Lyme disease is an infectious disease caused by the spirochete bacterium Borrelia burgdorferi. The bacterium is carried and transmitted by deer ticks ( Ixodes scapularis). In most cases, Lyme disease is first characterized by the appearance of a red skin lesion (erythema chronicum migrans), which begins as a small elevated round spot (papule) that expands to at least five centimeters in diameter. Symptoms may then progress to include low-grade fever, chills, muscle aches (myalgia), headaches, a general feeling of weakness and fatigue (malaise), and/or pain and stiffness of the large joints (infectious arthritis), especially in the knees. Such symptoms may tend to occur in recurrent cycles. In severe cases, heart muscle (myocardial) and/or neurological abnormalities may occur.
In many cases, the first symptom of Lyme disease is a characteristic skin lesion, known as erythema migrans (EM), that usually begins as a red discoloration (macule) or as an elevated round spot (papule). The skin lesion usually appears on an extremity or on the trunk, especially the thigh, the buttocks, or under the arms. The lesion typically expands, often with a central clearing, to a diameter as large as 50 cm (c. 12 in.). Approximately 25 percent of individuals with Lyme disease report having been bitten at the affected site by a small tick approximately three to 32 days before onset. The lesion may be warm to the touch. Soon after onset, nearly half of affected individuals develop multiple smaller lesions without hardened centers. EM generally lasts for a few weeks. Other types of lesions may subsequently appear during resolution. Former skin lesions may reappear faintly, in some cases, before recurrent attacks of inflammation of the joints (arthritis). (See below.)
The most common symptoms accompanying EM, or preceding it by a few days, may include a general feeling of ill health (malaise), fatigue, chills, low fever, headache, and a stiff neck. Less commonly, affected individuals may also experience backache, muscle aches (myalgias), nausea, vomiting, sore throat, swollen lymph glands, and/or abnormal enlargement of the spleen (splenomegaly). Although most symptoms associated with the disorder may be intermittent, malaise and fatigue may linger for weeks.
In approximately half of affected individuals, inflammation of the joints (arthritis) may occur within weeks to months following the onset of the disorder and may last as long as two or more years. Early in the disorder’s course, migratory inflammation of many joints (polyarthritis) may occur without joint swelling. Later in the course of the disease, attacks of swelling and pain may recur over several years for longer periods in several large joints, particularly the knees. In most such cases, the knees may be more affected by swelling than pain. In some cases, cysts may form in the knees (Baker’s cysts) and rupture. Approximately 10 percent of affected individuals develop chronic knee involvement, experiencing unremittent involvement for six months or longer. In some cases, malaise, fatigue, low fever, and/or other symptoms may accompany recurrent episodes of arthritis.
In approximately 15 percent of individuals with Lyme disease who have not received treatment, neurological abnormalities may develop within several weeks to months following onset of EM. Such abnormalities may be present for several months and usually resolve with appropriate treatment. Such neurological abnormalities may include inflammation of the brain and/or its surrounding membranes (lymphocytic meningitis or meningoencephalitis); irregular, involuntary movements (chorea); impaired coordination of voluntary movements due to dysfunction of the cerebellum (cerebellar ataxia); inflammation of certain nerves arising from the brain (cranial nerves, such as the 7th [facial] nerve), potentially resulting in facial weakness and loss of some motor functions in the facial area (such as Bell’s Palsy); injury to several different nerves simultaneously (mononeuritis multiplex); and/or inflammation of the spinal cord (myelitis). In some rare cases, affected individuals may experience chronic neurological manifestations associated with the disorder months to years after the initial infection, most commonly involving abnormalities of the brain (i.e., subacute encephalopathy) in which memory, mood, sleep patterns, and language may be affected.
In approximately five percent of individuals with Lyme disease who have not received treatment, heart abnormalities may occur within several weeks following the disorder’s onset. In some cases, affected individuals may experience interruption of the normal passage of electrical impulses (heart block) through the heart’s conducting system. As a result, although the two upper chambers of the heart (atria) may beat normally, the two lower chambers (ventricles) may contract less often or “fall behind” the atria. Such abnormalities usually fluctuate in degree over a short period. In rare cases, individuals with Lyme disease may exhibit inflammation of the membranous bag surrounding the heart (pericardium) and the muscular walls of the heart (myopericarditis), abnormal enlargement of the heart (cardiomegaly), and/or other associated symptoms and findings. In most cases, such cardiac abnormalities may be present for a few days to several weeks.
When Lyme disease is contracted during pregnancy, the developing fetus may or may not be adversely affected, or may contract congenital Lyme disease. In one study of nineteen pregnant women with Lyme disease, fourteen had normal pregnancies and normal babies. If Lyme disease is contracted during pregnancy, premature birth may occur in some cases.
According to the medical literature, in rare cases, individuals with Lyme disease may be simultaneously infected with human granulocytic ehrlichiosis (HGE), a rare bacterial disorder that, in some cases, is transmitted by deer ticks (which are also known tick vectors for Lyme disease). In such cases, affected individuals may experience symptoms and physical findings often associated with both Lyme disease and HGE such as headache, fever, muscle aches, weakness, and/or joint pain (arthralgia). They may also experience certain symptoms and findings specific to one disorder yet rarely found in the other, such as the appearance of the characteristic red skin lesion (erythema chronicum migrans) often associated with Lyme disease and/or a cough, decreased levels of circulating blood platelets (thrombocytopenia), and/or low levels of certain granular white blood cells (granulocytopenia), which often occur in those with HGE. According to the medical literature, it is not yet clear whether coinfection with Lyme disease and HGE may result in more serious disease than that typically associated with infection with Lyme disease or HGE alone. (For more information on ehrlichial disorders such as HGE, please see the “Related Disorders” section of this report below.)
Lyme disease is caused by a spirochete bacterium (Borrelia Burgdorferi) transmitted by deer ticks (Ixodes scapularis). The spirochete is probably injected into the victim’s skin or bloodstream at the time of the insect bite. After an incubation period of 3 to 32 days, the organism migrates outward in the skin, is spread through the lymphatic system, or is disseminated by the blood to different body organs or other skin sites.
Lyme disease was first described in 1909 in European medical journals. The first outbreak in the United States occurred in the early 1970s in Old Lyme, Connecticut. An unusually high incidence of juvenile arthritis in the area led scientists to investigate and identify the disorder. In 1981, Dr. Willy Burgdorfer identified the bacterial spirochete organism (Borrelia Burgdorferi) that causes this disorder.
Some researchers believe that genetic factors may determine whether a person with Lyme disease will be cured with antibiotics, or if they will not respond to antibiotics and consequently be affected by chronic arthritis. Their response is determined by their human leukocyte antigen (HLA) genes located on the 6th chromosome.
Researchers have decoded the genetic blueprint of the microbe (i.e., B. burgdorferi) they believe causes Lyme disease. They hope this discovery may lead to new treatments for Lyme disease in the future.
Lyme disease occurs in wooded or grassy areas that contain large populations of the deer that often carry the ticks. The ticks may be found in rural, suburban, and, less frequently, urban areas. Lyme disease may be contracted during any season of the year, although it usually occurs between May through November, particularly during the months of June and July. Lyme disease was first identified in 1975. Since the Centers for Disease Control and Prevention (CDC) began active surveillance in 1982, over 100,000 cases have been reported in at least 47 states with New York, Connecticut, Maryland, New Jersey, Rhode Island, Pennsylvania, Delaware, and Wisconsin accounting for approximately 88 percent of reported cases. Lyme disease has also been reported in the northern midwest, northern California, and Florida. Lyme disease is believed to affect six in 100,000 individuals in the United States. In areas where deer ticks are more common, Lyme disease may affect up to 1,247 in 100,000 individuals. Lyme disease has also been reported in Europe, Japan, Australia, the former Soviet Union, Scandinavia, and China. The National Institute of Allergy and Infectious Diseases estimates that each year there are 13,000 new cases of Lyme disease in the United States.
In rare cases, individuals with Lyme disease may be simultaneously infected with human granulocytic ehrlichiosis (HGE), an infectious disorder caused by a bacterium of the Ehrlichiosis family that has not yet been named. The bacterium may be carried and transmitted by deer ticks, which are also known tick vectors for Lyme disease. According to the medical literature, such coinfection may result because a percentage of deer ticks in certain geographic areas may be infected with the bacterial agents for both Lyme disease and HGE. For example, recent studies of deer ticks in certain areas where both disorders have occurred (such as Westchester County, New York) determined that from 2.2 to 26 percent of deer ticks were coinfected with the agents for HGE and Lyme disease. Thus, in rare cases, individuals may be simultaneously infected with Lyme disease and HGE due to exposure to one tick that transmitted both bacterial agents–or through exposure to two different ticks that each transmitted one of the disease agents.
In some cases, Lyme disease may result in persistent, long-term symptoms. However, the frequency of such cases is debated within the medical literature. Recent studies have shown that most cases of Lyme disease will resolve with prompt antibiotic treatments. It is unclear whether individuals who experience persistent symptoms represent failure of treatment options or misdiagnosis. Until clear diagnostic procedures are developed to identify late-stage Lyme disease such confusion will exist.
The diagnosis of Lyme disease may be confirmed by specialized laboratory tests (e.g. Enzyme Linked Immunoabsorbent Assay (ELISA) and the Western Blot test).
For adults with Lyme disease the antibiotics tetracycline, doxycycline, ceftriaxone, and minocycline are the drugs of choice. Penicillin V and erythromycin have also been used. In children, penicillin V is recommended rather than tetracycline. Penicillin V is now recommended for neurological abnormalities. It is not yet clear whether antibiotic treatment is helpful later in the illness when arthritis is the most predominant symptom. Treatment should be started as soon as the rash appears, even before the Enzyme Linked Immunoabsorbent Assay (ELISA) test is completed. Results of this test may be inaccurate if patients have had antibiotics soon after contracting Lyme disease, or in those who have weakened immune systems.
If Lyme disease is contracted during pregnancy, careful monitoring by physicians is highly recommended to avoid possible fetal abnormalities and/or complications. Treatment with penicillin should begin immediately to avoid the possibility of fetal abnormalities.
For tense knee joints due to increased fluid flowing in the joint spaces (effusions), the use of crutches is often helpful. Aspiration of fluid and injection of a corticosteroid may be beneficial. If an affected individual has marked functional limitation, excision of the membrane lining the joint (synovectomy) may be performed for chronic (6 months or more despite therapy) knee effusions, but spontaneous remission can occur after more than a year of continuous knee involvement.
In 1989 a new Lyme disease antibody test, manufactured by Cambridge Biosciences Corp., was approved by the Food and Drug Administration (FDA). This test is being used by local laboratories throughout the nation, making tests more available to the general population. However, it is 97% specific for antibodies to Lyme disease when compared to Western blot tests, but it cannot identify the live bacteria in patients who have not yet developed the antibodies.
Lyme disease may reoccur in some individuals resulting in chronic neurologic disorders such as polyneuropathy and encephalopathy. These after-effects are treated with antibiotics.
The drug cefurozine axetil (Ceftin) has been approved by the FDA for the treatment of early Lyme disease. Cefurozine axetil is manufactured by GlaxoWellcome, Inc.
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Wyngaarden JB, et al., eds. Cecil Textbook of Medicine. 19th ed. Philadelphia, PA: W.B. Saunders Company; 1992:1772-1777.
Mandell GL, et al., eds. Mandell, Douglas and Bennett’s Principles and Practice of Infectious Diseases. 4th ed. Philadelphia, PA: Churchill Livingstone Inc.; 1995:2143-2155.
Schutzer SE, et al. Borrelia burgdorferi-specific immune complexes in acute Lyme disease. JAMA. 1999;282:1942-1946.
Fix AD, et al. Tick bites and Lyme disease in an endemic setting. JAMA. 1998;279:206-210.
JD Young, et al. Underreporting of Lyme disease. New Eng J Med. 1998;338:1629.
Nadelman RB, et al. Simultaneous human granulocytic ehrlichiosis and Lyme borreliosis. New Eng J Med. 1997;337:27-30.
Schwartz I, et al. Prevalence of the rickettsial agent of human granulocytic ehrlichiosis in ticks from a hyperendemic focus of Lyme disease [letter]. New Eng J Med. 1997;337:49-50.
Daniels TJ, et al. Deer ticks (Ixodes scapularis) and the agents of Lyme disease and human granulocytic ehrlichiosis in a New York City park. Emerging Infectious Diseases. 1997;3:353-355.
Dattwyler RJ, et al. Ceftriaxone compared with doxycycline for the treatment of acute disseminated Lyme disease. New Eng J Med. 1997;337:289-294.
Eckman MH, et al. Cost effectiveness of oral as compared with intravenous antibiotic therapy for patients with early Lyme disease. New Eng J Med. 1997;337:357-363.
Mazzella FM, et al. A case of concurrent presentation of human ehrlichiosis and Lyme disease in Connecticut. Conn Med. 1996;60:515-519.
Nadelman RB, et al. The clinical spectrum of early Lyme borreliosis in patients with culture-confirmed erythema migrans. Am J Med. 1996;100:502-508.
Aguero-Rosenfeld ME, et al. Human granulocytic ehrlichiosis: a case series from a medical center in New York State. Ann Intern Med. 1996;125:904-908.
Pancholi P, et al. Ixodes dammini as a potential vector of human granulocytic ehrlichiosis. J Infect Dis. 1995;172:1007-1012.
Steere AC, et al. Association of chronic Lyme arthritis with HLA-DR4 AND HLA-DR2. New Eng J Med. 1990;323:219-223.
Logigian EL, et al. Chronic neurologic manifestations of Lyme disease. New Eng J Med. 1990;323:1438-1444.
Markowitz LE, et al. Lyme disease in pregnancy. JAMA. 1986;255:3394-96.
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