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| {{Lyme disease}}
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| {{CMG}} {{AE}} {{IMD}}
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| ==Overview==
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| Laboratory blood tests are helpful if used correctly and performed with validated methods. Laboratory tests are not recommended for patients who do not have symptoms typical of Lyme disease. [[Polymerase chain reaction]] (PCR) tests for Lyme disease have also been developed to detect the genetic material ([[DNA]]) of the Lyme disease spirochete.
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| ==Laboratory Findings==
| | {{CMG}}; {{AE}} {{Anmol}} |
| * Lyme disease is diagnosed based on:
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| #Signs and symptoms
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| #A history of possible exposure to infected blacklegged ticks
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| * Laboratory blood tests are helpful if used correctly and performed with validated methods.
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| * Laboratory tests are not recommended for patients who do not have symptoms typical of Lyme disease.
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| * Just as it is important to correctly diagnose Lyme disease when a patient has it, it is important to avoid misdiagnosis and treatment of Lyme disease when the true cause of the illness is something else.
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| ===Serology=== | | ==Tables== |
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| ==== Two-step Laboratory Testing Process<ref name="urlTwo-step Laboratory Testing Process| Lyme Disease | CDC">{{cite web |url=https://www.cdc.gov/lyme/diagnosistesting/labtest/twostep/index.html |title=Two-step Laboratory Testing Process| Lyme Disease | CDC |format= |work= |accessdate=}}</ref> ====
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| *The [[serology|serological]] laboratory tests most widely available and employed are the [[Western blot]] and [[ELISA]].
| | !Diagnosis |
| *A two-tiered protocol is recommended by the [[Centers for Disease Control|CDC]]: the more sensitive ELISA is performed first, if it is positive or equivocal, the more [[Specificity (tests)|specific]] Western blot is run. The reliability of testing in diagnosis remains controversial, however studies show the Western blot [[IgM]] has a specificity of 94–96% for patients with clinical symptoms of early Lyme disease.<ref name="Engstrom">{{cite journal | author=Engstrom SM, Shoop E, Johnson RC | title=Immunoblot interpretation criteria for serodiagnosis of early Lyme disease | journal=J Clin Microbiol | year=1995 | pages=419-27 | volume=33 | issue=2 | pmid = 7714202 | url=http://jcm.asm.org/cgi/reprint/33/2/419.pdf | format=PDF}}</ref><ref name="Sivak">{{cite journal | author=Sivak SL, Aguero-Rosenfeld ME, Nowakowski J, Nadelman RB, Wormser GP | title=Accuracy of IgM immunoblotting to confirm the clinical diagnosis of early Lyme disease | journal=Arch Intern Med | year=1996 | pages=2105-9 | volume=156 | issue=18 | pmid = 8862103}}</ref>
| | !Lab findings |
| *The two steps of Lyme disease testing are designed to be done together. CDC does not recommend skipping the first test and just doing the Western blot. Doing so will increase the frequency of false positive results and may lead to misdiagnosis and improper treatment.
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| * Erroneous test results have been widely reported in both early and late stages of the disease. These errors can be caused by several factors, including [[antibody]] cross-reactions from other infections including
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| *[[Epstein-Barr virus]]<ref name="Gossens">{{cite journal | author=Goossens HA, Nohlmans MK, van den Bogaard AE | title=Epstein-Barr virus and cytomegalovirus infections cause false-positive results in IgM two-test protocol for early Lyme borreliosis | journal=Infection | year=1999 | pages=231 | volume=27 | issue=3 | pmid= 10378140}}</ref><ref name="pmid3049839">{{cite journal| author=Berardi VP, Weeks KE, Steere AC| title=Serodiagnosis of early Lyme disease: analysis of IgM and IgG antibody responses by using an antibody-capture enzyme immunoassay. | journal=J Infect Dis | year= 1988 | volume= 158 | issue= 4 | pages= 754-60 | pmid=3049839 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3049839 }} </ref>
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| *[[Cytomegalovirus]]<ref name="Gossens">{{cite journal | author=Goossens HA, Nohlmans MK, van den Bogaard AE | title=Epstein-Barr virus and cytomegalovirus infections cause false-positive results in IgM two-test protocol for early Lyme borreliosis | journal=Infection | year=1999 | pages=231 | volume=27 | issue=3 | pmid= 10378140}}</ref>
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| *[[Varicella zoster virus]]<ref name="pmid1961232">{{cite journal| author=Feder HM, Gerber MA, Luger SW, Ryan RW| title=False positive serologic tests for Lyme disease after varicella infection. | journal=N Engl J Med | year= 1991 | volume= 325 | issue= 26 | pages= 1886-7 | pmid=1961232 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1961232 }} </ref><ref name="pmid9835449">{{cite journal| author=Woelfle J, Wilske B, Haverkamp F, Bialek R| title=False-positive serological tests for Lyme disease in facial palsy and varicella zoster meningo-encephalitis. | journal=Eur J Pediatr | year= 1998 | volume= 157 | issue= 11 | pages= 953-4 | pmid=9835449 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9835449 }} </ref>
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| *[[Herpes simplex virus]] type 2<ref name="Strasfeld">{{cite journal | author=Strasfeld L, Romanzi L, Seder RH, Berardi VP | title=False-positive serological test results for Lyme disease in a patient with acute herpes simplex virus type 2 infection | journal=Clin Infect Dis | year=2005 | pages=1826-7 | volume=41 | issue=12 | pmid= 16288417}}</ref>
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| *Rickettsial infections<ref name="pmid3049839">{{cite journal| author=Berardi VP, Weeks KE, Steere AC| title=Serodiagnosis of early Lyme disease: analysis of IgM and IgG antibody responses by using an antibody-capture enzyme immunoassay. | journal=J Infect Dis | year= 1988 | volume= 158 | issue= 4 | pages= 754-60 | pmid=3049839 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3049839 }} </ref>
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| *Syphilis<ref name="pmid3049839">{{cite journal| author=Berardi VP, Weeks KE, Steere AC| title=Serodiagnosis of early Lyme disease: analysis of IgM and IgG antibody responses by using an antibody-capture enzyme immunoassay. | journal=J Infect Dis | year= 1988 | volume= 158 | issue= 4 | pages= 754-60 | pmid=3049839 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3049839 }} </ref>
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| [[image:Two tiered testing for lyme disease 600px.jpg|center|600px|thumb|The Two-tier Testing Decision Tree describes the steps required to properly test for Lyme disease. The first required test is the Enzyme Immunoassay (EIA) or Immunofluorescence Assay (IFA). If this test yields negative results, the provider should consider an alternative diagnosis. Or in cases where the patient has had symptoms for less than or equal to 30 days, the provider may treat the patient and follow up with a convalescent serum. If the first test yields positive or equivocal results, two options are available: 1) if the patient has had symptoms for less than or equal to 30 days, an IgM Western Blot is performed; 2) if the patient has had symptoms for more than 30 days, the IgG Western Blot is performed. The IgM should not be used if the patient has been ill for more than 30 days.]]
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| ====Polymerase chain reaction====
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| * [[Polymerase chain reaction]] (PCR) tests for Lyme disease have also been developed to detect the genetic material ([[DNA]]) of the Lyme disease spirochete. PCR tests are rarely susceptible to [[Type I and type II errors|false-positive]] results but can often show [[Type I and type II errors|false-negative]] results, and the overall reliability of PCR in this role remains unclear.
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| * With the exception of PCR, there is no currently practical means for detection of the presence of the organism, as serologic studies only test for [[antibodies]] of ''Borrelia''.
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| * High titers of either immunoglobulin G (IgG) or immunoglobulin M (IgM) antibodies to ''Borrelia'' antigens indicate disease, but lower titers can be misleading.
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| * The IgM antibodies may remain after the initial infection, and IgG antibodies may remain for years.<ref>{{cite journal |author=Burdash N, Fernandes J |title=Lyme borreliosis: detecting the great imitator |journal=The Journal of the American Osteopathic Association |volume=91 |issue=6 |pages=573-4, 577-8 |year=1991 |pmid=1874654 |url=http://www.jaoa.org/cgi/content/abstract/91/6/573}}</ref>
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| * Western blot, ELISA and PCR can be performed by either blood test via [[venipuncture]] or [[cerebral spinal fluid]] (CSF) via [[lumbar puncture]].
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| * 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.
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| * The diagnosis of neurologic infection by ''Borrelia'' should not be excluded solely on the basis of normal routine CSF or negative CSF antibody analyses.<ref>{{cite journal |author=Coyle PK, Schutzer SE, Deng Z, ''et al'' |title=Detection of Borrelia burgdorferi-specific antigen in antibody-negative cerebrospinal fluid in neurologic Lyme disease |journal=Neurology |volume=45 |issue=11 |pages=2010-5 |year=1995 |pmid=7501150 }}</ref>
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| * New techniques for clinical evaluation if ''Borrelia'' infection are under investigation, and includes:
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| **Lymphocyte transformation tests <ref>{{cite journal |author=Valentine-Thon E, Ilsemann K, Sandkamp M |title=A novel lymphocyte transformation test (LTT-MELISA) for Lyme borreliosis |journal=Diagn. Microbiol. Infect. Dis. |volume=57 |issue=1 |pages=27-34 |year=2007 |pmid=16876371 |doi=10.1016/j.diagmicrobio.2006.06.008}}</ref>
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| **Focus floating microscopy<ref>{{cite journal |author=Eisendle K, Grabner T, Zelger B |title=Focus floating microscopy: "gold standard" for cutaneous borreliosis? |journal=Am. J. Clin. Pathol. |volume=127 |issue=2 |pages=213-22 |year=2007 |pmid=17210530 |doi=10.1309/3369XXFPEQUNEP5C}}</ref>
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| * New research indicates [[chemokine]] [[CXCL13]] may also be a possible marker for neuroborreliosis.<ref>{{cite journal |author=Cadavid D |title=The mammalian host response to borrelia infection |journal=Wien. Klin. Wochenschr. |volume=118 |issue=21-22 |pages=653-8 |year=2006 |pmid=17160603 |doi=10.1007/s00508-006-0692-0}}</ref>
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| ===Other Types of Laboratory Testing===
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| * Some laboratories offer Lyme disease testing using assays whose accuracy and clinical usefulness have not been adequately established. These tests include:<ref name="urlLaboratory tests that are not recommended| Lyme Disease | CDC">{{cite web |url=https://www.cdc.gov/lyme/diagnosistesting/labtest/otherlab/index.html |title=Laboratory tests that are not recommended| Lyme Disease | CDC |format= |work= |accessdate=}}</ref>
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| **Capture assays for antigens in urine
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| **Culture, immunofluorescence staining, or cell sorting of cell wall-deficient or cystic forms of B. burgdorferi
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| **Lymphocyte transformation tests
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| **Quantitative CD57 lymphocyte assays
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| **“Reverse Western blots”
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| **In-house criteria for interpretation of immunoblots
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| **Measurements of antibodies in joint fluid (synovial fluid)
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| **IgM or IgG tests without a previous ELISA/EIA/IFA
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| *In general, CDC does not recommend these tests.
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| *Patients are encouraged to ask their physicians whether their testing for Lyme disease was performed using validated methods and whether results were interpreted using appropriate guidelines.
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| ===Testing Ticks===
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| * Patients who have removed a tick often wonder if they should have it tested.
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| * In general, the identification and testing of individual ticks is not useful for deciding if a person should get antibiotics following a tick bite because:<ref name="urlTick removal and testing | Lyme Disease | CDC">{{cite web |url=https://www.cdc.gov/lyme/removal/index.html |title=Tick removal and testing | Lyme Disease | CDC |format= |work= |accessdate=}}</ref>
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| **If the test shows that the tick contained disease-causing organisms, that does not necessarily mean that the patient have been infected.
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| **If the patient have been infected, symptoms will develop probably before results of the tick test are available. So, appropriate treatment should not be withhold for availability tick testing results.
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| **Negative results can lead to false assurance. For example, the patient may have been unknowingly bitten by a different tick that was infected.
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| ==References== | | ==References== |
| {{reflist|2}} | | {{reflist|2}} |
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| [[Category:Needs overview]]
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| [[Category:Bacterial diseases]]
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| [[Category:Insect-borne diseases]]
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| [[Category:Lyme disease]]
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| [[Category:Zoonoses]]
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| [[Category:Spirochaetes]]
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| [[Category:Disease]]
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| [[Category:Infectious disease]]
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| [[Category:Dermatology]]
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| [[Category:Emergency medicine]]
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| [[Category:Intensive care medicine]]
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