This review examines the diagnostic application of saliva for systemic diseases. As a diagnostic fluid, saliva offers distinctive advantages over serum because it can be collected non-invasively by individuals with modest training. Furthermore, saliva may provide a cost-effective approach for the screening of large populations. Gland-specific saliva can be used for diagnosis of pathology specific to one of the major salivary glands. Whole saliva, however, is most frequently used for diagnosis of systemic diseases, since it is readily collected and contains serum constituents. These constituents are derived from the local vasculature of the salivary glands and also reach the oral cavity via the flow of gingival fluid. Analysis of saliva may be useful for the diagnosis of hereditary disorders, autoimmune diseases, malignant and infectious diseases, and endocrine disorders, as well as in the assessment of therapeutic levels of drugs and the monitoring of illicit drug use.

https://journals.sagepub.com/doi/pdf/10.1177/154411130201300209

The Diagnostic Applications of Saliva— A Review:

Health benefits of saliva: a review.

Lichen planus, a chronic autoimmune, mucocutaneous disease affects the oral mucosa (oral lichen planus or OLP) besides the skin, genital mucosa, scalp and nails. An immune mediated pathogenesis is recognized in lichen planus although the exact etiology is unknown. The disease most commonly affects middle-aged females. Oral lichenoid reactions (OLR) which are considered variants of OLP, may be regarded as a disease by itself or as an exacerbation of an existing OLP, by the presence of medication (lichenoid drug reactions) or dental materials (contact hypersensitivity). OLP usually presents as white striations (Wickham's striae), white papules, white plaque, erythema, erosions or blisters. Diagnosis of OLP is established either by clinical examination only or by clinical examination with histopathologic confirmation. Direct immunofluorescence examination is only used as an adjunct to the above method of diagnosis and to rule out specific autoimmune diseases such as pemphigus and pemphigoid. Histopathologic features of OLP and OLR are similar with suggestions of certain discriminatory features by some authors. Topical corticosteroids are the treatment of choice for OLP although several other medications have been studied including retinoids, tacrolimus, cyclosporine and photodynamic therapy. Certain OLP undergo malignant transformation and the exact incidence and mechanisms are still controversial. In this paper, etiopathogenesis, diagnosis, management and malignant transformation of OLP and OLR have been reviewed.

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Oral lichen planus and lichenoid reactions: etiopathogenesis, diagnosis, management and malignant transformation

Lichen planus (LP) is a relatively common disorder of the stratified squamous epithelia, which is, in many ways, an enigma. This paper is the consensus outcome of a workshop held in Switzerland in 1995, involving a selection of clinicians and scientists with an interest in the condition and its management. The oral (OLP) eruptions usually have a distinct clinical morphology and characteristic distribution, but OLP may also present a confusing array of patterns and forms, and other disorders may clinically simulate OLP. Lesions may affect other mucosae and/or skin. Lichen planus is probably of multifactorial origin, sometimes induced by drugs or dental materials, often idiopathic, and with an immunopathogenesis involving T-cells in particular. The etiopathogenesis appears to be complex, with interactions between and among genetic, environmental, and lifestyle factors, but much has now been clarified about the mechanisms involved, and interesting new associations, such as with liver disease, have emerged. T...

Update on oral lichen planus: etiopathogenesis and management.

Several therapeutic agents have been investigated for the treatment of oral lichen planus (OLP). Among these are corticosteroids, retinoids, cyclosporine, and phototherapy, in addition to other treatment modalities. A systematic review of clinical trials showed that particularly topical corticosteroids are often effective in the management of symptomatic OLP lichen planus. Systemic corticosteroids should be only considered for severe widespread OLP and for lichen planus involving other mucocutaneous sites. Because of the ongoing controversy in the literature about the possible premalignant character of OLP, periodic follow-up is recommended. There is a spectrum of oral lichen planus-like ("lichenoid") lesions that may confuse the differential diagnosis. These include lichenoid contact lesions, lichenoid drug reactions and lichenoid lesions of graft-versus-host disease. In regard to the approach to oral lichenoid contact lesions the value of patch testing remains controversial. Confirmation of the diagnosis of an oral lichenoid drug reaction may be difficult, since empiric withdrawal of the suspected drug and/or its substitution by an alternative agent may be complicated. Oral lichenoid lesions of graft-versus-host disease (OLL-GVHD) are recognized to have an association with malignancy. Local therapy for these lesions rests in topical agents, predominantly corticosteroids.

Oral lichen planus and oral lichenoid lesions: diagnostic and therapeutic considerations

Using saliva for disease diagnostics and health surveillance is a promising approach as collecting saliva is relatively easy and non-invasive. Over the past two decades, using salivary biomarkers specifically for early cancer detection has attracted much research interest, especially for cancers occurring in the oral cavity and oropharynx, for which the five-year survival rate (62%) is still one of the lowest among all major human cancers. More than 90% of oral cancers are oral squamous cell carcinoma (OSCC) and the standard method for detection is through a comprehensive clinical examination by oral healthcare professionals. Despite the fact that the oral cavity is easily accessible, most OSCCs are not diagnosed until an advanced stage, which is believed to be the major reason for the low survival rate, and points to the urgent need for clinical diagnostic aids for early detection of OSCC. Thus, much research effort has been dedicated to investigating potential salivary biomarkers for OSCC, and more than 100 such biomarkers have been reported in the literature. However, some important issues and challenges have emerged that require solutions and further research in order to find reliable OSCC salivary biomarkers for clinical use. This review article provides an up-to-date list of potential OSCC salivary biomarkers reported as of the fall of 2013, and discusses those emerging issues. By raising the awareness of these issues on the part of both researchers and clinicians, it is hoped that reliable, specific and sensitive salivary biomarkers may be found soon—and not only biomarkers for early OSCC detection but also for detecting other types of cancers or even for monitoring non-cancerous disease activity.

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A review of research on salivary biomarkers for oral cancer detection

The inflammatory components of plaque induced gingivitis and chronic periodontitis can be managed effectively for the majority of patients with a plaque control program and non-surgical and/or surgical root debridement coupled with continued periodontal maintenance procedures. Some patients may need additional therapeutic procedures. All of the therapeutic modalities reviewed in this position paper may be utilized by the clinician at various times over the long-term management of the patient's periodontal condition.

Treatment of plaque-induced gingivitis, chronic periodontitis, and clinical conditions.

Objectives To investigate if burning mouth syndrome (BMS) patients have differing health perceptions, medication, and life experiences compared with controls and to examine the role of vulnerability factors and differentiate them from the presenting symptomology in patients with BMS. Study design A nonprobability convenience sample of patients presenting with BMS and age- and sex-matched controls were recruited from Queen's University, Belfast, King's College London, and Baylor College of Dentistry, Dallas. Participants completed a questionnaire to assess 9 aspects of their medical and social history, including early and past life experiences. The subjects completed the Hospital Anxiety and Depression Scale to assess current distress. Results Participants with BMS had significantly higher experiences of adverse early life experiences compared with controls. They had statistically significantly higher mean scores for anxiety and depression compared with controls. A hierarchical multiple logistic regression analysis showed that the characteristics of BMS included cancer phobia, gastro-intestinal problems, and chronic fatigue. Conclusion BMS is a complex disorder. People who experience adverse life experiences may become vulnerable to developing BMS in later life.

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Vulnerability and presenting symptoms in burning mouth syndrome

Cyclosporine A (CsA) is a widely used immunosuppressant for transplant patients and is also used for the treatment of a wide variety of systemic diseases with immunologic components. A prominent side effect of CsA administration is gingival overgrowth. It has been postulated that CsA alters fibroblast activity through effects on various cytokines such as the interleukins, however, as yet, data concerning the molecular mechanisms involved in connective tissue proliferation are still preliminary in nature. The purpose of this study was to evaluate interleukin-6 (IL-6) gene expression in gingival tissues of patients receiving CsA therapy and exhibiting gingival overgrowth. Radioimmunoassay (RIA) demonstrated a significant difference in tissue levels of IL-6 as mean +/- SEM. IL-6 content in CsA-stimulated tissue was 184.3 +/- 30.2 ng/mg total protein versus 23.3 +/- 6.5 ng/mg total protein in control tissue. In situ hybridization indicated that overgrown gingival tissues from patients taking CsA had a significantly higher content of IL-6 mRNA when compared to control tissues. Expressing IL-6 mRNA levels as silver grains/cell, CsA-stimulated tissue had 166.9 +/- 12.0 grains of IL-6 mRNA/cell while control tissue had 12.8 +/- 3.0 grains of IL-6 mRNA/cell. These results demonstrate that CsA therapy results in increased levels of IL-6 protein and IL-6 mRNA in overgrown human gingival tissues. This is the first report of CsA-upregulated IL-6 gene expression in vivo, and may explain in part the molecular mechanisms responsible for CsA-induced gingival overgrowth.

Cyclosporine A Upregulates Interleukin‐6 Gene Expression in Human Gingiva: Possible Mechanism for Gingival Overgrowth

Background:Although mechanical non-surgical therapy (scaling and root planing) is the most common means of initial treatment of periodontal diseases, the relative clinical efficacy of various methods, including manual versus machine-driven, with or without adjunctive agents, has not been determined. Rationale:This systematic review analyzes the literature in an effort to identify the most effective therapies, based on both clinical and patient-centered outcomes. Focused Question:In patients with periodontitis, what is the effect of mechanically-driven instrumentation (e.g., power-driven) and/or subgingival irrigation with and without manual instrumentation compared to manual instrumentation alone? Search Protocol:Two investigators examined MEDLINE and the Cochrane Oral Health Group specialized registry for clinical trials published in English. Hand searches were performed of the International Journal of Periodontics & Restorative Dentistry, Journal of Clinical Periodontology, Journal of Periodontology, an...

Terry D. Rees

Papers

A review of research on salivary biomarkers for oral cancer detection

Treatment of plaque-induced gingivitis, chronic periodontitis, and clinical conditions.

Vulnerability and presenting symptoms in burning mouth syndrome

Cyclosporine A Upregulates Interleukin‐6 Gene Expression in Human Gingiva: Possible Mechanism for Gingival Overgrowth

Local anti-infective therapy: mechanical and physical approaches. A systematic review.