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Lyme disease

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 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 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. 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 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 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 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 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. Recent reports suggest that it is present in South America, too. Ticks that Most Commonly Transmit B. burgdorferi in the U. S. (These ticks are all quite similar in appearance. ) Ixodes dammini -most common in the northeast and midwest

Ixodes scapularis -found in south and southeast Ixodes pacificus -found on west coast 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 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.

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