Sjögren's syndrome

Editor-in-Chief: Wan-Fai Ng Associate Editor-in-Chief:

Overview
Sjögren's syndrome is an autoimmune disorder in which immune cells attack and destroy the exocrine glands that produce tears and saliva. It is named after Swedish ophthalmologist Henrik Sjögren (1899-1986), who first described it. Sjögren's syndrome is also associated with rheumatic disorders such as rheumatoid arthritis, and it is rheumatoid factor positive in 90 percent of cases. The hallmark symptoms of the disorder are dry mouth and dry eyes (part of what are known as sicca symptoms). In addition, Sjögren's syndrome may cause skin, nose, and vaginal dryness, and may affect other organs of the body, including the kidneys, blood vessels, lungs, liver, pancreas, and brain. Nine out of ten Sjögren's patients are women and the average age of onset is late 40s, although Sjögren's occurs in all age groups in both women and men. It is estimated to strike as many as 4 million people in the United States alone making it the second most common autoimmune rheumatic disease.

The primary form, often called sicca syndrome, involves both Keratoconjunctivitis sicca and Xerostomia. The secondary form includes, in addition, the presence of a connective tissue disease, usually rheumatoid arthritis.

Diagnosis
Diagnosing Sjögren’s syndrome is complicated by the range of symptoms a patient may manifest, and the similarity between symptoms from Sjögren's syndrome and those caused by other conditions. Nevertheless, the combination of several tests can lead to a diagnosis of Sjögren's syndrome.

Blood tests can be done to determine if a patient has high levels of antibodies that are indicative of the condition, such as anti-nuclear antibody (ANA) and rheumatoid factor, which are associated with autoimmune diseases. Typical Sjögren syndrome ANA patterns are SSA/Ro and SSB/La, of which SSB/La is far more specific; SSA/Ro is associated with numerous other autoimmune conditions but are often present in Sjögren's (Franceschini & Cavazzana I 2005).

The Schirmer test measures the production of tears: a strip of filter paper is held inside the lower eyelid for five minutes, and its wetness is then measured with a ruler. A slit-lamp examination is done to look for dryness on the surface of the eye. Salivary gland function can be tested by collecting saliva and determining the amount produced. A lip biopsy can reveal lymphocytes clustered around salivary glands, and damage to these glands due to inflammation.

A radiological procedure can also be used as a reliable and accurate way of diagnosing Sjögren's syndrome. A contrast is injected into Stensen's Duct (i.e., parotid duct, Steno's Duct), which is a duct opening from the cheek into the vestibule of the mouth opposite the neck of the upper second molar tooth. Widespread puddling of the injected contrast scattered throughout the gland indicates Sjögren's syndrome.

Classification Criteria
Revised Classification Criteria for Sjogren's Syndrome

A. Ocular symptoms: a positive response to at least one of the following questions:
 * 1. Have you had daily, persistent, troublesome dry eyes for more than 3 months?
 * 2. Do you have a recurrent sensation of sand or gravel in the eyes?
 * 3. Do you use tear substitutes more than 3 times a day?

B. Oral symptoms: a positive response to at least one of the following questions:
 * 1. Have you had a daily feeling of dry mouth for more than 3 months?
 * 2. Have you had recurrently or persistently swollen salivary glands as an adult?
 * 3. Do you frequently drink liquids to aid in swallowing dry food?

C. Ocular signs- that is, objective evidence of ocular involvement defined as a positive result for at least one of the following two tests:
 * 1. Schirmer's test, performed without anaesthesia ( ≦5 mm in 5 minutes )
 * 2. Rose bengal score or other ocular dye score ( ≧4 according to van Bijsterveld's scoring system )

D. Histopathology: In minor salivary glands (obtained through normal-appearing mucosa) focal lymphocytic sialoadenitis, evaluated by an expert histopathologist, with a focus score ≧1, defined as a number of lymphocytic foci (which are adjacent to normal-appearing mucous acini and contain more than 50 lymphocytes) per 4 mm2 of glandular tissue.

E. Salivary gland involvement: objective evidence of salivary gland involvement defined by a positive result for at least one of the following diagnostic tests:
 * 1. Unstimulated whole salivary flow ( ≦ 1.5 ml in 15 minutes )
 * 2. Parotid sialography showing the presence of diffuse sialectasias (punctate, cavitary,or destructive pattern ), without evidence of obstruction in the major ducts.
 * 3. Salivary scintigraphy showing delayed uptake, reduced concentration and/or delayed excretion of tracer

F. Autoantibodies: presence in the serum of the following autoantibodies:
 * 1. antibodies to Ro(SSA) or La(SSB) antigens, or both

For primary SS
In patients without any potentially associated disease, primary SS may be defined as follows:
 * a. The presence of any 4 of the 6 items is indicative of primary SS, as long as either item 4 (Histopathology) or 6 (Serology) is positive.
 * b. The presence of any 3 of the 4 objective criteria items (that is, items 3, 4, 5, 6)
 * c. The classification tree procedure represents a valid alternative method for classification, although it should be more properly used in clinical-epidemiological survey.

For secondary SS
In patients with a potentially associated disease (for instance, another well defined connective tissue disease), the presence of item 1 or item 2 plus any two from among items 3, 4, and 5 may be considered as indicative of secondary SS.

Exclusive criteria

 * Past head and neck radiation therapy
 * Hepatitis C infection
 * Acquired immunodeficiency syndrome (AIDS)
 * Pre-existing lymphoma
 * Sarcoidosis
 * Graft-versus-host disease
 * Use of anticholinergic drugs (since a time shorter than 4-fold life of the drug)

Treatment
There is neither a known cure for Sjögren's syndrome nor a specific treatment to permanently restore gland secretion. Instead, treatment is generally symptomatic and supportive. Moisture replacement therapies such as artificial tears may ease the symptoms of dry eyes (some patients with more severe problems use goggles to increase local humidity or have punctal plugs inserted to help retain tears on the occular surface for a longer time). Additionally, Cyclosporin (Restasis) is available by prescription to help treat chronic dry eye by suppressing the inflammation that disrupts tear secretion. Prescription drugs are also available that help to stimulate salivary flow, such as cevimeline and pilocarpine. Nonsteroidal anti-inflammatory drugs may be used to treat musculoskeletal symptoms. For individuals with severe complications, corticosteroids or immunosuppressive drugs may be prescribed. Also, disease-modifying antirheumatic drugs (DMARDs) such as methotrexate may be helpful.

Prognosis
Sjögren's can damage vital organs of the body with symptoms that may plateau, worsen, or go into remission. Some people may experience only the mild symptoms of dry eyes and mouth, while others go through cycles of good health followed by severe disease. Many patients are able to treat problems symptomatically. Others are forced to cope with blurred vision, constant eye discomfort, recurrent mouth infections, swollen parotid glands, hoarseness, and difficulty in swallowing and eating. Debilitating fatigue and joint pain can seriously impair quality of life. Some patients can develop renal involvement (autoimmune tubulointerstitial nephritis) leading to proteinuria, urinary concentrating defect and distal renal tubular acidosis.

Epidemiology
Sjogren's syndrome affects 1-4 million people in the United States. Most people are more than 40 years old at the time of diagnosis. Women are 9 times more likely to have Sjogren's syndrome than men.

Research
The goals of research on diseases such as Sjögren's syndrome focus on increasing knowledge and understanding of the disorder, improving diagnostic techniques, and finding ways to treat, prevent, and cure the disorder.

Many scientists are working on developing an animal model of Sjögren's syndrome. Dr Hal Scofield's lab at Oklahoma Medical Research Foundation have developed an animal model by immunizing mice with 60 kD Ro peptide. Days after immunization, salivary flow was decreased and lymphocyte infiltrates as well as salivary dysfunction was observed which are highly reminiscent of human Sjögren's syndrome.