Stakehold

of Lyme borreliosis in United Kingdom patients: A position statement by the British

Infection Association. J Infect. 2011 May;62(5):329-38. doi: 10.1016/j.jinf.2011.03.006.

http://www.aldf.com/pdf/BIA%202011statement%20on%20Lyme%20disease.pdf

Thank you for your comment on the issue of the classification of early and late Lyme disease as described in the consultation version of the scope. We have invited stakeholders to provide comment on this in a specific question at consultation to ensure that we collected the widest views on this issue. We now propose to present the guideline committee with the stakeholder feedback on this issue to allow them to determine the best approach for the guideline to take. As such, we have removed the detail linked to the definitions of early and late Lyme disease from the final scope.
Lyme Disease UK	3	79	The term 'definitive treatment’ should be replaced with ‘standard treatment’ as there is no proof that the treatment currently being offered for Lyme disease by the NHS is effective in the majority of cases. In fact this study showed that ‘over 63% of the Lyme disease cases had at least one diagnosis associated with PTLDS’ (post treatment Lyme disease symptoms) following early standard treatment (Adrion et al, 2015). Patients would argue that a continuation of symptoms does not mean that the treatment was ‘definitive’ or successful. This information is available on Lymedisease.org’s website: ‘The International Lyme and Associated Diseases Society (ILADS), recently published new treatment guidelines. These guidelines contained a rigorous assessment of the evidence and found treatment failure rates ranging from 16% to 39% for early treatment. Estimates for patients with chronic Lyme disease are much higher, ranging from 26% to 50%. (Johnson 2004)’ Whether ongoing symptoms are due to a continuing infection or due to a past infection is uncertain, but with many studies showing Borrelia’s ability to persist, ongoing infection cannot be ruled out and therefore treatment cannot be described as ‘definitive’. For those who have been treated, the patient experience often seems to be that people are told categorically by GPs that they cannot possibly still have Lyme disease following a standard course of antibiotics from the NHS. The ILADS guidelines state that, ‘there is no compelling evidence to support routinely withholding antibiotic retreatment from ill patients. While antibiotics are not always effective, the importance of providing patients with the opportunity to receive an adequate trial of antibiotic therapy is heightened by the lack of other effective treatment approaches. Palliative care may be helpful in addressing some symptoms in some cases, but it is important to bear in mind that palliative interventions also carry risks. Additionally, clinicians must not assume that palliative interventions would provide adequate treatment in the face of an underlying persistent infection. Therefore, in the panel’s judgment, antibiotic retreatment will prove to be appropriate for the majority of patients who remain ill’ (Cameron et al, 2014). References: 1. Adrion, ER, Aucott, J, Lemke, KW and Weiner, JP. Health care costs, utilization and patterns of care following Lyme disease. PLoS One. 2015 Feb 4;10(2):e0116767. doi: 10.1371/journal.pone.0116767. eCollection 2015 http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0116767 2. Lymedisease.org: Chronic https://www.lymedisease.org/lyme-basics/lyme-disease/chronic-lyme/ 3. Cameron DJ, Johnson LB, Maloney EL. Evidence assessments and guideline recommendations in Lyme disease: the clinical management of known tick bites, erythema migrans rashes and persistent disease. Expert Rev Anti Infect Ther. 2014 Sep;12(9):1103-35. doi: 10.1586/14787210.2014.940900 http://www.tandfonline.com/doi/full/10.1586/14787210.2014.940900 4. List of 700 Articles Citing Chronic Infection Associated with Tick-Borne Disease Compiled By Dr Robert Bransfield http://www.ilads.org/ilads_news/2015/list-of-700-articles- citing-chronic-infection-associated-with-tick-borne-disease-compiled-by-dr-robert- bransfield/	Thank you for your comment. The term ‘definitive’ has been removed.
Lyme Disease UK Lyme Disease UK	4 4	102- 108 94- 95	An extra point for ‘Main Outcomes’ needs to be included (point 8) and the evidence should be reviewed on issues of chronic complex sequelae and comorbidity which may relate to Lyme disease such as heart problems, gallbladder and thyroid disease, to name a few. Many Lyme disease patients appear to suffer from the conditions mentioned above and so searching for and assessing the literature on these issues and potential connections, may lead to a greater understanding and improvements in Lyme disease patient outcomes. An extra point should be added here (point 4.6) to include groups of patients who are immunocompromised, who have co-morbidities, who are pregnant, and who have other concurrent tick-borne infections. The BIA position statement from 2011 refers to immunocompromised patients on page 334. Children may also present differently clinically and require different treatment and this should be reflected in the guidelines. This article from Lymedisease.org highlights this point: ‘Children with Lyme disease have special issues. Since they can’t always explain what feels wrong, they may just come across as cranky and irritable. They suffer when their bodies hurt, when their illness disrupts their sleep at night, when they struggle in school, when they don’t even feel like playing. They may feel confused, lost and betrayed by parents and teachers who fail to recognize that they are sick and need help. Children with Lyme often have trouble in the classroom, because the disease can contribute to learning disabilities and behavioral problems.’ References: 1. British Infection Association. The epidemiology, prevention, investigation and treatment of Lyme borreliosis in United Kingdom patients: A position statement by the British Infection Association. J Infect. 2011 May;62(5):329-38. doi: 10.1016/j.jinf.2011.03.006. http://www.aldf.com/pdf/BIA%202011statement%20on%20Lyme%20disease.pdf 2. Lymedisease.org. Children with Lyme disease https://www.lymedisease.org/lyme-basics/lyme-disease/children/	Thank you for your comment. For the purpose of the scope, we believe this is already covered in the outcomes and would be addressed by the outcome ‘cure’ The guideline committee will agree the key outcomes for each review and will use their expertise to determine whether the results of relevant studies are significant. The guideline committee will review the evidence about diagnostic test accuracy and management strategies in pregnant women and immunocompromised people. It is anticipated that these populations will form sub-groups in each of our evidence reviews to ensure that, where evidence exists on these issues, the committee are able to make evidence-based recommendations to the NHS. These subgroups have been included in the equality impact assessment for this guideline. Children are already detailed in the scope and will form a separate group to ensure that the evidence is appropriately identified, considered and interpreted. We plan to recruit three paediatricians to the committee for this purpose. While people with co-infections will not be excluded from the evidence reviews, the focus of this guideline is the diagnosis and management of Lyme disease. However, the guideline committee will give mention to any groups who require special consideration when linking evidence to recommendations.
Lyme Disease UK	7	138- 139	The draft scope mentions that early symptoms of Lyme disease ‘are similar to those for flu.’ However, it is also important to note that Lyme disease can mimic many other conditions and present in numerous different ways, including neuropsychiatric manifestations. Fallon and Nields, in this study state that, ‘up to 40% of patients with Lyme disease develop neurologic involvement of either the peripheral or central nervous system. Dissemination to the CNS can occur within the first few weeks after skin infection’ and that ‘early signs include meningitis, encephalitis, cranial neuritis, and radiculoneuropathies.’ This quote reflects what appears to happen frequently in the patient community: ‘Time and again, Fallon, an expert in hypochondria, had seen frustrated doctors dismiss medically ill patients as psychiatric cases due to their own inability to diagnose the disease. With Lyme, the mistake was especially damaging since a delay in treatment could turn a curable, acute infection into a chronic, treatment-resistant disease’ (Weintraub, 2008). It is important to include in the scope and guidelines that initial symptoms of Lyme disease are not always concurrent with a dismissable flu-like illness. Doctors must be made aware of the wide variety of ways in which Lyme disease may present and not assume symptoms are restricted to those of flu in the initial stages, especially as without a known tick bite or EM rash, it is often hard to distinguish between an acute early infection and a disseminated infection. References: 1. Fallon, B. A. and Nields, J. A. (1994). Lyme disease: a neuropsychiatric illness. The American Journal of Psychiatry, 151(11), 1571–83. doi:10.1176/ajp.151.11.1571 http://www.ncbi.nlm.nih.gov/pubmed/7943444 2. Weintraub, P. Lyme Disease: The Great Imitator. Psychology Today, May 1st 2008. https://www.psychologytoday.com/articles/200805/lyme-disease-the-great-imitator	Thank you for your comment. We used the phrase “similar to flu” to reflect that the symptoms can be non- specific. We have amended the wording in the scope to read: “ …early symptoms are non-specific and can be similar to those for flu.”
Lyme Disease UK	7	141	The sentence ‘Lyme disease is frequently self-limiting and resolves spontaneously’ should be removed or rephrased. It is not representative of the general patient experience and it does not take into consideration existing and emerging evidence that Lyme disease can be a persistent infection. Furthermore, in the absence of 100% reliable tests, it cannot be proven that Lyme disease has been eradicated from a patient’s body. This is highlighted in this study: ‘Clinicians have no diagnostic tests to check for the persistence of live borreliae. B. burgdorferi, having a complex genetic structure, is a highly adaptable organism capable of evading immune response through different processes’ (Perronne, 2014). The ILADS guidelines state that ‘ongoing symptoms at the completion of active therapy were associated with an increased risk of long-term failure in some trials and therefore clinicians should not assume that time alone will resolve symptoms’ (Cameron et al, 2014). References: 1. List of 700 Articles Citing Chronic Infection Associated with Tick-Borne Disease Compiled By Dr Robert Bransfield http://www.ilads.org/ilads_news/2015/list-of-700-articles- citing-chronic-infection-associated-with-tick-borne-disease-compiled-by-dr-robert- bransfield/ 2. Perronne C (2014) Lyme and associated tick-borne diseases: global challenges in the context of a public health threat. Front. Cell. Infect. Microbiol. 4:74. doi: 10.3389/fcimb.2014.00074 http://journal.frontiersin.org/article/10.3389/fcimb.2014.00074/full 3. Cameron DJ, Johnson LB, Maloney EL. Evidence assessments and guideline recommendations in Lyme disease: the clinical management of known tick bites, erythema migrans rashes and persistent disease. Expert Rev Anti Infect Ther. 2014 Sep;12(9):1103- 35. doi: 10.1586/14787210.2014.940900 http://www.tandfonline.com/doi/full/10.1586/14787210.2014.940900	Thank you for your comment however we do not feel any change is required to the wording currently used. We continue to present information in this section linked to the issues when Lyme Disease has not resolved spontaneously to present the fullest range of experience.
Lyme Disease UK	7	143	As there is no test that can rule out an active Lyme disease infection, the term ‘post- infectious Lyme disease’ should not be used, especially when there is evidence that the infection can persist. This study states, ‘extensive evidence now shows that persistent symptoms of Lyme disease are due to chronic infection with the Lyme spirochete in conjunction with other tick-borne coinfections’ (Stricker and Johnson, 2011). It would be more effective to review evidence and consider alternative terminology for ongoing symptoms consistent with Lyme disease. References: 1. List of 700 Articles Citing Chronic Infection Associated with Tick-Borne Disease Compiled By Dr Robert Bransfield http://www.ilads.org/ilads_news/2015/list-of-700-articles- citing-chronic-infection-associated-with-tick-borne-disease-compiled-by-dr-robert- bransfield/ 2. Stricker, R.B, Johnson. L. Lyme disease: the next decade. Stricker, R.B, Johnson, Infect Drug Resist. 2011; 4: 1–9. doi: 10.2147/IDR.S15653 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3108755/	Thank you for your comment. We have deleted this phrase.
Lyme Disease UK	7	146	The evidence on how to define relapse should be reviewed as the ILADS guidelines state: ‘given that prior B. burgdorferi infections do not provide durable immunoprotection, clinicians should consider the possibility that the patient was re-infected and seek information to confirm or dispel that this occurred. In the absence of clear evidence of re- infection, clinicians and patients will need to consider the relative risks and benefits of assuming that relapsing symptoms such as EM lesions or flu-like symptoms in the summer are indicative of ongoing infection and not re-infection’ (Cameron et al, 2014). References: 1. Cameron DJ, Johnson LB, Maloney EL. Evidence assessments and guideline recommendations in Lyme disease: the clinical management of known tick bites, erythema migrans rashes and persistent disease. Expert Rev Anti Infect Ther. 2014 Sep;12(9):1103- 35. doi: 10.1586/14787210.2014.940900 http://www.tandfonline.com/doi/full/10.1586/14787210.2014.940900	Thank you for your comment. The definition of relapse has not been prioritised as an area for a review question; however, management of Lyme disease in people who have Lyme disease refractory to treatment will be addressed. The Guideline Committee will discuss and agree the exact protocol for this review question based on the scope.
Lyme Disease UK	7	148	The statement ‘early treatment is almost always successful’ requires an evidence review. This is not reflective of the overwhelming number of people in the patient community who report ongoing health problems despite standard treatment for Lyme disease. Follow ups often do not occur, especially if patients move on to seek private Lyme disease treatment after feeling let down by the NHS, as is often the case based on anecdotal evidence from patients. The ILADS guidelines observe that ‘the optimum duration of post-treatment observation for EM has not been determined, in part, because while disease relapse is known to occur, the duration of the latent period is variable and can be prolonged’ (Cameron et al, 2014). This study shows that following early treatment, 63% patients treated for Lyme disease still had symptoms which were then attributed to ‘post-treatment Lyme disease symptoms (PTLDS)’ (Adrion et al, 2015). In our opinion, this does not reflect ‘successful’ treatment. Furthermore, ‘clinicians have no diagnostic tests to check for the persistence of live borreliae. B. burgdorferi, having a complex genetic structure, is a highly adaptable organism capable of evading immune response’ (Perronne, 2014). The ILADS guidelines also state that ‘the harms associated with restricting treatment of an EM rash to 20 or fewer days of oral azithromycin, cefuroxime, doxycycline and phenoxymethylpenicillin/amoxicillin outweigh the benefits. In assessing the risk–benefit profile, the panel determined that the failure rates for antibiotic treatment of 20 or fewer days were unacceptably high and that for those who failed treatment, the magnitude of the potential harm created by delaying definitive treatment, which includes the increased risk of developing a chronic and more difficult to treat form of the disease, was too great’ (Cameron et al, 2014). References: 1. Cameron DJ, Johnson LB, Maloney EL. Evidence assessments and guideline recommendations in Lyme disease: the clinical management of known tick bites, erythema migrans rashes and persistent disease. Expert Rev Anti Infect Ther. 2014 Sep;12(9):1103- 35. doi: 10.1586/14787210.2014.940900 http://www.tandfonline.com/doi/full/10.1586/14787210.2014.940900 2. Adrion, ER, Aucott, J, Lemke, KW and Weiner, JP. Health care costs, utilization and patterns of care following Lyme disease. PLoS One. 2015 Feb 4;10(2):e0116767. doi: 10.1371/journal.pone.0116767. eCollection 2015 http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0116767 3. Perronne C (2014) Lyme and associated tick-borne diseases: global challenges in the context of a public health threat. Front. Cell. Infect. Microbiol. 4:74. doi: 10.3389/fcimb.2014.00074 http://journal.frontiersin.org/article/10.3389/fcimb.2014.00074/full	Thank you for your comment. The topic of early treatment will be addressed by an evidence review as outlined in section 1.5
Lyme Disease UK