Review Oral manifestations of Rheumatology Future Sjögren’s syndrome Carol M Stewart† & Kathleen Berg †Author for correspondence: University of Florida Center for Orphaned Autoimmune Disorders, PO Box, 100414 JHMHC, University of Florida College of Dentistry, Gainesville, FL 32610, USA n Tel:. +1 352 392 6775 n Fax: +1 352 392 2507 n [email protected] Sjögren’s syndrome is a chronic autoimmune disease complex characterized by inflammation of the exocrine glands, primarily resulting in keratoconjunctivitis sicca, hyposalivation and xerostomia, or dry mouth. Dry mouth is one of the most easily recognized components and may lead the clinician to diagnosis. Hyposalivation is more than an inconvenience, having a significant adverse effect on health and quality of life. Early recognition of this condition may minimize some of the adverse sequelae. A dental evaluation in patients with confirmed or suspected Sjögren’s is recommended. The focus of this review article is to highlight oral manifestations of Sjögren’s syndrome to include pathogenesis, clinical presentation, implications for health, diagnostic tools, management strategies and future perspectives. CME Medscape: Continuing Medical Education Online Medscape, LLC is pleased to provide online continuing medical education (CME) for this journal article, allowing clinicians the opportunity to earn CME credit. Medscape, LLC is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide CME for physicians. Medscape, LLC designates this educational activity for a maximum of 1.0 AMA PRA Category 1 Credits™. Physicians should only claim credit commensurate with the extent of their participation in the activity. All other clinicians completing this activity will be issued a certificate of participation. To participate in this journal CME activity: (1) review the learning objectives and author disclosures; (2) study the education content; (3) take the post-test and/or complete the evaluation at http://cme.medscape.com/public/futuremedicine; (4) view/print certificate. Learning objectives Upon completion of this activity, participants should be able to: n List the clinical features of Sjögren’s syndrome (SS) n Describe the prevalence of extraglandular manifestations of SS n Identify other conditions associated with SS n Describe the diagnostic criteria of the European–American Consensus Group for SS n Identify infections of concern in patients with SS Financial & competing interests disclosure CME Author Désirée Lie, MD, MSEd, Clinical Professor, Family Medicine, University of California, Orange, CA, USA; Director, Division of Faculty Development, UCI Medical Center, Orange, CA, USA Disclosure: Désirée Lie, MD, MSEd, has disclosed no relevant financial relationships. Editor Elisa Manzotti, Editorial Director, Future Science Group, London, UK. Disclosure: Elisa Manzotti has disclosed no relevant financial relationships. Keywords Authors & Credentials Carol M Stewart, MS, DDS, MS, University of Florida Center for Orphaned Autoimmune Disorders, University dry mouth n hyposalivation of Florida College of Dentistry, FL, USA n Sjögren’s syndrome n xerostomia Disclosure: Carol M Stewart, MS, DDS, MS, has disclosed no relevant financial relationships. Kathleen Berg, PhD, University of Florida Center for Orphaned Autoimmune Disorders, University of Florida part of College of Dentistry, FL, USA Disclosure: Kathleen Berg, PhD, has disclosed no relevant financial relationships. 10.2217/17460816.3.6.543 © 2008 Future Medicine Future Rheumatol. (2008) 3(6), 543–558 ISSN 1746-0816 543 Review Stewart & Berg Sjögren’s syndrome (SS) is a common, progres- regarding the oral manifestations of SS, as the sive autoimmune rheumatic disease character- disease often manifests with initial complaints ized by subjective dry mouth (xerostomia), dry of ‘dry mouth’ and related oral complaints. The eyes (keratoconjunctivitis sicca) and extreme concerns of oral dryness, increase in dental resto- fatigue. B- and T-cell lymphocytic infiltration of rations and crowns, oral ulcers and lack of taste the exocrine glands leads to diminished salivary and appetite, may be attributed to etiologies such and lacrimal and gland function. Symptoms as stress, dehydration, inadequate oral hygiene may be limited to a local effect on the salivary and medications, without a consideration of SS. and lacrimal glands, or extend to include wide- The astute physician can provide proper patient spread involvement of multiple organ systems education and necessary referral consultations [1,2] . SS may impact the peripheral and central to minimize the debilitating consequences of nervous system, muscles, bone marrow, joints, untreated oral complications of SS. kidneys, pancreas, thyroid and other glands. Research indicates that systemic extra glandular Diagnostic criteria manifestations, including lymphoma, may Several diagnostic protocols have been devel- appear in 40% of individuals with primary SS oped and revised as more is learned. To date, and present in two ways: the development of the American–European Consensus Group lymphoepithelial lesions in several extra-exo- (AECG) 2002 classification criteria appear to crine gland tissues (i.e., bronchi, renal tubules be most universally accepted (BOX 1) [20]. The or biliary ducts); and vasculitis related to the AECG criteria require the presence of four of deposition of immune complexes due to B-cell six criteria, which include objective criteria, hyperreactivity [3]. oral and ocular symptoms, and either positive The disorder may occur alone (primary SS), or serum autoantibodies Ro/SS-A and/or La/SS-B in combination with another rheumatic disease, or positive histopathology from a labial salivary such as systemic lupus erythematosus (SLE), gland biopsy. rheumatoid arthritis (RA), scleroderma or pri- mary biliary cirrhosis, in which case it is classified Oral symptoms as secondary SS. The disease affects women more As indicated in BOX 1, oral symptoms include frequently than men, with a reported female:male xerostomia for greater than 3 months and ratio of 9:1 [4]. A recent report from a Hungarian frequent water intake. To assist assessment of cohort indicated a higher involvement in men subjective dry mouth, positive responses to the than previously reported, with a female:male following questions are very useful: the need to ratio of 7:1 [5]. Although it has been described in drink water to swallow foods, the need to keep children and adolescents [6,7], the onset of symp- a glass of water by the bed or frequent awaken- toms occurs most often during middle age [8]. ing at night due to oral dryness, the amount Currently, the etiology of SS is not clearly under- of saliva in the mouth feels inadequate, and stood, but appears to be multi factorial. It has difficulty speaking[21,22] . been suggested that environ mental agents may Saliva is secreted from three major paired glands trigger SS in genetically predisposed individuals. (parotid, submandibular and sublingual) and Potential mechanisms underlying SS include dis- from hundreds of minor salivary glands located turbances in apoptosis [9–12], circulating autoanti- throughout the submucosa of the oral cavity, with bodies against the ribonucleo proteins Ro and La the exception of the anterior hard palate and gin- [13,14] or cholinergic muscarinic receptors [15–17] giva. Stimulated saliva, produced during eating, in salivary and lacrimal glands, or cytokines [18]. is controlled by the autonomic nervous system. It These processes interfere with normal glandular aids chewing of food, formation and swallowing function, and as the mucosal surfaces become of a food bolus and digestion via the enzymes sites of chronic inflammation, the disease appears amylase and lipase. The parotid gland, which pro- to enter a self-perpetuating inflammatory cycle. vides thin watery secretions, contributes signifi- Depending on the classification criteria cantly to stimulated saliva. Saliva secreted in the applied, estimates of its prevalence in the adult absence of apparent sensory stimuli related to eat- population range from 0.5 to 3% [19], making ing is referred to as resting or unstimulated saliva. it one of the most common autoimmune dis- The parotid gland contributes 25% to unstimu- orders. However, due to the vague and diverse lated flow. The submandibular gland, a mixed presentation of initial symptoms, the diagnosis mucous and serous gland, contributes 60%, and is difficult and often takes several years. It is of the sublingual and minor mucous glands each utmost importance for all clinicians to be vigilant contribute 7–8% of whole saliva [23–25]. 544 Future Rheumatol. (2008) 3(6) future science group Oral manifestations of Sjögren’s syndrome Review A continuous production of small amounts Box 1. European–American Consensus Group Criteria for of saliva occurs throughout the day, often from Sjögren’s syndrome. the minor salivary glands in response to dry- ness of the oral mucosa and stimulation from I. Ocular symptoms (positive response to at least one of three) movements of the jaw and tongue. This fluid n Daily, persistent, troublesome eyes for more than 3 months covers the oral and pharyngeal cavities and n Recurrent sensation of sand or gravel in the eyes is responsible for maintaining the integrity n Use of tear substitutes more than three times per day of the mucosa. As little time is spent eating II. Oral symptoms (positive response to at least one of three) during a 24-h period, resting saliva is a sig- n Daily