Lyme disease
Overview
Lyme disease, or Lyme borreliosis, is an emerging infectious disease caused by at least three species
Species
In biology, a species is one of the basic units of biological classification and a taxonomic rank. A species is often defined as a group of organisms capable of interbreeding and producing fertile offspring. While in many cases this definition is adequate, more precise or differing measures are...

 of bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...

 belonging to the genus
Genus
In biology, a genus is a low-level taxonomic rank used in the biological classification of living and fossil organisms, which is an example of definition by genus and differentia...

 Borrelia
Borrelia
Borrelia is a genus of bacteria of the spirochete phylum. It causes borreliosis, a zoonotic, vector-borne disease transmitted primarily by ticks and some by lice, depending on the species...

. Borrelia burgdorferi
Borrelia burgdorferi
Borrelia burgdorferi is a species of Gram negative bacteria of the spirochete class of the genus Borrelia. B. burgdorferi is predominant in North America, but also exists in Europe, and is the agent of Lyme disease....

 sensu stricto
is the main cause of Lyme disease in the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...

, whereas Borrelia afzelii
Borrelia afzelii
Borrelia afzelii is a species of Borrelia that can infect various species of vertebrate and invertebrates.Among thirty Borrelia known species, it is one of 4 which is likely to infect humans causing a variant of Lyme disease....

and Borrelia garinii
Borrelia garinii
Borrelia garinii is a spirochete bacteria and part of the Borrelia genus. - External links :****...

cause most Europe
Europe
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...

an cases. The disease is named after the town of Lyme
Lyme, Connecticut
Lyme is a town in New London County, Connecticut, United States. The population was 2,016 at the 2000 census. Lyme and its neighboring town Old Lyme are the namesake for Lyme disease.-Geography:...

, Connecticut
Connecticut
Connecticut is a state in the New England region of the northeastern United States. It is bordered by Rhode Island to the east, Massachusetts to the north, and the state of New York to the west and the south .Connecticut is named for the Connecticut River, the major U.S. river that approximately...

, USA, where a number of cases were identified in 1975. Although Allen Steere
Allen Steere
Allen C. Steere is a professor of rheumatology at Harvard University and previously at Yale University. Steere is credited with discovering and naming Lyme disease, and he published almost 200 scholarly articles on Lyme disease between 1977 and 2007. At a ceremony in Hartford, Connecticut in 1998,...

 realized that Lyme disease was a tick-borne disease
Tick-borne disease
Tick-borne diseases are diseases or illnesses transmitted by ticks. As the incidence of tick-borne illnesses increases and the geographic areas in which they are found expand, it becomes increasingly important that health professionals be able to distinguish the diverse, and often overlapping,...

 in 1978, the cause of the disease remained a mystery until 1981, when B.
Encyclopedia
Lyme disease, or Lyme borreliosis, is an emerging infectious disease caused by at least three species
Species
In biology, a species is one of the basic units of biological classification and a taxonomic rank. A species is often defined as a group of organisms capable of interbreeding and producing fertile offspring. While in many cases this definition is adequate, more precise or differing measures are...

 of bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...

 belonging to the genus
Genus
In biology, a genus is a low-level taxonomic rank used in the biological classification of living and fossil organisms, which is an example of definition by genus and differentia...

 Borrelia
Borrelia
Borrelia is a genus of bacteria of the spirochete phylum. It causes borreliosis, a zoonotic, vector-borne disease transmitted primarily by ticks and some by lice, depending on the species...

. Borrelia burgdorferi
Borrelia burgdorferi
Borrelia burgdorferi is a species of Gram negative bacteria of the spirochete class of the genus Borrelia. B. burgdorferi is predominant in North America, but also exists in Europe, and is the agent of Lyme disease....

 sensu stricto
is the main cause of Lyme disease in the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...

, whereas Borrelia afzelii
Borrelia afzelii
Borrelia afzelii is a species of Borrelia that can infect various species of vertebrate and invertebrates.Among thirty Borrelia known species, it is one of 4 which is likely to infect humans causing a variant of Lyme disease....

and Borrelia garinii
Borrelia garinii
Borrelia garinii is a spirochete bacteria and part of the Borrelia genus. - External links :****...

cause most Europe
Europe
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...

an cases. The disease is named after the town of Lyme
Lyme, Connecticut
Lyme is a town in New London County, Connecticut, United States. The population was 2,016 at the 2000 census. Lyme and its neighboring town Old Lyme are the namesake for Lyme disease.-Geography:...

, Connecticut
Connecticut
Connecticut is a state in the New England region of the northeastern United States. It is bordered by Rhode Island to the east, Massachusetts to the north, and the state of New York to the west and the south .Connecticut is named for the Connecticut River, the major U.S. river that approximately...

, USA, where a number of cases were identified in 1975. Although Allen Steere
Allen Steere
Allen C. Steere is a professor of rheumatology at Harvard University and previously at Yale University. Steere is credited with discovering and naming Lyme disease, and he published almost 200 scholarly articles on Lyme disease between 1977 and 2007. At a ceremony in Hartford, Connecticut in 1998,...

 realized that Lyme disease was a tick-borne disease
Tick-borne disease
Tick-borne diseases are diseases or illnesses transmitted by ticks. As the incidence of tick-borne illnesses increases and the geographic areas in which they are found expand, it becomes increasingly important that health professionals be able to distinguish the diverse, and often overlapping,...

 in 1978, the cause of the disease remained a mystery until 1981, when B. burgdorferi was identified by Willy Burgdorfer
Willy Burgdorfer
Willy Burgdorfer, an American scientist born and educated in Basel, Switzerland, is an international leader in the field of medical entomology. He is famous for his discovery of the bacterial pathogen that causes Lyme disease, a spirochete named Borrelia burgdorferi in his honor.-Background:Dr....

.

Lyme disease is the most common tick-borne disease in the Northern Hemisphere
Northern Hemisphere
The Northern Hemisphere is the half of a planet that is north of its equator—the word hemisphere literally means “half sphere”. It is also that half of the celestial sphere north of the celestial equator...

. Borrelia is transmitted to humans by the bite of infected ticks belonging to a few species of the genus Ixodes
Ixodes
Ixodes is a genus of hard-bodied ticks . It includes important disease vectors of animals and humans . Some ticks in this genus may transmit the pathogenic bacterium Borrelia burgdorferi responsible for causing Lyme disease...

("hard ticks"). Early symptoms may include fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...

, headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...

, fatigue, depression
Depression (mood)
Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...

, and a characteristic circular skin rash called erythema migrans
Erythema chronicum migrans
Erythema chronicum migrans refers to the rash often seen in the early stage of Lyme disease. It can appear anywhere from one day to one month after a tick bite. This rash does not represent an allergic reaction to the bite, but rather an actual skin infection with the Lyme bacteria, Borrelia...

. Left untreated, later symptoms may involve the joints, heart, and central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...

. In most cases, the infection and its symptoms are eliminated by antibiotics, especially if the illness is treated early. Delayed or inadequate treatment can lead to the more serious symptoms, which can be disabling and difficult to treat. Lyme disease is a biosafety level
Biosafety level
A biosafety level is the level of the biocontainment precautions required to isolate dangerous biological agents in an enclosed facility. The levels of containment range from the lowest biosafety level 1 to the highest at level 4 . In the United States, the Centers for Disease Control and...

 2 disease.

Signs and symptoms

Lyme disease can affect multiple body systems and produce a range of 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 with other diseases as well. The incubation period
Incubation period
Incubation period is the time elapsed between exposure to a pathogenic organism, a chemical or radiation, and when symptoms and signs are first apparent...

 from infection to the onset of symptoms is usually one to two 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
Asymptomatic
In medicine, a disease is considered asymptomatic if a patient is a carrier for a disease or infection but experiences no symptoms. A condition might be asymptomatic if it fails to show the noticeable symptoms with which it is usually associated. Asymptomatic infections are also called subclinical...

 infection exists, but occurs in less than 7% of infected individuals in the United States. Asymptomatic infection may be much more common among those infected in Europe.

Early localized infection

The classic sign of early local infection with Lyme disease is a circular, outwardly expanding rash called erythema chronicum migrans
Erythema chronicum migrans
Erythema chronicum migrans refers to the rash often seen in the early stage of Lyme disease. It can appear anywhere from one day to one month after a tick bite. This rash does not represent an allergic reaction to the bite, but rather an actual skin infection with the Lyme bacteria, Borrelia...

 (also erythema migrans or EM), which occurs at the site of the tick bite three to thirty days after the tick bite. 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
Bullseye (target)
The bullseye, or bull's-eye, is the centre of a target , and by extension the name given to any shot that hits the bullseye...

. However, partial clearing is uncommon, and the bullseye pattern more often involves central redness.

EM is thought to occur in about 80% of infected patients. Patients can also experience flu-like symptoms, such as headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...

, muscle soreness, fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...

, and malaise
Malaise
Malaise is a feeling of general discomfort or uneasiness, of being "out of sorts", often the first indication of an infection or other disease. Malaise is often defined in medicinal research as a "general feeling of being unwell"...

. Lyme disease can progress to later stages even in patients who do not develop a rash.

Early disseminated infection

Within days to weeks after the onset of local infection, the Borrelia
Borrelia
Borrelia is a genus of bacteria of the spirochete phylum. It causes borreliosis, a zoonotic, vector-borne disease transmitted primarily by ticks and some by lice, depending on the species...

bacteria may begin to spread through the bloodstream. EM 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, but occurs in Europe, is borrelial lymphocytoma, a purplish lump that develops on the ear lobe, nipple, or scrotum. Other discrete symptoms include migrating pain in muscles, joints, and tendons, and heart palpitations and dizziness caused by changes in heartbeat.

Various acute neurological problems, termed neuroborreliosis
Neuroborreliosis
Neuroborreliosis is a disorder of the central nervous system caused by infection with a spirochete of the genus Borrelia. The microbiological progression of the disease is similar to that of neurosyphilis, another spirochetal infection...

, appear in 10–15% of untreated patients. These include facial palsy
Bell's palsy
Bell's palsy is a form of facial paralysis resulting from a dysfunction of the cranial nerve VII that results in the inability to control facial muscles on the affected side. Several conditions can cause facial paralysis, e.g., brain tumor, stroke, and Lyme disease. However, if no specific cause...

, which is the loss of muscle tone on one or both sides of the face, as well as meningitis
Meningitis
Meningitis is inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges. The inflammation may be caused by infection with viruses, bacteria, or other microorganisms, and less commonly by certain drugs...

, which involves severe headaches, neck stiffness, and sensitivity to light. Radiculoneuritis causes shooting pains that may interfere with sleep, as well as abnormal skin sensations. Mild encephalitis
Encephalitis
Encephalitis is an acute inflammation of the brain. Encephalitis with meningitis is known as meningoencephalitis. Symptoms include headache, fever, confusion, drowsiness, and fatigue...

 may lead to memory loss
Memory loss
Memory loss can be partial or total and it is normal when it comes with aging. Sudden memory loss is usually a result of brain trauma and it may be permanent or temporary. When it is caused by medical conditions such as Alzheimers, the memory loss is gradual and tends to be permanent.Brain trauma...

, sleep disturbances, or mood changes. In addition, some case report
Case report
In medicine, a case report is a detailed report of the symptoms, signs, diagnosis, treatment, and follow-up of an individual patient. Case reports may contain a demographic profile of the patient, but usually describe an unusual or novel occurrence....

s have described altered mental status as the only symptom seen in a few cases of early neuroborreliosis.

Late persistent infection

After several months, untreated or inadequately treated patients may go on to develop severe and chronic symptoms that affect many parts of the body, including the brain, nerves, eyes, joints and heart. Many disabling symptoms can occur, including permanent paraplegia
Paraplegia
Paraplegia is an impairment in motor or sensory function of the lower extremities. The word comes from Ionic Greek: παραπληγίη "half-striking". It is usually the result of spinal cord injury or a congenital condition such as spina bifida that affects the neural elements of the spinal canal...

 in the most extreme cases.

Chronic neurologic symptoms occur in up to 5% of untreated patients. A polyneuropathy
Polyneuropathy
Polyneuropathy is a neurological disorder that occurs when many peripheral nerves throughout the body malfunction simultaneously. It may be acute and appear without warning, or chronic and develop gradually over a longer period of time. Many polyneuropathies have both motor and sensory...

 that involves 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. These patients may also experience profound fatigue. However, other problems, such as depression
Depression (mood)
Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...

 and fibromyalgia
Fibromyalgia
Fibromyalgia is a medical disorder characterized by chronic widespread pain and allodynia, a heightened and painful response to pressure. It is an example of a diagnosis of exclusion...

, are no more common in people who have been infected with Lyme than in the general population. Chronic encephalomyelitis
Encephalomyelitis
Encephalomyelitis is a general term for inflammation of the brain and spinal cord, describing a number of disorders:* Acute disseminated encephalomyelitis or postinfectious encephalomyelitis, a demyelinating disease of the brain and spinal cord, possibly triggered by vaccination or viral...

, which may be progressive, can involve cognitive impairment, weakness in the legs, awkward gait, facial palsy, bladder problems, vertigo
Vertigo (medical)
Vertigo is a type of dizziness, where there is a feeling of motion when one is stationary. The symptoms are due to a dysfunction of the vestibular system in the inner ear...

, and back pain. In rare cases untreated Lyme disease may cause frank psychosis, which has been mis-diagnosed as schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...

 or bipolar disorder
Bipolar disorder
Bipolar disorder or bipolar affective disorder, historically known as manic–depressive disorder, is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated energy levels, cognition, and mood with or without one or...

. Panic attacks and anxiety can occur; there may also be delusional behavior, including somatoform delusions, sometimes accompanied by a depersonalization
Depersonalization
Depersonalization is an anomaly of the mechanism by which an individual has self-awareness. It is a feeling of watching oneself act, while having no control over a situation. Sufferers feel they have changed, and the world has become less real, vague, dreamlike, or lacking in significance...

 or derealization syndrome, where the patients begin to feel detached from themselves or from reality.

Diffuse white matter pathology can disrupt grey matter
Grey matter
Grey matter is a major component of the central nervous system, consisting of neuronal cell bodies, neuropil , glial cells and capillaries. Grey matter contains neural cell bodies, in contrast to white matter, which does not and mostly contains myelinated axon tracts...

 connections, and could account for deficits in attention, memory, visuospatial ability, complex cognition, and emotional status. White matter disease may have a greater potential for recovery than gray matter disease, perhaps because neuronal loss is less common. Resolution of MRI white matter hyperintensities after antibiotic treatment has been observed.

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 cyst
Baker's cyst
A Baker's cyst, also known as a popliteal cyst, is a benign swelling of the semimembranous or more rarely some other synovial bursa found behind the knee joint. It is named after the surgeon who first described it, William Morrant Baker...

s may form and rupture. In some cases, joint erosion occurs.

Acrodermatitis chronica atrophicans
Acrodermatitis chronica atrophicans
Acrodermatitis chronica atrophicans is a skin rash indicative of the third or late stage of European Lyme borreliosis....

 (ACA) is a chronic skin disorder observed primarily in Europe among the elderly. ACA begins as a reddish-blue patch of discolored skin, often on the backs of the hands or feet. The lesion slowly atrophies over several weeks or months, chance 77 with the skin becoming first thin and wrinkled and then, if untreated, completely dry and hairless.

Cause

Lyme disease is caused by Gram-negative
Gram-negative
Gram-negative bacteria are bacteria that do not retain crystal violet dye in the Gram staining protocol. In a Gram stain test, a counterstain is added after the crystal violet, coloring all Gram-negative bacteria with a red or pink color...

, spirochetal bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...

 from the genus
Genus
In biology, a genus is a low-level taxonomic rank used in the biological classification of living and fossil organisms, which is an example of definition by genus and differentia...

 Borrelia
Borrelia
Borrelia is a genus of bacteria of the spirochete phylum. It causes borreliosis, a zoonotic, vector-borne disease transmitted primarily by ticks and some by lice, depending on the species...

. At least 11 Borrelia species have been discovered, three of which are known to be Lyme-related. The Borrelia species
Species
In biology, a species is one of the basic units of biological classification and a taxonomic rank. A species is often defined as a group of organisms capable of interbreeding and producing fertile offspring. While in many cases this definition is adequate, more precise or differing measures are...

 that cause Lyme disease are collectively known as Borrelia burgdorferi sensu lato, and show a great deal of genetic diversity
Genetic diversity
Genetic diversity, the level of biodiversity, refers to the total number of genetic characteristics in the genetic makeup of a species. It is distinguished from genetic variability, which describes the tendency of genetic characteristics to vary....

.

The group Borrelia burgdorferi sensu lato, made up of three closely related species, are probably responsible for the large majority of cases: B. burgdorferi sensu stricto (predominant in North America
North America
North America is a continent wholly within the Northern Hemisphere and almost wholly within the Western Hemisphere. It is also considered a northern subcontinent of the Americas...

, but also present in Europe
Europe
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...

), B. afzelii, and B. garinii (both predominant in Eurasia
Eurasia
Eurasia is a continent or supercontinent comprising the traditional continents of Europe and Asia ; covering about 52,990,000 km2 or about 10.6% of the Earth's surface located primarily in the eastern and northern hemispheres...

). Some studies have also proposed B. bissettii and B. valaisiana may sometimes infect humans, but these species do not seem to be important causes of disease.

Transmission

Lyme disease is classified as a zoonosis
Zoonosis
A zoonosis or zoonoseis any infectious disease that can be transmitted from non-human animals to humans or from humans to non-human animals . In a study of 1415 pathogens known to affect humans, 61% were zoonotic...

, as it is transmitted to humans from a natural reservoir
Natural reservoir
Natural reservoir or nidus, refers to the long-term host of the pathogen of an infectious disease. It is often the case that hosts do not get the disease carried by the pathogen or it is carried as a subclinical infection and so asymptomatic and non-lethal...

 among rodents by tick
Tick
Ticks are small arachnids in the order Ixodida, along with mites, constitute the subclass Acarina. Ticks are ectoparasites , living by hematophagy on the blood of mammals, birds, and sometimes reptiles and amphibians...

s that feed on both sets of hosts
Host (biology)
In biology, a host is an organism that harbors a parasite, or a mutual or commensal symbiont, typically providing nourishment and shelter. In botany, a host plant is one that supplies food resources and substrate for certain insects or other fauna...

. Hard-bodied ticks of the genus Ixodes
Ixodes
Ixodes is a genus of hard-bodied ticks . It includes important disease vectors of animals and humans . Some ticks in this genus may transmit the pathogenic bacterium Borrelia burgdorferi responsible for causing Lyme disease...

are the main vectors of Lyme disease. Most infections are caused by ticks in the nymphal stage
Nymph (biology)
In biology, a nymph is the immature form of some invertebrates, particularly insects, which undergoes gradual metamorphosis before reaching its adult stage. Unlike a typical larva, a nymph's overall form already resembles that of the adult. In addition, while a nymph moults it never enters a...

, as they are very small and may feed for long periods of time undetected. Larval ticks are very rarely infected. 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. However, transmission is quite rare, with only about 1% of recognized tick bites resulting in Lyme disease; this may be because an infected tick must be attached for at least a day for transmission to occur.

In Europe, the vector is Ixodes ricinus
Ixodes ricinus
Ixodes ricinus, the castor bean tick, is a chiefly European species of hard-bodied tick. It may reach a length of when engorged with a blood meal, and can transmit both bacterial and viral pathogens such as the causative agents of Lyme disease and tick-borne encephalitis.-Description:In common...

, which is also called the sheep tick or castor bean tick. In China, Ixodes persulcatus
Ixodes persulcatus
Ixodes persulcatus, the taiga tick, is a species of hard-bodied tick distributed throughout eastern Europe and Asia to the People’s Republic of China and Japan. The sexual dimorphism of the species is marked, the male being much smaller than the female...

(the taiga tick) is probably the most important vector. In North America, the black-legged tick or deer tick (Ixodes scapularis
Ixodes scapularis
Ixodes scapularis is commonly known as the deer tick or blacklegged tick , and in some parts of the USA as the bear tick. It is a hard-bodied tick of the eastern and northern Midwestern United States...

) is the main vector on the east coast. The lone star tick (Amblyomma americanum
Amblyomma americanum
Amblyomma americanum, or lone star tick, is a species of tick in the genus Amblyomma. It's average length is 1/4 inch.-Distribution:...

), which is found throughout the Southeastern United States
Southeastern United States
The Southeastern United States, colloquially referred to as the Southeast, is the eastern portion of the Southern United States. It is one of the most populous regions in the United States of America....

 as far west as Texas
Texas
Texas is the second largest U.S. state by both area and population, and the largest state by area in the contiguous United States.The name, based on the Caddo word "Tejas" meaning "friends" or "allies", was applied by the Spanish to the Caddo themselves and to the region of their settlement in...

, is unlikely to transmit the Lyme disease Spirochaete
Spirochaete
Spirochaetes belong to a phylum of distinctive Gram-negative bacteria, which have long, helically coiled cells...

Borrelia burgdorferi, though it may be implicated in a related syndrome called southern tick-associated rash illness
Southern tick-associated rash illness
Southern tick-associated rash illness or Masters' disease is an emerging infectious disease related to Lyme disease that occurs in southeastern and south-central United States. It is spread by tick bites, but the organism that causes the infection is unknown.-Causes:This illness is a tick-borne...

, which resembles a mild form of Lyme disease. On the West Coast of the United States
West Coast of the United States
West Coast or Pacific Coast are terms for the westernmost coastal states of the United States. The term most often refers to the states of California, Oregon, and Washington. Although not part of the contiguous United States, Alaska and Hawaii do border the Pacific Ocean but can't be included in...

, the main vector is the western black-legged tick (Ixodes pacificus
Ixodes pacificus
Ixodes pacificus, the Western blacklegged tick, is a species of Ixodes, a parasitic tick found on the western coast of North America. It is the principal vector of Lyme Disease in that region....

). The tendency of this tick species to feed predominantly on host species such as lizards that are resistant to Borrelia infection appears to diminish transmission of Lyme disease in the West.

While Lyme spirochetes have been found in insect
Insect
Insects are a class of living creatures within the arthropods that have a chitinous exoskeleton, a three-part body , three pairs of jointed legs, compound eyes, and two antennae...

s as well as ticks, reports of actual infectious transmission appear to be rare. Lyme spirochetes have been found in semen and breast milk, but transmission has not been known to take place through sexual contact. Transmission across the placenta
Placenta
The placenta is an organ that connects the developing fetus to the uterine wall to allow nutrient uptake, waste elimination, and gas exchange via the mother's blood supply. "True" placentas are a defining characteristic of eutherian or "placental" mammals, but are also found in some snakes and...

 during pregnancy has not been demonstrated, and no consistent pattern of teratogenicity or specific "congenital Lyme borreliosis" has been identified. As with a number of other spirochetal diseases, adverse pregnancy outcomes are possible with untreated infection; prompt treatment with antibiotics reduces or eliminates this risk. Pregnant Lyme-disease patients cannot be treated with the first-choice antibiotic, doxycycline (see below), as it is potentially harmful for the fetus. Instead, erythromycin is usually given; it is less effective against the disease but harmless for the fetus.

Tick-borne coinfections

Ticks that transmit B. burgdorferi to humans can also carry and transmit several other parasites, such as Theileria microti
Theileria microti
Theileria microti is a parasitic blood-borne piroplasm transmitted by deer ticks. It was previously in the taxonomic genus Babesia, as Babesia microti, until ribosomal RNA comparisons placed it in the sister genus Theileria. T...

and Anaplasma phagocytophilum
Anaplasma phagocytophilum
Anaplasma phagocytophilum is a gram-negative bacterium that is unusual in its tropism to neutrophils...

, which cause the diseases babesiosis
Babesiosis
Babesiosis is a malaria-like parasitic disease caused by infection with Babesia, a genus of protozoal piroplasms. After trypanosomes, Babesia are thought to be the second most common blood parasites of mammals and they can have a major impact on health of domestic animals in areas without severe...

 and human granulocytic anaplasmosis
Human granulocytic anaplasmosis
Human granulocytic anaplasmosis is an infectious disease caused by Anaplasma phagocytophilum, an obligate intracellular bacterium that is typically transmitted to humans by at least three kinds of ticks, including Ixodes scapularis, Ixodes pacificus, and Dermacentor variabilis...

 (HGA), respectively. Among early Lyme disease patients, depending on their location, 2–12% will also have HGA and 2–40% will have babesiosis. Ticks in certain regions, including the landscapes along the eastern Baltic Sea, also transmit tick-borne encephalitis.

Coinfections complicate Lyme symptoms, especially diagnosis and treatment. It is possible for a tick to carry and transmit one of the coinfections and not Borrelia, making diagnosis difficult and often elusive. The Centers for Disease Control studied 100 ticks in rural New Jersey
New Jersey
New Jersey is a state in the Northeastern and Middle Atlantic regions of the United States. , its population was 8,791,894. It is bordered on the north and east by the state of New York, on the southeast and south by the Atlantic Ocean, on the west by Pennsylvania and on the southwest by Delaware...

, and found 55% of the ticks were infected with at least one of the pathogens.

Pathophysiology

Borrelia burgdorferi can spread throughout the body during the course of the disease, and has been found in the skin, heart, joint, peripheral nervous system, and central nervous system. Many of the signs and symptoms of Lyme disease are a consequence of the immune response to the spirochete in those tissues.

B. burgdorferi is injected into the skin by the bite of an infected Ixodes tick. Tick saliva, which accompanies the spirochete into the skin during the feeding process, contains substances that disrupt the immune response at the site of the bite. This provides a protective environment where the spirochete can establish infection. The spirochetes multiply and migrate outward within the dermis
Dermis
The dermis is a layer of skin between the epidermis and subcutaneous tissues, and is composed of two layers, the papillary and reticular dermis...

. The host inflammatory response to the bacteria in the skin causes the characteristic circular EM lesion. Neutrophils, however, which are necessary to eliminate the spirochetes from the skin, fail to appear in the developing EM lesion. This allows the bacteria to survive and eventually spread throughout the body.

Days to weeks following the tick bite, the spirochetes spread via the bloodstream to joints, heart, nervous system, and distant skin sites, where their presence gives rise to the variety of symptoms of disseminated disease. The spread of B. burgdorferi is aided by the attachment of the host protease plasmin
Plasmin
Plasmin is an important enzyme present in blood that degrades many blood plasma proteins, most notably, fibrin clots. The degradation of fibrin is termed fibrinolysis. In humans, the plasmin protein is encoded by the PLG gene.- Function :...

 to the surface of the spirochete. If untreated, the bacteria may persist in the body for months or even years, despite the production of B. burgdorferi antibodies by the immune system. The spirochetes may avoid the immune response by decreasing expression of surface proteins that are targeted by antibodies, antigenic variation
Antigenic variation
Antigenic variation refers to the mechanism by which an infectious organism such as a protozoan, bacterium or virus alters its surface proteins in order to evade a host immune response. Immune evasion is particularly important for organisms that target long-lived hosts, repeatedly infect a single...

 of the VlsE surface protein, inactivating key immune components such as complement
Complement system
The complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime...

, and hiding in the extracellular matrix
Extracellular matrix
In biology, the extracellular matrix is the extracellular part of animal tissue that usually provides structural support to the animal cells in addition to performing various other important functions. The extracellular matrix is the defining feature of connective tissue in animals.Extracellular...

, which may interfere with the function of immune factors.

In the brain, B. burgdorferi may induce astrocytes to undergo astrogliosis (proliferation followed by apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...

), which may contribute to neurodysfunction. The spirochetes may also induce host cells to secrete products toxic to nerve cells, including quinolinic acid
Quinolinic acid
Quinolinic acid is a dicarboxylic acid. It may be prepared by the oxidation of quinoline, either electrochemically, or with acidic hydrogen peroxide.Quinolinic acid is a downstream kynurenine pathway metabolite of tryptophan...

 and the cytokines IL-6 and TNF-alpha, which can produce fatigue and malaise. Both microglia
Microglia
Microglia are a type of glial cell that are the resident macrophages of the brain and spinal cord, and thus act as the first and main form of active immune defense in the central nervous system . Microglia constitute 20% of the total glial cell population within the brain...

 and astrocytes secrete IL-6 and TNF-alpha in the presence of the spirochete. This cytokine response may contribute to cognitive impairment.

A developing hypothesis is that the chronic secretion of stress
Stress (medicine)
Stress is a term in psychology and biology, borrowed from physics and engineering and first used in the biological context in the 1930s, which has in more recent decades become commonly used in popular parlance...

 hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...

s as a result of Borrelia infection may reduce the effect of neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...

s, or other receptors
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...

 in the brain by cell-mediated proinflammatory pathways, thereby leading to the dysregulation of neurohormones, specifically glucocorticoids and catecholamines, the major stress hormones. This process is mediated via the hypothalamic-pituitary-adrenal axis
Hypothalamic-pituitary-adrenal axis
The hypothalamic-pituitary-adrenal axis , also known as thelimbic-hypothalamic-pituitary-adrenal axis and, occasionally, as the hypothalamic-pituitary-adrenal-gonadotropic axis, is a complex set of direct influences and feedback interactions among the hypothalamus, the pituitary gland ,...

. Additionally tryptophan
Tryptophan
Tryptophan is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in the standard genetic code as the codon UGG...

, a precursor to serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...

, appears to be reduced within the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...

 (CNS) in a number of infectious diseases that affect the brain, including Lyme. Researchers are investigating if this neurohormone secretion is the cause of neuropsychiatric
Neuropsychiatry
Neuropsychiatry is the branch of medicine dealing with mental disorders attributable to diseases of the nervous system. It preceded the current disciplines of psychiatry and neurology, in as much as psychiatrists and neurologists had a common training....

 disorders developing in some patients with borreliosis.

Immunological studies

Exposure to the Borrelia bacterium during Lyme disease possibly causes a long-lived and damaging inflammatory response, a form of pathogen-induced autoimmune disease. The production of this reaction might be due to a form of molecular mimicry
Molecular mimicry
Molecular mimicry is defined as the theoretical possibility that sequence similarities between foreign and self-peptides are sufficient to result in the cross-activation of autoreactive T or B cells by pathogen-derived peptides...

, where Borrelia avoid being killed by the immune system by resembling normal parts of the body's tissues. It is therefore possible that if some chronic symptoms come from an autoimmune reaction, this could explain why some symptoms persist even after the spirochetes have been eliminated from the body. This hypothesis may explain chronic arthritis that persists after antibiotic therapy, similar to rheumatic fever
Rheumatic fever
Rheumatic fever is an inflammatory disease that occurs following a Streptococcus pyogenes infection, such as strep throat or scarlet fever. Believed to be caused by antibody cross-reactivity that can involve the heart, joints, skin, and brain, the illness typically develops two to three weeks after...

, but its wider application is controversial.

Diagnosis

Lyme disease is diagnosed
Medical diagnosis
Medical diagnosis refers both to the process of attempting to determine or identify a possible disease or disorder , and to the opinion reached by this process...

 clinically based on symptoms, objective physical findings (such as erythema migrans
Erythema chronicum migrans
Erythema chronicum migrans refers to the rash often seen in the early stage of Lyme disease. It can appear anywhere from one day to one month after a tick bite. This rash does not represent an allergic reaction to the bite, but rather an actual skin infection with the Lyme bacteria, Borrelia...

, facial palsy or arthritis
Arthritis
Arthritis is a form of joint disorder that involves inflammation of one or more joints....

) or a history of possible exposure to infected ticks, as well as serological blood tests
Serology
Serology is the scientific study of blood serum and other bodily fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum...

. The EM rash is not always a bullseye, ie, it can be red all the way across. When making a diagnosis of Lyme disease, health care providers should consider other diseases that may cause similar illness. Not all patients infected with Lyme disease will develop the characteristic bullseye rash, and many may not recall a tick bite.

Because of the difficulty in culturing
Microbiological culture
A microbiological culture, or microbial culture, is a method of multiplying microbial organisms by letting them reproduce in predetermined culture media under controlled laboratory conditions. Microbial cultures are used to determine the type of organism, its abundance in the sample being tested,...

 Borrelia bacteria in the laboratory, diagnosis of Lyme disease is typically based on the clinical exam findings and a history of exposure to endemic
Endemic (epidemiology)
In epidemiology, an infection is said to be endemic in a population when that infection is maintained in the population without the need for external inputs. For example, chickenpox is endemic in the UK, but malaria is not...

 Lyme areas. The EM rash, which does not occur in all cases, is considered sufficient to establish a diagnosis of Lyme disease even when serologic blood tests are negative. Serological testing can be used to support a clinically suspected case, but is not diagnostic by itself.

Diagnosis of late-stage Lyme disease is often complicated by a multifaceted appearance and nonspecific symptoms, prompting one reviewer to call Lyme the new "great imitator." Lyme disease may be misdiagnosed as multiple sclerosis
Multiple sclerosis
Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...

, rheumatoid arthritis
Rheumatoid arthritis
Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...

, fibromyalgia
Fibromyalgia
Fibromyalgia is a medical disorder characterized by chronic widespread pain and allodynia, a heightened and painful response to pressure. It is an example of a diagnosis of exclusion...

, chronic fatigue syndrome
Chronic fatigue syndrome
Chronic fatigue syndrome is the most common name used to designate a significantly debilitating medical disorder or group of disorders generally defined by persistent fatigue accompanied by other specific symptoms for a minimum of six months, not due to ongoing exertion, not substantially...

, lupus
Systemic lupus erythematosus
Systemic lupus erythematosus , often abbreviated to SLE or lupus, is a systemic autoimmune disease that can affect any part of the body. As occurs in other autoimmune diseases, the immune system attacks the body's cells and tissue, resulting in inflammation and tissue damage...

, Crohn's disease
Crohn's disease
Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...

 or other autoimmune and neurodegenerative diseases.

Laboratory testing

Several forms of laboratory testing for Lyme disease are available, some of which have not been adequately validated. The most widely used tests are serologies
Serology
Serology is the scientific study of blood serum and other bodily fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum...

, which measure levels of specific antibodies in a patient's blood. These tests may be negative in early infection, as the body may not have produced a significant quantity of antibodies, but they are considered a reliable aid in the diagnosis of later stages of Lyme disease. Serologic tests for Lyme disease are of limited use in people lacking objective signs of Lyme disease because of false positive results and cost.

The serological laboratory tests most widely available and employed are the Western blot
Western blot
The western blot is a widely used analytical technique used to detect specific proteins in the given sample of tissue homogenate or extract. It uses gel electrophoresis to separate native proteins by 3-D structure or denatured proteins by the length of the polypeptide...

 and ELISA
ELISA
Enzyme-linked immunosorbent assay , is a popular format of a "wet-lab" type analytic biochemistry assay that uses one sub-type of heterogeneous, solid-phase enzyme immunoassay to detect the presence of a substance in a liquid sample."Wet lab" analytic biochemistry assays involves detection of an...

. A two-tiered protocol is recommended by the CDC: the sensitive
Sensitivity and specificity
Sensitivity and specificity are statistical measures of the performance of a binary classification test, also known in statistics as classification function. Sensitivity measures the proportion of actual positives which are correctly identified as such Sensitivity and specificity are statistical...

 ELISA test is performed first, and if it is positive or equivocal, then the more specific
Sensitivity and specificity
Sensitivity and specificity are statistical measures of the performance of a binary classification test, also known in statistics as classification function. Sensitivity measures the proportion of actual positives which are correctly identified as such Sensitivity and specificity are statistical...

 Western blot is run. The reliability of testing in diagnosis remains controversial. Studies show the Western blot IgM
IGM
IGM as an acronym or abbreviation can refer to:* Immunoglobulin M , the primary antibody against A and B antigens on red blood cells* International Grandmaster, a chess ranking* intergalactic medium* Intragroup medium - see: Intracluster medium...

 has a specificity of 94–96% for patients with clinical symptoms of early Lyme disease. The initial ELISA test has a sensitivity of about 70%, and in two-tiered testing, the overall sensitivity is only 64%, although this rises to 100% in the subset of people with disseminated symptoms, such as arthritis. ELISA testing, however, is typically done against region-specific epitopes, and may report a false negative if the patient has been infected with Borrelia from another region than that in which the patient is tested.

Erroneous test results have been widely reported in both early and late stages of the disease, and can be caused by several factors, including antibody cross-reactions from other infections, including Epstein-Barr virus
Epstein-Barr virus
The Epstein–Barr virus , also called human herpesvirus 4 , is a virus of the herpes family and is one of the most common viruses in humans. It is best known as the cause of infectious mononucleosis...

 and cytomegalovirus
Cytomegalovirus
Cytomegalovirus is a viral genus of the viral group known as Herpesviridae or herpesviruses. It is typically abbreviated as CMV: The species that infects humans is commonly known as human CMV or human herpesvirus-5 , and is the most studied of all cytomegaloviruses...

, as well as herpes simplex virus
Herpes simplex virus
Herpes simplex virus 1 and 2 , also known as Human herpes virus 1 and 2 , are two members of the herpes virus family, Herpesviridae, that infect humans. Both HSV-1 and HSV-2 are ubiquitous and contagious...

. The overall rate of false positives is low, only about 1 to 3%, in comparison to a false negative rate of up to 36% using two-tiered testing.

Polymerase chain reaction
Polymerase chain reaction
The polymerase chain reaction is a scientific technique in molecular biology to amplify a single or a few copies of a piece of DNA across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence....

 (PCR) tests for Lyme disease have also been developed to detect the genetic material (DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

) of the Lyme disease spirochete. PCR tests are susceptible to false positive
Type I and type II errors
In statistical test theory the notion of statistical error is an integral part of hypothesis testing. The test requires an unambiguous statement of a null hypothesis, which usually corresponds to a default "state of nature", for example "this person is healthy", "this accused is not guilty" or...

 results from poor laboratory technique. Even when properly performed, PCR often shows false negative
Type I and type II errors
In statistical test theory the notion of statistical error is an integral part of hypothesis testing. The test requires an unambiguous statement of a null hypothesis, which usually corresponds to a default "state of nature", for example "this person is healthy", "this accused is not guilty" or...

 results with blood and cerebrospinal fluid
Cerebrospinal fluid
Cerebrospinal fluid , Liquor cerebrospinalis, is a clear, colorless, bodily fluid, that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord...

 (CSF) specimens. Hence, PCR is not widely performed for diagnosis of Lyme disease, but it may have a role in diagnosis of Lyme arthritis, because it is a highly sensitive way of detecting ospA DNA in synovial fluid. With the exception of PCR, there is currently no practical means for detecting the presence of the organism, as serologic studies only test for antibodies of Borrelia. High titer
Titer
A titer is a way of expressing concentration. Titer testing employs serial dilution to obtain approximate quantitative information from an analytical procedure that inherently only evaluates as positive or negative. The titer corresponds to the highest dilution factor that still yields a positive...

s of either immunoglobulin G (IgG) or immunoglobulin M (IgM) antibodies to Borrelia antigens indicate disease, but lower titers can be misleading, because 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
Venipuncture
In medicine, venepuncture, venopuncture or venipuncture is the process of obtaining intravenous access for the purpose of intravenous therapy or for blood sampling of venous blood. This procedure is performed by medical laboratory scientists, medical practitioners, some EMTs, paramedics,...

 or CSF via lumbar puncture
Lumbar puncture
A lumbar puncture is a diagnostic and at times therapeutic procedure that is performed in order to collect a sample of cerebrospinal fluid for biochemical, microbiological, and cytological analysis, or very rarely as a treatment to relieve increased intracranial pressure.-Indications:The...

. 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
MELISA
A MELISA test is a blood test that detects Type-IV allergy to metals, chemicals, environmental toxins and molds from one single blood sample. It can also identify active Lyme disease . The test does not measure toxicity-that is to say, it will not measure the amounts of a harmful substance in the...

, although the results of studies are contradictory, and there is no study assessing the diagnostic sensitivity and specificity of the test. Others, such as focus floating microscopy, are under investigation. New research indicates chemokine
Chemokine
Chemokines are a family of small cytokines, or proteins secreted by cells. Their name is derived from their ability to induce directed chemotaxis in nearby responsive cells; they are chemotactic cytokines...

 CXCL13
CXCL13
C-X-C motif chemokine 13 also known as B lymphocyte chemoattractant is a protein that in humans is encoded by the CXCL13 gene.- Function :CXCL13 is a small cytokine belonging to the CXC chemokine family...

 may also be a possible marker for neuroborreliosis.

Some laboratories offer Lyme disease testing using assays whose accuracy and clinical usefulness have not been adequately established. These tests include urine antigen tests, PCR tests on urine, immunofluorescent staining for cell wall-deficient forms of Borrelia burgdorferi, and lymphocyte transformation tests. The CDC does not recommend these tests, and a 2005 review by Aguero-Rosenfeld et al. in Clinical Microbiology Reviews stated their use is "of great concern and is strongly discouraged".

In addition to laboratory testing on patients, ticks can be tested after removal from the host. Several laboratories perform PCR testing on live or dead ticks for a panel of tick-borne diseases, including Borrelia, Babesia
Babesia
Babesia is a protozoan parasite of the blood that causes a hemolytic disease known as Babesiosis. There are over 100 species of Babesia identified; however only a handful have been documented as pathogenic in humans....

, and Ehrlichia
Ehrlichia
Ehrlichia is a genus of rickettsiales bacteria. They are transmitted by ticks. Several species can cause infection in humans. The genus is named after German microbiologist Paul Ehrlich...

.

Imaging

Neuroimaging
Neuroimaging
Neuroimaging includes the use of various techniques to either directly or indirectly image the structure, function/pharmacology of the brain...

 does not provide specific patterns unique to neuroborreliosis
Neuroborreliosis
Neuroborreliosis is a disorder of the central nervous system caused by infection with a spirochete of the genus Borrelia. The microbiological progression of the disease is similar to that of neurosyphilis, another spirochetal infection...

, but may aid in differential diagnosis
Differential diagnosis
A differential diagnosis is a systematic diagnostic method used to identify the presence of an entity where multiple alternatives are possible , and may also refer to any of the included candidate alternatives A differential diagnosis (sometimes abbreviated DDx, ddx, DD, D/Dx, or ΔΔ) is a...

 and in understanding the pathophysiology of the disease.

Prevention

Protective clothing includes a hat, long-sleeved shirts and long trousers 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.

Attached ticks should be removed promptly, as removal within 36 hours can reduce transmission rates. One study concluded that a single dose of doxycycline given within 72 hours after a high-risk tick exposure can prevent the development of Lyme disease.

A community can prevent Lyme disease by reducing 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
Domesticated guineafowl
Guineafowl, sometimes called Pintade, are a family of birds originating from Africa, related to other game birds such as the pheasants, turkeys and partridges; they have a long history of domestication, mainly involving the Helmeted Guineafowl....

. Guineafowl are voracious consumers of insects and arachnid
Arachnid
Arachnids are a class of joint-legged invertebrate animals in the subphylum Chelicerata. All arachnids have eight legs, although in some species the front pair may convert to a sensory function. The term is derived from the Greek words , meaning "spider".Almost all extant arachnids are terrestrial...

s, and have a particular fondness for ticks. Localized use of domesticated guineafowl may reduce dependence on chemical pest-control methods.

Management of host animals

Lyme and all other deer tick-borne diseases can be prevented on a regional level by reducing the deer population on which the ticks depend for reproductive success. This has been demonstrated in the communities of Monhegan, Maine
Monhegan, Maine
Monhegan is a plantation on an island of the same name in Lincoln County, Maine, United States, about off the coast. The population was 75 at the 2000 census. As a plantation, Monhegan's governmental status falls between township and town...

 and 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, 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
Vaccine
A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe or its toxins...

 against Lyme disease, based on the outer surface protein A (OspA) of B. burgdorferi, was developed by GlaxoSmithKline
GlaxoSmithKline
GlaxoSmithKline plc is a global pharmaceutical, biologics, vaccines and consumer healthcare company headquartered in London, United Kingdom...

. In clinical trial
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...

s 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 effect
Adverse effect
In medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as surgery.An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. If it results from an unsuitable or incorrect dosage or...

s. 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 slow for a variety of reasons, including its cost, which was often not reimbursed by insurance companies. Subsequently, hundreds of vaccine recipients reported they had developed autoimmune
Autoimmunity
Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which allows an immune response against its own cells and tissues. Any disease that results from such an aberrant immune response is termed an autoimmune disease...

 side effects. Supported by some patient advocacy groups, a number of class-action lawsuits were filed against GlaxoSmithKline, alleging 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
Nature (journal)
Nature, first published on 4 November 1869, is ranked the world's most cited interdisciplinary scientific journal by the Science Edition of the 2010 Journal Citation Reports...

cited the withdrawal of LYMErix as an instance in which "unfounded public fears place pressures on vaccine developers that go beyond reasonable safety considerations." 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
Glycolipid
Glycolipids are lipids with a carbohydrate attached. Their role is to provide energy and also serve as markers for cellular recognition.-Metabolism:...

 as methods of immunization. Vaccines are available for dogs.

Tick removal

Folk remedies for tick removal tend to be ineffective, offer no advantages in preventing the transfer of disease, and may increase the risks of transmission or infection. The best method is simply to pull the tick out with tweezers as close to the skin as possible, without twisting, and avoiding crushing the body of the tick or removing the head from the body. The risk of infection increases with the time the tick is attached, and if a tick is attached for less than 24 hours, infection is unlikely. However, since these ticks are very small, especially in the nymph stage, prompt detection is quite 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. According to the Infectious Diseases Society of America
Infectious Diseases Society of America
The Infectious Diseases Society of America is a medical association representing physicians, scientists and other health care professionals who specialize in infectious diseases. As of 2010, IDSA had approximately 9,000 members...

 (IDSA) guidelines, the antibiotics of choice are doxycycline
Doxycycline
Doxycycline INN is a member of the tetracycline antibiotics group, and is commonly used to treat a variety of infections. Doxycycline is a semisynthetic tetracycline invented and clinically developed in the early 1960s by Pfizer Inc. and marketed under the brand name Vibramycin. Vibramycin...

 (in adults), amoxicillin
Amoxicillin
Amoxicillin , formerly amoxycillin , and abbreviated amox, is a moderate-spectrum, bacteriolytic, β-lactam antibiotic used to treat bacterial infections caused by susceptible microorganisms. It is usually the drug of choice within the class because it is better absorbed, following oral...

 (in children), erythromycin
Erythromycin
Erythromycin is a macrolide antibiotic that has an antimicrobial spectrum similar to or slightly wider than that of penicillin, and is often used for people who have an allergy to penicillins. For respiratory tract infections, it has better coverage of atypical organisms, including mycoplasma and...

 (for pregnant women) and ceftriaxone
Ceftriaxone
Ceftriaxone is a third-generation cephalosporin antibiotic. Like other third-generation cephalosporins, it has broad spectrum activity against Gram-positive and Gram-negative bacteria. In most cases, it is considered to be equivalent to cefotaxime in terms of safety and efficacy...

, with treatment lasting 10 to 28 days. Alternative choices are cefuroxime
Cefuroxime
Cefuroxime is a second-generation cephalosporin antibiotic that has been widely available in the USA as Ceftin since 1977. GlaxoSmithKline sells the antibiotic in the United Kingdom under the name Zinnat.-Indications:As for the other cephalosporins, although as a...

 and cefotaxime
Cefotaxime
Cefotaxime is a third-generation cephalosporin antibiotic. Like other third-generation cephalosporins, it has broad spectrum activity against Gram positive and Gram negative bacteria...

. Treatment of pregnant women is similar, but tetracycline should not be used.

A double blind, randomized, placebo
Placebo
A placebo is a simulated or otherwise medically ineffectual treatment for a disease or other medical condition intended to deceive the recipient...

-controlled multicenter clinical study indicated three weeks of treatment with intravenous ceftriaxone, followed by 100 days of treatment with oral amoxicillin did not improve symptoms any more than just three weeks of treatment with ceftriaxone. The researchers noted the outcome should not be evaluated after the initial antibiotic treatment, but rather 6–12 months afterwards. In patients with chronic posttreatment 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
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...

, making the infection more difficult to treat. Late diagnosed Lyme is treated with oral or intravenous antibiotics, frequently ceftriaxone
Ceftriaxone
Ceftriaxone is a third-generation cephalosporin antibiotic. Like other third-generation cephalosporins, it has broad spectrum activity against Gram-positive and Gram-negative bacteria. In most cases, it is considered to be equivalent to cefotaxime in terms of safety and efficacy...

 for a minimum of four weeks. Minocycline
Minocycline
Minocycline is a broad-spectrum tetracycline antibiotic, and has a broader spectrum than the other members of the group. It is a bacteriostatic antibiotic, classified as a long-acting type...

 is also indicated for neuroborreliosis
Neuroborreliosis
Neuroborreliosis is a disorder of the central nervous system caused by infection with a spirochete of the genus Borrelia. The microbiological progression of the disease is similar to that of neurosyphilis, another spirochetal infection...

 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 (coinfections), including ehrlichiosis
Ehrlichiosis
Ehrlichiosis is a tick-borne disease of dogs usually caused by the organism Ehrlichia canis. Ehrlichia canis is the pathogen of animals. Humans can become infected by E. canis and other species after tick exposure. German Shepherd dogs are thought to be particularly affected by the disease, other...

, babesiosis
Babesiosis
Babesiosis is a malaria-like parasitic disease caused by infection with Babesia, a genus of protozoal piroplasms. After trypanosomes, Babesia are thought to be the second most common blood parasites of mammals and they can have a major impact on health of domestic animals in areas without severe...

, and immune suppression in the patient.

A meta-analysis
Meta-analysis
In statistics, a meta-analysis combines the results of several studies that address a set of related research hypotheses. In its simplest form, this is normally by identification of a common measure of effect size, for which a weighted average might be the output of a meta-analyses. Here the...

 published in 2005 found some patients with Lyme disease have fatigue, joint or muscle pain, and neurocognitive
Neurocognitive
Neurocognitive is a term used to describe cognitive functions closely linked to the function of particular areas, neural pathways, or cortical networks in the brain substrate layers of neurological matrix at the cellular molecular level...

 symptoms persisting for years, despite antibiotic treatment. Patients with late stage Lyme disease have been shown to experience a level of physical disability
Disability
A disability may be physical, cognitive, mental, sensory, emotional, developmental or some combination of these.Many people would rather be referred to as a person with a disability instead of handicapped...

 equivalent to that seen in congestive heart failure
Congestive heart failure
Heart failure often called congestive heart failure is generally defined as the inability of the heart to supply sufficient blood flow to meet the needs of the body. Heart failure can cause a number of symptoms including shortness of breath, leg swelling, and exercise intolerance. The condition...

. In rare cases, Lyme disease can be fatal.

Many patients report a lack of understanding among employers, family, and friends as being the most frustrating aspect of Lyme disease. The fatigue that accompanies it may be perceived as malingering, especially after the disease enters its second and third week of treatment.

Epidemiology

Lyme disease is endemic
Endemic (epidemiology)
In epidemiology, an infection is said to be endemic in a population when that infection is maintained in the population without the need for external inputs. For example, chickenpox is endemic in the UK, but malaria is not...

 in Northern Hemisphere
Northern Hemisphere
The Northern Hemisphere is the half of a planet that is north of its equator—the word hemisphere literally means “half sphere”. It is also that half of the celestial sphere north of the celestial equator...

 temperate regions.

Africa

In northern Africa, B. burgdorferi sensu lato has been identified in Morocco
Morocco
Morocco , officially the Kingdom of Morocco , is a country located in North Africa. It has a population of more than 32 million and an area of 710,850 km², and also primarily administers the disputed region of the Western Sahara...

, Algeria
Algeria
Algeria , officially the People's Democratic Republic of Algeria , also formally referred to as the Democratic and Popular Republic of Algeria, is a country in the Maghreb region of Northwest Africa with Algiers as its capital.In terms of land area, it is the largest country in Africa and the Arab...

, Egypt
Egypt
Egypt , officially the Arab Republic of Egypt, Arabic: , is a country mainly in North Africa, with the Sinai Peninsula forming a land bridge in Southwest Asia. Egypt is thus a transcontinental country, and a major power in Africa, the Mediterranean Basin, the Middle East and the Muslim world...

 and Tunisia
Tunisia
Tunisia , officially the Tunisian RepublicThe long name of Tunisia in other languages used in the country is: , is the northernmost country in Africa. It is a Maghreb country and is bordered by Algeria to the west, Libya to the southeast, and the Mediterranean Sea to the north and east. Its area...

.

Lyme disease in sub-Saharan Africa is presently unknown, but evidence indicates it may occur in humans in this region. The abundance of hosts and tick vectors would favor the establishment of Lyme infection in Africa. In East Africa, two cases of Lyme disease have been reported in Kenya
Kenya
Kenya , officially known as the Republic of Kenya, is a country in East Africa that lies on the equator, with the Indian Ocean to its south-east...

.

Asia

B. burgdorferi sensu lato-infested ticks are being found more frequently in Japan
Japan
Japan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...

, as well as in northwest China
China
Chinese civilization may refer to:* China for more general discussion of the country.* Chinese culture* Greater China, the transnational community of ethnic Chinese.* History of China* Sinosphere, the area historically affected by Chinese culture...

, Nepal
Nepal
Nepal , officially the Federal Democratic Republic of Nepal, is a landlocked sovereign state located in South Asia. It is located in the Himalayas and bordered to the north by the People's Republic of China, and to the south, east, and west by the Republic of India...

, Thailand
Thailand
Thailand , officially the Kingdom of Thailand , formerly known as Siam , is a country located at the centre of the Indochina peninsula and Southeast Asia. It is bordered to the north by Burma and Laos, to the east by Laos and Cambodia, to the south by the Gulf of Thailand and Malaysia, and to the...

 and far eastern Russia
Russia
Russia or , officially known as both Russia and the Russian Federation , is a country in northern Eurasia. It is a federal semi-presidential republic, comprising 83 federal subjects...

. Borrelia has been isolated in Mongolia
Mongolia
Mongolia is a landlocked country in East and Central Asia. It is bordered by Russia to the north and China to the south, east and west. Although Mongolia does not share a border with Kazakhstan, its western-most point is only from Kazakhstan's eastern tip. Ulan Bator, the capital and largest...

, as well.

Australia

In Australia
Australia
Australia , officially the Commonwealth of Australia, is a country in the Southern Hemisphere comprising the mainland of the Australian continent, the island of Tasmania, and numerous smaller islands in the Indian and Pacific Oceans. It is the world's sixth-largest country by total area...

, there is no definitive evidence for the existence of B. burgdorferi or for any other tick-borne spirochete that may be responsible for a local syndrome being reported as Lyme disease. Cases of neuroborreliosis have been documented in Australia, but are often ascribed to travel to other continents. The existence of Lyme disease in Australia is controversial.
(See Karl Mcmanus Foundation)

Canada

Due to changing climate, the range of ticks able to carry Lyme disease has expanded from a limited area of Ontario to include areas of southern Quebec, Manitoba, northern Ontario, Southwest Nova Scotia and parts of the Prairie provinces, as well as British Columbia. Cases have been reported as far east as the island of Newfoundland.

Europe

In Europe, Lyme disease is caused by infection with one or more pathogenic European genospecies of the spirochaete B. burgdorferi sensu lato, mainly transmitted by the tick Ixodes ricinus. Cases of B. burgdorferi sensu lato-infected ticks are found predominantly in central Europe, particularly in Slovenia
Slovenia
Slovenia , officially the Republic of Slovenia , is a country in Central and Southeastern Europe touching the Alps and bordering the Mediterranean. Slovenia borders Italy to the west, Croatia to the south and east, Hungary to the northeast, and Austria to the north, and also has a small portion of...

 and Austria
Austria
Austria , officially the Republic of Austria , is a landlocked country of roughly 8.4 million people in Central Europe. It is bordered by the Czech Republic and Germany to the north, Slovakia and Hungary to the east, Slovenia and Italy to the south, and Switzerland and Liechtenstein to the...

, but have been isolated in almost every country on the continent. Incidence in southern Europe, such as Italy and Portugal, is much lower.

South America

In South America
South America
South America is a continent situated in the Western Hemisphere, mostly in the Southern Hemisphere, with a relatively small portion in the Northern Hemisphere. The continent is also considered a subcontinent of the Americas. It is bordered on the west by the Pacific Ocean and on the north and east...

, tick-borne disease recognition and occurrence is rising. Ticks carrying B. burgdorferi sensu lato, as well as canine and human tick-borne disease, have been reported widely in Brazil
Brazil
Brazil , officially the Federative Republic of Brazil , is the largest country in South America. It is the world's fifth largest country, both by geographical area and by population with over 192 million people...

, but the subspecies of Borrelia has not yet been defined. The first reported case of Lyme disease in Brazil was made in 1993 in Sao Paulo
São Paulo
São Paulo is the largest city in Brazil, the largest city in the southern hemisphere and South America, and the world's seventh largest city by population. The metropolis is anchor to the São Paulo metropolitan area, ranked as the second-most populous metropolitan area in the Americas and among...

. B. burgdorferi sensu stricto antigens in patients have been identified in Colombia
Colombia
Colombia, officially the Republic of Colombia , is a unitary constitutional republic comprising thirty-two departments. The country is located in northwestern South America, bordered to the east by Venezuela and Brazil; to the south by Ecuador and Peru; to the north by the Caribbean Sea; to the...

 and Bolivia
Bolivia
Bolivia officially known as Plurinational State of Bolivia , is a landlocked country in central South America. It is the poorest country in South America...

.

United States

Lyme disease is the most common tick-borne disease in North America and Europe, and one of the fastest-growing infectious diseases in the United States. Of cases reported to the United States CDC, the ratio of Lyme disease infection is 7.9 cases for every 100,000 persons. In the ten states where Lyme disease is most common, the average was 31.6 cases for every 100,000 persons for the year 2005.

Although Lyme disease has been reported in 49 of 50 states in the U.S, about 99% of all reported cases are confined to just five geographic areas (New England, Mid-Atlantic, East-North Central, South Atlantic, and West North-Central). New 2008 CDC Lyme case definition guidelines are used to determine confirmed CDC surveillance cases. Effective January 2008, the CDC gives equal weight to laboratory evidence from 1) a positive culture for B. burgdorferi; 2) two-tier testing (ELISA screening and Western blot confirming); or 3) single-tier IgG (old infection) Western blot. Previously, the CDC only included laboratory evidence based on (1) and (2) in their surveillance case definition. The case definition now includes the use of Western blot without prior ELISA screen.

The number of reported cases of the disease has been increasing, as are endemic regions in North America. For example, B. burgdorferi sensu lato was previously thought to be hindered in its ability to be maintained in an enzootic
Enzootic
Enzootic is the non-human equivalent of endemic and means, in a broad sense, "belonging to" or "native to", "characteristic of", or "prevalent in" a particular geography, race, field, area, or environment; native to an area or scope....

 cycle in California
California
California is a state located on the West Coast of the United States. It is by far the most populous U.S. state, and the third-largest by land area...

, because it was assumed the large lizard population would dilute the prevalence of B. burgdorferi in local tick populations; this has since been brought into question, as some evidence has suggested lizards can become infected. Except for one study in Europe, much of the data implicating lizards is based on DNA detection of the spirochete and has not demonstrated lizards are able to infect ticks feeding upon them. As some experiments suggest lizards are refractory to infection with Borrelia, it appears likely their involvement in the enzootic cycle is more complex and species-specific.

While B. burgdorferi is most associated with ticks hosted by white-tailed deer
White-tailed Deer
The white-tailed deer , also known as the Virginia deer or simply as the whitetail, is a medium-sized deer native to the United States , Canada, Mexico, Central America, and South America as far south as Peru...

 and white-footed mice
White-footed mouse
White-footed Mouse is a rodent native to North America. It ranges from Ontario, Quebec, Labrador and the Maritime Provinces to the southwest USA and Mexico. It is also known as the Woodmouse, particularly in Texas.Adults are in length, not counting the tail, which can add another . A young adult...

, Borrelia afzelii is most frequently detected in rodent-feeding vector ticks, and Borrelia garinii and Borrelia valaisiana appear to be associated with birds. Both rodents and birds are competent reservoir hosts for B. burgdorferi sensu stricto. The resistance of a genospecies of Lyme disease spirochetes to the bacteriolytic activities of the alternative complement pathway of various host species may determine its reservoir host association.

It should be noted that several similar but apparently distinct conditions may exist, caused by various species or subspecies of Borrelia in North America. A regionally restricted condition that may be related to Borrelia infection is southern tick-associated rash illness
Southern tick-associated rash illness
Southern tick-associated rash illness or Masters' disease is an emerging infectious disease related to Lyme disease that occurs in southeastern and south-central United States. It is spread by tick bites, but the organism that causes the infection is unknown.-Causes:This illness is a tick-borne...

 (STARI), also known as Masters' disease. Amblyomma americanum
Amblyomma americanum
Amblyomma americanum, or lone star tick, is a species of tick in the genus Amblyomma. It's average length is 1/4 inch.-Distribution:...

, known commonly as the lone-star tick, is recognized as the primary vector for STARI. In some parts of the geographical distribution of STARI, Lyme disease is quite rare (e.g., Arkansas), so patients in these regions experiencing Lyme-like symptoms-- especially if they follow a bite from a lone-star tick-- should consider STARI as a possibility. It is generally a milder condition than Lyme and typically responds well to antibiotic treatment.

History

The evolutionary history of Borrelia burgdorferi genetics has been the subject of recent studies. One study has found that prior to the reforestation that accompanied post colonial farm abandonment in New England and the wholesale migration into the mid-west that occurred during the early 19th century, Lyme disease was present for thousands of years in America and had spread along with its tick hosts from the Northeast to the Midwest. This is confirmed by the writings of Peter Kalm, a Swedish botanist who was sent to America by Linnaeus, and who found the forests of New York "abound" with ticks when he visited in 1749. When Kalm's journey was retraced 100 years later, the forests were gone and the Lyme bacterium had probably become isolated to a few pockets along the northeast coast, Wisconsin, and Minnesota. Perhaps the first detailed description of what is now known as Lyme disease appeared in the writings of Reverend Dr John Walker after a visit to the Island of Jura (Deer Island) off the west coast of Scotland in 1764. He gives a good description both of the symptoms of Lyme disease (with "exquisite pain (in) the interior parts of the limbs") and of the tick vector itself, which he describes as a "worm" with a body which is "of a reddish colour and of a compressed shape with a row of feet on each side" that "penetrates the skin". Many people from this area of Great Britain immigrated to North America between 1717 and the end of the 18th century.
The examination of preserved museum specimens has found Borrelia DNA in an infected Ixodes ricinus tick from Germany that dates back to 1884, and from an infected mouse from Cape Cod that died in 1894.

The early European studies of what is now known as Lyme disease described its skin manifestations. The first study dates to 1883 in Wrocław, Poland
Poland
Poland , officially the Republic of Poland , is a country in Central Europe bordered by Germany to the west; the Czech Republic and Slovakia to the south; Ukraine, Belarus and Lithuania to the east; and the Baltic Sea and Kaliningrad Oblast, a Russian exclave, to the north...

 (then known as Breslau, Free State of Prussia), where physician Alfred Buchwald described a man who had suffered for 16 years with a degenerative skin disorder now known as acrodermatitis chronica atrophicans
Acrodermatitis chronica atrophicans
Acrodermatitis chronica atrophicans is a skin rash indicative of the third or late stage of European Lyme borreliosis....

. At a 1909 research conference, Swedish dermatologist Arvid Afzelius
Arvid Afzelius
Arvid Afzelius was a Swedish dermatologist.As a student at the Karolinska institutet, Afzelius studied under the prominent dermatologist Moritz Kaposi in Vienna...

 presented a study about an expanding, ring-like lesion he had observed in an older woman following the bite of a sheep tick. He named the lesion erythema migrans. The skin condition now known as borrelial lymphocytoma was first described in 1911.

Neurological problems following tick bites were recognized starting in the 1920s. French physicians Garin and Bujadoux described a farmer with a painful sensory radiculitis accompanied by mild meningitis
Meningitis
Meningitis is inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges. The inflammation may be caused by infection with viruses, bacteria, or other microorganisms, and less commonly by certain drugs...

 following a tick bite. A large, ring-shaped rash was also noted, although the doctors did not relate it to the meningoradiculitis. In 1930, the Swedish dermatologist Sven Hellerström was the first to propose EM and neurological symptoms following a tick bite were related. In the 1940s, German neurologist Alfred Bannwarth
Alfred Bannwarth
German neurologist, 1903-1970. Munich. Credited for discovering cases of lymphocytic meningoradiculitis with facial nerve palsies, an early description of neuroborreliosis and called Bannwarth's syndrome in his honor....

 described several cases of chronic lymphocytic meningitis and polyradiculoneuritis, some of which were accompanied by erythematous skin lesions.

Carl Lennhoff, who worked at the Karolinska Institute in Sweden, believed many skin conditions were caused by spirochetes. In 1948, he used a special stain to microscopically observe what he believed were spirochetes in various types of skin lesions, including EM. Although his conclusions were later shown to be erroneous, interest in the study of spirochetes was sparked. In 1949, Nils Thyresson, who also worked at the Karolinska Institute, was the first to treat ACA with penicillin. In the 1950s, the relationship among tick bite, lymphocytoma, EM and Bannwarth's syndrome was recognized throughout Europe leading to the widespread use of penicillin
Penicillin
Penicillin is a group of antibiotics derived from Penicillium fungi. They include penicillin G, procaine penicillin, benzathine penicillin, and penicillin V....

 for treatment in Europe.

In 1970, a dermatologist in Wisconsin
Wisconsin
Wisconsin is a U.S. state located in the north-central United States and is part of the Midwest. It is bordered by Minnesota to the west, Iowa to the southwest, Illinois to the south, Lake Michigan to the east, Michigan to the northeast, and Lake Superior to the north. Wisconsin's capital is...

 named Rudolph Scrimenti recognized an EM lesion in a patient after recalling a paper by Hellerström that had been reprinted in an American science journal in 1950. This was the first documented case of EM in the United States. Based on the European literature, he treated the patient with penicillin.

The full syndrome
Syndrome
In medicine and psychology, a syndrome is the association of several clinically recognizable features, signs , symptoms , phenomena or characteristics that often occur together, so that the presence of one or more features alerts the physician to the possible presence of the others...

 now known as Lyme disease was not recognized until a cluster of cases originally thought to be juvenile rheumatoid arthritis was identified in three towns in southeastern Connecticut
Connecticut
Connecticut is a state in the New England region of the northeastern United States. It is bordered by Rhode Island to the east, Massachusetts to the north, and the state of New York to the west and the south .Connecticut is named for the Connecticut River, the major U.S. river that approximately...

 in 1975, including the towns Lyme
Lyme, Connecticut
Lyme is a town in New London County, Connecticut, United States. The population was 2,016 at the 2000 census. Lyme and its neighboring town Old Lyme are the namesake for Lyme disease.-Geography:...

 and Old Lyme, which gave the disease its popular name. This was investigated by physicians David Snydman and Allen Steere
Allen Steere
Allen C. Steere is a professor of rheumatology at Harvard University and previously at Yale University. Steere is credited with discovering and naming Lyme disease, and he published almost 200 scholarly articles on Lyme disease between 1977 and 2007. At a ceremony in Hartford, Connecticut in 1998,...

 of the Epidemic Intelligence Service
Epidemic Intelligence Service
The Epidemic Intelligence Service is a program of the United States' Centers for Disease Control and Prevention . Established in 1951, due to biological warfare concerns arising from the Korean War, it has become a hands-on two-year postgraduate training program in epidemiology, with a focus on...

, and by others from Yale University
Yale University
Yale University is a private, Ivy League university located in New Haven, Connecticut, United States. Founded in 1701 in the Colony of Connecticut, the university is the third-oldest institution of higher education in the United States...

. The recognition that the patients in the United States had EM led to the recognition that "Lyme arthritis" was one manifestation of the same tick-borne condition known in Europe.

Before 1976, elements of B. burgdorferi sensu lato infection were called or known as tick-borne meningopolyneuritis, Garin-Bujadoux syndrome, Bannwarth syndrome, Afzelius' disease, Montauk Knee
Montauk, New York
Montauk [ˈmɒntɒk] is a census-designated place that roughly corresponds to the hamlet with the same name located in the town of East Hampton in Suffolk County, New York, United States on the South Shore of Long Island. As of the United States 2000 Census, the CDP population was 3,851 as of 2000...

 or sheep tick fever. Since 1976 the disease is most often referred to as Lyme disease, Lyme borreliosis or simply borreliosis.

In 1980, Steere, et al., began to test antibiotic regimens in adult patients with Lyme disease. In the same year, New York State Health Dept. epidemiologist Jorge Benach
Jorge Benach
Jorge Benach is a medical researcher at the State University of New York at Stony Brook in New York state. Benach is the chair of the Department of Molecular Genetics and Microbiology...

 provided Willy Burgdorfer
Willy Burgdorfer
Willy Burgdorfer, an American scientist born and educated in Basel, Switzerland, is an international leader in the field of medical entomology. He is famous for his discovery of the bacterial pathogen that causes Lyme disease, a spirochete named Borrelia burgdorferi in his honor.-Background:Dr....

, a researcher at the Rocky Mountain Biological Laboratory
Rocky Mountain Biological Laboratory
The Rocky Mountain Biological Laboratory is a Colorado high-altitude biological field station located near Crested Butte, in the West Elk mountains) It offers courses for undergraduate students - including National Science Foundation funded REU students and provides support for researchers...

, with collections of I. dammini [scapularis] from Shelter Island, NY, a known Lyme-endemic area as part of an ongoing investigation of Rocky Mountain spotted fever. In examining the ticks for rickettsiae, Burgdorfer noticed “poorly stained, rather long, irregularly coiled spirochetes.” Further examination revealed spirochetes in 60% of the ticks. Burgdorfer credited his familiarity with the European literature for his realization that the spirochetes might be the “long-sought cause of ECM and Lyme disease.” Benach supplied him with more ticks from Shelter Island and sera
Blood serum
In blood, the serum is the component that is neither a blood cell nor a clotting factor; it is the blood plasma with the fibrinogens removed...

 from patients diagnosed with Lyme disease. University of Texas Health Science Center researcher Alan Barbour “offered his expertise to culture and immunochemically characterize the organism.” Burgdorfer subsequently confirmed his discovery by isolating from patients with Lyme disease spirochetes identical to those found in ticks. In June 1982 he published his findings in Science
Science (journal)
Science is the academic journal of the American Association for the Advancement of Science and is one of the world's top scientific journals....

, and the spirochete was named Borrelia burgdorferi in his honor.

After the identification of B. burgdorferi as the causative agent of Lyme disease, antibiotics were selected for testing, guided by in vitro antibiotic sensitivities, including tetracycline antibiotics
Tetracycline antibiotics
Tetracyclines are a group of broad-spectrum antibiotics whose general usefulness has been reduced with the onset of bacterial resistance. Despite this, they remain the treatment of choice for some specific indications....

, amoxicillin
Amoxicillin
Amoxicillin , formerly amoxycillin , and abbreviated amox, is a moderate-spectrum, bacteriolytic, β-lactam antibiotic used to treat bacterial infections caused by susceptible microorganisms. It is usually the drug of choice within the class because it is better absorbed, following oral...

, cefuroxime axetil, intravenous and intramuscular penicillin and intravenous ceftriaxone
Ceftriaxone
Ceftriaxone is a third-generation cephalosporin antibiotic. Like other third-generation cephalosporins, it has broad spectrum activity against Gram-positive and Gram-negative bacteria. In most cases, it is considered to be equivalent to cefotaxime in terms of safety and efficacy...

. The mechanism of tick transmission was also the subject of much discussion. B. burgdorferi spirochetes were identified in tick saliva in 1987, confirming the hypothesis that transmission occurred via tick salivary glands.

Jonathan Edlow, Professor of Medicine at Harvard Medical School, quotes the late Ed Masters (discoverer of STARI
Southern tick-associated rash illness
Southern tick-associated rash illness or Masters' disease is an emerging infectious disease related to Lyme disease that occurs in southeastern and south-central United States. It is spread by tick bites, but the organism that causes the infection is unknown.-Causes:This illness is a tick-borne...

, a Lyme-like illness) in his book Bull's-Eye, on the history of Lyme disease. Edlow writes:

Ecology

Urbanization
Urbanization
Urbanization, urbanisation or urban drift is the physical growth of urban areas as a result of global change. The United Nations projected that half of the world's population would live in urban areas at the end of 2008....

 and other anthropogenic
Anthropogenic
Human impact on the environment or anthropogenic impact on the environment includes impacts on biophysical environments, biodiversity and other resources. The term anthropogenic designates an effect or object resulting from human activity. The term was first used in the technical sense by Russian...

 factors can be implicated in the spread of Lyme disease to humans. In many areas, expansion of suburban neighborhoods has led to gradual deforestation of surrounding wooded areas and increased border contact between humans and tick-dense areas. Human expansion has also resulted in reduction of predators that hunt deer as well as mice, chipmunks and other small rodents – the primary reservoirs for Lyme disease. As a consequence of increased human contact with host and vector, the likelihood of transmission of the disease has greatly increased. Researchers are investigating possible links between global warming
Global warming
Global warming refers to the rising average temperature of Earth's atmosphere and oceans and its projected continuation. In the last 100 years, Earth's average surface temperature increased by about with about two thirds of the increase occurring over just the last three decades...

 and the spread of vector-borne diseases, including Lyme disease.

The deer tick (Ixodes scapularis, the primary vector in the northeastern U.S.) has a two-year life cycle, first progressing from larva to nymph, and then from nymph to adult. The tick feeds only once at each stage. In the fall, large acorn forests attract deer, as well as mice, chipmunks and other small rodents infected with B. burgdorferi. During the following spring, the ticks lay their eggs. The rodent population then "booms". Tick eggs hatch into larvae, which feed on the rodents; thus the larvae acquire infection from the rodents. At this stage, tick infestation may be controlled using acaricides (miticide
Miticide
Acaricides are pesticides that kill members of the Acari group, which includes ticks and mites.Acaricides are used both in medicine and agriculture, although the desired selective toxicity differs between the two fields.-Terminology:...

s).

Adult ticks may also transmit disease to humans. After feeding, female adult ticks lay their eggs on the ground, and the cycle is complete. On the West Coast of the United States
West Coast of the United States
West Coast or Pacific Coast are terms for the westernmost coastal states of the United States. The term most often refers to the states of California, Oregon, and Washington. Although not part of the contiguous United States, Alaska and Hawaii do border the Pacific Ocean but can't be included in...

, Lyme disease is spread by the western black-legged tick (Ixodes pacificus), which has a different life cycle.

The risk of acquiring Lyme disease does not depend on the existence of a local deer population, as is commonly assumed. New research suggests eliminating deer from smaller areas (less than 2.5 ha or 6 acre
Acre
The acre is a unit of area in a number of different systems, including the imperial and U.S. customary systems. The most commonly used acres today are the international acre and, in the United States, the survey acre. The most common use of the acre is to measure tracts of land.The acre is related...

s) may in fact lead to an increase in tick density and the rise of "tick-borne disease hotspots".

Harassment of researchers

In 2001, the New York Times Magazine reported that Allen Steere
Allen Steere
Allen C. Steere is a professor of rheumatology at Harvard University and previously at Yale University. Steere is credited with discovering and naming Lyme disease, and he published almost 200 scholarly articles on Lyme disease between 1977 and 2007. At a ceremony in Hartford, Connecticut in 1998,...

, chief of immunology and rheumatology at Tufts Medical Center
Tufts Medical Center
Tufts Medical Center is a medical institution in Boston, Massachusetts occupying space between Chinatown and the Theater District....

 and a codiscoverer and leading expert on Lyme disease, had been harassed, stalked, and threatened by patients and patient advocacy groups angry at his refusal to substantiate their diagnoses of chronic Lyme disease and endorse long-term antibiotic therapy. Because this intimidation included death threats, Steere was assigned security guards. Paul G. Auwaerter, director of infectious disease at Johns Hopkins School of Medicine
Johns Hopkins School of Medicine
The Johns Hopkins School of Medicine , located in Baltimore, Maryland, U.S., is the academic medical teaching and research arm of Johns Hopkins University. Hopkins has consistently been the nation's number one medical school in the amount of competitive research grants awarded by the National...

, cited the political controversy and high emotions as contributing to a "poisonous atmosphere" around Lyme disease, which he believes has led to doctors trying to avoid having Lyme patients in their practice.

Media

A 2004 study in The Pediatric Infectious Disease Journal stated 9 of 19 Internet websites surveyed contained what were described as major inaccuracies. Websites described as providing inaccurate information included several with the word "lyme" in their domain name (e.g. lymenet.org), as well as the website of the International Lyme And Associated Diseases Society
International Lyme And Associated Diseases Society
The International Lyme And Associated Diseases Society is a non-profit interest group which advocates for greater acceptance of the controversial medical entity of chronic Lyme disease....

. A 2008 article in the New England Journal of Medicine
New England Journal of Medicine
The New England Journal of Medicine is an English-language peer-reviewed medical journal published by the Massachusetts Medical Society. It describes itself as the oldest continuously published medical journal in the world.-History:...

argued media coverage of chronic Lyme disease ignored scientific evidence in favor of anecdotes and testimonials:
The 2008 documentary film Under Our Skin: The Untold Story of Lyme Disease
Under Our Skin
Under Our Skin: The Untold Story of Lyme Disease is a documentary film about Lyme disease, focusing on the controversy surrounding "chronic" Lyme disease. The film was directed by Andy Abrahams Wilson, who became interested in the subject after his sister contracted Lyme disease...

opened June 19, 2009 in New York City. This documentary, made by a director whose sister contracted the disease, argues that chronic Lyme disease exists. Lyme disease was also the focus of a major feature in The Times (London) in February 2010 which detailed the impact the disease had had on British author Alex Wade
Alex Wade
Alex Wade is a British writer, freelance journalist and media lawyer.-Writer:Wade is the author of Wrecking Machine: A Tale of Real Fights and White Collars and Surf Nation: In Search of the Fast Lefts and Hollow Rights of Britain and Ireland...

.

Notable cases

  • Alex Wade
    Alex Wade
    Alex Wade is a British writer, freelance journalist and media lawyer.-Writer:Wade is the author of Wrecking Machine: A Tale of Real Fights and White Collars and Surf Nation: In Search of the Fast Lefts and Hollow Rights of Britain and Ireland...

    —Author
  • Amy Tan
    Amy Tan
    Amy Tan is an American writer whose works explore mother-daughter relationships. Her most well-known work is The Joy Luck Club, which has been translated into 35 languages...

    —Author
  • Ben Petrick
    Ben Petrick
    Benjamin Wayne Petrick is a former Major League Baseball player.Petrick, who was born in Salem, Oregon, was a highly accomplished athlete while attending Glencoe High School in Hillsboro, Oregon...

    —Colorado Rockies catcher/outfielder from 1999–2003
  • Ben Stiller
    Ben Stiller
    Benjamin Edward "Ben" Stiller is an American comedian, actor, writer, film director, and producer. He is the son of veteran comedians and actors Jerry Stiller and Anne Meara....

    —Actor/Director
  • Chuck Schumer—New York Senator
  • Daryl Hall
    Daryl Hall
    Daryl Hall is an American rock, R&B and soul singer, keyboardist, guitarist, songwriter and producer, best known as the co-founder and lead vocalist of Hall & Oates . Hall scored several Billboard chart hits in the 1970s and early 1980s, and is regarded as one of the best blue eyed soul singers...

    —Musician
  • Diane Varsi
    Diane Varsi
    Diane Marie Antonia Varsi was an American film actress best known for her performances in Peyton Place – her film debut, and for which she was nominated for an Academy Award – and the cult film Wild in the Streets...

    —Actress
  • John Lurie
    John Lurie
    John Lurie is an American actor, musician, painter and producer. He is co-founder of The Lounge Lizards, a jazz ensemble. Lurie has acted in 19 films including Stranger than Paradise and Down by Law, composed and performed music for 20 television and film works, and he produced and starred in...

    —Actor, Artist & Musician
  • George W. Bush
    George W. Bush
    George Walker Bush is an American politician who served as the 43rd President of the United States, from 2001 to 2009. Before that, he was the 46th Governor of Texas, having served from 1995 to 2000....

    —former United States President
  • GG Allin
    GG Allin
    Kevin Michael "GG" Allin was an American punk rock singer-songwriter, who performed and recorded with many groups during his career. GG Allin is perhaps best remembered for his notorious live performances, which often featured transgressive acts, including coprophagia, self-mutilation, and...

    -Rock musician
  • Ötzi-Austrian Ice Man
  • Parker Posey
    Parker Posey
    Parker Christian Posey is an American actress. She became known during the 1990s after a series of roles in several well-received independent films. As a result, she has often been referred to as the "Queen of the Indies"....

    —Actress
  • Samantha Stosur
    Samantha Stosur
    Samantha "Sam" Jane Stosur is an Australian professional tennis player. She won the 2011 US Open singles title and was a finalist at the 2010 French Open. Stosur is ranked World No. 6 and her career high in singles is World No. 4, achieved on 21 February 2011. She is a former world No...

    Australia
    Australia
    Australia , officially the Commonwealth of Australia, is a country in the Southern Hemisphere comprising the mainland of the Australian continent, the island of Tasmania, and numerous smaller islands in the Indian and Pacific Oceans. It is the world's sixth-largest country by total area...

    n tennis
    Tennis
    Tennis is a sport usually played between two players or between two teams of two players each . Each player uses a racket that is strung to strike a hollow rubber ball covered with felt over a net into the opponent's court. Tennis is an Olympic sport and is played at all levels of society at all...

     player; contracted in 2007 (affected at the French Open
    2007 French Open
    The 2007 French Open was held in Paris, France from 27 May through to 10 June 2007. Followed two weeks later, as usual, by Wimbledon in London, United Kingdom. Rafael Nadal became the first man to win the tournament 3 times consecutively since Björn Borg, 1978–81; and maintained his unbeaten run...

    , did not play in 2007 after Wimbledon
    2007 Wimbledon Championships - Women's Singles
    Amélie Mauresmo was the defending champion but was knocked out in the fourth round by Nicole Vaidišová.23rd seed Venus Williams defeated Marion Bartoli in the final, 6–4, 6–1...

    )
  • Thalía
    Thalía
    Ariadna Thalía Sodi Miranda , known simply by the mononym Thalía , is a Mexican singer and actress. She has sold over 40 million albums worldwide...

    —Singer
  • Trevor Bayne
    Trevor Bayne
    Trevor Bayne is an American NASCAR Sprint Cup Series and Nationwide Series race car driver. He drives the No. 21 Motorcraft/QuickLane Ford Fusion for Wood Brothers Racing in the Sprint Cup Series, and the No. 16 Ford Mustang for Roush Fenway Racing in the Nationwide Series.Bayne began his racing...

    —current NASCAR
    NASCAR
    The National Association for Stock Car Auto Racing is a family-owned and -operated business venture that sanctions and governs multiple auto racing sports events. It was founded by Bill France Sr. in 1947–48. As of 2009, the CEO for the company is Brian France, grandson of the late Bill France Sr...

     driver
  • Wyatt Sexton
    Wyatt Sexton
    Wyatt Sexton is a former National Collegiate Athletic Association American football quarterback for the Florida State Seminoles. Sexton is well known for his performances on the field and for his suffering from the effects of Lyme disease...

    —Former Quarterback at Florida State University

Chronic Lyme disease

The term "chronic Lyme disease" or "post-Lyme disease syndrome" is often applied to several different sets of patients. One usage refers to people suffering from the symptoms of untreated and disseminated late-stage Lyme disease: arthritis
Arthritis
Arthritis is a form of joint disorder that involves inflammation of one or more joints....

, peripheral neuropathy
Peripheral neuropathy
Peripheral neuropathy is the term for damage to nerves of the peripheral nervous system, which may be caused either by diseases of or trauma to the nerve or the side-effects of systemic illness....

 and/or encephalomyelitis
Encephalomyelitis
Encephalomyelitis is a general term for inflammation of the brain and spinal cord, describing a number of disorders:* Acute disseminated encephalomyelitis or postinfectious encephalomyelitis, a demyelinating disease of the brain and spinal cord, possibly triggered by vaccination or viral...

. The term is also applied to people who have had the disease in the past and some symptoms remain after antibiotic treatment, which is also called post-Lyme disease syndrome. A third and controversial use of the term applies to patients with nonspecific symptoms, such as fatigue, who show no objective evidence they have been infected with Lyme disease in the past, since the standard diagnostic tests for infection are negative.

Up to one third of Lyme disease patients who have completed a course of antibiotic treatment continue to have symptoms, such as severe fatigue, sleep disturbance, and cognitive difficulties, with these symptoms being severe in about 2% of cases. While it is undisputed these patients can have severe symptoms, the cause and appropriate treatment is controversial. The symptoms may represent "for all intents and purposes" fibromyalgia
Fibromyalgia
Fibromyalgia is a medical disorder characterized by chronic widespread pain and allodynia, a heightened and painful response to pressure. It is an example of a diagnosis of exclusion...

 or chronic fatigue syndrome
Chronic fatigue syndrome
Chronic fatigue syndrome is the most common name used to designate a significantly debilitating medical disorder or group of disorders generally defined by persistent fatigue accompanied by other specific symptoms for a minimum of six months, not due to ongoing exertion, not substantially...

. A few doctors attribute these symptoms to persistent infection with Borrelia, or coinfections with other tick-borne infections, such as Ehrlichia
Ehrlichia
Ehrlichia is a genus of rickettsiales bacteria. They are transmitted by ticks. Several species can cause infection in humans. The genus is named after German microbiologist Paul Ehrlich...

and Babesia
Babesia
Babesia is a protozoan parasite of the blood that causes a hemolytic disease known as Babesiosis. There are over 100 species of Babesia identified; however only a handful have been documented as pathogenic in humans....

. Other doctors believe that the initial infection may cause an autoimmune reaction
Autoimmunity
Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which allows an immune response against its own cells and tissues. Any disease that results from such an aberrant immune response is termed an autoimmune disease...

 that continues to cause serious symptoms even after the bacteria have been eliminated by antibiotics.

Four randomized, controlled trial
Randomized controlled trial
A randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...

s have been performed in patients who have persisting complaints and a history of Borrelia infection. Some of these patients had evidence of an ongoing Borrelia infection, and almost all of them were previously treated with antibiotics. The authors of all four trials concluded their results did not support long-term antibiotic therapy:
  • Two studies showed no benefit from 30 days of intravenous ceftriaxone
    Ceftriaxone
    Ceftriaxone is a third-generation cephalosporin antibiotic. Like other third-generation cephalosporins, it has broad spectrum activity against Gram-positive and Gram-negative bacteria. In most cases, it is considered to be equivalent to cefotaxime in terms of safety and efficacy...

     and 60 days of oral doxycycline
    Doxycycline
    Doxycycline INN is a member of the tetracycline antibiotics group, and is commonly used to treat a variety of infections. Doxycycline is a semisynthetic tetracycline invented and clinically developed in the early 1960s by Pfizer Inc. and marketed under the brand name Vibramycin. Vibramycin...

    , concluding "treatment with intravenous and oral antibiotics for 90 days did not improve symptoms more than placebo".
  • One study showed an improvement only in fatigue after 28 days of intravenous antibiotics, an effect that was significant only in a group of patients that never had antibiotics previously. The results may have been compromised by unblinding, and detected a large placebo effect. This trial also saw several cases of life-threatening side effects, concluding "repeated courses of antibiotic treatment are not indicated for persistent symptoms following Lyme disease including those related to fatigue and cognitive dysfunction, particularly in light of the frequency of serious adverse events."
  • One study reported an improvement in fatigue in a subset of patients, and a transient improvement in cognition after 10 weeks of intravenous antibiotics, but concluded the treatment was "not an effective strategy for sustained cognitive improvement." These patients had also been ill for many years and had taken many antibiotic courses. Also, this study performed ad hoc statistical analysis and its results were questionably significant.


An advocacy group called the International Lyme And Associated Diseases Society (ILADS) argues the persistence of B. burgdorferi may be responsible for manifestations of late Lyme disease symptoms. It has questioned the generalizability and reliability of some of the above trials and the reliability of the current diagnostic tests. Major US medical authorities, including the Infectious Diseases Society of America
Infectious Diseases Society of America
The Infectious Diseases Society of America is a medical association representing physicians, scientists and other health care professionals who specialize in infectious diseases. As of 2010, IDSA had approximately 9,000 members...

, the American Academy of Neurology
American Academy of Neurology
The American Academy of Neurology is a professional society for neurologists and neuroscientists. As a medical specialty society it was established in 1949 by A.B. Baker of the University of Minnesota to advance the art and science of neurology, and thereby promote the best possible care for...

, and the National Institutes of Health
National Institutes of Health
The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...

, have stated there is no convincing evidence that Borrelia is involved in the various symptoms classed as chronic Lyme disease, and advise against long-term antibiotic treatment as ineffective and possibly harmful. Prolonged antibiotic therapy presents significant risks and can have dangerous side effects. One death has been reported from complications of a 27-month course of intravenous antibiotics for an unsubstantiated diagnosis of chronic Lyme disease.

Antibiotic treatment is the central pillar in the management of Lyme disease. However, in the late stages of borreliosis, symptoms may persist despite extensive and repeated antibiotic treatment. Although these chronic symptoms are possibly due to either autoimmunity
Autoimmunity
Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which allows an immune response against its own cells and tissues. Any disease that results from such an aberrant immune response is termed an autoimmune disease...

 or residual bacteria (see immunological studies below), no Borrelia DNA can usually be detected in the joints after antibiotic treatment, which suggests the arthritis may continue, even after the bacteria have been killed. Lyme arthritis that persists after antibiotic treatment may be treated with hydroxychloroquine
Hydroxychloroquine
Hydroxychloroquine is an antimalarial drug, sold under the trade names Plaquenil,Axemal, Dolquine, and Quensyl, also used to reduce inflammation in the treatment of rheumatoid arthritis and lupus...

 or methotrexate
Methotrexate
Methotrexate , abbreviated MTX and formerly known as amethopterin, is an antimetabolite and antifolate drug. It is used in treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions. It acts by inhibiting the metabolism of folic acid. Methotrexate...

. Corticosteroid
Corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte...

 injections into the affected joint are not recommended for any stage of Lyme arthritis.

Patients with chronic neuropathic pain responded well to gabapentin
Gabapentin
Gabapentin is a pharmaceutical drug, specifically a GABA analogue. It was originally developed for the treatment of epilepsy, and currently is also used to relieve neuropathic pain...

 monotherapy with residual pain after intravenous ceftriaxone
Ceftriaxone
Ceftriaxone is a third-generation cephalosporin antibiotic. Like other third-generation cephalosporins, it has broad spectrum activity against Gram-positive and Gram-negative bacteria. In most cases, it is considered to be equivalent to cefotaxime in terms of safety and efficacy...

 treatment in a pilot study. Some antibiotics may have a dual effect on Lyme disease, since minocycline
Minocycline
Minocycline is a broad-spectrum tetracycline antibiotic, and has a broader spectrum than the other members of the group. It is a bacteriostatic antibiotic, classified as a long-acting type...

 and doxycycline
Doxycycline
Doxycycline INN is a member of the tetracycline antibiotics group, and is commonly used to treat a variety of infections. Doxycycline is a semisynthetic tetracycline invented and clinically developed in the early 1960s by Pfizer Inc. and marketed under the brand name Vibramycin. Vibramycin...

 have anti-inflammatory effects in addition to their antibiotic actions, including anti-inflammatory effects specific to the inflammation caused by Lyme disease. Indeed, minocycline is used in other neurodegenerative and inflammatory
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...

 disorders, such as multiple sclerosis
Multiple sclerosis
Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...

, Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...

, Huntington's disease
Huntington's disease
Huntington's disease, chorea, or disorder , is a neurodegenerative genetic disorder that affects muscle coordination and leads to cognitive decline and dementia. It typically becomes noticeable in middle age. HD is the most common genetic cause of abnormal involuntary writhing movements called chorea...

, rheumatoid arthritis
Rheumatoid arthritis
Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...

 and ALS
Amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis , also referred to as Lou Gehrig's disease, is a form of motor neuron disease caused by the degeneration of upper and lower neurons, located in the ventral horn of the spinal cord and the cortical neurons that provide their efferent input...

.

Controversy and politics

While there is general agreement on the optimal treatment for early Lyme disease, there is considerable controversy over the existence, prevalence
Prevalence
In epidemiology, the prevalence of a health-related state in a statistical population is defined as the total number of cases of the risk factor in the population at a given time, or the total number of cases in the population, divided by the number of individuals in the population...

, diagnostic criteria, and treatment of chronic Lyme disease. The mainstream view is exemplified by a 2007 review in the New England Journal of Medicine
New England Journal of Medicine
The New England Journal of Medicine is an English-language peer-reviewed medical journal published by the Massachusetts Medical Society. It describes itself as the oldest continuously published medical journal in the world.-History:...

,
which noted the diagnosis of chronic Lyme disease is used by a few physicians despite a lack of "reproducible or convincing scientific evidence", leading the authors to describe this diagnosis as "the latest in a series of syndromes that have been postulated in an attempt to attribute medically unexplained symptoms to particular infections." Most medical authorities agree with this viewpoint: the IDSA
Infectious Diseases Society of America
The Infectious Diseases Society of America is a medical association representing physicians, scientists and other health care professionals who specialize in infectious diseases. As of 2010, IDSA had approximately 9,000 members...

, the American Academy of Neurology
American Academy of Neurology
The American Academy of Neurology is a professional society for neurologists and neuroscientists. As a medical specialty society it was established in 1949 by A.B. Baker of the University of Minnesota to advance the art and science of neurology, and thereby promote the best possible care for...

, the CDC, and the NIH
National Institutes of Health
The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...

 advise against long-term antibiotic treatment for chronic Lyme disease, given the lack of supporting evidence and the potential toxicities.
A minority view holds that chronic Lyme disease is responsible for a range of unexplained symptoms, sometimes in people without any evidence of past infection. This viewpoint is promoted by many patient advocates, notably an advocacy organization, the International Lyme And Associated Diseases Society. Groups of patients, patient advocates, and the small number of physicians who support the concept of chronic Lyme disease have organized to lobby for recognition of this diagnosis, as well as to argue for insurance coverage of long-term antibiotic therapy, which most insurers deny, as it is at odds with the guidelines of major medical organizations.

In 2006, Richard Blumenthal
Richard Blumenthal
Richard Blumenthal is the junior United States Senator from Connecticut and a member of the Democratic Party. Previously, he served as Attorney General of Connecticut....

, the Connecticut Attorney General
Connecticut Attorney General
The Connecticut Attorney General is the state attorney general of Connecticut.The Attorney General is elected to a four-year term. The current Attorney General is George Jepsen, a Democrat serving since January 5, 2011.-List of Attorneys General:...

, opened an antitrust
Antitrust
The United States antitrust law is a body of laws that prohibits anti-competitive behavior and unfair business practices. Antitrust laws are intended to encourage competition in the marketplace. These competition laws make illegal certain practices deemed to hurt businesses or consumers or both,...

 investigation against the IDSA, accusing the IDSA Lyme disease panel of undisclosed conflicts of interest
Conflict of interest
A conflict of interest occurs when an individual or organization is involved in multiple interests, one of which could possibly corrupt the motivation for an act in the other....

 and of unduly dismissing alternative therapies and chronic Lyme disease. The investigation was closed on May 1, 2008 without charges when the IDSA agreed to submit to a review of its guidelines by a panel of independent scientists and physicians which would occur on July 30, 2009. Views on the motivation and outcome of the investigation varied. Blumenthal's press release described the agreement as a vindication of his investigation and repeated his conflict-of-interest allegations. The IDSA focused on the fact that the medical validity of the IDSA guidelines was not challenged, and cited mounting legal costs and the difficulty of presenting scientific arguments in a legal setting as their rationale for accepting the settlement. A journalist writing in Nature Medicine
Nature Medicine
Nature Medicine is an academic journal publishing research articles, reviews, news and commentaries in the biomedical area, including both basic research and early-phase clinical research. Topics covered include cancer, cardiovascular disease, gene therapy, immunology, vaccines, and neuroscience...

suggested some IDSA members may not have disclosed potential conflicts of interest, while a Forbes piece described Blumenthal's investigation as "intimidation" of scientists by an elected official with close ties to Lyme advocacy groups. The Journal of the American Medical Association
Journal of the American Medical Association
The Journal of the American Medical Association is a weekly, peer-reviewed, medical journal, published by the American Medical Association. Beginning in July 2011, the editor in chief will be Howard C. Bauchner, vice chairman of pediatrics at Boston University’s School of Medicine, replacing ...

described the decision as an example of the "politicization of health policy" that went against the weight of scientific evidence and may have a chilling effect on future decisions by medical associations.

The state of Connecticut went on to enact a law on June 18, 2009 "to allow a licensed physician to prescribe, administer or dispense long-term antibiotics for a therapeutic purpose to a patient clinically diagnosed with Lyme disease." The states of Rhode Island California Massachusetts and New Hampshire have similar laws. The expert panel's review was published in 2010, with the independent doctors and scientists in the panel unanimously endorsing the guidelines, stating "No changes or revisions to the 2006 Lyme guidelines are necessary at this time," and concluding long-term antibiotic treatments are unproven and potentially dangerous. The IDSA welcomed the final report, stating that "Our number one concern is the patients we treat, and we’re glad patients and their physicians now have additional reassurance that the guidelines are medically sound."

Alternative therapies

A number of other alternative therapies have been suggested, though clinical trials have not been conducted, so the therapies are not known to be scientifically sound. For example, the use of hyperbaric oxygen therapy
Hyperbaric oxygen therapy
Hyperbaric medicine, also known as hyperbaric oxygen therapy , is the medical use of oxygen at a level higher than atmospheric pressure. The equipment required consists of a pressure chamber, which may be of rigid or flexible construction, and a means of delivering 100% oxygen...

 is claimed by CAM enthusiasts
Alternative medicine
Alternative medicine is any healing practice, "that does not fall within the realm of conventional medicine." It is based on historical or cultural traditions, rather than on scientific evidence....

 as an adjunct to antibiotics for Lyme has been discussed. Though there are no published data from clinical trials to support its use, preliminary results using a mouse model suggest its effectiveness against B. burgdorferi both in vitro
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...

and in vivo
In vivo
In vivo is experimentation using a whole, living organism as opposed to a partial or dead organism, or an in vitro controlled environment. Animal testing and clinical trials are two forms of in vivo research...

. Anecdotal clinical research has suggested antifungal azole
Azole
An azole is a class of five-membered nitrogen heterocyclic ring compounds containing at least one other non-carbon atom of either nitrogen, sulfur, or oxygen. The parent compounds are aromatic and have two double bonds; there are successively reduced analogs with fewer...

 medications, such as fluconazole
Fluconazole
Fluconazole is a triazole antifungal drug used in the treatment and prevention of superficial and systemic fungal infections. In a bulk powder form, it appears as a white crystalline powder, and it is very slightly soluble in water and soluble in alcohol. It is commonly marketed under the trade...

, could be used in the treatment of Lyme, but the use of these drugs has yet to be tested in a controlled study.

Alternative medicine
Alternative medicine
Alternative medicine is any healing practice, "that does not fall within the realm of conventional medicine." It is based on historical or cultural traditions, rather than on scientific evidence....

 approaches include bee venom, because it contains the peptide melittin
Melittin
Melittin is the principal active component of apitoxin and is a powerful stimulator of phospholipase A2. Melittin is a peptide consisting of 26 amino acids with the sequence GIGAVLKVLTTGLPALISWIKRKRQQ.-Biological effects:...

, which has been shown to exert inhibitory effects on Lyme bacteria in vitro
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...

; however, no clinical trials of this treatment have been carried out. Anecdotally, medical marijuana may aid joint pain, cognitive brain difficulties and other Lyme-associated issues, although clinical trials are lacking.

External links

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