Lyme disease is the most common vector-borne disease in the northern hemisphere (12). In North America, Lyme disease is caused by the bacterial spirochete, Borrelia burgdorferi, transmitted by the bite of an infected tick — most commonly the black-legged “deer” tick (Ixodes scapularis) on the east coast and the western black-legged tick (Ixodes pacificus) on the west coast (33). Ticks most commonly reside in wooded areas on the tips of grasses, shrubs, and other vegetation. They sense movement, moisture, warmth, and carbon dioxide by using a complex sensory organ to detect mammalian hosts (24). Thus athletes such as runners, hikers, and mountain bikers, who are active in forested areas endemic for B. burgdorferi, are at increased risk of contracting Lyme disease.
Among athletes of all levels, participation in outdoor activities continues to grow. Recent survey data showed that nearly 50% of Americans participated in outdoor activities in 2012. Participation in newer sports, such as adventure racing, which is made up of two or more outdoor events such as orienteering, paddling, running, or climbing, increased by 211% from 2007 to 2012 (44). More traditional outdoor sports, such as mountain biking, also have seen extensive growth over the past decade (2). Thus as more individuals participate in outdoor activities, the incidence of Lyme disease likely will continue to grow.
The purpose of this article was to review the epidemiology, clinical manifestations, diagnosis, treatment, and prevention strategies for Lyme disease with focus on the athletic population.
While the Borrelia species likely existed for thousands, if not millions, of years, it was not until 1977 that the term “Lyme arthritis” was used to describe a cluster of cases of children initially thought to have juvenile rheumatoid arthritis in Lyme, CT (17). Since discovery, the incidence of Lyme disease has been increasing steadily, with more than 20,000 cases reported annually in the United States (3,4). The true incidence of Lyme disease is likely much greater, as previous research has shown that most cases of Lyme disease go unreported by a factor of 10- to 12-fold (8). While the majority of cases occur in the northeastern and north-central states, Lyme disease has been reported in every state (3,34).
The life cycle of Ixodes ticks is divided into three stages, as follows: larva, nymph, and adult. While larvae feed primarily on rodents, which serve as the main reservoir for B. burgdorferi, nymphs and adults feed on larger mammals, such as deer and humans. The nymphal ticks most commonly transmit B. burgdorferi to humans, likely due to their smaller size, (2 mm) and ability to avoid detection (11).
Transmission can occur at any time during the year but occurs most commonly during late spring and early summer when nymphs are most active. Adult female ticks also transmit B. burgdorferi but typically feed during the fall (3). Studies have shown that it requires a minimum of 36 to 48 h after attachment for B. burgdorferi to migrate from the midgut of the tick to the salivary glands and into the host (10). The risk of transmission in the first 36 h is currently unknown but is thought to be very low. Thus if a tick is removed in less than 36 h after attachment, the chance of contracting Lyme disease greatly decreases (37).
In addition to B. burgdorferi, ticks may harbor other pathogens. Coinfections include the bacterium, Anaplasma phagocytophilum (formerly called Ehrlichia phagocytophila), which causes human granulocytic anaplasmosis (HGA), and the protozoan, Babesia microti, which causes Babesiosis, a malaria-like illness (46). A recent study showed that the overall prevalence rates of B. burgdorferi, A. phagocytophilum, and B. microti were 14.4%, 6.5%, and 2.7% in nymphs and 45.7%, 12.3%, and 2.5% in adult I. scapularis ticks respectively collected in various regions in New York (35).
Lyme disease symptoms generally can be divided into three phases, as follows: early localized, early disseminated, and late disease (Table). Symptoms typically begin 7 to 14 d after tick bite (range, 3 to 30 d) during the early localized phase. The pathognomonic “bull’s-eye” rash, erythema migrans (EM), occurs in approximately 80% of those infected (43). EM lesions are not typically painful or pruritic but may feel warm to touch. Although classically referred to as a “bull’s eye,” the EM rash can be varied in appearance and is homogenous (no centralized clearing) in most cases (36). The Centers for Disease Control and Prevention (CDC) defines EM as an expanding red macule or papule of at least 5 cm in size (with or without central clearing) (6). Flu-like symptoms often occur and may include fatigue, headache, anorexia, neck stiffness, myalgias, arthralgias, lymphadenopathy, and fever. Patients with Babesiosis or HGA coinfections typically present with more severe flu-like symptoms including high-grade fever (up to 105°F), chills, malaise, headaches, myalgias, and arthralgias (46).
Early disseminated disease occurs several weeks to months after tick bite as the bacteria migrate through the bloodstream and lymphatic system. This stage may include dermatological, neurological, and cardiac symptoms. Multiple EM rashes may be seen during this stage. Neurological symptoms may include unilateral or bilateral cranial nerve palsies, lymphocytic meningitis, radiculopathy, or, rarely, cerebellar ataxia or encephalitis. Bell’s palsy is paralysis of the facial nerve, which is the cranial nerve most commonly affected in Lyme disease. Symptoms may include unilateral facial droop, difficulty blinking and closing the eyes, smiling, frowning, or raising the eyebrow (15,46). Cardiac manifestations are less common (less than 5%) and may include acute-onset atrioventricular (AV) conduction defects or myopericarditis, sometimes referred to as “Lyme carditis” (16).
Late Lyme disease occurs months to years after tick bite and is characterized by arthritis and neurological symptoms. Although not common, patients may present in the late stage of Lyme disease after remaining asymptomatic during the early localized and disseminated phases. Arthritis, in one or multiple joints, is the most common feature of late Lyme disease and occurs in up to 60% of those untreated. Weight-bearing joints typically are affected, especially the knee. Symptoms may range from painless intermittent episodes of arthritis to chronic erosive disease (42). Therefore Lyme disease should be considered in any athlete living in an endemic region presenting with recurrent atraumatic knee effusions. Enthesitis and tendinitis may occur (13). Neurological symptoms may include a syndrome referred to as Lyme encephalopathy, represented by mild cognitive disturbance, sometimes described by patients as “brain fog” (26). Chronic axonal polyneuropathy has been described, which may include spinal radicular pain or distal paresthesia (32).
Lyme disease is diagnosed on the basis of clinical history, physical examination findings, and serological testing. The CDC defines Lyme disease as presence of EM rash or at least one advanced manifestation (described previously in early disseminated and late Lyme disease clinical manifestations) with laboratory confirmation of infection (6). Thus EM rash is the only clinical manifestation to warrant treatment of Lyme disease without further testing (5). If EM rash is not present, the CDC recommends two-step serological testing consisting of enzyme-linked immunosorbent assay (ELISA) followed by the more specific Western blot if ELISA is positive or equivocal.
Testing is not without limitations. Antibodies to spirochete antigens typically take between 2 to 4 wk to develop. As a result, testing in the early localized stage of Lyme disease is negative in over half of infected individuals (sensitivity range, 33% to 49%) (1,23,41,45). Repeat ELISA testing should be considered if initial testing is negative and suspicion remains, as sensitivity increases to 76% to 86% in the early disseminated stage and 95% to 100% in late Lyme disease (1,6,45). Western blot confirmatory testing sensitivity ranges from 50% to 97% with a specificity of 98% to 100% (1,23,45). Up to 5% of the healthy population will test positive with ELISA screening, mainly attributed to rheumatological conditions or other infections such as Helicobacter pylori or Epstein-Barr virus (6,28). Thus test results should not be used solely to establish or exclude diagnosis of Lyme disease (6,30).
While polymerase chain reaction (PCR) testing of synovial fluid is available, with median sensitivity of 83% (range, 76% to 100%) and sensitivity of 99% to 100%, it currently is not recommended by the CDC, as the accuracy and clinical usefulness have not been established (1,6,25). The Infectious Disease Society of America (IDSA) noted that PCR testing of synovial fluid can add to diagnostic certainty but should be performed only in addition to serological testing. Positive synovial PCR testing results with negative serology results should be interpreted with skepticism due to reports of contamination and a false positive rate of 3.6% (25,46). The IDSA recommends lumbar puncture to obtain cerebral spinal fluid (CSF) for PCR testing for intrathecal antibodies if there are signs of central nervous system (CNS) involvement (radiculitis or meningitis) (46). CSF testing typically reveals a pleocytosis but is limited due to low sensitivity ranging from 10% to 30% (9,46). Currently there are no PCR-based assays approved by the U.S. Food and Drug Administration for the diagnosis of Lyme disease (1,6).
In addition to limitations with laboratory testing, several factors warrant discussion that may complicate diagnosis of Lyme disease in athletes. First, Lyme disease symptoms are often nonspecific, common complaints in the athletic population including: fatigue, myalgias, rashes, tendinitis, enthesitis, radicular symptoms, arthralgias, or arthritis. Of note, the homogenous EM rash often is misdiagnosed as cellulitis and treated with medications ineffective against Lyme disease. Second, patients may present during any stage of Lyme disease with variable symptoms. Thus, histories may be complicated and inconsistent with the previously described progression of symptoms for Lyme disease. Third, a clinician should not rely solely on the history of a tick bite for diagnosis. One study showed that only 25% of those with early localized disease recalled a tick bite (31). Fourth, clinicians should be aware of the “invented mechanism” to account for unusual symptoms. For example, an athlete may attribute a unilateral knee effusion to “bumping their knee,” leading a clinician to overlook the possibility of monoarticular arthritis from Lyme disease. Lastly, coinfections may complicate diagnosis. Any patient experiencing high-grade fever for greater than 48 h after appropriate antibiotic treatment, unexplained leukopenia, thrombocytopenia, anemia, elevated liver function tests, or hyponatremia should be tested for coinfections (18,46).
When an attached tick is found, it should be removed promptly with tweezers or small forceps, grasping the tick as close to the skin surface as possible and pulling firmly without twisting or squeezing. Prophylactic treatment is recommended by the CDC and IDSA for patients who meet all of the following criteria: attached tick is identified as a nymphal or adult deer tick estimated to have been attached for at least 36 h, treatment is begun within 72 h of tick removal, and local rate of infection of ticks with B. burdorferi is greater than 20%. A single dose of doxycycline 200 mg in adults is recommended, with 4 mg·kg−1 (maximum, 200 mg) in children greater than 8 years of age. If contraindications exist for doxycycline (children less than 8 years of age or pregnant or lactating women), the IDSA recommends observation (6,46).
Treatment guidelines are highlighted in the Table and are based on current CDC and IDSA recommendations (6,46). Early localized Lyme disease should be treated with doxycycline unless contraindicated, as it also covers possible coinfection with A. phagocytophilum. Amoxicillin and cefuroxime should be used for children less than 8 years of age and pregnant or lactating women. If doxycycline, amoxicillin, and cefuroxime are contraindicated, macrolide antibiotics may be used, but these are less effective (46). A temporary worsening of symptoms can develop during initial treatment, called a Jarisch-Herxheimer reaction, in up to 15% of patients (27).
Treatment of early disseminated Lyme disease depends on the severity of neurological or cardiac symptoms. Isolated cranial nerve palsy should be treated with oral antibiotics; however more extensive neurological symptoms, such as radiculitis or meningitis, require IV antibiotics. Any patient with symptomatic Lyme carditis (chest pain, dyspnea, or syncope), second- or third-degree AV block, or first-degree heart block with markedly prolonged PR interval should be hospitalized and treated with IV antibiotics. Ceftriaxone is the IV treatment of choice; however cefotaxime or penicillin G may be used (46).
Late Lyme disease treatment depends on clinical manifestations. Treatment with a 28-d course of oral antibiotics is recommended for patients with arthritis without neurological involvement. If symptoms persist after antibiotic treatment, a second 28-d oral course or a 14- to 28-d course of IV antibiotics is advised. The use of intraarticular antibiotics, including doxycycline, currently is not recommended, as systemic antibiotics typically are required. Treatment of late Lyme disease with neurological symptoms is the same as that previously described for early disseminated Lyme disease (46).
Treatment guidelines issued by the CDC should be followed for patients diagnosed with HGA or Babesiosis (7).
Post-Lyme Disease Syndrome
Appropriate antibiotic treatment results in resolution of symptoms in most patients; however approximately 10% to 20% may experience lingering symptoms, such as fatigue, arthralgias, headaches, or cognitive complaints for weeks, months, and occasionally years after treatment (40). A definition of post-Lyme disease syndrome was proposed by the IDSA to include the following: documented episode of Lyme disease based on CDC criteria, with persistent or continuous symptoms of fatigue, widespread musculoskeletal pain, or cognitive difficulties for at least 6 months following appropriate antibiotic treatment, excluding other etiologies. Please see reference for additional exclusion criteria (46).
The etiology of post-Lyme disease syndrome remains unknown and has led to considerable controversy. There is evidence that persistent arthritis may be due to an autoimmune phenomenon, initially triggered by Borrelia infection (38,39). Other conditions such as fibromyalgia, chronic fatigue syndrome, and spondyloarthropathies also may be incited by or attributed falsely to Lyme disease (14,46). To date, there have been no convincing studies to show persistence of B. burgdorferi after appropriate treatment or benefit from prolonged courses of repeated antibiotics (20–22). Thus, treatment for patients experiencing post-Lyme disease syndrome should be individualized and include reevaluation.
Currently no vaccine is available to humans for the prevention of Lyme disease. A vaccine, known as LYMErix, was previously available but was withdrawn from the market in 2002 by the manufacturer, citing insufficient sales. There were also safety concerns based on the hypothesis that the vaccine induced arthritis through an autoimmune mechanism (34).
Athletes can lower their risk of contracting Lyme disease by several methods. First athletes should try to minimize exposure to wooded areas in endemic regions for Lyme disease, especially during late spring through summer months. As this is not realistic for many hikers, runners, mountain bikers, and other outdoor enthusiasts, wearing insect repellent containing DEET (N,N-diethyl-meta-toluamide) may help prevent tick bites. Light-colored protective clothing can be worn to allow better visualization of ticks. Permethrin- and nootkatone (a natural organic compound)-treated clothing has been shown to repel ticks (19,29). Lastly tick checks should be encouraged after exposure to wooded areas.
Athletes participating in outdoor activities in endemic regions are at increased risk of contracting Lyme disease. Diagnosis should be based on clinical findings, probability of tick exposure, and serological testing when indicated but may be complicated by nonspecific symptoms common in the athletic population and limitations in laboratory testing. Therefore a strong index of suspicion should be taken for athletes in endemic regions with any of the following: flu-like symptoms during late spring and summer, rash suggestive of EM (both “bull’s eye” and homogenous), unusual fatigue, unprovoked joint effusions, (typically the knee), or neurological symptoms including Bell’s palsy. Most patients fully recover following appropriate antibiotic treatment, but symptoms may persist for months or years. Risk of contracting Lyme disease can be reduced by minimizing exposure to wooded regions, wearing insect repellant and light-colored protective clothing, and performing tick checks.
The author declares no conflicts of interest and does not have any financial disclosures.
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