On 2018 Jan 13, Raphael Stricker commented:

An Outdated View of Lyme Neuroborreliosis

Raphael B. Stricker, MD. Union Square Medical Associates, San Francisco, CA, USA. rstricker@usmamed.com

The article by Halperin entitled "Diagnosis and Management of Lyme Neuroborreliosis" attempts to address "widespread misconceptions" about the clinical phenomenology, diagnostic approach and response to treatment of neuroborreliosis. Unfortunately the article promotes these misconceptions by ignoring progress in Lyme disease research over the past 20 years. In fact, with the exception of some cosmetic details such as mention of CxCL13, a nonspecific marker of neuroborreliosis, and C6 peptide testing, a relatively insensitive test for Lyme disease, this article could have been written in 1997. It is equally inaccurate and simplistic now, as described below.

The article uses an interesting approach to promote "Lyme denialism", the view that Lyme disease is a trivial illness that is easily diagnosed and treated as opposed to the worldwide epidemic of an often debilitating disease that affects more than 300,000 new cases annually in the USA alone (1). The discussion points to extensive uncertainties about various aspects of the neurological disease, and then concludes that, despite these worrisome unanswered questions, diagnosis and treatment of neuroborreliosis is relatively simple. There is no discussion of Borrelia cystic forms, biofilms or persister cells that complicate diagnosis and treatment. Relapsing fever Borrelia (RFB) and RFB-like strains such as B. miyamotoi and B. mayonii are brushed aside because "very few human infections" with these organisms have been identified, mainly because routine clinical testing for these Borrelia species does not exist. There is no mention of SPECT brain scans that may be useful in diagnosis of brain inflammation in neuroborreliosis patients (2), and tickborne coinfections such as Babesia microti, Babesia duncani, Anaplasma, Ehrlichia, Bartonella and Rickettsia that may cause significant neurological complications are completely ignored. Thus the article inhabits a simplistic world that was already obsolete 20 years ago.

A good example of the misinformation contained in this document is the statement that the erythema migrans (EM) "bullseye" rash is found in "90% of infected children" with Lyme disease. This exaggerated EM prevalence is based on a study that defines Lyme disease according to CDC surveillance criteria, which rely heavily on the EM rash for diagnosis. Thus due to this circular reasoning, patients with an EM rash were significantly over-represented in the study. A more realistic contemporary clinical study of neuroborreliosis in children put the rate of EM rash at 27% (3). This more realistic EM prevalence indicates that diagnosis may not be that simple in children with neuroborreliosis.

The article restates the myth that two-tier Lyme testing has "high sensitivity and specificity" for diagnosis. This statement ignores evidence for the dismal sensitivity of CDC-sanctioned two-tier testing (4,5). For patients with neuroborreliosis, the allegedly high test sensitivity is based on circular reasoning: to be included in this category, patients were required to have positive Lyme testing, and then they had positive Lyme testing! This type of faulty reasoning is presented uncritically throughout the article.

The article relies heavily on information from the review by Steere et al. (6), which has an extensive critique in PubMed Commons. Many of those criticisms apply to this article as well.

References

(1) Stricker & Johnson, PLoS Pathog 10(1): e1003796.

(2) Donta et al, Clin Nucl Med. 2012;37:e219.

(3) Bingham et al, Pediatrics. 1995;96:1053.

(4) Stricker et al, Expert Rev Anti Infect Ther. 2005;3:155.

(5) Cook & Puri, Int J Gen Med. 2017;10:113.

(6) Steere et al, Nature Rev Dis Primers. 2016;2:16090.

Disclosure: RBS is a member of the International Lyme and Associated Diseases Society (ILADS) and a director of LymeDisease.org. He has no financial or other conflicts to declare.

On 2018 Jan 13, Raphael Stricker commented:

An Outdated View of Lyme Neuroborreliosis

Raphael B. Stricker, MD. Union Square Medical Associates, San Francisco, CA, USA. rstricker@usmamed.com

The article by Halperin entitled "Diagnosis and Management of Lyme Neuroborreliosis" attempts to address "widespread misconceptions" about the clinical phenomenology, diagnostic approach and response to treatment of neuroborreliosis. Unfortunately the article promotes these misconceptions by ignoring progress in Lyme disease research over the past 20 years. In fact, with the exception of some cosmetic details such as mention of CxCL13, a nonspecific marker of neuroborreliosis, and C6 peptide testing, a relatively insensitive test for Lyme disease, this article could have been written in 1997. It is equally inaccurate and simplistic now, as described below.

The article uses an interesting approach to promote "Lyme denialism", the view that Lyme disease is a trivial illness that is easily diagnosed and treated as opposed to the worldwide epidemic of an often debilitating disease that affects more than 300,000 new cases annually in the USA alone (1). The discussion points to extensive uncertainties about various aspects of the neurological disease, and then concludes that, despite these worrisome unanswered questions, diagnosis and treatment of neuroborreliosis is relatively simple. There is no discussion of Borrelia cystic forms, biofilms or persister cells that complicate diagnosis and treatment. Relapsing fever Borrelia (RFB) and RFB-like strains such as B. miyamotoi and B. mayonii are brushed aside because "very few human infections" with these organisms have been identified, mainly because routine clinical testing for these Borrelia species does not exist. There is no mention of SPECT brain scans that may be useful in diagnosis of brain inflammation in neuroborreliosis patients (2), and tickborne coinfections such as Babesia microti, Babesia duncani, Anaplasma, Ehrlichia, Bartonella and Rickettsia that may cause significant neurological complications are completely ignored. Thus the article inhabits a simplistic world that was already obsolete 20 years ago.

A good example of the misinformation contained in this document is the statement that the erythema migrans (EM) "bullseye" rash is found in "90% of infected children" with Lyme disease. This exaggerated EM prevalence is based on a study that defines Lyme disease according to CDC surveillance criteria, which rely heavily on the EM rash for diagnosis. Thus due to this circular reasoning, patients with an EM rash were significantly over-represented in the study. A more realistic contemporary clinical study of neuroborreliosis in children put the rate of EM rash at 27% (3). This more realistic EM prevalence indicates that diagnosis may not be that simple in children with neuroborreliosis.

The article restates the myth that two-tier Lyme testing has "high sensitivity and specificity" for diagnosis. This statement ignores evidence for the dismal sensitivity of CDC-sanctioned two-tier testing (4,5). For patients with neuroborreliosis, the allegedly high test sensitivity is based on circular reasoning: to be included in this category, patients were required to have positive Lyme testing, and then they had positive Lyme testing! This type of faulty reasoning is presented uncritically throughout the article.

The article relies heavily on information from the review by Steere et al. (6), which has an extensive critique in PubMed Commons. Many of those criticisms apply to this article as well.

References

(1) Stricker & Johnson, PLoS Pathog 10(1): e1003796.

(2) Donta et al, Clin Nucl Med. 2012;37:e219.

(3) Bingham et al, Pediatrics. 1995;96:1053.

(4) Stricker et al, Expert Rev Anti Infect Ther. 2005;3:155.

(5) Cook & Puri, Int J Gen Med. 2017;10:113.

(6) Steere et al, Nature Rev Dis Primers. 2016;2:16090.

Disclosure: RBS is a member of the International Lyme and Associated Diseases Society (ILADS) and a director of LymeDisease.org. He has no financial or other conflicts to declare.