I never considered how much living in a Lyme endemic area would influence my training as an infectious diseases fellow; in fact, I didn’t really think much about Lyme disease at all until I began getting phone call after phone call from parents and pediatricians confused about the diagnosis and treatment of Lyme disease.
The stories often start off the same: a child with non-specific constitutional symptoms, perhaps some fevers, a vague history of a rash, sometimes headaches or diffuse joint pain who just doesn’t seem like he’s getting better. Perhaps there was even an antecedent tick bite, or at the very least, a camping trip or another kid at school with Lyme disease. So, Lyme serologies are sent and whether they are positive or negative, the caller – parent or physician – is uncertain how to proceed.
The Virginia state legislature has encapsulated this uncertainty and will likely add to the confusion by enacting the “Lyme Disease Testing Information Disclosure Act,” which will go into effect July 1 of this year. It states that health care providers must provide all patients with the following disclosure when ordering Lyme disease testing:
“According to the Centers for Disease Control and Prevention, as of 2011 Lyme disease is the sixth fastest growing disease in the United States.Your health care provider has ordered a laboratory test for the presence of Lyme disease for you. Current laboratory testing for Lyme disease can be problematic and standard laboratory tests often result in false negative and false positive results, and if done too early, you may not have produced enough antibodies to be considered positive because your immune response requires time to develop antibodies.”
“If you are tested for Lyme disease, and the results are negative, this does not necessarily mean you do not have Lyme disease. If you continue to experience symptoms, you should contact your health care provider and inquire about the appropriateness of retesting or additional treatment.”
On the surface, the statement is true, and it arguably offers good advice to patients and physicians alike.
The laboratory test they are likely referring to is serologic testing in which total serum IgG and IgM antibodies are quantified via enzyme immunoassay (EIA) or immunofluorescent antibody assay (IFA). If this screening test is positive, a confirmatory western blot for specific Borrelia burgdorferi antibodies is performed. A positive IgM test requires two out of three bands positive and a positive IgG test requires five out of ten bands positive; these positive bands reflect specific B. burgdorferi antibodies. Because IgM testing is notoriously non-specific, isolated IgM positivity likely represents a false positive. Anything short of these cutoffs represents a negative test.
It is absolutely true that if this serologic testing is done early in the course of illness (i.e. within 4 weeks of being bitten by an infected tick) it is not sufficiently sensitive to diagnose disease and therefore not recommended. If testing is inappropriately sent at this stage, and is negative, patients should still be treated based on clinical suspicion. These recommendations reflect the Infectious Diseases Society of America (IDSA) guidelines on diagnosis and treatment of Lyme disease.
The trouble is that this is not how this statement will be interpreted by those who choose not to follow these evidence-based guidelines. Namely, I suspect it will fuel an increasingly vocal “Lyme literate” community of physicians and patients who attribute all sorts of ailments from forgetfulness to chronic pain to fatigue to chronic Lyme disease and treat these symptoms with prolonged, often intravenous, courses of antibiotics despite there being no scientific evidence that these symptoms are actually caused by B. bordorferii. It is already being seen by some as legislative support for increasingly inclusive criteria for diagnosis of Lyme disease and will inevitably encourage patients – appropriately or inappropriately – to pursue this diagnosis.
This group aside, I know there many physicians who believe in evidence-based guidelines for Lyme disease who are unfamiliar, or perhaps misinformed, with the recommended diagnostic approach. These are the people I speak to on the phone and to them I offer this advice: Lyme disease causes several characteristic clinical syndromes, which occur at somewhat predictable intervals following infection. First, after 3-30 days, patients develop early localized disease, characterized by erythema migrans rash.
Diagnosis at this time is purely clinical and no serologic testing is recommended.
Over the course of weeks, B. burgdorferi disseminates to distant sites and can cause multiple erythema migrans, aseptic meningitis, cranial nerve palsies (most commonly involving cranial nerve VII), or carditis, collectively referred to as early disseminated disease. These may be accompanied by non-specific constitutional symptoms, including low-grade fever, fatigue, and myalgias. Finally, late disseminated disease occurs months to years after infection and is characterized by arthritis, generally involving a single joint, and causing significant swelling but little disability.
By the time a patient develops disseminated disease, serologies will be positive if the symptoms are due to Lyme disease and will remain positive for a lifetime. If a patient doesn’t have one of these clinical syndromes, don’t send Lyme testing.
In the end, what bothers me most about this bill is what it says about the medical community’s recent approach to managing Lyme disease. Whereas the bill suggests that there is a problem with Lyme disease testing, the real problem lies with the people ordering the tests.