Lyme disease is a medical condition caused by the bacterium Borrelia burgdorferi, which is transmitted by ticks that usually live on deer.
At the site of a tick bite, a red dot may appear and gradually expand into a circular area up to 15 cm across. Be aware, however, that there's not always a rash, or the rash may look different than a bull's-eye shape. Symptoms including fever, headache, and muscle pain usually develop; they are followed by joint inflammation, which typically affects the knees and other large joints. Symptoms of Lyme disease may vary in severity and occur in cycles lasting for about one to three weeks.
See below for more detailed articles and pictures.
If Lyme disease is not treated promptly, complications may develop; these include meningitis (inflammation of the membranes covering the brain), facial palsy, and an abnormal heartbeat. The most serious long-term complications of Lyme disease are Lyme arthritis and persistent neurological disorders that are similar to multiple sclerosis.
Treatment of Lyme disease is with antibiotic drugs and is most effective when given soon after initial infection. Non-steroidal anti-inflammatory drugs are given to relieve joint pain. In areas that are known to be infested with the ticks, people should take measures to prevent tick bites. Such action includes wearing clothes that cover the body and fit closely at the wrists and ankles, and taking care not to walk through thick undergrowth.
Above: picture of tic feeding on human leg
Lyme disease in more detail - non technical
Lyme disease is an infection transmitted by the bite of ticks carrying the spiral-shaped bacterium Borrelia burgdorferi. The effects of this infection can be long-term and disabling unless it is recognized and treated properly with antibiotics.
Controversy clouds the true incidence of Lyme disease because no test is 100% diagnostic for the disease, and many of its symptoms mimic those of so many other diseases. In the US cases of Lyme disease have been reported in 49 of the 50 states; however, distribution is not uniform. The United States Centers for Disease Control and Prevention (CDC) report that 93% of cases come from 10 states: Connecticut, Delaware, Maryland, Massachusetts, Minnesota, New Jersey, New York, Pennsylvania, Rhode Island, and Wisconsin. Oregon and northern California also report a significant number of cases.
Prevalence estimates range for 4 in 100,000 population to 9.1 per 100,000 population. In states where Lyme disease is more common, the rate can be as high as 37.4 per 100,000 population. In 2007, 27,000 new cases were reported in the United States. Some epidemiologists believe that the actual incidence of Lyme disease in the United States may be 5–10 times greater than that reported by the CDC. The reasons for this difference include the narrowness of the CDC’s case definition as well as frequent misdiagnoses of the disease.
Lyme disease has also been found in Canada, most countries in continental Europe, some countries of the former Soviet Union, Japan, China, and Australia. In Europe the disease has been found in Austria,Germany, Poland, Finland, and Norway, The highest rate reported as of mid-2010 was in Slovenia, where there were an estimated 206 cases per 100,000 population and in Austria where there were 135 cases per 100,000 population.
Lyme disease affects men and women equally. People ages 5–14 and 50–59 are most likely to contract Lyme disease because these groups are more likely to participate in outdoor activities where they are exposed to ticks. About one-quarter of cases occur in children under age 5, while the fewest cases are reported in the 20–24 year old age group.
Ticks carrying Lyme disease found in South London parks. Researchers at the London School of Hygiene & Tropical Medicine studied four London parks to see whether ticks were present, and if they carried the Borrelia burgdorferi bacterial pathogen that causes Lyme borreliosis (Lyme disease). The team found Ixodes ricinus ticks in Richmond and Bushy parks, but reported no evidence of the arthropod pests in Wimbledon Common or Hampton Court.
Lyme is named for Lyme, Connecticut, the town where it was first diagnosed in 1975 after a puzzling outbreak of arthritis. The organism causing the disease is named for its discoverer, Willy Burgdorfer. Lyme disease, which is also called Lyme borreliosis, is a vector-borne disease. This term means that it is delivered from one host to another. It is also classified as a zoonosis, which means that it is a disease of animals that can be transmitted to humans under natural conditions. In this case, a tick bearing the B. burgdorferi organism inserts it into a host’s bloodstream when it bites the host to feed on its blood. It is important to note that neither B. burgdorferi nor Lyme disease can be transmitted directly from one person to another or from pets to humans.
In the United States, Lyme disease accounts for more than 90% of all reported vector-borne illnesses. It is a significant public health problem and continues to be diagnosed in increasing numbers. The CDC attributes this increase to the growing size of the deer herd and the geographical spread of infected ticks rather than to improved diagnosis.
Above: picture of tic under microscope
People who spend a lot of time outdoors in wooded areas are at greatest risk of encountering ticks and developing Lyme disease. The risk for acquiring Lyme disease also depends on what stage in its life cycle a tick has reached. A tick passes through three stages of development—larva, nymph, and adult—each of which is dependent on a live host for food. In the United States, B. burgdorferi is borne by ticks of several species in the genus Ixodes, which usually feed on the white-footed mouse and deer (and are often called deer ticks). In the summer, the larval ticks hatch from eggs laid in the ground and feed by attaching themselves to small animals and birds. At this stage they are not a problem for humans. It is the next stage—the nymph—that causes most cases of Lyme disease. Nymphs are very active from spring through early summer, at the height of outdoor activity for most people. Because they are still quite small (less than 2 mm), they are difficult to spot, giving them ample opportunity to transmit B. burgdorferi while feeding. Although far more adult ticks than nymphs carry B. burgdorferi, the adult ticks are much larger, more easily noticed, and more likely to be removed before the 24 hours or more of continuous feeding needed to transmit B. burgdorferi.
Causes and symptoms
Lyme disease is caused by B. burgdorferi. Once B. burgdorferi gains entry to the body through a tick bite, it can move through the bloodstream quickly. Only 12 hours after entering the bloodstream, B. burgdorferi can be found in cerebrospinal fluid (which means it can affect the nervous system). Treating Lyme disease early and thoroughly is important because Lyme disease can hide for long periods within the body in a clinically latent state. That ability explains why symptoms can recur in cycles and can flare up after months or years, even over decades. It is important to note, however, that many people who are exposed to B. burgdorferi do not develop the disease.
Lyme disease usually is described in terms of length of infection (time since the person was bitten by a tick infected with Lyme disease) and whether B. burgdorferi is localized or disseminated (spread through the body by fluids and cells carrying B. burgdorferi). When and how symptoms of Lyme disease appear can vary widely from patient to patient. People who experience recurrent bouts of symptoms over time are said to have chronic Lyme disease.
Early localized Lyme disease
The most recognizable indicator of Lyme disease is a rash around the site of the tick bite. Often, the tick exposure has not been recognized. The eruption might be warm or itch. The rash—erythema migrans (EM)— generally develops within 3–30 days and usually begins as a round, red patch that expands outward. About 75% of patients with Lyme disease develop EM. Clearing may take place from the center out, leaving a bull’s-eye effect; in some cases, the center gets redder instead of clearing.
Be aware, however, that there's not always a rash, or the rash may look different than a bull's-eye shape.
The rash may look like a bruise on people with dark skin. Of those who develop Lyme disease, about 50% notice flu-like symptoms, including fatigue, headache, chills and fever, muscle and joint pain, and lymph node swelling. However, a rash at the site can also be an allergic reaction to the tick saliva rather than an indicator of Lyme disease, particularly if the rash appears in less than three days and disappears only days later.
Late disseminated disease and chronic Lyme disease
Weeks, months, or even years after an untreated tick bite, symptoms can appear in several forms, including:
- fatigue, forgetfulness, confusion, mood swings, irritability, numbness.
- neurologic problems, such as pain (unexplained and not triggered by an injury), Bell’s palsy (facial paralysis, usually one-sided but may be on both sides), and a mimicking of the inflammation of brain membranes known as meningitis; (fever, severe headache).
- arthritis (short episodes of pain and swelling in joints) and other musculoskeletal complaints. Arthritis eventually develops in about 60% of patients with untreated Lyme disease.
Less common effects of Lyme disease are heart abnormalities such as irregular rhythm (arrhythmias) or cardiac block and eye abnormalities such as swelling of the cornea, tissue, or eye muscles and nerves. A late-stage complication of Lyme disease that affects the skin is acrodermatitis chronica atrophicans, a disorder in which the skin on the person’s lower legs or hands becomes inflamed and paper-thin. This disorder is seen more frequently in Europe than in the United States.
A clear diagnosis of Lyme disease can be difficult and relies on information the patient provides and the doctor’s clinical judgment, particularly through elimination of other possible causes of the symptoms. Lyme disease may mimic other conditions, including chronic fatigue syndrome (CFS), multiple sclerosis (MS), and other diseases with many symptoms involving multiple body systems. Differential diagnosis (distinguishing Lyme disease from other diseases) is based on clinical evaluation with laboratory tests used for clarification, when necessary.
Doctors generally know which disease-causing organisms are common in their geographic area. The most helpful piece of information is whether a tick bite or rash was noticed and whether it happened locally or while traveling. Doctors may not consider Lyme disease if it is rare locally, but will take it into account if a patient mentions vacationing in an area where the disease is commonly found.
Children may have difficulty effectively verbalizing their symptoms and as such, their symptoms may be misdiagnosed. Parents who suspect Lyme disease in their children should inform their doctor about the possibility of the disease and be proactive in requesting further medical evaluation and treatment.
As of 2010, the United States Food and Drug Administration (FDA) had approved two blood tests for Lyme disease. This these looks for antigens (substances that stimulate the production of antibodies) produced by B. burgdorferi rather than for the bacterium itself. Prevue B is a rapid test that can give results within one hour. The C6 Lyme Peptide ELISA (enzyme-linked immunosorbent assay) test takes longer to give results, but is more sensitive. A positive result from either test can be confirmed by a second blood test known as the Western blot test, which must be done in a laboratory.
Early diagnosis and prompt treatment are critical to preventing the neurologic complications of Lyme disease. Fewer than 50% of children realize that they have been bitten by a tick. Any child that develops a round, bull’s-eye skin rash, joint pain, flu-like symptoms, and/or neurologic symptoms should see a doctor. Because the rash may not be readily visible (e.g., on the scalp under hair), children living in or visiting areas with a high incidence of Lyme disease and those participating in frequent outdoor activities during active tick months who develop joint pain and neurologic symptoms should see a doctor.
Immediate removal of an attached tick is the first step in treatment for people who know they have been bitten. Because black-legged ticks are slow feeders, it takes about 36 hours for B. burgdorferi to make its way into the body; infection is unlikely if the tick is removed within 24 hours of attachment. People who find ticks on themselves should not use a hot match, petroleum jelly, nail polish, or similar items to remove the tick. They should use fine-tipped tweezers, grasp the tick as close to the skin as possible, and pull the tick away from the skin with a steady motion. The area should then be cleansed with an antiseptic.
Because most children do not realize they have been in tick-infested areas or been bitten by a tick and because deer ticks can be the size of a poppy seed or smaller, parents should be diligent about checking children for ticks, especially if the family lives in or visits an area with a high incidence of Lyme disease or an area near tick habitats.
For most patients, initial therapy consists of oral antibiotics such as doxycycline (Doryx, Vibramycin) or amoxicillin (Amoxil, Trimox) for 14–21 days. If there poor response, alternative antibiotics such as Cefuroxime axetil (Ceftin, Zinnat), Clarithromycin (Biaxin, Klaricin), or azithromycin (Zithromax) are tried. When symptoms indicate nervous system involvement or a severe episode of Lyme disease, intravenous antibiotics such as ceftriaxone (Rocephin), cefotaxime (Claforan), or intravenous penicillin may be given for 14–30 days.
The physician may have to adjust the treatment regimen or change medications based on the patient’s response. Treatment can be difficult because B. burgdorferi comes in several strains, some may react to different antibiotics than others. Also, B. burgdorferi can shut itself up in cell niches, allowing it to hide from antibiotics. Finally, antibiotics can kill B. burgdorferi only while it is active rather than dormant.
Complementary and Alternative
Antibiotic therapy is essential in treating Lyme disease, however, complementary therapies may minimize symptoms of Lyme disease or improve the immune response. These include vitamin and nutritional supplements, mostly for chronic fatigue and increased susceptibility to infection. For example, yogurt and Lactobacillus acidophilus preparations help fight yeast infections, which are common in people on long-term antibiotic therapy. In addition, botanical medicine and homeopathy can be considered to help bring the body’s systems back to a state of health and well being. A Western herb, spilanthes (Spilanthes spp.), may have an effect on diseases like Lyme disease that are caused by spirochetes (spiral-shaped bacteria), although this effect has not been proven to the satisfaction of practitioners of conventional medicine.
Other complementary and alternative therapies used in treating Lyme disease include:
- Chinese medicine. Formulae used to treat systemic bacterial infections include Wu Wei Xiao Du Yin (Five-Ingredient Decoction to Eliminate Toxin), Yin Hua Jie Du Tang (Honeysuckle Decoction to Relieve Toxicity), and Huang Lian Jie Du Tang (Coptis Decoction to Relieve Toxicity). Inflammation at the site of infection may be treated externally with Yu Lu San (Jade Dew Extract) or Jin Huang San (Golden Yellow Powder). Specific Chinese herbs and treatments can be used for specific symptoms. For examples, for systemic bacterial infection, one may use honeysuckle flower, forsythia, isatidis, scutellaria, and phellodendron. Acupuncture and ear acupuncture treatments are also used.
- Herbals. Botanical remedies include Echinacea (Echinacea species) to clear infection and boost the immune system, goldenseal (Hydrastis canadensis) to clear infection and boost the immune system, garlic to clear bacterial infection, and spilanthes (Spilanthes species) for spirochete infections.
- Hydrotherapy. The joint pain associated with Lyme disease can be treated with hydrotherapy. Dull, penetrating pain may be relieved by applying a warm compress to the affected area. Sharp, intense pain may be relieved by applying an ice pack to the affected area.
- Guided imagery. The patient may treat Lyme disease by visualizing Bb as looking like ticks swimming in the bloodstream being killed by the flame of a candle.
- Probiotics. Probiotics is treatment with beneficial microbes either by ingestion or through a suppository. Probiotics can restore a healthy balance of bacteria to the body in cases in which long-term antibiotic use has caused diarrhea or yeast infection. Yogurt or Lactobacillus acidophilus preparations may be ingested.
If aggressive antibiotic therapy is given early, and the patient cooperates fully and sticks to the medication regimen, recovery should be complete. Only a small percentage of Lyme disease patients fail to respond or relapse (have recurring episodes). Most long-term effects of the disease result when diagnosis and treatment is delayed or missed. Co-infection with other infectious organisms spread by ticks in the same areas as B. burgdorferi (babesiosis and ehrlichiosis, for instance) may be responsible for treatment failures or more severe symptoms. Most fatalities reported with Lyme disease involved patients co-infected with babesiosis.
Minimizing risk of exposure
Precautions to avoid contact with ticks include moving leaves and brush away from living quarters. Most important are personal protection techniques when outdoors, such as:
- spraying tick repellent on clothing and exposed skin.
- wearing light-colored clothing to maximize ability to see ticks.
- tucking pant legs into socks or boot top.
- checking children and pets frequently for ticks.
- inspecting each individual living in high-risk areas daily for ticks in the spring and summer.
Minimizing risk of disease
The two most important factors are removing the tick quickly and carefully, and seeking a doctor’s evaluation at the first sign of symptoms of Lyme disease. When in an area that may be tick-populated:
- Check for ticks, particularly in the area of the groin, underarm, behind ears, and on the scalp.
- Stay calm and grasp the tick as near to the skin as possible, using tweezers.
- To minimize the risk of squeezing more bacteria into the bite, pull straight back steadily and slowly to remove the tick.
- Do not try to remove the tick by using petroleum jelly, alcohol, or a lit match.
- Place the tick in a closed container (for species identification later, should symptoms develop) or dispose of it by flushing.
- See a physician immediately for any sort of rash or patchy discoloration that appears three to 30 days after a tick bite.
Above: How to remove a tick. If you have a tick, it is important to remove it properly. Using fine-tipped tweezers, grasp the part of the tick that's closest to your skin -- you want to grab the head, not the belly. Slowly pull the tick straight out, without twisting it. Wash the bite site with soap and warm water. Apply antiseptic if available. Throw the dead tick into the trash. Do not use a lit match, nail polish, petroleum jelly, or other topical agents in an attempt to remove a tick.
A vaccine for Lyme disease was available from 1998 to 2002, when it was removed from the United States market. Protection provided by the vaccine fades over time. Anyone who was vaccinated at the time the vaccine was available likely no longer has any protection against the disease. A vaccine still exists for dogs, although veterinarians have mixed ideas about its use.
Weintraub, Pamela. Cure Unknown: Inside the Lyme Epidemic. New York: St. Martin’s Press, 2008
Learn About Lyme Disease. United States Centers for Disease Control and Prevention. March 10, 2010. http://www.cdc.gov/ncidod/dvbid/lyme
Lyme Disease. MedlinePlus. March 29, 2010. http:// www.nlm.nih.gov/medlineplus/lymedisease.html
American Lyme Disease Foundation, P. O. Box 466, Lyme, CT, 06371, http://www.aldf.com
Lyme Disease Network of NJ. , 43 Winton Road, East Brunswick, NJ, 08816, http://www.lymenet.org
Lyme disease (Lyme borreliosis) in detail - technical
Lyme borreliosis is a zoonotic bacterial infection caused by Borrelia burgdorferi sensu lato, a spirochaetal agent transmitted by certain species of Ixodes ticks. Small rodents and birds serve as reservoirs. It is the most common vector-borne infection in the United States of America and an important infection in many countries throughout the temperate regions of Europe and northern Asia, where a wider variety of borrelia species account for differences in clinical manifestations in Eurasia compared with the United States.
Clinical features—the commonest and earliest clinical manifestation is erythema migrans, a distinctive cutaneous lesion that occurs at the site of deposition of the spirochaete by the vector tick, beginning 7–14 days later as a red macule or papule, with the rash then expanding over days to weeks, with or without central clearing. This may be associated with ‘viral’ symptoms, fever and regional lymphadenopathy. Later manifestations include (1) carditis—usually manifested by fluctuating degrees of atrioventricular block; (2) neurological involvement—including cranial neuropathy (typically cranial nerve VII palsy), radiculopathy, and meningitis; (3) arthritis—typically migratory monoarthritis or asymmetric oligoarthritis; (4) acrodermatitis chronica atrophicans—a swollen, bluish-red appearing skin lesion in which the involved skin ultimately atrophies.
Diagnosis—the diagnosis of erythema migrans is purely clinical in geographical areas endemic for Lyme borreliosis: serological testing is not recommended because it is insufficiently sensitive on acute phase serum samples. In patients with suspected later clinical manifestations, serological testing is essential because clinical findings alone lack sufficient specificity. Polymerase chain reaction (PCR) testing of joint fluid and/or cerebrospinal fluid may be helpful in some cases.
Treatment—most people treated for Lyme borreliosis respond well to a 2-week course of antibiotic therapy (preferred oral regimen usually amoxicillin, doxycycline, or cefuroxime). Symptomatic treatment is recommended for patients who have or develop subjective complaints of unclear aetiology despite successful resolution of the objective manifestation of Lyme borreliosis following antibiotic therapy, since randomized double-blind placebo-controlled trials have shown that additional antibiotic treatment is not helpful.
Prevention—measures include avoiding exposure to ticks by limiting outdoor activities in tick-infested locations, using tick repellents, tucking in clothing to decrease exposed skin surfaces, and frequent inspection of the skin for early detection and removal of ticks.
Lyme borreliosis (also called Lyme disease) is named after Lyme, Connecticut, United States of America. It is caused by the spirochaete Borrelia burgdorferi sensu lato which is transmitted to humans by the usually asymptomatic bite of certain ticks of the genus Ixodes. Borrelia burgdorferi sensu stricto (hereafter referred to as B. burgdorferi) causes the disease in North America, while in Europe, several species of Borrelia in addition to B. burgdorferi cause this infection, including B. garinii which is probably the most common cause of classic Lyme neuroborreliosis (Bannwarth’s syndrome) and B. afzelii the most common cause of acrodermatitis chronica atrophicans, a late cutaneous complication. The entire chromosome and associated plasmids of one strain of B. burgdorferi have been completely sequenced. Representative strains of other pathogenic species, such as B. afzelii and B. garinii, have been partially sequenced.
In North America, more than 20 000 new cases of Lyme borreliosis are reported each year, making it the most common vector-borne disease. It occurs in north-eastern, mid-Atlantic, north-central, and far western regions of the United States of America and in limited foci in Canada (mainly in eastern Ontario). Elsewhere, it occurs in much of the temperate regions of Europe and northern Asia. Ticks acquire this borrelial infection in a complex tick–vertebrate transmission cycle. The white-footed mouse is the most important reservoir for B. burgdorferi in North America. White-tailed deer, an important host for adult Ixodes ticks, are not a competent reservoir for Lyme borreliae. In Europe a wide variety of small rodents and birds serve as reservoirs. Migrating birds may play a role in the spread of B. burgdorferi to new geographical locations.
Lyme borreliosis occurs slightly more frequently in males than in females. There is a bimodal age distribution with the highest rates in children between 5 and 9 years old and in adults 55–59 years old.
The somewhat different manifestations of Lyme borreliosis in Eurasia compared with North America (Table 1 below) may be explained by the wider variety of species of Lyme borrelia causing infection in Eurasia. Clinical features are similar in adults and children.
Erythema migrans (EM) (see picture below), the clinical hallmark of Lyme borreliosis, is recognized in approximately 90% of patients with objective clinical manifestations of B. burgdorferi infection. Typically, EM begins as a red macule or papule at the site of a tick bite that occurred 7 to 14 days earlier. The rash expands over days to weeks. Central clearing may or may not be present. Secondary cutaneous lesions may develop because of haematogenous spread of spirochaetes to other cutaneous sites. EM must be distinguished from local tick bite reactions, tinea, insect and spider bites, bacterial cellulitis, and plant dermatitis. Lesions eventually resolve spontaneously but may recur if antimicrobial therapy is not given.
Above: erythema migrans rash
Above: As the disease spreads. If the disease is not detected and treated in its early stages, it can extend to more areas of the body, affecting the joints, heart, and nervous system (about one to four months after the initial bite). Additional rashes may occur, and there may be intermittent periods of pain and weakness in the arms or legs. Facial-muscle paralysis (Bell's palsy), headaches, and poor memory are other symptoms at this stage, along with a rapid heartbeat and some loss of control.
|Table 1 Lyme borreliosis in North America compared to Eurasia|
|North American Lyme borreliosis||Eurasian Lyme borreliosis|
|Vector||Ixodes(dammini) scapularis or Ixodes pacificus||Ixodes ricinus or Ixodes persulcatus|
|Aetiological agent||B. burgdorferi sensu stricto||B. burgdorferi sensu stricto, B. afzelii, B. garinii, B. spielmanii|
|Clinical features||Erythema migrans is the most common manifestation.||Erythema migrans is the most common manifestation|
|Cranial nerve palsy (usually 7th) with or without meningitis is the most common neurological manifestation||Painful meningoradiculoneuritis with or without cranial palsy is the most common neurological manifestation|
Above: Do all ticks transmit Lyme Disease? No. In the northeastern and north-central U.S., the black-legged tick (or deer tick) transmits Lyme disease. In the Pacific coastal U.S., the disease is spread by the western black-legged tick. Other major tick species found in the U.S., including the lone star tick and the dog tick, have NOT been shown to transmit the Lyme disease bacterium. But beware: Lyme disease has been reported in all 50 states, as well as in Canada, Europe, Asia, Australia, and South America.Systemic symptoms, such as fatigue, myalgia, arthralgia, headache, fever and/or chills, and stiff neck, are less common in patients with EM caused by B. afzelii compared to either B. burgdorferi or B. garinii. Prominent respiratory and/or gastrointestinal symptoms are so infrequent that their presence should suggest an alternative diagnosis or coinfection with another tick-borne pathogen. Aside from the EM skin lesion itself, the most common objective physical findings are regional lymphadenopathy and fever. Occasional cases of a viral-like illness without EM have been attributed to Lyme borreliosis.
Typically, cardiac disease develops within weeks to months after infection, sometimes together with EM. It is usually manifested by fluctuating degrees of atrioventricular block that may cause the patient to complain of dizziness, palpitations, dyspnoea, chest pain, or syncope. Myocarditis may be present but pericarditis with effusion is rarely observed, and endocarditis is absent. The incidence of cardiac manifestations (as measured by ECG confirmed heart block) has been observed to be low in both the United States of America (<1%) and Europe (<4%).
The incidence of neurological Lyme disease in Europe may be higher than in the United States of America. One explanation may be the greater neurotropism of B. garinii (a genospecies which has not been isolated in North America). The principal early neurological manifestations are cranial neuropathy (typically peripheral seventh nerve palsy which can be bilateral), radiculopathy, and meningitis, which may occur alone or together. EM may be present concomitantly. Late neurological manifestations are uncommon and include peripheral neuropathy, encephalopathy, and encephalomyelitis.
Antibiotics appear to hasten the resolution of meningitis but most studies are uncontrolled. The rate of resolution of motor dysfunction, which is fully reversible in the vast majority of cases, is not enhanced by antimicrobial therapy. Symptoms of encephalopathy and peripheral neuropathy improve or do not progress after treatment with antibiotics.
Lyme arthritis occurs in both North America and Europe. In a study of 55 untreated patients with EM diagnosed in the United States of America between 1977 and 1979 and followed for a mean duration of 6 years, objective arthritis developed in more than one-half, occurring within 1 year for 90%. The majority of these patients developed intermittent attacks of migratory monoarthritis or asymmetric oligoarthritis, lasting a mean of 3 months per episode (range 3 days to 11.5 months). The knee was affected at some point in almost all patients, but other large and (less often) small joints could be affected. Temporomandibular joint involvement occurred in 11 (39%) of 28 patients with arthritis in one series. Although large effusions may occur, joint pain and erythema are often minimal. Baker’s cysts may develop. Typically, synovial fluid analysis reveals a modestly elevated white cell count (median 24 250 white cells/mm3 in one study) with a polymorphonuclear predominance and a normal glucose level. Synovitis lasting 1 year or more may ensue for a minority of United States patients, sometimes associated with joint destruction. Although B. burgdorferi DNA can be detected by polymerase chain reaction (PCR) in the synovial fluid of up to 85% of untreated patients with Lyme arthritis, B. burgdorferi has rarely been successfully cultured from joint fluid.
Above: Picture of osteoarthritis of knees. Late stage disease. This is the most serious stage of the disease, when treatment was either not successful or never started (usually occurring many months after the initial bite). Joint inflammation (arthritis), typically in the knees, becomes apparent, and may become chronic. The nervous system can develop abnormal sensation because of disease of peripheral nerves (peripheral neuropathy), and confusion. Heart problems are less common, but can include inflammation of the heart muscle and irregular heart beat.
Acrodermatitis chronica atrophicans (ACA)
This cutaneous manifestation of late Lyme disease develops insidiously on a distal extremity, mainly in elderly women. It is a swollen bluish-red appearing skin lesion in which the involved skin ultimately atrophies. One-third of patients have an associated (usually sensory) polyneuropathy. B. burgdorferi has been recovered from a skin biopsy specimen of an ACA lesion of more than 10 years duration. Since the usual causative agent B. afzelii does not occur in the United States of America, ACA is essentially a European disease.
Miscellaneous clinical manifestations
Borrelia lymphocytoma, principally caused by B. afzelii and B. garinii, is a tumour-like nodule which typically appears on the pinna of the earlobe or on the nipple or areola of the breast. Lesions will eventually resolve spontaneously but disappear within a few weeks after antibiotic therapy. This lesion is extremely rare in North America.
Direct involvement of the eye (e.g. uveitis, keratitis, vitritis, optic neuritis) has been attributed to B. burgdorferi infection. However, since ophthalmological disorders have almost never been associated with the isolation of B. burgdorferi in culture, the actual pathogenesis in these cases is uncertain. Conjunctivitis, originally described in 11% of patients with EM, was rare (<5%) in recent studies of culture-positive patients and may be unrelated to borrelia infection.
Case reports have suggested that adverse outcomes may be associated with pregnancies complicated by maternal Lyme borreliosis. However, prospective and epidemiological studies suggest that the risk of transplacental transmission of B. burgdorferi is probably minimal when appropriate antibiotics (Tables 2 and 3 below) are given to pregnant women with Lyme borreliosis. There are no published data to support a congenital Lyme borreliosis syndrome.
Where Lyme borreliosis is endemic, the diagnosis of EM is purely clinical. Laboratory testing is neither necessary nor recommended.
In patients with suspected extracutaneous Lyme borreliosis, serological testing is essential to support the diagnosis. Culture of B. burgdorferi has been a highly insensitive diagnostic technique for this group of patients, presumably because of inaccessibility of tissues containing the microorganism. PCR testing of joint fluid and sometimes of cerebrospinal fluid may aid in diagnosis, provided appropriate care is taken in performing the assay accurately.
A two-step approach to serological diagnosis is used in both the United States of America and Europe to increase the accuracy of a positive test. A positive or equivocal first-step test (usually an enzyme-linked immunosorbent assay (ELISA) or an indirect immunofluorescence assay (IFA)) is followed on the same serum sample by a second-stage test (immunoblot). Two-step testing, however, is not indicated for those with little or no clinical evidence of Lyme borreliosis because of a low positive predictive value. Since IgM and IgG antibodies to B. burgdorferi may persist in serum for years after clinical recovery, serology has no role in measuring response to treatment.
Patients with extracutaneous Lyme borreliosis almost always have diagnostic serum antibodies at time of presentation. In some patients with early neuroborreliosis, however, antibodies to Lyme borrelia may be present in cerebrospinal fluid before they are detected in serum.
Ixodes scapularis ticks are the vectors for several other infections that may be transmitted separately or simultaneously with B. burgdorferi, such as Babesia microti and the rickettsial agent Anaplasma phagocytophilum that causes human granulocytic anaplasmosis (HGA, formerly known as human granulocytic ehrlichiosis (HGE)). In Europe, species of Babesia and Anaplasma are present in Ixodes ricinus ticks , which are also vectors of the flavivirus causing tick-borne encephalitis. Coinfection may alter the clinical presentation and response to treatment of Lyme borreliosis.
Reinfection with Lyme borrelia can often be recognized clinically by the development of a repeat episode of EM occurring at a different skin site during the months when the vector tick is plentiful in the environment. The clinical manifestations of reinfection in Lyme borreliosis patients who have EM are indistinguishable from initial infection.
|Table 2 Recommended antimicrobial regimens for treatment of patients with Lyme borreliosis|
|Drug||Dosage for adults||Dosage for children|
|Preferred oral regimens|
|Amoxicillin||500 mg three times dailya||50 mg/kg per day in three divided doses (maximum 500 mg per dose)a|
|Doxycycline||100 mg twice dailyb||<8 years: not recommended|
|≥8 years: 4 mg/kg per day in two divided doses (maximum 100 mg/dose)|
|Cefuroxime axetil||500 mg twice daily||30 mg/kg per day in two divided doses (maximum 500 mg per dose)|
|Selected macrolidesc||Azithromycin 500 mg orally daily for 7–10 days, clarithromycin 500 mg orally twice daily for 14–21 days (if not pregnant), or erythromycin 500 mg orally four times per day for 14–21 days||Azithromycin 10 mg/kg daily (maximum of 500 mg per day), clarithromycin 7.5 mg/kg twice daily (maximum of 500 mg per dose), or erythromycin 12.5 mg/kg four times daily (maximum of 500 mg per dose)|
|Preferred parenteral regimen|
|Ceftriaxone||2 g intravenously once daily||50–75 mg/kg intravenously once daily (maximum 2 g)|
|Alternative parenteral regimens|
|Cefotaxime||2 g intravenously every 8 hd||150–200 mg/kg per day intravenously in 3 or 4 divided doses (maximum 6 g per day)d|
|Penicillin G||3–4 million units intravenously every 4 hd||200 000–400 000 units/kg per day divided into six doses given every 4 hd (not to exceed 18–24 million units/day)|
a Although higher dosage given twice daily might be equally as effective, in view of the absence of data on efficacy, twice daily administration is not recommended.
b Tetracyclines are relatively contraindicated in pregnant or lactating women and in children less than 8 years of age.
c Due to their lower efficacy, macrolides are reserved for patients who are unable to take or who are intolerant of tetracyclines, penicillins, and cephalosporins. Patients treated with macrolides should be closely followed to ensure resolution of the clinical manifestations.
d Dosage should be reduced for patients with impaired renal function.
Modified from Wormser GP, et al. (2006). The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis and babesiosis. Clinical practices guidelines by the Infectious Diseases Society of America. Clin Infect Dis, 43, 1089–134.
Although most manifestations of Lyme borreliosis resolve spontaneously, antibiotics may speed the resolution of some and will almost certainly prevent the progression of disease. An approach to treatment is summarized in Tables 2 and 3. Presently available fluoroquinolones, sulphonamides, first-generation cephalosporins, rifampicin, and aminoglycosides have no appreciable activity against B. burgdorferi and should not be used. There is no evidence to support combination antimicrobial therapy, prolonged (more than 1 month) or repeated courses of antibiotics, and ‘pulse’ or intermittent antibiotic therapy. Within 24 h after initiation of antibiotics, approximately 15% of patients with EM may develop transient intensification of signs (e.g. rash and fever) and symptoms (e.g. arthralgias) consistent with a Jarisch–Herxheimer reaction. Treatment is symptomatic.
Most people treated for Lyme borreliosis have an excellent prognosis. Although a minority of patients treated for EM in recent series continue to have a variety of mild nonspecific complaints following antibiotic therapy, the development of objective extracutaneous disease after treatment is extremely rare. When such complaints are disabling and last for 6 months or more they have been referred to as post-Lyme disease syndrome (PLDS). Randomized double-blind placebo-controlled antibiotic treatment trials of patients with PLDS have failed to show evidence that the benefit of additional antibiotic therapy outweighs the complications of such treatment. Symptomatic therapy is recommended.
Patients with carditis and neurological disease tend to do well, but may sometimes have residual deficits (e.g. mild seventh nerve palsy) after treatment. In patients with arthritis, clinical recovery occurs typically with oral antibiotic therapy (often in conjunction with a nonsteroidal anti-inflammatory medication (NSAID)). Occasionally patients with Lyme arthritis with subtle signs of neuroborreliosis who are treated with oral antibiotics will develop overt late neuroborreliosis and require parenteral therapy. A small number of American patients with Lyme arthritis continue to have synovial inflammation for months or even several years after the apparent eradication of B. burgdorferi from the joint following antibiotic therapy (based on negative PCR testing). Such patients have improved after synovectomy. An immunological mechanism rather than active infection appears to be responsible for the continued inflammatory response in these patients.
In North America predominantly, but also in Europe, several patients with a variety of symptoms of uncertain aetiology, including pain and fatigue syndromes, have been labelled as having ‘chronic Lyme disease’, irrespective of tick exposure in an endemic area for Lyme borreliosis or credible clinical or laboratory evidence of infection due to Lyme borrelia. There is no scientific evidence that such patients have active infection due to borreliae.
Preventive measures include avoiding exposure by limiting outdoor activities in tick-infested locations, using tick repellents, tucking in clothing to decrease exposed skin surfaces, and frequent skin inspections for early detection and removal of ticks. Use of acaricides on property and construction of deer fences have also been proposed.
|Table 3 Recommended therapy for patients with Lyme borreliosisa|
|Indication||Treatment||Duration (days)||Range (days)|
|Tick bite in the USA||Doxycycline 200 mg (4 mg/kg in children ≥8 years of age) and/or observation||Single doseb|
|Erythema migrans||Oral regimenc,d||14||10–21e|
|Early neurological disease|
|Meningitis or radiculopathy||Parenteral regimenc,f||14||10–28|
|Cranial nerve palsyg||Oral regimenc||14||14–21|
|Cardiac disease||Oral regimenc,hor||14||14–21|
|Borrelial lymphocytoma||Oral regimenc,d||14||14–21|
|Arthritis without neurological disease||Oral regimenc||28||28|
|Recurrent arthritis after oral regimen||Oral regimenc,i||28||28|
|Antibiotic-refractory arthritisj||Symptomatic therapyk|
|Central or peripheral nervous system disease||Parenteral regimenc||14||14–28|
|Acrodermatitis chronica atrophicans||Oral regimenc||21||14–28|
|Post-Lyme disease syndrome||Consider and evaluate other potential causes of symptoms, if none found then symptomatic therapy|
a Regardless of the clinical manifestation of Lyme disease, complete response to treatment may be delayed beyond the treatment duration. Relapse may occur with any of these regimens; patients with objective signs of relapse may need a second course of treatment.
b A single dose of doxycycline may be offered to adult patients and to children ≥8 years of age in the United States of America only when all of the following circumstances exist: (a) the attached tick can be reliably identified as an adult or nymphal I. scapularis tick that is estimated to have been attached for ≥36 h based on the degree of engorgement of the tick with blood or on certainty about the time of exposure to the tick; (b) prophylaxis can be started within 72 h of the time that the tick was removed; (c) ecological information indicates that the local rate of infection of these ticks with B. burgdorferi is ≥20%; and (d) doxycycline is not contraindicated. For patients who do not fulfil these criteria, observation is recommended.
c See Table 2.
d For adult patients intolerant of amoxicillin, doxycycline, and cefuroxime axetil, a macrolide may be given (Table 126.96.36.199). Patients treated with macrolides should be closely followed to ensure resolution of the clinical manifestations.
e If doxycycline is used, 10 days of therapy is effective; the efficacy of 10-day regimens with the other first-line agents is unknown.
f Data from European studies of neuroborreliosis indicate that oral doxycycline and parenteral antibiotic therapy are equally effective in Lyme meningitis. Similar studies have not been conducted in the United States of America. For nonpregnant adult patients intolerant of β-lactam agents, the recommended dosage of doxycycline, 200–400 mg/day orally (or intravenously if unable to take oral medications) in two divided doses, may be adequate. For children ≥8 years of age the recommended dosage of doxycycline for this indication is 4–8 mg/kg per day in two divided doses (maximum daily dosage of 200–400 mg).
g Most patients may be treated successfully with an oral regimen. Parenteral antibiotic therapy is recommended for patients with both clinical and laboratory evidence of coexistent meningitis. Systematic studies of oral antibiotic therapy in patients with cranial nerve palsy have only evaluated doxycycline. Other oral agents such as amoxicillin or cefuroxime axetil may be effective in patients who should not receive or cannot tolerate doxycycline, but clinical trials with these antibiotics are lacking. Most of the experience in the use of oral antibiotic therapy is for patients with seventh cranial nerve palsy. Whether oral therapy would be as effective for patients with other cranial neuropathies is unknown. The decision between oral and parenteral antimicrobial therapy for patients with other cranial neuropathies should be individualized.
h A parenteral antibiotic regimen is recommended at the start of therapy for patients who have been hospitalized for cardiac monitoring; an oral regimen may be substituted to complete a course of therapy or to treat ambulatory patients. A temporary pacemaker may be required for patients with advanced heart block.
i A second course of oral antibiotic therapy is preferred for the patient whose arthritis has substantively improved but has not yet completely resolved. Consideration of retreatment of such patients is often postponed for several months because of the anticipated slow resolution of inflammation after antibiotic treatment. During this interval use of nonsteroidal anti-inflammatory agents (NSAIDs) may be beneficial. Parenteral antibiotic therapy is reserved for those patients whose arthritis failed to improve at all or worsened.
j Antibiotic-refractory Lyme arthritis is operationally defined as persistent synovitis for at least 2 months after completion of a course of intravenous ceftriaxone (or after completion of two 4-week courses of an oral antibiotic regimen for patients unable to tolerate cephalosporins); in addition, PCR on synovial fluid (and synovial tissue if available) is negative for B. burgdorferi nucleic acids.
k Symptomatic therapy might consist of NSAIDs, intra-articular injections of corticosteroids, or other medications. If persistent synovitis is associated with significant pain or if it limits function, arthroscopic synovectomy should be considered.
Modified from Wormser GP, et al. (2006). The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis and babesiosis. Clinical practices guidelines by the Infectious Diseases Society of America. Clin Infect Dis, 43, 1089–134.
Antibiotic prophylaxis with single-dose doxycycline given after recognized I. scapularis tick bites has been shown to be 87% effective in reducing further the low (less than 5%) risk of acquiring Lyme borreliosis after tick bites in the United States of America. Vaccination with a single recombinant outer surface protein A (OspA) preparation has been found to be safe and effective for preventing Lyme borreliosis in the United States of America, but this vaccine is no longer available. Canine vaccines for prevention of Lyme borreliosis, however, are widely used in North America.
- Aguero-Rosenfeld M, et al. (2005). Diagnosis of Lyme borreliosis. Clin Microbiol Rev, 18, 484–509.
- Feder HM Jr, et al. (2007). A critical appraisal of ‘chronic Lyme disease’. N Engl J Med, 357, 1422–30.
- Günther G, Haglund M (2005). Tick-borne encephalopathies. Epidemiology, diagnosis, treatment and prevention. CNS Drugs, 19, 1009–32.
- Halperin JJ, et al. (2007). Practice parameter: treatment of nervous system Lyme disease (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology, 69, 91–102.
- Kaplan RF, et al. (2003). Cognitive function in post-treatment Lyme disease. Do additional antibiotics help? Neurology, 60, 1916–22.
- Klempner MS, et al. (2001). Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. N Engl J Med, 345, 85–92.
- Mygland A, et al. (2009). EFNS guidelines on the diagnosis and management of European Lyme neuroborreliosis. Eur J Neurol (E pub ahead of print).
- Nau R, et al. (2009). Lyme disease—Current state of knowledge. Dtsch Arztebl Int, 106, 72–82.
- Stanek G, et al. (1996). European Union concerted action on risk assessment in Lyme borreliosis: clinical case definitions for Lyme borreliosis. Wien Klin Wochenschr, 108, 741–7.
- Wormser GP, et al. (2006). The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis, 43, 1089–134.