TABLE 5 Extraglandular Manifestations in Primary SS

Hashimoto's thyroiditis/Graves' disease

Interstitial nephritis/renal tubular acidosis

Autoimmune hepatitis/primary biliary cirrhosis

Peripheral neuropathies


Interstitial lung disease

Atrophic gastritis

Non-Hodgkin's lymphoma (extraglandular or glandular)

Abbreviation: SS, Sjogren's syndrome.

ocular surface of both eyes is observed through the slit lamp using the cobalt blue filter. The amount of time between the last blink and the break-up of the fluorescein-stained precorneal tear film is determined by noting the first blue spot that appears on the surface of the cornea. A BUT of less than 10 seconds is suggestive of an aqueous or mucous tear deficiency, consistent with the ocular component of SS. Fluorescein is also used to assess the integrity of the corneal epithelium through the number of punctate epithelial erosions, their location, and presence or absence of confluence. Corneal filaments may be present in severe KCS.

Rose bengal or lissamine green can be used interchangeably to assess the integrity of the conjunctival epithelium. Both dyes stain devitalized, desiccated, and keratinized conjunctival cells, as well as goblet cells. Rose bengal is irritating to the eye, particularly in patients with moderate to severe disease, while lissamine green produces no irritation, even in extremely dry eyes. The staining pattern of the interpalpebral bulbar conjunctiva is equivalent to both. Ocular dryness symptoms can be exacerbated by various conditions unrelated to SS (Table 1) and this should be considered when evaluating a patient for the ocular component of SS.

Current diagnostic criteria for SS offer alternatives for assessing salivary function that need to be understood before applying them. The range of tests recommended for evaluation of the salivary component by the American-European Consensus criteria is not diagnostically equivalent (Table 4).

A labial salivary gland biopsy can provide the most disease-specific diagnosis of the salivary component of SS. The biopsy technique and specimen acquisition are critical to a successful outcome. Following local anesthetic infiltration of the lower labial mucosa, an approximately 1.5 cm incision is made through the epithelium, but no deeper (Fig. 1A). After blunt dissection of the incision margin, at the level of the lamina propia, approximately five minor salivary glands are dissected free from the underlying connective tissue, one at a time (Fig. 1B). Clear visualization of the field during dissection permits sensory nerves in the area to be preserved. The incision is then closed with approximately three interrupted, resorbable sutures. If histological examination reveals focal lymphocytic sialadenitis, the pathologist must then determine a focus score (11), which provides a diagnostic threshold and severity estimate. A punch or wedge biopsy is not recommended, as it is a blind procedure with a greater risk of missing the minor salivary glands and includes significant probability of sensory nerve damage.

Determination of unstimulated whole salivary flow rate is simple to perform in the outpatient office. Sialography is a technically difficult radiographic technique exhibiting anatomic changes in parotid or submandibular duct structure; this is somewhat

FIGURE 1 Minor salivary gland biopsy. (A) Incision is made to the right or left of midline of the inner lip halfway between the vermillion border and vestibule. Minor glands and nerves can be visualized. (B) Individual minor salivary glands are individually dissected.

FIGURE 1 Minor salivary gland biopsy. (A) Incision is made to the right or left of midline of the inner lip halfway between the vermillion border and vestibule. Minor glands and nerves can be visualized. (B) Individual minor salivary glands are individually dissected.

uncomfortable for the patient and examines only one major gland at a time. If utilized, water-soluble contrast media are preferable to fat-soluble media in individuals with decreased salivary flow, because of the risk of medium retention in the salivary gland with subsequent foreign body reaction. In the case of scintigraphy, there are currently no clear guidelines to assess what constitutes delayed uptake, reduced concentration, and/or delayed excretion of the tracer. Assessment of the rate of uptake and release of the tracer by the salivary gland is a judgment that can vary from practitioner to practitioner.

RF and antinuclear antibody occur in about 90% of patients with SS, but lack specificity and have been deleted from the most recent classification criteria (1). Testing for the presence of autoantibodies directed toward two ribonuclear antigens (SS-A and SS-B) is the only serologic test used in current classification criteria. The prevalence of these autoantibodies in SS varies as a function of the diagnostic criteria used to define the study population as well as the sensitivity of the methodology used to detect the autoantibody. Neither anti-SS-A nor anti-SS-B is specific for SS, as approximately 50% of patients with SLE will be positive and a small percentage of normal adults will also have a low titer.

Diagnosis of SS also requires exclusion of other conditions that can mimic it. These include previous radiation therapy to the head and neck, amyloidosis, sarcoidosis, lymphoma, graft versus host disease, hepatitis C virus infection, HIV-diffuse infiltrative lymphocytosis syndrome, medication-induced dryness, and uncontrolled diabetes mellitus.

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