Pathogenesis of Dental Biofilm-Induced Gingivitis PDF

Dental Clinical Practice 2 Pathogenesis of Dental Biofilm-Induced Gingivitis D R. A B I E R A B D U L S A T TA R M O H A M M E D  Learning Objectives: List the stages of plaque -induced gingivitis development. Describe the histological changes in each stage of plaque -induced gingivitis development...

Dental Clinical Practice 2 Pathogenesis of Dental Biofilm-Induced Gingivitis D R. A B I E R A B D U L S A T TA R M O H A M M E D  Learning Objectives: List the stages of plaque -induced gingivitis development. Describe the histological changes in each stage of plaque -induced gingivitis development. Relate the histological changes with the clinical changes in each stage Recognize gingivitis development in children Sep./12/2024 ABIER A. MOHAMMED 2  Introduction The epithelial barrier, immune response, crevicular fluid, and saliva maintain gingival health. Inflammation is the fundamental response of living tissues to injury and provides a rapid first line of defense against damage and infection. Pathologic changes in gingivitis are associated with oral microorganisms attached to the tooth and perhaps in or near the gingival sulcus. These organisms can synthesize products (e.g., collagenase, protease, and endotoxin) that cause damage to epithelial and connective tissue cells, as well as inter-cellular constituents, such as collagen and ground substance. The sequence of events cumulating in clinically apparent gingivitis is categorized into initial, early, and established stages, with periodontitis as the advanced stage. One step evolves into the next, with no clear-cut dividing lines. Sep./12/2024 ABIER A. MOHAMMED 3 Despite extensive research, researchers still cannot distinguish definitively between normal gingival tissue and the initial stage of gingivitis Page and Schroeder (1977) classified the development of gingivitis into three stages, are: Stage I gingivitis (Initial lesion). Stage II gingivitis (Early lesion). Stage III gingivitis (Established lesion). Stage IV gingivitis (Advanced lesion)/Periodontitis. Sep./12/2024 ABIER A. MOHAMMED 4  Normal Neutrophil Functions Rolling Margination Diapedesis: moving out of blood vessels and into tissues Chemotaxis: moving toward sites of infection Adherence to the tissues: Phagocytosis: engulfing, lysing, digesting antigens Opsonization Oxidative mechanisms Nonoxidative mechanisms Inflammatory mediator secretion— prostaglandins (PGE2), leukotrienes (LTB4), cytokines (IL-1) Sep./12/2024 ABIER A. MOHAMMED 5  STAGE I GINGIVAL INFLAMMATION: THE INITIAL LESION Histological Changes: The initial lesion is said to appear within 2 to 4 days of plaque accumulation at a previously plaque-free site with no visible inflammation. This initial lesion is like the histological picture of healthy gingival tissues. It involves a low-grade inflammation characterized by the expansion of the vascular network and increased vascular permeability. This allows neutrophils and monocytes to migrate from the gingival vasculature through the connective tissues toward the source of the bacterial products in the gingival sulcus. Microscopically, some classic features of acute inflammation can be seen in the connective tissue beneath the junctional epithelium. Changes in blood vessel morphologic features (e.g., widening of tiny capillaries or venules) and adherence of neutrophils to vessel walls (margination) occur within one week and sometimes as early as two days after plaque has been allowed to accumulate. Sep./12/2024 ABIER A. MOHAMMED 6  Human biopsy sample, experimental gingivitis. After 4 days of plaque accumulation, the blood vessels immediately adjacent to the junctional epithelium are distended and contain polymorphonuclear leukocytes (neutrophils) (PMNs). Neutrophils have also migrated between the cells of the junctional epithelium (JE). OSE, Oral sulcular epithelium. (Magnification, ×500.) From Payne WA, Page RC, Ogilvie AL, et al. Histopathologic features of the initial and early stages of experimental gingivitis in man. J Periodontal Res. 1975;10:51. Sep./12/2024 ABIER A. MOHAMMED 7 Sep./12/2024 ABIER A. MOHAMMED 8 Exudation of fluid from the gingival sulcus and extravascular proteins is present Subtle changes can also be detected in the junctional epithelium and perivascular connective tissue at this early stage. For example, the perivascular connective tissue matrix becomes altered, and fibrin is exuded and deposited in the affected area. In addition, lymphocytes soon begin to accumulate. The increased migration of leukocytes and their accumulation within the gingival sulcus may correlate with an increased gingival fluid flow into the sulcus. The character and intensity of the host response determine whether this initial lesion resolves rapidly, with restoration of the tissue to a normal state; alternatively, it may evolve into a chronic inflammatory lesion. If the latter occurs, an infiltrate of macrophages and lymphoid cells appears within a few days. Clinical Sign: There is no apparent change in the gingiva (subclinical gingivitis). Sep./12/2024 ABIER A. MOHAMMED 9  STAGE II GINGIVAL INFLAMMATION: THE EARLY LESION The early lesion evolves from the initial lesion within about one week after the beginning of plaque accumulation. Clinically, the early lesion may appear as early gingivitis, and it overlaps with and evolves from the initial lesion with no clear-cut dividing line. Gingival fluid flow and the numbers of transmigrating leukocytes reach their maximum between6 and 12 days after the onset of clinical gingivitis Microscopic examination of the gingiva reveals Leukocyte infiltration in the connective tissue beneath the junctional epithelium The infiltration consists mainly of lymphocytes (75%, with the majority being T cells) Presence of migrating neutrophils, macrophages, plasma cells, and mast cells At the junctional epithelium and gingival sulcus, there is a dense infiltration of neutrophils and may begin to show the development of rete pegs or ridges Sep./12/2024 ABIER A. MOHAMMED 10 Alterations in blood vessel morphologic features and vascular bed patterns have also been described. The amount of collagen destruction also increases 70% of the collagen is destroyed around the cellular infiltrate The main fiber groups that are affected appear to be the circular and dentogingival fiber assemblies Alterations in blood vessel morphologic features and vascular bed patterns PMNs that have left the blood vessels in response to chemotactic stimuli from plaque components travel to the epithelium and cross the basement lamina; they are found in the epithelium, emerging in the pocket area PMNs are attracted to bacteria and engulf them during phagocytosis. In association with the ingestion of bacteria, PMNs release their lysosomes. Sep./12/2024 ABIER A. MOHAMMED 11  Human biopsy, experimental gingivitis. (A) Control biopsy specimen from a patient with good oral hygiene and no detectable plaque accumulation. The junctional epithelium is on the left. The connective tissue (CT) shows few cells other than fibroblasts, blood vessels, and a dense background of collagen fibers (magnification, ×500.) (B) Biopsy specimen taken after 8 days of plaque accumulation. The connective tissue is infiltrated with inflammatory cells, which displace the collagen fibers. A distended blood vessel (V) is seen in the center (magnification, ×500). (C) After 8 days of plaque accumulation, the connective tissue next to the junctional epithelium (JE) at the base of the sulcus shows a mononuclear cell infiltrate and evidence of collagen degeneration (i.e., clear spaces around the cellular infiltrate (magnification, ×500). (D) The inflammatory cell infiltrate at higher magnification (×1250). After 8 days of plaque accumulation, numerous small (SL) and medium- sized (ML) lymphocytes are seen within the connective tissue. Most of the collagen fibers around these cells have disappeared, presumably as a result of enzymatic digestion. From Payne WA, Page RC, Ogilvie AL, et al. Histopathologic features of the initial and early stages of experimental gingivitis in man. J Periodontal Res. 1975;10:51. Sep./12/2024 ABIER A. MOHAMMED 12 Clinical Signs: As time passes, clinical signs of erythema may appear, mainly because of the proliferation of capillaries and the increased formation of capillary loops between rete pegs or ridges. Bleeding on probing (BOP) may also be evident Sep./12/2024 ABIER A. MOHAMMED 13 STAGE III GINGIVAL INFLAMMATION: THE ESTABLISHED LESION Over time, the established lesion evolves. It is characterized by a predominance of plasma cells and B lymphocytes and the creation of a small gingival pocket lined with a pocket epithelium. Chronic gingivitis occurs 2 to 3 weeks after the beginning of plaque accumulation A key feature differentiating the established lesion is increased plasma cells, which become the primary inflammatory cell type. Plasma cells invade the connective tissue immediately below the junctional epithelium and deep into the connective tissue, around blood vessels, and between bundles of collagen fibers. The junctional epithelium reveals widened intercellular spaces filled with lysosomes derived from disrupted neutrophils, lymphocytes, and monocytes. The lysosomes contain acid hydrolases that can destroy tissue components. The junctional epithelium develops rete pegs or ridges that protrude into the connective tissue Sep./12/2024 ABIER A. MOHAMMED 14 Sep./12/2024 ABIER A. MOHAMMED 15 In the connective tissue, collagen fibers are destroyed around the infiltrate of intact and disrupted plasma cells, neutrophils, lymphocytes, monocytes, and mast cells However, several studies of human experimental gingivitis have failed to demonstrate plasma cell predominance in the affected connective tissues, including one study of 6 months duration. Increases in the proportions of plasma cells were evident with long-standing gingivitis, but the time for developing the classic “established lesion” may exceed 6 months. An inverse relationship appears between the number of intact collagen bundles and the number of inflammatory cells. Collagenolytic activity is increased in inflamed gingival tissue by the enzyme collagenase. While collagenase is normally present in gingival tissues, in disease, it is produced in high amounts by oral bacteria and innate immune cells, including PMNs Sep./12/2024 ABIER A. MOHAMMED 16 Clinical Signs In chronic gingivitis, which occurs 2 to 3 weeks after the beginning of plaque accumulation, the blood vessels become engorged and congested, venous return is impaired, and the blood flow becomes sluggish The result is localized gingival anoxemia, which superimposes a somewhat bluish hue on the reddened gingiva Extravasation of erythrocytes into the connective tissue and breakdown of hemoglobin into its component pigments can also deepen the color of the chronically inflamed gingiva. The established lesion can be described as moderately to severely inflamed gingiva. Sep./12/2024 ABIER A. MOHAMMED 17 Established lesions: two types appear to exist; some remain stable and do not progress for months or years, and others seem to become more active and convert to progressively destructive lesions. The established lesions appear reversible in that the sequence of events occurring in the tissues due to successful periodontal therapy seems Marginal supragingival plaque and gingivitis to be essentially the reverse of the series of events observed as gingivitis develops. Sep./12/2024 ABIER A. MOHAMMED 18  STAGE IV GINGIVAL INFLAMMATION: THE ADVANCED LESION Extension of the lesion into alveolar bone characterizes a fourth stage known as the advanced lesion OR Phase of periodontal Breakdown. Gingivitis will progress to periodontitis only in susceptible individuals. Sep./12/2024 ABIER A. MOHAMMED 19  Stages of Gingivitis Stage the initial lesion the early lesion the established lesion Time (Days) 2–4 days 4–7 days 14–21 days Blood Vessels Vascular dilation Vascular proliferation Same as stage II, plus blood Vasculitis stasis Junctional and Sulcular Infiltration by PMNs Same as stage I Same as stage II but more Epithelia Rete pegs advanced Atrophic areas Predominant Immune PMNs Lymphocytes Plasma Cells Cells Collagen Perivascular loss. Increased loss around infiltrate Continued loss Clinical Findings Gingival fluid flow Erythema Changes in color, size, Bleeding on probing texture, and so on Sep./12/2024 ABIER A. MOHAMMED 20  Course & Duration Gingivitis can occur with sudden onset and short duration and can be painful. A less severe phase of this condition can also occur. Chronic gingivitis develops slowly and has a long duration. It is painless unless acute or sub-acute exacerbations complicate it, and it is the type most often encountered. Chronic gingivitis is a fluctuating disease in which inflammation persists or resolves and normal areas become inflamed. Recurrent gingivitis reappears after having been eliminated by treatment or disappearing spontaneously. Sep./12/2024 ABIER A. MOHAMMED 21 Description Localized gingivitis, confined to single tooth Or group of teeth, (BoP more than 10% and less than 30% of sites). Generalized gingivitis, involves the entire mouth ( BoP equal to or more than 30% of the sites) Marginal gingivitis, involving gingival margin and it can include a portion of the contiguous attached gingiva. Papillary gingivitis, involving the interdental papilla, & extends to the adjacent portion of the gingival margin. Diffuse gingivitis, involves the gingival margin, attached gingiva & interdental papilla. (example, generalized chronic diffuse gingivitis, or localized chronic marginal gingivitis) Sep./12/2024 ABIER A. MOHAMMED 22 Localized Marginal gingivitis is confined to one or more areas of the marginal gingiva Localized diffuse gingivitis extends from the margin to the mucobuccal fold in a limited area Localized, diffuse, intensely red area on the facial surface of tooth #7 and dark-pink marginal changes in the remaining anterior teeth. Sep./12/2024 ABIER A. MOHAMMED 23 Localized papillary gingivitis is confined to one or more interdental spaces in a limited area. Generalized marginal gingivitis involves the gingival margins in relation to all the teeth. The interdental papillae are usually affected. Generalized diffuse gingivitis involves the entire gingiva. The alveolar mucosa and attached gingiva are affected, so the mucogingival junction is sometimes obliterated. Sep./12/2024 ABIER A. MOHAMMED 24  Clinical Features of Gingivitis Systematic approach is required in evaluation for the clinical features of gingivitis. The clinician should focus on subtle tissue alterations because these may be of diagnostic significance. A systematic clinical approach requires an orderly examination of the gingiva for color, contour, consistency, position, and ease and severity of bleeding and pain. Sep./12/2024 ABIER A. MOHAMMED 25  Gingival Bleeding on Probing The two earliest signs of gingival inflammation preceding established gingivitis are (1) increased gingival crevicular fluid production rate and (2) bleeding from the gingival sulcus on gentle probing. Bleeding on Probing : Varies in severity, duration, and ease of provocation. Is easily detected clinically and, therefore, is of value for the early diagnosis and prevention of more advanced gingivitis. Appears earlier than a change in color or other visual signs of inflammation. Is advantageous in that bleeding is a more objective sign that requires less subjective estimation by the examiner than color changes. Sep./12/2024 ABIER A. MOHAMMED 26 Gingival Bleeding on Probing Bleeding on probing. A, Mild edematous gingivitis; a probe has been introduced to the bottom of the gingival sulcus. B, Bleeding appears after a few seconds. Sep./12/2024 ABIER A. MOHAMMED 27  Colors Changes in the Gingiva The color of the gingiva is determined by several factors, including: the number and size of blood vessels. epithelial thickness, the quantity of keratinization. pigments within the epithelium. The normal gingival color is "coral pink," produced by the tissue's vascularity and modified by the overlying epithelial layers. Chronic inflammation: red/bluish-red color, vascular proliferation, and reduction of keratinization. It starts at the interdental papilla/gingival margin and spreads. Acute gingival inflammation: marginal, diffuse, or Patch-like. Sep./12/2024 ABIER A. MOHAMMED 28 Changes in Consistency of the Gingiva The gingiva is firm, resilient, and tightly bound to the underlying bone except for the movable free margin. Both chronic and acute inflammations produce changes in the normal firm and resilient consistency of the gingiva. As previously noted, in chronic gingivitis, both destructive (edematous) and reparative (fibrotic) changes coexist. Chronic gingivitis. Swelling, loss of stippling, and discoloration occur when inflammatory exudate and edema are the predominant microscopic changes. The gingiva is soft and friable, and it bleeds easily. Sep./12/2024 ABIER A. MOHAMMED 29  Chronic gingivitis. Firm gingiva is produced when fibrosis predominates in the inflammatory process. Sep./12/2024 ABIER A. MOHAMMED 30  Changes in Surface Texture of the Gingiva The surface of normal gingiva usually exhibits numerous small depressions and elevations, giving the tissue an orange-peel appearance referred to as Stippling. It is restricted to the attached gingiva and extends to the interdental papillae's central portion. Although the biological significance of gingival stippling is unknown, some investigators conclude that loss of stippling is an early sign of gingivitis. Sep./12/2024 ABIER A. MOHAMMED 31 Changes in Gingival Contour The marginal gingiva envelops the teeth in collar like fashion and follows a scalloped knife edge outline on the facial and lingual surfaces. Sep./12/2024 ABIER A. MOHAMMED 32 Different degrees of recession. Recession is slight in teeth #26 and #29 and marked in teeth #27 and #28. The change in gingival contour and the recession, as seen in tooth #28, are referred to as Stillman’s clefts. Sep./12/2024 ABIER A. MOHAMMED 33 Size of the Gingiva The size of the gingiva corresponds with the sum total of the bulk of cellular and intercellular elements and their vascular supply. Alteration in size is a common feature of gingival disease. Sep./12/2024 ABIER A. MOHAMMED 34  Gingivitis in children Dental Plaque Biofilm-Induced Gingivitis is extremely common among children and adolescents, affecting up to 70% of children over 7 years old. Inflammation is generally limited to the marginal gingiva, with undetectable connective tissue attachment or bone loss in most cases. Although gingivitis does not always progress to periodontitis, diagnosing and managing gingival disease in children and adolescents is essential because periodontitis is always preceded by gingivitis. In children and adults, the primary cause of gingivitis is dental plaque related to poor oral hygiene. Although gingivitis is highly prevalent in children, its severity is generally less intense than in adults. Similar oral hygiene conditions produce less severe forms of disease among children than adults. As children age, their tendency to develop gingivitis increases. The prevalence of the disease is lowest during the preschool years and increases throughout childhood, peaking during puberty. However, increases in gingival inflammation do not fully correlate with the amount of plaque, suggesting other factors influence it. Sep./12/2024 ABIER A. MOHAMMED 35 Clinical Features The most prevalent type of gingival disease in childhood is marginal gingivitis. Red, linear inflammation accompanies underlying chronic changes, including swelling, increased vascularization, and hyperplasia. Bleeding and increased pocket depth are not found as often in children as in adults, but they may be observed if severe gingival hypertrophy or hyperplasia occurs. Marginal gingivitis in children is characterized by a loss of collagen in the area around the JE and an infiltrate that consists primarily of lymphocytes, with small numbers of polymorphonuclear leukocytes, plasma cells, monocytes, and mast cells. Lesions generally have relatively few plasma cells, resembling the early nondestructive, nonprogressive lesions seen in adults. Furthermore, gingivitis in children differs from adult gingivitis in that the response is dominated by T lymphocytes, with few B lymphocytes and plasma cells in the infiltrate (which could explain why gingivitis in children rarely progresses to periodontitis). The JE of the primary dentition tends to be thicker than in the permanent dentition, which is thought to reduce the permeability of the gingival structures to bacterial toxins that initiate the inflammatory response Sep./12/2024 ABIER A. MOHAMMED 36 Eruption Gingivitis Gingivitis associated with tooth eruption is so common that the term eruption gingivitis has come into everyday use. Tooth eruption per se does not cause gingivitis. However, inflammation associated with plaque accumulation around erupting teeth, perhaps secondary to discomfort caused by brushing these friable areas, may contribute to gingivitis. The gingiva around erupting teeth may appear reddened because gingival margins have not yet keratinized fully, and sulcus development is incomplete. Microbes are believed to start colonizing the tooth surface and the newly formed JE immediately after the eruption. Events occurring during tooth formation and eruption could predispose to such colonization with specific bacteria and potentially contribute to the onset of gingivitis and/or periodontal diseases. Sep./12/2024 ABIER A. MOHAMMED 37  Exfoliating upper primary right central incisor and erupting upper left permanent central incisor showing inflamed gingiva in both areas. Copyright Dr. Daniela Silva. All rights reserved. Exfoliating and severely carious primary teeth often contribute to gingivitis caused by plaque accumulation due to pain during brushing or food impaction in areas of cavitation. The discomfort of chewing on severely infected teeth often leads to unilateral chewing on the unaffected side. Sep./12/2024 ABIER A. MOHAMMED 38 Reference : Newman, M. G., Klokkevold, P. R., Elangovan, S., & Kapila, Y. (2023). Newman and Carranza's Clinical Periodontolog y and Implantolog y (14th ed.). Elsevier - OHCE. 1. Chapter 15: Dental Biofilm-Induced Gingivitis and Its Management. Joseph P. Fiorellini, Dennis Sourvanos, David M. Kim, Yu-Cheng Chang, Marcelo Freire, Kevin W. Luan, and Hector L. Sarmiento. 2. Chapter 20: Periodontal Health and Disease in Children and Adolescents. Daniela Rodrigues P. Silva Karan, M.N.I.D.S.E. (2021). Newman and Carranza's Essentials of Clinical Periodontology E-Book. Elsevier - OHCE. Chapter 4: Periodontal Disease Pathogenesis Sep./12/2024 ABIER A. MOHAMMED 39