LYME DISEASE : CLINICAL ASPECTS
Lyme borreliosis is a highly variable disease involving multiple body systems. It occurs in overlapping patterns that come and go at different times. The skin lesion spreading from the site of the tick bite is its most distinctive feature. Relapsing arthritis is the most persistent finding and the one most likely to become chronic. Lyme disease is rarely fatal, but if untreated, it is often a source of chronic ill health.
The primary lesion begins sometime in the first month after a tick bite, which is often unnoticed. A macule or papule appears at the site of the bite and expands to become an annular lesion with a raised, red border and central clearing forming a “bull’s eye” pat-tern. As the bull’s eye ring expands, the lesion known as erythema migransforms. Along with the skin lesions fever, fatigue, myalgia, headache, joint pains, and mild neck stiff-ness are often present. Approximately 50% of untreated patients develop secondary skin lesions that closely resemble the primary one but are not at the site of the tick bite. In un-treated patients, the skin lesions usually disappear over a period of weeks, but constitu-tional symptoms may persist for months.
Days, weeks, even months after the onset of the primary lesion, a second stage may develop in which involvement of the nervous or cardiovascular system may be superim-posed. Neurologic abnormalities include a fluctuating meningitis, cranial nerve palsies, and peripheral neuropathy. Cardiac disease is usually limited to conduction abnormalities (atrioventricular block), but in some cases acute myocarditis can lead to cardiac enlarge-ment. Both neurologic and cardiac abnormalities fluctuate in intensity but generally re-solve completely in a matter of weeks.
Weeks to years after the onset of infection, arthritis marks the continuing state of the disease. It develops in almost two thirds of untreated patients. Typically, it too follows a fluctuating or intermittent course, generally involving the large joints, particularly the knees. The arthritis may become chronic with erosion of the bone and cartilage although the spiro-chetes are rarely demonstrable in the lesions. Less frequent chronic neurologic dysfunctions include subtle encephalitis affecting memory, mood, or sleep, and peripheral neuropathies.
Presently, the diagnosis of early Lyme disease is based on exposure and typical clinical findings. Although B. burgdorferi can be cultured from erythema migrans skin lesions, blood, joint fluid, and CSF, few laboratories stock the special medium required. The spirochetes are seldom detected on any kind of direct microscopic examination. Poly-merase chain reaction (PCR) procedures able to detect B. burgdorferi– specific DNA sequences in body fluids have been developed but are expensive and not standardized for routine use.
With culture generally unavailable, the diagnosis in later stages of disease usually rests on the demonstration of circulating antibodies to B. burgdorferi. Despite consid-erable progress these tests still lack the sensitivity and specificity to be considered more than supportive of a clinical diagnosis. The current recommendation is to first perform a sensitive screening test (enzyme immunoassay or fluorescent antibody) fol-lowed by a more specific Western blot. Even with this two-step approach, patients in the early stages may be seronegative and cross-reactive antigens may cause false-posi-tive results.
Doxycycline and amoxicillin are the first-line antimicrobics for the treatment of early Lyme disease and arthritis. For individuals who cannot tolerate either of these agents, cefuroxime is a much more expensive alternative for oral therapy. Intravenous therapy with ceftriaxone or penicillin G is recommended for patients with neurologic involve-ment or cardiovascular findings such as atrioventricular heart block. The response to treatment is typically slow requiring the continuation of antimicrobics for 30 to 60 days.
The most useful preventive measures in endemic areas are the use of clothes that reduce the likelihood of the infected nymph reaching the legs or arms, careful search for nymphs after potential exposure, and removal of the tick by its head with tweezers. Duration of tick attachment to humans is also a factor in transmission; the risk is greatest when the tick has been feeding for at least 48 to 72 hours. Some insect repellents may provide added protection. The risk of Lyme disease following a random tick bite is too low to jus-tify administration of antimicrobics prophylactically.
A vaccine for Lyme disease composed of recombinant OspA is now licensed for use in the United States. Unlike typical vaccines directed at a molecule known to be impor-tant in human infection, the Lyme disease vaccine is designed to act in the feeding tick, not the human. As indicated above OspA is expressed by B. burgdorferi in tick infection but downregulated when the spirochetes enter mammalian tissues. The antibodies stimu-lated by OspA immunization are intended to reach the midgut of feeding ticks and medi-ate killing of spirochetes before transmission can occur. In addition, the spirochetes may retain enough OspA to render them susceptible to the antibody shortly after transmission. The vaccine has been shown to be protective with an efficacy of approximately 75%. Its widespread use is controversial, because the benefits depend on the relation between the morbidity and cost of complicated cases and the incidence of Lyme disease in any popu-lation. By some estimates, the incidence in even the highest risk areas in Connecticut and Massachusetts does not justify immunizing everyone.