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Sjögren Syndrome

The information in NORD’s Rare Disease Database is for educational purposes only. It should never be used for diagnostic or treatment purposes. If you have questions regarding a medical condition, always seek the advice of your physician or other qualified health professional. NORD’s reports provide a brief overview of rare diseases. For more specific information, we encourage you to contact your personal physician or the agencies listed as “Resources” on this report.

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Synonyms of Sjögren Syndrome

Disorder Subdivisions

General Discussion

Sjögren syndrome is an autoimmune disorder characterized by degeneration of the mucus-secreting glands, particularly the tear ducts of the eyes (lacrimal) and saliva glands of the mouth. Autoimmune disorders are caused when the body's natural defenses (antibodies, lymphocytes, etc.) against invading organisms suddenly begin to attack healthy tissue. Sjögren syndrome is also associated with inflammatory disorders such as arthritis or lupus.

Symptoms

Sjögren Syndrome generally has a sudden onset. Primary Sjögren Syndrome is characterized by inflammation of the cornea of the eyes and the delicate membranes that line the eyelids (keratoconjunctivitis) due to insufficient tear production, and dryness of the mouth (sicca xerostemia) due to lack of saliva from the salivary glands. In secondary Sjögren Syndrome, dry eyes and/or mouth may occur with diseases of the tissue that holds together and supports different structures of the body (connective tissue disease). Most often rheumatoid arthritis (RA), Lupus or other autoimmune diseases are present with secondary Sjögren Syndrome.

Most patients with Sjögren Syndrome have the primary type of Sjögren Syndrome. The onset of symptoms is usually sudden. Decreased production of saliva and the resulting dry mouth make chewing and swallowing food difficult. The lack of saliva causes pieces of food to stick to the cheeks, gums and throat. Teeth decay easily, leading to cavities (dental caries), inflammation of the gums (gingivitis) and advanced gum disease (pyorrhea).

As the tear ducts of the eyes (lacrimal glands) waste away (atrophy), the amount of tears produced decreases, causing a feeling of grittiness and burning in the eyes. The eyelids may stick together, glands under the jaw may be swollen and painful, and gastrointestinal symptoms may occur.

Dryness may extend to the skin and to the mucous membranes lining the nose, throat and vagina. Muscle pain and weakness may also occur (Fibromyalgia).

In secondary Sjögren Syndrome, patients may experience arthritis, rash (palpable purpura) on the lower extremities, and light sensitive rashes (photosensitive dermatitis) on the face, arms and other exposed areas. Fever and neurologic symptoms may occur.

Patients with systemic Sjögren Syndrome (symptoms in addition to the eyes and mouth) usually have blood tests that are positive for certain antibodies (anti-nuclear antibodies to Ro and La antigens). Antibodies are substances made by the body that defend the body against bacteria, viruses, or other foreign invaders (antigens).

All patients suspected of having Sjögren Syndrome should be examined by an ophthalmologist, a physician who specializes in the care and treatment of eyes. Patients with Sjögren Syndrome who have positive blood tests for anti- Ro antibodies should be evaluated by a physician who specializes in the care and treatment of inflammatory diseases (rheumatologist) for evidence of disease outside of the eyes and mouth (extra-glandular involvement).

Causes

Sjögren Syndrome is an autoimmune disorder. It has no known cause. Autoimmune disorders are caused when the body's natural defenses (e.g., antibodies) against "foreign" or invading organisms begin to attack healthy tissue for unknown reasons.

People with Sjögren Syndrome often have a genetic predisposition (HLA- DR3). A genetic predisposition means that a person may carry a gene for a disease but it may not be expressed unless something in the environment triggers the disease. Secondary Sjögren Syndrome often occurs in patients with rheumatoid arthritis, systemic lupus erythematosus and other connective tissue diseases.

Alpha fodrin is an antigen that is the target of humoral or cell-mediated immune response (autoantigen) and is believed to be a cause of Sjögren Syndrome in some cases. Fodrin is a protein found in internal cell structures (cytoskeleton). It binds a muscle protein (actin) and may also be involved in secretion. It is broken down when it is exposed to certain enzymes that degrade protein (proteases). These enzymes become activated during the process of programmed cell death (apoptosis).

Affected Populations

Sjögren Syndrome affects approximately nine females to every male. Ninety percent of women with the disorder have already gone through menopause (post-menopausal), although symptoms may be apparent at an earlier age. Recent data suggest that men who show symptoms of HIV infection may develop a syndrome similar to Sjögren Syndrome. Although the exact figure is unknown, one estimate suggests that one to two million people may have Sjögren Syndrome in the United States. Sjögren Syndrome is believed to be the second most common autoimmune connective tissue disorder.

Related Disorders

Symptoms of the following disorders can be similar to those of Sjögren Syndrome. Comparisons may be useful for a differential diagnosis:

Mikulicz Syndrome is a benign chronic disorder that causes the enlargement of the tonsils, the saliva glands located near the ear (parotid), the glands beneath the upper jaw bone (submaxillary), glands that produce tears (lacrimal glands), and the salivary glands of the mouth. Symptoms may include dryness of the mouth, difficulty swallowing and tooth decay. There may be absent or decreased tears and blurred vision. (For more information on this disorder, choose "Mikulicz" as your search term ion the Rare Disease Database.)

Keratomalacia is an eye disease caused by a deficiency of vitamin A. Vitamin A (retinol) is found mainly in fish liver oils, liver, egg yolk, cream and butter. The human body stores vitamin A mainly in the liver. Once it is released by the liver, vitamin A is converted to light sensitive pigments in the retina of the eye which is involved in night, day and color vision. Vitamin A also helps to maintain healthy body tissues. A lack of Vitamin A may cause night blindness, abnormal dryness of the inner surface of the eyelid (xerosis) and the transparent covering of the eyes (cornea). This dryness may result in a feeling of grittiness in the eyes and a painful sensitivity to light (photophobia). (For more information on this disorder, choose "Keratomalacia" as your search term in the Rare Disease Database.)

Ligneous Conjunctivitis is a rare disorder that is characterized by lesions in the mucous producing membranes especially of the eye. This disorder usually presents itself in childhood. Mucous membranes of the voice box (larynx), vocal chords, nose, trachea, wind pipe, vagina, cervix and gums (gingiva) may also be affected. The lesions in the membranes have a "wood- like" (ligneous) texture. They are thick, firm, knotty and tough. The cause of this disorder is not known although there have been some cases that suggest an autosomal recessive genetic inheritance. (For more information on this disorder, choose "Ligneous Conjunctivitis" as your search term in the Rare Disease Database.)

Fibromyalgia is a chronic muscle disorder characterized by muscle pain throughout much of the body. This may begin gradually or have a sudden onset. Other symptoms include muscle spasms, fatigue, muscle tissue stiffness and unrefreshing (non-restorative) sleep. The exact cause of this disorder is not known. Some patients with Fibromyalgia may have chest pain, headaches, diarrhea, constipation, dryness in the eyes and mouth (Sjögren syndrome), swelling of a tendon (tendinitis), or swelling of the connective tissue surrounding a joint (bursitis). (For more information on this disorder, choose "Fibromyalgia" as your search term in the Rare Disease Database.)

Lupus (Systemic Lupus Erythematous or SLE) is a multisystem inflammatory disease of the connective tissue of the body. Sjögren syndrome may occur in conjunction with Lupus. Fatigue is an early and frequent symptom. Other symptoms may include fever, swollen glands, skin rash, profound weight loss, headaches, hair loss (alopecia) and water retention (edema). Arthritis, joint and muscle pain occurs in 90 percent of the cases. These symptoms may occur years before the illness is actually diagnosed. The arthritis symptoms come and go and tend to appear most often in either knees, fingers, or wrist joints. There is no bone loss associated with this joint involvement. (For more information on this disorder, choose "Lupus" as your search term in the Rare Disease Database.)

Rheumatoid Arthritis (RA) is an autoimmune inflammatory disorder. Its cause is unknown. It is characterized by morning stiffness and arthritis mainly in the hands, wrists, knees, feet, shoulders and hips. Once a joint is involved, it may remain painful for weeks, months, and even years. About 25 percent of RA patients also have Sjögren Syndrome (secondary). (For more information on this disorder, choose "Rheumatoid Arthritis" as your search term in the Rare Disease Database.)

Standard Therapies

Diagnosis
A number of tests are available for the diagnosis of Sjögren Syndrome. They may include a careful examination of the eyes, including measurement of tear production; evaluation of salivary gland secretion; X-ray imaging of the salivary glands; and removal and microscopic examination of small samples of tissue from the salivary glands (biopsy).

Diagnostic assessment may also require blood studies to measure the levels of red and white blood cells and platelets; testing to measure the rate at which red blood cells settle in a tube of unclotted blood (erythrocyte sedimentation rate [ESR]), potentially providing a nonspecific indicator of inflammation; and studies to detect abnormal antibodies that may be highly specific to Sjögren Syndrome or characteristic of other autoimmune disorders.

Treatment
The treatment of Sjögren Syndrome is directed toward the specific symptoms and physical findings that are present in each individual. For example, symptomatic measures may include the use of artificial tears in the form of eye drops to alleviate dryness of the eyes, artificial saliva to help moisturize the mouth, and vaginal lubricants to replace insufficient secretions. Administration of certain medications such as corticosteroids, anti-inflammatory drugs, or immunosuppressive agents (e.g., Cytoxan) may be needed for certain extra-glandular manifestations potentially associated with Sjögren Syndrome.

The drug Salagen has been approved by the Food and Drug Administration (FDA) for the treatment of dry mouth (xerostomia) and dry eyes associated with Sjögren Syndrome. Salagen Tablets have been shown to stimulate secretions of certain glands (e.g., certain salivary glands) to increase their activity. Salagen Tablets are manufactured by MGI Pharma. Oral pilocarpine is the active ingredient of Salagen Tablets.

In addition, the FDA has approved the orphan drug Evoxac (cevimeline) for the treatment of dry mouth associated with Sjögren Syndrome. The medication is manufactured by SnowBrand Pharmaceuticals of Rockville, Maryland, and is marketed by Daiichi in the United States.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.

For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

Current studies include a natural history of salivary gland dysfunction and Sjögren's syndrome, sponsored by the National Institute of Dental and Craniofacial Resaerch (NIDCR), and a studied sponsored by Allergan Pharmaceuticals of the drug Ophthalmic Emulsion for treating patients with moderate or severe dry eye syndrome. Information on these studies is available at www.clinicaltrials.gov.

Bromhexine is a drug used in Europe and Canada for the treatment of Sjögren Syndrome. However, at this time, no clinical trials are underway in the United States.

The immunosuppressive drug, cyclosporin A, is being developed as a special formulation for use as an eye medication with the hope that it may reduce destruction of the tear ducts in individuals with Sjögren Syndrome. Recent studies have shown that cyclosporin A significantly reduced symptoms associated with dry eye syndrome. Further research is needed to determine the long-term safety and effectiveness of this medication as a treatment for dry eyes associated with Sjögren Syndrome.

Scientists have studied OcuNex ophthalmic solution for severe dry eyes associated with Sjögren Syndrome.

Amarillo Biosciences is investigating the use of low dose oral interferon alpha (IFNalpha) as a treatment for Sjögren Syndrome. The drug entered Phase III clinical trials in 2001. More studies are needed to determine the long-term safety and effectiveness of this therapy as a treatment for individuals with Sjögren Syndrome.

Sjögren Syndrome Resources

NORD Member Organizations:

(To become a member of NORD, an organization must meet established criteria and be approved by the NORD Board of Directors. If you're interested in becoming a member, please contact Susan Olivo, Membership Manager, at solivo@rarediseases.org.)

Other Organizations:

References

TEXTBOOKS
McKusick VA., ed. Mendelian Inheritance in Man. Baltimore. MD: The Johns Hopkins University Press; Entry No: 270150, 1994:2195-96.

Thoene JG., ed. Physicians' Guide to Rare Diseases. Montvale, NJ: Dowden Publishing Company Inc; 1995:783-84.

Bennett JC, Plum F., eds. Cecil Textbook of Medicine. 20th ed. Philadelphia, PA: W.B. Saunders Co; 1996:1488-90.

JOURNAL ARTICLES
Stevenson D, et al., Efficacy and safety of cyclosporin A ophthalmic emulsion in the treatment of moderate-to-severe dry eye disease: a dose-ranging, randomized trial. The Cyclosporin A Phase 2 study. Ophthalmology. 2000;107:967-74.

Sall K, et al., Two multicenter, randomized studies of the efficacy and safety of cyclosporin ophthalmic emulsion in moderate to severe dry eye disease. CsA Phase 3 Study Group. Ophthalmology. 2000;107:631-9.

Ship JA, et al., Treatment of primary Sjögren's syndrome with low-dose natural human interferon-alpha administered by the oral mucosa route: a phase II clinical trial. IFN Protocol Study Group. J Interferon Cytokine Res. 1999;19:943-51.

Bell M, et al., Sjögren's syndrome: a critical review of clinical management. J Rheumatol. 1999;26:2051-61.

Nusair S, et al., The use of oral pilocarpine in xerostomia and Sjögren's syndrome. Semin Arthritis Rheum. 1999; 28:360-7.

Papas AS, et al., Oral pilocarpine for symptomatic relief of dry mouth and dry eyes in patients with Sjögren's syndrome. Adv Exp Med Biol. 1998;438:973-8.

Haneji N, et al., Identification of alpha-fodrin as a candidate autoantigen in primary Sjögren's syndrome. Science. 1997;276:604-7.

Simmons TJ, et al., Molecular characterization of a major auto-antibody associated cross-reactive idiotype in Sjögren's syndrome. J Immunol. 1989;142:4261-8.

Fox RI, et al., Treatment of primary Sjögren's syndrome with hydrochloroquine. Am J Med. 1988;85:62-7.

Molina R, et al., Primary Sjögren's syndrome in men. Clinical, serologic, and immunogenetic features. Am J Med. 1986;80:23-31.

Report last updated: 2007/08/07 00:00:00 GMT+0