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Lyme disease

Sunday 13 March 2005

Lyme borreliosis

Definition: Lyme disease is a borelliosis .

It was named for the Connecticut town where, in the mid-1970s, there was an epidemic of arthritis associated with skin erythema, is caused by several subspecies of the spirochete Borrelia burgdorferi.

The disease, transmitted from rodents to people by Ixodes deer ticks, is a common arthropod-borne disease in the United States, Europe, and Japan.

In the United States, the incidence of Lyme disease has risen steadily, with approximately 17,000 cases in 2000, almost as many as new cases of tuberculosis. Most cases occur in the Northeastern states and in some parts of Midwestern states.

In endemic areas, as many as 50% of ticks are infected with B. burgdorferi, and ticks may also be infected with Ehrlichia and Babesia (discussed later).


Lyme disease involves multiple organ systems and is divided into three stages.

- In stage 1, spirochetes multiply and spread in the dermis at the site of a tick bite, causing an expanding area of redness, often with a pale center. This skin lesion, called erythema chronicum migrans, may be accompanied by fever and lymphadenopathy but usually disappears in 4 to 12 weeks.

- In stage 2, the early disseminated stage, spirochetes spread hematogenously throughout the body and cause secondary skin lesions, lymphadenopathy, migratory joint and muscle pain, cardiac arrhythmias, and meningitis often with cranial nerve involvement.

- In stage 3, the late disseminated stage, 2 or 3 years after the initial bite, Lyme borreliae cause a chronic arthritis sometimes with severe damage to large joints and an encephalitis that varies from mild to debilitating.


B. burgdorferi does not produce lipopolysaccharide (LPS), and the initial immune response is instead stimulated by binding of bacterial lipoproteins to toll-like receptor 2 (TLR2) expressed by macrophages. In response, these cells release proinflammatory cytokines (IL-6 and TNF) and generate bactericidal nitric oxide, reducing but usually not eliminating the infection.

The adaptive immune response to Lyme disease is mediated by CD4+ T-helper cells and B-cells.

Borrelia-specific antibodies, made 2-4 weeks after infection, drive complement-mediated killing of the bacteria, however B. burgdorferi escapes the antibody response through antigenic variation.

Similar to Borrelia hermsii, a cause of relapsing fever, B. burgdorferi has a plasmid with a single complete expression site for a gene encoding an antigenic surface protein, VlsE, and several variant coding sequences for VlsE that can shuttle into the expression site. Thus, as the antibody response to one VlsE protein is mounted, bacteria expressing an alternate VlsE protein can escape immune recognition.

Chronic manifestations of Lyme disease, such as the late arthritis, are probably caused by persistence of bacteria, although an autoimmune response stimulated by the bacteria has also been suggested to have a role.


Skin lesions caused by B. burgdorferi are characterized by edema and a lymphocytic- plasma cell infiltrate.

In early Lyme arthritis, the synovium resembles that of early rheumatoid arthritis, with villous hypertrophy, lining cell hyperplasia, and abundant lymphocytes and plasma cells in the subsynovium.

A distinctive feature of Lyme arthritis is an arteritis, with onionskin-like lesions resembling those seen in lupus.

In late Lyme disease, there may be extensive erosion of the cartilage in large joints.

In Lyme meningitis, the CSF is hypercellular, shows a marked lymphoplasmacytic infiltrate, and contains anti-spirochete IgGs.

See also

- chronic Lyme disease


- Feder HM Jr et al. A critical appraisal of "chronic Lyme disease".N Engl J Med. 2007 Oct 4;357(14):1422-30. PMID: 17914043

- Wormser GP. Early Lyme disease. N Engl J Med. 2006 Jun 29;354(26):2794-801. PMID: 16807416

- Guerau-de-Arellano M, Huber BT. Chemokines and Toll-like receptors in Lyme disease pathogenesis. Trends Mol Med. 2005 Mar;11(3):114-20. PMID: 15760769

- The surgical pathology of human Lyme disease. An enlarging picture. Duray PH. Am J Surg Pathol. 1987;11 Suppl 1:47-60. PMID: 3812878