Antistreptolysin O around 300 for 1 year --- antibiotics warranted?

[Wonkmonk]

Interestingly, there seems to be pretty sound evidence that Herpes Simplex Virus (HSV) infection is associated with the occurrence of rash and skin reactions (erythema multiforme).

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3276871/

https://www.ncbi.nlm.nih.gov/pubmed/12639459

In an earlier post, @Gingergrrl speculated that that the rash I had in response to Ampicillin could have been caused by some kind of active EBV infection (which may also cause the CFS). Ampicillin exanthema has been specifically tied to active EBV infection and mononucleosis.

But I have fairly low titers against EBV (all sorts). But I do have super-high titers against Herpes Simplex Virus 1 (IgG ">1:20,000", IgM negative).

Maybe the Herpes Simplex is causing the rash and also the CFS. But I have seen no study so far that ties HSV-1 specifically to antibiotics-induced rash.

But next thing I'll probably do is try another course of Valacyclovir directed against HSV-1 plus some anti-HSV-1 supplements (L-Lysin, propolis) and a low-arginine diet.

 

[Wonkmonk]

I received the first penicillin injection a two hours ago. We planned to do some more days with benzylpenicillin before checking antibodies again next week.

I had no adverse reaction immediately, but just like with the last two ampicillin trials, it feels like it starts itching again. And this time the dose was less than 1/3 of what it was with ampicillin (600mg vs. 2000mg).

 

[Wonkmonk]

Case report of suspected Ampicillin-induced rash on a herpes zoster patient:

https://www.ncbi.nlm.nih.gov/pubmed/23163077

I have VZV titers >1:1000, too.

 

[Wonkmonk]

Herpes viruses generally seem to play a role in many cases of Drug-induced Hypersensitivity Syndrome (DIHS).

"...we describe how sequential reactivations of herpesviruses occur during the course of DiHS and discuss how the reactivation events could influence the initiation and maintenance of drug-specific immune responses, resulting in severe immunopathology."

https://www.sciencedirect.com/science/article/pii/S1027811713000803

The ampicillin rash may indeed be a sign of chronic herpes virus infection, as suggested by @Gingergrrl, but probably not EBV, but rather HSV-1 or VZV.

 

[Gingergrrl]

In an earlier post, @Gingergrrl speculated that that the rash I had in response to Ampicillin could have been caused by some kind of active EBV infection (which may also cause the CFS). Ampicillin exanthema has been specifically tied to active EBV infection and mononucleosis.

I had been curious b/c when I had severe mono from EBV (in 2012), and they were initially trying to determine if it was mono vs. strep, they said if I was given an antibiotic in the amoxicillin/penicillin class and it was indeed mono, it could cause a severe rash but it would be due to the EBV/Mono. However in my case, I actually AM allergic to this class of antibiotics so it was not given to me at all. I was put on the Z-Pack which did nothing and then two strep tests came back negative, and all the mono/EBV tests came back positive, and they had been negative all my life prior to that illness (and I'd somehow managed to avoid EBV exposure for 40 yrs)!

But I have fairly low titers against EBV (all sorts). But I do have super-high titers against Herpes Simplex Virus 1 (IgG ">1:20,000", IgM negative).

I did not realize that and I thought that you had high EBV titers like I did.

I had no adverse reaction immediately, but just like with the last two ampicillin trials, it feels like it starts itching again.

How is it going now and did you end up getting the rash? Is your ASO/ Streptozyme test still elevated?

The ampicillin rash may indeed be a sign of chronic herpes virus infection, as suggested by @Gingergrrl, but probably not EBV, but rather HSV-1 or VZV.

That is interesting and I had only heard of this rash as induced by amoxicillin if you have Mono/ EBV. I did not know it could be induced with HSV-1 or VZV (which I also tested IgM+ to for several years post Mono). I am thrilled if anything I said helped you to figure this out... although I suspect you figured it out on your own!

 

[Wonkmonk]

I did not realize that and I thought that you had high EBV titers like I did.

I actually never had high EBV titers. Even in 2009, when the disease was already slowly progressing,I had IgG 1:64 and EBNA in the 20s. During the entire last year, it was IgG 1:128 and EBNA 20-30.

The reason why I suspected EBV involvement was a positive EBV EA IgG, which Dr Lerner says is a sign of abortive infection. But that also was only 1:16 or 1:32, i.e. very low (negative is <1:16) on several occasions during the past year.

I am beginning to think that I was barking on the wrong tree the whole time.

How is it going now and did you end up getting the rash? Is your ASO/ Streptozyme test still elevated?

I will test ASO next week. The rash did not appear after over 6 infusions of 600mg Penicillin G so far. I think it is very likely to say that it was a specific viral interaction with the ampicillin that caused the rash.

It's probably safe to say that i'm not allergic to penicillin (#FamousLastWords).

I did not know it could be induced with HSV-1 or VZV (which I also tested IgM+ to for several years post Mono).

I have not seen evidence for this either, but I suspect it can, because all these herpes viruses involve skin conditions, like Mono, too which sometimes involves a rash even without ABs.

If my rash is not an allergic reaction, which it seems it isn't, it's at least a possibility that viral involvement plays a role.

EBV and HHV6 seem to be well under control. HSV and VZV have very high titers. All others are negative.

So it might well be triggered by HSV or VZV (or of course some other, non-diagnosed virus).

 

[Gingergrrl]

I actually never had high EBV titers. Even in 2009, when the disease was already slowly progressing,I had IgG 1:64 and EBNA in the 20s. During the entire last year, it was IgG 1:128 and EBNA 20-30.

I did not realize that and my EBV titers were insanely high (in the thousands) until they finally went negative and I shifted over into autoimmunity. I have not tested them in 2+ years but they would not be accurate anyway b/c of doing IVIG.

I will test ASO next week. The rash did not appear after over 6 infusions of 600mg Penicillin G so far. I think it is very likely to say that it was a specific viral interaction with the ampicillin that caused the rash.

That is great you did not get the rash and I am curious what your ASO titer will show.

It's probably safe to say that i'm not allergic to penicillin (#FamousLastWords).

Thank you and that made me LOL ... I will have to remember #FamousLastWords for other situations...

EBV and HHV6 seem to be well under control. HSV and VZV have very high titers. All others are negative. So it might well be triggered by HSV or VZV (or of course some other, non-diagnosed virus).

I was never at any point IgM+ for HHV-6 and my IgG was low. But I was IgM+ for HSV1 and VZV for several years (even though I have never had shingles and I had chicken pox only once at age 11). It was all very weird.

 

[Wonkmonk]

But I was IgM+ for HSV1 and VZV for several years (even though I have never had shingles and I had chicken pox only once at age 11).

It's funny, but in the past few days, it seems that adding 4 grams of L-Lysine and reducing arginine in my diet has a very positive effect on my symptoms. And that happened very fast, I felt it after a day.

It may (like so often) be a false positive again, but so far this is encouraging.

The Lysine-Arginine balance is strongly suspected to affect HSV-1 outbreaks. Several studies and a lot of experiences out there on the web that say so.

I am beginning to think that may problem might have been HSV-1 all along.

Anyway, will try ampicillin at lower dose tomorrow again. I have some spare bottles and don't want to throw them away.

 

[Wonkmonk]

Took a 2000mg/1000mg dose Ampicillin/Sulbactam this morning with no adverse effects, no rash so far. Just a little itching of the skin for two hours, which went away.

I think the appearance of the rash is dose-dependent. Maybe I can tolerate 1-2 doses of ampicillin a day without the rash reappearing. If everything's OK, I'll try another dose this evening.

 

[Wonkmonk]

Latests lab test still shows antistreptolysin O elevated at 281 (normal <200).

There are some patients whose ASO titre never returns to normal after strep infection, without that being of concern, so it seems I am one of those patients.

Additionally, antideoxyribonuclease B and antistreptococcal hyaluronidase were checked, which indicate streptococcal infection. Both were not elevated (and pretty low in fact).

Chlamydia Pneumonia, which is hypothesized to play a role in some CFS patients was negative and Mycoplasma pneumonia was veeeery low at 10 (negative is <9), so I assume both are not an issue.

Oh, and I also tested negative for Toxoplasma gondii.

In total, I think I can now conclude that bacteria are not the cause of my CFS and also not why the antiviral treatment didn't work as I had hoped.

I still think the antibiotics have helped quite a bit, which I think was due to immune modulation/stimulation, which likely also created the rash. I think it was necessary trying the antibiotics in the face of the elevated ASO titer, in order to be sure bacteria are not the issue. If I hadn't done it an further treatments didn't work, I would also be wondering if this could all be because of the ASO. At least that's now settled.

Adverse effects were minimal, apart from the rash. The rash in my case is obviously a toxicity or - as I think - an interaction with some kind of ongoing viral infection that is probably the cause of the CFS. It is - in my case - not an allergy against Penicillins, because I was able to use benzylpenicillin and in the last few days even 12 more infusions of ampicillin/sulbactam at a lower daily dose without the rash reappearing.

Minor adverse effects were a discoloration of the tongue, which got better with chlorohexidine treatment and a temporary worsening of tinnitus during the erythromycin treatment.

But the lab test again showed a ridiculously high HSV-1 IgG titer at 1:32000, so that's what I am going to aim at next, probably using supplements and the Pridgen protocol.

 

[Gingergrrl]

But the lab test again showed a ridiculously high HSV-1 IgG titer at 1:32000, so that's what I am going to aim at next, probably using supplements and the Pridgen protocol.

Wow, that is a really high titer! Is your HSV IgM titer high, too? Good luck with your next course of treatment. Is the Pridgen Protocol Famvir and Celebrex (or am I totally confused)?!

 

[Wonkmonk]

I measured the HSV-1 IgG I think five times over the past year and it always came back 1:32000 or ">1:20000", so very high. The IgM was always negative. No PCR was done. I can't remember when I had a cold sore last time, I'd say it must have been 10 years ago, probably before the CFS. Very strange.

But there are indications, my CFS could indeed be because of HSV-1, first and foremost of course the ridiculously high titer over a long period of time, second I responded to Valacyclovir to some extent and Valacyclovirs traditional indication is against HSV-1 and third, for the past couple of days I am improving substantially on a low-arginine diet and Lysine supplementation which is recommended to suppress HSV-1 outbreaks.

Actually I can't say if I really improved because of the Lysine, because it could also be because of the antibiotics. There probably were no bacteria in the first place, but it still could have worked either because of immune stimulation or because of changes in the gut microbiome. But I think the Lysine really did help.

But against this background, the next logical step is to use the Pridgen Protocol which - I think at least - is Famvir + Celebrex plus a proton pump inhibitor for gastric protection (e.g. esomeprazol).

I will use Valtrex instead of Famvir because Famvir is four times as expensive in Germany, but the effect should be similar.

The goal of the Pridgen Protocol is to fight herpes simplex, actually in fibro patients. The famvir stops replication and the celebrex inhibits Cox-2 and is suspected to supress HSV-1 reactivation. Plus I found a third drug named Impavido which, according to studies, stops HSV-1 from entering cells.

So that would mean attacking the HSV-1 from multiple angles, first stopping it from entering the cells (Impavido), then inhibiting replication in the cell (Famvir/Valtrex) and finally suppressing reactivation (Celebrex).

So if HSV-1 is responsible, I should improve quickly and substantially with this mix of drugs. I will probably not start Impavido immediately, because it's not in the official protocol and see how I do with Valtrex and Celebrex and maybe add Impavido at a later stage.

At least that's the plan

 

[Intuition]

@Wonkmonk : just wondering, did you get any symptomatic imptovement at all from the antibiotics. My ASO titre has remained around 400 for the past 6 months, but antidnaseB was consistently negative.

 

[Wonkmonk]

I had some improvement, mainly from the ampicillin and not so much from the erythromycin, but I do not think it is because of the antibacterial effect.

Ampicillin is also an immunomodulator that stimulates leukocytes. I think that was responsible for the minor improvement I felt.

In retrospect, I do not think I had a bacterial problem, but there was no way to be sure, so I still think a few weeks ago it was the right decision to try.

 

[Wonkmonk]

There is something I should note in case someone who is considering a high-dose antibiotic treatment with a similarly unclear situation reads this.

I've had severe pollen allergy for 10 years, but it was only a short 4-6 week period in June (rye pollen). I was always allergy free for the entire year except in this few weeks.

After the antibiotics this year, I became allergic to Birch pollen starting in April and I also have hay fever now and it probably isn't rye because they don't start to appear until the end of May, so I am probably allergic to something now, too (perhaps some weed or grass pollen).

So this year, for the first time ever, I am continuously allergic since the start of April and I may have newly acquired at least two more pollen sensitivities. I don't think this is a coincidence.

It is of course impossible to know for sure, but it is reasonable to expect that this was the result of the high-dose antibiotics. In the patient information, it says the antibiotics should be used carefully in people with atopic allergies without further elaboration. So maybe that's the reason and you are at risk of picking up more allergies if you are already atopic and you do the antibiotics.

It may also have to do with the microbiome, since these are broad-spectrum antibiotics that probably destroyed much of it (I am taking probiotics to repair it now). Since the antibiotics, I've had a slight discoloration and yellow-whitish covering of my tongue, which indicates colonization with bad bacteria. This still hasn't gone away for 6 weeks since the end of the antibiotics course, so it indicates the microbiome has changed and that change doesn't seem to be easily reversible. I assume that what has happened with the tongue also happened in the gut, but of course I can't look into it.

I also believe that my tinnitus, which did not bother me so far, has worsened (ototoxicity is a known side effect of erythromycin), although this may well be a nocebo effect. But even if it's a nocebo effect, it didn't bother me before and it bothers me now. But I expect this problem to get better over time. The allergies are probably permanent.

So looking back, it was probably a mistake to try the antibiotics, but I stand by the decision to do it because it seemed like the only thing we could do at the time and after you tried something you always know better.

I am not advising anyone for or against trying it, but I just wanted to note that it seems like I paid a price for my trial and even though these antibiotics are considered very safe medicines, everyone should think carefully before doing it.

 

[Wonkmonk]

There seems to be some research that lends support to my interpretation:

https://www.news-medical.net/news/2004/05/27/1969.aspx

 

[used_to_race]

https://www.sciencedirect.com/science/article/pii/S0091674904001927

"Elevated ASO titers occur without streptococcal pharyngitis. Polyclonal activation of B-cells due to autoimmunity, drug allergy or viral infections, is a likely mechanism."

My ASO and AntiDNAse B are both negative, so I don't suspect strep infection, nor do I necessarily suspect B cell problems in my case. However, it could be that ASO titers can indicate B-cell mediated disease. Could this mean that someone with high ASO is more likely to respond to rituximab?

 

[Wonkmonk]

Viral infections...I suspect herpes simplex infection is causing my CFS. That could explain my the elevated ASO titers.

What cut-off value for ASO is your lab using?

 

[used_to_race]

Viral infections...I suspect herpes simplex infection is causing my CFS. That could explain my the elevated ASO titers.

What cut-off value for ASO is your lab using?

For my lab, the standard range is <= 200 IU/mL. My value is shown as < 50 IU/mL.

 

[Wonkmonk]

My value is shown as < 50 IU/mL.

Lucky you