Sjögren’s disease is a chronic autoimmune disorder where the immune system mistakenly targets the body’s own healthy cells instead of defending against harmful invaders like bacteria or viruses. This misdirected attack primarily affects the moisture-producing glands, such as the salivary and lacrimal glands, leading to hallmark symptoms of dry mouth and dry eyes.
The lymphocytes (white blood cells that participate in immune reactions) that invade and attack the glands are also considered another prominent sign of autoimmunity. Exocrine glands are glands that empty through ducts and produce body fluids, hence the nickname “moisture-producing glands”. We have exocrine glands all over the body, and therefore Sjögren’s can actually cause “whole-body dryness”.
The term "sicca," which comes from the Latin word "siccus" meaning dry or thirsty, is commonly used to refer to dryness symptoms associated with Sjögren’s. However, the phrase "sicca syndrome" is no longer utilized, as it is now broadly understood that Sjögren’s is a systemic condition that extends beyond just sicca symptoms.
However, Sjögren’s can extend beyond these areas, impacting the joints, skin, lungs, kidneys, and even the nervous system. First discovered in 1933 by Swedish ophthalmologist Henrik Sjögren, the condition is classified into two forms: primary Sjögren’s, which occurs independently, and secondary Sjögren’s, which develops alongside other autoimmune diseases, such as rheumatoid arthritis or lupus.
Sjögren’s is classified as a rheumatic disease since it often leads to musculoskeletal discomfort and occasionally arthritis, which includes joint pain and inflammation symptoms. It can appear on its own or alongside another connective tissue or autoimmune disorder. Historically, the terms "primary" and "secondary" were used to differentiate between these scenarios, but they are no longer in use. This change mirrors the approach to diseases like rheumatoid arthritis, systemic lupus, and scleroderma, which are simply identified as present or absent.
Causes and Risk Factors of Sjögren’s Disease
The exact cause of Sjögren’s disease remains unclear, but research suggests it results from a combination of genetic, environmental, and hormonal factors. These factors may work together to trigger an abnormal immune response where the body attacks its own healthy tissues.
Genetic Predisposition: The prevalence of Sjögren’s disease in relatives of patients with the disease is 12x higher than that in the general population, and genetic distance is associated with the magnitude of risk. However, having a genetic predisposition alone is not enough to cause the disease. A triggering event, such as an infection, is often needed to activate the disease.
Environmental Triggers: Infections caused by viruses or bacteria may act as a trigger for Sjögren’s disease. These infections can set off an immune response that spirals out of control, leading to the body's immune system attacking moisture-producing glands like the salivary and lacrimal glands. Some viruses that are linked to Sjögren’s disease include:
Hepatitis C
Cytomegalovirus (CMV)
Epstein-Barr virus
Human T-lymphotropic virus 1 (HTLV)
COVID-19
Hormonal Influences: Hormonal changes, especially in women, are thought to contribute to the development of Sjögren’s disease. The fact that the disease occurs predominantly in women, suggests that hormones like estrogen may play a role in disease onset.
Key Risk Factors: Several risk factors have been identified that increase the likelihood of developing Sjögren’s disease:
]Gender: Women are about 9 times more likely to develop Sjögren’s than men.
Age: Although Sjögren’s can occur at any age, it is most commonly diagnosed in people over the age of 40. There are two peak ages of onset, 30s and 50s.
Other Autoimmune Disorders: Individuals with other autoimmune diseases, such as rheumatoid arthritis or lupus, have a higher risk of developing secondary Sjögren’s disease. Nearly half of all individuals with Sjögren’s also suffer from another autoimmune condition.
Symptoms of Sjögren’s Disease
The symptoms of Sjögren’s disease can vary widely among individuals, ranging from mild to severe, and may affect different parts of the body. Some people experience only a few symptoms, while others have a broader spectrum of manifestations. The condition is primarily characterized by two hallmark symptoms: dry eyes and dry mouth. However, it can also lead to widespread systemic symptoms affecting multiple organs.
Primary Symptoms
The primary symptoms of Sjögren’s disease involve the body’s moisture-producing glands:
Dry Eyes: Symptoms of dry eyes may include:
Burning or itching sensation
Gritty or sandy feeling in the eyes
Blurry vision
Sensitivity to light
Redness, irritation, and inflammation of the eyelids
Corneal ulcerations
Infections
Dry Mouth: Symptoms of dry mouth may include:
Chalky or cotton-like feeling in the mouth
Difficulty swallowing, tasting, or speaking
Tooth decay, cavities, and gum disease including receding gums
Increased risk of oral infections, such as oral thrush (yeast infections in the mouth)
Dentures
Note: Certain factors, such as smoking, air travel, overhead fans, air conditioning, or windy environments, can trigger the allergic symptoms of Sjogren’s disease.
Systemic Symptoms
In addition to dry eyes and dry mouth, Sjögren’s disease can cause a range of systemic symptoms that may affect various organs and tissues:
Dryness in Other Areas:
Dry throat, lips, or skin
Nasal dryness (i.e. dry nose, recurrent sinusitis, nose bleeds, etc.)
Vaginal dryness, leading to discomfort during intercourse (i.e. vulvodynia)
Fatigue: 3rd highest prevalence in Sjogren’s patients (80%) after dry eyes (92%) and dry mouth (92%)
Head and Neck Involvement:
Changes in taste or smell
Swollen glands in the neck and face (i.e. parotids, lacrimals, salivary)
Skin and Joint Symptoms:
Skin rashes and sensitivity to UV light
Swelling, pain, and stiffness in the joints (i.e. arthritis)
Muscle pain or weakness
Respiratory and Digestive Symptoms:
Dry cough or shortness of breath (i.e. recurrent bronchitis)
Heartburn or acid reflux
Burning sensation moving from the stomach to the chest
Esophagitis
Interstitial lung disease
Pneumonia
Gastroparesis
Autoimmune pancreatitis
Abnormal liver function tests
Chronic active autoimmune hepatitis
Primary biliary cirrhosis
Irritable bowel syndrome
Interstitial cystitis
Neurological Symptoms:
Difficulty concentrating or remembering things (i.e. "brain fog"and memory loss)
Headaches
Numbness or tingling in certain areas of the body
Dysautonomia
Peripheral neuropathy
Other Symptoms and Involvements:
Persistent fatigue or feeling tired
Raynaud’s Syndrome
Vasculitis
Lymphoma
Complications of Sjögren’s Disease
Sjögren’s patients tend to have more aggressive lymphocytes compared to patients with other autoimmune disorders. This factor is reflected in an elevated frequency of lymphomas or infiltration into other organs such as nerves, the lungs, or the kidneys. As a result, Sjögren’s disease can lead to several complications.
The most frequently reported complications involve the moisture-producing glands, leading to issues with dental health and vision:
Dental Cavities: Saliva plays a crucial role in protecting teeth by neutralizing harmful bacteria. With a dry mouth, you're more prone to developing cavities and tooth decay.
Yeast Infections: Individuals with Sjögren’s disease are at a higher risk of developing oral thrush, a yeast infection in the mouth due to reduced saliva production.
Vision Problems: Persistent dry eyes can cause light sensitivity, blurry vision, and even damage to the cornea if left untreated.
In several cases, Sjögren’s disease can lead to serious complications involving various organs:
Lung, Kidney, and Liver Issues: Inflammation may affect the lungs, causing conditions such as pneumonia or bronchitis. It can also impair kidney function or lead to liver issues such as hepatitis or cirrhosis.
Lymph Nodes: A small percentage of people with Sjögren’s disease develop lymphoma (cancer of the lymph nodes).
Nerve Problems: Peripheral neuropathy may occur, resulting in numbness, tingling, or burning sensations in the hands and feet.
Increased Risk of Cancer: People with Sjögren’s disease also face an increased risk of developing certain types of cancers, such as lymphoma and multiple myeloma.
Diagnosing Sjögren’s Disease
Diagnosing Sjögren’s disease can be challenging because there is no single test that can definitively identify the condition. Diagnosis typically involves a team of specialists, such as a rheumatologist, ophthalmologist, and dentist/oral medicine specialist, who will look for key indicators like insufficient tear production, decreased saliva, salivary gland inflammation, and signs of an underlying autoimmune disorder.
Diagnosing Sjögren’s disease involves gathering extensive information from various sources, including medical history, physical exams, and specific tests. Because its symptoms overlap with other conditions and can develop gradually, the diagnosis is usually part of a differential diagnosis. This means that your healthcare provider will use several tests to rule out other conditions before confirming Sjögren’s disease diagnosis. A combination of clinical evaluation, laboratory tests, and imaging studies are typically used to make a final diagnosis.
Key Diagnostic Tests for Sjögren’s Disease
To accurately diagnose Sjögren’s disease, healthcare providers look for specific antibodies in your blood and a pattern of inflammation, particularly in the salivary glands. Because approximately 30% of Sjogren’s patients are SERONEGATIVE, meaning that they do not carry Sjogren’s SSA/SSB antibodies, the diagnostic phase may take much longer than the average Sjogren’s patient. The following tests may be recommended:
Blood and Urine Tests: One test typically referred to as the “traditional test” is used to look for antibodies commonly found in Sjögren’s disease, such as antinuclear antibodies (ANA), which can indicate an autoimmune disorder. A second test typically referred to as the “early Sjogren Panel” is used to look for antibodies to murine paratid tissue proteins (anti-SSA and anti-SSB). Anti-SSA antibodies are often found together with anti-SSB antibodies. However, anti-SSA often appears before anti-SSB.
Schirmer’s Test: This test measures tear production to determine if your tear glands are producing enough moisture to keep your eyes lubricated.
Ocular Surface Staining: A dye is used to examine the surface of your eyes for signs of damage or dryness, which are characteristic of Sjögren’s disease.
Salivary Gland Function Scans: These scans assess the salivary glands located around your neck, below your ears, and under your jaw to evaluate their function.
Lip Biopsy: A biopsy of the lip’s inner surface may be done to check for inflammation in the salivary glands. This is a key diagnostic tool for assessing the severity and type of inflammation characteristic of Sjögren’s disease.
Sialometry: This test measures the flow of saliva, helping to identify reduced saliva production—a hallmark of Sjögren’s disease.
Ultrasonography of Major Salivary Glands: An ultrasound can reveal structural changes in the salivary glands, aiding in the diagnosis by identifying abnormalities typical of Sjögren’s disease.
Managing Sjögren’s Disease
While there is no cure for Sjögren’s disease, various treatment options can help manage symptoms and reduce complications. The choice of treatment depends on the areas affected and the severity of the symptoms.
Treatments for Dryness (Eyes, Mouth, or Vagina):
Artificial Tears and Prescription Eye Drops: Over-the-counter (OTC) artificial tears can help lubricate the eyes. For more severe cases, doctors may recommend prescription drops like cyclosporine (Restasis) or lifitegrast (Xiidra).
Punctal Plugs: In some cases, an ophthalmologist may suggest a minor surgical procedure to close tear ducts to help retain natural moisture.
Saliva Substitutes: OTC saliva substitutes or medications like pilocarpine (Salagen) or cevimeline (Evoxac) may be prescribed to increase saliva production, though side effects like sweating or flushing can occur.
Special Dental Care: Dentists may recommend fluoride treatments, prescription toothpaste, or more frequent cleanings to help prevent tooth decay.
Vaginal Lubricants: Moisturizers or lubricants can be used to manage vaginal dryness, with hormone therapy being an option for some individuals.
Treatments for Pain and Other Symptoms:
Nonsteroidal Anti-inflammatory Drugs (NSAIDs): Medications like aspirin or ibuprofen may relieve joint pain.
Disease-Modifying Antirheumatic Drugs (DMARDs): For systemic symptoms such as joint pain or fatigue, DMARDs like hydroxychloroquine (Plaquenil) or methotrexate may be considered.
Steroid Therapy: In cases involving significant organ inflammation, steroid use might be prescribed to reduce inflammation.
Antifungal Medications: For those experiencing oral thrush, antifungal treatments may be recommended, in addition to prescription mouthwashes.
Nerve/neuropathy medications: Amitriptyline and gabapentin are commonly used to relieve neurological pain.
Biologics: b-cell depleting infusions such as rituximab/rituxan have also been used to treat systemic symptoms.
Conclusion
Sjögren’s disease is a multifaceted autoimmune disorder that affects much more than just the eyes and mouth. While no cure currently exists, understanding the variety of symptoms and potential complications can help patients and healthcare providers work together to manage the conditions effectively. Diagnostic tests and treatment options can vary depending on the individual’s specific symptoms and/or organ involvement, and early diagnosis is key to minimizing complications and slowing down disease progression. Ongoing research continues to uncover more about the underlying causes of the disease, offering hope for improved treatments in the future. Raising awareness about Sjögren’s and encouraging regular medical checkups is crucial to improving the quality of life for those affected.
The number of clinical trials with potential therapies for Sjӧgren’s symptoms such as fatigue, pain, neuropathies, pulmonary complications, and dryness has more than doubled over the last decade. This alone brings hope to patients and those who manage and treat them. In addition, key research programs focused on understanding the immune system, the gut microbiome, and genetics, to name just a few, are experiencing an explosion of new information and are identifying more potential targets for treatments.
"We currently are on the cusp of a new era in medicine with precision medicine, in which therapies can be targeted to individual patients for greater success. The next decade is expected to bring discoveries that will enlighten us further about Sjӧgren’s and offer the first-ever Sjӧgren’s-specific therapies”. (The Sjögren's Book (p. 441). Oxford University Press
Resources
https://www.mayoclinic.org/diseases-conditions/sjogrens-syndrome/symptoms-causes/syc-20353216
https://www.mayoclinic.org/diseases-conditions/sjogrens-syndrome/diagnosis-treatment/drc-20353221
https://my.clevelandclinic.org/health/diseases/4929-sjogrens-syndrome#management-and-treatment
“The sjogrens book” 5th edition, by Daniel J wallace and the board of sjogren’s foundation. https://pmc.ncbi.nlm.nih.gov/articles/PMC5034806/
Reviewed by Mahsa Pazokifard
About Mahsa Pazokifard
Mahsa Pazokifard has navigated a challenging journey through life, marked by health issues that began at birth. After years of pain, discomfort, and organ failure, a pivotal incident led to the diagnosis of Mikulicz and Sjogren's disease, shedding light on the rare and autoimmune conditions that had long affected her well-being. Throughout countless medical visits and procedures, Mahsa emerged as a passionate advocate, not only for herself but also for others facing similar struggles. Her commitment to advocacy has flourished into global and community-based efforts, including collaborations with various nonprofit organizations, leading support groups and research platforms, and founding her own nonprofit organization aimed at serving and empowering the patient community.
Mahsa’s vision revolves around promoting equitable health care and research for patients with rare and autoimmune diseases, standing as a testament to the strength of perseverance and the importance of patient empowerment in overcoming adversity.
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