Autoimmune disease and PN, please explain
 

I am hoping somebody can explain HOW an autoimmune disease causes peripheral neuropathy?

I was recently diagnosed with rheumatoid arthritis by a positive rheumatoid factor and a positive anti-ccp. My ANA was negative and all other autoimmune tests were negative.

I have scoured the internet and this forum and I still do not understand how the two are connected? Is my immune system literally attacking my nerves? Is the inflammation causing the PN? What can I do about it or is there nothing that can be done? I am now taking methotrexate. Will treating the RA help the PN?

I feel so lost because I just don't understand what is happening to me and now my hands, in addition to my feet, are experiencing progressing PN. I don't understand my disease or what my future holds for me. I feel so hopeless.

Can somebody please explain?

Hi there,

So sorry you have had to join us as a result of your health problems. There are a few of us on here in the same situation. I have ankylosing spondylitis - an autoimmune rheumatic disease and more recently developed full body ( non length dependant) neuropathy. After so many appointments, it's still not entirely clear how this is happening and what the connection is. The inflammation from the RA could indeed be responsible but it may be a separate disease in its own right via a separate autoimmune mechanism. It's all so complicated. Controlling the RA may help but there's chance it won't. Often times a process is underway which may not be linked to the original autoimmune. I've spent two years trying to get a definitive answer on it but no neurologist or rheumatologist has been able to give me this.
Have you had the nerve tests? Emg, nerve conduction? Skin biopsy?
Have you tried steroids since this started?

autoimmune disease is when the body makes antibodies to an invader that has peptide sequences in its cell walls that resemble those of the antibodies. When the invader is gone, those antibodies for some reason linger and start attacking tissues of the host, and nerve tissue is often commonly attacked. In some people these antibodies do not shut off and the body continues to make them. It is thought that some autoimmune processes are inherited.

The vaccine for Lyme only caused attacks on hosts' joints, that carried certain markers on their white cells.

I used to have a very old cat..who had terrible arthritis...and our vet at the time told us that AUTOIMMUNE disease is
becoming epidemic in cats. (today our poor pets are vaccinated to death IMO) Pet vaccines were causing sarcomas in cats, so now they vaccinate in the leg...so if the sarcoma (cancer) occurs the vets can amputate the leg and save the cat. Some compassion? Think about that.

Infections can also trigger autoimmunity in those who have certain genetic markers making them at risk.

Historically rabies vaccines, have been the worst offenders, until that Lyme vaccine showed up. Even the newer rabies types have studies on PubMed about reactions. If you search
"rabies" on PN you will find the posters here over the years who have gone into detail about neurological reactions.

So today there is quite a bit of concern about too many vaccines. I am sure you could Google to find the process by which micro-organisms trigger autoimmunity, but the ones I have seen are very complex explanations and involve genetic data and terminology.

Adding a bit to what mrsD has explained:

Antibodies are made by blood cells called plasma cells which are produced from B lymphocytes (B cells). Each clone of B cells and plasma cells produces a unique kind of antibody.

Production of plasma cells needs help from a class of T lymphocytes called helper T cells. Helper T cells need to get activated before they can do their job. This happens when they recognise a complex of a peptide (a small part of a protein) bound to Class II MHC proteins on cells called antigen-presenting cells. There are many different kinds of Class II MHC proteins - everybody inherits a specific pattern of them from their parents.

Usually that peptide is derived from a protein made by a pathogen (virus, bacterium, etc). Most often clones of helper T cells get specifically activated by recognising a peptide:Class II MHC complex. They go on to activate specific clones of B cells with the same peptide:Class II MHC complex on their cell surfaces. The plasma cells derived from them secrete specific antibodies which lead to destruction of the pathogen which made the protein.

However, sometimes this goes wrong. A combination of pathogen peptide:Class II MHC protein might, in a chemical sense, "look like" a combination of normal body cell peptide:Class II MHC protein. The effect of this is that the immune system will damage the normal body cells which made that peptide, "thinking" that those cells are pathogens - this is an auto-immune disease.

Inheritance of a specific pattern of Class II MHC proteins is often a risk factor for specific auto-immune diseases. For example, inheritance of forms of a Class II MHC protein called HLA-DRB1 is a risk factor for RA. Presumably this is because complexes of pathogen peptide:HLA-DRB1 can "look like" complexes of joint tissue peptides and HLA-DRB1, leading to immune system damage of joint tissue.

I hope that this is not too complicated and makes sense.

Thank you for explaining. I was never very good at science or biology, so it's been a struggle trying to figure this out and wrap my mind around what is happening. I've never contemplated this side of me before. I guess until something goes wrong, you don't really question the process.

I just feel like I'm broken, or in the process of breaking apart, and nobody can do anything about it. I feel like every day I am just helplessly witnessing my own demise. Sometimes I reluctantly accept that and other times I have full breakdowns. I know it's all science and bodily chemistry, but sometimes I wonder what I did so wrong in life to end up here.

To answer you Joanna, I have an EMG coming up in August. I have not had a nerve biopsy done yet. I am more than certain at this point that I am dealing with a small fiber neuropathy, but my neurologist looked at me like I was an idiot when I said that. So I guess I will go through the EMG and hopefully at some point we can get to the nerve biopsy and the SFN can be confirmed. I am having an MRI on Wednesday to rule out MS, I assume. No steroids as of yet. So far just the anti-inflammatory and the methotrexate. I was expecting side effects from the mtx, but so far nothing. But joints still hurt like crazy but it's only been a few weeks of the meds.

I try really, really hard not to be a baby about it. I think about little children who are diagnosed with cancer and lose the fight. Sometimes when I want to cry about how unfair this feels, I am thankful that I least got to 30 relatively healthy and I enjoyed my twenties. If things have to fall apart now and I can't do anything about it, then I am glad to have enjoyed life to the extent that I have. This sounds somber and I apologize for that. More or less just realizing that what is happening is not going to go away and this is my life now. Out of all the pills and supplements I am taking, that reality is the hardest one to swallow.

Can anyone explain the relationship between autoimmunity and inflammation? I have SFN and "the antibody profile of a lupus patient" and am followed by a rheumie as well as neuro, but have no signs of inflammation in blood work, skin biopsy, or muscle biopsy. My CRP and sed rate are always at the low end of normal. Nothing but my ANA, anti-dsDna, and anti-Ro come up positive. Everything I read about autoimmune conditions seems to assume that there is inflammation.

Thanks for the explanation.
We have got some autoimmune disorders in our family, is it possible to test for the patterns of class II MHC ?


I hope your tests would point to a treatable cause.
The test for SFN is a skin biopsy and not a nerve biopsy.
And if your neurologist doesn’t take you seriously or doesn’t know enough about SFN maybe it would be better to search for a new neuro.
Only the 3rd neuro that I have met suggested SFN and referred me to the skin biopsy, which showed a severe damage. The other two, based on negative EMG, said I’ve got no neuro problems.
Don’t give up, it takes time to adjust to the new situation, find the right doctors, diagnosis and treatment.

Yes, it is possible - your health care team should be able to advise you about this.

However, please remember that different forms of Class II MHC proteins are just risk factors in the context of auto-immune diseases - they are not "genetic destiny". In my example above, some people with RA have not inherited the forms of HLA-DRB1 which are risk factors for it. Other people who have inherited those forms of HLA-DRB1 do not have RA.

Just to clarify a bit--
 

--people with autoimmune diseases can see the effects, especially nerve effects, from several separate mechanisms, each acting individually or in concert.

A specific chemical attack on tissue, as kiwi has been describing, obviously can cause nerve damage. The body erroneously attacks its own tissue through chemical mechanisms by misidentifying it as foreign, and this process can literally dissolve functional parts of nerve. Often this is referred to as a "molecular mimicry" process--in vulnerable people, a pathogen of other foreign body may kick things off in that the body will mount an immune response to the pathogen, but since this is, on the most fundamental level, based on molecular shape (the body produces antibodies that fit into parts of the cellular structure of the pathogen, like manufacturing a key for a specific type of "lock"), if any body tissue have a similar shape, the now-activated immune system attacks anything that looks like such a "lock" and an autoimmune process ensues.

But, in addition to this, autoimmune attack typically results in swelling and fluid accumulation at the sites where this is ongoing. That swelling in itself can cause compressive forces on nerve, and nerves do not function well when constricted. So damage may occur in this way, in addition to and/or independently of the chemical damage.

This has sometimes been referred to as a "double crush hypothesis" in medical literature, with the symptomolgic effect more than what one would expect from the sum of the parts.

A lot of good information here. Thank you! Last night was a rough one, as you can tell, but I stayed up most of the night researching autoimmune diseases and what I have come to find true is that once an autoimmune disease occurs, the body is 3 times more likely to develop another one. Hence several existing at once. Right?

That got me looking at materials about "healing" the immune system. Leaky gut, toxins, infections, gluten and grains. What are your thoughts on this? Can the immune system really be healed through diet, fixing the gut, ridding toxins, and resolving existing infections? I found a few approaches that were very against medications such as NSAIDS and immunosuppressants and seemed to be very adamant that one can ditch medication and turn their immune system around, essentially switching "off" the genes that caused the immune system to turn against the body.

Any thoughts on this?

The potential to develop an autoimmune disease is thought today to be inherited. So yes, it is always there for some people.

The leaky gut issue, is one way to develop one. There are spaces between the GI lining's cells called Zonulin channels.
It these are open, then large peptides (allergenic proteins) can leak into the blood and stimulate antibodies.

There was a study in 1999 that suggested NSAIDs block the Cox-2 protections in the GI tract that keep out peptides as well. So using drugs to block Cox-2 is thought to increase food allergies and intolerances. The study did not prove 100% but it was highly suggestive of the role of NSAIDs in promoting leaky gut.

The non medication suggestions however are not 100% effective either. There is not much in medicine that is 100% for trestments.

Thank you MrsD for all of your input. I do have one last question for you that I am hoping you can answer for me.

the PN in my hands is really weird, it isn't a numbness or loss of sensation so much, it happens randomly. Well, I used to think it was random but I have noticed lately that it happens after my hands get cold. My fingers turn almost white and then once they warm up, my fingers turn bright red and they hurt like hell. It's like a stinging, tingling, hyper sensitivity in my fingertips and my fingers burn. The uncomfortable sensations don't last too long, but it can linger a bit and have mini flare ups after.

It just happened after holding a glass of ice water and it happened yesterday after I went from my AC apartment into the humidity outside and it happened when I was out of town last week after I went swimming in a freezing cold lake.

Do you know much about this? Is this part of the PN too? :confused:

Did you have the test for cryoglobulins ?

Is that this one? Neutrophilic Cytoplasmic Ab IgG

If so, it was negative.

No
I'm too tired and brain fogged to write now, you can read about it here -
Cryoglobulinemia - Mayo Clinic

My skin is deathly white now but goes bright burning red when I warm up or go in a bath. Sfn damage can cause issues relating to erythromelalgia or that can cause Sfn. That mightn't be the case for you but the redness and burning pain with it could be something related to that. Sfn damage in itself will cause issues with blood flow in the skin so I think all sorts of issues can arise with it.
I spent months going down the restrictive diet route but for me it didn't halt anything. Alcohol and alot of sugar does however intensify the nerve pain. Cutting back on alcohol and sugar can only help.
Don't blame yourself. At the beginning of my problems I read every article going and still search many times a month now. The top listed articles on autoimmunity in all my searches were from persons flogging some book or diet. There was often the feeling that this was entirely in your control and if it doesn't work then it's because you just aren't trying hard enough. I now avoid those types of articles because I have no doubt there are often strong genetic tendencies towards these things. I know people who abuse themselves terribly and not a dicky wrong with them. Some of us are sadly more susceptible to whatever external factors may have triggered it. But like you I still often feel responsible, and wonder if crying too much brought it on!
I got through a few neuros, only the third for me knew what he was talking about. I pursued the skin biopsy myself after researching it.
I don't think the methotrexate would help the neuropathy but I asked my neurologist about having more than one drug and I understand methotrexate can be used with other disease modifying drugs like steroids. The key things to try for suspected autoimmune neuropathy would be intravenous steroids and ivig.
I'm only 36 so feel the same upset at what has unfolded at a relatively young age. Like you Im so grateful I had an eventful 20's! Still crap though.

That sounds like Raynaud's phenomenon. I've had that in the past and yes, it hurts like hell!

"Raynaud's disease signs and symptoms include:
Cold fingers or toes
Color changes in your skin in response to cold or stress
Numb, prickly feeling or stinging pain upon warming or stress relief
During an attack of Raynaud's, affected areas of your skin usually first turn white. Then, the affected areas often turn blue and feel cold and numb. As you warm and circulation improves, the affected areas may turn red, throb, tingle or swell. The order of the color changes isn't the same for everyone, and not everyone experiences all three colors." (mayoclinic.org)

Alessio Fasano, a gastroenterologist and leading expert on celiac and autoimmunity, has written a very accessible and short article on the subject. I can't find the entire article online, even though it's only a few pages long. Here is a link to the one I have in mind: Leaky gut and autoimmune diseases. - PubMed - NCBI. Think of it as a triangulation between genetic susceptibility, environmental triggers and the gut. As the abstract of the article states, "This new paradigm subverts traditional theories underlying the development of these diseases and suggests that these processes can be arrested if the interplay between genes and environmental triggers is prevented by re-establishing the zonulin-dependent intestinal barrier function."

What's interesting is that traditional medicine has thought this in one form or other for centuries going back to ancient China and Greece. Fasano's account is more detailed, nuanced and based on trials and conventional science, so it's a step forward. But what remains true is that intestinal permeability and zonulin deregulation are key to this terrible process.

I have SFN likely of autoimmune etiology, though still not certain, and I have had great results from healing my gut. Diet and supplementation aimed at healing my intestinal barrier, so leaky gut, has been the only thing helping me so far and allowing me to avoid meds entirely and to live relatively normal life, emphasis on 'relatively', since SFN takes a lot out of you. But perhaps in a few years time I'll be in a better place. Healing the damage I've done to my gut over many years will take many years itself.

Here's an article by him that I could locate: Zonulin, regulation of tight junctions, and autoimmune diseases

Good luck!

That is strange - do you have any non-immunological clinical signs of SLE?

My guess is that in some auto-immune diseases there may be tissue damage leading to release of nuclear antigens (Ro and the other ANA targets). These intra-nuclear antigens are not usually "seen" by the immune system so there will be production of antibodies specific for them.

If I am right all this says is that there has been some tissue damage - an elevated ANA titre confirms this and may be important in a diagnostic sense but does not say much about the underlying pathology of the auto-immune disease.

Hi David,

The links are really interesting reads, thank you. I'm always interested when the articles aren't trying to flog a book or diet.

No clinical signs other than PN. My rheumie can't say that I don't have lupus, but doesn't want to say that I do unless I develop skin or joint, etc symptoms. Thanks!

Great information. Thank you David and all.

Joanna, I know it's not fun for anybody to be suffering from any of these issues, but I feel a little less alone knowing somebody else relatively "young" is having similar issues.

I had an MRI this morning to rule out MS. It was my very first MRI and I am a very anxious person, so of course I had a full blown panic attack when they put me in the machine and I had to be taken out twice. My mouth, face, and even teeth were tingling and buzzing during my panic attack, before they ever turned on the machine. Sure made me think about how a stress reaction contributes to nerves. Anyway, I did eventually get back in that tube and I made it through the entire scan. Growing up at age 30! hahaha

Very interesting discussion with lots of useful links - thanks everyone.

Just to throw in my 2 cents worth - I've been looking recently for scientific research on possible links between MTHFR gene mutations and prevalence of autoimmune disease, (specifically Fibromyalgia and/or Addison's Disease). This may have some relevance to the discussion of genetic influence and disregulation of the immune system. I know MTHFR has been discussed on other threads here on NT, so the link below may already be known.

Association study between methylenetetrahydrofolate reductase gene polymorphisms and Graves' disease. - PubMed - NCBI

While it's only an abstract, and it specifically discusses Graves Disease, it does say: "Previous studies have provided evidence that a high prevalence of MTHFR gene polymorphisms is frequently detected in patients with autoimmune disease, suggesting a novel genetic association with autoimmune disorders." (Interestingly this study's conclusion is that in the case of Graves Disease - MTHFR actually provides a protective effect in women.)

I've only just started looking so will post any further sites I come across later. There's plenty of anecdotal supposition online, (of the flog the book, treatment or supplement type), but finding definitive information is more elusive.

Would appreciate if anyone else who comes across anything connected could post a link. Thanks

I can't find anything for Addison's Disease but this suggests an association between MTHFR and Fibromyalgia in a Turkish cohort Angiotensin converting enzyme and methylenetetrahydrofolate reductase gene variations in fibromyalgia syndrome. - PubMed - NCBI .

I'm chiming in late, but my basic Immune system uses biochemicals (probably cytokines, but not clear yet) to attack organs/systems of my body.

The first was my skin with severe eczema for the first 27 years of my life. And then it stopped.

Later it was my arteries, and the the inflammation caused Coronary Artery Disease.

Then my moisture glands were attacked, taking away my saliva and my tears.

Then my bladder was attacked, causing inflammation and bleeding of the lining (very painful).

And my hearing, with Meniere's and moderate deafness.

Then it was the nerves of my legs and feet, and now I have profound PN, atrophy of both legs, walk with braces ( and great difficulty)

The my lungs were diagnosed with small airway obstruction (a form of COPD).

My arms, hands, face, lips and tongue burn, itch tingle, and have stabbing pain: Small Fiber Neuropathy.

And I have Immune Deficiency (CVID) and must have transfusion of Immune Cells from donors, IgG, monthly, or I am subject to constant infections due to my lack of protection.

Our Immune system can use autoantibodies to attack and organ/system of our body. This is Lupus, Rheumatoid Arthritis, PN, over 100 conditions.

And in my case it uses some other mechanism is attack me. The result is the same, unfortunately.

Hugs, ElaineD

Hi Elaine - are you familiar with MAI ? I was told by my primary care doc that a second c-scan of my lungs shows suspected inflammation (Mycobacterium Avium Intrace). I am 8 months into dealing with a severe axonal polyneuropathy and am scheduled for a nerve biopsy tomorrow. Now I'm wondering if there is a link between inflammation in lungs and painful axonal polyneuropathy.

No,rec60661, I haven't heard of MAI. There are so many marvelous and bizarre conditions in the world that I learn about every day on these forums.

I'm so sorry you have that infection. It often accompanies compromised Immune System, I read. Is your Immune System 'compromised'? Mine is because I have Immune Deficiency, a Primary Form. But I doubt if I have that infection, tho' I wouldn't know, I guess. The assumption is, I think, that my small airway obstruction is often associated with my form of CVID, but is not from infection.

Perhaps I should see a Pulmonologist for clear diagnosis of my compromised lung condition. But I've had several c-scans of my lungs, one recently. And what shows up is more like scaring and not inflammation.

I don't cough often, but I do have a sort of 'wheeze and whistle' sound if I expel my breath forcefully. And I have trouble taking a really full inhaled breath, if that makes any sense.

Since I have so many conditions I tend to ignore the ones that don't bother me terribly.

Thanks for your suggestion.

Hugs, Elaine

Hi Joanna,

I'm glad to hear that. His work is very interesting and worth reading. Fasano is a conventional physician so unfortunately he doesn't focus on natural methods, so no diets or the like, but like most who know about autoimmunity, he does say no gluten for those dealing with an autoimmune disease. The diet for healing the gut or dealing with problems with intestinal permeability and so autoimmunity is pretty standard, since there's research indication what makes it worse and what better. You'll find numerous books and sites on the subject and you can find studies on PubMed. But they all pinpoint the same things to stay away from: grains, fairy, nightshades, nuts and seeds, alcohol, certain fats high in omega 6, etc. You can find good stuff that's based on research on the Paleo Mom's site, under autoimmune protocol, and the info is all there without needing to spend money and buy her book.

That's interesting, Bluesfan. Thanks. The human body is so complex and interesting.

So here's a question for you or for MrsD. or any other takers, though I'm sure it has been answered somewhere already and perhaps I've asked it myself: What is the fallout, if one does have MTHFR mutation? I haven't been tested and likely won't be tested or would prefer not to spend the time and money for testing. Is it simply that one can't process folate and B12? If so, I can just keep taking those as I've been doing over the last year. For what it's worth, I don't think I have the mutation as there's no evidence of it in my family.

Thanks in advance.

While it may not be possible to stop autoimmune processes, we might be able to reduce them some. And also with supplements we may be able to repair better. Cleaning up the diet will provide more nutrients for repair also and reduce inflammation.

I just read a thing on Yahoo about this:

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why fast food is not good for you or me.

Hello. I'm very sorry about your RA diagnosis but very glad of this post and the resulting thread. I have been asking the same questions here for a while but am not a great deal the wiser, even though I do at least know a lot more than I did, thanks to these wonderfully well-informed people who have replied to your question. I'm also a non scientist so struggle to take in all the info about B cells and T cells a but it doesn't stop me trying and as Kiwi says "knowledge is power".

My own story is that I was diagnosed in 2011 with seronegative RA. Five years on and my CRP, PV/ ESR are still highly fluctuating and always raised despite no longer having signs or symptoms of active RA. Furthermore my Rheumatoid Factor has gone from weak positive to negative but my ANA is now a clear positive and some of my immunoglobulins are too.

My small fibre neuropathy is widespread and has been for some years - it probably started prior to my RA symptoms. I'm also hypothyroid. I have had many investigations including lumbar puncture, skin biopsies, colonoscopy, cystoscopy and have been unable to continue with Sulfasalazine, Methotrexate, Hydroxichloraquine or Azathioprone (sorry but I'm based in Scotland so may be using different brand names if you are based in US) because of severe allergies to these.

I am shortly to have a lip biopsy for Sjogren's Syndrome. My third rheum feels it is very unlikely that seronegative, non erosive RA would cause a small fibre neuropathy of this magnitude. I'm guessing that he's now looking for a different diagnosis for me thinking that I never had RA - or perhaps have a very mild version that coexists with other connective tissue diseases. I think the idea is that RA is principally a disease that affects the synovial fluid around the joints and tendons. It would have to be aggressive and erosive to cause the small nerve fibres to respond in the way that mine have. So he is sure RA is not the cause in my case. But then he never saw my very classic presentation of this disease in my hands and wrists five years ago.

He is looking at primary Sjogrens because this can often damage the peripheral nerves and present sometimes in a very similar way to MS - as mine appears to be doing. Failing a positive result from the lip biopsy I suspect he will rediagnose me with UCTD - an undifferentiated mix of connective tissue diseases including RA and possibly Vasculitis. Increasingly I believe I have a broad mix that includes CREST/ Scleroderma and RA. My skin is changing on my hands and feet and I have many tiny tengliestasis all over my face and palms of my hands and nail bed, indicating Systemic Scleroderma. But this is just self diagnostic stuff. We will see!

Meanwhile the neuropathy is flaring terribly just now and I'm not aware of any vitamin deficiencies, dietary changes or lifestyle changes that might have triggered this flare up. I've tried being gluten free, dairy free, deadly nightshade avoidance, no caffeine, no sugar etc - none have helped apart from avoiding refined foods which inevitably gives us a more fighting chance. I'm totally fatigued and find it hard to stand up for more than a few minutes. All is stinging and burning just now - including my mouth, cheek and one eye, but I refuse to take any more meds that will only address my symptoms rather than modifying the cause of my problems. I have recurrent yeast infections and strange new constipation and vertigo. I take several suppliments but the only ones that have helped to date are AdCal D3 and possibly Acidophilus. Best of luck with the Methotrexate. It was very effective for me but finally made me too nauseous even by injection.

I hope this helps. Mat

Hi David

Like you I'm hesitant to get any genetic testing - as yet have found no connection between MTHFR and autoimmune Addison's (I'm researching the Fibromyalgia link for a friend) - however I suspect there may be a genetic component to my Addison's as there are other autoimmune conditions in my family.

I'm using the MTHFR acronym very generally in my above post as there are at least 40 different variations of MTHFR and different variations can produce different effects which require different management. So B12/Folate may be only one part of the answer. To me, that would be the main reason for testing - if test results indicated a specific variant then it may help me manage the Addison's better.

Addison's is incurable and management is the key to trying to have a somewhat normal life. The stubborn side of me refuses to accept that this is as good as it gets - which is why I keep researching.

Hi Bluesfan,

Thanks. I hear you. We all need to keep striving, I think, and to be stubborn. I mean, as long as we don't get crushed if it doesn't improve or if we have setbacks. I'm realistic, but I also don't want to give into despair or to assume that just because conventional medicine and science don't know much here or don't invest in research we should just give up, quietly sitting aside and letting things get worse. I won't go down with a fight. :)

Well, I think I'll stick to taking my B12 and folate and not have the testing. I don't think it will help me. So we are indeed in the same boat in that regard.

I do hope you find relief somehow and in some way. I'm still looking for the cause of my SFN and other symptoms and working my way through the natural approach.

Have a great weekend!