The Mystery of Sjogren’s Syndrome
If one were to inquire about Sjogren’s syndrome, their immediate understanding would be as follows: An immune disorder characterized by dry eyes and a dry mouth.1 Unfortunately, this limited understanding of such a complex disease can be debilitating for patients and families dealing with the severity of Sjogren’s syndrome. Clinically, the two symptoms of dry eyes and mouth are the most prevalent and easily diagnosable characteristics of the disease.1 Nonetheless, as a rare autoimmune disorder, its effects on the body are vast and are generally accompanied by other severe and even life-threatening conditions, such as Lupus.1 Lupus is extremely severe and attacks an array of normal and healthy tissue throughout the entire body. Therefore, uncovering the veil that hides the severe implications of Sjogren’s syndrome is critical to providing the proper care to every patient that is affected.
As an autoimmune disorder, it is important to understand this condition involves the body attacking its own healthy tissues and cells.2 Normally, the immune system plays a key role in microbial, bacterial, and anti-infectious defence within the body. Certain genetic or environmental stressors can result in the malfunctioning of the immune system, leading to very prevalent autoimmune diseases such as celiac disease, diabetes mellitus type 1, and rheumatoid arthritis as well as rare diseases, like Sjogren’s syndrome.3 Due to the widespread role of the immune system in maintaining homeostasis, the mistaken identification of cells and organs as harmful can cause systemic damage throughout the entire body. In Sjogren's syndrome, the white blood cells of the immune system initially attack the salivary and tear glands.2 The mechanism by which this condition develops and the reason behind the initial attack of moisture-producing tissues is still unknown and will require extensive research.2 Nevertheless, the disease ultimately results in the most identifiable symptoms being dry mouth and eyes caused by a decrease in saliva and tear production.2 As these symptoms may not be immediately life-threatening, Sjogren’s syndrome often goes undiagnosed in a majority of patients, which is when the complexity and severity of the disease begin to take hold.1
This condition is clinically classified as either primary or secondary.2 Primary Sjogren’s syndrome describes the disease in the absence of another condition. The cause of both conditions is still unknown, however a triggering mechanism, such as infection with hepatitis C or the Epstein-Barr virus, may be necessary for development.2 Research also indicates that the nervous system and the endocrine, or hormone-producing, system have been implicated in the onset of Sjogren’s.3 As the majority of people who develop Sjogren's are female, the implication of estrogen in disease progression and development is still an active area of research.4 Within this scope, as menopause is the most common time of diagnosis, some studies theorize that estrogen may play a protective role against Sjogren’s, and falling levels of the hormone may alter immune function, triggering the condition.4 At this time, extraglandular (outside of the glands) problems in Sjogren's syndrome may also develop.2,3 These include fatigue, joint pain or arthritis, lung inflammation and lymph node enlargement, as well as kidney, nerve, joint pain, muscle disease and muscle pain and weakness.2,3 Due to the later onset of some of the more severe symptoms, diagnosis usually occurs at age 40.1 Thus, even though prevention of the disease progression is critical, early diagnosis remains rare.
Recent research funded in part by the NIH’s National Institute of Arthritis and Musculoskeletal and Skin Diseases has also uncovered several genes that are directly implicated in Sjogren’s syndrome.5 Dr. Kathy Sivils, of the Oklahoma Medical Research Foundation, set out to identify genes associated with it, explaining that “By analyzing a large collection of DNA samples from people with Sjogren’s, we can identify gene variants that these patients tend to have in common. Then, by studying the roles these genes play, we can begin to understand how they disrupt the immune system and cause the destruction of moisture-producing glands.”5 Dr. Sivils and her team succeeded in comparing roughly 2,000 Sjogren’s patient DNA samples to 7,000 samples from healthy volunteers.5 Through genetic analysis, they were able to identify six genes associated with the condition: IRF5 and STAT4, involved in the stimulation of the immune response, CXCR5, a gene implicated in immune cell migration, TNIP1, a protein that plays a role in limiting inflammation, and BLK and IL12A, both of which produce proteins that aid in immune cell activation.5 Interestingly, these genes have been linked to other autoimmune diseases.5 IRF5, STAT4, and TNIP1 have been linked to systemic lupus erythematosus and rheumatoid arthritis and IRF5 and IL12A have been previously identified in the chronic liver disease primary biliary cirrhosis.5
This genetic connection is the possible mechanism behind secondary Sjogren’s syndrome, which occurs alongside another severe autoimmune disease; most commonly, systemic lupus erythematosus.2,6 Other disorders, such as rheumatoid arthritis and primary biliary cirrhosis, are also commonly associated with Sjogren’s, as suggested by the aforementioned genetic similarity.2,6 It is important to note that even though primary Sjogren’s is not correlated with another condition, it can be just as severe as the secondary classification of the disease. Nonetheless, the complexity of this co-occurrence makes it difficult to categorize the disease in every individual. As every patient with secondary Sjogren’s syndrome has a second autoimmune disease, it is critical to understand both diseases and their implications especially if there's any interplay between the two conditions. Specifically, rheumatoid arthritis is a severe autoimmune condition that causes long-lasting and progressive inflammation and pain in the joints, the tissue around the joints, and other organs within the body.7 Moreover, the most common co-occurring disease is lupus, an extremely severe and chronic autoimmune disease in which the body's immune system becomes hyperactive and attacks an array of normal and healthy tissue throughout the entire body.8 The severity of lupus resides in its lack of targeted tissue, as any part of the body can be affected, owing to an array of clinical manifestations that affect the skin, joints, brain and other internal organs.7 Patients suffering from secondary Sjogren’s syndrome present many different symptoms, making diagnosis and treatment difficult. Until the underlying causes can be recognized, proper care for patients remains limited.
Therefore, understanding the complex nature of Sjogren’s syndrome is imperative to foster more research and insight into this disease for its patients and those it affects. Currently, no treatment has been identified, and the current standard of care is antibiotics that can only manage the patient's symptoms. Thus, gaining further insight into how Sjogren’s syndrome correlates with other autoimmune disorders as well as the various hormonal, environmental, infectious, and genetic causes, could be critical to providing patients with early diagnoses and the healthcare they require to flourish in the face of this rare disease.
1. Sjogren's syndrome - Mayo Clinic. Mayoclinic.org. 2017. https://www.mayoclinic.org/diseases-conditions/sjogrens-syndrome/symptoms-causes/syc-20353216.
2. Sjögren's Syndrome Foundation. Sjogrens.org. 2017. https://www.sjogrens.org/home/about-sjogrens/sjoegrens-faqs.
3. Sjögren's Syndrome: Current issues. American College of Physicians, Annals.org. 2017. http://annals.org/aim/article-abstract/693719/sj-gren-s-syndrome-sicca-syndrome-current-issues.
4. Brandt J, Priori R, Valesini G, Fairweather D. Sex differences in Sjögren’s syndrome: a comprehensive review of immune mechanisms. Biol Sex Differ. 2015;6(1). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4630965/.
5. Lessard CJ, Li H, Adrianto I, et al. Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjögren's syndrome. Nat Genet. 2013;45:1284. https://www.nature.com/ng/journal/v45/n11/full/ng.2792.html.
6. Montefusco P, Geiss A, Bronzo R, Randall S, Kahn E, McKinley M. Sclerosing cholangitis, chronic pancreatitis, and sjogren's syndrome: A syndrome complex. Amer Jr Surgery. 2017. http://www.americanjournalofsurgery.com/article/0002-9610(84)90212-5/pdf.
7. Rheumatoid arthritis - Mayo Clinic. mayoclinic.org. 2017. https://www.mayoclinic.org/diseases-conditions/rheumatoid-arthritis/symptoms-causes/syc-20353648.
8. Lupus - Mayo Clinic. Mayoclinic.org. 2017. https://www.mayoclinic.org/diseases-conditions/lupus/symptoms-causes/syc-20365789.
Cite This Article:
McKee H., Chan G., Zhang B., Palczewski K., Lewis K., Ho J. The Mystery of Sjogren’s Syndrome. Illustrated by W. Zhang. Rare Disease Review. December 2018. DOI:10.13140/RG.2.2.30894.97600.