Last updated: November 4, 2014
ICD-9 Code: 088.81.
Definition: Lyme disease is a spirochetal tick-borne infection with acute and chronic sequelae capable of affecting the skin, heart, joints, and nervous system.
Etiology: The spirochete Borrelia burgdorferi causes Lyme disease and is transmitted by a variety of ticks. Transmission occurs after tick bites in ~10% of cases. The Ixodes species of deer ticks facilitate transmission in the endemic areas of the northeastern United States (Ixodes dammini and Ixodes scapularis) and on the Pacific Coast of the United States (Ixodes pacificus). In the mid-Atlantic United States and Texas, the lone star tick (Amblyomma americanum), and in endemic areas of Europe, the sheep tick (Ixodes ricinus), are vectors. The whitefooted mouse is an intermediate reservoir host for immature stages of the tick.
Pathology: There is evidence that both persisting infection and parainfectious (reactive) etiologies contribute to the pathogenesis of Lyme disease. Perhaps secondary to molecular mimicry, persistence of the spirochete in tissues (CNS) leads to an intense inflammatory reaction. Patients with HLA-DR4 and HLA- DR2 are at higher risk to develop a chronic, erosive arthropathy mimicking seronegative RA. B. burgdorferi has been isolated by PCR from synovial fluid in untreated or partially treated disease. However, it is unclear whether chronic arthritis is from persistent infection or a reactive immunologic mechanism.
Demographics: In the United States, most Lyme disease cases have been reported in the northeast and around the Great Lakes (particularly in northern Wisconsin and Minnesota). Lyme disease is seasonal and determined by the feeding patterns of the tick nymphs, which are most active in the late spring and early summer. Lyme disease is distributed worldwide, with cases reported in Europe, China, Australia, Russia, and Sweden.
Cardinal Findings: Three stages of Lyme disease have been described (Fig. 6). However, many patients do not experience an orderly progression of disease manifestations. Some patients may have overlapping features or skip stages entirely. The stages of Lyme disease serve only as a guideline to approximate a time course for the most common clinical symptoms.
—Stage 1 (3 days to 4 weeks postinfection): Constitutional symptoms of malaise, fatigue, and fever predominate. The hallmark manifestation of early Lyme disease is the rash of erythema chronicum migrans. Erythema chronicum migrans commonly occurs on an extremity or near an intertriginous zone (thigh, groin, axilla) at the site of the tick bite. Erythema chronicum migrans has a central zone of partial clearing surrounded by an annular area of erythema with an expanding margin that can enlarge to as much as 20 cm. Lesions may last as long as a month and can be asymptomatic, painful, or occasionally indurated. Secondary annular skin lesions may also develop in other locations. Diffuse arthralgias or myalgias are early musculoskeletal manifestations. Other nonspecific early symptoms may include headache, pharyngitis, conjunctivitis, regional lymphadenopathy, and testicular swelling.
—Stage 2 (weeks to months post-infection): Approximately 8% of people develop cardiac sequelae including atrioventricular heart block (first degree, Wenckebach, or complete), myopericarditis, and, rarely, cardiomyopathy. Neurologic features occur in 15% of patients and include meningoencephalitis, cranial neuropathies (in particular, Bell’s palsy), and radiculoneuritis. Migratory myalgias, arthralgias, and bone or tendon pain may also be detected. Anterior and posterior uveitis and panophthalmitis have been rarely reported.
—Stage 3 (>5 months after onset): In the United States, episodic oligoarticular arthritis predominantly of the lower extremities is the most common late Lyme disease manifestation, occurring in 50% to 70% of patients. Knees frequently have large effusions and occasional popliteal cysts. Chronic neurologic sequelae may result in diffuse CNS symptoms that resemble organic brain syndromes. Demyelinating encephalopathy and chronic radiculoneuropathy are other late neurologic complications. Acrodermatitis chronica atrophicans (a sclerotic or atrophic skin change resembling morphea) is a late cutaneous manifestation seen in Europe but rarely in the United States.
Diagnostic Testing: Serologic studies for Lyme disease have been fraught with considerable difficulties and should only be done when Lyme disease is strongly suspected. Serologic diagnosis is suspected with an increase in IgG antibodies against B. burgdorferi and/or a specific IgM. Serologic increases do not begin until 2 to 4 weeks after infection. ELISA is the current standard for Lyme disease serology, with most confirmatory tests performed by Western blot. Significant intra- and interlaboratory variation in serologic assays coupled with substantial false-positive and false-negative results hinder interpretation of this test. Early antibiotics may abort or curtail antibody production. Additionally, significant cross-reactivity exists with Treponema pallidum and other spirochetes. In early Lyme disease, microscopic hematuria, proteinuria and elevated liver enzymes may be detected in addition to nonspecific indicators of acute inflammation such as an increased ESR and mild anemia. Inflammatory synovial fluid with an average of 25,000 WBCs/mm3 (mostly neutrophils) is commonly seen. In the setting of CNS Lyme disease, lymphocytic pleocytosis and mildly elevated CSF protein are commonly noted. B. burgdorferi antibodies may be greater in the CSF than serum in patients with neuroborreliosis. Skin biopsy of the leading edge of erythema chronicum migrans uncommonly reveals spirochetes.
Keys to Diagnosis: The characteristic erythema chronicum migrans rash (antedated by a tick bite) is most helpful diagnostically. Unfortunately, only 50% of afflicted individuals recall a tick bite, and erythema chronicum migrans may be missed or not occur at all. Lyme disease is a clinical diagnosis with laboratory confirmation.
Differential Diagnosis: Early Lyme disease should be distinguished from other causes of febrile arthritis syndromes with rash, including viral arthritis, rheumatic fever, SLE, and Still’s disease. The Lyme disease rash may be mistaken for erythema multiforme. Later stages of Lyme disease may be confused with other causes of oligoarticular arthritis such as the spondyloarthropathies. The migratory nature of Lyme disease arthritis and involvement of tendons also may suggest gonococcal arthritis. Polyarthritis may be confused with RA. In the north-east, ehrlichiosis and babesiosis may be co-infections with overlapping clinical manifestations. Severe chronic fatigue and myalgias may indicate fibromyalgia rather than chronic Lyme disease (especially in nonendemic patients).
Therapy: Primary prevention of tick bites includes appropriate protective clothing, use of insecticides, and prompt tick removal. The value of preventive antibiotics after a tick bite in an endemic area versus removal of the tick followed by cautious surveillance is controversial. Preventive antibiotic therapy may be cost effective if the risk of Lyme disease is regionally >1% after a tick bite. Therapeutic recommendations based on the stage of Lyme disease and particular disease manifestations are shown in Table 24. Early manifestations without cardiac or neurologic symptoms may be appropriately managed with oral agents such as doxycycline. Mild cardiac disease, limited neurologic involvement (Bell palsy), and early arthritis may be effectively managed with oral antibiotic therapy. Significant joint, heart, or neurologic involvement requires intravenous therapy, most commonly with ceftriaxone. Significant arthropathy may also respond to intraarticular therapy with corticosteroids and rarely synovectomy. Transient use of cardiac pacing is indicated for symptomatic heart block. A clinical conundrum exists when patients, particularly those who have already received appropriate Lyme disease antibiotic therapy, experience chronic arthralgias and fatigue. Intravenous antibiotics are not cost effective in patients with positive serology whose only manifestations are myalgias and fatigue. There appears to be no value to prophylactic antibiotics for asymptomatic individuals, even in endemic areas. A Lyme vaccine was introduced in 1998, but was withdrawn in 2002 for poor sales, musculoskeletal side effects and litigation. Progress on a 2nd generation vaccine has been slow.
Prognosis: With appropriate antibiotic therapy within 4 weeks of disease onset, Lyme disease is a potentially curable infectious illness that may not result in chronic complications. Delayed recognition and therapeutic failure can result in persisting constitutional symptoms, arthralgias, and neurologic complications in as many as 34% of cases. An increasing number of late neurologic complications of Lyme disease have been reported. More sustained musculoskeletal impairment and a higher prevalence of verbal memory loss have been associated with late disease. Active persistent infection, particularly after appropriate antibiotic therapy, is an unlikely explanation for these findings. Careful clinical evaluation of these patients shows a high proportion with fibromyalgia or a poorly characterized chronic pain syndrome.
Eppes SC. Diagnosis, treatment, and prevention of Lyme disease in children. Paediatr Drugs 2003;5:363–372. PMID: 12765486
Lightfoot RW, Luft BJ, Rahn DW, et al. Empiric parenteral antibiotic treatment of patients with fibromyalgia and fatigue and a positive serologic result for Lyme disease: a cost effectiveness analysis. Ann Intern Med 1993;119:503–509. PMID: 8357117
Shadick NA, Phillips CB, Logigian EL, et al. The long-term clinical outcomes of Lyme disease: a population-based retrospective cohort study.Ann Intern Med 1994;121:560–567. PMID: 8085687
Steere AC, Levin RE, Molloy PJ, et al. Treatment of Lyme disease. Arthritis Rheum 1994; 37:878–888. PMID: 8003060
Stanek G, Strle F. Lyme borreliosis. Lancet 2003;362:1639–1647. PMID: 14630446