Sjogren’s syndrome. Controversies & progress

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Diagnostic criteria for Sjogren's syndrome (SS) are required
by both physicians and patients to (1) provide a rational
basis for their symptoms, assess their prognosis, and guide
therapy; (2) identify a group of patients who are most likely
to share a common etiopathogenesis, in order to identify those
genetic and environmental factors that are crucial in
pathogenesis; (3) fill out the myriad medical insurance forms
that require a diagnosis code; and (4) serve as a "shorthand"
code that alerts specialists in different fields (oral
medicine, ophthalmology, and a variety of specialists in
internal medicine) to search for particular clinical problems
found in the SS patient.

The key question in this article is
whether the term "Sjogren's syndrome" should apply to a rather
restricted group of individuals (those with an autoimmune
basis for exocrinopathy) or to a rather large group of
individuals who share a similar symptom complex of dry eyes
and mouth. Primary SS, as defined by San Diego criteria, is a
systemic autoimmune disease that is characterized by
keratoconjunctivitis sicca and xerostomia resulting from
lymphocytic infiltrates of the lacrimal and salivary glands.
The criteria for the diagnosis of SS continues to be
controversial, leading to confusion in the clinical and
research literature. It is important to distinguish SS (an
idiopathic autoimmune process) from other processes including
hepatitis C infection, retroviral infection, lymphoma,
autonomic neuropathy, depression, primary fibromyalgia, and
drug side effects that can result in sicca symptoms.

Recent studies on pathogenesis of SS in human and animal models
have examined the clonality of the T-cell infiltrates, the
production of cytokines by lymphocytes and glandular
epithelial cells, neuroendocrine and hormonal factors that
affect glandular secretion, and the fine structure of antigens
recognized by T cells and B cells. Studies in SS have allowed
comparison of lymphocytes in blood and in the glandular tissue
lesions; important differences in the gland microenvironment
play an important role in the initiation and perpetuation of
the autoimmune process. For example, apoptotic death depends
on the balance of Fas, Fas ligand, nuclear factors (such as
bcl-2, bax, and myc), cytokines, neuropeptides, and cell
membrane interactions with extracellular matrix. Although
increased rates of apoptosis may be present in the blood T
cells of SS patients, some glandular T cells are resistant to
apoptosis. Recent advances have led to improved understanding
of signal transduction in response to cytokines and hormones
that play a role in the local and systemic manifestations of
SS.

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