Synonym
Tubes
Blood
- Red, tiger top, or gel separator tube
- 5-7 mL of venous blood
CSF/Spinal Fluid
- Spinal fluid collection tube
- 0.5-1 mL of CSF
Additional information
- Paired sample testing of acute and convalescent phases is preferred
- Fasting 12 hrs prior to test, but can take fluids
- Handle specimen gently to prevent hemolysis
- Reject lipemic or hemolyzed sample
- Send sample to lab immediately
Info
- Lyme antibody testing is a qualitative and quantitative analysis of antibodies to B. burgdorferi, the organism responsible for Lyme disease
- Lyme disease (LD) is a multisystem inflammatory bacterial disorder caused by a spirochete, Borrelia burgdorferi, which is transmitted by the bite of an infected tick (Ixodes species/deer tick)
- The definitive host of this spirochete is deer and mice
- Serologic tests to detect antibodies to Lyme disease include:
- Indirect immunofluorescent test (IFA)
- Enzyme linked immunoassay (ELISA)
- C6 Lyme Peptide ELISA
- Western blot analysis
- PreVue B. burgdorferi Antibody Detection Assay
Clinical
- Lyme disease antibody test is indicated in the following conditions:
- To confirm the diagnosis of Lyme disease in persons presenting with classic symptoms and signs
- In persons suspected to have Lyme disease or nonspecific symptoms who reside in an endemic area
- To monitor therapeutic progress in Lyme disease (C6 Lyme Peptide ELISA)
- To distinguish Lyme disease from other spirochete and tick borne diseases such as:
- Babesiosis
- Colorado tick fever
- Ehrlichiosis
- Relapsing fever
- Rocky Mountain spotted fever
- Tick paralysis
- Tularemia
- Guidelines by AmericanCollege of Physicians for laboratory testing of Lyme disease:
- Rash resembling erythema migrans or arthritis, history of rash resembling erythema migrans and a previous tick bite
- Objective clinical signs and pretest probability of 0.20-0.80 (determination of the pretest probability of Lyme disease is based on the clinical examination and incidence of Lyme disease in the population)
- Follow two-test protocol:
- ELISA or IFA, followed by Western blotting of all specimens found to be indeterminate
- Positive test is an indication for therapy
- Negative test decreases probability of Lyme disease
- Antibiotics and testing is not recommended in persons with myalgia and low pretest probability of Lyme disease
- The CDC recommends testing to be a screening test using the ELISA polyvalent test; if positive or equivocal, then confirmation should be made with Western blot
- Once infected by B. burgdorferi the patient may remain asymptomatic, but will be seropositive. The disease may spread throughout the body and produce symptoms by direct invasion, particularly in the early stages of the disease, or may induce an immune response that may lead to symptoms in various organs, with little evidence of direct spirochete infection
- The clinical spectrum of Lyme disease includes three stages:
- Early or localized
- Early disseminated
- Late, persistent, or chronic Lyme disease
- Early or first stage may clinically present as:
- Localized erythema migrans (EM) at the tick bite site
- Occurs in 80-90% of all LD cases
- Usually appears 3-30 days after disease transmission and persists for 3-5 weeks
- Appears either as a solid red expanding rash with an area of central clearing; this gives the typical "bull's eye appearance" to these lesions
- In dark skinned persons, it may appear as a dark bruise
- Has an average diameter of 5 to 6 inches
- Usually not painful or itchy
- Mild constitutional symptoms in 75% of persons with EM
- Arthralgias
- Chills and fever
- Headache
- Malaise
- Neck stiffness
- Other skin lesions
- Early disseminated disease occurs weeks to months after the bite by an infected tick and is clinically seen as:
- Cardiac involvement (15%)
- Congestive heart failure
- Fever
- Myocarditis
- Pericarditis
- Syncope due to atrioventricular block
- Intermittent inflammatory arthritis
- Usually begins as migratory polyarticular process, which evolves over 1-2 days into a monoarticular process involving the knee, ankle, and wrist
- Occurs within 6 months of EM lesion and resolves within a week
- Two-thirds of patients have 3 recurrences approximately 2-3 months apart
- Neurologic (8%)
- Bell's palsy or other cranial nerve neuropathy
- Lymphocytic meningitis or encephalitis
- Meningoradiculoneuritis (Bannwarth syndrome)
- Pseudotumor cerebri
- Miscellaneous
- Conjunctivitis
- Hepatitis
- Iritis
- Lymphadenitis (Regional or generalized)
- Microscopic hematuria
- Proteinuria
- Late Lyme disease can occur weeks, months, or years after infection, and may clinically present as:
- Large joint arthritis
- Occurs in 10% of untreated Lyme disease typically involving the knee
- Monoarticular or asymmetric oligoarticular arthritis
- Neurologic
- Axonal polyneuropathy
- Leukoencephalopathy
- Psychiatric disorders
- Subacute encephalopathy
- Fibromyalgia and chronic fatigue syndrome may co-exist
- Serologic evaluation of Lyme disease:
- IgM antibodies to B. burgdorferi are detectable 3-4 wks after the onset of Lyme disease, peak at 6-8 wks and gradually decline
- IgG antibodies to B. burgdorferi are detectable at 2-3 months and may remain elevated for years
- The presence of IgM antibodies is indicative of acute infection and the presence of IgG antibodies is indicative of current or past infection
- Indirect immunofluorescent assay (IFA): This method is time consuming, requires fluorescence microscopy, and specially trained personnel. This assay has now largely been replaced by the ELISA as a screening test, both due to the difficulty of performing the IFA test and that is has a lower sensitivity than the ELISA test
- Enzyme linked immunoassay (ELISA):
- This assay is the first line screening test for Lyme disease
- The diagnostic sensitivity and specificity of ELISA in early stage of the disease is 59% and 93% respectively, whereas in the late stage of the disease, it is 95% and 81% respectively
- C6 Lyme Peptide ELISA
- This is a peptide-based immunoassay that identifies antibodies to a consistent surface protein present on every known strain of B. burgdorferi
- This is more sensitive for diagnosing all stages of Lyme disease, including those patients with late stage Lyme disease
- This test may also be utilized to assess effect and outcome of therapy as a 4 fold decline in C6 titers is expected by 6 months
- Western blot
- This is the confirmatory test utilized when an IFA or ELISA test returns positive or equivocal
- The diagnostic sensitivity and specificity of Western blot in both early and late stage of the disease is 55-75% and 99-100% respectively.
- The CDC recommends Western blot testing for both IgM and IgG antibodies on samples less than four weeks after appearance of erythema migrans, and only IgG antibody on samples greater than four weeks after the disease onset.
- PreVue B. (Borrelia) burgdorferi Antibody Detection Assay
- A single-use, rapid membrane assay for the qualitative presumptive (first step) detection of IgG and IgM antibodies to Borrelia burgdorferi in human serum or whole blood
- Results can be obtained in 20 minutes
- Uses antigenic proteins developed by recombinant DNA techniques rather than the whole-cell B burgdorferi preparations used in the laboratory tests
- The CDC recommends it as an acceptable first step in testing of a patient suspected to have Lyme disease
Additional information
- LD occurs worldwide but is most prevalent in certain geographic locations in the United States, including the Northeast, upper Midwest, and along the Pacific coast in the US
- Lyme borreliosis is the most common vector-borne disease in the U.S.with >285,000 cases reported to the CDC between 1980-2007
- Transmission of Lyme disease peaks during the spring, summer, and early fall months
- Persons infected with Lyme disease do not develop resistance and may continue to be at high risk, especially if they live, work, or recreate in areas where Lyme disease is prevalent
- CDC criteria for the laboratory diagnosis of Lyme disease include the following:
- Isolation of B. burgdorferi from a clinical specimen
- IgM and IgG antibodies in blood or CSF
- Paired acute and convalescent blood samples showing significant antibody response to B. burgdorferi
- Problems associated with serologic testing for Lyme disease
- Assay insensitivity and nonspecificity
- Interlaboratory variability
- Asymptomatic seroconversion
- Related laboratory tests include:
- Antinuclear antibody
- Complete blood count
- Culture for B. burgdorferi
- Direct visualization or staining
- Erythrocyte sedimentation rate
- Rheumatoid factor
- Synovial fluid analysis
- T-cell proliferation assay
- Testing for other tick borne diseases
Nl Result
A negative result on all studies is considered normal. False positives can occur as can false negatives. The clinical scenario must be matched with the laboratory results.
| Method | Normal Result |
|---|
| ELISA for IgG / IgM | Negative |
| Western blot IgG / IgM | Negative |
| Indirect immunofluorescence | Negative |
| ELISA for C6 Peptide Antibody | Negative |
High Result
Conditions associated with positive or high result includes:
- Lyme disease
- Asymptomatic individuals living in endemic areas
- Immunization with recombinant OspA Lyme disease vaccine
Conditions associated with false positive test results include:
- Cross-reactivity with other spirochete infections, such as Rickettsia or Treponema
- Epstein-Barr virus infection
- HIV
- Laboratory error
- Rheumatoid factor (RF)
- Subacute bacterial endocarditis
- Systemic lupus erythematosus (SLE)
- Tick-borne relapsing fever (Borrelia hermsii)
Low Result
A negative result must be considered in the context of the clinical scenario. In patients where clinical suspicion is high; additional testing is often indicated. There may be a delay between onset of symptoms and development of antibody. A false negative rate is present on any laboratory test.
Conditions associated with false negative test results include:
- Aborted antibody response due to early antibiotic treatment
- Antibody sequestration in immune complexes
- Delayed immune response with late seroconversion
- High cutoff for positive result in some laboratories
- Laboratory error
- Pregnancy
- Samples contaminated bacterial contamination
- Serological tests performed in the early phase of disease (first 5 weeks)
- Genetic heterogeneity (300 strains in U.S.)
- Spirochete may be in the dormant phase
- Immunosuppression as with concomitant infection with babesia
References
- Aguero-Rosenfeld ME et al. Diagnosis of lyme borreliosis. Clin Microbiol Rev. 2005;18(3):484-509.
- ARUP's Laboratories®. Borrelia burgdorferi Antibodies, Total by ELISA. [Homepage on the Internet] ©2007. Last accessed on February 16, 2007. Available at URL: http://www.aruplab.com/guides/ug/tests/0050216.jsp
- ARUP's Laboratories®. Borrelia burgdorferi C6 Peptide Antibodies, Total by ELISA. [Homepage on the Internet] ©2007. Last accessed on February 16, 2007. Available at URL: http://www.aruplab.com/guides/ug/tests/0051044.jsp
- ARUP's Laboratories®. Borrelia burgdorferi Antibodies, IgG & IgM by Western Blot. [Homepage on the Internet] ©2007. Last accessed on February 16, 2007. Available at URL: http://www.aruplab.com/guides/ug/tests/0050254.jsp
- Bratton,R.L., Corey,R. Tick-borne disease. Am Fam Physician. 2005;71(12):2323-2330. Available at URL: http://www.aafp.org/afp/20050615/2323.html
- Buckingham,S.C. Tick-borne infections in children: epidemiology, clinical manifestations, and optimal management strategies. Paediatr Drugs. 2005;7(3):163-176.
- Centers for Disease Control: Lyme Disease --- United States, 2001--2002. MMWR. May 7, 2004 / 53(17);365-369. [Homepage on the Internet]. Last reviewed on May 6, 2004. Last accessed on February 16, 2007. Available at URL: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5317a4.htm
- DePietropaolo,D.L., Powers,J.H., Gill,J.M., Foy,A.J. Diagnosis of lyme disease. Am Fam Physician. 2005;72(2):297-304. Available at URL: http://www.aafp.org/afp/20050715/297.html
- eMedicine from WebMD®. Lyme Disease. [Homepage on the Internet] ©1996-2006. Last updated on January 4,2007. Last accessed on February 16, 2007. Available at URL: http://www.emedicine.com/med/topic1346.htm
- Halperin JJ. Diagnosis and treatment of the neuromuscular manifestations of lyme disease. Curr Treat Options Neurol. 2007 Mar;9(2):93-100.
- Kaplan M. Reasons for False Negative Lyme Disease Blood Test Results [Homepage on the Internet] Last updated on March 23, 2004. Last accessed on February 26, 2007. Available at URL: http://www.anapsid.org/lyme/lymeseroneg.html
- LabTestsOnline®. Lyme Disease. [Homepage on the Internet] ©2001-2007. Last reviewed on June 29, 2006. Last accessed on February 16, 2007. Available at URL: http://www.labtestsonline.org/understanding/analytes/lyme/glance.html
- New Test for Lyme Disease Cleared. Medscape Today. Current Healthcare Events. [Homepage on the Internet] ©1994-2007. Last updated in April 1999. Last accessed on February 26, 2007. Available at URL: http://www.medscape.com/viewarticle/416859