Sjögren's Syndrome

Sjögren's is a systemic, autoimmune, rheumatic disease that can affect many different body parts, especially the moisture-producing glands, and cause widespread dryness and other serious problems. Although dry mouth and dry eyes are the most common symptoms, dryness can also occur in the nose, sinuses, ears, throat, skin, and, in women, the vagina. There is speculation that, in men with Sjögren's, the prostate might be affected similarly to other organs. These problems may interfere with work, social activities, and quality of life. Patients may notice irritation, a gritty feeling, or painful burning in the eyes; dry eyes are at increased risk for infection and susceptible to corneal damage if not treated. Dry mouth can lead to difficulty eating and swallowing dry foods. It can lead to dental cavities, chipping, breaking, and loss of teeth. Dry mouth may increase gingivitis (gum inflammation) and oral yeast infections (candida) that may cause pain and burning. Sjögren's frequently causes swelling of the parotid glands (the glands below the ears and run along the jawline). Dryness can increase infections in the eyes, mouth, sinuses, lungs, and vagina.

Sjögren's can also affect the joints, muscles, nervous system (central nervous system and peripheral nervous system, including the autonomic nervous system), gastrointestinal tract (including the pancreas and liver), skin, blood vessels, lungs, and kidneys. Joint pain and stiffness with mild swelling are common, even in those without rheumatoid arthritis. Rashes may occur, including inflammation of small blood vessels (vasculitis), most commonly on the lower legs. Sun-sensitive rash is more common on the back, chest, face, and arms. Peripheral neuropathy can cause numbness and tingling, especially in the feet, and can frequently pre-date symptoms of dryness.Fatigue, cognitive dysfunction, and sleep abnormalities are frequently reported symptoms.Patients should also be monitored for depression and anxiety. .

Sjögren's can be accompanied by other autoimmune connective tissue disorders, such as systemic lupus erythematosus, rheumatoid arthritis, scleroderma, autoimmune thyroid disease, antiphospholipid syndrome, sarcoidosis, and celiac disease. It can occasionally be confused with fibromyalgia, multiple sclerosis, and a newly described disease called IgG4-related disease.

The cause of Sjögren's is unknown, but we know it is an autoimmune disorder. This suggests that the immune system, which normally protects the body against cancers and infections, is reacting against its own tissues. The formation of abnormal antibodies (called autoantibodies) in blood that react to self-proteins is a marker and/or contributor to this process. The decrease in tears and saliva occurs when the glands that produce these fluids become dysfunctional and damaged by inflammation and infiltration by blood cells called lymphocytes. Research suggests that genetic factors and sex hormones when combined with an environmental agent, such as a viral infection, may trigger development of the disease.

Diagnosis depends on a combination of symptoms, physical examination, blood tests, and special studies to look for objective evidence of dry eyes and dry mouth. The diagnosis of Sjögren’s cannot be based on symptoms alone because dry eyes and mouth are highly prevalent symptoms in the general population and can be caused by many other conditions or medications. Special tests may assess for decreases in tear or saliva production. An eye examination with staining of the cornea and conjunctiva with vital dyes helps detect and assess for damage (i.e. dry spots) to the outer surface of the eyes caused by dryness. Blood tests can look for autoantibodies that often occur in this disease. Typical antibodies include anti-nuclear antibodies (ANA), anti-SSA/Ro, SSB/La antibodies or rheumatoid factor. Biopsy of the minor salivary glands (usually taken from the inner lower lip) may also be used to make a diagnosis when autoantibodies are absent.

Children and young adults often present with different signs and symptoms of Sjögren's compared to older adults. Initial symptoms more commonly include swollen parotid glands and arthralgias (joint pains). The pediatric population also may have neurologic and kidney manifestations. Dryness features might or might not be present at diagnosis.

Currently, no systemic immunomodulating therapies are FDA-approved for Sjögren's. Hydroxychloroquine (Plaquenil™), an antimalarial drug, may be helpful in some patients with Sjögren's and reduce joint pain, fatigue, or rash. Patients with systemic problems, such as fever, severe rash, , lung disease, neurologic problems or kidney involvement may require treatment with corticosteroids (such as prednisone and methylprednisolone) and/or immunosuppressive drugs like methotrexate, azathioprine (Imuran™), mycophenolate mofetil (CellCept™), leflunomide (Arava™), or cyclophosphamide (Cytoxan™). In addition, biological therapies, such as rituximab (Rituxan™), may be used, especially in severe disease.

Dry eyes usually respond to artificial tears applied regularly during the day or to ointment applied at night. Other measures, such as plugging or blocking tear ducts by the opthalmologist, can be used in more severe cases. Eye drops that reduce inflammation in the glands around the eyes, such as cyclosporine (Restasis™ and Cequa™) and lifitegrast (Xiidra™), may significantly improve symptoms and decrease the need for artificial tears. Drinking water, using sugar free gums and candies sweetened with xylitol, or using saliva substitutes may relieve dry mouth. Many patients benefit from using prescription medications that stimulate saliva flow, such as pilocarpine (Salagen™) or cevimeline (Evoxac™). If patients develop yeast infections, anti-fungal therapies may be needed. Humidifiers and nasal saline irrigation may improve nasal dryness. Medications that reduce gastric acid (such as proton-pump inhibitors and H2 blockers) may lessen symptoms of acid reflux

All patients should receive regular dental care to prevent cavities and tooth loss. Fluoride in the form of prescription-strength toothpaste or varnishes administered by the dentist is known to prevent these complications. Patients with dry eyes should regularly see an eye doctor (ophthalmologist or optometrist) to monitor for signs of damage to the cornea. Patients with excessive redness and pain in the eyes should be evaluated for infections.

Symptoms vary in type and intensity, but the burden of illness for many people with Sjögren's is high. Regular medical care, follow-up, and referral to other specialists as needed are important for optimal care. In addition to having a rheumatologist or knowledgeable primary care provider who understands Sjögren's to coordinate a patient's care, all Sjögren's patients should regularly see an eye doctor and dentist or oral medicine specialist. Doctors who specialize in the blood (hematologist), nerves (neurologist), lungs (pulmonologist), intestinal tract (gastroenterologist), kidneys (nephrologist and urologist), gynecologist, and other specialists may be called upon as needed.

One of the most severe potential complications of Sjögren's is lymphoma, a cancer of the lymph glands. Lymphoma occurs in up to 10% of Sjögren's patients. The highest risk is for B-cell non-Hodgkin lymphoma, with the parotid gland being a common site. Other cancers occurring at a higher rate in Sjögren's include multiple myeloma, thyroid, and stomach cancer.

Recognition of potential lung involvement in Sjögren's has increased in recent years. Ten percent of patients are diagnosed with interstitial lung disease in the first year following diagnosis with Sjögren's and 20% within five years. Cystic lung disease is identified more frequently in Sjögren's compared to other connective tissue diseases. As many as 65% of Sjögren's patients with no lung disease symptoms will have abnormal imaging studies.

Neurological manifestations may include numbness and tingling, especially in the feet and legs. However, the hands, face, and other areas may also be involved. Weakness and abnormal gait may occur in severe cases. Involvement of the autonomic nervous system has come to the fore with long-term COVID. More attention is being paid to symptoms of autonomic nerve dysfunction (dysautonomia) in Sjögren's. Symptoms of dysautonomia can include heart rate abnormalities, sweating, blood pressure fluctuations, and temperature regulation, and affect digestion, bladder control, and balance. One type of dysautonomia is POTS (postural orthostatic tachycardia syndrome), which can cause dizziness and faintness, especially upon standing.

Fetal heart block due to anti-SSA/Ro autoantibodies may occur in babies of pregnant mothers. Monitoring for this potential complication in the fetus is paramount, so treatment can be initiated in utero or upon birth. The need for monitoring Sjögren's patients for cardiovascular disease, including pulmonary arterial hypertension, atherosclerosis, and other cardiovascular events, also should be recognized.

Sjögren's cannot be cured, but in many cases, proper treatment helps to alleviate symptoms and prevent complications. Rheumatologists are musculoskeletal and autoimmune disease specialists and, therefore, more likely to make a correct diagnosis of Sjogren’s than other care providers. They also can advise patients about the best available treatment options and coordinate care from other specialists when needed.

People with Sjögren's usually can live full lives with proper self-care and the care of knowledgeable healthcare professionals. Patients should be monitored regularly for the development of severe complications, such as lymphoma, vasculitis, and pulmonary, kidney, and liver disease, any pain or redness in the eyes should be evaluated promptly, as this may signal an infection or corneal damage. To reduce the risk for cavities and other dental problems, patients must follow protocols for dry mouth, such as regular use of fluoride, follow a strict oral hygiene regimen, and seek regular dental care.

Patients should see their physician regularly for general health screening and preventative medicine. They should also pay close attention to any abnormal persistent swelling in the glands around the face or neck, under the arms, or in the groin areas, as this may signify lymphoma.