Update in Sjogren syndrome

Sjogren syndrome (SS), the second most common autoimmune rheumatic disease, refers to keratoconjunctivitis sicca and xerostomia resulting from immune lymphocytes that infiltrate the lacrimal and salivary glands. However, diff erential diagnosis remains confusing due to the high prevalence of vague sy mptoms of dryness, fatigue, and myalgias in the general population, The pro blems of diagnosis are further compounded by the finding of "positive" anti nuclear antibodies in a high percent of the general population. Unless mino r salivary gland biopsies are read by experienced observers, nonspecific ch anges of sialadenitis are frequently confused with the focal lymphocytic in filtrates that are characteristic of SS. The distinction between fibromyalg ia patients with low titer antinuclear antibodies and primary SS remains di fficult, Even in patients fulfilling strict criteria for SS, the genomic se arch for critical genes has proven difficult due to the multigenic pattern of inheritance and strong role of currently undefined environmental factors , No single environmental factor has been detected in the majority of SS pa tients. SS-like syndrome has been detected in certain patients with HTLV-1 and hepatitis C infection, providing clues to pathogenesis. Even in SS patients with marked sicca symptoms, minor salivary gland biopsy shows that almost 50% of glandular cells are still detected on biopsy, The se results imply the importance of immune factors such as cytokines and aut oantibodies in decreasing neuro-secretory circuits and induction of glandul ar dysfunction, Of potential importance, an antibody against muscarinic M3 receptor that can decrease secretory function when injected into rodents is frequently found in the sera of SS patients. Newly developed topical and oral therapies can ease the oral and ocular dry ness, Orally administered agonists of the muscarinic M3 receptor (pilocarpi ne and cevimeline) have recently been approved by the US Food and Drug Admi nistration to increase salivary secretion, Topical ocular use of low-dose c orticosteroids or cyclosporin may decrease conjunctival surface inflammatio n. In a Phase II double-blind study, orally administered interferon alpha ( 150 U) led to improved saliva flow and symptoms, In pregnant patients with evidence of fetal distress, oral dexamethasone is preferred because this ag ent crosses the placenta effectively. in animal models, antagonists of tumo r necrosis factor and inhibitors of de novo pyrimidine synthesis appear pro mising. (C) 2000 Lippincott Williams & Wilkins, Inc.