lyme disease

Lyme disease is a bacterial infection that features a skin rash, swollen joints and flu-like symptoms. You get the disease from the bite of an infected tick. Sometimes it is hard to know if you have Lyme disease because you may not have noticed a tick bite. Also, many of its symptoms are like those of other diseases. Symptoms may include

* A skin rash, often resembling a bulls-eye
* Fever
* Headache
* Muscle pain
* Stiff neck
* Swelling of knees and other large joints


Lyme disease, or borreliosis, is an emerging infectious disease caused by at least three species of bacteria belonging to the genus Borrelia. Borrelia burgdorferi is the predominant cause of Lyme disease in the United States, whereas Borrelia afzelii and Borrelia garinii are implicated in most European cases.
Borrelia is transmitted to humans by the bite of infected hard ticks belonging to several species of the genus Ixodes. 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 a majority of cases, symptoms can be 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.

Some patients with Lyme disease have fatigue, joint or muscle pain, and neurocognitive symptoms persisting for years despite antibiotic treatment Randomized controlled trials found that only fatigue, but not neurocognitive symptoms, were sometimes improved with prolonged antibiotic treatment.These trials identified significant side effects and risks of prolonged antibiotic therapy, and most expert groups including the Infectious Diseases Society of America and the American Academy of Neurology have found that existing scientific evidence does not support a role for Borrelia nor ongoing antibiotic treatment in such cases.

In the early stages, doctors look at your symptoms and medical history to figure out whether you have Lyme disease. In the later stages of the disease, lab tests can confirm whether you have it.

Symptoms

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.

Erythema migrans 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.

Acute neurological 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 w

ith 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, bladd

er 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.

Diagnosis

Lyme disease is diagnosed clinically based on symptoms, objective ph

ysical 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. 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.

Because 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 conside

red 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. Clinicians who diagnose strictly based on the CDC Case Definition for Lyme may be in error, since the CDC explicitly states that this definition is intended for surveillance purposes only and is "not intended to be used in clinical diagnosis."

Diagnosis of late-stage Lyme disease is often difficult because of the multi-faceted appearance which can mimic symptoms of many other diseases. For this reason, L

yme has often been called the new "great imitator".Lyme disease may be misdiagnosed as multiple sclerosis, rheumatoid arthritis, fibromyalgia, chronic fatigue syndrome (CFS), lupus, or other autoimmune and neurodegenerative diseases.

Lyme 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.

Acrodermatitis 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.

Laboratory testing

Several forms of laboratory testing for Lyme disease are available, some of which have not been adequately validated. Most recommended tests are blood tests that measure antibodies made in response to the infection. These tests may be falsely negative in patients with early disease, but they are quite reliable for diagnosing later stages of disease.

The serological laboratory tests most widely available and em

ployed are the Western blot and ELISA. A two-tiered protocol is recommended by the CDC: the more sensitive ELISA is performed first, if it is positive or equivocal, the more specific Western blot is run. The reliability of testing in diagnosis remains controversial,however studies show the Western blot IgM has a specificity of 94–96% for patients with clinical symptoms of early Lyme disease.

Erroneous test results have been widely reported in both early and late stages of the disease. These errors can be caused by several factors, including antibody cross-reactions from other infections including Epstein-Barr virus and cytomegalovirus, as well as herpes simplex virus.^[51]

Polymerase chain reaction (PCR) tests for Lyme disease have also been developed to detect the genetic material (DNA) of the Lyme disease spirochete. PCR tests are su

sceptible to false-positive results from poor laboratory technique.Even when properly performed, PCR often shows false-negative results with blood and CSF specimens.Hence PCR is not widely performed for diagnosis of Lyme disease. However PCR may have a role in diagnosis of Lyme arthritis because it is highly sensitive in detecting ospA DNA in synovial fluid. With the exception of PCR, there is no currently practical means for detection of the presence of the organism, as serologic studies only test for antibodies of Borrelia. High titers of either immunoglobulin G (IgG) or immunoglobulin M (IgM) antibodies to Borrelia antigens indicate disease, but lower titers can be misleading. The IgM antibodies may remain after the initial infection, and IgG antibodies may remain for years.

Western blot, ELISA and PCR can be performed by either blood test via

venipuncture or cerebrospinal fluid (CSF) via lumbar puncture. Though lumbar puncture is more definitive of diagnosis, antigen capture in the CSF is much more elusive; reportedly CSF yields positive results in only 10–30% of patients cultured. The diagnosis of neurologic infection by Borrelia should not be excluded solely on the basis of normal routine CSF or negative CSF antibody analyses.

New techniques for clinical testing of Borrelia infection have been developed, such as LTT-MELISA, which is capable of identifying the active form of Borrelia infection (Lyme disease). Others, such as focus floating microscopy, are under investigation.New research indicates chemokine CXCL13 may also be a possible marker for neuroborrel

iosis.

Some laboratories offer Lyme disease testing using assays whose accuracy and clinical usefulness have not been adequately established. These tests include urine antigen tests, immunofluorescent staining for cell wall-deficient forms of Borrelia burgdorferi, and lymphocyte transformation tests. In general, CDC does not recommend these tests.

Prevention

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 pop

ulation 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 i

nvolving 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.

Following 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 numbe

r 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 complaints.

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 pulled."

New vaccines are being researched using outer surface protein C (OspC) and glycolipoprotein as methods of immunization.

Tick removal

Many urban legends 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 straigh

t 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

Antibiotic-resistant therapies

Antibiotic treatment is the central pillar in the management of Lyme disease. In the late stages of borreliosis, symptoms may persist despite extensive and repeated antibiotic treatment. Lyme arthritis which is antibiotic resistant may be treated with hydroxychloroquine or methotrexate. Experimental data are consensual on the deleterious consequences of systemic corticosteroid therapy. Corticosteroids are not indicated in Lyme disease

.

Antibiotic refractory patients with neuropathic pain responded well to gabapentin monotherapy with residual pain after intravenous ceftriaxone treatment in a pilot study. The immunomodulating, neuroprotective and anti-inflammatory potential of minocycline may be helpful in late/chronic Lyme disease with neurological or other inflammatory manifestations. Minocycline is used in other neurodegenerative and inflammatory disorders such as multiple sclerosis, Parkinson's disease, Huntington's disease, rheumatoid arthritis (RA) and ALS.