How do you Diagnose Sjogren's Syndrome?
Frederick B. Vivino, MD, FACR
"The Moisture Seekers" Newsletter. April 2005
Many patients know from personal experience that the diagnosis of Sjögren’s syndrome (SS) can be long and difficult. According to some studies, the average time between symptom onset and diagnosis can be six years or longer. The most important reasons for this delay include lack of disease awareness by patients and professionals as well as confusion over diagnostic criteria and diagnostic tests.
Because Sjögren’s syndrome can affect many organs, it often is mistaken for other conditions including menopause, depression, fibromyalgia, rheumatoid arthritis, chronic fatigue syndrome, and even multiple sclerosis. About 80% of patients present with the insidious onset of dryness of the mouth, eyes and other body parts (sicca syndrome) that evolves over a period of months to years. The other 20% of Sjögren’s cases begin with atypical presentations such as overwhelming fatigue, polyarthritis, peripheral neuropathy, an MS-like picture, fever, lung disease or tumor-like swelling of the parotid gland. When patients in this latter group seek medical attention, their sicca symptoms often are minimal or nil. Therefore, without that high index of suspicion, the diagnosis of Sjögren’s can be easily overlooked.
Even the best clinician frequently is challenged by the confusing observation from prior studies that the correlation between severity of symptoms and objective evidence of dry eyes and dry mouth is very poor. Symptoms alone are insufficient to make a definitive diagnosis of Sjögren’s syndrome since other conditions also cause dryness (TMS February 2005, p.10). Conversely, in people who are not dry but have other problems that suggest Sjögren’s one still can make this diagnosis if objective tests are positive. So with these caveats in mind, how is the diagnosis of Sjögren’s syndrome currently made?
At the present time most Sjögren’s centers around the world perform a comprehensive evaluation and utilize the American-European criteria published in 2002 in the Annals of Rheumatic Diseases by Claudio Vitali, MD and colleagues (Table I). These criteria originally were designed to define homogeneous populations of patients for research studies but since have proven useful for diagnosis as well. They examine several different parameters including key symptoms, objective tests for dry eyes and dry mouth and tests for autoimmunity.
TABLE 1 - Summary of Sjogren's Syndrome Classification Criteria
1. Ocular symptoms (any 1 of 3)
2. Oral symptoms (1 of 3)
3. Ocular signs (1 of 2)
4. Oral signs (1 of 3)
5. Positive lip biopsy
6. Positive Anti-SSA and / or SSB antibodies
Exclusions: hepatitis C, graft vs. host disease, use of drying medications, etc.
Although Sjögren’s patients develop many disabling symptoms, the ones most important for diagnosis are those listed in the table. The ophthalmologist can demonstrate objective evidence of dry eyes by placing strips of filter paper inside the lower eyelids (Schirmer test) to measure the degree of wetting and to look for decreased tear production. Alternatively, vital dyes can be used to stain the surface of the eye to look for damage (i.e. dry spots) due to chronic dryness.
There are several ways to demonstrate objective evidence of dry mouth. A salivary gland scan is a nuclear medicine test (similar to a bone or thyroid scan) that can show abnormalities in salivary gland function. Parotid sialography is a radiology study in which water soluble contrast dye is injected through a catheter into the opening of the parotid (salivary) glands in the mouth to look for abnormalities in the size or shape of the parotid ducts. The simplest test for dry mouth is sialometry. The patient is asked to spit into a cup for 15 minutes so saliva flow can be measured.
Since many other conditions besides Sjögren’s can cause dry mouth, it is also imperative to prove that the patient actually has an autoimmune disease. This is most easily done with blood tests for the two autoantibodies that are specific for Sjögren’s, i.e. anti-SSA (a.k.a. anti-Ro) and anti-SSB (a.k.a. anti-La). Finally, when all else fails, a small incision can be made in the lower lip to excise 4-5 tiny salivary glands (labial minor salivary gland biopsy) to look for salivary gland inflammation. A scoring system is used to grade the degree of inflammation, and the result must be above a certain threshold to be significant.
According to the American-European criteria, the diagnosis of 1° SS (dry eyes and dry mouth in a patient with no pre-existing history of connective tissue disease) requires the fulfillment of 4 out of 6 criteria. One of the 4 positive criteria must be either anti-SSA/SSB positivity or a positive lip biopsy. Diagnosis of 2° SS (dry eyes and dry mouth in a patient with rheumatoid arthritis or another pre-existing connective tissue disease) requires one dryness symptom plus 2 out of 3 objective tests (# 3-5). The diagnosis of SS in a patient with no sicca symptoms can be made if 3 of 4 objective criteria are fulfilled (items 3-6).
These criteria reportedly facilitate the proper identification of SS patients in more than 90% of cases. In the rare instances in which the cause of patient symptoms remains obscure, repeat testing and sometimes even additional salivary gland biopsies may be required. Recently, an International Sjögren’s Syndrome Registry was established at the University of California, San Francisco by Dr. Troy Daniels and coworkers to foster genetics and other types of basic research. Hopefully, this work will lead to new diagnostic tests or criteria that will make the whole process easier for future patients and their providers.