Problems of Proving a Lyme Disease Diagnosis

Lyme disease is the most commonly reported vector-borne illness in the United States. A new CDC report found that the number of counties in the northeastern states identified as having a high incidence of Lyme disease increased by over 320% between 1993 and 2012.

Proving a person has Lyme disease is not as straightforward as proving a person has any other infectious disease. Some infectious diseases have unique signs and symptoms. For the many infectious diseases with similar signs and symptoms, tests of bodily fluids may indicate the presence of the particular microbe that is causing a person’s illness. Two aspects of Lyme disease make proving an infection especially challenging. First, the signs and symptoms of Lyme disease, particularly if it goes undiagnosed within the first month, are similar to a wide range of infectious diseases and disorders. Second, the tests for Lyme disease have a high risk of false positives.

According to the CDC, Lyme disease is diagnosed by signs and symptoms and a history of possible exposure to infected blacklegged ticks. Between three and 30 days after being bitten by a tick, most people with Lyme disease will have a red, expanding rash that looks like a bull’s-eye called erythema migrans (EM), in addition to general symptoms of fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. However, some people experience the general symptoms without an EM rash. Over a month after being bitten by a tick, the telltale EM rash fades, leaving only the general symptoms. The general symptoms of Lyme disease resemble a number of other diseases and disorders. The CDC only recommends laboratory blood tests for Lyme disease for patients who do have symptoms typical of Lyme disease.

The CDC currently recommends a two-step process when testing blood for evidence of antibodies against the Lyme disease bacteria. The first step uses a testing procedure called “EIA” (enzyme immunoassay) or rarely, an “IFA” (indirect immunofluorescence assay). If this first step is negative, the CDC recommends no further testing of the specimen. If the first step is positive or indeterminate (sometimes called “equivocal”), then the CDC recommends that the second step should be performed. The second step uses a test called an immunoblot test, commonly, a “Western blot” test. Results are considered positive only if the EIA/IFA and the immunoblot are both positive.

The CDC does not recommend skipping the first test and just doing the Western blot because doing so increases the frequency of false positive results and may lead to misdiagnosis and improper treatment. The Western blot test is also subject to error because it requires human interpretation of bands. The test produces something that looks like a bar code used on grocery items, with several lines known as bands. Each band represents antibodies to a different component of the bacteria. As with bar codes, the presence of any one or two lines is not particularly meaningful. Instead, it is the combination of multiple, specific lines that identifies the infection as being due to Borrelia burgdorferi. For a Western blot test to be interpreted as positive, the CDC requires at least five IgG bands to be positive, which reflects the fact that people with Lyme disease have at least five antigens (specific molecules) detectable. The CDC explained that it is not correct to interpret a test result that has only some bands that are positive as being “mildly” or “somewhat” positive for Lyme disease.

Failure to respond to antibiotic treatment does not exclude Lyme disease. Approximately 10% to 20% of patients with Lyme disease have symptoms that last months to years after treatment with antibiotics. These symptoms can include muscle and joint pains, cognitive difficulties, sleep disturbances, or fatigue – many of the symptoms of Lyme disease. The cause of these symptoms is not known, and, according to current research, these symptoms are not due to ongoing infection with B. burgdorferi. This condition is referred to as Post-treatment Lyme disease syndrome (PTLDS). There is some evidence that PTLDS is caused by an autoimmune response, in which a person’s immune system continues to respond, doing damage to the body’s tissues, even after the infection has been cleared. Studies have shown that continuing antibiotic therapy is not helpful and can be harmful for persons with PTLDS.

A recent case, involving an insurer’s denial of long-term disability benefits for a plan participant who had a marginal diagnosis of Lyme disease, illustrates the problems of proof described above. In Dutkewych v. Standard Ins. Co., 2015 WL 1412590 (C.A.1 (Mass.), March 30, 2015) (not designated for publication), a man began to experience symptoms including severe fatigue, intense back pain, and stomach irritation. His symptoms worsened as he developed a painful rash, began bruising and bleeding, suffered severe joint pain, and experienced cognitive issues, including trouble with reading comprehension, concentration, short term memory, directions, organization, and sense of time.

His primary care physician could not determine the cause of the man’s symptoms and referred him to a hematologist-oncologist, who considered the possibility of Lyme disease. The man reported no recent viral exposure or tick exposure that he was aware of. Five months after the onset of symptoms, a blood test returned negative results for Lyme disease. The test results warned that false negatives are possible in the early stages of the disease before the patient produces detectable levels of antibodies. However, in the progression of Lyme disease, five months after onset of symptoms is not considered the early stages of the disease. At that point, Lyme disease is in the late disseminated stage.

Three months later the man had an appointment with a family practitioner. The man reported experiencing no tick bites, but noted that ticks had been seen in his house. The family practitioner ordered additional tests for Lyme disease. In its review of the facts, the First Circuit did not state whether the testing protocol followed the CDC’s two-step process, and if so, whether the tests conducted in the first step were positive. The court did note that the Western blot test returned positive results for Lyme disease under the IGeneX IGG criteria (which requires only two bands to be present), but negative results under CDC/NYS and Babesia FISH criteria (which require five bands to be present).

Fifteen months after the onset of symptoms, a primary care physician, conducted a spinal tap. She found elevated levels of proteins, which she interpreted as evidence of Lyme disease. Based on this diagnosis, the man began intravenous (“IV”) antibiotic treatment for Lyme disease. A recent medical journal article indicated that in patients whose untreated Lyme disease affects their central nervous system, spinal fluid often contains evidence of the production of anti-B. burgdorferi antibodies. See: Halperin JJ. Nervous system Lyme disease. Infect Dis Clin North Am. 2015 Jun;29(2):241-53. PMID: 25999221. However, to diagnose Lyme disease the spinal fluid has to be tested for anti-B. burgdorferi antibodies, not just elevated protein levels. See: Henningsson AJ, Christiansson M, Tjernberg I, et al. Laboratory diagnosis of Lyme neuroborreliosis: a comparison of three CSF anti-Borrelia antibody assays. Eur J Clin Microbiol Infect Dis. 2014 May;33(5):797-803. PMID: 24263552.

Twenty months after the onset of symptoms and five months after starting IV antibiotics, a psychiatrist conducted a SPECT scan, a nuclear medicine tomographic imaging technique using gamma rays, and a clinical evaluation of the man. The psychiatrist diagnosed the man with Lyme disease. A medical journal article has suggested the use of SPECT scans to provide objective evidence in support of the clinical diagnosis of Lyme disease. See: Donta ST, Noto RB, Vento JA. SPECT brain imaging in chronic Lyme disease. Clin Nucl Med. 2012 Sep;37(9):e219-22. PMID: 22889796.

Eight months after starting IV antibiotic treatment, the man reported improved symptoms and he stopped the treatment. After a month, his symptoms reappeared and he went back on the IV antibiotics. Two months later, his port became infected so he had to stop the IV antibiotic treatment.

Thirty-two months after the onset of symptoms, a neurologist ordered an additional Western blot test. The results were the same as those of the test conducted two years earlier: the Western blot test returned positive results for Lyme disease under the IGeneX IGG criteria (which requires only two bands to be present), but negative results under CDC/NYS and Babesia FISH criteria (which require five bands to be present). Two months later, a new port was installed and the man restarted his IV antibiotic treatment.

In its review of the man’s long-term disability benefits claim, the insurer used an independent physician consultant board-certified in internal medicine and rheumatology to review the man’s medical records. The consultant was a leading figure in both the treatment and research of chronic Lyme disease. The consultant found that man’s Lyme disease diagnosis was speculative. He discounted the positive results of the Western blot test under the IGeneX IGG criteria because of the likelihood of a false-positive result under its less stringent standard. He disagreed with the primary care physician’s conclusion that elevated levels of proteins in the man’s spinal fluid were evidence of Lyme disease. He noted that the spinal fluid had normal glucose, a trivially elevated protein, and no inflammatory white or red blood cells counted. He concluded that it was essentially normal.

In addition to the lack of explicit clinical and laboratory evidence, the consultant noted that the man did not respond to month after month of multiple antibiotic therapies. In addition to the possibility that the man suffered from PTLDS, the expert’s reliance on the lack of response to antibiotics does not take into account the lack of evidence regarding the type and duration of antibiotic treatment for Lyme disease. As one medical journal article explained, “[O]ften cited recommendations about the duration of treatment, e.g., four weeks is adequate treatment, have no factual basis to support that recommendation, often leading to the conclusion that there is another, perhaps psychosomatic reason, for the continuing symptoms.” See: Donta ST. Issues in the diagnosis and treatment of Lyme disease. Open Neurol J. 2012;6:140-5. PMID: 23248715.

The difficulty of diagnosing Lyme disease results in not just the potential for physical suffering by the patient but potentially problematic litigation.

By Sarah Kelman, JD, and the experts and editors at Medical Law Perspectives.

For more details about Dutkewych v. Standard Ins. Co., 2015 WL 1412590 (C.A.1 (Mass.), March 30, 2015) (not designated for publication), see the Scalpel Weekly News, April 13, 2015.

To Sign Up for the FREE Scalpel Weekly News giving you the latest FDA, CDC, and DOJ alerts, warnings, and announcements, and curated medical litigation cases, CLICK HERE.

See also Medical Law Perspectives, April 2014 Report: Danger and Controversy: Lyme Disease Liability Risks

MLPThumbnail

The content of this blog is provided for informational purposes only, and does not constitute legal advice.
This entry was posted in courts, law and medicine, law practice, litigation and tagged , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , . Bookmark the permalink.

Leave a Reply

Your email address will not be published. Required fields are marked *

You may use these HTML tags and attributes: <a href="" title=""> <abbr title=""> <acronym title=""> <b> <blockquote cite=""> <cite> <code> <del datetime=""> <em> <i> <q cite=""> <strike> <strong>