Lyme Disease
A review by William H. McMicken, M.D.

Definition
Lyme disease is a multisystem illness with dermatologic, rheumatic, neurologic, and cardiac features. It is a tick-borne disease caused by the spirochete Borrelia burgdorferi. Although named for an epidemic of infectious arthritis in Lyme, Connecticut, investigated in 1975, the disease now has been reported in 43 of the 50 United States, as well as many countries world-wide. In the United States the incidence is highest in the Northeast and Mid-Atlantic regions, in the upper Midwest, and, to a lesser degree, along the Pacific coast.
Etiology and Epidemiology
The vectors of Lyme disease are hard-shelled Ixodes ticks. Ixodes dammini is the most common vector in the United States. The Ixodes species pictured on this page is I. scapularis. Other species of Ixodes are vectors in the Pacific coast of the United States, and in Europe and Asia. I. dammini is transmitted among immature ticks in the late spring and summer through infected mice. Nymphal ticks are the most common source of human infection. Adult ticks feed in the fall, winter, and early spring,

preferentially choosing the white-tailed deer and their preferred host. Ixodes ticks also feed on human beings in the larval, nymphal, and adult forms. Because the nymph forms are only about the size of a pin head (1 - 2 mm.), only 30% to 40% of patients are aware of a preceding tick bite, and the recalled tick bite may not have been the one that transmitted the disease. Ixodes ticks are slow feeders, requiring 4 to 6 days to become engorged. Experimentally, attachment for at least 24 hours is required for disease transmission. Prevention of the disease therefore is enhanced by daily inspection for ticks of persons in endemic areas, and removal of ticks when found.
The highest number of cases of Lyme Disease are found in children ages 2 to 15 years, and in adults ages 30 to 55 years. Lyme disese has been report to occur througout the year. Peak incidence varies by region. The primary risk factor for Lyme disease is exposure to wooded or grassy areas inhabited by infected ticks. Such areas may include woods, fields, golf courses, or even residential yards in an endemic area. Cases have been reported in which the only exposure was during a vacation in an endemic area.

Clinical Features
The clinical features of Lyme disease may be discussed as three distinct stages, although an enormous amount of overlap exists between stages and only one or two stages may be evident in a given case.

Stage I begins 3 days to 3 weeks after exposure. Erythema migrans (EM) is the characteristic finding in Stage I. This is a bright, expanding patch of redness that tends to clear in the middle as it enlarges with a sharply defined border. As the center clears, it may develop a bluish color. Lesions can attain a diameter as large as 50 cm. and are usually located on the trunk or proximal part of an extremity. In about 60% to 80% of cases this is the presenting symptom.

Multiple lesions are fairly common; where these occur, one spot is usually clearly older than the others. About half the cases in Stage I will have a flu-like illness with fever, headache, stiff neck, arthralgia, and myalgia. Lymph node enlargement in the area of the EM is common. The primary illness may last from a few days to a few weeks. In rare cases the EM persists several months before resolving. Variations in the appearance of the skin lesions are not uncommon, and atypical presentations of the rash may be vesicular lesions, or appear to be cellulitis. Also, the rash may not be apparent, and may not be noticed at all.

Stage II disease usually begins weeks to months later (but may occur earlier). Up to 8% of patients experience transient cardiac dysfunction. Varying degrees of atrioventricular block, including complete heart block, are more common than myocarditis and left ventricular dysfunction. Neurologic abnormalities include headache, profound fatigue, meningitis, cranial neuropathies (especially facial palsies), and sensory and motor radiculopathies. Some combination of neurologic symptoms is present in about one-third of cases. Other organs that are occasionally involved include lung, muscle, bone, liver, subcutaneous fat, and eye.

Stage III may involve joints, the central nervous system, and skin. Arthritis can develop a few days to several years after Stage I, but most commonly a few weeks to months after the initial illness. At least one episode of arthritis occurs in about 60% of patients with untreated EM. The arthritis is usually asymmetric, with involvement of one or a few joints, often migratory, with a predilection for large joints, especially knees. Attacks may last days to weeks, with asymptomatic periods of weeks to months. Although attacks tend to become less frequent over time and eventually disappear, a chronic arthritis occurs about 10% of the time. Chronic neurologic disease may develop either as a late manifestation or as a continuation of secondary disease. Chronic neurologic problems may include fatigue, chronic encephalomyelitis, paraparesis, ataxia, radiculopathies, depression and dementia. Acrodermatitis chronica atrophicans and lymphocytoma may develop as tertiary skin manifestations. In Europe, skin and neurologic manifestations are more common, and arthritis is less common, than in the United States.