Diagnosis 
Lyme disease should be considered when any of the following conditions is present: monoarticular or oligoarticular arthritis, aseptic meningitis, cranial and peripheral neuritis, and primary cardiac conduction abnormalities. Bell's Palsy, once always considered to be "idiopathic" may be a symptom of Lyme disease. History of exposure to an endemic area within a few weeks of onset of illness should be sought, but inquiry as to tick bites is not particularly helpful because attachment of the Ixodes tick is usually unnoticed and non-vector ticks are common in endemic areas. Because Lyme disease in its early stages can mimic many other conditions, accurate diagnosis is important before committing the patient to a prolonged course of antibiotics. 

The diagnosis of Lyme Disease is based primarily on clinical findings. Treatment without absolute confirmation of the disease is often appropriate if the signs and symptoms fit. However, good judgment is necessary, since patients are often very fearful and may insist on being tested for infection or treated for Lyme disease when little evidence of it exists. Serologic testing for antibodies may provide supportive information in patients in endemic areas with findings suggesting chronic or later stages of disseminated Lyme Disease. A positive antibody result in the face of vague symptoms can add to the problem. A positive antibody test may signal a previous infection that has resolved without complications. Physicians should explain to these patients the differences in "background" seropositivity in various geographic locations and the drawbacks of instituting unnecessary treatment for inactive disease. A newer test in which the DNA of the Lyme organism can be detected and amplified by the polymerase chain reaction (PCR) for identification and quantification. If the patient has a classic EM lesion or provides an unambiguous history of this rash, in association with typical symptoms, the diagnosis is confirmed. Atypical rashes, a vague history, or no rash at all do not exclude the diagnosis, but then additional evidence is obviously necessary. If the illness involves more than one system with a compatible dysfunction, the diagnosis is more likely if other conditions can be excluded. The unusual skin lesion acrodermatitis chronica atrophicans is also pathognomonic.

In cases in which clinical features are equivocal, the following tests may be approriate. 1) Lyme Western Blot, IgG, IgM; 2) Lyme ELISA; 3) Lyme DNA by PCR (skin, blood, synovial fluid, cererbrospinal fluid, urine). Tests for other tick-borne diseases with similar symptoms may need to be excluded with Babesia DNA by PCR, Ehrlichia HGE and HME Western Blot antibody testing. Other disease that may have similar vague symptoms include Bartonella, Tularemia, Brucella, Mycoplasma and Chlamdia.

Lyme disease has become a controversial and politicized disease. This has occurred because of the seriousness of the disease and the degree of disability it can produce. This is especially true if there is a delay in diagnosis and treatment. There is no doubt that much needs to be done to prevent such complications, and to treat such sufferers effectively. There are excesses on both sides of the problem; those who diagnose Lyme disease too frequently and treat when not necessary, and those who never treat without unequivocal proof of Lyme disease. Cloning of the DNA for several of B. burgdorferi antigens has been accomplished. Further development of methods utilizing this technology should allow rapid detection of the presence of the organism itself, and would confirm difficult cases in the future. Those interested in following new developments in Lyme disease may want to subscribe to the Internet newsgroup sci.med.diseases.lyme, or participate in other Internet sites dedicated to Lyme disease and its victims.

Isolation of the organism B. burgdorferi is a difficult and low-yield procedure. Direct examination of tissues rarely reveals the spirochetes, but has been reported in brain biopsy in a patient with subacute encephalitis.  

Serologic analysis is the laboratory diagnostic method. Both immunofluorescent and enzyme-linked immunosorbent assay techniques are widely available although not standardized. IgM response peaks in the third to sixth week of the disease, followed by IgG and IgA responses. The IgM titer normalizes after recovery, while the IgG titer could persist over years or decades. Serologic tests are frequently negative in early disease, and early antibiotic therapy may prevent or modify the antibody response. Also, some patients become seronegative with antibiotic therapy even though the disease remains active. Cross reactivity exists between the spirochete of syphilis (Treponema pallidum), the Borrelia of relapsing fever, and B. burgdorferi. Syphilis can be differentiated by the RPR test, but confusion with relapsing fever might be a diagnostic problem in areas in which both diseases are endemic. 

The current immunodiagnostic tests for Lyme disease have to be interpreted with caution mainly because of low sensitivity in some clinical situations. There are reports that serologic tests my be falsely negative in patients partially treated with an antibiotic early in the disease. Lyme titers may be elevated in patients whose symptoms are from other conditions since asymptomatic infection with B. burgdorferi also occurs. 

In early Lyme disease patients may have elevations of the sedimentation rate, and moderate elevations of transaminase are not unusual. Tests for Rheumatoid Factor and Antinuclear Antibodies are usually negative. Synovial fluid is usually Type II (i.e., 2000 to 25,000 WBCs/.L), but occasional patients have very high cell counts (>100,000 WBCs/.L). A mild lymphocytosis may be present in the cerebrospinal fluid when neurologic abnormalities are present. Antibodies to B. burgdorferi may be present in synovial fluid and cerebrospinal fluid. The cerebrospinal fluid may show oligoclonal bands. 

Management 
Lyme disease is usually a relatively self-limited illness. At times, however, it is a debilitating, chronic disease. Death from Lyme disease is rare. 

Early disease is best treated with Doxycycline orally in a dose of 100 mg two or three times a day for 21 to 30 days, or with Amoxicillin 500 - 1000 mg three times a day for 21 to 30 days. Benemid 500 mg three times a day is sometimes given along with amoxicillin to give a higher and more prolonged blood level of the antibiotic. Another alternate oral therapy is Tetracycline, 500 mg 4 times a day for 21 to 30 days. These oral regimens can also be used in the presence of facial palsy, or mild cardiac abnormalities. Early arthritis, synovitis, and the skin lesions of acrodermatitis chronica atrophicans and lymphocytoma are treated with this oral antibiotic dose for 30 days. Treatment regimens of more than 30 days have not yet been evaluated and therefore are not currently indicated. In children who are allergic to penicillin, Erythromycin is used, but this antibiotic does not reliably prevent sequelae. Prophylactic antibiotic treatment for a tick bite is not advisable. 

Lyme disease that is manifest as serious central nervous system disease, high-degree atrioventricular block, or persistent, proliferative synovitis is treated with intravenous antibiotics: Cefotaxime, 3 Grams every 12 hours for 14 to 21 days; or Ceftriaxone, 2 Grams daily for 14 - 21 days; or Penicillin G, 20 million units in divided doses daily for 14 - 21 days. Intravenous antibiotic therapy as described is also used, in a 14 day course, for a treatment failure with oral antibiotics. Some sequelae respond well to antibiotic therapy while others, such as chronic arthritis or advanced central nervous system disease may not. This fact should be considered before subjecting patients to repeated courses of adequate intravenous therapy. Persistent symptoms, especially fibrositis and fibromyalgia, may be caused by a process that is no longer antibiotic-sensitive. Special care in the management of so-called chronic Lyme disease. is crucial to prevent prolonged or unending courses of antibiotics for such noninfectious problems. 

Optimal therapy for pregnant women with active Lyme disease has not been established. In early pregnancy the intravenous therapy for serious central nervous system disease should be used. In the third trimester, oral Amoxicillin, 1000 mg 3 or 4 times a day for 30 days is probably adequate. 

Corticosteroids may be useful to supplement antibiotics in complete heart block, facial palsies, and neuritis, and locally in chronic arthritis. In severe or chronic arthritis and synovitis, orthopedic surgery may be indicated.

Prevention
A vaccine to prevent Lyme disease was developed a few years ago by SmithKline Beacham, and was approved for use in the United States. The name of the vaccine was LYMErix™. It was approved for persons between ages 15 and 70 years. It was given in a series of three doses, the second dose one month after the first, and the third dose one year after the first dose. Maximum immunity may not occur until after the third dose. LYMErix™ will not prevent the disease in persons who have unrecognized infection at the time of vaccination; it is NOT a cure for Lyme disease. Protection from other tick borne illnesses, such as babesiosis or ehrlichiosis, does not result from treatment with LYMErix™. SmithKline Beacham subsequently merged to form GlaxoSmithKline Pharmaceutical Company. Sales of the vaccine were low because of problems with degree of immunity obtained and the delay of a year for full effectiveness because of the need for three timed injections. There were also law suits and reports of side effects that may or may not have have been related the use of the vaccine. Review by the Food and Drug Administration resulted in no recommendation to discontinue its use. However, GlaxoSmithKline, citing "cost effectiveness" reasons, withdrew Lymerix™ vaccine from the market in February 2002. While Lymerix vaccine is no longer marketed here, there are other manufacturers. The Center for Disease Control still has guidelines on Lyme vaccine at this link: Lyme Disease: Vaccine Recommendations on their website.
Immunity from the vaccine is not 100%, and the duration of immunity that does develop is not well established. Previous infection with Lyme disease does not necessarily result in immunity, and reinfection is possible. Therefore, the vaccine may also be useful in persons who have a history of previous Lyme disease. Persons most at risk who might benefit from the vaccine would seem to be those who work outdoors, in tick-infested wooded and grassy areas. Occupations that would appear to be at higher risk are landscapers, foresters, wildlife and park managers, as well as those who engage in hiking, camping, fishing and hunting in such areas. Most cases of Lyme disease in the United States are thought to be acquired in the peri-residential environment, through routine activities of property maintenance, recreation (including golf), and /or exercising pets.
Common sense preventive methods include wearing long sleeved shirts, long pants rather than shorts, tucking pants into socks, treating clothing with tick repellant, and checking for and removing attached ticks.

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Links 
Lyme Disease. a public information guide from the Centers for Disease Control and Prevention, National Center for Infectious Diseases, Division of Vector-Borne Infectious Diseases, Atlanta, Georgia 30333 
American College of Physicians Lyme Disease Initiative