Stakehold

Caudwell LymeCo	4	85- 94	4. Refractory Lyme disease, i.e. treated but infection persists, and symptoms continue to worsen or new ones appear - In this category, the billion dollar question is, For how long do you treat with antibiotics before deciding a patient is a refractory case? Patients who can afford it will often keep paying privately for prolonged antibiotic treatment for as long as they feel their symptoms are improving under that treatment. Taking a lot of antibiotics for months or years causes a lot of side effects, which should be telling doctors something important about how bad it really is to live with Lyme disease. The guidelines should try to find a reliable, objective way to find out if patients really have refractory Lyme disease or Lyme disease sequelae rather than simply assuming this is the case after a standard course of antibiotics. For a patient who has been very ill with Lyme disease for a long time to be told that they are not getting any more antibiotics, and that they are never going to get rid of their symptoms, is a devastating, life-changing experience, and one that should only happen on the basis of objective medical testing if at all possible. 5. Lyme disease sequelae, post bacteriologic cure i.e. organ damage remains as a result of past infection but symptoms are no longer getting worse - This is what some researchers mean when they use the eccentric phrase "Post treatment Lyme disease syndrome" which patients universally find infuriating. The patient experience is that their doctors usually tell them they fit this category after a short course of antibiotics (without objective evidence that this is the case) and refuse to listen when they say that their symptoms are actually still progressing and getting worse. 6. Definite tick bite - patient may or may not be infected with Borrelia. Secondly, cutting across these categories, there will be particular treatment considerations based on the patient's symptoms. These will include thyroid, cardiac, gastrointestinal and gall bladder symptoms, for example. A full list of such examples would be far too voluminous to complete here, but should form the focus of a thorough investigation by the committee. Thirdly, there will be some patients with special circumstances that need to be taken into consideration when planning antibiotic treatment, which may also cut across the categories above. These would include: 7. Pregnant women: some antibiotics cannot be used in this group but adequate treatment is essential to protect the fetus. 9. Children: I would recommend making a specific review of the evidence as regards appropriate antibiotic treatment in paediatric cases, and management of symptoms in the context of full-time education. As I understand it there will be three paediatricians on the guidelines committee and I presume their presence is required for this purpose? 10. Patients with additional tick-borne infections: overlooking other infections may result in treatment failure for Lyme disease, or a failure to resolve Lyme disease symptoms even if Lyme disease is cured. REASON Treating Lyme disease is not simply a question of finding out if the patient has been infected for more or less than 6 months and then deciding which antibiotics to prescribe and at what dosage. Six months is an arbitrarily chosen time period and has no relationship with disease progression. More importantly, the important factor to consider is symptoms. Example 1 Around 10% of patients with Lyme disease that persists for months or years develop hypothyroid or hyperthyroid conditions which require treatment with thyroid hormone replacement or thyroidectomy (SOURCE: Caudwell LymeCo survey of around 500 Lyme disease patients; our results were the same as the statistics published in some books about Lyme disease, and found by doctors who treat many Lyme patients). Some develop Hashimoto's disease whilst others have low thyroid activity without this condition. In Lyme disease patients with low T4, TSH is also typically low. This means that standard NHS screening tests of TSH will miss the Lyme patients with hypothyroidism because their TSH will normally scrape into the bottom end of the normal range. Example 2 Many Lyme disease patients develop persistent gastro-intestinal disturbances, either	Thank you for your response and detailed comments on our questions. We will bring the detail of your response to the Guideline Committee's attention. The information will be used to inform the Committee's decision making as they develop the review protocols that guide the searches for and review of the evidence for the questions outlined in the guideline scope. We acknowledge the very specific issues related to pregnant women and children. We will ensure that the needs of these groups (and the immunocompromised) are addressed as part of each of our evidence reviews. The recruitment of paediatricians to this group is to ensure that the protocols that are developed are meaningful for children and that the evidence is correctly interpreted and appropriate recommendations drafted for children. Further expertise can be co-opted if necessary to inform the guideline group. We will bring your comments on the issue of co-infection to the guideline committee’s attention to ensure that this issue is appropriately addressed as part of our evidence reviews or in our sections where we link the consideration of the evidence to the recommendations made as appropriate. We will not however address the specific management of any co-infection.
			diarrhoea or constipation or, most often, both in alternation. According to a Caudwell LymeCo patient survey, 26% of them (120 patients out of 464) were diagnosed with irritable bowel syndrome by NHS doctors. Patients who can afford private healthcare, on the other hand, are sometimes tested for small intestinal bacterial overgrowth. When these patients are treated with suitable doses of Xifaxan they can achieve dramatic improvements in their gastro-intestinal symptoms. This not only saves them from considerable pain and social embarrassment but also enables them to achieve a better level of nutrition. Example 3 Lyme carditis causes heart block (and sometimes other arrhythmias) and is the commonest cause of death from Lyme disease, according to the Centre for Disease Control in America. The CDC says this affects 1% of Lyme patients but, based on anecdotal evidence, I think in the UK it is far more common than this. Like all arrhythmias, this phenomenon is not continuous but occurs episodically. The patient experience in the UK is that patients go to A&E departments with symptoms of palpitations, chest pain and or breathlessness etc, and are sent away after an ECG, without adequate investigation, or follow up with Holter monitoring etc. Management of this life-threatening complication of Lyme disease should be overseen by a competent electrophysiologist. General observation: The medical profession already has a standard vocabulary that can describe each category of patient unambiguously. I think it would be much clearer to use this than terms like "early" or "late" coined exclusively for Lyme disease, especially as these terms lump several different scenarios into one. If we simply replace the term "Chronic Lyme disease" with "Late disease" we don't address this problem of imprecise thinking. For example, I have read some research papers talking about "chronic Lyme disease" which hadn't clarified if the researchers actually meant untreated active Lyme disease infection, refractory Lyme disease or Lyme disease sequelae. Trying out a treatment protocol on a group of patients selected at random from all these categories and then trying to draw general conclusions about the efficacy of that therapy is not going to produce meaningful results.	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.
Caudwell LymeCo	6	128	SUGGESTED AMENDMENT Remove proposed category definitions. Replace with the category definitions, based on conventional and unambiguous medical terminology, which I suggested in point 8. REASON As explained above, I believe this would be far more intuitive to clinicians than these arbitrarily chosen 'early' and 'late' groupings which may mislead practitioners not specialised in Lyme disease into assuming that they are based on an inherent progression of Lyme infection when in fact they are not.	Thank you for your comment. 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. The Lyme disease overview is intended as a framework for how the NICE pathway might look based on the scope. It will be updated to reflect the categorisation agreed by the guideline committee.
Caudwell LymeCo	6	131	SUGGESTED AMENDMENT Remove "tick-borne". REASON Lyme disease is transmitted not only by ticks but also congenitally and by blood transfusion. There is also preliminary evidence that Lyme disease may be transmitted sexually, through breastfeeding, by other biting insects and through eating unpasteurised dairy foods from infected cattle. It is no longer valid to define Lyme as a purely tick-borne disease when there is a considerable body of research casting doubt on this. EVIDENCE Congenital transmission: The published medical research papers documenting babies born infected with Lyme disease are far too numerous to list here. Transmission by blood transfusion: For example, J Infect Dis. 1990 Aug, "Borrelia Burgdorferi: survival in experimentally infected human blood processed for transfusion." Johnson SE1, Swaminathan B, Moore P, Broome CV, Parvin M.; Sexual transmission: A preliminary finding in humans which corresponds with previous findings in other mammals, "Culture and identification of Borrelia spirochetes in human vaginal and seminal secretions" Marianne J. Middelveen et al.	Thank you for your comment. In response to stakeholder comments we have added person-to-person transmission to the scope of this guideline.
Caudwell LymeCo	6	135	SUGGESTED AMENDMENT Delete "from a few days to one month" and replace with "of unknown length." REASON Assessing time from infection to becoming symptomatic is challenging because many people with Lyme disease have no idea when they were first infected. 90% of Lyme disease patients have no recollection of ever seeing a tick, for example, based on patient survey results and the assessment of a well known clinic in Germany. EVIDENCE There is no valid evidence that the maximum incubation period of Lyme disease is one month. In line 134 the document states that Lyme disease can be asymptomatic. This can indeed be the case for years before a patient develops symptoms.	Thank you for your comment. It is widely accepted that the incubation period ranges from a few days to about a month. However, the course of a disease is different for each individual and some people might experience a much longer incubation period. People who experience the onset of symptoms after more than one month from the time of infection will be included in the relevant reviews.
Caudwell LymeCo	6	136	SUGGESTED AMENDMENT Delete "approximately two thirds of people" and replace with "in approximately one third of people" or else "in some people" REASON This oft-quoted figure, based on surveys of patients in the USA, does not correspond with the observations of doctors who treat significant numbers of Lyme disease patients in Europe. EVIDENCE For example, the BCA clinic in Augsburg, which currently has 4,000 patients under its care and whose founder has treated over 10,000 patients, has on its patient records that one ONE third of patients manifest an EM at any time during the course of their illness.	Thank you for your comment. We have changed the wording in the scope to read: “ …..in some people this is followed by …..” to reflect the uncertainty about the true proportion of people. We note the study in Germany but have not used these figures as they do not relate to the population in England and Wales.
Caudwell LymeCo	7	138- 139	SUGGESTED AMENDMENT Delete "early symptoms are similar to those for flu" and replace with "doctors lack training in recognising the symptoms." REASON The claim that "early symptoms are similar to those for flu" is true only if you condense a few randomly chosen symptoms from the whole gamut of manifestations down to a brief list of keywords. Saying that Lyme symptoms are like flu does nothing to help GPs distinguish Lyme patients from the large number of flu cases they must see each year. The weirder symptoms of Lyme disease are the ones that make many a GP dismiss their Lyme patient as a hypochondriac, but these are the very symptoms that could be telling them they have a case of Lyme disease on their hands, if only they were better informed. There is also a significant proportion of patients who only have the "other" symptoms and not the "flu-like" ones at all. The kind of "slam-dunk" Lyme symptoms that should be in the list given to doctors include: "The soles of my feet feel burning hot" "I keep dropping things and bumping into things but I never used to be clumsy" "I get random itchiness which moves around my body" "I get headaches that hurt all the way down my neck and the pain instantly gets much worse at the back when I lie down" "I keep forgetting words, right in the middle of a sentence" EVIDENCE Based on anecdotal evidence, I think that when Lyme disease patients recognise the symptoms of Lyme in other people and suggest they get a blood test, their prediction accuracy rate is extremely high.	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.” Symptoms will be addressed by a review of the evidence (see section 2.1 and 2.2) and we hope to be able to make recommendations that will enable healthcare practitioners to be aware of the symptoms that may indicate Lyme disease.
Caudwell LymeCo	7	141	SUGGESTED AMENDMENT Delete "Lyme disease is frequently self-limiting and resolves spontaneously." REASON There is absolutely no evidence that Lyme disease is a self-limiting infection. EVIDENCE To prove that, you would have to prove seropositivity, not treat at all, and later prove a total absence of any symptoms after a long enough period of time to be certain the disease was not just in remission, but bacteriologically cured. Based on the patterns of remission and relapse which I have observed in patient support groups over the years, I would say five years would be the bare minimum "all-clear" period, but a more meaningful and reliable criterion would be that the patient had gone through a major insult to the immune system with no Lyme relapse. Such a research project has never been done and I think it never will be, because once you have proven seropositivity for Borrelia, how can you ethically deny the patient treatment?	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.
Caudwell LymeCo	7	143	SUGGESTED AMENDMENT Change "Post infectious Lyme disease" to "which may be Refractory Lyme disease or may be Lyme disease sequelae." REASON Symptoms do often persist after treatment but this may be for two separate reasons: the patient may have Refractory Lyme disease, with persistent infection after the standard antibiotic treatment; or, the patient may have Lyme disease sequelae following bacteriologic cure. AN ADDITIONAL QUESTION The choice of the somewhat ambiguous term "Post-infectious Lyme disease" implies that, prior to being treated, Lyme disease in humans IS infectious. But infectious to whom? To other people? To ticks?