Sjögren's Syndrome

Sjögren's syndrome is a common cause of immune neuropathy. It is treatable, so it’s worth knowing if you have it.

By Anna Harrison, research assistant intern, MGH Nerve Unit, with MaryEllen Talbot

9.9.9AnnaHarrisonMaryEllenPrimary Sjögren's syndrome is an autoimmune disease, the type of condition where your body’s immune system gets confused. Instead of attacking foreign cells that could be dangerous like bacteria, the body’s immune system mistakenly attacks and destroys some of its own cells. There are different types of autoimmune conditions depending on what type of body cell is attacked. Sjögren's is one of the most common types of autoimmune attacks on nerve cells (neuropathies), and the sensory and autonomic peripheral nerve cells are most often attacked1.

In Sjögren's, non-nerve cells are attacked as well, and the disease is defined by damage to the gland cells that produce saliva and tears. The hallmark symptoms of Sjögren's are painful dry eyes and dry mouth caused by death of these gland cells.

In many patients, Sjögren's affects other organs and tissues as well, resulting in symptoms such as peripheral neuropathy, lung problems, skin rashes or dry skin, joint pain, and fatigue2. Rare Sjögren's patients do not develop dry eye or dry mouth3. The variable clinical presentation makes Sjögren's easy to overlook. Below, we summarize how best to diagnose Sjögren's syndrome.

Diagnosing Sjögren's: From Blood Tests to Biopsy

Many patients with Sjögren's have one of two specific abnormal auto-antibodies that can be detected in their blood: anti-SSA and anti-SSB, also known as “anti-Ro” and “anti-La.” Most hospitals and doctors’ offices can send patients’ blood for these tests. If either or both are present, it is considered evidence that a patient could have Sjögren's or a closely related autoimmune condition. However, these tests have high “false-negative” rates, where only about half of patients with Sjögren's neuropathy will have these autoantibodies in their blood, even after repeated testing4. Thus, if no autoantibodies are detected, it doesn’t eliminate the possibility that Sjögren's is present1. Other inflammatory markers (“rheumatoid factor” and “antinuclear antibodies”) can be detected in blood tests in people with Sjögren's syndrome, but they are not specific and are insufficient to diagnose it. Often the combination of clinical symptoms and autoantibodies are used to confirm a diagnosis5. Risk factors such as age, sex, and family history should also be considered. Sjögren's syndrome patients tend to be female, 40 to 60 years of age, and about half have another autoimmune disorder. A family history of autoimmune issues is a risk factor as well.

Patients with negative tests for antinuclear antibodies, anti-SSA/B, and rheumatoid factor, and/or with an absence of either dry eye or mouth may require further testing for Sjögren's syndrome if they have other symptoms such as small-fiber neuropathy, trigeminal neuralgia, or joint or muscle pain6. Two other objective tests are recommended. The “Schirmer tear test” is performed to measure eye dryness7. Here, an eye doctor places a small strip of paper in the lower margin of the eye and to measure tear production. Very low tear production is evidence of Sjögren's.

The other recommended diagnostic test is a biopsy of tiny salivary glands located on the inside of the lower lip3,8. These minor salivary glands feel like small lumps if you rub your tongue along the inner surface of your lip. Typically, an oral surgeon will inject local anesthetic in the inner bottom lip, make two small incisions, and remove 3-6 salivary glands for pathological studies9. Worried you’ll miss those glands? Don’t be! You have about 900 more to take over. Resorbable sutures are used to close the incision and the lip is typically painful for only a few days10.

The characteristic Sjögren's syndrome lip biopsy finding is clumps of immune cells next to the salivary gland tissue and ducts. The number of these foci is measured to make the diagnosis10.

Precautions should be taken when considering lip biopsy testing. False-negative results can be obtained if patients are taking or have recently taken immunosuppressive medication including corticosteroids, in patients who have had Sjögren's syndrome for long enough for salivary glands to entirely degenerate, and in cigarette smokers. False positives can occur in older people, after trauma, or in people with hepatitis C, lymphoma, or sarcoidosis11. Salivary gland biopsies are an important tool for the diagnosis of Sjögren's in people with negative blood tests and no dry mouth or eye, but with other Sjögren's-like symptoms.

The type of doctors who put together all the test results to confirm suspected diagnoses are known as rheumatologists. They specialize in diagnosing and treating autoimmune diseases.

A Patient’s Perspective: A Long Road and an Important Answer

MaryEllen Talbot describes her path to a Sjögren’s diagnosis:

I have had vison problems since I was five years old. As an adult, I started seeing an ophthalmologist. My eyes were so dry it felt like I had sand in them. My contacts would crack into pieces in my eyes after brief wear. I had zero tear production and a dry mouth. My ophthalmologist noticed that there were issues with my corneas, and referred me to a corneal specialist.
 
My eye pain was never ending, regardless of what medications we tried. It felt like I had shards of glass in both eyes, and especially when I shifted my eyes from side to side. I constantly wore sunglasses, even indoors, because the lights and glare gave me severe headaches. The corneal specialist suspected Sjögren’s and referred me to another specialist, a top corneal immunologist.
 
The next year, I formed a medical dream team at Massachusetts General Hospital. My first lip biopsy was inconclusive. Still searching for an answer to my pain, I had a second lip biopsy four years later. The surgeon took more salivary glands and definitively diagnosed Sjögren’s.
 
The diagnosis was very important to me. As a patient, it was an essential to make me eligible for medication trials, to get insurance coverage, and to help my other doctors understand my symptoms. Even after I had a clinical diagnosis of Sjögren’s, some doctors continued to question it. This was very challenging to me, and highlights the necessity of educating everyone about this disease and how it is diagnosed.
 
One of the most important things I have learned in my life comes from my 22-year-old son, who suffers from life-threatening medical problems: Happiness is all about your perspective and how you see yourself. He has taught me to fight for today, have a positive attitude about my medical problems, and be my own best advocate!
 
My eye problems are severe and go beyond the symptoms of Sjögren’s. I also have a severe corneal neuropathy, corneal lesions, vision loss, and have had a prosthetic eye lens for two years. My medical team has me on an intense regimen of eye medications and intravenous immunoglobulin (IVIG) to try to prevent further vision loss.
 
Due to the care I received after my Sjögren’s diagnosis, I am still able to drive, work as a trauma therapist, and, most importantly, care for my son! Our message is all about perspective, positive attitude, and fighting hard... life is good! I am so grateful for my medical team that continues to research ways to improve my quality of life.
Treatment of Sjögren's: Many Options

A diagnosis of Sjögren's can be of great relief to patients like MaryEllen who have suffered for years and faced skepticism from doctors, peers, and insurance companies. Once they are diagnosed, patients should discuss treatment options with their doctors, who might include rheumatologists, ophthalmologists, dentists, and neurologists. Some treatments are tailored to relieve specific symptoms, such as eye drops for dry eyes, or artificial saliva, while others are intended to dampen inflammation throughout the body. These improve quality of life for many patients. Most patients with Sjögren's require ongoing medical supervision, but in some cases, the symptoms improve on their own.

References

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6. Predictive and prognostic value of antinuclear antibodies and rheumatoid factor in primary Sjögren's syndrome.
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7. “Sjögren’s Syndrome.” Mayo Clinic, Mayo Foundation for Medical Education and Research, 9 Aug. 2017.

8. Clinical characteristics and biopsy accuracy in suspected cases of Sjögren's syndrome referred to labial salivary gland biopsy.
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 9. Minor salivary gland biopsy. Dr. K, MD, PhD, director. Minor Salivary Gland Biopsy. YouTube, 18 Nov. 2018.

10. “Labial Gland (Lip) Biopsy.” Johns Hopkins Sjögren's Center.

11. “Iowa Head and Neck Protocols.” Sjögren's Syndrome | Iowa Head and Neck Protocols, The University of Iowa, 10 Jan. 2020.