Rheumatoid and Osteo Arthritis and Much More: Where to Begin in THIS case?

(This is a sample entry from the SAFM Q&A Treasure Chest, a tool with hundreds of entries to support students with their clinical cases. Students gain unlimited access as part of SAFM’s functional medicine training program.)

Student Question:

This is a patient who is 67, Dx rheumatoid arthritis and osteoarthritis.  Renal reconstruction surgery at age 30 and has frequent bladder and yeast infections.  Also stomach bloating and hypertension.

She wants to lose weight and has lost 10 lb since going gluten-free and is now 150 lb @ 5’4″.

Her daily Medications are Amlodipine, Benicar, Crestor, Zetia, Methotrexate 2.5mg-5 tabs weekly, Veramyst nasal spray, and Allegra.

Her supplements are cranberry capsules, Fish oil 1200mg, Vit C 1000mg, and Raw probiotics vaginal care (38 strains, 80 Billion CFU).

We’ve just gotten started. She was also taking folic acid 1mg (I recommended a switch to methylfolate) and aspirin 81mg (which I suggested may be aggravating intestinal permeability given the AI activation). Her PCP recently added Vitamin D3 5000 based on moderate lab values, but I am concerned about her serum calcium of 10.8 mg/dl. She states this value has been high “for a long time” but has never been flagged as notable or investigated.  All other basic labwork seems optimal – or at least WNL.

My challenge is that she is not open to any functional testing (e.g. stool test) at all.  She is open to follow-on bloodwork, but not until after her return from an upcoming six-week vacation roadtrip. I know we have much to investigate and explore over time. My question is this:  where would you begin?

SAFM Response:

A fascinating case!  If you haven’t yet already, we highly recommend you read some of the other posts on various autoimmune diseases and common contributors and etiological factors on our site, especially this one  (searching by “autoimmune” in the Q&A Treasure Chest will bring up many more).  But the details of this case are also a perfect example of why we need to approach every patient with Beginner’s Mind and look for their unique factors and contributors with fresh eyes and an open perspective.

A key best practice in complex cases like this is to put a balanced focus (50/50) upfront on both Rapid Relief and Root Cause investigation and resolution, right from the beginning.  You don’t mention whether there is ongoing pain in spite of the methotrexate (MTX).  However, it’s key to aim to reduce joint inflammation in pursuit of minimizing any ongoing damage in addition to symptoms of pain, discomfort, and/or stiffness.  Then here are some interesting thoughts for you with regard to root cause interconnectedness.

In terms of Rapid Relief:

• Check the quality of her fish oil supplement and add to it the anti-inflammatory GLA (an essential omega-6 fatty acid) such as 500mg bid evening primrose oil or borage oil, taking both together in split doses with meals (to maximize absorption). GLA can be  helpful in arthritis via a few pathways; it directly counters IL-6, which is implicated as a major inflammatory mediator in rheumatoid arthritis (part of what the MTX is countering) and has also been shown to reduce platelet aggregation.
• Given the likelihood of its contribution to enhanced intestinal permeability (and dysregulation of immune function in the gut due to damage to the gut lining), consider stopping the daily aspirin use for now unless there are immediate signs of cardiovascular disease or event risk (check fibrinogen and hsCRP; check with the patient too re: any plans for a long plane flight).
• Add a CoQ10 supplement (ideally ubiquinol) 100mg BID to counter the depleting effects of the statin drug.
• Given the existing autoimmune diagnosis, your focus on excessive intestinal permeability is appropriate. Food sensitivities associated with leaky gut are often at play in Both rheumatoid and osteoarthritis. Consider a focused (partial) elimination diet – including both gluten and dairy foods and, in the case of RA, adding nightshade vegetables (and perhaps other lectins) to that list, as they are common cross-reactive triggers for this particular AI target. Prioritize gluten first.
  • While a full elimination diet might be most helpful for this woman, we are sensitive to the travel ahead and what may or may not be feasible vs. theoretically optimal for her to achieve while away from home. It is important to not promote overwhelm upfront in atypical circumstances, as it might erode her belief that she can make sustainable lifestyle change in a more normal, supportive environment after her return.
• Lastly, consider adding Undenatured Type 2 Collagen. The link is to a helpful research review. The mechanism is not agreed conclusively, but it appears UC-II works primarily by promoting oral tolerance to collagen that can stop the cycle of ongoing inflammation to endemic tissue, arresting the process. It appears at least 40mg/day is required; 60mg in divided doses on an empty stomach (key!) is often effective. This is available in many products, some combined with anti-inflammatory agents, especially bromelain and boswellia e.g. Life Extension ArthroMax Advanced, Pure Encapsulations’ Joint Complex, Metagenics OsteoVantiv (note: though it’s <50mg dose, the magnesium oxide may not be well tolerated in this latter option for individual’s with optimal or loose stools).

In terms of Root Cause (but there are some urgent factors in here as well):

• We agree that the high serum calcium level is a notable concern.  For now, until you can get additional labwork, consider stopping the Vitamin D3 supplement entirely and add in both a Vitamin K2 and Magnesium glycinate supplement instead.  High Vitamin D is just going to encourage more calcium absorption which, for the moment, is not helpful and potentially dangerous.  These supportive nutrients will help to channel available calcium into bone tissue and prevent calcification of soft tissue (which she may already be vulnerable to from both a cardiovascular as well as renal perspective given her meds and history). The parathyroid gland is largely responsible to maintain optimal levels of calcium in the blood.  At your first opportunity, recheck Vitamin D (both 1,25-OH and 25-OH), serum calcium, and parathyroid hormone (PTH) simultaneously. Sustained high serum Calcium in an adult (especially above 10 mg/dl at her age) may be indicative of a parathyroid gland tumor or other dysfunction.  This is an online resource we have found to be particularly helpful and clinically sound on the topic of parathyroid issues. 
• When you can seek bloodwork, also order a full thyroid panel. There is clinical association (just one example) between hypothyroidism and the development of hyperparathyroidism, and chronic inflammation from dynamics such as RA can naturally promote hypothyroid function over time. We also know that elevated LDL cholesterol (evidence her hypercholesterolemia meds) and gastrointestinal dysmotility (e.g. constipation, IBS-like symptoms) are common symptoms of a hypothyroid state. Thyroid hormone is also key for bile synthesis and gallbladder emptying (see below).
• Unfortunately, sustained, elevated levels of serum calcium may also have been a key driver of her arthritis by promoting build-up of calcification in the joints.  Arthritis-like complaints are an acknowledged symptom of hyperparathyroidism. Is it also possible that elevated serum calcium contributed to her kidney dysfunction years ago? Or impaired filtration downstream from damaged kidneys is promoting higher calcium in the years since (and now)? Either or both are possibilities worth exploring. Powerful examples of functional interconnectedness.
• We know that LPS-mediated inflammation from the gut (promoting both more NF-kB activation and enhanced intestinal permeability) can be a common contributors to rheumatoid arthritis. The appropriate food eliminations (e.g. gluten and its common cross-reactive foods) and healing the gut lining are key. But…
• We recommend you also investigate the likelihood of impaired bile flow AND synthesis. Check alkaline phosphatase, bilirubin, and liver enzymes (ALT, AST, GGT) in the next CMP you order; ask to make sure she still has her gallbladder (a surprisingly common item overlooked on intake form submissions!). This woman may need help with clearing out bile ducts and improving both bile flow and gallbladder emptying (e.g., taurine, artichoke) and/or improving liver bile synthesis (e.g., choline, milk thistle, d-limonene), especially given the liver’s current burden of multiple medications and the statin impairing mitochondrial function. Those with RA are significantly more likely (50%!) to have gallstones or have had their gallbladder removed. This is part of the strong connection with the impact of LPS, which bile plays an important role in degrading.

Your patient is taking medication to both suppress synthesis of cholesterol (statin) and block reabsorption of cholesterol (zetia) from the gut. It’s quite logical that this may be impairing bile function overtly and present a fascinating example of interconnectedness where medication to try to prevent disease in one system (cardiovascular) may actually be promoting it in another (gut, joint, kidneys).  Through the functional medicine lens, this type of medication-mediated interconnectedness is common in situations of long-standing disease.

As a final comment, this patient may or may not have a pathogenic or other dysbiotic microbial issue at play in her gut or as an etiology of the RA.  Part of the “catch 22” of using an immunosuppressive agent like MTX for relief is that it suppresses immune function and can be actively exacerbating a triggering infection while simultaneously providing key protection of the joints from dysregulated immune function. Supporting this type of patient to be able to remove the MTX (by addressing rapid relief via other agents and at least significantly beginning the journey to address root causes) will likely be key to her having sustainable relief from this dis-ease process.  However, as you well understand, we must progressively reduce inflammation through other measures first in order to enable the safe titration and removal of medications such as this in a unique individual.