<unk>  is diagnosed based on symptoms, objective physical findings (such as erythema migrans (EM) rash, facial palsy, or arthritis), history of possible exposure to infected ticks, and possibly laboratory tests. People with symptoms of early<unk>  should have a total body skin examination for EM rashes and asked whether EM-type rashes had manifested within the last 1–2 months. Presence of an EM rash and recent tick exposure (i.e., being outdoors in a likely tick habitat where<unk>  is common, within 30 days of the appearance of the rash) are sufficient for<unk>  diagnosis; no laboratory confirmation is needed or recommended. Most people who get infected do not remember a tick or a bite, and the EM rash need not look like a bull's eye (most EM rashes in the U.S. do not) or be accompanied by any other symptoms. In the U.S.,<unk>  is most common in the New England and Mid-Atlantic states and parts of Wisconsin and Minnesota, but it is expanding into other areas. Several bordering areas of Canada also have high<unk>  risk. In the absence of an EM rash or history of tick exposure,<unk>  diagnosis depends on laboratory confirmation. The bacteria that cause<unk>  are difficult to observe directly in body tissues and also difficult and too time-consuming to grow in the laboratory. The most widely used tests look instead for presence of antibodies against those bacteria in the blood. A positive antibody test result does not by itself prove active infection but can confirm an infection that is suspected because of symptoms, objective findings, and history of tick exposure in a person. Because as many as 5–20% of the normal population have antibodies against<unk> , people without history and symptoms suggestive of<unk>  should not be tested for<unk>  antibodies: a positive result would likely be false, possibly causing unnecessary treatment. In some cases, when history, signs, and symptoms are strongly suggestive of early disseminated<unk> , empiric treatment may be started and reevaluated as laboratory test results become available. Laboratory testing Tests for antibodies in the blood by ELISA and Western blot is the most widely used method for<unk>  diagnosis. A two-tiered protocol is recommended by the Centers for<unk>  Control and Prevention (CDC): the sensitive ELISA test is performed first, and if it is positive or equivocal, then the more specific Western blot is run. The immune system takes some time to produce antibodies in quantity. After<unk>  infection onset, antibodies of types IgM and IgG usually can first be detected respectively at 2–4 weeks and 4–6 weeks, and peak at 6–8 weeks. When an EM rash first appears, detectable antibodies may not be present. Therefore, it is recommended that testing not be performed and diagnosis be based on the presence of the EM rash. Up to 30 days after suspected<unk>  infection onset, infection can be confirmed by detection of IgM or IgG antibodies; after that, it is recommended that only IgG antibodies be considered. A positive IgM and negative IgG test result after the first month of infection is generally indicative of a false-positive result. The number of IgM antibodies usually collapses 4–6 months after infection, while IgG antibodies can remain detectable for years. Other tests may be used in neuroborreliosis cases. In Europe, neuroborreliosis is usually caused by Borrelia garinii and almost always involves lymphocytic pleocytosis, i.e. the densities of lymphocytes (infection-fighting cells) and protein in the cerebrospinal fluid (CSF) typically rise to characteristically abnormal levels, while glucose level remains normal. Additionally, the immune system produces antibodies against<unk>  inside the intrathecal space, which contains the CSF. Demonstration by lumbar puncture and CSF analysis of pleocytosis and intrathecal antibody production are required for definite diagnosis of neuroborreliosis in Europe (except in cases of peripheral neuropathy associated with acrodermatitis chronica atrophicans, which usually is caused by Borrelia afzelii and confirmed by blood antibody tests). In North America, neuroborreliosis is caused by Borrelia burgdorferi and may not be accompanied by the same CSF signs; they confirm a diagnosis of central nervous system (CNS) neuroborreliosis if positive, but do not exclude it if negative. American guidelines consider CSF analysis optional when symptoms appear to be confined to the peripheral nervous system (PNS), e.g. facial palsy without overt meningitis symptoms. Unlike blood and intrathecal antibody tests, CSF pleocytosis tests revert to normal after infection ends and therefore can be used as objective markers of treatment success and inform decisions on whether to retreat. In infection involving the PNS, electromyography and nerve conduction studies can be used to monitor objectively the response to treatment. In<unk>  carditis, electrocardiograms are used to evidence heart conduction abnormalities, while echocardiography may show myocardial dysfunction. Biopsy and confirmation of Borrelia cells in myocardial tissue may be used in specific cases but are usually not done because of risk of the procedure. Polymerase chain reaction (PCR) tests for<unk>  have also been developed to detect the genetic material (DNA) of the<unk>  spirochete. Culture or PCR are the current means for detecting the presence of the organism, as serologic studies only test for antibodies of Borrelia. PCR has the advantage of being much faster than culture. However, PCR tests are susceptible to false positive results, e.g. by detection of debris of dead Borrelia cells or specimen contamination. Even when properly performed, PCR often shows false-negative results because few Borrelia cells can be found in blood and cerebrospinal fluid (CSF) during infection. Hence, PCR tests are recommended only in special cases, e.g. diagnosis of<unk>  arthritis, because it is a highly sensitive way of detecting ospA DNA in synovial fluid. Although sensitivity of PCR in CSF is low, its use may be considered when intrathecal antibody production test results are suspected of being falsely negative, e.g. in very early (< 6 weeks) neuroborreliosis or in immunosuppressed people. Several other forms of laboratory testing for<unk>  are available, some of which have not been adequately validated. OspA antigens, shed by live Borrelia bacteria into urine, are a promising technique being studied. The use of nanotrap particles for their detection is being looked at and the OspA has been linked to active symptoms of<unk> . High titers of either immunoglobulin G (IgG) or immunoglobulin M (IgM) antibodies to Borrelia antigens indicate<unk> , but lower titers can be misleading, because the IgM antibodies may remain after the initial infection, and IgG antibodies may remain for years. The CDC does not recommend urine antigen tests, PCR tests on urine, immunofluorescent staining for cell-wall-deficient forms of B. burgdorferi, and lymphocyte transformation tests. Imaging Neuroimaging is controversial in whether it provides specific patterns unique to neuroborreliosis, but may aid in differential diagnosis and in understanding the pathophysiology of the<unk> . Though controversial, some evidence shows certain neuroimaging tests can provide data that are helpful in the diagnosis of a person. Magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT) are two of the tests that can identify abnormalities in the brain of a person affected with this<unk> . Neuroimaging findings in an MRI include lesions in the periventricular white matter, as well as enlarged ventricles and cortical atrophy. The findings are considered somewhat unexceptional because the lesions have been found to be reversible following antibiotic treatment. Images produced using SPECT show numerous areas where an insufficient amount of blood is being delivered to the cortex and subcortical white matter. However, SPECT images are known to be nonspecific because they show a heterogeneous pattern in the imaging. The abnormalities seen in the SPECT images are very similar to those seen in people with cerebral vacuities and Creutzfeldt–Jakob<unk> , which makes them questionable. Differential diagnosis Community clinics have been reported to misdiagnose 23–28% of Erythema migrans (EM) rashes and 83% of other objective manifestations of early<unk> . EM rashes are often misdiagnosed as spider bites, cellulitis, or shingles. Many misdiagnoses are credited to the widespread misconception that EM rashes should look like a bull's eye. Actually, the key distinguishing features of the EM rash are the speed and extent to which it expands, respectively up to 2–3 cm/day and a diameter of at least 5 cm, and in 50% of cases more than 16 cm. The rash expands away from its center, which may or may not look different or be separated by ring-like clearing from the rest of the rash. Compared to EM rashes, spider bites are more common in the limbs, tend to be more painful and itchy or become swollen, and some may cause necrosis (sinking dark blue patch of dead skin). Cellulitis most commonly develops around a wound or ulcer, is rarely circular, and is more likely to become swollen and tender. EM rashes often appear at sites that are unusual for cellulitis, such as the armpit, groin, abdomen, or back of knee. Like<unk> , shingles often begins with headache, fever, and fatigue, which are followed by pain or numbness. However, unlike<unk> , in shingles these symptoms are usually followed by appearance of rashes
Lyme disease
Cellulitis
Mumps
Bell's palsy
Rabies
Meningitis
Rickettsialpox
Scarlet fever