Reaction to bacterial and possibly modified dietary proteins

Roadback

It appears that everything I seem to find about arthritis at the moment is talking about gut bacteria and immune response based on different types.

In the press last year was a big splash about high levels of Prevotella (a gut / oral bacteria) being detected in early RA - then I realised there was also decades of research on gingivitis bacteria - and a few other bacteria that mostly live in harmony and might not be expected to cause autoimmune disease.

Question - Has anyone here ever been referred for antibiotics for their arthritis? It is something I might consider myself - as my guts are definitely not right most of the time. But I am really confused because they say it is used for mild to medium disease - but then they also use it (apparently with some success) in refractory arthritis when other drugs have failed?

It seems as though the current researchers are pretty much saying what some were saying 70 or more years ago and that low-level infections may have a big role in autoimmune disease.

Here are a few medical papers that I found this evening for anyone interested -

From 2013 - Rheumatoid arthritis is an autoimmune disease caused by periodontal pathogens

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3668087/

From 2014 - Antibiotics for the treatment of rheumatoid arthritis

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3883615/

The conclusion on this one states -

"Conclusion - The studies with various antibiotics confirm the efficacy of these drugs in the treatment of RA. Therefore, it is possible that the pathogen that causes RA is a microorganism (most likely periodontopathic bacteria)"

Then from 2015 - the most interesting one I found was this one about the origin of Citrullinated Proteins -

http://www.ncbi.nlm.nih.gov/pubmed/25892475

It says - 'countless environmental factors, including microbes and diet, may trigger the generation of ACPAs that then cross-react with various citrullinated human autoantigens through molecular mimicry to induce RA'

Others that are worth googling too -

1995 - Minocycline was safe and effective for patients with mild to moderate rheumatoid arthritis

2003 - Evidence that patients with rheumatoid arthritis have asymptomatic UTI [infection]

2009 - Distinct bacterial colonization patterns of Escherichia coli subtypes associate with rheumatoid factor status in early inflammatory arthritis

There are 100s - and interestingly one from 100 years ago where a dentist noticed that treatment of periodontal gum disease vastly reduces arthritis symptoms in one of his patients.

I'd be really interested to have other opinions - especially if there is anyone medically trained that can tell me why they don't use this treatment more often.

dreamdaisy

This has cropped up on here before. When I first joined there was a lady who was being treated with antibiotics for her auto-immune arthritis but I can't remember if she was UK-based or hailed from the USA (where I believe this is an accepted treatment).

You say 'refractory' arthritis - was that meant to be reactive (predicitive text striking again?) If so then the use of anti-bios is logical because that form results as an infection and can clear completely. DD

Roadback

Hi DD

No it's not a typo this time

It appears that antibiotics can be used as a last resort when lots of other drugs fail - they call this 'refractory'

1998 - An evaluation of efficacy of minocycline as an anti-rheumatic drug in patients with active and refractory rheumatoid arthritis

http://www.ncbi.nlm.nih.gov/pubmed/10047718

It says in conclusion....

The present study indicates that minocycline may be an effective DMARD with highly safe performance for patients with active and refractory RA. This is the first demonstration of the benefit of minocycline in the Japanese patients.

But I have also read recent stuff that says that antibiotics are effective in early RA / AS / PsA too.

So covering all these medical studies we have early, active (with moderate severity) and difficult to treat RA all being favorably treated with antibiotics.

You mentioned Reactive arthritis - my AS is heavily related to reactive arthritis - and gut inflammation drives most of my joint pain.

I found this a few weeks ago which relates to you point about 'clearing completely'.... regarding Rheumatoid Factor..

'Two classical clinical diseases associated with high titer RF (rheumatoid factor) are subacute endocarditis and RA. In subacute bacterial endocarditis the culprit is frequently a Streptococcus. Once the offending agent is removed (Streptococcus) with successful antibiotic therapy, the RF disappears'

It annoys me a bit to see medical papers from say 30 years ago saying - more studies are required - then you see more studies are there in the medical literature - then more then more - yet the status quo of drug treatments stays the same.

It seems though the 'infection theory' stays as a mute point - I would question who's interests are served by not using low dose antibiotics more widely for some forms of arthritis. They must surely be much cheaper (I think Minocyline is even out of patent) - and might have less side effects than some other drugs.

My non-medically trained opinion (having tried hard to understand these papers) is that antibiotics might not just be about infection - but especially with the gingivitis / gum bacteria association that they are modifying the disease process - by stopping new cittrulination of proteins.

They'll probably recycle / repackage antibiotics as a re-purposed drug and due to NEW research patent the treatment and charge the NHS a small fortune as a new treatment.

I noticed earlier how many post you have made on this forum... WOW!

stickywicket

Try this from ARUK:

http://tinyurl.com/ne67624

In particular re minocycline

I think it is fair to say that the effect of minocycline is not usually very marked, in comparison to methotrexate for example. No other antibiotics have been found to have such a definite clinical benefit as far as I know. It is also worth noting that minocycline and related drugs can also cause a lupus-like syndrome – I have seen several cases in my practice. The good news is that it usually resolves when the drug is stopped.

Sorry to be so brief but got to cook

trepolpen

sticky , they been claiming this since early 1950s & if there was a magic cure think we would know about it , I asked my consultant about it & he said dont you think we would use minocycline/antibiotics if it worked

Sulphasalazine is a mixture & antibiotic & anti inflamatory drug but is not so effective as methotrexate let alone the new biologics ,

those of us with RA for 20 years will remember seeing people with severe deformities because of RA but you go to hospital now & things have changed for the better

dreamdaisy

Hello again, Roadback, many thanks for clearing that up for me, I defiantly didn't know that! I don't have RA but know of some women whose RA began after childbirth: this would hint that hormones too have a role to play but surely only for females. As for those with PsA, AS, reactive etc. well, who knows? The human body is weird and wonderful but, in our cases, mostly weird.

I enjoy watching QI and in one series they had a 'bonus card', namely the 'Nobody Knows' offering. I suspect that auto-immune arthritis and its various triggers may come under that heading: to my way of thinking it all depends on gender, genes and chance. For me the gender and genes were a done deal but luckily, thanks to embryonic medical knowledge, I chose to avoid the chance element. DD

Roadback

Hi Sticky

Thank-you for the link to the article from one of the medical contributors (Dr Philip Helliwell) to AR in 2012 - Hope you don't mind me commenting.

He hints at citrullination in his article but doesn't elaborate as he keeps it in layman's terms - he says

'Minocycline, in particular, has beneficial effects on both the enzymes that can cause damage to joint tissues and the cells that cause inflammation'

I think what is describing, in this short description is that Minocyline inhibits PAD1 enzyme produced by P. gingivalis bacteria stopping the creation of cittrulinated proteins - as described in RA here -

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3280043/

BTW - this paper above was cited by another paper in 2014

What I am wondering is how gingivitis bacteria get into the joints?

I just thought it was interesting from all these very recent studies from 2013,14 and 15 - I cannot believe that all these new researchers might be hanging on to some outdated belief from the 1950s and wasting their time.

Dr. Helliwell also mentioned that if there were enough signals then there would be medical trials - but there have been trials in the US - with at least 3 double blinded clinic trials - with this paper reviewing evidence from all trials up that date in the year 2000 -

http://www.ncbi.nlm.nih.gov/pubmed/10830256

'The third double-blind study enrolled only seropositive rheumatoid arthritis patients with early disease....later reported that about half of these patients were in or near remission after 3 years of follow up. No adverse effects were reported in this study.

This was also cited by papers in 2013 and 2014 by others doing related research.

I guess it's difficult for busy doctors to compare different therapies in short timescales and know about all the studies that have been done especially if treatments have different mode of operation.

How do bonafide studies and trials translate in to treatment anyway and become 'signals' - I guess the supply chain is different in the US because the medical insurers or private patient often pick up the bill?

As DD says - Perhaps nobody knows

dreamdaisy

I cheerfully admit that I hold very little interest in the whys and wherefors of my troubles: they're here and have to be dealt with because they won't be going away and life trundles on regardless. It is what it is and it will do what it will do, so get on with life, Daisy, as best you can because it's the only one you have. The ultimate cure will arrive in due course.

Research may well be lacking. Arthritis is not glamorous, it isn't life threatening (merely life ruining), research is expensive and maybe the drugs companies do not have that much interest in finding a 'cure' - think of the income they would lose. We also vary so much in what helps and what doesn't, one man's miracle med is another's poison, diet helps some but not others so we have to find out for ourselves what we can control and how to cope with what we cannot. It's a time-consuming condition, yes? DD

stickywicket

Of course I don't mind you commenting. That's one of the main values of this forum – exchanging information and views.

I admit, however, that, personally, I have no great interest in causes (My cause is already lost ) Maybe I should for my grandsons' sakes though, these auto-immune diseases having a genetic component, I tend to fear less for my adopted grandson.

I can't see that gum disease played any part in my RA as I've never had it. Nor can I see why it would affect very small children. Perhaps I'm being naïve but surely, if gum disease were a major factor, the onset of RA would be more prevalent in older people who are much more prone to it?

My only other observation is that, with resistance to antibiotics now reaching scary proportions, I'm rather glad my RA isn't dependent on them.

Roadback

Hi Sticky

I don't think it is about having gum-disease - it is about having enough of the bacteria to undertake the citrulination process (enzyme activity against other proteins) - you certainly don't have to have gum disease.

The bacterial proteins that get citrullinated - do not need to be at infection levels either - but once they are citrullinated and get in to the blood stream they are a burden to the immune system - this is because some of these 'modified' proteins are hard for the immune system to differentiate from self (to be a bit technical - it is all about similar amino acid sequences - which is where genetics comes in if we have tissues that carry those similar sequences).

From what I have read once there are high levels of citrullinated proteins and their associated antibodies the immune system can create antibodies that 'spread' to attack us

I read that with sero-positive RA they are suspicious that the priming bacteria from which the 'spread' occurs is e-coli which is present to a smaller or greater amount in all our guts. So that it why gut permeability is so key.

So in effect - It's all very similar to how Celiac disease works with it's priming antigen being gliadin protein in wheat gluten - which then gets modified by a very similar process to citrullination, called deamination - the enzyme that does this is TTG (Tissue Transglutanimase) causing antibodies to 'spread' to attack gut, brain (ataxia), skin (dermatitis herpitiformis) and sometime bones and cartilage too.