Lyme Disease in Emergency Medicine
- Author: William E Caputo, MD; Chief Editor: Rick Kulkarni, MD more...
Background
Lyme disease is a multisystem illness caused by the spirochete Borrelia burgdorferi sensu lato. It is a vector-borne disease transmitted to humans by infected ticks of the Ixodes genus. Lyme disease is the most common vector-borne illness in the United States, accounting for 29,959 reported cases in 2009. It is also endemic in the rest of North America, Europe, and Asia.[1]
Normal and engorged Ixodes ticks. Although various parts of the syndrome were described in Europe more than 100 years ago, the full spectrum had not begun to be identified until 1975, when a cluster of statistically improbable cases of juvenile arthritis occurred in Connecticut. This outbreak stimulated intensive clinical and epidemiologic research that led to the discovery of the causative agent, the ecology, an expanding list of clinical manifestations, and the geographic range. Furthermore, the initial antibiotic responsiveness of the cutaneous manifestations described in the European literature was confirmed and extended.[2]
Pathophysiology
The pathophysiology of Lyme disease is incompletely understood. While active infection by the spirochete causes many manifestations, others may be caused by immunopathogenic mechanisms. Although any body part can be involved, the organism shows a distinct tropism for the skin, CNS, heart, joints, and eyes.
The bacterium is introduced into the skin with a bite from an infected Ixodes tick. In the northeastern and upper midwestern United States, Ixodes scapularis is the vector. In other parts of the country and world, other Ixodes species serve that function. Other ticks (eg, Amblyomma americanum) and insects can carry B burgdorferi, but Ixodes tick bites are thought to cause the vast majority of cases. In the southern and mid-central United States, a Lymelike illness has been reported; the vector appears to be A americanum, and the causative organism or organisms is likely to be a related spirochete.[3, 4] One such organism, named Borrelia lonestarii, has been cultured in a single case.
Once in the skin, the spirochete can (1) be overwhelmed and eliminated by host defense mechanisms; (2) remain viable and localized in the skin where it produces the pathognomonic skin lesion, or erythema migrans (EM); or (3) disseminate through the lymphatics or blood. Hematogenous dissemination can occur within days to weeks of initial infection; the organism can travel to the skin, heart, joints, CNS, and other parts of the body.
Study findings show that in roughly 10% of patients with isolated EM and no systemic symptoms, B burgdorferi can be cultured or that its DNA can be detected in the bloodstream. Using high volume (9 mL) of plasma for culture, one 2005 study suggests that nearly 44% of patients are spirochetemic, some of them with a single skin lesion and no systemic symptoms.[5] Also, early in the course of the disease when EM is still present, the spirochete and its DNA have been isolated from the cerebrospinal fluid (CSF), indicating early CNS penetration. This penetration can occur even in the absence of neurologic symptoms.
Data published in November 2008 show that some genotypes of B burgdorferi are responsible for the large majority of cases of disseminated disease.[6] At the present time, this information likely has greater significance for future vaccines or diagnostic tests than it does in routine practice.
The organism can also persist in skin (and possibly in the CNS) for years without causing symptoms. Experimentally, the spirochete can penetrate human fibroblasts and live intracellularly, even when the extracellular medium contains ceftriaxone well above bacteriocidal levels for the spirochete. Clinically, organisms have been cultured from skin many years after primary infection. This mechanism may allow the spirochete to elude the normal host defense mechanisms directed against it.
Stages of Lyme disease
As with syphilis, the disease classically is divided into stages: early localized, early disseminated, and late. However, distinct cutoff points between the stages are frequently unclear.
Stage 1 is also known as primary or early localized infection. It generally occurs within 30 days of the tick bite. Most patients present with a characteristic expanding rash (erythema migrans) at the site of the tick bite 7-14 days after the tick is removed. Several other nonspecific symptoms can occur and include fatigue, myalgias, arthralgias, headache, fever, chills, and neck stiffness.
Stage 2 is also known as early disseminated disease, occurring generally weeks to months after the bite. Musculoskeletal and neurologic symptoms are the most common; less common symptoms are cardiac and dermatologic.
Stage 3 or chronic Lyme disease happens months to years after infection, which sometimes involves a period of latency. Musculoskeletal (mainly joints) and neurologic systems are most commonly affected.
Epidemiology
Frequency
United States
In January 2008, the Council of State and Territorial Epidemiologists (CSTE) approved a revised national surveillance case definition for Lyme disease. This allowed for the addition of probable cases to the total case count, which differs from previous years.
Overall in the United States, incidence is 9.21-11.67 cases per 100,000 population (2007 and 2008 data). The total number of reported cases in 2008 in the US was 35,198 (including 28,921 confirmed and 6,277 probable cases).
The total number of cases have been increasing over time. The total number of cases in 1995,2000, and 2005 were 11,700, 17,730, and 23,305, respectively. The increase in incidence is not simply a result of increased recognition; in states that perform active surveillance, true incidence and geographic range have increased. The likely causes of this increase are expansion of deer herds and the expanded range of the vector.[1]
Epidemiologic data suggest that the actual incidence of Lyme disease could be as much as 10 times higher than the CDC data indicate. This probably is a result of a restrictive case definition from the CDC, inevitable misdiagnosis, and the fact that physicians tend to underreport reportable diseases of all kinds.
The risk of Lyme disease follows a general geographic pattern. More than 90% of cases come from 10 states: Connecticut, Delaware, Maryland, Massachusetts, Minnesota, New Jersey, New York, Pennsylvania, Rhode Island, and Wisconsin.[7]
Lyme disease risk in the United States is shown in the map below.
Approximately 90% of Lyme disease cases are reported from the northeastern and upper midwestern United States. A rash that can be confused with early Lyme disease sometimes occurs following bites of the lone star tick (Amblyomma americanum). These ticks, which do not transmit the Lyme disease bacterium, are common human-biting ticks in the southern and southeastern United States. International
Lyme disease exists throughout the world, including Scandinavia; central, southern, and western Europe; the former Soviet Union; Japan; and China. While Lyme disease is far more common in the northern hemisphere, occasional cases have been reported in more tropical locales, and it may exist in Australia. Ecology for the disease differs in various parts of the world. Furthermore, different strains of the organism are present in Europe and very likely account for differences in clinical manifestations; these have implications for diagnostic testing and vaccination strategies.
Mortality/Morbidity
Rare fatalities are reported in patients with Lyme disease, with 5 deaths reported in the United States in 2006.[1] Some fatal cases occur in patients who were simultaneously co-infected with other tick-borne pathogens such as Ehrlichia species and B microti, and in Europe, tick-borne encephalitis.
Morbidity is usually neurologic and rheumatic. Patients with neurologic disease who are not diagnosed and treated promptly can suffer from neurologic and cognitive dysfunction that can be difficult to treat. Some patients may have fixed neurologic deficits that are unresponsive to antibiotics. Patients with cardiac disease rarely exhibit chronic morbidity from their heart involvement. Similarly, some genetically predisposed individuals with arthritis may have ongoing joint inflammation that is not responsive to further antibiotic therapy.
Race
No known differential frequency exists in patients of different races; however, EM maybe more difficult to diagnose in dark-skinned individuals.
Sex
Males compromise 54.8 % of cases of Lyme disease, owing to an increase in males to tick exposure.
Age
As with other tick-borne diseases, the incidence of Lyme disease has a bimodal distribution with respect to age. Rates are highest among children aged 5-9 years and among adults aged 55-59 years. This distribution is also a function of tick exposure, rather than age.
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| Disease Stage | Clinical Manifestations | Treatment | Duration |
| Early localized | Erythema migrans | Oral | 14-21 days |
| Early disseminated | Multiple erythema migrans | Oral | 14-21 days |
| Isolated cranial nerve palsy | Oral | 14-21 days | |
| Meningoradiculoneuritis | Oral | 14-28 days | |
| Meningitis | Intravenous or oral | 14-21 days | |
| Carditis | |||
| -Ambulatory | Oral | 14-21 days | |
| -Hospitalized | Intravenous followed by oral | 14-21 days | |
| Borrelial lymphocytoma | Oral | 14-21 days | |
| Late | Arthritis | Oral | 28 days |
| Recurrent arthritis after oral therapy | Oral or intravenous | 28 days or 14-28 days | |
| Encephalitis | Intravenous | 14-28 days | |
| Acrodermatitis chronica atrophicans | Oral | 14-28 days |
| Treatment | Adult Dose | Pediatric Dose | |
| Oral Therapy | Doxycycline (patients ≥8 y) | 100 mg twice a day | 4 mg/kg (up to 100 mg) twice a day |
| Amoxicillin | 500 mg three times a day | 50 mg/kg (up to 500 mg) three times a day | |
| Cefuroxime axetil | 500 mg twice a day | 30 mg/kg (up to 500 mg) twice a day | |
| Intravenous therapy | Ceftriaxone | 2 g once a day | 50-75 mg/kg (up to 2 g) once a day |
| Cefotaxime | 2 g every 8 h | 150-200 mg/kg (up to 2 g) every 8 h | |
| Penicillin G | 18-24 million U/d divided every 4 h | 200,000-400,000 mg/kg (up to 2 g) every 8 h |

