Issue Description Lyme disease is the most common tick-borne
disease in the Northern Hemisphere. Borrelia is transmitted to humans
by the bite of infected ticks belonging to certain species of the
genus Ixodes (the hard-bodied 'hard ticks'). Early manifestations of
infection may include fever, headache, fatigue, depression, and a
characteristic skin rash called erythema migrans. Left untreated, late
manifestations involving the joints, heart, and nervous system can
occur. In most cases, the infection and its symptoms are eliminated
with antibiotics, especially if diagnosis and treatment occur early in
the course of illness. Late, delayed, or inadequate treatment can lead
to late manifestations of Lyme disease which can be disabling and
difficult to treat Other Names Lyme Disease
Symptoms Lyme disease can affect multiple body systems,
producing a range of potential symptoms. Not all patients with Lyme
disease will have all symptoms, and many of the symptoms are not
specific to Lyme disease but can occur in other diseases as well. The
incubation period from infection to the onset of symptoms is usually
1-2 weeks, but can be much shorter (days), or much longer (months to
years). Symptoms most often occur from May through September because
the nymphal stage of the tick is responsible for most cases.
Asymptomatic infection exists but is found in less than 7% of infected
individuals in the United States. Asymptomatic infection may be much
more common among those infected in Europe.
Stage 1 - Early Localized Infection The classic sign of early local infection is a
circular, outwardly expanding rash called erythema chronicum migrans
(also erythema migrans or EM), which occurs at the site of the tick
bite 3 to 32 days after being bitten. The rash is red, and may be
warm, but is generally painless. Classically, the innermost portion
remains dark red and becomes indurated; the outer edge remains red;
and the portion in between clears - giving the appearance of a
bullseye. However, the partial clearing is uncommon, and thus a true
bullseye occurs in as few as 9% of cases.
is thought to occur in about 80% of infected patients. Patients can
also experience flu-like symptoms such as headache, muscle soreness,
fever, and malaise. Lyme disease can progress to later stages even in
patients who do not develop a rash.
Stage 2 - Early Disseminated Infection Within days to weeks after the onset of local
infection, the borrelia bacteria may begin to spread through the
bloodstream. Erythema migrans may develop at sites across the body
that bear no relation to the original tick bite. Another skin
condition, which is apparently absent in North American patients, is
borrelial lymphocytoma, a purplish lump that develops on the ear lobe,
nipple, or scrotum. Other discrete symptoms include migrating pain in
muscles, joint, and tendons, and heart palpitations and dizziness
caused by changes in heartbeat.
problems, which appear in 15% of untreated patients, encompasses a
spectrum of disorders. One is facial or Bell's palsy, which is the
loss of muscle tone on one or both sides of the face. Another common
neurologic manifestation is meningitis, characterized by severe
headaches, neck stiffness, and sensitivity to light. Radiculoneuritis
causes shooting pains that may interfere with sleep and abnormal skin
sensations. Mild encephalitis may lead to memory loss, sleep
disturbances, or changes in mood or affect. In addition, simple
altered mental status as the sole presenting symptom has been reported
in early neuroborreliosis.
Stage 3 - Late Persistent Infection After several months, untreated or inadequately
treated patients may go on to develop severe and chronic symptoms
affecting many organs of the body including the brain, nerves, eyes,
joints and heart. Myriad disabling symptoms can occur.
Chronic neurologic symptoms occur in up to 5% of untreated patients. A
polyneuropathy manifested primarily as shooting pains, numbness, and
tingling in the hands or feet may develop. A neurologic syndrome
called Lyme encephalopathy is associated with subtle cognitive
problems such as difficulties with concentration and short term
memory. Such patients may also experience profound fatigue. Other
problems such as depression and fibromyalgia are no more common in
people who have been infected with Lyme than in the general
population. Chronic encephalomyelitis, which may be progressive, may
involve cognitive impairment, weakness in the legs, awkward gait,
facial palsy, bladder problems, vertigo, and back pain. In rare cases,
frank psychosis has been attributed to chronic Lyme disease effects,
including mis-diagnoses of schizophrenia and bipolar disorder. Panic
attack and anxiety can occur, also delusional behavior, including
somatoform delusions, sometimes accompanied by a depersonalization or
derealization syndrome similar to what was seen in the past in the
prodromal or early stages of general paresis.
arthritis usually affects the knees. In a minority of patients
arthritis can occur in other joints, including the ankles, elbows,
wrist, hips, and shoulders. Pain is often mild or moderate, usually
with swelling at the involved joint. Baker's cysts may form and
rupture. In some cases joint erosion occurs.
chronica atrophicans (ACA) is a chronic skin disorder observed
primarily in Europe. ACA begins as a reddish-blue patch of
discolored skin, usually in sun-exposed regions of the upper or lower
limbs. The lesion slowly atrophies, and the skin may become so thin
that it resembles wrinkled cigarette paper.
Cause Lyme disease is caused by Gram-negative
spirochetal bacteria from the genus Borrelia. At least 11 Borrelia
species have been described, 3 of which are Lyme related. The Borrelia
species known to cause Lyme disease are collectively known as Borrelia
burgdorferi sensu lato, and have been found to have greater strain
diversity than previously estimated.
species of spirochetes are well-established as causing Lyme disease
and are probably responsible for the large majority of cases: B.
burgdorferi sensu stricto (predominant in North America, but also in
Europe), B. afzelii, and B. garinii (both predominant in Eurasia).
Some studies have also proposed that B. bissettii and B. valaisiana
may sometimes infect humans, but these species do not seem to be
important causes of disease.
Transmission Hard-bodied ticks of the genus Ixodes are the
primary vectors of Lyme disease. The majority of infections are caused
by ticks in the nymph stage, since adult ticks are more easily
detected and removed as a consequence of their relatively large size.
Transmission is relatively rare, with only about 1% of recognized tick
bites resulting in Lyme disease: this may be due to the fact that an
infected tick has to be attached for at least a day for transmission
In Europe, the sheep tick, castor bean tick, or European castor bean
tick (Ixodes ricinus) is the transmitter.
In North America,
the black-legged tick or deer tick (Ixodes scapularis) has been
identified as the key to the disease's spread on the east coast. Only
about 20% of people who become infected with Lyme disease by the deer
tick can remember having been bitten, making early detection difficult
in the absence of a rash. Tick bites often go unnoticed because of the
small size of the tick in its nymphal stage, as well as tick
secretions that prevent the host from feeling any itch or pain from
the bite. The lone star tick (Amblyomma americanum), which is found
throughout the Southeastern United States as far west as Texas, is
unlikely to transmit the Lyme disease spirochete Borrelia burgdorferi,
though it may be implicated in a related syndrome called southern
tick-associated rash illness, which resembles a mild form of Lyme
On the West Coast, the primary vector is the western black-legged tick
(Ixodes pacificus). The tendency of this tick species to feed
predominantly on host species that are resistant to Borrelia infection
appears to diminish transmission of Lyme disease in the West.
While Lyme spirochetes have been found in insects other than ticks,
reports of actual infectious transmission appear to be rare. Sexual
transmission has been anecdotally reported; Lyme spirochetes have been
found in semen and breast milk, however transmission of the spirochete
by these routes is not known to occur.
transmission of Lyme disease can occur from an infected mother to
fetus through the placenta during pregnancy, however prompt antibiotic
treatment appears to prevent fetal harm.
Diagnosis Lyme disease is diagnosed clinically based on
symptoms, objective physical findings (such as erythema migrans,
facial palsy, or arthritis), a history of possible exposure to
infected ticks, as well as serological tests. When making a diagnosis
of Lyme disease, health care providers should consider other diseases
that may cause similar illness. Most but not all patients with Lyme
disease will develop the characteristic bulls-eye rash, and many may
not recall a tick bite. Laboratory testing is not recommended for
persons who do not have symptoms of Lyme disease.
of the difficulty in culturing Borrelia bacteria in the laboratory,
diagnosis of Lyme disease is typically based on the clinical exam
findings and a history of exposure to endemic Lyme areas. The EM rash,
which does not occur in all cases, is considered sufficient to
establish a diagnosis of Lyme disease even when serologies are
negative. Serological testing can be used to support a clinically
suspected case but is not diagnostic.
late-stage Lyme disease is often difficult because of the
multi-faceted appearance which can mimic symptoms of many other
diseases. Lyme disease may be misdiagnosed as multiple sclerosis,
rheumatoid arthritis, fibromyalgia, chronic fatigue syndrome (CFS),
lupus, or other autoimmune and neurodegenerative diseases.
Prevention Attached ticks should be removed promptly.
Protective clothing includes a hat and long-sleeved shirts and long
pants that are tucked into socks or boots. Light-colored clothing
makes the tick more easily visible before it attaches itself. People
should use special care in handling and allowing outdoor pets inside
homes because they can bring ticks into the house.
effective, community wide method of preventing Lyme disease is to
reduce the numbers of primary hosts on which the deer tick depends
such as rodents, other small mammals, and deer. Reduction of the deer
population may over time help break the reproductive cycle of the deer
ticks and their ability to flourish in suburban and rural areas.
An unusual, organic approach to control of ticks and prevention of
Lyme disease involves the use of domesticated guineafowl. Guinea Fowl
are voracious consumers of insects and have a particular fondness for
ticks. localized use of domesticated guineafowl may reduce dependence
on chemical pest-control methods. Many victims of ticks and others
with concern often turn to the Guinea Fowl Breeders Association for
advice on this topic.
Management of Host Animals Lyme and all other deer-tick-borne diseases can
be prevented on a regional level by reducing the deer population that
the ticks depend on for reproductive success. This has been
demonstrated in the communities of Monhegan, Maine and in Mumford
Cove, Connecticut. The black-legged or deer tick (Ixodes scapularis)
depends on the white-tailed deer for successful reproduction.
For example, in the US, it is suggested that by reducing the deer
population to levels of 8 to 10 per square mile (from the current
levels of 60 or more deer per square mile in the areas of the country
with the highest Lyme disease rates), the tick numbers can be brought
down to levels too low to spread Lyme and other tick-borne diseases.
However, such a drastic reduction may be impractical in many areas.
Vaccination A recombinant vaccine against Lyme disease,
based on the outer surface protein A (OspA) of B. burgdorferi, was
developed by GlaxoSmithKline. In clinical trials involving more than
10,000 people, the vaccine, called LYMErix, was found to confer
protective immunity to Borrelia in 76% of adults and 100% of children
with only mild or moderate and transient adverse effects. LYMErix was
approved on the basis of these trials by the U.S. Food and Drug
Administration (FDA) on December 21, 1998.
approval of the vaccine, its entry in clinical practice was slower
than expected for a variety of reasons including its cost, which was
often not reimbursed by insurance companies. Subsequently, hundreds of
vaccine recipients reported that they had developed autoimmune side
effects. Supported by some patient advocacy groups, a number of
class-action lawsuits were filed against GlaxoSmithKline alleging that
the vaccine had caused these health problems. These claims were
investigated by the FDA and the U.S. Centers for Disease Control
(CDC), who found no connection between the vaccine and the autoimmune
Despite the lack of evidence that the complaints were caused by the
vaccine, sales plummeted and LYMErix was withdrawn from the U.S.
market by GlaxoSmithKline in February 2002 in the setting of negative
media coverage and fears of vaccine side effects. The fate of LYMErix
was described in the medical literature as a "cautionary tale"; an
editorial in Nature cited the withdrawal of LYMErix as an instance in
which "unfounded public fears place pressures on vaccine developers
that go beyond reasonable safety considerations," while the original
developer of the OspA vaccine at the Max Planck Institute told Nature:
"This just shows how irrational the world can be... There was no
scientific justification for the first OspA vaccine [LYMErix] being
New vaccines are being researched using outer
surface protein C (OspC) and glycolipoprotein as methods of
Tick Removal Many old wives' tales exist about the proper
and effective method to remove a tick, however it is generally agreed
that the most effective method is to pull it straight out with
tweezers. Data have demonstrated that prompt removal of an infected
tick, within approximately 36 hours, reduces the risk of transmission
to nearly zero; however the small size of the tick, especially in the
nymph stage, may make detection difficult.
Treatment Antibiotics are the primary treatment for Lyme
disease; the most appropriate antibiotic treatment depends upon the
patient and the stage of the disease. The antibiotics of choice are
doxycycline (in adults), amoxicillin (in children), and ceftriaxone.
Alternative choices are cefuroxime and cefotaxime. Macrolide
antibiotics have limited efficacy when used alone.
of a recent double blind, randomized, placebo-controlled multicenter
clinical study, done in Finland, indicated that oral adjunct
antibiotics were not justified in the treatment of patients with
disseminated Lyme borreliosis who initially received intravenous
antibiotics for three weeks. The researchers noted the clinical
outcome of said patients should not be evaluated at the completion of
intravenous antibiotic treatment but rather 6-12 months afterwards. In
patients with chronic post-treatment symptoms, persistent positive
levels of antibodies did not seem to provide any useful information
for further care of the patient.
In later stages, the
bacteria disseminate throughout the body and may cross the blood-brain
barrier, making the infection more difficult to treat. Late diagnosed
Lyme is treated with oral or IV antibiotics, frequently ceftriaxone
for a minimum of four weeks. Minocycline is also indicated for
neuroborreliosis for its ability to cross the blood-brain barrier.
Prognosis For early cases, prompt treatment is usually
curative. However, the severity and treatment of Lyme disease may be
complicated due to late diagnosis, failure of antibiotic treatment,
and simultaneous infection with other tick-borne diseases
(co-infections) including ehrlichiosis, babesiosis, and bartonella,
and immune suppression in the patient.
published in 2005 found that some patients with Lyme disease have
fatigue, joint or muscle pain, and neurocognitive symptoms persisting
for years despite antibiotic treatment. Patients with late stage Lyme
disease have been shown to experience a level of physical disability
equivalent to that seen in congestive heart failure. In rare cases,
Lyme disease can be fatal.