Lyme disease

Lyme disease

Lyme disease, or borreliosis, is an emerging infectious disease caused by at least three species of bacteria belonging to the genus Borrelia.[1] Borrelia burgdorferi sensu lato[2] is the main cause of Lyme disease in the United States, whereas Borrelia afzelii and Borrelia garinii cause most European cases. The disease is named after the village of Lyme, Connecticut where a number of cases were identified in 1975. Although Allen Steere realized in 1978 that Lyme disease was a tick-borne disease, the cause of the disease remained a mystery until 1982, when B. burgdorferi was identified by Willy Burgdorfer.

Lyme disease is the most common tick-borne disease in the Northern Hemisphere. Borrelia is transmitted to humans by the bite of infected ticks belonging to a few species of the genus Ixodes (the so-called "hard ticks").[3] Early symptoms may include fever, headache, fatigue, depression, and a characteristic circular skin rash called erythema migrans. Left untreated, later symptoms may involve the joints, heart, and central nervous system. In most cases, the infection and its symptoms are eliminated by antibiotics, especially if the illness is treated early. Late, delayed, or inadequate treatment can lead to the more serious symptoms, which can be disabling and difficult to treat.[4] Occasionally, symptoms such as arthritis persist after the infection has been eliminated by antibiotics, prompting suggestions that Borrelia causes autoimmunity.[5]

Some groups have argued that "chronic" Lyme disease is responsible for a range of medically unexplained symptoms beyond the recognized symptoms of late Lyme disease, and that additional, long-term antibiotic treatments are needed.[6] Of four randomized controlled trials of long-term ceftriaxone and doxycycline treatment in patients with ongoing symptoms, two found no benefit,[7][8] and two found inconsistent benefits with significant side effects and risks from the antibiotic treatment.[9][10][11] Most expert groups, including the Infectious Diseases Society of America and the American Academy of Neurology, have found that existing scientific evidence does not support a role for Borrelia nor ongoing antibiotic treatment in such cases.[12][13] However, the area is controversial, with some doctors, patient advocacy groups, and politicians continuing to argue that long-term treatment is beneficial. This dispute has led to legal action over treatment guidelines.

Lyme disease 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 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.[14] Asymptomatic infection exists, but occurs in less than 7% of infected individuals in the United States.[15] Asymptomatic infection may be much more common among those infected in Europe.[16]

Stage 1: Early localized infection

The classic sign of early local infection with Lyme disease is a circular, outwardly expanding rash called erythema chronicum migrans (also erythema migrans or EM), which occurs at the site of the tick bite 3 to 30 days after the tick bite [17][18] The rash is red, and may be warm, but is generally painless. Classically, the innermost portion remains dark red and becomes indurated; the outer edge remains red; and the portion in between clears, giving the appearance of a bullseye. However, partial clearing is uncommon, and the bullseye pattern more often involves central redness.[19]

Erythema migrans is thought to occur in about 80% of infected patients.[18] Patients can also experience flu-like symptoms such as headache, muscle soreness, fever, and malaise.[20] Lyme disease can progress to later stages even in patients who do not develop a rash.[21]

Stage 2: Early disseminated infection

Within days to weeks after the onset of local infection, the borrelia bacteria may begin to spread through the bloodstream. Erythema chronicum migrans may develop at sites across the body that bear no relation to the original tick bite.[22] 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.[23] Other discrete symptoms include migrating pain in muscles, joint, and tendons, and heart palpitations and dizziness caused by changes in heartbeat.

Acute neurological problems, which appear in 15% of untreated patients, encompass a spectrum of disorders.[20] These include facial or Bell's palsy, which is the loss of muscle tone on one or both sides of the face, as well as meningitis, 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 may lead to memory loss, sleep disturbances, or mood changes. In addition, some case reports have described altered mental status as the only symptom seen in a few cases of early neuroborreliosis.[24]

Stage 3: 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. Myriad disabling symptoms can occur, including permanent paraplegia in the most extreme cases.[25]

Chronic neurologic symptoms occur in up to 5% of untreated patients.[20] A polyneuropathy 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.[26] However, other problems such as depression and fibromyalgia are no more common in people who have been infected with Lyme than in the general population.[26][27] Chronic encephalomyelitis, which may be progressive, can involve cognitive impairment, weakness in the legs, awkward gait, facial palsy, bladder problems, vertigo, and back pain. In rare cases untreated Lyme disease may cause frank psychosis, which has been mis-diagnosed as schizophrenia or bipolar disorder. Panic attack and anxiety can occur, also delusional behavior, including somatoform delusions, sometimes accompanied by a depersonalization or derealization syndrome, where the person begins to feel detached from themselves or from reality.[28][29]

Lyme arthritis usually affects the knees.[30] In a minority of patients arthritis can occur in other joints, including the ankles, elbows, wrist, hips, and shoulders. Pain is often mild or moderate, usually with swelling at the involved joint. Baker's cysts may form and rupture. In some cases joint erosion occurs.

Acrodermatitis chronica atrophicans (ACA) is a chronic skin disorder observed primarily in Europe among the elderly.[23] 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, with the skin becoming first thin and wrinkled and then, if untreated, completely dry and hairless.[31]

Lyme disease Cause

Lyme disease is caused by Gram-negative spirochetal bacteria from the genus Borrelia. At least 11 Borrelia species have been discovered, 3 of which are known to be Lyme-related.[32][33] The Borrelia species that cause Lyme disease are collectively known as Borrelia burgdorferi sensu lato, and show a great deal of genetic diversity.[34]

The group Borrelia burgdorferi sensu lato is made up of three closely-related species that are probably responsible for the large majority of cases: B. burgdorferi sensu stricto (predominant in North America, but also present in Europe), B. afzelii, and B. garinii (both predominant in Eurasia).[32] Some studies have also proposed that B. bissettii and B. valaisiana may sometimes infect humans, but these species do not seem to be important causes of disease.[35][36]

Tick borne co-infections

Ticks that transmit B. burgdorferi to humans can also carry and transmit several other parasites such as Theileria microti and Anaplasma phagocytophilum, which cause the diseases babesiosis and human granulocytic anaplasmosis (HGA), respectively.[53] Among early Lyme disease patients, depending on their location, 2–12% will also have HGA and 2–40% will have babesiosis.[54]

Co-infections complicate Lyme symptoms, especially diagnosis and treatment. It is possible for a tick to carry and transmit one of the co-infections and not Borrelia, making diagnosis difficult and often elusive. The Centers for Disease Control studied 100 ticks in rural New Jersey and found that 55% of the ticks were infected with at least one of the pathogens.[55]

Lyme disease Diagnosis

Lyme disease is diagnosed clinically based on symptoms, objective physical findings (such as erythema migrans, facial palsy, or arthritis), a history of possible exposure to infected ticks, as well as serological blood tests. When making a diagnosis of Lyme disease, health care providers should consider other diseases that may cause similar illness. Most but not all patients with Lyme disease will develop the characteristic bulls-eye rash, but many may not recall a tick bite.[56] Laboratory testing is not recommended for persons who do not have symptoms of Lyme disease.

Because of the difficulty in culturing Borrelia bacteria in the laboratory, diagnosis of Lyme disease is typically based on the clinical exam findings and a history of exposure to endemic Lyme areas.[1] 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.[57][58] Serological testing can be used to support a clinically suspected case but is not diagnostic by itself.[1]

Diagnosis of late-stage Lyme disease is often difficult because of the multi-faceted appearance which can mimic symptoms of many other diseases. For this reason, a reviewer called Lyme the new "great imitator."[59] Lyme disease may be misdiagnosed as multiple sclerosis, rheumatoid arthritis, fibromyalgia, chronic fatigue syndrome (CFS), lupus, or other autoimmune and neurodegenerative diseases.

Lyme disease Prevention

Attached ticks should be removed promptly, as removal within 36 hours can reduce transmission rates to close to zero.[82] Protective clothing includes a hat and long-sleeved shirts and long trousers that are tucked into socks or boots. Light-colored clothing makes the tick more easily visible before it attaches itself. People should use special care in handling and allowing outdoor pets inside homes because they can bring ticks into the house.

A more effective, community wide method of preventing Lyme disease is to reduce the numbers of primary hosts on which the deer tick depends such as rodents, other small mammals, and deer. Reduction of the deer population may over time help break the reproductive cycle of the deer ticks and their ability to flourish in suburban and rural areas.[83]

An unusual, organic approach to control of ticks and prevention of Lyme disease involves the use of domesticated guineafowl. Guineafowl are voracious consumers of insects and have a particular fondness for ticks. Localized use of domesticated guineafowl may reduce dependence on chemical pest-control methods.[84]

Lyme disease Treatment

Antibiotics are the primary treatment for Lyme disease; the most appropriate antibiotic treatment depends upon the patient and the stage of the disease.[1] The antibiotics of choice are doxycycline (in adults), amoxicillin (in children), erythromycin (for pregnant women) and ceftriaxone, with treatment lasting 14 to 21 days.[97] Alternative choices are cefuroxime and cefotaxime.[1] Treatment of pregnant women is similar, but tetracycline should not be used.[97]

A double blind, randomized, placebo-controlled multicenter clinical study indicated that 3 weeks of treatment with intravenous ceftriaxone, followed by 100 days of treatment with oral amoxicillin did not improve symptoms any more than just 3 weeks of treatment with ceftriaxone. The researchers noted that the outcome should not be evaluated after the initial antibiotic treatment but rather 6–12 months afterwards. In patients with chronic post-treatment symptoms, persistent positive levels of antibodies did not seem to provide any useful information for further care of the patient.[98]

In later stages, the bacteria disseminate throughout the body and may cross the blood-brain barrier, making the infection more difficult to treat. Late diagnosed Lyme is treated with oral or IV antibiotics, frequently ceftriaxone for a minimum of four weeks. Minocycline is also indicated for neuroborreliosis for its ability to cross the blood-brain barrier.[99]

Post-Lyme disease symptoms and "chronic" Lyme disease

Confusingly, the term "chronic Lyme disease" is often applied to several different sets of patients. One usage refers to people with the symptoms of untreated and desseminated late-stage Lyme disease who are suffering from the symptoms of this stage of the disease: these are arthritis, peripheral neuropathy and/or encephalomyelitis. The term is also applied to people who have had the disease in the past and some symptoms remain after antibiotic treatment, this is also called post-Lyme disease syndrome. A third and controversial use of the term applies to patients with non-specific symptoms such as fatigue who show no objective evidence that they have been infected with Lyme disease in the past, since the standard diagnostic tests for infection are negative.[12]

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.[4][100] While it is undisputed that these patients can have severe symptoms, the cause of these symptoms and appropriate treatment is controversial. The symptoms may represent "for all intents and purposes" fibromyalgia/chronic fatigue syndrome.[101] A few doctors attribute these symptoms to persistent infection with Borrelia, or coinfections with other tick-borne infections such as Ehrlichia and Babesia.[102][103] Other doctors believe that the initial infection may cause an autoimmune reaction that continues to cause serious symptoms even after the bacteria have been eliminated by antibiotics.[104]

Four randomized controlled trials 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 that their results did not support long-term antibiotic therapy. Of these four studies,

two studies showed no benefit from 30 days of IV ceftriaxone and 60 days of oral doxycycline, concluding that "treatment with intravenous and oral antibiotics for 90 days did not improve symptoms more than placebo".[7][8]
one study showed an improvement only in fatigue after 28 days of IV antibiotics, an effect that was significant only in a group of patients that never had antibiotics previously.[11] The results may have been compromised by unblinding, and detected a large placebo effect.[105] This trials also saw several cases of life-threatening side effects, concluding that "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 IV antibiotics, but concluded that the treatment was "not an effective strategy for sustained cognitive improvement."[9][10] These patients had also been ill for many years and had taken many antibiotic courses. Also, this study performed ad hoc statistical analysis[106] and its results were questionably significant.[100]

Additionally, a non-profit interest group called the International Lyme And Associated Diseases Society (ILADS)[107] argues that "chronic" Lyme disease is responsible for a range of medically unexplained symptoms beyond the known manifestations of late Lyme disease, with or without evidence of past or present infection.[6] It has questioned the generalizability and reliability of some of the above trials and the reliability of the current diagnostic tests.[6][108][103] Major US medical authorities, including the Infectious Diseases Society of America, the American Academy of Neurology, and the National Institutes of Health, have stated that 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.[12][109][110][111] There are significant side effects and risks of prolonged antibiotic therapy, and at least one death has been reported from complications of a 27-month course of intravenous antibiotics for an unsubstantiated diagnosis of "chronic Lyme disease".[112]

Treatment of post-Lyme disease symptoms

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.[113] Although it is possible that these chronic symptoms are due to either autoimmunity or residual bacteria (see immunological studies below), no Borrelia DNA can usually be detected in the joints after antibiotic treatment, which suggests that the arthritis may continue even after the bacteria have been killed.[104] Lyme arthritis that persists after antibiotic treatment may be treated with hydroxychloroquine or methotrexate.[114] Corticosteroid injections into the affected joint are not recommended for any stage of Lyme arthritis.[115]

Patients with chronic neuropathic pain responded well to gabapentin monotherapy with residual pain after intravenous ceftriaxone treatment in a pilot study.[116] Some antibiotics may have a dual effect on Lyme disease, since minocycline and doxycycline have anti-inflammatory effects in addition to their antibiotic actions including anti-inflammatory effects specific to the inflammation caused by Lyme Disease.[117][118] Indeed, minocycline is used in other neurodegenerative and inflammatory disorders such as multiple sclerosis, Parkinson's disease, Huntington's disease, rheumatoid arthritis (RA) and ALS.[119]

Lyme disease
Norovirus Marfan syndrome Nasal Cancer Marburg Hemorrhagic Fever Malignant Hyperthermia Male Breast Cancer Lyme disease Lung cancer Legionellosis Latex Allergy Lassa Fever Jaundice / Kernicterus Hypothyroidism Kawasaki disease Genetic-Brain-Disorders Gallbladder-Diseases Fetal alcohol syndrome Diabetes Crimean-Congo Hemorrhagic Fever Dengue-and-Dengue-Hemorrhagic-Fever Chikungunya-Fever Cat Scratch Disease Cancer Larynx Cancer Among Children Borderline Personality Disorder Bladder cancer Baylisascaris Infection Benign tumor Skin Cancer African trypanosomiasis Coming Soon	Lyme disease Lyme disease, or borreliosis, is an emerging infectious disease caused by at least three species of bacteria belonging to the genus Borrelia.[1] Borrelia burgdorferi sensu lato[2] is the main cause of Lyme disease in the United States, whereas Borrelia afzelii and Borrelia garinii cause most European cases. The disease is named after the village of Lyme, Connecticut where a number of cases were identified in 1975. Although Allen Steere realized in 1978 that Lyme disease was a tick-borne disease, the cause of the disease remained a mystery until 1982, when B. burgdorferi was identified by Willy Burgdorfer. Lyme disease is the most common tick-borne disease in the Northern Hemisphere. Borrelia is transmitted to humans by the bite of infected ticks belonging to a few species of the genus Ixodes (the so-called "hard ticks").[3] Early symptoms may include fever, headache, fatigue, depression, and a characteristic circular skin rash called erythema migrans. Left untreated, later symptoms may involve the joints, heart, and central nervous system. In most cases, the infection and its symptoms are eliminated by antibiotics, especially if the illness is treated early. Late, delayed, or inadequate treatment can lead to the more serious symptoms, which can be disabling and difficult to treat.[4] Occasionally, symptoms such as arthritis persist after the infection has been eliminated by antibiotics, prompting suggestions that Borrelia causes autoimmunity.[5] Some groups have argued that "chronic" Lyme disease is responsible for a range of medically unexplained symptoms beyond the recognized symptoms of late Lyme disease, and that additional, long-term antibiotic treatments are needed.[6] Of four randomized controlled trials of long-term ceftriaxone and doxycycline treatment in patients with ongoing symptoms, two found no benefit,[7][8] and two found inconsistent benefits with significant side effects and risks from the antibiotic treatment.[9][10][11] Most expert groups, including the Infectious Diseases Society of America and the American Academy of Neurology, have found that existing scientific evidence does not support a role for Borrelia nor ongoing antibiotic treatment in such cases.[12][13] However, the area is controversial, with some doctors, patient advocacy groups, and politicians continuing to argue that long-term treatment is beneficial. This dispute has led to legal action over treatment guidelines. Lyme disease 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 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.[14] Asymptomatic infection exists, but occurs in less than 7% of infected individuals in the United States.[15] Asymptomatic infection may be much more common among those infected in Europe.[16] Stage 1: Early localized infection The classic sign of early local infection with Lyme disease is a circular, outwardly expanding rash called erythema chronicum migrans (also erythema migrans or EM), which occurs at the site of the tick bite 3 to 30 days after the tick bite [17][18] The rash is red, and may be warm, but is generally painless. Classically, the innermost portion remains dark red and becomes indurated; the outer edge remains red; and the portion in between clears, giving the appearance of a bullseye. However, partial clearing is uncommon, and the bullseye pattern more often involves central redness.[19] Erythema migrans is thought to occur in about 80% of infected patients.[18] Patients can also experience flu-like symptoms such as headache, muscle soreness, fever, and malaise.[20] Lyme disease can progress to later stages even in patients who do not develop a rash.[21] Stage 2: Early disseminated infection Within days to weeks after the onset of local infection, the borrelia bacteria may begin to spread through the bloodstream. Erythema chronicum migrans may develop at sites across the body that bear no relation to the original tick bite.[22] 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.[23] Other discrete symptoms include migrating pain in muscles, joint, and tendons, and heart palpitations and dizziness caused by changes in heartbeat. Acute neurological problems, which appear in 15% of untreated patients, encompass a spectrum of disorders.[20] These include facial or Bell's palsy, which is the loss of muscle tone on one or both sides of the face, as well as meningitis, 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 may lead to memory loss, sleep disturbances, or mood changes. In addition, some case reports have described altered mental status as the only symptom seen in a few cases of early neuroborreliosis.[24] Stage 3: 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. Myriad disabling symptoms can occur, including permanent paraplegia in the most extreme cases.[25] Chronic neurologic symptoms occur in up to 5% of untreated patients.[20] A polyneuropathy 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.[26] However, other problems such as depression and fibromyalgia are no more common in people who have been infected with Lyme than in the general population.[26][27] Chronic encephalomyelitis, which may be progressive, can involve cognitive impairment, weakness in the legs, awkward gait, facial palsy, bladder problems, vertigo, and back pain. In rare cases untreated Lyme disease may cause frank psychosis, which has been mis-diagnosed as schizophrenia or bipolar disorder. Panic attack and anxiety can occur, also delusional behavior, including somatoform delusions, sometimes accompanied by a depersonalization or derealization syndrome, where the person begins to feel detached from themselves or from reality.[28][29] Lyme arthritis usually affects the knees.[30] In a minority of patients arthritis can occur in other joints, including the ankles, elbows, wrist, hips, and shoulders. Pain is often mild or moderate, usually with swelling at the involved joint. Baker's cysts may form and rupture. In some cases joint erosion occurs. Acrodermatitis chronica atrophicans (ACA) is a chronic skin disorder observed primarily in Europe among the elderly.[23] 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, with the skin becoming first thin and wrinkled and then, if untreated, completely dry and hairless.[31] Lyme disease Cause Lyme disease is caused by Gram-negative spirochetal bacteria from the genus Borrelia. At least 11 Borrelia species have been discovered, 3 of which are known to be Lyme-related.[32][33] The Borrelia species that cause Lyme disease are collectively known as Borrelia burgdorferi sensu lato, and show a great deal of genetic diversity.[34] The group Borrelia burgdorferi sensu lato is made up of three closely-related species that are probably responsible for the large majority of cases: B. burgdorferi sensu stricto (predominant in North America, but also present in Europe), B. afzelii, and B. garinii (both predominant in Eurasia).[32] Some studies have also proposed that B. bissettii and B. valaisiana may sometimes infect humans, but these species do not seem to be important causes of disease.[35][36] Tick borne co-infections Ticks that transmit B. burgdorferi to humans can also carry and transmit several other parasites such as Theileria microti and Anaplasma phagocytophilum, which cause the diseases babesiosis and human granulocytic anaplasmosis (HGA), respectively.[53] Among early Lyme disease patients, depending on their location, 2–12% will also have HGA and 2–40% will have babesiosis.[54] Co-infections complicate Lyme symptoms, especially diagnosis and treatment. It is possible for a tick to carry and transmit one of the co-infections and not Borrelia, making diagnosis difficult and often elusive. The Centers for Disease Control studied 100 ticks in rural New Jersey and found that 55% of the ticks were infected with at least one of the pathogens.[55] Lyme disease Diagnosis Lyme disease is diagnosed clinically based on symptoms, objective physical findings (such as erythema migrans, facial palsy, or arthritis), a history of possible exposure to infected ticks, as well as serological blood tests. When making a diagnosis of Lyme disease, health care providers should consider other diseases that may cause similar illness. Most but not all patients with Lyme disease will develop the characteristic bulls-eye rash, but many may not recall a tick bite.[56] Laboratory testing is not recommended for persons who do not have symptoms of Lyme disease. Because of the difficulty in culturing Borrelia bacteria in the laboratory, diagnosis of Lyme disease is typically based on the clinical exam findings and a history of exposure to endemic Lyme areas.[1] 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.[57][58] Serological testing can be used to support a clinically suspected case but is not diagnostic by itself.[1] Diagnosis of late-stage Lyme disease is often difficult because of the multi-faceted appearance which can mimic symptoms of many other diseases. For this reason, a reviewer called Lyme the new "great imitator."[59] Lyme disease may be misdiagnosed as multiple sclerosis, rheumatoid arthritis, fibromyalgia, chronic fatigue syndrome (CFS), lupus, or other autoimmune and neurodegenerative diseases. Lyme disease Prevention Attached ticks should be removed promptly, as removal within 36 hours can reduce transmission rates to close to zero.[82] Protective clothing includes a hat and long-sleeved shirts and long trousers that are tucked into socks or boots. Light-colored clothing makes the tick more easily visible before it attaches itself. People should use special care in handling and allowing outdoor pets inside homes because they can bring ticks into the house. A more effective, community wide method of preventing Lyme disease is to reduce the numbers of primary hosts on which the deer tick depends such as rodents, other small mammals, and deer. Reduction of the deer population may over time help break the reproductive cycle of the deer ticks and their ability to flourish in suburban and rural areas.[83] An unusual, organic approach to control of ticks and prevention of Lyme disease involves the use of domesticated guineafowl. Guineafowl are voracious consumers of insects and have a particular fondness for ticks. Localized use of domesticated guineafowl may reduce dependence on chemical pest-control methods.[84] Lyme disease Treatment Antibiotics are the primary treatment for Lyme disease; the most appropriate antibiotic treatment depends upon the patient and the stage of the disease.[1] The antibiotics of choice are doxycycline (in adults), amoxicillin (in children), erythromycin (for pregnant women) and ceftriaxone, with treatment lasting 14 to 21 days.[97] Alternative choices are cefuroxime and cefotaxime.[1] Treatment of pregnant women is similar, but tetracycline should not be used.[97] A double blind, randomized, placebo-controlled multicenter clinical study indicated that 3 weeks of treatment with intravenous ceftriaxone, followed by 100 days of treatment with oral amoxicillin did not improve symptoms any more than just 3 weeks of treatment with ceftriaxone. The researchers noted that the outcome should not be evaluated after the initial antibiotic treatment but rather 6–12 months afterwards. In patients with chronic post-treatment symptoms, persistent positive levels of antibodies did not seem to provide any useful information for further care of the patient.[98] In later stages, the bacteria disseminate throughout the body and may cross the blood-brain barrier, making the infection more difficult to treat. Late diagnosed Lyme is treated with oral or IV antibiotics, frequently ceftriaxone for a minimum of four weeks. Minocycline is also indicated for neuroborreliosis for its ability to cross the blood-brain barrier.[99] Post-Lyme disease symptoms and "chronic" Lyme disease Confusingly, the term "chronic Lyme disease" is often applied to several different sets of patients. One usage refers to people with the symptoms of untreated and desseminated late-stage Lyme disease who are suffering from the symptoms of this stage of the disease: these are arthritis, peripheral neuropathy and/or encephalomyelitis. The term is also applied to people who have had the disease in the past and some symptoms remain after antibiotic treatment, this is also called post-Lyme disease syndrome. A third and controversial use of the term applies to patients with non-specific symptoms such as fatigue who show no objective evidence that they have been infected with Lyme disease in the past, since the standard diagnostic tests for infection are negative.[12] 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.[4][100] While it is undisputed that these patients can have severe symptoms, the cause of these symptoms and appropriate treatment is controversial. The symptoms may represent "for all intents and purposes" fibromyalgia/chronic fatigue syndrome.[101] A few doctors attribute these symptoms to persistent infection with Borrelia, or coinfections with other tick-borne infections such as Ehrlichia and Babesia.[102][103] Other doctors believe that the initial infection may cause an autoimmune reaction that continues to cause serious symptoms even after the bacteria have been eliminated by antibiotics.[104] Four randomized controlled trials 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 that their results did not support long-term antibiotic therapy. Of these four studies, two studies showed no benefit from 30 days of IV ceftriaxone and 60 days of oral doxycycline, concluding that "treatment with intravenous and oral antibiotics for 90 days did not improve symptoms more than placebo".[7][8] one study showed an improvement only in fatigue after 28 days of IV antibiotics, an effect that was significant only in a group of patients that never had antibiotics previously.[11] The results may have been compromised by unblinding, and detected a large placebo effect.[105] This trials also saw several cases of life-threatening side effects, concluding that "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 IV antibiotics, but concluded that the treatment was "not an effective strategy for sustained cognitive improvement."[9][10] These patients had also been ill for many years and had taken many antibiotic courses. Also, this study performed ad hoc statistical analysis[106] and its results were questionably significant.[100] Additionally, a non-profit interest group called the International Lyme And Associated Diseases Society (ILADS)[107] argues that "chronic" Lyme disease is responsible for a range of medically unexplained symptoms beyond the known manifestations of late Lyme disease, with or without evidence of past or present infection.[6] It has questioned the generalizability and reliability of some of the above trials and the reliability of the current diagnostic tests.[6][108][103] Major US medical authorities, including the Infectious Diseases Society of America, the American Academy of Neurology, and the National Institutes of Health, have stated that 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.[12][109][110][111] There are significant side effects and risks of prolonged antibiotic therapy, and at least one death has been reported from complications of a 27-month course of intravenous antibiotics for an unsubstantiated diagnosis of "chronic Lyme disease".[112] Treatment of post-Lyme disease symptoms 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.[113] Although it is possible that these chronic symptoms are due to either autoimmunity or residual bacteria (see immunological studies below), no Borrelia DNA can usually be detected in the joints after antibiotic treatment, which suggests that the arthritis may continue even after the bacteria have been killed.[104] Lyme arthritis that persists after antibiotic treatment may be treated with hydroxychloroquine or methotrexate.[114] Corticosteroid injections into the affected joint are not recommended for any stage of Lyme arthritis.[115] Patients with chronic neuropathic pain responded well to gabapentin monotherapy with residual pain after intravenous ceftriaxone treatment in a pilot study.[116] Some antibiotics may have a dual effect on Lyme disease, since minocycline and doxycycline have anti-inflammatory effects in addition to their antibiotic actions including anti-inflammatory effects specific to the inflammation caused by Lyme Disease.[117][118] Indeed, minocycline is used in other neurodegenerative and inflammatory disorders such as multiple sclerosis, Parkinson's disease, Huntington's disease, rheumatoid arthritis (RA) and ALS.[119]
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