Lyme Misdiagnosis: A Serious Problem

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“In seven studies conducted in endemic areas, comprising a total of 1902 patients referred for suspected Lyme disease, only 7–31% had active Lyme disease and 5–20% had previous Lyme disease. Among the remainder, 50–88% had no evidence of ever having had Lyme disease.”

Source: Lantos, Paul “Chronic Lyme disease: the controversies and the science” Expert Rev. Anti Infect. Ther. 9(7), 787–797 (2011)

Results of 1261 patients who visited Johns Hopkins for presumptive Lyme disease from 2000 to 2013: 72% had no Lyme disease, but 84% of the patients with no Lyme disease received unnecessary antibiotics

So what is causing the symptoms of “chronic Lyme” patients?

The CDC and NIH emphasize that experts do not support the use of the term “chronic Lyme disease” because of confusion. Writing in the New England Journal of Medicine, 31 doctors and scientists classified those with the chronic Lyme label into four predominant groups:

  • Category 1: Symptoms of unknown cause, with no evidence of Borrelia burgdorferi infection
  • Category 2: A well-defined illness unrelated to B. burgdorferi infection
  • Category 3: Symptoms of unknown cause, with antibodies against B. burgdorferi but no history of objective clinical findings that are consistent with Lyme disease
  • Category 4: Post–Lyme disease syndrome

Feder et al observed “Only patients with category 4 disease have post–Lyme disease symptoms.” Looking at references 31-33 below, Feder et al stated:

Data from studies of patients who underwent reevaluation at academic medical centers suggest that the majority of patients presumed to have chronic Lyme disease have category 1 or 2 disease.

In other words, evidence indicates that the symptoms of most “chronic Lyme” patients were clearly not caused by Lyme disease. In addition, most “chronic Lyme” stories contain a number of red flags of quackery, including multiple false diagnoses.

References pointing to a massive problem of false positive diagnosis of Lyme disease:

Inappropriate use of testing leads to false positive diagnosis

As discussed on the LymeScience testing and red flags of chronic Lyme quackery pages, there are many ways to receive a false positive Lyme disease diagnosis.

False positives are facilitated by predatory labs, discredited testing, and testing that has not been scientifically validated. But misinterpretation of conventional testing is also a problem. Examples include:

  • Using the IgM Western blot test more than 30 days after the appearance of symptoms
    • Why? In a true Lyme infection, IgG antibodies can usually be detected by 4-6 weeks. Plus other infections, such as Epstein-Barr virus, can cause a false positive.
  • Ignoring or failing to perform the first tier ELISA test
    • Why? The American Society for microbiology explains: “The Lyme immunoblot test is designed only as a confirmatory test, so it is important not to test screen-negative samples. Some antigens on the blot react with non-Lyme antibodies, and the immunoblot can be over-interpreted in the absence of a positive screening test.”
  • Ignoring or failing to perform the second tier, confirmatory test
    • Why? First tier ELISA testing can be falsely positive (or equivocal) for a number of reasons, including due to other infections or due to autoimmune diseases. In North America, Lyme disease testing is only validated if interpreted based on CDC and Health Canada recommendations.
  • Misinterpreting fewer than 5 bands on the IgG Western blot as positive
    • Why? Many people without Lyme disease will test positive for some bands, especially band 41, which is commonly positive in healthy people.
  • Interpreting faint (but negative) Western blot bands as positive
    • Note: Some predatory labs—such as IgeneX and Medical Diagnostic Laboratories (MDL)—return results that allow people to misinterpret indeterminate (IND) or faint bands as positive.
  • Using non-standard Western blot bands such as bands 31 and 34
    • Why? Using these bands has not been shown to improve testing. (more on bands 31 and 34)
  • Using any non-standard “in-house” criteria for Western blot interpretation
    • Why? CDC explains: “This indicates the laboratory has modified the test and the clinical validity and safety is not certain.”
  • Misinterpreting persistent antibodies as persistent infection after a cured infection or asymptomatic infection that the immune system cleared on its own
    • Why? Our immune systems have memories such that antibodies can be detected many years after infection.

According to the consensus of experts:

Immunoglobulin G (IgG) seronegativity in an untreated patient with months to years of symptoms essentially rules out the diagnosis of Lyme disease, barring laboratory error or a rare humoral immunodeficiency state.

References on false positive ELISA testing

References describing false positive IgM testing

🧒 = Focusing on children and young people

 

References from Figure 1 :

31. 🇺🇸 Reid MC, et al. The consequences of overdiagnosis and overtreatment of Lyme disease: an observational study. Ann. Intern. Med. 128(5), 354–362 (1998). (Commentary: Overdiagnosis and overtreatment of Lyme disease leads to inappropriate health service use)

32. 🇺🇸 Sigal LH. Summary of the first 100 patients seen at a Lyme disease referral center. Am. J. Med. 88(6), 577–581 (1990).

33. 🇺🇸 Steere AC, et al. The overdiagnosis of Lyme disease. JAMA 269(14), 1812–1816 (1993).

34. 🇺🇸 Hassett AL, et al. Psychiatric comorbidity and other psychological factors in patients with “chronic Lyme disease”. Am. J. Med. 122(9), 843–850 (2009).

35. 🇺🇸 🧒 Qureshi MZ, et al. Overdiagnosis and overtreatment of Lyme disease in children. Pediatr. Infect. Dis. J. 21(1), 12–14 (2002).

36. 🇺🇸 🧒 Rose CD, et al. The overdiagnosis of Lyme disease in children residing in an endemic area. Clin. Pediatr. (Phila.) 33(11), 663–668 (1994).

37. 🇩🇪 Djukic M, et al. The diagnostic spectrum in patients with suspected chronic Lyme neuroborreliosis – the experience from one year of a university hospital’s Lyme neuroborreliosis outpatients clinic. Eur. J. Neurol. 18(4), 547–555 (2010).

38. 🇨🇦 Burdge DR, O’Hanlon DP. Experience at a referral center for patients with suspected Lyme disease in an area of nonendemicity: first 65 patients. Clin. Infect. Dis. 16(4), 558–560 (1993)

Untreated Late Lyme Disease

In the United States, the typical manifestation of Lyme disease that is untreated for months or longer involves Lyme arthritis. In this stage, antibody tests are expected to be positive.

See also: LymeScience’s infographic on Lyme arthritis

According to Steere and Arvikar:

Patients with Lyme arthritis have intermittent or persistent attacks of joint swelling and pain in one or a few large joints, especially the knee, usually over a period of several years, without prominent systemic manifestations.

Swollen knee is a typical symptom of late stage Lyme disease, source: CDC

In Europe, a skin manifestation called acrodermatitis chronica atrophicans can occur in late stage Lyme infection.

References on Untreated Late Lyme

Arvikar SL, Steere AC. Diagnosis and treatment of Lyme arthritis. Infect Dis Clin North Am. 2015.

Schoen RT. A case revealing the natural history of untreated Lyme disease. Nat Rev Rheumatol. 2011.

Brummitt SI, et al. Molecular Characterization of Borrelia burgdorferi from Case of Autochthonous Lyme Arthritis. Emerg Infect Dis. 2014.

Washington Post: Medical Mysteries: Nurse solves mysterious ailment that puzzled orthopedists, oncologist

New York Times: My Son Got Lyme Disease. He’s Totally Fine

Hirsch AG, et al. Obstacles to diagnosis and treatment of Lyme disease in the USA: a qualitative study. BMJ Open. 2018.

Steere AC, Schoen RT, Taylor E. The clinical evolution of Lyme arthritis. Ann Intern Med. 1987.

European specific

Mahieu R, et al. A 59-year-old woman with chronic skin lesions of the leg. (photo quiz and article) Clin Infect Dis. 2013;57(12):1751, 1782.

Moniuszko-malinowska A, et al. Acrodermatitis chronica atrophicans: various faces of the late form of Lyme borreliosis. Postepy Dermatol Alergol. 2018;35(5):490-494.

updated February 19, 2024