“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)
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:
- LymeScience: How chronic Lyme recruits followers
- Marzec NS, et al. Serious Bacterial Infections Acquired During Treatment of Patients Given a Diagnosis of Chronic Lyme Disease – United States. MMWR Morb Mortal Wkly Rep. 2017;66(23):607-609. [press coverage]
- 🇺🇸 Fallon BA, et al. A comparison of lyme disease serologic test results from 4 laboratories in patients with persistent symptoms after antibiotic treatment. 2014.
- 🇫🇷 Hansmann Y, et al. Feedback on difficulties raised by the interpretation of serological tests for the diagnosis of Lyme disease. Med Mal Infect. 2014.
- 🇬🇧 Cottle LE, et al. Lyme disease in a British referral clinic. QJM. 2012. [LymeScience discussion and infographic]
- 🇨🇦 Patrick DM, et al. Lyme Disease Diagnosed by Alternative Methods: A Phenotype Similar to That of Chronic Fatigue Syndrome. Clin Infect Dis. 2015.
- 🇦🇺 LymeScience: Australia has no Lyme disease- So why are activists promoting it?
- 🇳🇱 New test has no added value in Lyme disease of the central nervous system
- 🇺🇸 🧒 Ettestad PJ, et al. Biliary complications in the treatment of unsubstantiated Lyme disease. J Infect Dis. 1995.
- 🇺🇸 Wormser GP, Shapiro ED. Implications of Gender in Chronic Lyme Disease. J Womens Health (Larchmt). 2009.
- 🇺🇸 Role of Psychiatric Comorbidity in Chronic Lyme Disease
- 🇺🇸 Neoplasms Misdiagnosed as “Chronic Lyme Disease”
- 🇺🇸 Serious Bacterial Infections Acquired During Treatment of Patients Given a Diagnosis of Chronic Lyme Disease — United States
- 🇺🇸 Barclay SS, et al. Misdiagnosis of late-onset Lyme arthritis by inappropriate use of Borrelia burgdorferi immunoblot testing with synovial fluid. Clin Vaccine Immunol. 2012.
- 🇺🇸 NIH: Chronic Lyme disease
- 🇺🇸 CDC: Post-treatment Lyme disease syndrome (and Dangers of long-term or alternative treatments for Lyme disease)
- 🇺🇸 Seriburi V, et al. High frequency of false positive IgM immunoblots for Borrelia burgdorferi in clinical practice. Clin Microbiol Infect. 2012.
- 🇺🇸 🧒 Lantos PM, et al. False Positive Lyme Disease IgM Immunoblots in Children. J Pediatr. 2016.
- 🇺🇸 Medscape: Lyme Culture Test Causes Uproar
- 🇫🇷 Jacquet C, et al. Multidisciplinary management of patients presenting with Lyme disease suspicion. Med Mal Infect. 2018; [open manuscript]
- 🇫🇷 Haddad E, et al. Holistic approach in patients with presumed Lyme borreliosis leads to less than 10% of confirmation and more than 80% of antibiotics failure. Clin Infect Dis. 2018. [Français, commentary]
- 🇫🇷 Voitey M, et al. Functional signs in patients consulting for presumed Lyme borreliosis. Med Mal Infect. 2019;
- 🇫🇷 Haddad E, Caumes E. Experience of three French centers in the management of more than 1,000 patients consulting for presumed Lyme Borreliosis. Med Mal Infect. 2019; [open manuscript]
- 🇺🇸 CDC: Notes from the Field: Reference Laboratory Investigation of Patients with Clinically Diagnosed Lyme Disease and Babesiosis – Indiana, 2016. MMWR Morb Mortal Wkly Rep. 2018.
- 🇦🇹 Markowicz M, et al. Testing patients with non-specific symptoms for antibodies against Borrelia burgdorferi sensu lato does not provide useful clinical information about their aetiology. Clin Microbiol Infect. 2015.
- 🇨🇦 Gasmi S, et al. Practices of Lyme disease diagnosis and treatment by general practitioners in Quebec, 2008-2015. BMC Fam Pract. 2017.
- 🇳🇴 Roaldsnes E, et al. Lyme neuroborreliosis in cases of non-specific neurological symptoms. Tidsskr Nor Laegeforen. 2017..
- 🇳🇱 Zomer TP, et al. Non-specific symptoms in adult patients referred to a Lyme centre. Clin Microbiol Infect. 2018.
- 🇳🇱 🧒 Zomer TP, et al. Nonspecific Symptoms in Children Referred to a Lyme Borreliosis Center. Pediatr Infect Dis J. 2020.
- 🇳🇱 Nijman G, et al. Antibiotic treatment in patients that present with solely non-specific symptoms and positive serology at a Lyme centre. Eur J Intern Med. 2020;
- 🇺🇸 Kwit NA, et al. Notes from the Field: High Volume of Lyme Disease Laboratory Reporting in a Low-Incidence State — Arkansas, 2015–2016. MMWR Morb Mortal Wkly Rep 2017.
- 🇫🇷 Bouiller K, et al. Consultation for presumed Lyme borreliosis: the need for a multidisciplinary management. Clin Infect Dis. 2018.
- 🇺🇸 Lantos PM, et al. Poor Positive Predictive Value of Lyme Disease Serologic Testing in an Area of Low Disease Incidence. Clin Infect Dis. 2015.
- 🇩🇪 Csallner G, et al. Patients with “organically unexplained symptoms” presenting to a borreliosis clinic: clinical and psychobehavioral characteristics and quality of life. Psychosomatics. 2013.
- 🇺🇸 Tseng YJ, et al. Incidence and Patterns of Extended-Course Antibiotic Therapy in Patients Evaluated for Lyme Disease. Clin Infect Dis. 2015. (commentary)
- 🇺🇸 Nelson RE, et al. Evaluation of serological testing for Lyme disease in Military Health System beneficiaries in Germany, 2013-2017. MSMR. 2019.
- 🇳🇱 Coumou J, et al. Ticking the right boxes: classification of patients suspected of Lyme borreliosis at an academic referral center in the Netherlands. Clin Microbiol Infect. 2015.
- 🇸🇪 Svenungsson B, Lindh G. Lyme borreliosis–an overdiagnosed disease? Infection. 1997.
- 🇵🇱 Moniuszko A. The problem of overreporting and overdiagnosing Lyme disease in Poland. ECCMID 2018 Abstract. 2018.
- 🇺🇸 Molloy PJ, et al. False-positive results of PCR testing for Lyme disease. Clin Infect Dis. 2001.
- 🇳🇴 Ljøstad U, Mygland Å. The phenomenon of ‘chronic Lyme’; an observational study. Eur J Neurol. 2012. [paper mirror]
- 🇧🇷 De oliveira SV, et al. Lack of serological evidence for Lyme-like borreliosis in Brazil. Travel Med Infect Dis. 2018.
- 🇮🇹 🧒 Peri F, et al. Somatic symptom disorder should be suspected in children with alleged chronic Lyme disease. Eur J Pediatr. 2019. [excerpts]
- 🇺🇸 Kobayashi et al. Misdiagnosis of Lyme Disease with Unnecessary Antimicrobial Treatment Characterize Patients Referred to an Academic Infectious Diseases Clinic. Open Forum Infectious Diseases. 2019.
- 🇺🇸 Fix AD, et al. Tick bites and Lyme disease in an endemic setting: problematic use of serologic testing and prophylactic antibiotic therapy. JAMA. 1998.
- 🇺🇸 Clayton JL, et al. Enhancing Lyme Disease Surveillance by Using Administrative Claims Data, Tennessee, USA. Emerging Infect Dis. 2015.
- 🇺🇸 Bashir M, et al. A Rare but Fascinating Disorder: Case Collection of Patients with Schnitzler Syndrome. Case Rep Rheumatol. 2018.
- 🇺🇸 Boyce RM, et al. Errors in diagnostic test use and interpretation contribute to the high number of Lyme disease referrals in a low-incidence state. Open Forum Infectious Diseases. 2020.
- 🇺🇸 Webber BJ, et al. Lyme Disease Overdiagnosis in a Large Healthcare System: A Population-based, Retrospective Study. Clin Microbiol Infect. 2019.
- 🇺🇸 Aguirre LE, et al. Anchoring Bias, Lyme Disease, and the Diagnosis Conundrum. Cureus. 2019.
- 🇺🇸 Lowry L, et al. Anchoring Bias on Lyme Disease Leading to Delayed Diagnoses. Mil Med. 2020.
- 🇫🇮 Kortela E, et al. Suspicion of Lyme borreliosis in patients referred to an infectious diseases clinic: what did the patients really have? Clinical Microbiology and Infection. 2020.
- 🇩🇰 Gynthersen RM, et al. Classification of patients referred under suspicion of tick-borne diseases, Copenhagen, Denmark. Ticks and Tick-borne Diseases. 2020.
- 🇩🇪 Hanses F, et al. Verdacht auf Borreliose – Was hat der Patient? [Suspected borreliosis – what’s behind it?]. Dtsch Med Wochenschr. 2011.
- 🇮🇹 D’Alessandro R, et al. Tendency for overdiagnosis of neuroborreliosis. Ital J Neurol Sci. 1994.
- 🇳🇱 Blaauw AA, Bijlsma JW. Musculoskeletale klachten vaak ten onrechte aan Lyme-ziekte toegeschreven [Musculoskeletal symptoms often incorrectly attributed to Lyme disease]. Ned Tijdschr Geneeskd. 1997.
- 🇺🇸 Sigal LH. Persisting complaints attributed to chronic Lyme disease: possible mechanisms and implications for management. Am J Med. 1994.
- 🇫🇷 Itani, Oula. Focus on patients receiving long-term antimicrobial treatments for Lyme borreliosis: no Lyme but mostly mental disorders. 2020.
- 🇫🇷 Raffetin, A, et al. Lyme borreliosis or not Lyme borreliosis? A multidisciplinary approach to enable a right diagnosis and a better personalised medical support [conference abstract]. 2019.
- 🇫🇷 Bouilller, K, et. al. Presumed Lyme borreliosis: patients with confirmed Lyme borreliosis are less symptomatic than other patients [conference abstract]. 2019.
- 🇺🇸 Greco TP Jr, et al. Antiphospholipid antibodies in patients with purported ‘chronic Lyme disease’. Lupus. 2011.
- 🇺🇸 Wormser GP, et al. Studies that report unexpected positive blood cultures for Lyme borrelia – are they valid? Diagn Microbiol Infect Dis. 2017.
- 🇺🇸 McCarthy ML, et al. Lessons Learned from a Rhode Island Academic Out-Patient Lyme and Tick-Borne Disease Clinic. Rhode Island Medical Journal. 2020.
- 🇺🇸 Beeson AM, et al, 1428. Lyme Disease Treatment in the United States: Prescribing Patterns from a Nationwide Commercial Insurance Database, 2016-2018, Open Forum Infectious Diseases. 2020.
- 🇫🇷 Guellec D, et al. Diagnostic impact of routine Lyme serology in recent-onset arthritis: results from the ESPOIR cohort. RMD Open. 2016.
- 🇺🇸 Hudman DA. Exposure to Ticks and their Pathogens in Northeast Missouri. Mo Med. 2018.
- 🇸🇪 Nilsson K, et al. A comprehensive clinical and laboratory evaluation of 224 patients with persistent symptoms attributed to presumed tick-bite exposure. PLoS One. 2021.
- 🇺🇸 Hsu VM, et al. “Chronic Lyme disease” as the incorrect diagnosis in patients with fibromyalgia. Arthritis Rheum. 1993.
- 🇺🇸 🧒 Sigal LH, Patella SJ. Lyme arthritis as the incorrect diagnosis in pediatric and adolescent fibromyalgia. Pediatrics. 1992.
- 🇺🇸 Kaell AT, et al. Positive Lyme serology in subacute bacterial endocarditis. A study of four patients. JAMA. 1990.
- 🇦🇺 Schnall J. Characterising DSCATT: A case series of Australian patients with debilitating symptom complexes attributed to ticks. Aust N Z J Psychiatry. 2021.
🧒 = 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.
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.
Brummitt SI, et al. Molecular Characterization of Borrelia burgdorferi from Case of Autochthonous Lyme Arthritis. Emerg Infect Dis. 2014.
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.
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 September 25, 2021