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Lime Disease

Lime disease is a tick-borne multisystem infectious syndrome of substantial medical importance and public concern. It is the most frequently reported vector-borne illness in the United States, occurring in 48 of the 50 states at rates of up to 12,000 cases annually. Lime disease also has been seen on four other continents. Highly endemic regions include the northeastern and upper midwestern regions of the

The causative organism, Borrelia burgdorferi, is a flagellated spirochete transmitted from small-mammal reservoirs to humans through bites from infected ticks of Ixodes species (I scapularis in the eastern and upper midwestern United States, I pacificus in California, I ricinus in Europe, and I persulcatus in Asia). Commonly known as deer ticks in the United States and sheep ticks in Europe, these Lime disease vectors are, limes disease, lime's

Ticks must obtain a blood meal in order to molt and lay eggs, leading to obligatory parasitism of suitable hosts: mammals, reptiles, amphibians, and birds in various locales. Humans become suitable alternative hosts when participating in activities in wooded habitats in areas where ixodid ticks are prevalent. In endemic regions, B burgdorferi moves through enzootic cycles between ticks and reservoir hosts capable of sustaining B burgdorferi infection. Humans are at risk for Lime disease when exposed to infected ticks questing for a blood meal. In nonendemic regions, immature ticks preferentially parasitize hosts that are

Genetic variation in B burgdorferi isolates from different geographic regions may explain observed differences in the clinical manifestations of lime disease in Europe and North America. Arthritis is more common in the United States, where all human isolates have belonged to the species B burgdorferi sensu stricto. In parts of Europe, chronic dermatologic manifestations (eg, acrodermatitis chronica atrophicans) are often associated with Borrelia afzelii and some neurologic manifestations (notably meningopolyneuritis, or Bannwarth's syndrome) with Borrelia garinii lime disease, lime disease, limes disease, lime's

Early disease

The symptoms and signs of Lyme disease are categorized according to

Clinical manifestations

The hallmark of early localized Lime disease is erythema migrans an expanding erythematous patch or ring appearing within 30 days (mean, 9 days) after inoculation of skin with B burgdorferi by an infected tick (figures 1 through 3). According to surveillance criteria from the Centers for Disease Control and Prevention (CDC), the rash must exceed 5 cm in diameter, show expansion, and persist for more than 1 week. The features of the skin lesion that are most suggestive of B burgdorferi infection are expansion at a rate of

A minority of patients with erythema migrans report a range of systemic symptoms, including transient chills, fever, myalgias, arthralgias, headache, sore throat, stiff neck, and fatigue within the first month after B burgdorferi infection. Although this spectrum of symptoms has been termed flu-like, respiratory symptoms (cough and sore throat) that

Not all cases of Lime disease present with erythema migrans. In early studies, about one third of patients presented with manifestations of disseminated or late disease. According

Laboratory findings

Although visual recognition of erythema migrans is the best indicator of early localized Lime disease, supportive laboratory data can be helpful in confirming the diagnosis. Isolation of

Serologic testing is the only routinely available laboratory diagnostic aid for Lime disease.

A two-step approach involving enzyme-linked immunosorbent assay (ELISA) with subsequent testing of equivocal or positive samples by Western immunoblot technique for specific B burgdorferi antigenic bands can reveal IgM or IgG directed at B burgdorferi with

Although serologic testing is less sensitive in early Lime disease than in later manifestations it can help clinch the diagnosis in cases in which clinical recognition of erythema migrans is un certain. Laboratory confirmation of B burgdorferi infection may be especially crucial in geographic areas not known to be endemic for Lime disease, where erythema migrans or similar lesions occur but have not yet been conclusively linked to a specific spirochete or other cause, lime disease

Disseminated disease

After a period of localized skin infection at the site of inoculation, B burgdorferi infection may spread hematogenously to various target organs. Disseminated Lime disease occurs 1 to 4 months after an infected tick bite and can include cutaneous, rheumatic, neurologic, and cardiac manifestations." Clinical acumen is required at this stage of illness, because involvement of any of these organ systems may be the first indication of disseminated infection.

The principal cutaneous manifestation of disseminated infection is multiple erythema migrans lesions remote from the original tick bite. These secondary lesions are similar to primary erythema migrans but show less expansion and may be evanescent. B burgdorferi has been cultured from biopsy specimens of secondary skin lesions.

The classic rheumatic manifestation is intermittent large-joint arthritis, which presents most often as acute monarthritis of the knee. Attacks of arthritis appear suddenly with the development of large effusions. White cell counts in joint fluid usually range from 10,000 to

Serologic testing

Indiscriminate use of serologic testing for screening can lead to results that have very low positive predictive value (ie, the likelihood that a positive test indicates true presence of disease). Care must be taken to not rely excessively on serologic testing as the foundation of clinical diagnosis. If the pretest likelihood of Lime disease (based on clinical evaluation) is estimated to be only 5%, a positive ELISA increases the likelihood to only 20%. If the pretest likelihood is considered to be lower yet (eg, 1%), a positive ELISA increases the likelihood to only 5%. In both of these scenarios, a false-positive is as likely as or more likely than a true positive. This is the case even though the specificity of serologic testing for disseminated Lime disease is generally considered 80% or better. Patient selection has a dramatic effect on the posttest predictive value of positive serologic results.

To optimize the predictive value of a positive test, serologic testing should be performed only in patients who are considered to be at risk epidemiologically and have clinical

Late disease

The designation "late Lime disease" is generally reserved for manifestations occurring more than 4 months after disease onset. Skin, nervous system, and joints are most often affected.

Persistent skin inflammation may cause a distinctive plaque-like lesion called acrodermatitis chronica atrophicans. The lesion is most common with B afzelii infection in

Issues in Disease Management

An erythema migrans-like rash associated with Amblyomma americanum tick bites has been reported in the southeastern United States, particularly Missouri, North Carolina, and Georgia and South Carolina (M. W. Felz, MD, unpublished data, 2002). Two carefully done studies showed no association between this lesion and B burgdorferi infection. In addition, an uncultivable Borrelia species has been identified in A americanum ticks collected in

Primary care physicians in endemic areas are often confronted with the dilemma of whether to prescribe antibiotics prophylactically following tick bites. Randomized controlled trials have shown that watchful waiting is the best strategy,