Patient education: Sjögren's disease (Beyond the Basics)

SJÖGREN'S DISEASE OVERVIEW — Sjögren's disease is a chronic autoimmune disease in which the body's immune system inappropriately attacks self-tissues, particularly the glands that produce moisture in the eyes, the mouth, and elsewhere in the body; this causes the most common symptoms of Sjögren's disease, which are dry eyes and dry mouth. This disorder was known for many years as Sjögren's syndrome, but it is now increasingly referred to as Sjogren's disease or simply Sjogren's.

Sjögren's disease can also affect other body organ systems. These organs include the skin, joints, muscles, blood, lung, heart, kidney, and nerves. Symptoms or signs related to involvement of the nerves (such as burning pain in the extremities), lungs (cough, shortness of breath), blood (anemia, low white blood cell or platelet count), and kidneys (frequent urination, low potassium) affect less than 20 percent of people with Sjögren's. These types of involvement are referred to as systemic manifestations. People with Sjögren's also have an increased risk of developing lymphoma, a cancer of the lymphatic system.

Sjögren's disease may occur by itself or in association with another autoimmune condition, such as systemic lupus erythematosus (also called SLE or just lupus), rheumatoid arthritis, or scleroderma (a condition that affects the skin and connective tissue).

Although there is no cure for Sjögren's disease, a number of treatments are available. This article discusses the possible causes, symptoms, diagnostic process, and treatments of Sjögren's disease.

SJÖGREN'S DISEASE CAUSES — Sjögren's disease is thought to be caused by an abnormal reaction of the body's immune system. Lymphocytes are cells in the body's immune system which travel between the blood and the lymphatic system (including the spleen and lymph nodes) to protect the body from infection and cancer. In Sjögren's disease, these cells recognize certain tissues in the body, particularly the glands that produce tears and saliva, as "foreign" and attack them, causing inflammation and damage.

A person who develops Sjögren's disease probably inherits the risk from one or both parents and is then exposed to some type of environmental trigger (eg, a viral infection), but the exact cause is not known. Thus, both genetic and non-genetic factors play a role. Genome-wide testing of people with Sjögren's disease in both the United States and Asia has added greatly to experts' understanding of the genetic factors by identifying at least 25 different risk-related major gene regions.

SJÖGREN'S DISEASE SYMPTOMS — The classic symptoms of Sjögren's disease are dry mouth (due to decreased production of saliva) and dry eyes (due to decreased production of tears). Such symptoms of dryness are commonly reported by otherwise healthy people, but people with Sjögren's disease will typically report that the dryness is present every day for at least three months. These symptoms can also be caused by conditions other than Sjögren's disease. Therefore, it is important to identify medications or other conditions that could be responsible. (See "Clinical manifestations of Sjögren's disease: Exocrine gland disease" and "Clinical manifestations of Sjögren’s disease: Extraglandular disease".)

The decreased fluid production in the eyes and mouth can lead to additional problems, including:

●Eye pain and blurred vision, resulting from injury to the cornea

●Development of cavities in the teeth and infections in the mouth, including painful fungal infections (a yeast infection or thrush)

SJÖGREN'S DISEASE DIAGNOSIS

General approach to diagnosis — The diagnosis of Sjögren's disease typically requires the expertise of a rheumatologist (specialist in autoimmune diseases and arthritis), ophthalmologist (eye specialist), and dentist or oral medicine specialist. In a person with daily persistent symptoms of dry eyes and/or mouth, a diagnosis of Sjögren's disease requires an objective measure of dry eyes (see 'Eye tests' below) or deficient saliva production (see 'Salivary gland tests' below) as well as evidence of an underlying autoimmune disorder. (See 'Blood tests' below and 'Lip biopsy' below and "Diagnosis and classification of Sjögren’s disease".)

Two international medical organizations endorsed a common set of criteria for the classification of Sjögren's disease in 2016. These criteria are intended primarily to ensure international agreement as to what constitutes Sjögren's disease; their fulfillment is typically a requirement for entry into clinical trials and other research studies. These criteria are commonly used to establish a formal diagnosis of Sjögren's disease in clinical practice but occasionally fail to enable this diagnosis in people with early disease or unusual presentations.

Eye tests — Tests are usually recommended to determine if you produce an abnormally low amount of tears and to find out if any parts of your eyes have been damaged as a result of dryness.

●Schirmer test – In the Schirmer test, a small strip of sterile filter paper is inserted gently between your eye and lower eyelid in the outer corner of the eye. It is removed after five minutes, and the wetness on the paper is then measured. A below-normal amount of wetting is characteristic of Sjögren's disease, although decreased tear production can also occur with other conditions. An ophthalmologist or a rheumatologist may perform this test.

●Ocular surface staining tests – Damage to the surface of the eye develops as a result of chronic dryness and inflammation. The damage is best revealed with dyes that can safely be applied to the eye surface (using eye drops). Using a low-power microscope and thin light beam (called a "slit lamp"), an ophthalmologist can examine the surface of your eye and detect this damage, with the aid of the special dyes. The two most commonly used stains are lissamine green and fluorescein, which cause minimal irritation to the eye. Rose bengal stain is used less commonly since it can be irritating. Lissamine green and rose bengal stain the whites of the eyes blue-green and pink-red, respectively, but this staining disappears after a few hours.

Salivary gland tests — Saliva flow rates may be tested by several different methods. The most common is measurement of the volume of saliva that accumulates in your mouth at rest over a period of 5 to 15 minutes and collected by drooling or spitting into a pre-weighed cup. The test can also be performed with a stimulant, such as chewing on gum or paraffin or taking a medicine known to provoke saliva flow. Low saliva flow at rest that is overcome with a stimulant is often an indication of dry mouth provoked by side effects of certain medications.

Ultrasonography — The ultrasound test uses echoes of ultrasound pulses to define the structural characteristics of the major salivary glands, located at the angle of the jaw and under the jaw. It does not involve any radiation. The presence of certain structural changes in the glands can provide a good indication of the presence and severity of salivary gland inflammation and damage, as is seen in Sjögren's disease. However, the test has limited sensitivity, and not all patients with Sjögren's disease have an abnormal ultrasound.

Blood tests — A number of blood tests are typically done in people with suspected Sjögren's disease. One of the most important is a test for the presence of certain antibodies that are markers for autoimmune disorders. These include the antinuclear antibody (ANA) and the Sjögren's-associated Ro/SSA and La/SSB antibodies. Rheumatoid factor (another kind of antibody) may also be present. (See "Patient education: Antinuclear antibodies (ANA) (Beyond the Basics)".)

Lip biopsy — A salivary gland biopsy may be recommended to aid in the diagnosis of Sjögren's disease, particularly if the tests for Ro/SSA and La/SSB antibodies are negative. The biopsy is done typically by removing five to seven small minor salivary glands that are situated just under the lining of the inner portion of your lip. There are over 1000 of these glands that line the inside of your mouth and so removal of only five to seven does not exacerbate mouth dryness. A distinct pattern of lymphocytic infiltration in these glands, known as focal lymphocytic sialadenitis, is characteristic of Sjögren's disease, particularly if the number of these infiltrates is one or more per 4 square millimeters of gland tissue (known as “focus score 1 or greater”).

Relationship between Sjögren's disease and SLE — Sjögren's disease and systemic lupus erythematosus (SLE; lupus) have many similar genetic, clinical, and laboratory features. However, the types of rashes, lung involvement, renal involvement, and frequency of lymphoma are different in Sjögren's disease and SLE. Detailed genetic studies have shown differences between the two disorders.

SYSTEMIC MANIFESTATIONS — In addition to the classic symptoms associated with Sjögren's disease (dry mouth and dry eyes), people with the disorder also have a higher risk of developing diseases of the lung (called interstitial pneumonitis), diseases of the kidneys (interstitial nephritis), and thyroid gland abnormalities. Some may develop inflammation of blood vessels (vasculitis). Vasculitis can cause a characteristic rash and can lead to skin, nerve, and/or internal organ damage. (See "Patient education: Vasculitis (Beyond the Basics)".)

Sjögren's disease also increases the risk of a cancer of the lymphatic system (most commonly non-Hodgkin lymphoma). The lymphatic system includes the tissues and organs that produce and store cells that fight infection, including the bone marrow, spleen, thymus, and lymph nodes. (See "Clinical manifestations of Sjögren’s disease: Extraglandular disease" and "Patient education: Diffuse large B cell lymphoma in adults (Beyond the Basics)" and "Patient education: Follicular lymphoma in adults (Beyond the Basics)".)

The skin may be affected by dryness (xerosis) and various types of rashes, including small "blood spots" on the lower legs (purpura, stemming from inflammation of the blood vessels), vasculitis (particularly small vessel involvement), and red ring-like lesions with a central pale area (annular erythema).

Neurologic involvement includes damage to peripheral nerves, leading to uncomfortable sensations in the skin and/or distal parts of the extremities, such as the hands and feet, including burning, numbness, or discomfort with light touch. Less common forms can lead to imbalance and poor coordination. Sjögren's disease can also affect the brain and spinal cord. The most common form of this involvement is demyelination (damage to the myelin, which is the material that covers and protects nerves), leading to symptoms and signs similar to what is seen in multiple sclerosis.

Blood involvement can result in low red blood cell counts or anemia (sometimes leading to fatigue and shortness of breath), low white cell counts (sometimes leading to frequent infections), and low platelet counts (sometimes leading to bleeding).

SJÖGREN'S DISEASE TREATMENT — Treatment of Sjögren's disease can be divided into three basic areas (see "Treatment of dry eye in Sjögren’s disease: General principles and initial therapy" and "Treatment of dry mouth and other non-ocular sicca symptoms in Sjögren’s disease" and "Overview of the management and prognosis of Sjögren's disease"):

●Treatment of dry eyes and mouth.

●Treatment of problems such as oral yeast infections, eyelid irritation (blepharitis), and acid reflux. These problems can complicate Sjögren's disease and can make the condition less responsive to other therapies.

●Treatment of fatigue and/or vague symptoms of poor concentration and of impaired memory (such as fibromyalgia). (See "Patient education: Fibromyalgia (Beyond the Basics)".)

Treatment of systemic manifestations has been the subject of multiple trials, but none of the investigational therapies have yet been approved by the US Food and Drug Administration (FDA) for this purpose. Fortunately, trials are continuing to find ways to improve the dry eye and dry mouth symptoms and the other manifestations of Sjögren's disease.

Treatment of dry eyes and dry mouth — Most people use artificial tears (eye drops) to treat dry eyes. Many different solutions are available; a clinician can recommend an appropriate choice based upon your pattern of dryness and fluid production in the eye.

Some people are sensitive to the preservatives found in artificial tears. If you notice a burning or itching feeling, you can try a brand with a non-irritating preservative. Alternatively, there are preservative-free versions of moisturizing eye drops. These should be used if you instill the drops in your eyes four or more times a day. They come in small, single-dose containers that may be hard to open for some people who have joint and/or vision problems. Prescription eye drops containing the medications cyclosporine or lifitegrast, which suppress part of the local immune reaction, are also available. Some people with severe eye dryness require use of a tear made from their own serum. Scleral lenses, a contact lens that vaults over the cornea and rests on the whites of your eyes, can also be helpful for those with severe dry eye. A space between the cornea and the back of the scleral lens acts as a reservoir for artificial tear fluid to bathe the cornea continuously.

At night, you can use an eye ointment to provide moisture. It is important to use only a small amount (about 1/8 inches or 3 mm) of the ointment, because overuse can block the ducts and can lead to a condition called blepharitis. (See 'Blepharitis (eyelid inflammation)' below.)

Some people try taking omega-3 fatty acid supplements (eg, fish oil) to help with their dry eyes, although evidence is mixed and it is not clear whether this is effective.

Preserving natural tears — There are various measures you can try to preserve your own tears. Shields can be fitted on the sides of glasses, helping to protect the eyes from air and wind and reducing evaporation of tears. Goggles or wraparound sunglasses serve a similar function.

Another approach is a simple procedure called punctal occlusion. In this procedure, an ophthalmologist inserts tiny plugs into the tear ducts in the corner of the lower eyelid, nearest the nose, where the tears normally collect and drain into the nose. By blocking this duct, your tears stay on the eye longer. There are several types of plugs, one of which does not touch the surface of the eyeball; these plugs are generally preferred.

Stimulating saliva — Simply sucking on sugar-free candy or lozenges or chewing sugar-free gum can stimulate the flow of saliva. Products that contain xylitol can help reduce the risk for dental decay. In some people who do not respond adequately to such measures, medications (eg, pilocarpine or cevimeline) can be given to increase saliva production.

Replacing secretions in the mouth — Sipping on water throughout the day is an easy and effective treatment of dry mouth for many people. The water does not have to be swallowed. It can be rinsed around the mouth and then spit out.

If this does not help, an artificial saliva product (spray or lozenge) may be helpful. If you have painful gums, a gel that relieves dry mouth can be helpful.

Preventing cavities — People with Sjögren's disease are at increased risk for dental cavities. You should brush and floss after eating meals and snacks. An electric toothbrush is preferred. It is important for you to visit your dentist at least every six months for a cleaning and evaluation.

Toothpastes designed specifically for people with dry mouth are available. These lack the detergents that are present in many types of toothpaste but can irritate a dry mouth. Toothbrushes with special features that help clean between the teeth (including electric toothbrushes) may also help to keep your teeth clean.

Toothpaste with fluoride (or a special fluoride rinse or varnish) may help to prevent cavities. A fluoride treatment after each dental cleaning may also be helpful. Other products that help preserve dental integrity include chewing gums that keep the pH neutral on the dental surface and toothpastes that bind calcium and phosphate ions to tooth surfaces.

Dryness in other areas — People with Sjögren's disease may have dryness in other areas, including the lips, the skin, and the vagina. For dry lips, you can use petroleum jelly or lip balms or salves. Dry skin usually improves with frequent and liberal use of a moisturizing cream or ointment. "Extra dry skin" lotion can be applied in the morning and at bedtime (and after baths or showers).

Some women with Sjögren's disease have difficulty with vaginal dryness, especially after menopause. There are several products specifically designed for vaginal dryness, including vaginal moisturizers, estrogen cream, vitamin E oil, hyaluronic acid suppositories, and vaginal lubricants. Adequate artificial lubrication applied to BOTH partners can prevent painful intercourse. (See "Patient education: Vaginal dryness (Beyond the Basics)".)

Treating other Sjögren’s-related problems

Fungal infections in the mouth — Prescription medications are available to treat painful mouth lesions due to oral candidiasis (yeast infection, also called thrush). These are taken as either a daily pill or as a topical treatment, in the form of a troche (which is allowed to dissolve in the mouth) or a solution (which is swished around in the mouth before swallowing).

If you wear dentures and have had a fungal infection, be sure to disinfect them overnight to prevent the fungus from coming back. Your dentist can prescribe a nystatin suspension for this purpose.

Dry nose — It is important to treat dry nose or stuffiness because blocked nasal passages can increase mouth breathing and can worsen dry mouth. Saline nasal sprays are available in most drugstores.

Other causes of nasal blockage, including allergy or sinus infection, should be treated promptly. (See "Patient education: Allergic rhinitis (Beyond the Basics)" and "Patient education: Nonallergic rhinitis (runny or stuffy nose) (Beyond the Basics)".)

Blepharitis (eyelid inflammation) — Eyelid inflammation, also called blepharitis, causes symptoms that are similar to those of dry eye (swollen lids and redness of the inside of the lids). Gently washing the skin of the eyelids can relieve blepharitis. You can do this with a warm, wet washcloth and a small amount of "no tears" shampoo or non-soap face cleanser. With the eyes closed, the excess debris should be rubbed from the inner eye outward to the outer eye area. (See "Blepharitis".)

Reflux (heartburn) — Acid reflux is more common in people with Sjögren's disease. This is probably due to the decreased production of saliva, which normally helps to reduce the acidity of stomach acid. Treatment of reflux in people with Sjögren's disease is similar to treatment in other people. (See "Patient education: Gastroesophageal reflux disease in adults (Beyond the Basics)".)

Joint and muscle pain — Nonsteroidal antiinflammatory drugs (NSAIDs) such as ibuprofen are recommended for the joint pain that may accompany Sjögren's disease. (See "Patient education: Nonsteroidal antiinflammatory drugs (NSAIDs) (Beyond the Basics)".)

Low-dose glucocorticoids (also called steroids) such as prednisone may also improve joint pain but are generally recommended for short-term treatment. Serious side effects may occur with long-term use (eg, weight gain, high blood pressure, diabetes, bone thinning).

A class of medications called disease-modifying antirheumatic drugs (DMARDs) is commonly used in people with lupus and rheumatoid arthritis to slow the immune system's destructive effects. Similar treatments have been used in patients with Sjögren's disease. The most common is hydroxychloroquine, an antimalarial drug, which is widely used in the treatment of lupus and rheumatoid arthritis. (See "Patient education: Disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (Beyond the Basics)" and "Treatment of Sjögren's disease: Constitutional and non-sicca organ-based manifestations", section on 'Musculoskeletal pain'.)

Fatigue — Fatigue is common in Sjögren's disease. Fatigue may be due to the active inflammation associated with the disease itself, fibromyalgia, and/or sleep disturbances. Sleep problems can result if you drink a lot of water to treat dry mouth and then need to get up frequently at night to urinate.

General treatment for fatigue includes the attention to diet and exercise that has been helpful in people with fibromyalgia. In addition, in people with Sjögren's disease, it is important to adequately control symptoms of dry mouth and dry eye that interfere with sleep (table 1). (See "Patient education: Insomnia (Beyond the Basics)".)

Fibromyalgia — Some people with Sjögren's disease also have a condition called fibromyalgia. Fibromyalgia causes muscle aching and fatigue. The treatment of fibromyalgia is discussed separately. (See "Patient education: Fibromyalgia (Beyond the Basics)".)

Vasculitis — Vasculitis is inflammation of blood vessels. Damage to arteries or veins may result in bleeding, pain, and damage to skin, nerves, and internal organs. When vasculitis occurs, it often requires treatment with drugs that suppress the immune system. Medications such as rituximab, cyclophosphamide, azathioprine, or mycophenolate mofetil may be prescribed by clinicians experienced in their use. Careful monitoring for side effects and for response to treatment is necessary. (See "Patient education: Vasculitis (Beyond the Basics)".)

Anesthesia and Sjögren's disease — If you need surgery, the anesthesiologist should be made aware of your diagnosis of Sjögren's disease. This is because Sjögren's disease can increase the risks of general anesthesia. There may be an increased risk of developing mucous plugs in the airways during and after surgery, and medications used during the surgery can dry the airways further. If aware of the diagnosis of Sjögren's disease, the anesthesiologist can take special measures to lower the risk of these complications.

Pregnancy — Pregnancy outcomes in women with Sjögren's disease are generally similar to those of healthy women. However, women with Sjögren's disease who have anti-Ro/SSA antibodies have a small risk of giving birth to a baby with a condition called "neonatal lupus," which sometimes includes the baby being born with a potentially serious heart problem called congenital heart block. (See 'Blood tests' above.)

Neonatal lupus with congenital heart block occurs in about 2 to 4 percent of newborns of mother with Sjögren's disease who have these antibodies. Other features of neonatal lupus, including skin rashes (which are seen more often than the heart block), abnormal blood counts, and liver abnormalities, are all usually temporary, unlike the heart block. It is important to detect the heart block early, which can be done by monitoring during pregnancy. Thus, women with these antibodies who become pregnant should be monitored by a maternal-fetal medicine specialist as part of their care during pregnancy.

WHERE TO GET MORE INFORMATION — Your health care provider is the best source of information for questions and concerns related to your medical problem.

This article will be updated as needed on our web site (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for health care professionals, are also available. Some of the most relevant are listed below.

Patient level information — UpToDate offers two types of patient education materials.

The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.

Patient education: Sjögren's disease (The Basics)
Patient education: Antinuclear antibodies (The Basics)

Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.

Patient education: Antinuclear antibodies (ANA) (Beyond the Basics)
Patient education: Diffuse large B cell lymphoma in adults (Beyond the Basics)
Patient education: Follicular lymphoma in adults (Beyond the Basics)
Patient education: Fibromyalgia (Beyond the Basics)
Patient education: Vaginal dryness (Beyond the Basics)
Patient education: Allergic rhinitis (Beyond the Basics)
Patient education: Nonallergic rhinitis (runny or stuffy nose) (Beyond the Basics)
Patient education: Gastroesophageal reflux disease in adults (Beyond the Basics)
Patient education: Nonsteroidal antiinflammatory drugs (NSAIDs) (Beyond the Basics)
Patient education: Disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (Beyond the Basics)
Patient education: Insomnia (Beyond the Basics)

Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.

Diagnosis and classification of Sjögren’s disease
Clinical manifestations of Sjögren's disease: Exocrine gland disease
Clinical manifestations of Sjögren’s disease: Extraglandular disease
Interstitial lung disease associated with Sjögren's disease: Clinical manifestations, evaluation, and diagnosis
Neonatal lupus: Epidemiology, pathogenesis, clinical manifestations, and diagnosis
Pathogenesis of Sjögren’s disease
Kidney disease in primary Sjögren's disease
Treatment of dry eye in Sjögren’s disease: General principles and initial therapy
Treatment of dry mouth and other non-ocular sicca symptoms in Sjögren’s disease
Overview of the management and prognosis of Sjögren's disease

The following organizations also provide reliable health information.

●National Library of Medicine

(www.medlineplus.gov/healthtopics.html)

●National Institute of Neurological Disorders and Stroke (https://www.ninds.nih.gov/health-information/disorders/sjogrens-syndrome)

●Sjögren's Foundation

(www.sjogrens.org)

●The Arthritis Foundation

(www.arthritis.org/diseases/sjogrens-syndrome)

●American College of Rheumatology

Phone: 404-633-3777

(www.rheumatology.org)

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