primary care MDs to make the diagnosis of SLE or SS based solely on the Þnding of an abnormal autoantibody test result. The correct role for an ANA is to conÞrm the clinical diagnosis.

The recent increased use of enzyme-linked assays (ELISA) to measure ANA has been driven by the lower cost of this method. However, the ELISA tests have a lower sensitivity. Rheumatologists and patients may be confronted with the same serum sample that exhibits a strongly positive ANA by IFA and negative result by ELISA assay. An example of the importance of this discrepancy in laboratory method was the delay in diagnosis reported in a New England Journal clinical case study until the ÒnegativeÓ ELISA test result was replaced by positive result obtained using the conventional IFA measurement [15].

The laboratory tests for antibody to SS-A and SS-B showed a higher level of speciÞcity for SS diagnosis but signiÞcant variation in results were dependent on the ÒvendorÓ of the substrate used in the assay [16].

The pathologist may be asked to help conÞrm the diagnosis of SS with a minor salivary gland biopsy [17]. Jonsson et al. present examples of salivary gland biopsies from an SS patient in Chapter 14. The key features in reading the minor salivary gland biopsy include an adequate number of valuable lobules (at least four) and the determination of an average focus score (a ÒfocusÓ refers to a cluster of at least 50 lymphocytes) based on a survey of at least four lobules. Lobules that have been ruptured due to non-immune mechanisms (called ÒsialadenitisÓ due to rupture of ducts that release mucus) need to be discarded from the quantization of the focus score [18, 19]. The biopsy should not be taken from a region of the buccal mucosa where there is inßammation, as this can give false-positive results [19]. The sensitivity and speciÞcity of the focus scoring method may be improved by looking at serial sections of salivary gland [20].

Non-speciÞc sialadenitis including focal inÞltrates was a relatively frequent Þnding in minor salivary gland biopsies taken in a Òcontrol populationÓ studied at the National Institutes of

Health, particularly among older patients [21]. The Þnding of germinal centers in a minor salivary gland biopsy of an SS patient may be prognostically important [22]. However, most pathologists are not experienced in reading these samples and rarely report the Òfocus scoreÓ or germinal centers. In one recent report, almost 50% of biopsies obtained for entrance into a clinical study of SS were reclassiÞed when examined by a pathologist experienced in SS [23, 24]. Biopsies previously read as positive were reclassiÞed as not fulÞlling criteria and an equal proportion of negative biopsies were felt to be positive for focal inÞltrates.

1.3Methods to Assess Disease Activity

The recent introduction of a Òdisease activity indexÓ by Vitali et al. will facilitate the clinical course and therapeutic trials of SS patients. Also, a recently standardized Disease Damage Index scale (Chapter 5 by Vitali et al.) will allow comparison of different patient populations and therapeutic protocols. This will facilitate studies on disease frequency, extraglandular manifestations, prognosis, and diagnostic markers and provide a basis for therapeutic studies. Seror et al. review this important step in standardization of the nomenclature and collaboration among different cohorts of SS patients in Chapter 30.

1.4Summary

This volume on SjogrenÕs syndrome is different from the reviews that have been published in recent years or as Òseminars in rheumatologyÓ or as Òcurrent opinionÓ articles.

We have included a group of world-renowned experts in the Þeld of ophthalmology, oral medicine and pathology, neurology, otolaryngology, nephrology, oncology, and other disciplines to present their points of view on diagnosis and therapy. Since each group of medical and surgical specialists reads and writes in their different journals, as well as attends different meetings,

this volume is intended to help each specialty understand the opinions and treatments of other specialties.

We have included experts from different parts of the world, since the health-care resources and systems of delivery of health care in the USA differ substantially from those in other parts of the world.

Finally, we have tried to move the information into the Internet age. We feel that Òfrequently asked questionsÓ may be best answered by making validated information available to patients and other health-care specialists over the Internet. For a disease that largely is a Òquality of lifeÓ disorder, in contrast to an acute vasculitis or a heart attack, the time available to provide instruction about treatment of ÒdrynessÓ or ÒfatigueÓ or ÒcognitiveÓ changes is increasingly limited by our time during patient revisits. Thus, we have provided a series of Òfrequently asked questionsÓ as well as Òmyths and pearlsÓ that can easily be modiÞed by each clinician and placed on their web sites for patients or other clinicians to access.

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