooner such therapy is begun following infection, the quicker and more complete the recovery.
Antibiotics, such as doxycycline, cefuroxime axetil, or amoxicillin taken orally for a few weeks, can speed the healing of the erythema migrans rash and usually prevent subsequent symptoms such as arthritis or neurological problems. Doxycycline will also effectively treat most other tick-borne diseases.
Patients younger than 9 years or pregnant or lactating women with Lyme disease are treated with amoxicillin, cefuroxime axetil, or penicillin because doxycycline can stain the permanent teeth developing in young children or unborn babies. Patients allergic to penicillin are given erythromycin.
Lyme disease patients with neurological symptoms are usually treated with the antibiotic ceftriaxone given intravenously once a day for a month or less. Most patients experience full recovery.
Lyme arthritis may be treated with oral antibiotics. Patients with severe arthritis may be treated with ceftriaxone or penicillin given intravenously. To ease these patients' discomfort and further their healing, the physician might also give anti-inflammatory drugs, draw fluid from affected joints, or surgically remove the inflamed lining of the joints.
Lyme arthritis resolves in most patients within a few weeks or months following antibiotic therapy, although it can take years to disappear completely in some people. Some Lyme disease patients who are untreated for several years may be cured of their arthritis with the proper antibiotic regimen. If the disease has persisted long enough, however, it may irreversibly damage the structure of the joints.
Physicians prefer to treat Lyme disease patients experiencing heart symptoms with antibiotics such as ceftriaxone or penicillin given intravenously for about two weeks. If these symptoms persist or are severe enough, patients may also be treated with corticosteroids or given a temporary internal cardiac pacemaker. People with Lyme disease rarely experience long-term heart damage.
Following treatment for Lyme disease, some people still have muscle achiness, neurologic symptoms such as problems with memory and concentration, and persistent fatigue. NIH-sponsored researchers are conducting studies to determine the cause of these symptoms and how to best treat them.
Researchers are also currently conducting studies to assess the optimal duration of antibiotic therapy for the various manifestations of Lyme disease. Investigators are also testing newly developed antibiotics for their effectiveness in countering the Lyme disease bacterium.
A bout with Lyme disease is no guarantee that the illness will be prevented in the future. The disease can strike more than once in the same individual if he or she is reinfected with the Lyme disease bacterium.
Lyme Disease Prevention
Avoidance of ticks: Although a Lyme disease-prevention vaccine, LYMErix is on the market, experts say the best way to avoid Lyme disease is to avoid deer ticks. Although generally only about 1 percent of all deer ticks are infected with the Lyme disease bacterium, in some areas more than half of them harbor the microbe.
Most people with Lyme disease become infected during the summer, when immature ticks are most prevalent. Except in warm climates, few people are bitten by deer ticks during winter months.
Deer ticks are most often found in wooded areas and nearby shady grasslands, and are especially common where the two areas merge. Because the adult ticks feed on deer, areas where deer are frequently seen are likely to harbor sizable numbers of deer ticks.
To help prevent tick bites, people entering tick-infested areas should walk in the center of trails to avoid picking up ticks from overhanging grass and brush.
To minimize skin exposure to ticks, people outdoors in tick-infested areas should wear long pants and long-sleeved shirts that fit tightly at the ankles and wrists. As a further safeguard, people should wear a hat, tuck pant legs into socks, and wear shoes that leave no part of the feet exposed. To make it easy to detect ticks, people should wear light-colored clothing.
To repel ticks, people can spray their clothing with the insecticide permethrin, which is commonly found in lawn and garden stores. Insect repellents that contain a chemical called DEET (N,N-diethyl-M-toluamide) can also be applied to clothing or directly onto skin. Although highly effective, these repellents can cause some serious side effects, particularly when high concentrations are used repeatedly on the skin. Infants and children may be especially at risk for adverse reactions to DEET.
Pregnant women should be especially careful to avoid ticks in Lyme-disease areas because the infection can be transferred to the unborn child. Although rare, such a prenatal infection may make the woman more likely to miscarry or deliver a stillborn baby.
Checking for and removing ticks: Once indoors, people should check themselves and their children for ticks, particularly in the hairy regions of the body. The immature deer ticks that are most likely to cause Lyme disease are only about the size of a poppy seed, so they are easily mistaken for a freckle or a speck of dirt. All clothing should be washed. Pets should be checked for ticks before entering the house, because they, too, can develop symptoms of Lyme disease. In addition, a pet can carry ticks into the house. These ticks could fall off without biting the animal and subsequently attach to and bite people inside the house.
If a tick is discovered attached to the skin, remove it: Tug gently but firmly with blunt tweezers near the "head" of the tick until it releases its hold on the skin. To lessen the chance of contact with the bacterium, try not to crush the tick's body or handle the tick with bare fingers. Swab the bite area thoroughly with an antiseptic to prevent bacterial infection. Studies by NIH-supported researchers suggest that a tick must be attached for at least 48 hours to transmit the Lyme disease bacterium, so prompt tick removal could prevent the disease.
The risk of developing Lyme disease from a tick bite is small, even in heavily infested areas, and most physicians prefer not to treat patients bitten by ticks with antibiotics unless they develop symptoms of Lyme disease.
Tick eradication: In the meantime, researchers are trying to develop an effective strategy for ridding areas of deer ticks. Studies show that spraying of pesticide in wooded areas in the spring and fall can substantially reduce for more than a year the number of adult deer ticks residing there. Spraying on a large scale, however, may not be economically feasible and may prompt environmental or health concerns.
Scientists are also pursuing biological control of deer ticks by introducing tiny stingerless wasps, which feed on immature ticks, into tick-infested areas. Researchers are currently assessing the effectiveness of this technique.
Successful control of deer ticks will probably depend on a combination of tactics. More studies are needed before wide-scale tick control strategies can be implemented.
The National Institute of Allergy and Infectious Diseases is a component of the National Institutes of Health, an agency of the U.S. Department of Health and Human Services.
