Lymes Disease Flashcards
Lyme’s - Signs and symptoms
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).[21]
Early localized infection can occur when the infection has not yet spread throughout the body. Only the site where the infection has first come into contact with the skin is affected. The classic sign of early local infection with Lyme disease is a circular, outwardly expanding rash called erythema migrans (EM), which occurs at the site of the tick bite three to 32 days after the tick bite.[2] The rash is red, and may be warm, but is generally painless. Classically, the innermost portion remains dark red and becomes indurated (thicker and firmer), the outer edge remains red, and the portion in between clears, giving the appearance of a bull’s eye, known as a target lesion. However, partial clearing is uncommon, and the bull’s-eye pattern more often involves central redness.[2]
The EM rash associated with early infection is found in about 70–80% of people infected.[1] It can have a range of appearances including the classic bull’s-eye pattern and non-target appearing lesions. The 20–30% without the EM and the non-target lesions can often cause misidentification of Lyme disease.[24] Affected individuals can also experience flu-like symptoms, such as headache, muscle soreness, fever, and malaise.[25] Lyme disease can progress to later stages even in people who do not develop a rash.[23][26]
Early disseminated infection
Within days to weeks after the onset of local infection, the Borrelia 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.[27] Another skin condition, apparently absent in North American patients, but found in Europe, is borrelial lymphocytoma, a purplish lump that develops on the ear lobe, nipple, or scrotum.[28] Various acute neurological problems, termed neuroborreliosis, appear in 10–15% of untreated people.[25][29] These include facial 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. Inflammation of the spinal cord’s nerve roots can cause 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.[30] The disease may adversely impact the heart’s electrical conduction system and can cause abnormal heart rhythms such as atrioventricular block.[31]
Late disseminated infection
After several months, untreated or inadequately treated people 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 impairment of motor or sensory function of the lower extremities in extreme cases.[23] The associated nerve pain radiating out from the spine is termed Bannwarth syndrome,[32] named after Alfred Bannwarth.
The late disseminated stage is where the infection has fully spread throughout the body. Chronic neurologic symptoms occur in up to 5% of untreated people.[25] 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 difficulties, insomnia, a general sense of feeling unwell, and changes in personality.[33] Other problems, however, such as depression and fibromyalgia, are no more common in people with Lyme disease than in the general population.[34][35]
Chronic encephalomyelitis, which may be progressive, can involve cognitive impairment, brain fog, migraines, balance issues, 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 misdiagnosed as schizophrenia or bipolar disorder. Panic attacks and anxiety can occur; also, delusional behavior may be seen, including somatoform delusions, sometimes accompanied by a depersonalization or derealization syndrome, where the patients begin to feel detached from themselves or from reality.[36][37]
A number of studies have found the causative agent of Lyme Borrelia burgdorferi in both the meninges and brains of people with neurological symptoms.[38]
Lyme arthritis usually affects the knees.[39] In a minority of people, arthritis can occur in other joints, including the ankles, elbows, wrists, 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.[28] 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.[
Lyme’s - Cause
Lyme disease is caused by spirochetes, spiral bacteria from the genus Borrelia. Spirochetes are surrounded by peptidoglycan and flagella, along with an outer membrane similar to other Gram-negative bacteria. Because of their double-membrane envelope, Borrelia bacteria are often mistakenly described as Gram negative despite the considerable differences in their envelope components from Gram-negative bacteria.[41] The Lyme-related Borrelia species are collectively known as Borrelia burgdorferi sensu lato, and show a great deal of genetic diversity.
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.
it is transmitted to humans from a natural reservoir among small mammals and birds by ticks that feed on both sets of hosts.[46] Hard-bodied ticks of the genus Ixodes are the main vectors of Lyme disease (also the vector for Babesia).[47] Most infections are caused by ticks in the nymphal stage, because they are very small and thus may feed for long periods of time undetected.[46] In New Jersey, USA, nymphal ticks are generally the size of a poppy seed and sometimes with a dark head and a translucent body.[48] (The younger larval ticks are very rarely infected.[49]) Although deer are the preferred hosts of adult deer ticks, and tick populations are much lower in the absence of deer, ticks generally do not acquire Borrelia from deer, instead they obtain them from infected small mammals such as the white-footed mouse, and occasionally birds.[50]
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.[70] Among early Lyme disease patients, depending on their location, 2–12% will also have HGA and 2–40% will have babesiosis.[71] Ticks in certain regions, including the lands along the eastern Baltic Sea, also transmit tick-borne encephalitis.[72]
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 and Prevention studied 100 ticks in rural New Jersey, and found 55% of the ticks were infected with at least one of the pathogens.[73]
Lyme’s - Pathophysiology
B. burgdorferi can spread throughout the body during the course of the disease, and has been found in the skin, heart, joints, peripheral nervous system, and central nervous system.[52][74] Many of the signs and symptoms of Lyme disease are a consequence of the immune response to the spirochete in those tissues.[25]
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.[75] This provides a protective environment where the spirochete can establish infection. The spirochetes multiply and migrate outward within the dermis. The host inflammatory response to the bacteria in the skin causes the characteristic circular EM lesion.[52] 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.[76]
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 the disseminated disease. The spread of B. burgdorferi is aided by the attachment of the host protease plasmin to the surface of the spirochete.[77]
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.[78] The spirochetes may avoid the immune response by decreasing expression of surface proteins that are targeted by antibodies, antigenic variation of the VlsE surface protein, inactivating key immune components such as complement, and hiding in the extracellular matrix, which may interfere with the function of immune factors.[79][80]
In the brain, B. burgdorferi may induce astrocytes to undergo astrogliosis (proliferation followed by apoptosis), which may contribute to neurodysfunction.[81] The spirochetes may also induce host cells to secrete quinolinic acid, which stimulates the NMDA receptor on nerve cells, which may account for the fatigue and malaise observed with Lyme encephalopathy.[82] In addition, diffuse white matter pathology during Lyme encephalopathy may disrupt gray matter 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 the neuronal loss is less common. Resolution of MRI white matter hyperintensities after antibiotic treatment has been observed.[83]
Tryptophan, a precursor to serotonin, appears to be reduced within the central nervous system in a number of infectious diseases that affect the brain, including Lyme.[84] Researchers are investigating if this neurohormone secretion is the cause of neuropsychiatric disorders developing in some patients with borreliosis.[85
Immunological studies
Exposure to the Borrelia bacterium during Lyme disease possibly causes a long-lived and damaging inflammatory response,[86] a form of pathogen-induced autoimmune disease.[87] The production of this reaction might be due to a form of molecular mimicry, where Borrelia avoids being killed by the immune system by resembling normal parts of the body’s tissues.[88][89]
Chronic symptoms from an autoimmune reaction could explain why some symptoms persist even after the spirochetes have been eliminated from the body. This hypothesis may explain why chronic arthritis persists after antibiotic therapy, similar to rheumatic fever, but its wider application is controversial.[90][91]
Lyme’s - Diagnosis
Lyme disease is diagnosed clinically based on symptoms, objective physical findings (such as EM, facial palsy, or arthritis), or a history of possible exposure to infected ticks, as well as serological blood tests. The EM rash is not always a bull’s eye, i.e., it can be solid red. When making a diagnosis of Lyme disease, health care providers should consider other diseases that may cause similar illnesses. Not all individuals infected with Lyme disease develop the characteristic bull’s-eye rash, and many may not recall a tick bite.[
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.[47] 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.[93][94] Serological testing can be used to support a clinically suspected case, but is not diagnostic by itself.[47]
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”.[95] Lyme disease may be misdiagnosed as multiple sclerosis, rheumatoid arthritis, fibromyalgia, chronic fatigue syndrome, lupus, Crohn’s disease, HIV, or other autoimmune and neurodegenerative diseases. As all people with later-stage infection will have a positive antibody test, simple blood tests can exclude Lyme disease as a possible cause of a person’s symptoms.[96]
Lyme’s - Treatment
Antibiotics are the primary treatment.[2][144] The specific approach to their use is dependent on the individual affected and the stage of the disease.[144] For most people with early localized infection, oral administration of doxycycline is widely recommended as the first choice, as it is effective against not only Borrelia bacteria but also a variety of other illnesses carried by ticks.[144] Doxycycline is contraindicated in children younger than eight years of age and women who are pregnant or breastfeeding;[144] alternatives to doxycycline are amoxicillin, cefuroxime axetil, and azithromycin.[144] Individuals with early disseminated or late infection may have symptomatic cardiac disease, refractory Lyme arthritis, or neurologic symptoms like meningitis or encephalitis.[144] Intravenous administration of ceftriaxone is recommended as the first choice in these cases;[144] cefotaxime and doxycycline are available as alternatives.[144]
These treatment regimens last from one to four weeks.[144] If joint swelling persists or returns, a second round of antibiotics may be considered.[144] Outside of that, a prolonged antibiotic regimen lasting more than 28 days is not recommended as no clinical evidence shows it to be effective.[144][146] IgM and IgG antibody levels may be elevated for years even after successful treatment with antibiotics.[144] As antibody levels are not indicative of treatment success, testing for them is not recommended.[144]
Lyme’s - Prognosis
simultaneous infection with other tick-borne diseases (coinfections), including ehrlichiosis, babesiosis, and immune suppression[citation needed] in the patient.
It is believed that less than 5% of people have lingering symptoms of fatigue, pain, or joint and muscle aches at the time they finish treatment.[148] These symptoms can last for more than 6 months. This condition is called post-treatment lyme disease syndrome. As of 2016 the reason for the lingering symptoms was not known; the condition is generally managed similarly to fibromyalgia or chronic fatigue syndrome.[149]
Lyme’s - Epidemiology
Countries with reported Lyme disease cases.
Lyme disease occurs regularly in Northern Hemisphere temperate regions (africa/america/asia)Tests on pet dogs, carried out throughout the country in 2009 indicated that around 2.5% of ticks in the UK may be infected, considerably higher than previously thought
