Mistaken Identity: Many Diagnoses are Frequently Misattributed to Lyme Disease

Abstract:

Background: Prior studies have demonstrated that Lyme disease is frequently over-diagnosed. However, few studies describe which conditions are misdiagnosed as Lyme disease.

Methods: This retrospective observational cohort study evaluated patients referred for Lyme disease to a Mid-Atlantic academic center between 2000-2013 who lacked evidence for Borrelia burgdorferi infection. The primary outcome is clinically described diagnoses contributing to symptoms. Secondary outcomes included symptom duration and determination whether diagnoses were new or attributed to existing medical conditions.

Results: Of 1261 referred patients, 1061 (84%) had no findings of active Lyme disease, with 690 (65%) receiving other diagnoses resulting in 405 (59%) having newly diagnosed medical conditions, 134 (19%) attributed to pre-existing medical issues, and 151 (22%) had both new and pre-existing conditions. Among the 690 patients, the median symptom duration was 796 days, and a total of 139 discrete diagnoses were made. Infectious disease diagnoses comprised only 3.2%. Leading diagnoses were anxiety/depression 222 (21%), fibromyalgia 120 (11%), chronic fatigue syndrome 77 (7%), migraine disorder 74 (7%), osteoarthritis 62 (6%) and sleep disorder/apnea 48 (5%). Examples of less frequent but non-syndromic diseases newly diagnosed included multiple sclerosis (11), malignancy (8), Parkinson’s disease (8), sarcoidosis (4) or amyotrophic lateral sclerosis (4).

Conclusions: Most patients with long-term symptoms have either new or pre-existing disorders accounting for their symptoms other than Lyme disease, suggesting overdiagnosis in this population. Patients referred for consideration of Lyme disease for chronic symptoms deserve careful assessment for diagnoses other than Borrelia burgdorferi infection.

Source: Kobayashi T, Higgins Y, Melia MT, Auwaerter PG. Mistaken Identity: Many Diagnoses are Frequently Misattributed to Lyme Disease. Am J Med. 2021 Nov 30:S0002-9343(21)00792-0. doi: 10.1016/j.amjmed.2021.10.040. Epub ahead of print. PMID: 34861197. https://www.sciencedirect.com/science/article/pii/S0002934321007920  (Full text)

Characterising DSCATT: A case series of Australian patients with debilitating symptom complexes attributed to ticks

Abstract:

Objectives(s): To characterise the clinical profile, aetiology and treatment responsiveness of ‘Australian Lyme’, or Debilitating Symptom Complexes Attributed to Ticks.

Methods: Single-centre retrospective case analysis of patients referred to the Infectious Diseases Unit at Austin Health – a tertiary health service in Heidelberg, Australia – between 2014 and 2020 for investigation and treatment of suspected Debilitating Symptom Complexes Attributed to Ticks. Patients were included if they had debilitating symptoms suggested by either themselves or the referring clinician as being attributed to ticks.

Results: Twenty-nine Debilitating Symptom Complexes Attributed to Ticks cases were included in the analysis. Other than Lyme disease (83%), the most common prior medical diagnoses were Epstein-Barr virus (38%), chronic fatigue syndrome (28%) and fibromyalgia (24%). Prior histories of anxiety (48%) and depression (41%) were common. The most frequently reported symptoms included fatigue (83%), headache (72%) and arthralgia (69%). National Association of Testing Authorities/Royal College of Pathologists of Australasia-accredited serology was not diagnostic of acute infective causes, including Lyme disease, in any patient. Of 25 cases with available data, 23 (92%) had previously been prescribed antimicrobials, with 53% reporting benefit from them. The most common diagnoses made by our hospital were chronic fatigue syndrome (31%), migraines (28%) and fibromyalgia (21%). Only one patient’s symptoms were not accounted for by other diagnoses.

Conclusion: This is the first case series of patients with Debilitating Symptom Complexes Attributed to Ticks. They had high rates of other medically unexplained syndromes, and no evidence of acute Lyme disease, or any common organic disease process. Debilitating Symptom Complexes Attributed to Ticks remains medically unexplained, and may therefore be due to an as yet unidentified cause, or may be considered a medically unexplained syndrome similar to conditions such as chronic fatigue syndrome.

Source: Schnall J, Oliver G, Braat S, Macdonell R, Gibney KB, Kanaan RA. Characterising DSCATT: A case series of Australian patients with debilitating symptom complexes attributed to ticks. Aust N Z J Psychiatry. 2021 Sep 1:48674211043788. doi: 10.1177/00048674211043788. Epub ahead of print. PMID: 34465249. https://pubmed.ncbi.nlm.nih.gov/34465249/

The Putative Role of Viruses, Bacteria, and Chronic Fungal Biotoxin Exposure in the Genesis of Intractable Fatigue Accompanied by Cognitive and Physical Disability

Abstract:

Patients who present with severe intractable apparently idiopathic fatigue accompanied by profound physical and or cognitive disability present a significant therapeutic challenge. The effect of psychological counseling is limited, with significant but very slight improvements in psychometric measures of fatigue and disability but no improvement on scientific measures of physical impairment compared to controls. Similarly, exercise regimes either produce significant, but practically unimportant, benefit or provoke symptom exacerbation. Many such patients are afforded the exclusionary, non-specific diagnosis of chronic fatigue syndrome if rudimentary testing fails to discover the cause of their symptoms.

More sophisticated investigations often reveal the presence of a range of pathogens capable of establishing life-long infections with sophisticated immune evasion strategies, including Parvoviruses, HHV6, variants of Epstein-Barr, Cytomegalovirus, Mycoplasma, and Borrelia burgdorferi. Other patients have a history of chronic fungal or other biotoxin exposure. Herein, we explain the epigenetic factors that may render such individuals susceptible to the chronic pathology induced by such agents, how such agents induce pathology, and, indeed, how such pathology can persist and even amplify even when infections have cleared or when biotoxin exposure has ceased. The presence of active, reactivated, or even latent Herpes virus could be a potential source of intractable fatigue accompanied by profound physical and or cognitive disability in some patients, and the same may be true of persistent Parvovirus B12 and mycoplasma infection. A history of chronic mold exposure is a feasible explanation for such symptoms, as is the presence of B. burgdorferi. The complex tropism, life cycles, genetic variability, and low titer of many of these pathogens makes their detection in blood a challenge. Examination of lymphoid tissue or CSF in such circumstances may be warranted.

 

Source: Morris G, Berk M, Walder K, Maes M. The Putative Role of Viruses, Bacteria, and Chronic Fungal Biotoxin Exposure in the Genesis of Intractable Fatigue Accompanied by Cognitive and Physical Disability. Mol Neurobiol. 2016 May;53(4):2550-71. doi: 10.1007/s12035-015-9262-7. Epub 2015 Jun 17. https://www.ncbi.nlm.nih.gov/pubmed/26081141

 

A case of lyme disease requiring over 1 year to diagnose at an infectious-disease clinic

Abstract:

A 42-year-old woman presenting with years of fever and vague symptoms could not be satisfactorily diagnosed in physical examination or conventional workups. She was presumptively diagnosed with chronic fatigue syndrome and treated symptomatically. Fourteen months after the initial visit, she developed left facial palsy. Lyme disease serology was positive. Four weeks of oral amoxicillin ameliorated symptoms. Only 5 to 15 cases of Lyme disease are reported annually in Japan, mostly from the northeastern-most island of Hokkaido. It may occur anywhere in Japan, however; probably is underdiagnosed. Lyme disease may cause fevers of unknown origin. Astute clinical suspicion and appropriate workups are thus needed to diagnose this infection.

 

Source: Iwata K, Shimada T, Kawabata H. A case of lyme disease requiring over 1 year to diagnose at an infectious-disease clinic. Kansenshogaku Zasshi. 2013 Jan;87(1):44-8. [Article in Japanese] https://www.ncbi.nlm.nih.gov/pubmed/23484378

 

Lyme disease in a British referral clinic

Abstract:

BACKGROUND: Concerns about over-diagnosis and inappropriate management of Lyme disease (LD) are well documented in North America and supported by clinical data. There are few parallel data on the situation in the UK.

AIM: To describe the patterns of referral, investigation, diagnosis and treatment of patients with suspected LD referred to an infectious disease unit in Liverpool, UK. Previous management by National Health Service (NHS) and non-NHS practitioners was reviewed.

DESIGN: Descriptive study conducted by retrospective casenotes review.

METHODS: Retrospective case notes review of adults referred with possible LD to an infectious disease unit in Liverpool, UK, over 5 years (2006-2010).

RESULTS: Of 115 patients, 27 (23%) were diagnosed with LD, 38 (33%) with chronic fatigue syndrome (CFS) and 13 (11%) with other medical conditions. No specific diagnosis could be made in 38 (33%). At least 53 unnecessary antibiotic courses had been given by non-NHS practitioners; 21 unnecessary courses had been prescribed by NHS practitioners. Among 38 patients, 17 (45%) with CFS had been misdiagnosed as having LD by non-NHS practitioners.

CONCLUSION: A minority of referred patients had LD, while a third had CFS. LD is over-diagnosed by non-specialists, reflecting the complexities of clinical and/or laboratory diagnosis. Patients with CFS were susceptible to misdiagnosis in non-NHS settings, reinforcing concerns about missed opportunities for appropriate treatment for this group and about the use of inappropriate diagnostic modalities and anti-microbials in non-NHS settings.

Comment in: [Borreliosis]. [Orthopade. 2013]

 

Source: Cottle LE, Mekonnen E, Beadsworth MB, Miller AR, Beeching NJ. Lyme disease in a British referral clinic. QJM. 2012 Jun;105(6):537-43. doi: 10.1093/qjmed/hcs003. Epub 2012 Feb 1. http://qjmed.oxfordjournals.org/content/105/6/537.long (Full article)

 

Factors affecting duration of chronic fatigue syndrome in pediatric patients

Abstract:

OBJECTIVE: To determine factors affecting duration of chronic fatigue syndrome (CFS) in pediatric patients.

METHODS: This Retrospective cohort consisted of patients with CFS at the regional referral infectious disease clinic for evaluation of fatigue in children and adolescents. Demographic, clinical, and laboratory data were analyzed to identify the impact on duration and severity of pediatric CFS.

RESULTS: A total number of 53 predominantly white (98.1%) patients with CFS, aged 9-18 years, were included in the study. Other than fatigue, headaches and sleep disturbance were the most common symptoms of pediatric CFS. Seropositive status for Borrelia burgdorferi (B. burgdorferi) and Epstein-Barr virus (EBV) was identified in 66% of the patients with the diagnosis of CFS by CDC criteria. No association was found between the CFS symptoms, gender, or age at diagnosis and duration of fatigue symptoms. Duration of CFS was associated with high Body-Mass Index (BMI) in a regression model after adjustment for patient’s age, gender, and seropositive status for B. burgdorferi and/or EBV (0.34 ± 0.15, P < 0.04).

CONCLUSIONS: BMI is significantly associated with prolonged duration of CFS.

 

Source: Petrov D, Marchalik D, Sosin M, Bal A. Factors affecting duration of chronic fatigue syndrome in pediatric patients. Indian J Pediatr. 2012 Jan;79(1):52-5. doi: 10.1007/s12098-011-0463-4. Epub 2011 May 27. https://www.ncbi.nlm.nih.gov/pubmed/21617905

 

Distinct cerebrospinal fluid proteomes differentiate post-treatment lyme disease from chronic fatigue syndrome

Abstract:

BACKGROUND: Neurologic Post Treatment Lyme disease (nPTLS) and Chronic Fatigue (CFS) are syndromes of unknown etiology. They share features of fatigue and cognitive dysfunction, making it difficult to differentiate them. Unresolved is whether nPTLS is a subset of CFS.

METHODS AND PRINCIPAL FINDINGS: Pooled cerebrospinal fluid (CSF) samples from nPTLS patients, CFS patients, and healthy volunteers were comprehensively analyzed using high-resolution mass spectrometry (MS), coupled with immunoaffinity depletion methods to reduce protein-masking by abundant proteins. Individual patient and healthy control CSF samples were analyzed directly employing a MS-based label-free quantitative proteomics approach. We found that both groups, and individuals within the groups, could be distinguished from each other and normals based on their specific CSF proteins (p<0.01). CFS (n = 43) had 2,783 non-redundant proteins, nPTLS (n = 25) contained 2,768 proteins, and healthy normals had 2,630 proteins. Preliminary pathway analysis demonstrated that the data could be useful for hypothesis generation on the pathogenetic mechanisms underlying these two related syndromes.

CONCLUSIONS: nPTLS and CFS have distinguishing CSF protein complements. Each condition has a number of CSF proteins that can be useful in providing candidates for future validation studies and insights on the respective mechanisms of pathogenesis. Distinguishing nPTLS and CFS permits more focused study of each condition, and can lead to novel diagnostics and therapeutic interventions.

 

Source: Schutzer SE, Angel TE, Liu T, Schepmoes AA, Clauss TR, Adkins JN, Camp DG, Holland BK, Bergquist J, Coyle PK, Smith RD, Fallon BA, Natelson BH. Distinct cerebrospinal fluid proteomes differentiate post-treatment lyme disease from chronic fatigue syndrome. PLoS One. 2011 Feb 23;6(2):e17287. doi: 10.1371/journal.pone.0017287. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3044169/ (Full article)

 

Chronic fatigue syndrome in patients with Lyme borreliosis

Abstract:

Several authors have reported a chronic fatigue-like syndrome in patients that have suffered from Lyme borreliosis in the past. To further investigate this suspicion of an association without sample bias, we carried out a prospective, double-blind study and tested 1, 156 healthy young males for Borrelia antibodies. Seropositive subjects who had never suffered from clinically manifest Lyme borreliosis or neuroborreliosis showed significantly more often chronic fatigue (p = 0.02) and malaise (p = 0.01) than seronegative recruits. Therefore we believe it is worth examining whether an antibiotic therapy should be considered in patients with chronic fatigue syndrome and positive Borrelia serology.

Copyright 2000 S. Karger AG, Basel.

 

Source: Treib J, Grauer MT, Haass A, Langenbach J, Holzer G, Woessner R. Chronic fatigue syndrome in patients with Lyme borreliosis. Eur Neurol. 2000;43(2):107-9. http://www.ncbi.nlm.nih.gov/pubmed/10686469

 

Absence of Borrelia burgdorferi-specific immune complexes in chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) and Lyme disease often share clinical features, especially fatigue, contributing to concern that Borrelia burgdorferi (Bb), the cause of Lyme disease, may underlie CFS symptoms. We examined 39 CFS patients and 40 healthy controls with a Bb immune complex test. Patients and controls were nonreactive. Centers for Disease Control and Prevention-defined CFS patients lacking antecedent signs of Lyme disease–erythema migrans, Bell’s palsy, or large joint arthritis–are not likely to have laboratory evidence of Bb infection.

 

Source: Schutzer SE, Natelson BH. Absence of Borrelia burgdorferi-specific immune complexes in chronic fatigue syndrome. Neurology. 1999 Oct 12;53(6):1340-1. http://www.ncbi.nlm.nih.gov/pubmed/10522896

 

Clinical and serologic follow-up in patients with neuroborreliosis

Abstract:

The authors performed a clinical and serologic follow-up study after 4.2 +/- 1.2 years in 44 patients with clinical signs of neuroborreliosis and specific intrathecal antibody production. All patients had been treated with ceftriaxone 2 g/day for 10 days. Although neurologic deficits decreased significantly, more than half the patients had unspecific complaints resembling a chronic fatigue syndrome and showed persisting positive immunoglobulin M serum titers for Borrelia in the Western blot analysis.

Comment in: Neuropsychological deficits in neuroborreliosis. [Neurology. 1999]

 

Source: Treib J, Fernandez A, Haass A, Grauer MT, Holzer G, Woessner R. Clinical and serologic follow-up in patients with neuroborreliosis. Neurology. 1998 Nov;51(5):1489-91. http://www.ncbi.nlm.nih.gov/pubmed/9818893