March 2022 Issue
CPE Monthly: Sjögren’s Syndrome
By Danielle VenHuizen, MS, RD, CLT
Vol. 24, No. 3, P. 46
The Latest Research and Updates on How to Counsel Patients
Suggested CDR Performance Indicators: 8.1.1, 8.1.5, 8.2.1, 8.2.4
CPE Level 2
Sjögren’s syndrome (SS) is a complex autoimmune disease. Named after Swedish ophthalmologist Henrik Sjögren, this disorder uniquely affects the exocrine glands but can affect multiple systems in the body.1 The hallmark feature is the immune-mediated destruction of exocrine glands, which typically leads to symptoms such as dry eye, dry mouth, dryness in other mucous membranes, and even decreases in pancreatic enzymes.2 However, these complaints of dryness in the exocrine glands, known as sicca syndrome, aren’t the only symptoms. Unfortunately, SS appears to be a multisystem disorder that isn’t yet fully understood.2,3 In fact, three-quarters of SS patients will have at least one extraglandular manifestation.4
SS can be separated into two categories: primary SS and secondary SS. The former is diagnosed without comorbid autoimmune conditions, while the latter is associated with these conditions, such as rheumatoid arthritis, lupus, and scleroderma. While most of this article will address primary SS, it’s important to note that this condition can commonly present with other autoimmune diagnoses.5
SS targets females at a much higher rate than males. Current research suggests a ratio of 9:1 with an onset often in the postmenopausal years, which suggests estrogen and androgen imbalances may be involved in disease progression.5 Besides hormonal components, there may be genetic, environmental, and immunological risk factors that contribute to the overall pathophysiology.6 Likely due to this array of risk factors, each case can present a distinct clinical picture, making SS challenging to diagnose and treat.2
The symptoms of sicca syndrome are the most common and usually the first noted in those later diagnosed with SS. These may be mild initially but often lead to more severe complaints including ocular damage and pain, voice problems, chronic cough, swollen salivary glands, skin rashes, yeast infections, and even dental cavities and tooth loss.2 Nonspecific symptoms such as fatigue and pain also are common, leading to significant decreases in quality of life.7
Other organ systems that can be affected and produce symptoms include the renal system, the peripheral nervous system, and the lungs.4 Small fiber neuropathy, a condition in which the small fibers of the peripheral nervous system are damaged, has been associated with SS, and it’s clear that the risk of cardiovascular events also increases.2 Another concerning complication of SS is the increased risk of non-Hodgkin’s lymphoma.8 Because these symptoms and conditions appear to increase in severity over time, early and accurate diagnosis is crucial.
This continuing education course examines current research in SS and the potential role diet and supplementation intervention play in disease management.
Diagnosing SS can be difficult given that the clinical presentations can vary significantly. Furthermore, there’s no gold-standard diagnostic method, but there are classification criteria established by the American College of Rheumatology/European League Against Rheumatism. Focus score, determined using labial salivary gland biopsy to assess and quantify the level of glandular inflammation, is considered the best predictor of SS.9 A common secondary tool is assessing for autoantibodies to the autoantigens Ro/SSA and La/SSB.1
Other biomarkers commonly are assessed, specifically antinuclear antibodies and rheumatoid factor, but they aren’t emphasized in the American College of Rheumatology criteria. Still others being investigated include muscarinic type 3 receptor activity, which helps modulate insulin secretion; salivary calprotectin levels, which can suggest inflammation in the oral cavity; and carbamylated protein levels, which may become elevated years before symptoms develop in autoimmune diseases.1
Standard Medical Interventions
There’s no one targeted treatment for SS. Interventions are individualized based on symptoms and severity of disease activity with the goal of improving quality of life. Because the manifestations can be so varied, a multidisciplinary team should be assembled to address the various organ systems. This (team) can include the primary care physician, rheumatologist, ophthalmologist, gynecologist, RD, dentist, and ear, nose, and throat specialist.7
Sicca syndrome symptoms typically are managed with tear substitutes and anti-inflammatory eye drops, along with appropriate dental care to address lower levels of saliva. Common pharmacologic interventions to target systemic manifestations include NSAIDs, corticosteroids, hydroxychloroquine, and immunosuppressive drugs.7
Apart from pharmacotherapy, general health education may be needed to address lifestyle factors that may be affecting fatigue or other related symptoms. Topics may include diet, sleep hygiene, smoking status, alcohol intake, and level of physical activity.7 This is where dietitians should be considered an integral part of the care team, as they tend to be best suited to address these areas of behavior change.10
No standardized treatment or cure currently is available for SS; however, research suggests that a specialized eating pattern may help modulate the immune response and thereby improve symptomatology, or even help prevent the condition. Research is limited, but there’s some evidence to draw upon concerning the Mediterranean diet, anti-inflammatory diet, Autoimmune Protocol (AIP), and gluten-free (GF) diets, as well as the use of various supplements.
Numerous studies have touted the disease-mitigating effects of the Mediterranean diet. This pattern of eating emphasizes high-fiber plant foods; lean meats, especially fish; and moderation of red meat, dairy, and alcohol, particularly red wine. Research consistently shows the Mediterranean diet may be helpful for managing or preventing diabetes, high blood pressure, and high cholesterol.4 Other studies suggest it helps reduce the risk of autoimmune conditions, notably rheumatoid arthritis (RA). These potential benefits are attributed to the dietary pattern’s anti-inflammatory effects; thus, it also has been postulated to be helpful in SS.6
Several studies examining RA and lupus found benefits from a Mediterranean-style diet, but few have looked at SS specifically.11-14 One recent study by Machowicz and colleagues, however, found that those following a Mediterranean diet had a lower risk of being diagnosed with SS. Components of the diet such as vitamin A, vitamin C, and omega-3 fatty acids were associated with lower odds of developing SS.6
One of the hallmarks of the Mediterranean diet is its inclusion of omega-3–rich foods. Another recent study, by Castrejón-Morales and colleagues, examined fatty acid intake in 108 SS patients, showing that these patients tended to have lower omega-3 fatty acid intake compared with controls. They also noted that those with higher omega-3 intakes had lower ocular and salivary symptoms, suggesting the anti-inflammatory benefit of omega-3s influenced symptomatology.15
The anti-inflammatory diet, which has been popularized in recent years, also has been examined. While similar to the Mediterranean diet in some ways, it goes a step further in reducing or eliminating what proponents claim are inflammatory foods, such as dairy, red meat, gluten and refined grains, highly processed foods, added sugars, and sometimes eggs, soy, and nightshade vegetables.13,14
There are no consistent or defined criteria for this diet, and evidence is extremely limited as to whether it can benefit those with autoimmune conditions; there’s almost no information regarding SS. Observing specific parts of the diet and their effects on other autoimmune conditions may provide some clues about its potential efficacy.
Some evidence suggests that lower red meat intake decreases the risk of RA, while increased fruit and vegetable intake helps promote prevention. As for dairy products, results are mixed. The Iowa Women’s Health Study showed an inverse relationship between dairy intake and RA risk, while a large Swedish study following a cohort of more than 35,000 females showed no association between dairy intake and risk for RA.13
Anti-inflammatory diets often promote greater omega-3 fatty acid consumption, which results in a more healthful balance with omega-6 and -9 fatty acids. In addition, omega-3 intake appears to correlate with lower inflammatory markers and decreased risk of autoimmune disease.15
Nightshade vegetables, including tomatoes, eggplants, potatoes, and peppers, are rich in the compound solanine, which may increase inflammation, according to some studies. Though the reasons are unclear, recent research in participants with RA suggests solanine may induce intestinal permeability and thereby increase the risk of immune activation.14
All of these reasons could explain why an anti-inflammatory diet may help prevent or alleviate certain symptoms of some autoimmune conditions. While SS-specific studies are lacking, extrapolating from research on RA lends some support to the role of these diets.
Autoimmune Protocol Diet
The Autoimmune Protocol diet (AIP diet) also has gained more interest in recent years. It follows the general principles of the Paleo diet, which emphasizes foods believed to have comprised human diets in the Paleolithic era and eschews many “modern” foods, such as grains, dairy, nuts, seeds, legumes, and sugars. Proponents believe the latter foods promote inflammation due to industry processing, and/or that they contain naturally occurring compounds, namely phytates, that hamper digestion; in their view, the result is a cascade of immune responses that leads to autoimmune disease.16
The AIP diet, which proponents see as effective for all autoimmune conditions, eliminates all grains, dairy, nuts and seeds, legumes, processed foods, sugar, artificial sweeteners, dried fruit, nightshades, vegetable oils, coffee, alcohol, and chocolate. It emphasizes a variety of fruits, vegetables, and meats, including organ meats, preferably grass-fed.16
While the AIP diet is popular in the autoimmune community and has some anecdotal evidence of its success in reducing or eliminating symptoms, there’s almost no peer-reviewed research on this diet. One small study in 2019 by Abbott and colleagues looked at the AIP diet in relation to Hashimoto’s thyroiditis in a group of 17 females aged 20 to 45. Using the AIP over a 10-week period along with health coaching, they found that the diet lowered inflammation levels in subjects as evidenced by a significant decrease in high-sensitivity C-reactive protein. Although they found no significant changes in thyroid function, researchers concluded that there were some potential benefits of the diet, but more research is needed, especially with more participants and of longer duration.16
While the AIP diet may be beneficial for some, there’s not enough evidence showing that the benefits outweigh the potential harms. Restricting a diet to this degree can lead to nutrient deficiencies and trigger disordered eating or eating disorder behaviors, and be too difficult for most individuals to follow.17
GF diets are highly popular and commonly followed, regardless of medical necessity. While the protein gluten is known as the main antagonist in celiac disease (CD) (ie, a condition in which elevated antibodies to gluten and gliadin initiate destruction of the villi of the small intestine), it also has been theorized to be a driver of other autoimmune conditions. There may be some shared mechanism of action between SS and CD. In 1984, Teppo and colleagues found that, as in patients with CD, individuals with SS showed increased autoantibodies to gluten and gliadin, which led them to conclude that small bowel injury may be a part of SS pathology.18 A 2004 study noted a link between gluten and oral inflammation, concluding that a GF diet may alleviate autoimmune inflammation.19
But more recent studies also are finding connections. In 2015, Koszarny and colleagues reported that SS patients had higher levels of anti-gliadin antibodies than the general population.20
Balaban and colleagues conducted a 2020 literature review on the prevalence of CD in SS. Studies showed correlations from 1% to 14.7%.21 Even more recently, a study on mice found that inflammation in salivary glands was reduced on a GF diet, suggesting a link between SS and CD markers.22
While more research into these possible links is needed, there may be justification for considering a GF diet to help manage SS. Patients with SS should be recommended to be tested for CD first before removing gluten; however, if someone already is following a GF diet, test results may not be accurate, given antibody levels typically decrease once gluten is eliminated. For those who have been following a GF diet, it’s typically recommended that gluten-containing foods should be incorporated for two to eight weeks before testing for proper diagnosis.23
Overall, there’s some evidence that diet modification could contribute to SS management, and clinicians should consider diet education as part of the treatment plan. While strict diets likely shouldn’t be recommended, focusing on nutrient-dense foods may be helpful, with little risk of harm.
The Role of Supplementation
The use of dietary supplements for autoimmune conditions has been studied, often with mixed results. Vitamin D; other micronutrients including vitamins A, C, and E; essential fatty acids (EFA); and curcumin have been the primary topics of research.
Vitamin D has been researched for its potential role in many conditions, especially autoimmune diseases. Vitamin D deficiency has been observed in diseases such as RA, Hashimoto’s thyroiditis, lupus, and multiple sclerosis, but there has been very little research on SS specifically, and results have been mixed.24-26
A study of 235 SS patients conducted in India by Sandhya and colleagues showed that vitamin D deficiency in this group wasn’t more prevalent than in the general population, but deficiency in SS patients correlated with higher focus scores and increased markers for rheumatoid factor. They didn’t find links with any other markers of SS.27
A recent review study by Björk and colleagues showed no statistically significant increase in SS risk with low vitamin D levels and concluded there’s little support for the role of vitamin D in the development or activity of SS.28 Alternatively, two other review studies showed a link between adequate vitamin D levels and decreases in dry eye symptoms and other extraglandular manifestations. This was hypothesized to be due to lowered levels of inflammation resulting from normal vitamin D status.29,30
While the results thus far are varied, vitamin D still may be a beneficial addition to overall diet recommendations for SS. There may be potential for symptom reduction, especially when deficiency is known, and the supplementation presents little risk. However, more research is needed, especially in terms of understanding what vitamin D levels are optimal for symptom reduction and what doses of vitamin D are advised for people with SS.
Various other micronutrients have been examined over the years for associations with autoimmune diseases. Notably, vitamins A, C, and E have been assessed for their role in immunoregulatory processes. While they’ve shown, either alone or in combination, antioxidant and anti-inflammatory effects in the body, none have been suggested to significantly reduce symptomatology. There’s some evidence that patients deficient in these vitamins had higher levels of inflammatory cytokines and higher symptom scores, but contemporary research is lacking.31-34
It’s safe to assume nutrient deficiency isn’t ideal for any disease state, especially with autoimmune disorders, as evidence suggests low levels of nutrients such as the aforementioned vitamins may exacerbate inflammation and worsen symptoms.33,34 While more research is much needed, these findings demonstrate another reason why dietary improvements for these patients may be important for overall disease management.
In recent years, more research has investigated the effect of EFA supplements on inflammation and whether they may benefit those with autoimmune conditions. These include omega-3 and -6 fatty acids that aren’t produced endogenously and therefore must come from the diet.
As discussed previously, dietary intake of EFAs may be one of the primary ways the Mediterranean diet appears to help reduce symptoms in autoimmune conditions. In light of this, supplementation with EFAs on their own might be expected to do the same. Research shows SS patients have lower intakes of EFAs, which is correlated with higher symptom scores, but we have little information on whether supplementing with these fatty acids has the same effect as obtaining them from foods.15
Older studies have suggested both omega-3 and -6 fatty acids can improve ocular symptoms, but recent research in those with SS is lacking.35,36 A 2013 randomized, double-blind clinical trial of 38 SS patients found that long-term supplementation with EFAs improved symptoms of keratoconjunctivitis sicca (dry eye disease).37 However, research in 2018, including one clinical trial on 329 patients with dry-eye disease and another review study comprising more than 2,900 participants with dry eye, suggests that omega-3 supplements on their own didn’t improve symptoms significantly over placebo.38,39
Once again, results are mixed; however, as with vitamin D, EFAs should be another consideration in the dietary recommendations for SS. While obtaining EFAs from the diet is preferable, supplementation may play an important role as well, especially in cases where an individual has clear deficiency and difficulty following intake recommendations. Hopefully, more research will be conducted in the future to further elucidate the role of EFAs in SS and establish more guidance for dietary or supplemental intake.
Much research has been done on the use of turmeric, especially its compound curcumin, as an anti-inflammatory aid. Countless studies have established that turmeric exhibits potent antioxidative and anti-inflammatory benefits in chronic diseases.40
As with most supplements, studies on the relationship between SS and curcumin are limited. There are a couple of studies showing benefits with turmeric supplementation, but nothing in recent years. A 2010 in vitro study by Kurien and colleagues found that curcumin decreased the binding of autoantibodies in SS, which could slow disease progression.41 A mouse study in 2015 demonstrated significantly reduced levels of inflammation in salivary glands following several weeks of curcumin supplementation.42
More recent research on other autoimmune conditions show benefit, hinting that turmeric likely helps quell inflammation, slow disease progression, and reduce symptomatology.43-45
Given this research, turmeric added to food or taken as a dietary supplement might be helpful in a comprehensive nutrition plan to target inflammation. The main drawbacks are limited absorption and variation in formulations of turmeric and curcumin supplements on the market. More research needs to be done on which forms are best absorbed and how they should be administered—via food, supplementation, or both. For now, RDs can safely suggest clients use turmeric as a spice in food, and practitioners can consider supplementation for symptom management. Risk of use is low, but those taking blood thinners should discuss supplementation first with their doctors, as curcumin can exhibit similar anticoagulant properties.46
Supplementation may be helpful in managing SS symptoms. While research is limited, correcting vitamin deficiencies and suggesting potentially anti-inflammatory foods and nutrients such as omega-3s and turmeric could be useful. Generally, these supplements are safe, provided high-quality and third party–tested products are used, and side effects are few.
Role of the Microbiome in SS
The potential role of the microbiome in disease states has become a topic of considerable interest to researchers. Humans possess a host of immune cells in the mucous layer of the intestines and also in saliva. There’s a delicate balance between the gut bacteria and immune system. It’s theorized that, when bacterial balance is lost and there’s a disruption of the gut barrier, bacteria may interact with the immune system and send immune complexes into the bloodstream, causing symptoms in other systems of the body.47
The evidence seems to suggest that gut dysbiosis contributes to the pathophysiology of autoimmune diseases.48 However, much of this research is still in its infancy because so much is unknown about the microbiome; less than 50% of the bacteria present in the oral cavity and only 20% in the gut have been cultivated. The remaining bacteria are thus far “unculturable” and require considerable workarounds to be studied.49 There may be many potential bacterial contributors to diseases yet to be thoroughly explored.
Many people with autoimmune conditions, including SS, have microbiome compositions different from those of healthy subjects. In a recent study of 36 participants by Moon and colleagues, SS patients had higher levels of Bacteroidetes and a lowered ratio of Firmicutes to Bacteroidetes, along with less microbial diversity overall. Higher levels of dysbiosis were found in diagnosed SS patients compared with those with sicca symptoms without SS and controls.47
While these associations are still preliminary, more research has been investigating how to preserve a healthy microbiome or promote positive shifts in bacterial balance to reduce inflammation, which in turn may help reduce the incidence of SS or slow its progression.50
Certain dietary changes, including the addition of probiotic-containing foods and prebiotic fibers to support healthy bacterial growth and correct gut barrier dysfunction, may be beneficial. Probiotic supplements also may be warranted, specifically strains of Lactobacillus and Bifidobacterium, both of which are shown in some research to be critical in restoring microbiota balance.50 There’s ample evidence from studies on other autoimmune conditions that probiotic administration can reduce the risk of disease or decrease the inflammatory markers in conditions such as type 1 diabetes, RA, and multiple sclerosis.51 While there’s no clear evidence for the impact of these actions on SS, it could be extrapolated that probiotic use may be helpful.
Putting It Into Practice
SS is a complex autoimmune condition likely caused by a host of factors, and it produces a wide range of symptoms that can drastically reduce quality of life. Unfortunately, there’s no cure or standardized treatment. The clinician’s role should be to support appropriate and evidence-based dietary and supplemental means to reduce systemic inflammation, which may slow disease progression and help alleviate symptoms.
It appears that diets focused on reducing inflammation may positively impact symptomatology. While there’s no clear evidence on which diet is preferential, it’s likely that guiding patients toward more healthful eating patterns that meet their nutritional needs can only help in disease management. RDs shouldn’t enforce one specific way of eating but instead support patients in finding a healthful diet pattern they can follow. Adding key nutrients also may help, especially where deficiency or insufficiency is known.
To promote microbiome health, RDs should suggest clients add more foods that include probiotics and prebiotic fiber and consider probiotic supplementation.
Hopefully, more research will be conducted on SS to better elucidate which dietary components or eating patterns are key for reducing symptoms, which supplements and dosages best target symptoms, and how to change the microbiome for optimal health.
— Danielle VenHuizen, MS, RD, CLT, is a Seattle-based dietitian and owner of Food/Sense Nutrition.
After completing this continuing education course, nutrition professionals should be better able to:
1. Define Sjögren’s syndrome and evaluate its clinical manifestations.
2. Counsel patients on the current methods of diagnosis and treatment.
3. Distinguish the risk factors for Sjögren’s syndrome.
4. Assess evidence-based dietary recommendations with Sjögren’s patients, and discuss benefits and risks of supplement use.
CPE Monthly Examination
1. What is one of the main symptoms of Sjögren’s syndrome (SS)?
a. Hair loss
b. Dry eyes and dry mouth
c. Loss of taste
d. Nerve pain
2. Why might SS affect women more than men?
a. Environmental factors
b. Dietary differences
c. Imbalances in estrogen and androgens
d. Differences in metabolism
3. Supplementation with which of the following micronutrients may show some benefit in SS?
a. Vitamin D
b. Vitamins B6 and B12
c. Vitamins A and K
d. Choline and magnesium
4. Which ratio appears to be lowered in those with SS?
a. Lactobacillus to Bifidobacterium
b. Omega-3s to omega-9s
c. Vitamin B12 to Vitamin D blood levels
d. Firmicutes to Bacteroidetes
5. Which marker for inflammation was decreased in patients consuming an Autoimmune Protocol diet, according to Abbott and colleagues?
a. Sed rate
b. Focus score
c. High-sensitivity C-reactive protein
d. Ratio of omega-3s to omega-6s
6. What percentage of SS patients will demonstrate at least one other extraglandular manifestation?
7. Which supplement has evidence for its anti-inflammatory properties?
b. Vitamin A
c. Vitamin C
d. Vitamin E
8. Why is it difficult to understand the role of the microbiome in SS?
a. There’s little interest in microbiome research.
b. Studies on the microbiome have been inconclusive.
c. No patterns in type of bacteria present have been found.
d. There are many types of bacteria currently unable to be studied.
9. Castrejón-Morales and colleagues noted that patients with higher intakes of which nutrient had lower ocular and salivary symptoms?
a. Omega-3 fatty acids
b. Omega-6 fatty acids
c. Vitamin D
d. Vitamin E
10. Which of the following is one of the best predictors of SS?
a. High-sensitivity C-reactive protein
b. Ratio of Firmicutes to Bacteroidetes
c. Focus score
d. Antinuclear antibodies
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