Oral mucosal changes associated with primary diseases in other body systems

Systemic diseases may manifest in the oral cavity. This chapter reviews the oral mucosal pathology in blood diseases, gastrohepatic diseases, kidney diseases, immunologic and connective tissue diseases, endocrine diseases, pulmonary diseases, nutritional deficiencies, dermatologic diseases, as well as cancer‐associated oral mucosal conditions. The oral mucosa is one of the most commonly affected tissues and may present with unique clinical appearances. Oral mucosal involvement may be the first presentation of the systemic disease or reflect activity or progression of the primary condition. Therefore, it is of importance to be familiar with oral mucosal manifestations of these systemic diseases.     

Mast cell heterogeneity in various oral mucosal sites in the rat.

Two distinct types of mast cells are recognized in the rat: connective tissue mast cells (CTMCs), found in the peritoneal cavity, skin, tongue, etc. and mucosal mast cells (MMCs), found in the intestinal mucosa. The two subsets differ functionally and can be defined by histochemical methods. The aim here was to characterize the mast cell population in various oral mucosal sites. Biopsies were taken from the tongue, buccal mucosa, gingival mucosa and intestine (jejunum) of 20 rats. For optimal preservation of the MMCs, a fixative with low aldehyde concentration and low pH was used. The biopsies were embedded in paraffin. The first of three consecutive sections (5 microns) was stained with toluidine blue for 30 s, the second with toluidine blue for 7 days and the third with astra blue/safranine. Cells positive with toluidine blue after 30 s were classified as CTMCs, and those positive after 7 days but not after 30 s as MMCs. Cells positive to safranine in the astra blue/safranine staining sequence were classified as CTMCs and those positive to astra blue as MMCs. The total number of mast cells was similar in the superficial layers of all oral tissues studied. There were more mast cells in the deeper than in the superficial portions of the tongue. Mast cells with staining characteristics and size similar to those observed in the intestinal mucosa (MMCs) were found together with 'classical' connective tissue mast cells (CTMCs). The results suggest that the mast cell population of oral mucosal tissues of the rat contains both CTMC- and MMC-like cells.     

Scleroderma: considerations for dental hygienists

Abstract:  Scleroderma, the general name of a group of progressive diseases affecting the connective tissues is the most deadly of the varying connective tissue disorders. Characterized by abnormal thickening of the skin, this collagen-vascular disease is associated with immune dysfunction. Hallmark signs of scleroderma include fibrosis, vascular instability and initial inflammation resulting from excessive collagen deposition. Oral facial involvement is considerable, necessitating adaptations in patient oral self-care and influencing oral hygiene. Appropriate dental hygiene management of patients with this autoimmune disorder requires an understanding of clinical characteristics, the recognition of oral facial involvement, treatment considerations and pharmacological interventions. With this information, dental hygienists will be better prepared to provide compassionate, safe and effective dental hygiene management and care to patients with scleroderma.     

Lipopolysaccharide stimulates histamine-forming enzyme (histidine decarboxylase) activity in murine dental pulp and gingiva

To examine the potential role of the histamine-forming enzyme, histidine decarboxylase (HDC), in oral inflammation and disease, we studied HDC activity in oral tissue after induction by bacterial agents. Following injection of E. coli-derived lipopolysaccharide (LPS) into mice, we measured the quantitative changes in HDC activity over time in dental pulp and gingiva. Oral tissue taken from individual mice was insufficient for detecting precise HDC activity, thus, we combined dental pulp or gingival tissues from four mice and assayed them over the course of 24 h. Our results indicate that LPS stimulated marked elevations of HDC activity in dental pulp and gingiva. This increase reached a maximum at 6 h after LPS injection and remained detectable at for least 24 h. Since mast cells are known to produce histamine through a difference mechanism than HDC induction, we compared LPS-induced HDC activity in dental pulp and gingiva to that in ear skin (a tissue rich in mast cells) and liver (a tissues lacking in mast cells). LPS also induced a marked increase in the HDC activity in liver and ear skin at 6 h after LPS injection. By contrast, saline injection had no effect on the HDC activity in any of the four tissues, although basal levels of HDC activity in ear skin was markedly higher than basal HDC activity in the other three kinds of tissues. Still, the relative increase in LPS-induced HDC activity in dental pulp and gingiva were much greater than that in ear skin. Since liver are devoid of mast cells and ear skin is considered the tissue richest in mast cells, the differences in HDC activity between tissues indicates that histamine induced by LPS may be produced by cells other than mast cells through another mechanism of action. These results also suggest that histamine produced in oral tissues in response to bacterial agents such as LPS could be involved in development of pulpitis or gingivitis (periodontitis), the most common diseases in the dental clinic, and that efforts to inhibit HDC activity, which elevates histamine levels in oral tissues, might offer the basis for novel treatment strategies.     

Dental management of a pediatric patient with mastocytosis: a case report

Mastocytosis is a heterogeneous group of clinical disorders characterized by an excessive number of normal mast cells in a variety of tissues (skin, bone marrow, liver, spleen and lymph nodes). It is most often seen in the skin in pediatric-onset mastocytosis presenting as urticaria pigmentosa. Children with this disorder are on a strict avoidance protocol of triggering factors to decrease the likelihood of life-threatening anaphylactic reactions. Close monitoring and the avoidance of known histamine-releasing drugs is necessary in the pediatric dental office, as is a readiness to use resuscitative measures. A case of a 4-year, 6-month-old pediatric dental patient with mastocytosis is presented. Dental treatment was provided in an ambulatory setting utilizing nitrous oxide, oxygen analgesia and H1 and H2 antihistamines to prevent mast cell degranulation and to provide sedation.     

Increase of mast cells and tumor angiogenesis in oral squamous cell carcinoma

BACKGROUND: Although mast cells (MCs) have been implicated in promoting angiogenesis in some malignant tumors, especially of the aerodigestive tract, little is known in oral squamous cell carcinoma (SCC). METHODS: A retrospective study was conducted to elaborate upon the correlation between MCs and tumor angiogenesis in 26 cases of oral SCC, six cases of oral pre-malignant dysplasia, 10 cases of oral hyperkeratosis, and six cases of normal oral mucosa by means of immunohistochemical technique. RESULTS: The MCs in all lesions and normal oral mucosa strongly expressed tryptase. The densities of MCs and microvessels appeared to increase with disease progression. The MC and microvascular counts were significantly higher in oral SCC than in hyperkeratosis and normal oral mucosa (P < 0.05). A significant correlation between MC and microvascular densities was observed in oral SCC (r = 0.5; P = 0.012). CONCLUSIONS: These findings suggest that MCs may upregulate tumor angiogenesis in oral SCC, perhaps via MC tryptase.     

Nonsquamous cell malignant tumours of the oral cavity: an overview

Many malignant tumours other than squamous cell carcinoma may present in the oral cavity. Melanomas of the oral cavity are usually pigmented, aggressive tumours associated with a poor prognosis. Neoplasms of the minor salivary glands have a greater tendency to be malignant than those of the major glands, and some exhibit a predilection for occurring in the mouth. Many types of connective tissue malignant tumours (sarcomas) may arise in the mouth, including soft-tissue cancers and lesions of hematologic cells such as lymphoma, whereas osteosarcoma is the most common malignancy of the hard tissues found in the mouth. Cancers from distant organs such as breast, lung and prostate may metastasize to the oral cavity. This paper presents a brief overview of nonsquamous cell oral cancers, with emphasis on those most likely to be encountered by the practising dentist.     

Involvement of the jaw bones in systemic mastocytosis

Systemic mastocytosis is characterised by proliferation of mast cells and infiltration of organs. Severe bony pain may result from release of chemical mediators from mast cells and affected patients are at an increased risk of anaphylaxis. Traditional analgesics such as non-steroidal anti-inflammatory agents and opioids are contraindicated. Diagnosis is based on presentation, biopsy of bone marrow, and magnetic resonance imaging of the affected area. In the head and neck, the disease may present as facial pain, localised osteomyelitis, oral sinus formation, and oral ulceration. Treatment is with histamine antagonists and bisphosphonates to control symptoms. An adrenaline pen is provided for use in case of anaphylaxis.     

Oral health status, salivary factors and microbial analysis in patients with active gastro-oesophageal reflux disease

Aim: To present a complex oral health status including salivary factors, microbial analysis and periodontal and hygiene indices in patients with active gastro‐oesophageal reflux disease (GORD). Return of stomach contents is quite common in cases of gastro‐oesophageal reflux. Pathological acid movement from the stomach into the oesophagus and oral cavity may lead to a development of dental erosion. Long‐lasting untreated GORD may damage hard dental and periodontal tissues and alter the oral microbial environment. The quality and amount of the saliva play an important role in hard and soft oral tissues changes. Method: Fifty patients with diagnosed GORD using 24‐hour pH manometry underwent dental examination; 24 patients had active GORD and had been waiting for surgical therapy. In this patient group oral health status and salivary analysis were evaluated. Results: Indicated low salivary flow rates and buffering capacity with a low caries risk but a high risk for dental erosion progression.     

Oral manifestations of gastrointestinal disease.

A variety of gastrointestinal diseases can be associated with lesions of the oral cavity. The lesions usually correlate to active intestinal disease, but they may present prior to any other evidence of the disease and even be used to initiate diagnosis and treatment. This paper reviews the more common oral manifestations of gastrointestinal disease and their dental management.     

Relationship between mast cell degranulation and inflammation in the oral cavity

Mast cells are granule-containing secretory cells which are distributed preferentially about the microvascular bed in oral mucosa. This work examined the contribution of mast cell mediators to inflammation in the oral cavity. Mast cells in oral tissues expressed the serine proteases, tryptase and chymase, with a minor subpopulation being chymase-negative. Mast cells contained the cytokine tumour necrosis factor-α (TNF) in their granules. Degranulation of mast cells was a consistent feature of inflammation lesions (lichen planus, gingivitis, pulpitis, periapical inflammation). In lichen planus, intracellular stores of TNF were depleted, and expression of mRNA for TNF was upregulated, indicating ongoing production and release of the cytokine. The density of mast cells in tissue compartments was related to the level of expression of E-selectin, an endothelial adhesion molecule which is known to be induced in skin by TNF derived from degranulating mast cells. Further attention should be directed toward the role of mast cell products, particularly TNF, in inflammation in the oral cavity.     

Quantitative assessment of mast cells in recurrent aphthous ulcers (RAU)

Previous studies on the frequency of mast cells (MCs) in recurrent aphtous ulcers (RAU) have yielded conflicting results. Monoclonal antibodies specific for tryptase (AA1) and anti-IgE (polyclonal antibody) were used to identify density and distribution of MCs in an immunohistochemical study of RAU (n=15), induced oral traumatic ulcers (TUs) (n=9), and control clinically healthy oral mucosa (n=15). Results were quantified by means of a VIDAS image analyzer. In all sections studies, IgE-positive cells showed similar frequency and distribution to tryptase-positive MCs. In RAU lesions, numerous tryptase-positive MCs were found in the sub-epithelial lamina propria, but MC numbers in the epithelium were low and present only in some RAU biopsies. MCs were also more numerous in RAU-inflammatory infiltrates (118±31 cells/mm²) than those seen in TU-inflammatory infiltrates (75±18 cells/mm², P < 0.001). MC activation/degranulation, as judged by diffuse extracellular tryptase staining, was a common feature within RAU-inflammatory infiltrates and at RAU-inflammatory infiltrates-connective tissue interfaces, which were often associated with connective tissue disruption. MC counts in the RAU connective tissue, lateral to the inflammatory infiltrates, were significantly greater than in the connective tissue of TUs and of control biopsies (124±36 vs 73±13 vs 69±21 cells/mm², respectively; P<0.001). Overall, MCs were significantly increased in aphthae (116±26 cells/mm²) compared with TU lesions (72±11 cells/mm², P<0.001) and controls (71±16 cells/mm², P<0.001). In conclusion, MC numbers are increased in a typical topographical pattern, and the local MCs show signs of activation/degranulation suggesting active involvement of this cell type in RAU pathogenesis.     

Dental symptomatology associated with connective tissue anomalies

Subjects affected with inherited disorders, of the connective tissue make up an important population, carrying high risks as to distinct aspects of oral health and dental treatment. These generalized conditions may produce serious clinical symptoms in different orofacial structures, which have to be dealt with, or anticipated, when considering dental treatment. The most prevalent disorders result from deficiency of Type I collagen, an important extracellular matrix protein regulating both the structural and mechanical properties of most of the orofacial tissues. Recurrent jaw fractures, an increased liability for development of temporomandibular disorders, periodontal disease and mucosal fragility, an abnormal tooth color and/or shape, and pulp obliteration may feature as major clinical manifestations of the respective disorders. Deficiency of fibrillin, a protein providing soft tissues with elastic capacities, may produce a long face with a high and narrow palate, an increased liability for the developnet of temporomandibular disorders and periodontal disease, and root dsyplasia. Whenever present, these manifestations/risk factors have to be integrated in dental treatment strategies. In cases with high risk for cardiovascular complications, specific preventive measures, such as cardiac output monitoring and the administration of appropriate local anesthetics, have to be taken before starting any invase dental treatment. The present paper aims to provide the practitioner with an appreciation of the most prevalent inherited disorders of the connective tissue with their respective genetics, molecular aspects of pathology, medical and oral manifestations, and guidelines for dental treatment.     

Oral presentation of histoplasmosis in an immunocompetent patient: a diagnostic challenge

Histoplasmosis is a rare systemic fungal infection, primarily affecting the pulmonary system. Oral lesions are usually a manifestation of the disseminated form of the disease and most frequently observed in severely immunocompromised patients, such as those with advanced human immunodeficiency virus infection and/or frank acquired immune deficiency syndrome. The clinical presentation of the oral lesions may be difficult to distinguish from oral squamous cell carcinoma. The histopathological features are usually characteristic, but occasionally the organisms are scanty and not readily identified, which can preclude obtaining the correct diagnosis and ensuring appropriate management. Histoplasmosis is an unusual and rare cause of chronic non‐healing ulceration in the oral cavity. A case of histoplasmosis involving the oral cavity in an immunocompetent patient is reported, which was not recognized, resulting in the inappropriate management of the condition.     

Sotos Syndrome: A case report

Sotos Syndrome ie a genetic condition characterized by accelerated bone development abnormal craniofacial morphology and psychomotor developmental retardation. The behavioral problems usually associated with the syndrome Include poor social skills, anxiety and/or irritability. Oral findings include prognathism and a high‐arched palate with premature eruption of the teeth. Delayed psychomotor development increases the risk for carles. A personalized preventive treatment plan with dose supervision of the patient's oral health cars is required. This paper documents a child diagnosed with Sotos Syndrome and describes the primary clinical features, the disease‐specific craniofacial, oral and dental findings, and dental care management of this patient.     

Immunopathogenesis of oral lichen planus

Oral lichen planus (LP) is a common mucosal disorder in which cell mediated immunity is thought to play a major role. In this paper, a unifying hypothesis which attempts to integrate cellular and molecular signals in the local immune response in oral LP is presented. In this model, modified keratinocyte surface antigens are the target for the cytotoxic cell response which characterizes oral LP, whereas mast cells and antigen presenting Langerhans cells are key cellular elements in the evolving lesion. It has been established that mast cell degranulation induces adhesion molecule expression on endothelium which facilitates lymphocyte homing to the tissues. These adhesive interactions between lymphocytes and keratinocytes are postulated to be important determinants in the effector phase of the lesion. Cytokines produced by both lymphocytes and keratinocytes which influence the local immune response could promote chronicity. Accordingly, modulation of immunologic events is a potential therapeutic approach for oral LP.     

Optical diagnostics in the oral cavity: an overview

Oral Diseases (2010) 16 , 717–728 As the emphasis shifts from damage mitigation to disease prevention or reversal of early disease in the oral cavity, the need for sensitive and accurate detection and diagnostic tools become more important. Many novel and emergent optical diagnostic modalities for the oral cavity are becoming available to clinicians with a variety of desirable attributes including: (i) non‐invasiveness, (ii) absence of ionizing radiation, (iii) patient‐friendliness, (iv) real‐time information (v) repeatability, and (vi) high‐resolution surface and subsurface images. In this article, the principles behind optical diagnostic approaches, their feasibility and applicability for imaging soft and hard tissues, and their potential usefulness as a tool in the diagnosis of oral mucosal lesions, dental pathologies, and other dental applications will be reviewed. The clinical applications of light‐based imaging technologies in the oral cavity and of their derivative devices will be discussed to provide the reader with a comprehensive understanding of emergent diagnostic modalities.     

Management of patients with foreign body gingivitis: report of 2 cases with histologic findings

Foreign body gingivitis is an inflammation of the gingiva, characterized by foci containing particles of foreign material in the connective tissue, which can have either a granulomatous or a lichenoid microscopic appearance. In clinical terms, it differs from other immune-mediated gingival disorders in its limited involvement of tissues other than the gingiva, as well as its relative resistance to treatment by topical corticosteroids. Two cases are presented, with a review of the clinical features, including characteristic desquamation and mottling of the marginal gingiva and symptoms of localized tenderness and pain; gingival recession was observed in both of the reported cases. Histologic examination revealed damaged epithelium and degeneration of the basal layer, as well as a mixed inflammatory cell infiltrate in the connective tissue with refractile or opaque particles of foreign material. Gingival inflammation and the severity of gingival erosions improved dramatically with careful debridement, improved home care and more frequent, diligent periodontal maintenance therapy. Free gingival grafts, together with excision of affected tissues, served to stabilize and reinforce the marginal tissues, as well as eliminating further clinical signs of the disease; excision alone was not as effective. Patients require careful dental and periodontal management as well as appropriate oral home care to avoid further mechanical damage to the gingiva; in addition, the use of dental abrasives and polishing agents should be restricted, particularly if gingival lesions are present. Home care recommendations include avoidance of dentifrices with certain chemical additives and rinses with a high alcohol content.     

Macrophages, dendritic cells and T lymphocytes in rat buccal mucosa and dental pulp following 5-fluorouracil treatment

Cancer chemotherapeutic drugs may affect immunocompetent cells of oral soft tissues, causing an impaired capacity to induce immune defence reactions. This study was designed to investigate changes in the number of macrophages, dendritic cells and T lymphocytes in the oral mucosa and dental pulp following treatment with the antineoplastic agent 5-fluorouracil (5-FU). Rats were given 5-FU (30 mg/kg or 50 mg/kg) i.v. on days 0, 1, 2, 5, 6 and 7. The number of cells in buccal epithelium and dental pulp expressing ED2, MHC class II, or CD2 molecules was analyzed following immunohistochemical peroxidase staining. Major histocompatibility complex (MHC) class II molecules were analyzed in epithelial sheets and in epithelial cell suspensions by flow cytometry. Increasing concentrations of 5-FU changed the morphology of the epithelial Langerhans cells with a reduced dendritic appearance as the most prominent feature. At 50 mg/kg of 5-FU, the oral epithelium detached from the connective tissue at the basement membrane. MHC class II molecule-expressing cells were reduced in number in the lamina propria of the buccal mucosa and in the dental pulp after both low and high dose of 5-FU, but only after high dose in the epithelium. The number of ED2- and CD2-expressing cells in the dental pulp was only slightly reduced by 5-FU treatment at both low and high dose, while these cells decreased in number in the oral mucosa. The varying sensitivity to 5-FU by macrophages, dendritic cells, and T cells depending on the tissues in which they reside may be due to differences in cell origin or differences in antigenic load.     

Mast cells in periodontal disease.

Since the roles of mast cells in periodontal tissues are not clear, this study aimed to count the number of mast cells in gingival tissues of healthy volunteers and patients with chronic periodontal disease before and three weeks after surgical treatment. The numbers of mast cells were found to be increased on postoperative healed tissues and inflamed tissues respectively, compared to healthy tissues. This increase is closely related to fibrosis in connective tissues.