Decoding RA – Shedding Light On The Hidden Causes of Rheumatoid Arthritis (RA)

I have found one of the biggest frustrations with RA patients is that traditional treatment approaches seem palliative at best. Many seek answers beyond medication regimens on what they can do to treat the disease. In this blog I will explain how functional medicine offers new insight into this disease and will shed some light on the (hidden) causes of RA and what you can do about it.

1. Genetics

Since RA is an autoimmune disease, one needs to consider any genetic predisposition. This means taking a close look at your family history for RA as well as other autoimmune and inflammatory conditions. Next, you should consider getting tested for any genetic predisposition.

Seventy percent of RA patients show positive for a variation in the human leukocyte antigen (HLA) genes, such as HLA-DRB1 and its serotype HLA-DR4. Other genes connected to RA include: STAT4, a gene that plays important roles in the regulation and activation of the immune system; TRAF1 and C5, two genes relevant to chronic inflammation; and PTPN22, a gene associated with both the development and progression of rheumatoid arthritis. These genes are but a few that we are aware of that can play a role in RA. Services such as 23andMe can provide you with an extensive data set that can help you identify genetic variants. Your functional medicine practitioner will be able to help you make sense of the genetic reports and look into other important factors such as impairments in your methylation and detoxification pathways or neurotransmitter balance.

Now, if you learn that you are genetically pre-disposed to RA, it is important to note that simply because you have a genetic variant does not mean you will develop the disease. Furthermore, many RA patients are often told that there is little they can do due to their genetics, however the emerging field of epigenetics shows much promise on how we can turn off dysfunctional genes through lifestyle, diet, and improving our environment. This means there is much you can do, so keep reading!

2. Infections

Most patients that I see for RA, or for any other autoimmune or inflammatory condition, either have a known history of infections and/or testing reveals an occult infection. These infections may be of parasitic, viral, and/or bacterial nature and can even present as a combination. Successful treatment of RA can often only be accomplished by first addressing any existing infection(s) and re-establishing immunological balance within the system.

Bacterial

The most common presentation I see with RA patients is that an overwhelming number have a compromised microbiome (dysbiosis) and/or overgrowth of bacteria in their small intestine (SIBO). This may or may not present with gastrointestinal (GI) symptoms and hence is often overlooked by traditional treatment regimes. Clinical evidence and studies show that the severity of bacterial overgrowth seems to correlate with the severity of the musculoskeletal symptoms and levels of inflammation. This may be explained by the increase in endotoxins such as lipopolysaccharides (LPS) that are produced by the bacteria, leading to systemic or localized (joint) inflammation. Citrobacter, Klebsiella, E. Coli, mycoplasma, and Proteus mirabilis microbes have been implicated in RA. In addition, there is evidence that prolonged periodontal disease can play a role in the formation of the condition.

Viral

Literature suggests that an increased viral load may be associated with RA. Cytomegalovirus and Rubella viruses have been cultured from the synovium of patients with RA. There is also evidence of Hepatitis C and Epstein-Barr Virus (EBV), Parvovirus B19, and retroviruses as a possible trigger for this disease. In addition, other viruses are known to cause viral arthritis which can mimic the symptoms of RA. The good news is that this type of arthritis tends to be self limiting and, with successful treatment, the joint pain can be resolved.

Mycotoxin

I have found that many autoimmune patients will often present with a history of toxic mold exposure and resulting sensitivities. Identifying past and present exposure and eliminating possible sources is often needed before remission of the disease can occur.

Parasitic

Gastrointestinal parasitic infections such as with Entamoeba histolytica have been linked to autoimmunity and RA. Other parasites such as Endolimax nana and G. lamblia have been found to result in systemic inflammation that can mimic RA. Similar to viral arthritis, eradication of these pathogens tends to often resolve the joint pain.

On a side note, there is some interesting data on Helminth parasites having a beneficial effect on autoimmune conditions. Their immune modulating affect is most likely a defensive mechanism of the parasite, leading to decreased immune activation and, in the case of RA, to a decrease in inflammation. The therapeutic application of using parasites as a treatment in autoimmune conditions is still in its infancy and further data is still needed, but it may prove to be a possible treatment for autoimmune patients in the future.

3. Hormones

There is evidence that sex hormones, especially estrogen, play a role in RA. During pregnancy, women tend to experience remission of the disease, hence some postulate that elevated estrogen levels may be beneficial. However, current research on hormone replacement therapy (HRT) to treat RA is still inconclusive other than it may be helpful with improving bone density.

Another hypothesis to consider is that disease remission may be the result of the immunological shift from TH1 to TH2, which occurs naturally during pregnancy. Since RA is considered a TH1 dominant disease, the immunological shift to TH2 most likely helps ‘balance’ the immune system and aid in disease remission.

When looking at hormones with my RA patients, I will often find an elevation of prolactin and estradiol along with insufficiencies in DHEA, cortisol, and testosterone. This presentation is indicative of estrogen dominance in combination with an imbalance of the brain, thyroid, and adrenal hormonal axis. I have found that improving any endocrine imbalance will often drastically improve patients symptoms as a whole.

4. Increased Intestinal Permeability “Leaky Gut”

Clinical experience and current literature suggest that intestinal permeability is present with most autoimmune conditions, including RA. It further tends to be a contributing factor in most chronic inflammatory conditions such as psoriasis, ankylosing spondylitis, seronegative spondyloarthritis, juvenile idiopathic arthritis, and lupus.

The cause of leaky gut is manyfold. Chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs), acid reflux medications (PPI’s), dysbiosis, SIBO, infections, trauma, chronic stress, adrenal insufficiency, and the presence of food allergies and sensitivities (gluten, dairy, etc.) are but a few that need to be considered.

When dealing with any chronic inflammatory and/or autoimmune condition, it is my opinion that one should always begin with the gut. Your gut is the foundation for your health and houses seventy to eighty percent of your immune system. If your gut is inflamed, wouldn’t it make sense that your immune system will become imbalanced, over-active, and may lead to mistakenly attacking your joints? Assessing and treating your GI system is essential for any long lasting treatment and remission of the disease.

5. Heavy Metals

When looking at the body from a functional medicine point of view, heavy metals can often be the culprit for many chronic and seemingly unexplainable symptoms. Having elevated toxic metals in your body such as mercury, lead, and cadmium can lead to altering and damaging cells of your body. This can result in your immune system mistaking the altered cells for invaders and initiating an immune response. Studies show that individuals with elevated heavy metal burden have an increased risk of getting an autoimmune disease.

If you decide to look into heavy metals and chelation therapy, I would like to caution you to make sure that your body is capable of detoxifying these compounds and assess your chemical tolerance to these compounds. Many autoimmune patients develop an immune reaction to chemicals and heavy metals and releasing them through chelation can sometimes do more harm than good. Working with a well versed functional medicine practitioner in collaboration with a holistic dentist is a must to make sure this is done safely and correctly.

Conclusion

I hope this article was helpful in understanding some of the key elements that make up the root causes for RA. I would love to hear your comments and am always glad to answer any questions that you may have.

  

 

 

References:

SNPwatch: Three New Genetic Variants Associated With Rheumatoid Arthritis Risk. November 11, 2009. Published by Shwu under SNPWatch. Read more at http://blog.23andme.com/23andme-research/snpwatch/snpwatch-three-new-genetic-variants-associated-with-rheumatoid-arthritis-risk/#4KQzAfu4GZPUFhCf.99

C. R. Holroyd , C. J. Edwards. The effects of hormone replacement therapy on autoimmune disease: rheumatoid arthritis and systemic lupus erythematosus: Climacteric. Vol. 12, Iss. 5, 2009

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Mayes MD. Epidemioloic studies of environmental agents and systemic autoimmune diseases. Environ Health Perspect 1999;107(suppl. 5):743-748

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Toivanen P. Normal intestinal microbiota in the aetiopathogenesis of rheumatoid arthritis. Ann Rheum. Dis. 1993 Jul;52(7):503-10

Vasquez A. Integrative Rheumatology, concepts, perspectives, algorithms, and protocols, 2nd edition

ZACCONE P, FEHERVARI Z, PHILLIPS JM, DUNNE DW, COOKE A. Parasitic worms and inflammatory diseases. Parasite Immunology. 2006;28(10):515-523. doi:10.1111/j.1365-3024.2006.00879.x.

Bigazzi PE1. Autoimmunity and heavy metals. Department of Pathology, University of Connecticut Health Center, Farmington 06032. Lupus. 1994 Dec;3(6):449-53.