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.
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).
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).
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.
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.
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.
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
For information about clinical trials sponsored by private sources, contact:
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.
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