Re: What causes Jarisch-Herxheimer reactions ?

May 29, 2006

Sorry youve had such wavy results with abx. Youre smart to be

sceptical of the herx concepts out there; theres no shortage of herx

BS.

The the spectrum of concievable models for your experience is pretty

broad and I guess many of those models are not very evaluable. Hence

I would consider going empirical - reading a (whole) lot of patient

reports and seeing how many report long-term imrpovement (or lack

thereof) after sustained dis-improvement in early months.

> Here are some points made in the article which seem significant to

me :

>

> · JH-R is a passing worsening of symptoms after an adequate

> dose of an appropriate antibiotic. It consists of a sudden rise

followed

> by a gradual fall in body temperature, a transient increase

followed by

> a more profound drop in blood pressure and worsening of

constitutional

> symptoms (can be life-threatening).

> If there is no drop in blood pressure, can it still be JRH ?

These may be the classic observations in syphilis and sepsis, but to

me it seems very reasonable that inflammation due to antigen release

caused by abx might not necessarily conform to this.

For one thing, reactions that dont change the above-listed

objectively measurable values dont attract much scientific attention

in the first place, because they cant be studied rigorously. For

another, chronic idiopathic diseases have many interesting

differences from syphilis and sepsis and the disease pathways may be

different, hence it might make sense that the herx would be a lil

different.

> And my questions :

>

> If the cytokine-storm explanation is correct, can it explain why

someone

> would experience severe symptoms for months on end to antibiotics ?

Whether its endotoxin (LPS) or instead specific protein antigens

that are at work, it seems like if one is herxing the pool of

antigen has got to be progressively depleted. Something should

change. However, its perhaps possible that there could be a very

slow cleanup of killed organisms - say, because they are inside

cells. Thus one might have a sustained increase in activation of the

TLR, lectin, and TCR receptors that bind bacterial molecules and

cause inflammation.

I dont have any strong support for that model (but see below a

phenomenon that may bear on this, or not). Its just a hypothesis.

Empirically, I believe at least a few successful abx users have

reported fairly long periods of initial exacerbation. But I havent

paid much attention to this, not having had that problem myself. (My

problem was that I never herxed at all, and many claim, mistakenly

IMO, that this predicts poor treatment response.)

Lots of patient reports can be read at places like lymenet, cpnhelp,

roadback, rheumatic.org, etc. Unfortunately alot of people have

highly speculative theories about their experience which probably

impair the quality of their observation/reporting.

> What about claims that JHR is caused by toxins released by dying

> organisms? This seems like one of those explanations which we can

> readily visualize, those masses of dying organisms causing a

temporary

> flare, while en route we are getting well. Very seductive

reasoning but

> is it accurate?

Well... maybe no one has proved it, but it makes molecular sense. It

does make sense that drug-killed organisms are going to be broken

down fairly rapidly, liberating their molecules. This may be the

weak point. In leprosy, dead organisms are very resiliant. After 99%

of the organisms are killed, it takes a YEAR for the count of dead

cells to go down ten-fold in lepromatous leprosy. This is probably

why lesions sometimes dont heal until after the (quite long) therapy

is already over. It must be because they are intracellular and/or

because they have a robust architecture and/or because of the

mysterious immunologic abnormalities of the disease. In contrast, in

syphilis I think it may have been shown that penicillin treatment

causes rapid increase in phagocytosis of organisms. I may be

remembering wrong; its been a while since I read that one. Anyway,

the primary and secondary lesions of syphilis heal rather rapidly

with treatment, I believe, suggesting a rapid breakdown of the

organism and subsequent rapid resolution of inflammation. For

intracellular organisms breakdown might be less rapid.

As for the rest of the logical chain, its pretty solid - we know

that injecting mice with LPS or with protein antigens they are

immune to, will cause nasty symptoms. We know the receptors that

recognize those molecules, we know those receptors release

inflammatory cytokines upon activation, and we know that those

cytokines cause symptoms (treating hepatitis patients with injected

cytokines causes a CFS phenotype as a side effect, for example).

May 29, 2006

Oops, I misread and thought youd explicitly said that you personally

had had a multi-month " perma-herx. " I guess you didnt necessarily

imply that. Just wanted to clarify that in case of confusion.

> Sorry youve had such wavy results with abx. Youre smart to be

> sceptical of the herx concepts out there; theres no shortage of herx

> BS.

>

> The the spectrum of concievable models for your experience is pretty

> broad and I guess many of those models are not very evaluable. Hence

> I would consider going empirical - reading a (whole) lot of patient

> reports and seeing how many report long-term imrpovement (or lack

> thereof) after sustained dis-improvement in early months.

May 29, 2006

Thanks for your response, . Yes, that is in fact what I meant to say. For almost 3 months, frequent days with either drops or consistently low bp, bad malaise, etc. I would back off on the minocycline for awhile, which sometimes helped, sometimes worsened my case. Finally stopped as I realised that what was most important was knowing what infections I would be fighting (thanks in particular to Penny's very strong arguments about testing here and on other lists) .

Have stopped the abx for over a month now (while waiting for further testing) and during recent worsening of my symptoms, I noticed also that my bp would be in the lowish range (95/65 or thereabouts) during those days. This would be consistent with the "cytokine storm" explanation for JH . I am curious to know if drops in bp or low bp are present with others who go through these types of reactions with infections, on abx or not.

I just don't know if I have enough "gumph" in me to be trying treatments that make me worse and there is just so much wishful thinking that I can allow myself to believe.

Carole

-- In infections , " " <usenethod@...> wrote:> Oops, I misread and thought youd explicitly said that you personally had had a multi-month >"perma-herx." I guess you didnt necessarily imply that. Just wanted to clarify that in case of >confusion. > > Sorry youve had such wavy results with abx. Youre smart to be sceptical of the herx concepts >out there; theres no shortage of herx BS.

May 29, 2006

> I am curious to know if drops in bp or low bp are present with

> others who go through these types of reactions with infections, on

abx

> or not.

I dont know whats considered low, but in '04 I hit 85/55, and I think

85/45, on my US$40 home meter several times. Thats low. Other times it

was pretty normal. I was on nothing but antidepressants that summer. I

took my bp about 100 times before becoming satisfied that it didnt

correlate with whether I was totally agonized at the moment or not.

Neither did my oral temp (usually subnormal) or blood glucose yield a

correlation. (Except during one single hypoglycemic episode I had.)

I know someone else, Jelly, who also reported some very low figures

while taking benicar, possibly very high dose benicar. But I dont know

how her bp was without benicar, which is an anti-hypertensive agent. I

think she was alredy 90% recovered at that time.

My sympathies for your dilemma, which doesnt sound very fun. I'm

curious have you returned to baseline during your month off abx?

May 29, 2006

For about 2 weeks, had overall improvement and bp back up to around 110/75, which is way high for me (and usually correlates with feeling better!). Then this past week, more symptoms (low-grade fever, aches, weakness) accompanied by lower bp (lingers around 90-100/60-70).

BTW, I have been diagnosed with neurally mediated hypotension, with inconsistent tilt-table results and have had a couple of fainting spells.

Thanks for the sympathy, !

Carole

> I am curious to know if drops in bp or low bp are present with others who go through these types of reactions with infections, on abx or not." I dont know whats considered low, but in '04 I hit 85/55, and I think 85/45, on my US$40 home meter several times. " "My sympathies for your dilemma, which doesnt sound very fun. I'm curious have you returned to baseline during your month off abx?"

May 29, 2006

Hi Carol, low & high BP is a feature of CFS , I haven't a satisfactory explanation as to why the extremes, you would think we all should experience one or the other.My BP is on the high side. I am at the moment looking at the role of Potassium http://www.oralchelation.com/ingred/blank7.htm It may play a part.

Herx, is the most over used word in our world of Chronic infection , The principle of herxing is that ABx's mass kill our pathogens & the resulting toxins from dead microbes poison us ..not an allergic reaction but direct poisoning ..Now clearly that situation is self limiting . If we had an infectious load enough to fuel months /years of herxing then its questionable that we could function at all ,in fact we wouldn't survive such an insult .Feeling worse when taking antibiotics has many reasons Read wishful thinking for Herx effect ..IMO of course ..

-----Original Message-----From: infections [mailto:infections ]On Behalf Of carolesierpienSent: 29 May 2006 22:09infections Subject: [infections] Re: What causes Jarisch-Herxheimer reactions ?

Thanks for your response, . Yes, that is in fact what I meant to say. For almost 3 months, frequent days with either drops or consistently low bp, bad malaise, etc. I would back off on the minocycline for awhile, which sometimes helped, sometimes worsened my case. Finally stopped as I realised that what was most important was knowing what infections I would be fighting (thanks in particular to Penny's very strong arguments about testing here and on other lists) .

Have stopped the abx for over a month now (while waiting for further testing) and during recent worsening of my symptoms, I noticed also that my bp would be in the lowish range (95/65 or thereabouts) during those days. This would be consistent with the "cytokine storm" explanation for JH . I am curious to know if drops in bp or low bp are present with others who go through these types of reactions with infections, on abx or not.

I just don't know if I have enough "gumph" in me to be trying treatments that make me worse and there is just so much wishful thinking that I can allow myself to believe.

Carole

-- In infections , " " <usenethod@...> wrote:> Oops, I misread and thought youd explicitly said that you personally had had a multi-month >"perma-herx." I guess you didnt necessarily imply that. Just wanted to clarify that in case of >confusion. > > Sorry youve had such wavy results with abx. Youre smart to be sceptical of the herx concepts >out there; theres no shortage of herx BS.

May 30, 2006

My blood pressure was often in the 80/50s range prior to benicar and is often still in those ranges after benicar. No noticeable bp changes for me with different treatments. penny <usenethod@...> wrote: > I am curious to know if drops in bp or low bp are present with> others who go through these types of reactions with infections, on abx> or not.I dont know whats considered low, but in '04 I hit 85/55, and I think 85/45, on my US$40 home meter several times. Thats low. Other times it was pretty normal. I was on nothing but antidepressants that summer. I took my bp about 100 times before becoming satisfied that it didnt correlate with whether I was totally agonized at the moment or not. Neither did my oral temp

(usually subnormal) or blood glucose yield a correlation. (Except during one single hypoglycemic episode I had.)I know someone else, Jelly, who also reported some very low figures while taking benicar, possibly very high dose benicar. But I dont know how her bp was without benicar, which is an anti-hypertensive agent. I think she was alredy 90% recovered at that time.My sympathies for your dilemma, which doesnt sound very fun. I'm curious have you returned to baseline during your month off abx?

May 30, 2006

CArol

Were all interested in getting better. I can't see how foolish

people with foolish protocols think you can harm the body by

thrashing you to an inch of your life for a year and were supposed

not to suffer any residual damage.I explained myself clearly on the

herxheimer angle frequently on the unmentionable regime- I stated

that if you had a baseline red cell count after experienciung this

crappy BS you'd find your red blood cells damaged so your counts

would go down. The first person that looked found this to be exactly

true.The other spastic angle is that you harm your already fragile

circulation you can't have acid like substances constantly running

around your body it will take it's toll and possably start turning

you into a statue.The microcirculation suffers enough of a knock let

alone bring one on constantly to satisfy a mid last century theory-

if a scientist is talking molecular scientific stuff and throws out

a german spastics idea of what may be occuring as part of his

molecular science, that person better go back to the drawing board

IMO.

There's a rebound problem I find with quinolones- african kids that

suffered meningitis outbreaks have been left with some pretty

strange arthritic complaints at 12 years of age from this group of

drugs.I feel it kills a lot of bugs quickly but when the bugs pick

up the resistant traits they come back at you 100 miles per hour.

Also these drugs are very poor bone penetrators which makes those

tough deep down bugs a bad rebound to get.I just can't really see

where this group of drugs best fits in therapies but I wouldn't

trust them on there own- they are no penicillins.You'll also notice

Bleu had cipro and loved it, but he also did it alongside

clarithromyacin.

tony

>

> Hello,

>

> I am pretty new to the group, mostly a lurker as I have no real

> scientific knowledge or understanding that will help others (just a

> hungry mind!).

>

> I wanted to understand what causes Jarisch-Herxheimer reactions,

> especially since my doctor had been trying antibiotic treatments

to see

> if it will improve my CFS/ME condition (no active infection has

been

> found, but tests have not been as thorough as I would like). I

tried

> Cipro and saw improvement for a few weeks, then a slide back down

(along

> with many new joint aches!). Then came Minocylcine, which gave me

severe

> reactions after a few days, pronounced drops in blood pressure,

> increased malaise, weakness, etc. After 2 months of Mino, I

stopped as I

> await further testing.

>

> I searched the Web for scientific studies on JH and was amazed that

> little has really been published on its physiological causes or its

> process. I did find the following article published in 1992 in the

> Journal of Antimicrobial Chemotherapy by E. : " New

> insights into the pathophysiology of the Jarisch-Herxheimer

reaction " :

> http://jac.oxfordjournals.org/cgi/reprint/29/6/613

> <http://jac.oxfordjournals.org/cgi/reprint/29/6/613>

>

> Here are some points made in the article which seem significant to

me :

>

> · JH-R is a passing worsening of symptoms after an adequate

> dose of an appropriate antibiotic. It consists of a sudden rise

followed

> by a gradual fall in body temperature, a transient increase

followed by

> a more profound drop in blood pressure and worsening of

constitutional

> symptoms (can be life-threatening).

>

> · The mediators causing the reaction have not yet been

clearly

> identified.

>

> · In one study with syphilitic patients, JHR was noted in

the

> absence of endotoxins (which had been thought to mediate JHR) :

other

> arguments are also given against the endotoxin explanation.

>

> · Similarities are seen between JRH and the results of

> administering Tumor Necrosis Factor (TNF) to humans. The author

> hypothesises that it is the orchestrated release of cytokines that

cause

> the immune, physiologic and metabolic effects of infection.

>

> And my questions :

>

> If the cytokine-storm explanation is correct, can it explain why

someone

> would experience severe symptoms for months on end to antibiotics ?

>

> If there is no drop in blood pressure, can it still be JRH ?

>

> What about claims that JHR is caused by toxins released by dying

> organisms? This seems like one of those explanations which we can

> readily visualize, those masses of dying organisms causing a

temporary

> flare, while en route we are getting well. Very seductive

reasoning but

> is it accurate?

>

> Carole

>

May 30, 2006

Hi Tony,

I am glad you wrote this. I have also heard

the Lyme docs state that quinolones can be amazing. However, I would suspect

that the strange arthritic pains of the African children are NOT rebounding

infections, but the rather permanent damage from the quinolones. The

documentation of this reality is quite extensive now. I certainly am one small

example. The pain and damage is completely different from any symptom prior to

the quinolones.

I am now finding relief by taking massive

doses of magnesium taurinate, which Rich V recommended to me, and drinking

Recuperation. My hunch is those African kids are malnourished and their magnesium

levels are depleted by infection and poor diet. They would be sitting ducks for

tendon damage. What is really scary is that quinolones can cause permanent CNS

damage. Are we looking at a massive surge in mental illness with no clue where

it is coming from?

a