1970s Arthritis Cluster in Connecticut Analysis

In the early 1970s, a mysterious clustering of arthritis occurred among children in Lyme, Connecticut, and surrounding towns. Medical researchers soon recognized the illness as a distinct disease, which they called. They subsequently described the clinical features of, 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.

Is still mistaken for other diseases, and it continues to pose many other challenges: it can be difficult to diagnose because of the inadequacies of today’s laboratory tests; it can be troublesome to treat in its later phases; and its prevention through the development of an effective vaccine is hampered by the elusive nature of the bacterium.

Arthritis was first recognized in 1975 after researchers investigated why unusually large numbers of children were being diagnosed with juvenile rheumatoid arthritis in Lyme and two neighboring towns. The investigators discovered that most of the affected children lived near wooded areas likely to harbor 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 had been described in medical literature dating back to the turn of the century.

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may have spread from Europe to the United States in the early 1900s but only recently became common enough to be detected.

The ticks most commonly infected with B. burgdorferi usually feed and mate on deer during 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 commonness.

The number of reported cases of, as well as the number of geographic areas, in which it is found, has been increasing. 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. Is endemic in large areas of Asia and Europe. Recent reports suggest that it is present in South America, too.

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 that expands over a period of days or weeks, forming a circular, triangular, or oval shaped rash. Sometimes the rash resembles a bull’s eye because it appears as a red ring surrounding a central clear area. 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, several 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.

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 to 20 percent of untreated patients will go on to develop chronic arthritis.

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 signaled 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.

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.

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. 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.

Unfortunately, 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.

Some patients experiencing nervous system symptoms may also undergo a spinal tap. Through this procedure doctors can detect brain and spinal cord inflammation and can look for antibodies in the spinal fluid.

The inadequacies of the currently available antibody tests may prevent them 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.

Because some tests cannot distinguish Lyme disease antibodies from antibodies to similar organisms, patients may test positive for Lyme disease when their symptoms actually stem from other bacterial infections. A lack of standardization of antibody tests and poor quality control also contribute to inaccuracies in test results.

Due to these pitfalls, 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 history of a tick bite, the patient’s symptoms, a thorough ruling out of other diseases that might cause those symptoms, and other implicating evidence. This evidence could include such factors as an initial appearance of symptoms during the summer months when tick bites are most likely to occur, outdoor exposure in an area where Lyme disease is common, and a clustering of Lyme disease symptoms among family members.

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. Some of these detect distinctive protein fragments of the Lyme disease bacterium in fluid samples.

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.

Several new methods to detect infection are under development in NIH laboratories. Scientists have isolated a protein of B. burgdorferi, called p39, that reacts strongly on blood tests. The presence of antibodies to this protein was found to be a strong indicator of the presence of B. burgdorferi. Although further research will be needed to determine how soon after infection it can detect the bacterium, p39 may prove to be an ideal test for Lyme disease.

A somewhat different approach is the use of an assay based on two closely related spirochetal proteins that are not found in other species of bacterial spirochetes. This assay differs from blood tests now in use because it detects products of the spirochete itself rather than detecting human antibodies to the bacterium.

Most Common Symptoms of Lyme Disease (One or more may be present at different times during infection) Early Infection:

• Rash (erythema migrans)
• Muscle and joint aches
• Headache
• Stiff neck
• Significant fatigue
• Fever
• Facial paralysis (Bell’s palsy)
• Meningitis
• Brief episodes of joint pain and swelling

Less common:

• Eye problems such as conjunctivitis
• Heart abnormalities such as heart block and myocarditis

Late Infection:

• Arthritis, intermittent or chronic

Even Less common:

• Neurologic conditions such as encephalitis or confusion

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 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.

Patients younger than 9 years or pregnant or lactating women with Lyme disease are treated with amoxicillin 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 2 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 persistent fatigue and achiness. This general malaise can take months to subside, although it generally does so spontaneously without requiring additional antibiotic therapy.

Researchers are 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.

Unfortunately, a bout with Lyme disease is no guarantee that the illness will be pre-vented 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.

At present, the best way to avoid Lyme disease is to avoid deer ticks. Although generally only about one 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 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 both ticks and insect repellents, 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, NdiethyIM- 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. Such a prenatal infection can make the woman more likely to miscarry or deliver a stillborn baby.

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, it should be pulled out gently with tweezers, taking care not to squeeze the tick’s body. An antiseptic should then be applied to the bite. Studies by NIH supported researchers suggest that a tick must be attached for many 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.

Because Lyme disease is difficult to diagnose and sometimes does not respond to treatment, researchers are trying to create a vaccine that will protect people from the disorder. Vaccines work in part by prompting the body to generate antibodies. These custom shaped molecules lock onto specific proteins made by a virus or bacterium-often those proteins lodged in the microbe’s outer coat. Once antibodies attach to an invading microbe, other immune defenses are evoked to destroy it.

Development of an effective vaccine for Lyme disease has been difficult to create for a number of reasons. Scientists need to find out how the immune system protects against the bacterium because people who have been infected once can acquire the infection again. In addition, there are several different strains of the bacterium, each with its own distinct set of proteins, and bacteria within an individual strain may change the shape of their proteins over time so that antibodies can no longer identify and lock onto them.

Tick Eradication. In the meantime, researchers are trying to develop an effective strategy for ridding areas of deer ticks. Studies show that a single fall spraying of pesticide in wooded areas can substantially reduce the number of adult deer ticks residing there for as long as a year. 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.

Tips for Personal Protection

• Avoid tick-infested areas, especially in May, June, and July.
• Wear light-colored clothing so that ticks can be easily spotted.
• Wear long-sleeved shirts and closed shoes and socks.
• Tuck pant legs into socks or boots and tuck shirt into pants.
• Apply insect repellent containing permethrin to pants, socks, and shoes, and compounds containing DEET on exposed skin. Do not overuse these products.
• Walk in the center of trails to avoid overgrown grass and brush.

After being outdoors in a tick-infested area, remove, wash, and dry clothing. Inspect the body thoroughly and remove carefully any attached ticks. Check pets for ticks. 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. Although Lyme disease poses many challenges, they are challenges the medical research community is well equipped to meet.