ABSTRACT
BACKGROUND: Salivary dysfunction in Sjögren disease can lead to serious and costly oral health complications. Clinical practice guidelines for caries prevention in Sjögren disease were developed to improve quality and consistency of care. METHODS: A national panel of experts devised clinical questions in a Population, Intervention, Comparison, Outcomes format and included use of fluoride, salivary stimulants, antimicrobial agents, and nonfluoride remineralizing agents. The panel conducted a systematic search of the literature according to pre-established parameters. At least 2 members extracted the data, and the panel rated the strength of the recommendations by using a variation of grading of recommendations, assessment, development, and evaluation. After a Delphi consensus panel was conducted, the experts finalized the recommendations, with a minimum of 75% agreement required. RESULTS: Final recommendations for patients with Sjögren disease with dry mouth were as follows: topical fluoride should be used in all patients (strong); although no study results link improved salivary flow to caries prevention, the oral health community generally accepts that increasing saliva may contribute to decreased caries incidence, so increasing saliva through gustatory, masticatory, or pharmaceutical stimulation may be considered (weak); chlorhexidine administered as varnish, gel, or rinse may be considered (weak); and nonfluoride remineralizing agents may be considered as an adjunct therapy (moderate). CONCLUSIONS AND PRACTICAL IMPLICATIONS: The incidence of caries in patients with Sjögren disease can be reduced with the use of topical fluoride and other preventive strategies.
Subject(s)
Dental Caries/prevention & control , Sjogren's Syndrome/complications , Administration, Topical , Anti-Infective Agents/therapeutic use , Dental Care/standards , Dental Caries/etiology , Fluorides/administration & dosage , Fluorides/therapeutic use , Humans , Salivation/drug effects , Sjogren's Syndrome/therapy , Xerostomia/etiology , Xerostomia/therapyABSTRACT
A hallmark of the oral component of Sjögren's syndrome (SS) is the complaint of dry mouth thought to be secondary to dysfunction of the salivary glands. This article describes how treatment may be optimized for individuals who have dry mouth.
Subject(s)
Saliva, Artificial/therapeutic use , Salivary Glands/metabolism , Sjogren's Syndrome/therapy , Xerostomia/therapy , Dental Caries/etiology , Dental Caries/therapy , Humans , Male , Middle Aged , Mouth Diseases/etiology , Mouth Diseases/therapy , Mouth Mucosa/metabolism , Mouth Mucosa/physiopathology , Salivary Glands/physiopathology , Sjogren's Syndrome/complications , Tooth Remineralization , Xerostomia/etiologyABSTRACT
PURPOSE: Squamous metaplasia occurs in ocular surface diseases like Sjögren's syndrome (SS). It is a phenotypic change whereby epithelial cells initiate synthesis of squamous cell-specific proteins such as small proline-rich protein 1B (SPRR1B) that result in pathologic keratin formation on the ocular surface. The authors hypothesized that inflammation is a key inducer of pathologic keratinization and that SPRR1B represents an analytical biomarker for the study of the molecular mechanisms. METHODS: Real-time quantitative RT-PCR and immunohistochemistry were used to examine SPRR1B mRNA and protein in two different mouse models of dry eye and patients with SS. Adoptive transfer of mature lymphocytes from mice lacking the autoimmune regulator (aire) gene was performed to examine the role of inflammation as an inducer of squamous metaplasia. SPRR1B expression in response to several cytokines was examined in vitro, whereas the expression of cytokines IL1beta and IFNgamma was quantified in ocular tissues of aire-deficient mice and patients with SS. RESULTS: SPRR1B was increased across the ocular surface of mice with both desiccating stress and autoimmune-mediated, aqueous-deficient dry eye and in patients with SS. Adoptive transfer of CD4(+) T cells from aire-deficient mice to immunodeficient recipients caused advanced ocular surface keratinization. IL1alpha, IL1beta, IL6, IFNgamma, and TNFalpha induced SPRR1B expression in vitro and the local expression of IL1beta and IFNgamma was elevated in ocular tissues of patients with SS and aire-deficient mice. CONCLUSIONS: SPRR1B is a valid biomarker for the study of the molecular mechanisms of squamous metaplasia. There is a definitive link between inflammation and squamous metaplasia in autoimmune-mediated dry eye disease, with IL1beta and IFNgamma likely acting as key participants.
Subject(s)
Epithelium, Corneal/metabolism , Membrane Proteins/metabolism , Sjogren's Syndrome/metabolism , Adoptive Transfer , Animals , Biomarkers/metabolism , Blotting, Western , CD4-Positive T-Lymphocytes/physiology , Cells, Cultured , Cornified Envelope Proline-Rich Proteins , Disease Models, Animal , Epithelium, Corneal/pathology , Female , Fluorescent Antibody Technique, Indirect , Humans , Interferon-gamma/metabolism , Interleukin-1beta/metabolism , Male , Membrane Proteins/genetics , Metaplasia , Mice , Mice, Inbred BALB C , Mice, Inbred NOD , Middle Aged , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Sjogren's Syndrome/genetics , Sjogren's Syndrome/pathologyABSTRACT
The labial salivary gland biopsy is a diagnostic test for the oral component of Sjögren's syndrome (SS) that has been the subject of controversy and re-examination for many years. Despite multiple recent challenges to the significance of this test, when correctly done, it remains one of the most informative, specific, and technically simple tests available for the oral component of SS. Because of compromised salivary gland function, patients with SS are at risk for dental caries. Within the past decade, a paradigm shift has occurred within the field of caries research. The caries process was previously thought irreversible once initiated. Research has shown that the "early" carious lesion can be remineralized. Thus, the "early" carious lesion may be prevented and even repaired. The process of remineralization requires appropriate conditions to occur, and one of those conditions is pH. Because water is often the preferred wetting agent/beverage for patients with SS, the data show that, with regard to pH, not all waters are created equal.
Subject(s)
Dental Caries/etiology , Salivary Glands/pathology , Sjogren's Syndrome/complications , Sjogren's Syndrome/diagnosis , Xerostomia/diagnosis , Biopsy/methods , Humans , Hydrotherapy , Salivation , Sjogren's Syndrome/pathologyABSTRACT
The mechanism by which tumor necrosis factor-alpha (TNF) differentially modulates type I diabetes mellitus in the nonobese diabetic (NOD) mouse is not well understood. CD4+CD25+ T cells have been implicated as mediators of self-tolerance. We show (i) NOD mice have a relative deficiency of CD4+CD25+ T cells in thymus and spleen; (ii) administration of TNF or anti-TNF to NOD mice can modulate levels of this population consistent with their observed differential age-dependent effects on diabetes in the NOD mouse; (iii) CD4+CD25+ T cells from NOD mice treated neonatally with TNF show compromised effector function in a transfer system, whereas those treated neonatally with anti-TNF show no alteration in ability to prevent diabetes; and (iv) repeated injection of CD4+CD25+ T cells into neonatal NOD mice delays diabetes onset for as long as supplementation occurred. These data suggest that alterations in the number and function of CD4+CD25+ T cells may be one mechanism by which TNF and anti-TNF modulate type I diabetes mellitus in NOD mice.
