Bastyr University San Diego Clinic: Student Case Reports

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Vitamin D and Its Role in Autoimmunity: A Case Report


By Alexandra Carlton, ND

edited by Baljit Khamba, ND, MPH

Ankylosing spondylitis (AS) is a type of inflammatory arthritis that affects the spine. It is a very rare disease that causes inflammation of the spinal joints leading to severe, chronic pain. The hallmark feature of AS is the involvement of the sacroiliac joints during the progression of the disease. We will investigate treatments for autoimmune conditions, specifically related to ankylosing spondylitis.  Vitamin D plays an important role in autoimmunity since there is a correlation between vitamin D deficiency and an increased risk for autoimmunity. Being deficient in vitamin D is a global epidemic that has been linked to numerous diseases. Vitamin D is an endocrine hormone known for its important role in regulating calcium and phosphorus metabolism as well as proper bone formation. Nevertheless, vitamin D is a vital modulator of our immune system. Vitamin D deficiency has been associated with increased risk of cancer, diabetes, and cardiovascular disease.  Is vitamin D an effective treatment for autoimmune diseases? Given the research, there appears to be a significant correlation between vitamin D deficiency and an increased risk of autoimmunity. Increasing her serum vitamin D levels correlates with her overall improvement. Ultimately, the need for increased research interest on the role of vitamin D in autoimmune disease is warranted.

Ankylosing spondylitis (AS) is a type of inflammatory arthritis that affects the spine. It is a very rare disease that causes inflammation of the spinal joints leading to severe, chronic pain. The hallmark feature of AS is the involvement of the sacroiliac joints during the progression of the disease. We will investigate treatments for autoimmune conditions, specifically related to ankylosing spondylitis.

Vitamin D plays an important role in autoimmunity since there is a correlation between vitamin D deficiency and an increased risk for autoimmunity. Being deficient in vitamin D is a global epidemic that has been linked to numerous diseases. Vitamin D is an endocrine hormone known for its important role in regulating calcium and phosphorus metabolism as well as proper bone formation. Nevertheless, vitamin D is a vital modulator of our immune system. Vitamin D deficiency has been associated with increased risk of cancer, diabetes, and cardiovascular disease.

Is vitamin D an effective treatment for autoimmune diseases? Given the research, there appears to be a significant correlation between vitamin D deficiency and an increased risk of autoimmunity. Increasing her serum vitamin D levels correlates with her overall improvement. Ultimately, the need for increased research interest on the role of vitamin D in autoimmune disease is warranted.

Introduction

Although the exact cause of AS is unknown, research believes that genetics play a key role in this disease. Around ninety percent of individuals with AS have a genetic marker called HLA-B27. This gene, however, does not need to be positive to have AS. Analogously, one who has this genetic marker, may not develop AS during their lifetime. Researchers believe that this genetic marker might have an influence on one’s microbiome. There is a strong association with intestinal dysbiosis and AS patients.

Scientists suspect that other genes along with a triggering environmental exposure such as an infection are necessary to activate AS in susceptible people. Researchers have found over sixty genes that are associated with this disease such as ERAP 1, IL-12, IL-17, and IL-23.  Scientists also have found that complications of autoimmune patients stem from the gastrointestinal system when the defense mechanisms and barriers of the intestines are disrupted, allowing bacteria to pass through the bloodstream. This immune dysregulation leads to changes in the microbiome, resulting in alterations in the immune response. Microbial peptides trigger HLA-B27 to start an autoimmune response through molecular mimicry. Inflammation eventually leads to triggering new bone formation and fusion of spinal joints.

Ankylosing spondylitis is diagnosed under these parameters: pain persisting for more than three months, back pain with stiffness that worsens with immobility, that occurs especially at night and early morning. The onset of this disease usually begins under forty-five years of age. Upon physical examination, there will be inflammation and pain along the back, pelvic bones, sacroiliac joints, chest, and heels. There can also be decreased spinal mobility in all directions and chest expansion restriction.

Case Description

A.Z, a 20-year-old Hispanic female, presented to Bastyr University Clinic in San Diego seeking treatment for her diagnosis of ankylosing spondylitis. Her chief complaints of sacroiliac pain, joint pain, fatigue, insomnia, anxiety, and depression have significantly impacted her quality of life. She was diagnosed in 2016 with being HLA-B27 positive. Imaging revealed inflammation, but no spinal fusion. Her MRI without contrast showed mild erosions of the upper aspect of the left sacroiliac joint, associated with patchy bone marrow edema involving both the adjacent sacrum and iliac wing. There was small joint effusion with no osteonecrosis present. Pain is better with movement, worse in the morning and night. Starting at our clinic, her pain was 7/10 persistent pain (10/10 being extreme pain, needing to present to emergency room), with 9/10 severe pain on occasions.

Objective

Her review of systems is positive for fatigue, palpitations, constipation, muscle pain, joint pain, stiffness, back pain, dizziness, nervousness, anxiety, and full of despair. Her family history is pertinent for arthritis, anxiety, hypertension, heart failure, Alzheimer’s disease, COPD, diabetes, thyroid disease, and cancer.  On physical examination, her blood pressure was 100/58, pulse 85 bpm, respiratory rate 14 bpm, oxygen saturation of 98%, weight: 125.5 lbs, height 5 feet 6 inches, and BMI: 20.21. Patient was in no apparent distress and dressed appropriately for time and place. Her head is normocephalic; atraumatic, slightly tachycardia. All lung fields clear to auscultation with effort and breath sounds normal. Abdominal exam revealed bowel sounds in all four quadrants with no tenderness or masses on light and deep palpitation. No hepatosplenomegaly was present. Positive for back and joint pain, with swelling and pain on palpation on left iliosacral junction.

Her labs were positive for ANA, MTHFR A1298C heterozygous genotype mutation. Her homocysteine is slightly elevated, high globulin, elevated liver enzymes, and low vitamin D levels. Her stool analysis reports high beta glucuronidase and high E. coli with low diversity of bacteria in her stool. Since then, her liver enzymes have normalized, sufficient vitamin D levels, and her non-specific inflammatory markers such as CRP and ESR have decreased.

Her current treatment protocol is as followed. She is now fully compliant with the autoimmune paleo diet (no gluten, no processed food or food additives, grains, dairy, nightshades, sugar or artificial sweeteners, coffee, alcohol, eggs, soy, nuts).  Her medications include Motrin 600mg/ES Tylenol PRN for migraines, Escitalopram (SSRI) 40 mg/day for depression and anxiety short term, Spironolactone (diuretic) 50 mg for Propionibacterium acnes, Buspirone 10 mg PRN for anxiety, Meloxicam (NSAID) 15 mg for rheumatoid arthritis. Supplements are listed in Table 1.

 

Table 1

Supplements

  • Supplements - Dosage

  • BCQ by Vital Nutrients - 2-3 capsules TID

  • Bio-Gest Digestive Enzyme by Thorne - 1-2 capsules QD with meals

  • Pro Omega by Nordic Naturals - 3 capsules QD

  • Vitamin D by Genestra - 10,000 IU QD

Added Supplements

  •  Boswellia Extract - 450 mg TID

  • Calcium-D-Glucarate by Pure Encapsulations 500 mg QD

  • Mediclear Protein Plus by Thorne 2 scoops QD

  • Active B Complex 1 capsule QD

  • SPM Active by Metagenics - 2 capsules QD

  • Castor oil packs with arnica essential oil   - PRN on flare-ups

  • Candibactin BR by Metagenics   - 2  capsules BID

  • HPA Axis: Daytime Maintenance by Gaia Herbs - 2 capsules BID

 

From the patient’s timeline, she has been exposed to many viruses and bacteria throughout her life. She has taken numerous rounds of antibiotics and medications. This is shown through her gastrointestinal dysbiosis. The root cause of many imbalances can be healed by fixing digestive dysfunction. Our ideal focus for her is to heal her gastrointestinal system as well as control and manage her pain since that is affecting her quality of life.

We also recommended increasing acupuncture from every other week to every week since it seems to be benefiting her and helping with her inflammatory flare-ups. The supplements that have most benefited her and notably made the most difference with pain relief were vitamin D, omega-3, and Boswellia extract. We also gave her a support network to connect with others that are in similar situations. In addition, since there is such a mental emotional component with autoimmunity, we made sure to address this by finding sweetness in her life. We encouraged a gratitude journal, which brought her much joy. In addition, adding stress management techniques such as breath work and meditation were pertinent.

Results

She has improved drastically since starting at our clinic in October 2016. When she first started treatment with us, she walked with a cane and occasionally needed a walker. As treatment progressed, she walked without a cane, only using the cane twice during the treatment period for severe local inflammatory flare ups, with ultimately not needing a cane and walking extensively every day. Her recent labs, such as CRP and sedimentation rate, indicate less inflammatory cascades happening in her body. She reports 1/10 everyday pain and 2-3/10 pain occasionally when stressed, since it is a trigger for her. Patient has tapered off all medications with a conventional doctor, with only taking Tylenol PRN and Meloxicam as a backup when in pain. She also has less overall inflammation and pain to palpation. She is now able to swim for twenty minutes weekly, has gained more endurance overall, and recently has joined a sports league.

Discussion

Her diagnosis of ankylosing spondylitis showed us that not only does she have an inflammatory arthritis affecting her spine, but also has chronic inflammation throughout her body. Patient was born premature which may have contributed to the formation of the immature immune system and possible dysbiosis. Her current medication, escitalopram (a selective serotonin reuptake inhibitor), can also be contributory to the dysregulation of the gut motility. Her current NSAID regiment may also be causing gastrointestinal mucosa inflammation contributing to a possible intestinal permeability. Patient’s exposure to antibiotics and current symptoms of bloating and gas during the menstrual cycle suggests dysbiosis. Patient has been exposed to a high toxic burden with environmental factors, such as personal care items and polypharmacy at a young age, which may further dysregulate the immune system and the microbiome. Furthermore, the patient’s diet of gluten and processed foods may exacerbate the inflammatory process. Additionally, being HLA-B27 positive is associated with certain autoimmune and immune-mediated diseases, suggesting a predisposition to ankylosing spondylitis. She also has been receiving steroid injections every couple of months from her conventional physician, which suppresses immunity and inflammation acutely, however can increase susceptibility to infections, decreased productions of hormones, and increased risk of heart disease with chronic use, especially at a young age. Her high beta-glucuronidase in the stool is shown to predispose someone to autoimmunity.

Her blood lab results show MTHFR heterozygous gene mutation, functionally high homocysteine, and high globulin levels. We explained that this mutation deceases the active form of folate and can cause a buildup of homocysteine levels. Excess homocysteine can be harmful to our bodies, increasing inflammation, becoming more susceptible to certain cancers, increasing risk of cardiovascular disease, as well as affecting immunity. Her globulin levels can be high due to chronic inflammatory conditions, autoimmunity, or poor digestion and absorption, which is all indicated for this patient.

In my research, vitamin D plays a crucial role in autoimmune patients. Serum vitamin D deficiency is considered a risk factor for several chronic inflammatory or autoimmune conditions, including infectious diseases, type 1 diabetes, multiple sclerosis, and especially autoimmune rheumatic diseases, AS being one of these. Vitamin D deficiency seems to play a role in increasing autoantibody production by B cells, with seasonal vitamin D declines triggering flares in autoimmune rheumatic diseases. A severe serum vitamin D deficiency in genetically predisposed subjects can compromise immune responses by dysregulating dendritic cells and T and B cell functions. Optimal levels of vitamin D regulates both innate and adaptive immunity, allowing our immunity to decrease antigen presentation. Furthermore, serum vitamin D deficiency involves decreased immunity and increased inflammation in patients with rheumatic disease. This study noted that with vitamin D supplementation, there was major improvement with inflammation symptoms and suppressed immunity (Cutolo, 2014).

Studies have shown that vitamin D has immunologic activity. This fat-soluble vitamin has immunosuppressant effects in patients with autoimmunity. Therefore, this justifies why increased vitamin D intake is associated with a lower risk of autoimmune disease (Natural Medicines Databases, 2017).

In a meta-analysis, results suggest that vitamin D plays a protective role in AS. This study concluded that higher levels of serum vitamin D are associated with a decreased risk of AS. Inadequate vitamin D levels can cause imbalances in bone density and dysregulation of calcium resorption, which makes sense when you look at the physiology, that osteoporosis is a complication of AS. This also indicates that parathyroid hormone levels are linked, with high levels of PTH increasing activity of osteoclasts and serum calcium levels. In this study, it showed that PTH levels in AS patients are lower than the healthy controls, therefore warranting more studies between the correlation of PTH and vitamin D (Guoqi, 2015).

One study compared patients with AS versus healthy controls, concluding that vitamin D levels were significantly higher in the healthy control group (P < 0.01) and patients with AS have lower vitamin D levels. Another stimulating topic discussed how tumor necrosis factor alpha plays a role in chronic inflammation and inhibits the binding of vitamin D receptors. There is some discussion that systemic inflammation can lower vitamin D serum levels. Vitamin D can inhibit the expression of TNF-alpha, concluding that being deficient in vitamin D can cause the cascade of inflammation (Pokhai, 2014). 

Another study showed that chronic vitamin D deficiency can result in a permanently altered intestinal environment that no longer favors the healthy bacteria in our gut. Many articles link vitamin D to the normal function of the immune system. In this scientific article, it stated that sustained deficiency of both vitamin D as well as pantothenic acid (B5), since it is needed to produce cortisol, can result in an abnormal pro-inflammatory state (Gominak, 2016). 

Not only does vitamin D play an important role in ankylosing spondylitis, it plays an important role in all autoimmune diseases, such as Hashimoto’s thyroiditis, systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, and irritable bowel disease.  Studies have shown that low vitamin D levels contribute to the development of autoimmune thyroid diseases. Furthermore, this article shows that vitamin D reduces levels of thyroid antibodies and suppresses autoimmune reaction. In this study, by doing a vitamin D replacement therapy, thyroid antibody titers decreased (Yasin, 2016). These studies on adequate vitamin D levels and decreased risk of autoimmunity seems to be promising for autoimmune conditions.  

There is much research regarding serum vitamin D deficiency and its role in autoimmunity. Further studies are warranted to investigate the link between vitamin D levels and disease activity in AS patients. There is much research with preventing AS, however further research is indicated to understand how to decrease pain and symptoms when being diagnosed with AS. Future research should make an effort towards well-designed larger experimental groups as opposed to smaller sample sizes. Ultimately, research about the association of vitamin D receptor defects and AS susceptibility is warranted.

Conclusion

The use of vitamin D supplementation is vital for its role in autoimmunity, showing effectiveness in decreasing the risk of developing an autoimmune condition, such as ankylosing spondylitis. Vitamin D is shown to play a protective role in AS, signifying that without vitamin D, there can be permanent alterations of intestinal microbiota, causing inflammation. These results are favorable in treating this rare autoimmune condition, however more studies are warranted. We must note that the patient was on other medications and supplements. Future plan is to continue monitoring and increasing her quality of life and social abilities by keeping inflammation and pain under control, reintroducing foods that had been limited, and retesting labs to make sure we have stabilized her deficiencies and eradicated infections.

 

Alexandra Carlton, ND

Alexandra Carlton, ND

Alexandra Carlton is a naturopathic doctor and medial resident at the Susan Samueli Center for Integrative Medicine, University of California-Irvine. She received her Doctorate in Naturopathic Medicine from Bastyr University, California, and her bachelor of science at the University of Southern California in human physiology. Her passions include autoimmune diseases, mental health, women’s health, and pediatrics. She is a conduit for healing by educating and inspiring optimal health through highly individualized and dedicated patient care. She enjoys hiking, dancing, cooking is a travel enthusiast, and sports fanatic. 

 

 

REFERENCES

  • “About Spondylitis.” Spondylitis Association of America, SSA, www.spondylitis.org/Ankylosing-Spondylitis/Diagnosis.

  •  Agmon-Levin N, et al. Vitamin D in systemic and organ-specific autoimmune diseases. Clin Rev Allergy Immunol.  October 2013.

  • Costello ME, et al. Brief Report: Intestinal Dysbiosis in Ankylosing Spondylitis. Arthritis Rheumatol. 2015;67(3):686-691.

  •  Cutolo, M, et al. Vitamin D, Steroid Hormones, and Autoimmunity. New York Academy of Sciences. 16 Apr. 2014.

  • Dankers W, et al. Vitamin D in Autoimmunity: Molecular Mechanisms and Therapeutic Potential. Frontier Immunol. January 2017.

  • Gominak SC. Vitamin D Deficiency Changes the Intestinal Microbiome Reducing B Vitamin Production in the Gut. The Resulting Lack of Pantothenic Acid Adversely Affects the Immune System, Producing a "pro-Inflammatory" State Associated with Atherosclerosis and Autoimmunity. Clinical Key. 1 Sept. 2016.

  • Guoqi CG. Vitamin D in Ankylosing Spondylitis: Review and Meta-Analysis. Science Direct. Jan. 2015.

  • Pokhai GG, et al. Vitamin D Levels in Ankylosing Spondylitis: Does Deficiency Correspond to Disease Activity? Rev Bras Rheumatol. 2014; 54 (4): 330–334.

  • Vitamin D Monograph. Natural Medicines. 20 May 2017, naturalmedicinestherapeuticresearch-com.buproxy.bastyr.edu/databases/food-herbs supplements/mechanismofaction.

  • Yasin S, et al. Effects of Vitamin D treatment on thyroid autoimmunity. J Res Med Sci. June 2016.

  • Yu D. Assessment and Treatment of Ankylosing Spondylitis in Adults, UpToDate, July 2017.