Discussion in 'Lyme Disease and Co-Infections' started by bakercape, Jun 2, 2010.
Where are you getting your information from??? I have never heard this before.
May I recommend Pamela Weintraub's book "Cure Unknown: Inside the Lyme Epidemic"? I gave away my copy so I don't have it in front of me, but it has a lot of information about the different tests and their interpretation. The story bears a resemblence to Hillary Johnson's "Osler's Web," and in fact, Hillary wrote the introduction to it.
I agree that it's a great book. And thankfully shorter than Osler's Web! :Retro smile:
Here is some info that might be useful...
What drives me nuts is what they make people go through when veterinary medicine has an 8 minute SNAP test for the C6 antibody.
The clinical manifestations of Lyme disease can generally be divided into three phases: early localized, early disseminated, and late disease . However, the clinical features of each stage can overlap and some patients present in a later stage of Lyme disease without a history of prior signs or symptoms suggestive of earlier Lyme disease:
Early localized disease is characterized by the appearance of the characteristic skin lesion, erythema migrans (EM), with or without constitutional symptoms. EM usually occurs within one month following the tick bite.
Early disseminated disease is characterized by multiple erythema migrans lesions (that typically occur days to weeks after infection) and/or neurologic and/or cardiac findings (that typically occur weeks to months after infection). Some of these patients have no history of antecedent early localized Lyme disease.
Late Lyme disease is typically associated with intermittent or persistent arthritis involving one or a few large joints, especially the knee (sometimes preceded by migratory arthralgias); and/or certain rare neurologic problems, primarily a subtle encephalopathy or polyneuropathy. Late Lyme disease may develop months to a few years after the initial infection. Arthritis may be the presenting manifestation of the disease.
The diagnosis of early Lyme disease can be made on clinical grounds alone in the presence of a characteristic EM lesion. It is important to recognize that the patient who presents with an EM lesion will likely be seronegative, since the lesion often appears prior to development of a diagnostic, adaptive immune response. A positive serology is not needed to make the diagnosis.
A skin lesion indistinguishable from erythema migrans occurs in Southern tick-associated rash illness (STARI), an illness principally found in the southeast and south central regions of the United States. Thus, the geographic distribution of Lyme disease and STARI generally differ (although Maryland, Delaware, and New Jersey are states in which both Lyme disease and STARI are endemic). STARI follows the bite of the Amblyomma americanum tick, not the Ixodes species tick, which is the tick that harbors B. burgdorferi. The potential diagnosis of STARI is a reason to obtain a careful travel and residence history and to determine the likelihood of tick exposure during time in endemic areas. The cause of STARI is not known.
By the time the patient has findings of early disseminated disease, (eg, multiple EM skin lesions, lymphocytic meningitis, facial palsy, radiculoneuropathy, or carditis with heart block), serologic tests are usually positive for IgM antibodies to B. burgdorferi, and for IgG antibodies as well. Patients suspected of having early neuroborreliosis or Lyme carditis should undergo a complete skin examination to search for an EM skin lesion that the patient may not have noticed. In patients with late disease (eg, Lyme arthritis) serologic tests should be positive for IgG antibodies to B. burgdorferi. In patients with either early disseminated or late disease, the diagnosis of Lyme disease is based on a compatible clinical syndrome in a patient who resides in or has visited an endemic region in conjunction with a positive serologic test.
Now that patients with EM are usually treated with antibiotic therapy, patients with neurologic, cardiac, or rheumatologic complications of Lyme disease often do not have a history of an EM skin lesion. Some of the patients with early disseminated disease have an EM lesion that can be found on a careful skin examination; others do not. The absence of either an EM skin lesion or a tick bite or both should not be interpreted as excluding the diagnosis of Lyme disease.
For clinicians practicing in nonendemic areas for Lyme disease who see patients with possible Lyme disease, it is especially important to obtain a detailed travel and activity history, with inquiries about prior residences and prior clinical findings that might be consistent with manifestations of Lyme disease. For example, an EM-like skin lesion is often misdiagnosed as either a spider bite or as community-acquired cellulitis due to pyogenic bacteria. Such patients are often treated with a first-generation cephalosporin (eg, cephalexin), which is ineffective for treating Lyme disease.
Lyme disease should not be diagnosed solely on the basis of serologic testing. Lyme disease serologic testing is inadvisable in the absence of epidemiologic evidence of exposure to B. burgdorferi and clinical findings that are compatible with a diagnosis of Lyme disease.
CDC criteria The Centers for Disease Control and Prevention (CDC) have developed a definition of Lyme disease. This definition was not intended to be used by clinicians to make a diagnosis of Lyme disease, since it is not comprehensive. However, the vast majority of cases of Lyme disease in practice do fulfill the case definition.
Distinction from fibromyalgia Many patients with nonspecific articular or neurologic symptoms are incorrectly diagnosed with "chronic Lyme disease." In patients with noninflammatory musculoskeletal pain, cognitive complaints, fatigue, and/or irritability, the diagnosis is more likely fibromyalgia. Fibromyalgia is a common chronic disorder that is characterized by pain in muscles and associated fibrous tissue and occurs in 2 percent of the general population . Physical examination reveals multiple "trigger points" near joints. However, in contrast to Lyme disease, fibromyalgia is not an inflammatory or infectious disorder. Thus, an important distinction between these two clinical entities is the presence of objective evidence of inflammation or organ system dysfunction in patients with late features of B. burgdorferi infection.
Post-Lyme disease syndrome In untreated patients, objective manifestations of late Lyme disease, such as monoarticular or oligoarticular arthritis, may persist for several years. However, there is no evidence that persistent subjective symptoms after antibiotic treatment, so called post-Lyme disease syndrome or chronic Lyme disease, is due to active infection . Lyme disease should never be a diagnosis of exclusion to explain puzzling complaints, particularly when they are not accompanied by objective markers of organ damage and/or inflammation.
SEROLOGIC TESTS The American College of Physicians has published a position paper on laboratory evaluation in the diagnosis of Lyme disease. The Infectious Diseases Society of America (IDSA) has issued guidelines for the clinical assessment and treatment of patients suspected of having Lyme disease. The conclusions of these reports are that the clinician should not test or treat the patient in whom the clinical assessment does not suggest a high degree of probability that the individual has Lyme disease. A report from the Food and Drug Administration (FDA) also underscores the fact that positive serologic testing does not constitute proof of a diagnosis of Lyme disease.
Recommended approach The diagnosis of Lyme disease should be considered on the basis of historical and physical features that suggest the diagnosis. Serologic studies should be used to support the diagnosis in patients without EM. Serologic testing should not be used as tools to screen populations without evidence of clinical disease for possible exposure to Lyme disease.
For serologic testing, a two tier conditional strategy is recommended to support the diagnosis of Lyme disease. This approach uses a sensitive enzyme-linked immunosorbent assay (ELISA) followed by a Western blot. An immunofluorescent assay (IFA) may be substituted for the ELISA. If the ELISA is positive or equivocal, then the same serum sample should be tested by Western blot (IgM and IgG immunoblots if early disease is suspected; IgG Western blot alone if late disease is suspected.) If the ELISA is negative, the sample needs no further testing. The recommended criteria for interpretation of Western blots are shown in the Table.
The CDC and the FDA have cautioned clinicians that some commercial laboratories are performing assays for Lyme disease whose accuracy and clinical usefulness have not been adequately established. These tests include urine antigen tests, immunofluorescent staining for cell wall-deficient forms of B. burgdorferi, lymphocyte transformation tests, and polymerase chain reaction (PCR) on inappropriate specimens such as blood and urine.
Enzyme linked immunosorbent assay An ELISA is the most common initial serologic test used to support the diagnosis of Lyme disease. The antigen is usually derived from the whole organism.
False positives with ELISA The ELISA is associated with a high rate of false positive results. Thus, all sera that are positive or equivocal should be then tested by Western blot. To optimize specificity and to be considered seropositive, both the ELISA and the Western blot must meet criteria for a positive response.
Conditional two tier testing can usually differentiate Lyme disease from other infections or conditions that may produce cross-reacting antibodies. These include patients with other Borrelial diseases (eg, relapsing fever), other spirochetal diseases (eg, syphilis, leptospirosis, pinta, yaws, gingivitis), other bacterial infections such as infective endocarditis, viral illnesses, and autoimmune diseases (eg, systemic lupus erythematosus, or rheumatoid arthritis). In addition, cross-reacting antibodies may be produced due to nonspecific activation of immunoglobulin production (eg, polyclonal B cell activation). Epstein Barr virus and malaria can cause such activation, resulting in a positive ELISA for Lyme disease. At least 5 percent of the normal population will test positive for antibodies to B. burgdorferi by ELISA due to cross-reacting antibodies elicited either by other infections or by the immune response to normal flora. Vaccination with the previously licensed Lyme disease vaccine regularly caused a positive result on whole cell-based ELISAs.
Western blot The Western blot (or immunoblot) allows detection of antibodies to individual components of the organism and thus provides more information regarding which antigens of B. burgdorferi are reacting with serum antibodies than does a whole cell-based ELISA. Information learned from studies correlating cases of clinically diagnosed Lyme disease with patterns of reactivity on Western blot have enabled the CDC to recommend evidence-based criteria for Western blot interpretation. These criteria should be used in interpreting Western blot results. Results from laboratories that have established their own criteria should be viewed with skepticism.
The intralaboratory reliability of the Western blot in confirming a diagnosis of Lyme disease is illustrated by a study of 31 persons (21 patients with acute Lyme disease who had residual symptoms lasting for more than six months and 10 healthy controls). Serum samples were taken from each patient and divided into two aliquots; one used for immediate testing and the other stored frozen and tested within six months. There was 100 percent concordance for both positive and negative tests.
Although the Western blot is more difficult to interpret in patients vaccinated for Lyme disease, it can still be informative.
Lack of sensitivity in early disease In Lyme disease, IgM antibodies to B. burgdorferi typically appear within one to two weeks and IgG antibodies usually appear within two to six weeks following the onset of EM. Both IgM and IgG antibodies may remain elevated despite successful antibiotic therapy and complete resolution of symptoms.
Approximately 20 to 40 percent of patients with early localized Lyme disease (erythema migrans) are seropositive at the time of presentation using the two tier serological method. Thus, patients with skin lesions that are typical of EM do not require confirmatory serologic testing. The presence of EM is in itself sufficient to make a diagnosis of Lyme disease. If the cause of the skin lesion is in doubt, acute and convalescent phase (approximately two to four weeks after the acute serum sample) serologic testing may be helpful.
In comparison to the findings in early localized disease, most patients with early disseminated extracutaneous Lyme disease (eg, early neuroborreliosis or Lyme carditis) are seropositive. Those with suspected early disseminated Lyme disease who are initially seronegative should undergo repeat serologic testing approximately two weeks after the initial evaluation. Patients with late Lyme disease (eg, Lyme arthritis) are almost invariably IgG seropositive.
Effects of antibiotic therapy Administration of antibiotics in early Lyme disease may prevent seroconversion. In that case, however, the illness has been treated successfully, and symptoms resolve.
Interlaboratory variation Testing performed in different laboratories may show some variability. Most of the well-known commercial laboratories provide reliable testing, as do laboratories associated with academic medical centers doing research on Lyme disease.
Vaccine recipients Although the Lyme vaccine (LYMErix) is no longer available, the need may arise for serologic testing in previously vaccinated individuals. Immunization with LYMErix induces antibodies that can interfere with the serologic diagnosis of Lyme disease by causing a positive ELISA. Patients who have been vaccinated for Lyme disease also may display several positive bands on Western blot testing; usually this does not result in interpretation of the Western blot as a false positive, although it can in some cases. The duration of vaccine-induced interference with diagnostic testing by ELISA is not clear, but it may be at least several years.
Usefulness of serologic tests Seropositivity by two tier testing indicates the presence of antibodies to the spirochete that causes Lyme disease. Seropositivity alone, however, is insufficient to make a diagnosis of active Lyme disease. Antibodies may persist for years after Lyme disease has been treated and cured. The diagnosis of extracutaneous Lyme disease, as noted above, depends upon having the appropriate clinical features in conjunction with seropositivity. Serologic tests have great value when used in the right settings:
If serologic testing is used in a population where Lyme disease is very likely, (ie, patients with isolated monoarthritis or bilateral facial nerve palsy), a positive test strongly supports the clinical diagnosis of Lyme disease.
In late Lyme disease, such as late neuroborreliosis or Lyme arthritis, seropositivity by two tier testing with a positive IgG Western blot, specifically, is virtually universal. Absence of IgG seroreactivity in such a patient should raise significant doubts about the diagnosis of Lyme disease.
Positive Lyme disease serology does not prove that the patient's current clinical findings are due to infection with B. burgdorferi. For example, if a patient with a prior history of EM and persistent antibodies to B. burgdorferi after adequate therapy for acute Lyme disease develops acute arthritis associated with urate crystals in the joint fluid, the diagnosis is gout, not Lyme disease.
Follow-up testing Antibody titers to B. burgdorferi decline gradually after successful antibiotic treatment of Lyme disease. However, positive responses often persist for years, albeit at lower titers, after successful treatment. In one study of 40 patients who had early Lyme disease 10 to 20 years earlier, 10 percent still had IgM responses to B. burgdorferi and 25 percent still had IgG reactivity by ELISA and Western blot. Among 39 patients who had had Lyme arthritis 10 to 20 years earlier, 15 percent still had IgM responses and 62 percent still had IgG responses by two-tier testing. Thus, routine follow-up serologic testing is not recommended in assessing the patient who is cured or slowly improving.
VlsE antibody testing The VlsE C6 peptide ELISA is a one step test that measures IgG; the notation stands for variable major protein-like sequence-expressed (VlsE) sixth invariant region (C6). It appears to have sensitivity and specificity comparable to the two tier testing. In a prospective study of 134 patients at various stages of Lyme disease, 89 patients with other illnesses, and 136 healthy controls, both assays were negative in over 80 percent of patients with erythema migrans without evidence of disseminated disease, and both assays had 100 percent sensitivity in patients with neurologic, cardiac, or joint manifestations of Lyme disease. Specificity was 96 and 99 percent, respectively.
Another study assessed the sensitivity of a commercial VlsE C6 peptide ELISA in patients with erythema migrans, the initial skin lesion of Lyme disease. The results were stratified based upon which of the three B. burgdorferi subtypes (defined by ribosomal spacer typing) caused infection. The VlsE C6 peptide ELISA had comparable sensitivity to two tier serological testing in patients with B. burgdorferi subtype ribosomal spacer type (RST) 1 infections, and higher sensitivity in patients with either RST 2 or 3 infections.
The benefits of the VlsE C6 peptide ELISA compared with two tier testing are the relative ease of testing and result interpretation, the earlier development of the IgG response, and the ability to standardize results between laboratories. The major advantages of sonicate Western blot are its slightly greater specificity compared with the VlsE C6 peptide ELISA, and the fact that the degree of expansion of the antibody response gives information about the duration of infection. Thus, a two-tiered approach that includes Western blotting is still recommended because of its greater specificity.
Combination assays Two tiered immunoglobulin G (IgG) testing is useful for the diagnosis of late Lyme disease, although IgM testing early in the course of illness may be difficult to interpret. The two tier approach combined with VlsE testing appears to perform as well as standard testing, without the drawbacks of IgM Western blotting.
In a study evaluating this approach, serum from patients with Lyme disease and controls were tested using standard two tier IgM and IgG testing (whole-cell ELISAs), followed by IgM and IgG blots with recombinant VlsE added to the IgG blots. Results were comparable; the new IgG assay (with VlsE band) had comparable sensitivity and high specificity, eliminating the need for IgM testing. However, this algorithm has not been adopted yet by CDC, and such testing is not yet generally available.
Population screening Serologic tests for Lyme disease should not be used to screen populations of asymptomatic patients. Most positive tests will be false-positives and those few individuals with a true positive test may have had a prior infection that resolved spontaneously. About 10 percent of B. burgdorferi infections in the United States are subclinical or asymptomatic. Further study of such patients, however, is warranted.
I've read the study before publication. We got it when discussing specificity and sensitivity for another project.
I'mgoing to try to see him.
mine was diagnosed by live blood microscopy
Thanks for the info JT, I tried to PM you but your mailbox is full. FYI
I thought that sometimes only a SPECT and/or spinal fluid check was required to obtain a true dx of lyme.
An abnormal spect scan can show that something is wrong. It cannot tell you what caused the problem. I did show moderate, global hypoperfusion on my spect scan. It is likely that the cause of that was infectious in nature. You cannot say what infection caused it, just by looking at the scan. Lab work can give a clue though.
Does anyone know anything about the Elispot test for Lyme disease?
Does anyone have any experience with the Centrum Borreliose Augsburg in Germany (treatment and diagnostic centre for Lyme disease)?
You can also try a Google Site Search
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