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Autoimmune Disease

We have not made progress in our battle to ease suffering caused by autoimmune disorders. The National Institutes of Health estimates that between 14 and 22 million people in the United States have an autoimmune disease with the most common being systemic lupus erythematosus (SLE), multiple sclerosis (MS), type 1 diabetes, thyroid (Graves and Hashimoto), myasthenia gravis, scleroderma, and rheumatoid arthritis (RA). These disorders affect more women than men and are among the 10 leading causes of death for women in all age groups up to the age of 64. The physical, emotional, social, and financial burden of these diseases cannot be overstated.

Autoimmune disorders can be some of the most challenging illnesses to treat because etiology can be difficult to determine and disease progression can be complex and dangerous. With more than 80 different types of autoimmune disorders presently identified, the complexity begins with diagnosis. The wrong or delayed diagnosis can not only be frustrating for the patient but can also reduce the chance of successful treatment and possible remission.
Once a proper diagnosis is in place, conventional medicine looks to steroid and other drugs to help the patient manage symptoms. According to clinician, Kara Fitzgerald, ND, this is where an integrative approach can shine. We asked to her describe her clinical strategy. 


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Q & A

Dr. Kara Fitzgerald clarifies some key issues regarding integrative strategies to autoimmune disease.


A: Because nearly all patients with autoimmune disorders have some type of gut involvement, nutrient depletion is common. Over time, these deficiences can further disease progression. . Common deficiencies include vitamin D, B12, zinc, potassium, and magnesium. This is because inflammation is metabolically demanding. Poor diet and/or dysinsulinemia can contribute to EPA and DHA deficiency, and favor production of proinflammatory AA arachidonic acid.
Identifying and treating nutrient deficiencies can have an immediate impact. For example, giving B12 to a patient with pernicious anemia is a welcome relief for that patient. Potassium and magnesium deficiency are prevalent in my clinical practice in general, not only with my patients who have autoimmune conditions. Correcting those two deficiencies can help patients feel better quickly with resolution of symptoms such as myalgia, insomnia, mood disorders and IBS symptoms. Amino acids can also swiftly enhance mood and energy because they are bioavailable with no digestive effort required.  Of course, while correcting deficiency, significant attention needs to be paid to gut repair because if the gut is leaky and digestion is compromised these needed nutrients aren’t being well-absorbed.
Another critical area of dysfunction in people with autoimmune disorders is mitochondrial lesions. It’s not always clear if the mitochondrial damage is antecedent to the autoimmunity, or if it occurs during the course of the disease – perhaps as a result of the disease itself.  In any case, mitochondrial dysfunction contributes to disease progression and worsening of symptoms if not addressed. Again, this is another area where lab results are useful, although there are some limitations to our ability to assess mitochondrial function reliably. The gold standard for diagnosis of mitochondropathy is muscle biopsy. Unfortunately, this is a difficult test to obtain, and functional or subclinical mitochondropathies will be missed.. At this point in time, I think the most important laboratory analyses are:  elevated lactate to pyruvate ratio in blood, and organic acids in urine. Also consider amino acids, oxidative stress biomarkers and acylcarnitine levels.
I also keep in mind that mitochondrial imbalances relate to the complete patient picture, being, in some ways, barometers of the overall health of the body. Oftentimes, the treatment strategy to repair the gut, work on diet and lifestyle, and identify triggers automatically brings balance to the mitochondria. These baseline interventions directly or indirectly support mitochondrial health by restoring more optimal redox balance, removing mitochondrial toxins and improving mitochondrial nutrition. That said, if imbalances are pronounced and clinically relevant, I focus on specific mitochondrial support alone or in combination with agents such as CoQ10, glutathione, vitamin C, lipoic acid, fish oil, B complex, magnesium, and/or carnitine.
Hormonal imbalances are certainly involved in triggering and mediating autoimmunity, as evidenced by the preponderance of autoimmunity occurring in females. Thus, assessment of sex hormones, including estrogens and estrogen metabolites, progesterone, DHEA-sulfate, free and total testosterone and prolactin are an important part of my investigation.  Pro-inflammatory derived estrogens, (the AA eicosanoid PGE2 can stimulate aromatase and estrogen production) have been shown to promote disease pathogenesis in rheumatoid arthritis. Since aromatase converts testosterone to estrogens, it’s not surprising that testosterone and DHEA can be lower in both men and women with autoimmunity. In fact, newer research suggests that low testosterone in men may precede the onset of diease. Overall, in my assessment, I may also rely on imaging. Xrays, CT scans, and ultrasounds as these imaging tests all help provide more data on the state of organ health and rule out structural issues. In my treatment approach, data is how I create the treatment strategy, monitor that strategy, and measure outcomes. Of course, symptom relief and the patient’s subjective view are also critical outcome measurements.
Related Published Research:
Kulie T, Groff A, Redmer J, Hounshell J, Schrager S. Vitamin D: an evidence-based review. J Am Board Fam Med. 2009;22(6):698-706. [abstract]
Kibirige D, Mwebaze R. Vitamin B12 deficiency among patients with diabetes mellitus: is routine screening and supplementation justified? Journal of Diabetes & Metabolic Disorders. 2013;12:17. [abstract]
A: I remind practitioners that this is an area where integrative treatment can shine and it is incredibly rewarding to help these patients gain better quality of life and get well again.
From a foundational standpoint, my advice revolves around paying close attention to the sequence of treatments and properly prioritizing care. In complex cases, it can be overwhelming to do everything at once. In addition, lack of proper sequence and prioritization can result in poor outcomes that can include symptom exacerbation and disease progression. Prescribing lots of nutrients, for example, is not prudent if dysbiosis is not corrected or at least eased to some degree. Gut inflammation can hinder nutrient digestion/absorption so I begin by addressing severe depletion and deficiencies that are hindering quality of life and treatment success, while concurrently repairing the gut.
My motto in terms of sequence and prioritization is similar to other integrative practitioners working with autoimmune conditions: food first. My goal is to gain a thorough understanding of the past diet, existing diet, and any food allergies or sensitivities. I then help the patient remove food toxins and provide dietary advice that I feel is sustainable, as well as effective.  Concurrently, if there are clear toxin exposures, we need to remove those and initiate very gentle detoxification measures such as sauna or Epsom salt baths.
From there, I focus on repairing the gut, reversing nutrient deficiencies, and balancing hormones and mitochondrial function. I also address the mind-body connection, which can play a significant role in autoimmune flares and progression. More aggressive detoxification can be initiated once we get a good foundation in place. Our patients are a unique constellation of genetics, epigenetics, thoughts, feelings, and actions. The entire constellation must be considered if our patients are to regain their health.
Here are a few other aspects to keep in mind:
  • Autoimmune diseases can appear together; I often see Hashimoto’s thyroiditis and pernicious anemia together, and while there is some debate about this, it appears that gluten sensitivity is linked to other autoimmune conditions in addition to celiac.
  • Don’t underestimate the power of the biochemical inflammatory cascade and the intimate interplay between the immune, endocrine, and gastrointestinal systems; they provide valuable clues and information that will help you prioritize and create effective strategies.
  • The intake assessment is critical and worth the extra time in order to get as much information as possible as early in the process as possible; the data you gather will also help shape solid outcome measurements to track progress.
  • Be ready for the extremes associated with autoimmunity; sometimes something as simple as removing gluten is all that is needed, but oftentimes, it’s much more complex.
  • I screen for certain autoantibodies like ANA and thyroid peroxidase in all of my patients. Research suggests that autoantibodies will appear long before the condition is clinically relevant. If we can address these findings early on, I believe we can prevent the occurrence altogether.
While there are foundational steps we can take and treatment strategies that apply to most of our autoimmune patients, at the core of these strategies are built-in mechanisms that accommodate personalization and celebrate the individual. After all, our focus on individualization is a key reason why our patients come to see us in the first place.
Related Published Research:
Hyman MA. The right order of things: Peeling the onion of chronic disease. Altern Ther Health Med. 2009;15(2):18-20. [abstract]
Kumar V, Rajadhyaksha M, Wortsman J. Celiac disease-associated autoimmune endocrinopathies. Clin Vaccine Immunol. 2001;8(4):678-685. [abstract]
A: In general the causes of most autoimmune conditions are unknown by the greater conventional medical community. Once proper diagnosis is established, “gold standard” conventional care focuses on symptom relief via pharmaceutical interventions.
With integrative medicine, the goal is quite different. The main objective is to identify likely causes or contributing factors. We can then address those factors through a variety of means that include diet, lifestyle counseling, and dietary supplements.
Some of the more common underlying issues I have found in my practice include: poor diet, food allergens, infection, toxin exposure, genetic susceptibility, and poor gut health to mention a few. Increasingly, environmental exposures can be key antecedents to autoimmunity.
In the scientific literature Fasano et al describes a “trio” of autoimmune underlying factors: genetic susceptibility, an environmental trigger, and intestinal permeability (“leaky gut”). Fasano’s work shifts the paradigm away from the traditional theories of autoimmune disease development as an isolated immune disorder and instead emphasizes the significance of the intestinal barrier function. This makes logical sense when one considers that tolerance and immunity to nonself-antigens is controlled via a combination of the gut-associated lymphoid tissue (GALT), neuroendocrine network, intestinal epithelial barrier and the tight intercellular junctions in that intestinal barrier. By identifying environmental triggers and repairing the leaky gut, it is possible to halt progression of autoimmunity and even cause remission of these disorders. Fasano et al also mention dysbiosis as a variable underlying autoimmunity.
Identifying the environmental trigger can be key. There is increasing recognition of the role of acquired infections in RA. Notably, Proteus infections (resulting in urinary tract infections and/or P. gingivitis causing periodontitis) have been implicated in the development of anti-CCP antibodies and RA symptoms. Other types of infections can also be triggers. I have a patient with RA whose trigger was severe mold exposure following a flood. I have another patient whose polymyopathy trigger appears to have been multiple childhood and early adult strep infections. I also have a polymyalgia rheumatica patient whose lab work and history indicate that the trigger may have been infection with strongyloides. Note that all of these aforementioned microbes have been associated with rheumatologic conditions. Sometimes the trigger can be quite obvious as indicated by my Hashimoto patient whose trigger is gluten. In this patient, merely removing gluten caused her antibodies and thyroid function to normalize. In all of these patients, as well as others, in concert with antecedent evaluation, I also work to repair typically dysbiotic intestines and their hyperpermeable barrier.
This is where lab tests become critical because they can help me to measure outcomes to determine if the trigger(s) has been correctly identified and the intestinal lining has been successfully repaired. Of course, this is not the whole story. Because these conditions can be multifactorial, always keep your eye out for additional underlying factors that should be considered. 
Related Published Research:
Fasano A. Surprises from celiac disease. Scientific American. 2009;301(2):54-61. [abstract]
Fasano A, Shea-Donohue T. Mechanisms of disease: the role of intestinal barrier function in the pathogenesis of gastrointestinal autoimmune diseases. Nat Clin Pract Gastroenterol Hepatol. 2005;2(9):416-422. [abstract]
Ebringer A1, Rashid T. Rheumatoid arthritis is caused by a Proteus urinary tract infection. APMIS. 2014 May;122(5):363-8.[abstract]
Rutger Persson G. Rheumatoid arthritis and periodontitis – inflammatory and infections connections. Review of the literature. J Oral Microbiol. 2012;4. [abstract]
A: As with chronic disease in general, integrative medicine has much to offer the autoimmune patient. Multiple systems are involved in autoimmune pathogenesis that must be investigated. The integrative practitioner is trained and attuned to this type of methodical exploration.
Because of the complicated nature of most of these disorders, these patients typically require more of the clinician’s time. For example, extra care must be taken when doing the clinical history. I utilize the Functional Medicine Matrix ™ to capture systems information and to help identify needed areas of investigation. I also use a comprehensive medical symptom questionnaire (available in the resources section of TAP website) and intake forms. My goal is to dig deeply into all aspects of the patient’s health and lifestyle. This includes discussing environmental exposures (including toxins and history of infections)dietary habits, sleep patterns, etc. I also do a physical exam and obtain past labs and medical history. Based on the medical records, I generate a symptom and previous diagnosis timeline and place that into the patient chart.
I also ask all of my patients to describe their goals of treatment and we determine how motivated they are to do the things I may ask of them. I list the goals at the top of the chart (and on their take-home treatment plan) and we track those at every visit.
I use the visual analogue scale (VAS) frequently which is a measurement tool for subjective experience. VAS has been validated for pain, mood, fatigue/energy and sleep, among other things, and very easy to use. I gather as much data as possible.Data helps me track outcomes and gives the patient information as we take this journey together.
Keep in mind, the past provides significant data as well. Perhaps a diet was tried, administered successfully and did not work. There is no need to try that diet again. But sometimes an intervention was tried but the dosage was wrong or something else was amiss. For example, a patient may not have experienced health improvement results with a gluten-free diet because they are also reactive to egg or soy so the symptoms continued with no noticeable change.
The physical exam also provides important data. In addition to the typical aspects of the physical exam (heart, brain, musculoskeletal, neurological, abdominal), I also pay close attention to skin, hair, nails, oral mucosa, teeth and tongue. I even take a snapshot of significant findings of the skin, nails, and tongue and place it in the file to track against baseline. The finger nails are a six-month living medical record (six months is the approximate time they take to grow out) Here are some basic examples:  poorer digestion (vertical ridging, brittle nails), protein status (brittle nails, white transverse bands), mineral status (white spots), significant illness causing malnutrition (Beau’s lines) and toxin exposures (yellowing nails, white spots or bands). Findings can be non-specific, for instance- white spots on multiple nails, called leukonychia, can suggest injury, zinc deficiency, selenium toxicity or arsenic exposure. Yellow nails can suggest toxicity, but also may be found in RA. History and/or laboratory testing will help you answer what the causal factor is. Of course, we know koilonychia (spooning of the nails) is common in iron deficiency, but it can also be caused by zinc deficiency. Punctate nail lesions are associated with psoriasis, may precede the onset of psoriatic arthritis. Multiple autoimmune diseases can cause nail changes.  A pounded brass appearance is common in severe atopic dermatitis, but also seen in vitiligo or alopecia areata. In addition to nail changes, a scalloped tongue can suggest mild allergic reactions,  maldigestion,  and dysbiosis. Since we know hypochlorhydria can increase vulnerability to food allergies and promote bacterial overgrowth, this finding can be particularly useful. Look for rosacea in such patients, too. Again, we’re thinking about bacterial overgrowth and possible hypochlorhydria. I have seen this in two individuals with pernicious anemia. Expect to see some variation of this picture in those on acid blocking therapy. In fact, you might see leukonychia or other nail abnormalities in this population as their mineral levels drop over time.
Another area where the integrative practitioner can excel is in specialty testing. These tests are in addition to standard labs including disease-specific autoantibody testing, sex hormones, inflammatory markers, and general chemistries. For example, here are some of the tests I often use:
  • Celiac and celiac genetics (a patient can be gluten sensitive if they have the genetics even when serology is negative)
  • IgG food panel (including gluten containing grains, dairy, eggs, soy, nuts, corn)
  • Stool test to identify dysbiosis and inflammation (and specific microbes such as Klebsiella pneumoniae or Yersina enterocolitica, both which have been linked to triggering autoimmunity, inflammatory markers, parasites, etc)
  • Organic acids test (for assessing the status of nutrients such as B12 and folate, oxidative stress, mitochondrial issues, detox issues, and microbial-produced compounds)
  • 4-point salivary (cortisol with DHEA, total sIgA and if available an IgA antigliadin antibody)  Saliva has been shown to be a reasonably reliable specimen for total IgA and antigliadin antibody (AGA), as well as tissue transglutaminase and endomysial antibodies (Pastore et al) That said,  I use saliva AGA as a screening tool rather than a diagnostic test. 
Of course, this is just a short list because there are numerous other tests available that can help provide significant data. When combined, all of the information gathered provides a clear picture that will help influence the most effective treatment strategy.
From a clinical standpoint, nearly all autoimmune patients have nutrient deficiencies because absorption and digestion are commonly compromised. In addition, increased inflammation is nutrient demanding and when combined with a potentially poor diet can cause significant deficiencies. Integrative practitioners are well-versed at correcting nutrient deficiencies.
Related Published Research:
Hawker GA, Mian S, Kendzerska T, French M. Measures of adult pain. Arthritis Care & Research. 2011;63(S11):S240-S252. [abstract]
Pastore L, Campisi G, Compilato D, Lo Muzio L. Orally based diagnosis of celiac disease: current perspectives. J Dent Res. 2008;87:1100-7. [abstract]
Sapone A, et al. Spectrum of gluten-related disorders: consensus on new nomenclature and classification. BMC Medicine. 2012;10:13. [abstract]
Dr. Kara Fitzgerald clarifies some key issues regarding this important integrative clinical strategy.


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Expert Bio

Kara Fitzgerald

Kara Fitzgerald, ND, received her doctorate of naturopathic medicine from National College of Natural Medicine in Portland, Oregon. She completed the first CNME-accredited post-doctorate position in nutritional biochemistry and laboratory science at Metametrix Clinical Laboratory under the direction of Richard Lord, Ph.D.
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