I conducted a research project - enrolling from 2001-2006 a total of 50 danish / nordic patients who themselves suspected to suffer from chronic Borrelia infection, who also displayed symptoms / signs I found to be compatible with chronic Borreliosis / "post-Lyme syndrome", who also came out positive on specific immune stain on EDTA fullblood sample for Borrelia burgdorferi by using the RIBb test, that was developed and World- and US-Patented by Whitaker and al. in 2005 i.e. I followed the patients with by POSITIVE SPECIFIC BORRELIA ANTIGEN TEST verified chronic (symptomatic >5 months) Borrelia burgdorferi infection.
For evaluation of their symptoms / log the course long time, I had developed and asked patients to keep track of all their symptoms by using a symptom-diary in Excel, which made it possible for me to follow course of untreated as well as treated patients, and document by visual analog scale how symptomatic / debilitated these patients are, and not the least could log the response to trial treatment, no matter which treatment was tried by the patient (conventional antibiotic, longterm/highdose antibiotic, alternative/supplementary immune supporting treatment), no matter who prescribed the trial treatment.
Unfortunately some project participants dropped out of the symptomdiary, when they tried alternative/supplementary treatment without antibiotics - thus I can not present any cases using such treatment yet - and some dropped out of the symptomdiary, when prescribed antibiotic treatment by other MDs than myself! - despite I told all of them how important it is to document treatment effect as well as side effects - since this is the only way we can get past the "no evidence" of what works and what does not work for chronic Borrelia infection!
But a few - especially those who were not offered any treatment elsewhere - had to comply to do the symptomdiary in order to get antibiotic treatment prescribed by me!
Two cases (#49 and #50) who had used the Excel symptomdiary and also came to me for repeated blood-microscopies during the course of different long-term antibiotic treatment (two regimes illustrated: doxycycline vs. a combination of metronidazole plus azithromycin) were presented at the LDA-UK - http://www.lymediseaseaction.org.uk - conference for Lyme borreliosis and other tickborne infections, held in Leicester 2007.
My PowerPoint can be found here.
The Excel symptomdiary was translated into English and made a FREE download from the guide. Thus since 2007 any chronically ill patient - with access to a personal computer and Microsoft Excel 2003+ (it seems OpenOffice Calc works well too!) - can download and use the symptomdiary for getting overview over a complex symptom pattern and become able to track the development over long time! - become able to document their disease severity and activity.
When we can easily spot on the curves which symptoms fluctuate together in which way, and which symptoms are constant, and it is possible to follow the day-to-day development of symptoms / side effects during and after course of trial treatment - no matter with what the patient is in treatment with, no matter who prescibe the treatment (at least 3 months after ending antibiotic to catch the earliest sign of early relapse of Borrelia infection!), we can calculate the individual and total symptom scores and % of change as a result of the tried intervention.
Special fluctuating patterns - like the Borrelia weekly/monthly cycle and Babesia 4-5 day cycle, Malaria 2-4 day cycle etc. - might give us a clue to which pathogen could be involved in causing the disease, i.e. might give us a clue which tests it will be reasonable to order!
The symptomdiary can be used not only by patients who suspect Borrelia infection, but by any patient with chronic illness, of course!
It soon became apparent to me that the pattern of symptom fluctuations is the very best clinical indicator of ACTIVE Borrelia infection, i.e. that active Borreliosis fluctuate in two patterns:
1. very active Borrelia infection, i.e. when the new growth is not under control by either the hosts immune-system or by antibiotic treatment => weekly flares at 8-10 (6-14) days or
2. flares come at monthly (3-5 weeks) interval, which indicate that new growth is suppressed / under control either spontaneously by the hosts immune system or by antibiotic treatment.
The observed patterns are very consistent with Brorsons observation, that young "cysts" of Borrelia burgdorferi will revert back to spirochete form in about 9 days, while older "cysts" will take about 4 weeks to revert into spirochete form again!
The weekly symptom relapse pattern is also consistent with old knowledge about fluctuations in "relapsing fever Borreliosis", so it seems that Lyme borreliosis is not very different from relapsing fever Borreliosis, clinically!
That Borreliosis symptoms fluctuate over time with monthly relapses is not a new observation either. Indeed, the monthly Borrelia relapse pattern during antibiotic treatment, was described by Dr. Burrascano already in the early 1990ies; he also found that monthly flares may continue for more than a year despite continuing the antibiotic treatment, and this finding was also confirmed by my study!
It is apparently mostly the spirochete form, when it wanders from the tissues into the blood, where it can be found by microscopy especially if this is done on day one of a new flare! - that probably elicit a fierce immune attack, that gives the chronic Borreliosis patients most of his/her symptoms, which are related to a raised pro-inflammatory cytokine response; both the symptoms of Borrelia flare and Jarisch-Herxheimer reaction is found related to an increase in tumor necrosis factor (TNF), when this can be measured; it has unfortunately NOT been possible for me to measure TNF and other cytokines, these tests are not routine measures in Denmark!
TNF has many actions, the main function is induction of programmed cell death (apoptosis) in damaged host cells, thus to regulate cell growth, remove old cells, before replacement with new cells.
In view of our knowledge about TNFs effect on the vascular endothel (vasculitis (perivascular lymphocytic inflammation), increased permeability (hemorrhages, oedema) and reduced blood flow, which - if extensive and prolonged - may eventually result in necrosis (death) of the affected tissues! - and in view of TNFs metabolic effect (insulin receptor blockade, created insulin resistance ... read more ... lead to lack of intracellular energy, when depot of glucose is used up and can not be quickly restored, both because the bloodflow is reduced and insulin receptor is blocked - the cell can not get new energy quickly enough, can readily explain the cardinal symptoms of chronic fatigue syndrome which are: quick exhaustion, very slow recovery! - thus most of the chronic / recurrent symptoms which chronic Borrelia patients or ME/CFS patients display, can readily be understood / the patophysiology of such symptoms can be explained by known changes in the biochemistry - thus the symptoms are NOT just "all in the head" of the patient, really!
In this new paradigm / perspective it also becomes easy to understand why the symptomatology is very similar between all kinds of CHRONIC INTRACELLULAR INFECTIONs, where the same type of CELLULAR immune responses are raised; in order to combat all the intracellular infections, the host immune system - mainly T-cells and cytokines like TNF - will attack and try to kill all the infected host cells (self / auto-immune attack); the host cell death must preferably occur at a time when the microbes inside are not mature and ready to infect new host cells; but when the kill-off does not succeed in eradicating all the microbes at once, when just a few microbes survives and continue the infection and continue to stimulate the pro-inflammatory response, chronic / relapsing illness becomes the result.
Many of the intracellular germs who have been found associated with chronic illness, protect the host cells they inhabit - thus themselves - against degradation by TNF, via activation of host NFkB; when NFkB is activated, the host cell become insensitive to TNF apoptosis induction!
It makes a lot of sense to me, that microbes have an advantage if/when the microbes rule and delay the point in time, where the host cell is being degraded so microbes are not released until they are mature and ready to go on attacking new host cells!
The NFkB activation can be counteracted by selenium and arsenic which inhibit degradation of inhibitor of NFkB; arsenic is a very old treatment remedy used about 100 years ago against chronic diseases / infections like syphilis! - however, such treatment is also very toxic in overdose. Selenium has been accepted as a necessary micro-nutrient, its neighbor in the period system, arsenic, has not!
Since antibiotics can only kill / suppress growth of active microbes, but rarely cure infection in the sense of eradicating all the microbes (dormant forms can not be hit by antibiotics until they go into growth again!) and because microbes may become resistant to antibiotics - we should study methods by which we can enhance host immune function; only a wellfunctioning immune system can prevent new growth / developing relapses, whenever hitherto dormant microbes later go into growth / action!
Also confirmed in my study was dr. Burrascano's finding that chronic Borreliosis patients - especially those who were ill for a longer time (> 3-4 months, i.e. late diagnosed Borrelia infection - often serum-antibody negative!) before treatment, and who chose to stop their antibiotic treatment, while they still displayed a weekly or monthly ongoing Borrelia flare-cycle, usually developed another recurrence/relapse of symptoms, that were reduced / or totally gone during beneficial antibiotic treatment; it takes 2-3 months after stopping the antibiotic treatment before symptom-status returns to the level it was before start of antibiotic treatment! - they usually responded well to re-treatment with same drugs again, but some had sign of other (immune depressing?) co-infections and had to change to other drugs, that could hit the other bugs also besides Borrelia! - indeed, whenever a Borrelia patient responds (s)lower to antibiotic that usually works for Borrelia, it is time to look meticulously for hitherto unrecognized co-infection(s)!
Regarding choice of treatment for tickborne infections, I must refer you to read
dr. Burrascano's guidelines (look it up at ILADS website), since he is much more experienced in treating these infections than I am; because many drugs are not registered in Denmark or are not offered for sale in drug-stores, but are only accessible in hospital, like IV antibiotics, I have not had access to try/use more than but very few of the drugs that dr. Burrascano describe may work well against Borrelia and other tickborne infections! - besides I conducted a TEST / SYMPTOM CORRELATION OBSERVATIONAL STUDY, it was not a treatment study, however, effects of treatment were registrered by those who got treatment and logged it all in their symptomdiary!
So the symptomdiary made it possible to DOCUMENT EVERYTHING in a way that is not easy to dismiss as "it is all in your head"! - made it possible to get quick overview over complex symptoms, severity, follow longterm course of any chronic illness / treatment result - exactly because every symptom is scored prospectively on a visual analog scale, and curves are automatically drawn over every symptom, plus summary curves per organ-system, and a total symptom log curve compared to logged trial treatment!
If you are a physician - FEEL FREE to tell all your chronically ill patients to use the symptomdiary to track their symptoms for a while, so this can help you get a clue to what could be cause of the often very complex symptomatology!
If you are a patient with chronic illness and no certain diagnosis or you just feel the need to follow your course longterm and document your disease severity and activity and/or treatment results - FEEL FREE TO USE THE SYMPTOMDIARY!
It is my experience that patients who do the symptomdiary and are able to document the symptoms / course longterm, have a better chance their illness is taken seriously by the physician, and is less likely to be dismissed with "it imust all be in your head" - meaning psychiatric: psychosomatic / hypochondriac - because "you look so healthy today and all your routine tests came out normal!"
The calculations and charts will show the individual and total symptom scores and % of change over time, that might be a result of a trial intervention?
=> chronic / persistent / recurrent symptoms are clear indication for a thorough diagnostic work-up, and may also give indication for trial treatment, especially if the tentative diagnosis become supported by positive test results pointing to specific infection(s) AND when the patient has shown capability of keeping track of the course during treatment, so effect can be measured, the doctor feel safer to try if some treatment might have effect on your symptoms! - and BY LOGGING SYMPTOMS / COURSE YOU WILL MAKE IT POSSIBLE FOR OTHERS TO LEARN FROM YOUR PERSONAL EXPERIENCE!
Only patients who get a chance to try a treatment that is different from the usual recommendation, may show us if what they try works or not, if the symptoms are logged in the same way during at least a month before (longer may be needed to demonstrate chronic recurrencies at monthly cycle!), during course of treatment and a while after treatment (at least 3 months), so data/status before and after trial treatment can be compared! - I urge all patients who are allowed to try non-conventional treatment to do their trial treatment in a way so it become possible for others to learn from that experience - we can't learn from / doctors don't believe in mere "hear-say"! - and we need to collect experience from at lot of patients, trying different treatments - because drawing lots between treatment / placebo (no treatment) can not be ethically defended when the patient has a debilitating and potentially very damaging / potentially fatal infection, supported by positive antigen test - besides patients have so many differences in age, duration of illness, number and combination of co-infections (that is hard to find!) and inborn differences in metabolism / genetic susceptibilities etc. - that a huge amount of patients would be needed for stratification / statistical calculation, that is is not possible for a single MD seeing / treating a few patients per year to conduct - and because such a study would cost a lot of money (millions), large "scientifically correct" studies are not very likely to be supported, especially not in times of economic regression!
If you need my evaluation of your diary, I'll be happy to do so (as long as I'm capable), but then you must also write down your full history in chronological order and tell me results of all tests done on you, so I get the full picture for evaluation and may give you personal advice on your case.
However, I can not offer you my evaluation / advice for free!
All the danes / nordic patients, who want my evaluation/advice, must join and pay a yearly fee - currently 200 DKr. per year - to the danish patient society - DanInfekt - where they get access to more information and a support forum in danish/nordic language; this is not usefull for non-nordic patients, so instead I suggest donating at least 50 Euro (or more if you can spare the money and you feel helped by my work/advice!) to DanInfekt's "research account", NOT TO ME PERSONALLY! - this is because we need to raise a lot of money for funding further research in chronic illness due to infections!
On the DanInfekt webpage KONTINGENT, you'll find information on IBAN/SWIFT account [IBAN nr. DK9430003330402504, SWift DABADKKK] you will need for money transfer via your bank; you must also pay for the money transfer of course. Please remember to write full name, address and "MK evaluation/research account" as a note - to ensure that the amount paid become registered correctly by the society!
NOTE also, that when you ask me for evaluation of your symptomdiary / case in my function as DanInfekt's medical advisor, you permit me / DanInfekt to save and use your data / history, in anonymous form of course!
Finally, it is my hope that the Excel diary will in future be exchanged by an online MySql database register, so patients can log into their personal account online and fill in their symptom scores via any computer connected to Internet, i.e. patients no longer will need to have a personal computer at home to edit and store their Excel diary, and will no longer need to buy the Microsoft Excel program, for using the symptomdiary!
To fulfill this idea, I'll need help from a programmer that is much more skilled than I am, in programming the extraction of MySql data, calculate statistics and draw curves both per individual patient/symptoms, and calculate summaries for all patients - tendency curves. I have no money to pay a programmer for the programming - it must be voluntary free work! - if you are interested - perhaps a chronic Borreliosis sufferer yourself? - skilled in programming MySql, Php (?) and think you can help, please write me by using the [Contact Webmaster] form.
Marie Kroun, MD
Founder and webmaster of LymeRICK.