CHAPTER  14 

Gingival Inflammation
Joseph P. Fiorellini, David M. Kim, and Panagiota G. Stathopoulou

CHAPTER OUTLINE
Stage I Gingival Inflammation: The Initial Lesion
Stage II Gingival Inflammation: The Early Lesion
Stage III Gingival Inflammation: The Established Lesion
Stage IV Gingival Inflammation: The Advanced Lesion

The pathologic changes of gingivitis are associated with the pres-

ence of oral microorganisms attached to the tooth and perhaps in Stage I Gingival Inflammation:
or near the gingival sulcus. The Initial Lesion
These organisms are capable of synthesizing products (e.g., The first manifestations of gingival inflammation are vascular
collagenase, hyaluronidase, protease, chondroitin sulfatase, endo- changes that consist of dilated capillaries and increased blood flow.
toxin) that cause damage to epithelial and connective tissue cells These initial inflammatory changes occur in response to the micro-
as well as to intercellular constituents such as collagen, ground bial activation of resident leukocytes and the subsequent stimula-
substance, and glycocalyx (cell coat). The resultant widening tion of endothelial cells. Clinically, this initial response of the
of the spaces between the junctional epithelial cells during early gingiva to bacterial plaque (i.e., subclinical gingivitis26) is not
gingivitis may permit injurious agents derived from bacteria or apparent.
bacteria themselves to gain access to the connective tissue.10,44,48
Microbial products activate monocytes and macrophages to
Microscopically, some classic features of acute inflammation can be
produce vasoactive substances such as prostaglandin E2, inter-
seen in the connective tissue beneath the junctional epithelium.
feron, tumor necrosis factor, and interleukin-1.25,38 In addition,
Changes in blood vessel morphologic features (e.g., the widening of
interleukin-1β alters the properties of gingival fibroblasts by delay-
small capillaries or venules) and the adherence of neutrophils to
ing their death via mechanism-blocking apoptosis. This stabilizes
vessel walls (margination) occur within 1 week and sometimes as
the gingival fibroblast population during inflammation.54
early as 2 days after plaque has been allowed to accumulate18,41
Morphologic and functional changes in the gingiva during
(Figure 14-1). Leukocytes—mainly polymorphonuclear neutrophils
plaque accumulation have been thoroughly investigated, especially
(PMNs)—leave the capillaries by migrating through the walls via
in beagle dogs and humans.36 A useful framework for the organiza-
diapedesis and emigration25,50,51 (Figure 14-2). They can be seen in
tion and consideration of these data has been devised on the basis
increased quantities in the connective tissue, the junctional epithe-
of histopathologic, radiographic, and ultrastructural features and
lium, and the gingival sulcus2,3,24,34,41,45,46 (Figures 14-3 and 14-4). The
biochemical measurements.37,39 The sequence of events that culmi-
exudation of fluid from the gingival sulcus18 and extravascular pro-
nates in clinically apparent gingivitis is categorized as the initial,
teins are present.20,21
early, and established stages of disease, with periodontitis desig-
nated as the advanced stage38 (Table 14-1). One stage evolves into
the next, with no clear-cut dividing lines. However, these findings are not accompanied by manifestations
Despite extensive research, we still cannot distinguish defini- of tissue damage that are perceptible at the light microscopic or
tively between normal gingival tissue and the initial stage of gin- ultrastructural level; they do not form an infiltrate, and their pres-
givitis.36 Most biopsies of clinically normal human gingiva contain ence is not considered to indicate pathologic change.36
inflammatory cells; these consist predominantly of T cells, with Subtle changes can also be detected in the junctional epithelium
very few B cells or plasma cells.36,49,50 These cells do not create and the perivascular connective tissue at this early stage. For
tissue damage, but they appear to be important in the day-to-day example, the perivascular connective tissue matrix becomes
host response to bacteria and other substances to which the gingiva altered, and there is exudation and deposition of fibrin in the
is exposed.36 Therefore, under normal conditions, a constant stream affected area.36 In addition, lymphocytes soon begin to accumulate
of neutrophils is migrating from the vessels of the gingival plexus (see Figure 14-2, D). The increase in the migration of leukocytes
through the junctional epithelium, to the gingival margin, and into and their accumulation within the gingival sulcus may be corre-
the gingival sulcus and the oral cavity.43 lated with an increase in the flow of gingival fluid into the sulcus.4

219
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220 PART 1  Biologic Basis of Periodontology

TABLE 14-1  Stages of Gingivitis

Time Junctional and Predominant
Stage (Days) Blood Vessels Sulcular Epithelia Immune Cells Collagen Clinical Findings
I. Initial lesion 2 to 4 Vascular dilation Infiltration by PMNs PMNs Perivascular loss Gingival fluid flow
Vasculitis
II. Early lesion 4 to 7 Vascular proliferation Same as stage I Lymphocytes Increased loss Erythema
Rete pegs around infiltrate Bleeding on probing
Atrophic areas
III. Established 14 to 21 Same as stage II, Same as stage II but Plasma cells Continued loss Changes in color, size,
lesion plus blood stasis more advanced texture, and so on

PMNs, Polymorphonuclear leukocytes (neutrophils).

Microscopic examination of the gingiva reveals leukocyte infiltration

in the connective tissue beneath the junctional epithelium, which
consists mainly of lymphocytes (75%, with the majority being T
OSE JE cells)41,47 but that also includes some migrating neutrophils as well
as macrophages, plasma cells, and mast cells. All of the changes
seen in the initial lesion continue to intensify with the early
lesion.15,28,30,35,47 The junctional epithelium becomes densely infil-
trated with neutrophils, as does the gingival sulcus, and the junc-
PMN tional epithelium may begin to show the development of rete pegs
or ridges.

The amount of collagen destruction also increases12,28,47; 70%

of the collagen is destroyed around the cellular infiltrate. The main
fiber groups that are affected appear to be the circular and dento-
gingival fiber assemblies. Alterations in blood vessel morphologic
features and vascular bed patterns have also been described.18,19
PMNs that have left the blood vessels in response to chemotac-
tic stimuli from plaque components travel to the epithelium and
cross the basement lamina; they are found in the epithelium,
Figure 14-1  Human biopsy sample, experimental gingivitis. After emerging in the pocket area (see Figure 14-3). PMNs are attracted
4 days of plaque accumulation, the blood vessels immediately
to bacteria and engulf them during the process of phagocytosis
adjacent to the junctional epithelium are distended and contain
polymorphonuclear leukocytes (neutrophils) (PMNs). Neutrophils (Figure 14-6). PMNs release their lysosomes in association with
have also migrated between the cells of the junctional epithelium the ingestion of bacteria.23 Fibroblasts show cytotoxic alterations,40
(JE). OSE, Oral sulcular epithelium. (×500.) (From Payne WA, Page with a decreased capacity for collagen.
RC, Ogilvie AL, et al: J Periodontal Res 10:51, 1975.) Meanwhile, on the opposite side of molecular events, collagen
degradation is related to matrix metalloproteinases (MMPs). Dif-
ferent MMPs are responsible for extracellular matrix remodeling
The character and intensity of the host response determine within 7 days of inflammation, which is directly related to MMP-2
whether this initial lesion resolves rapidly, with the restoration of and MMP-9 production and activation.54
the tissue to a normal state; alternatively, it may evolve into a
chronic inflammatory lesion. If the latter occurs, an infiltrate of Stage III Gingival Inflammation:
macrophages and lymphoid cells appears within a few days. The Established Lesion
Over time, the established lesion evolves. It is characterized by a
Stage II Gingival Inflammation: predominance of plasma cells and B lymphocytes, and it is prob-
The Early Lesion ably in conjunction with the creation of a small gingival pocket
The early lesion evolves from the initial lesion within about 1 week lined with a pocket epithelium.46 The B cells that are found in the
after the beginning of plaque accumulation.35,41 Clinically, the early established lesion are predominantly of the immunoglobulin G1
lesion may appear as early gingivitis, and it overlaps with and and G3 subclasses.36
evolves from the initial lesion with no clear-cut dividing line. As With chronic gingivitis, which occurs 2 to 3 weeks after the
time goes on, clinical signs of erythema may appear, mainly beginning of plaque accumulation, the blood vessels become
because of the proliferation of capillaries and the increased forma- engorged and congested, venous return is impaired, and the blood
tion of capillary loops between rete pegs or ridges (Figure 14-5). flow becomes sluggish (Figure 14-7). The result is localized gin-
Bleeding on probing may also be evident.1 Gingival fluid flow and gival anoxemia, which superimposes a somewhat bluish hue on the
the numbers of transmigrating leukocytes reach their maximum reddened gingiva.17 The extravasation of erythrocytes into the con-
between 6 and 12 days after the onset of clinical gingivitis.26 nective tissue and the breakdown of hemoglobin into its component

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 CHAPTER 14  Gingival Inflammation 221

JE

Figure 14-2  Human biopsy, experimental gingivitis. V

A, Control biopsy specimen from a patient with good
oral hygiene and no detectable plaque accumulation.
The junctional epithelium is on the left. The connec-
CT
tive tissue (CT) shows few cells other than fibroblasts,
blood vessels, and a dense background of collagen
fibers. (×500.) B, Biopsy specimen taken after 8 days
of plaque accumulation. The connective tissue is infil-
trated with inflammatory cells, which displace the col-
lagen fibers. A distended blood vessel (V) is seen in
the center. (×500.) C, After 8 days of plaque accumu-
lation, the connective tissue next to the junctional epi- A B
thelium at the base of the sulcus shows a mononuclear
cell infiltrate and evidence of collagen degeneration JE
(i.e., clear spaces around the cellular infiltrate). (×500.)
D, The inflammatory cell infiltrate at higher magnifi-
cation (×1250). After 8 days of plaque accumulation,
numerous small (SL) and medium-sized (ML) lympho- SL
cytes are seen within the connective tissue. Most of
the collagen fibers around these cells have disap-
peared, presumably as a result of enzymatic digestion.
(From Payne WA, Page RC, Ogilvie AL, et al: J Periodontal
Res 10:51, 1975.) ML

C D

pigments can also deepen the color of the chronically inflamed

gingiva. The established lesion can be described as moderately to rete pegs or ridges that protrude into the connective tissue, and the
severely inflamed gingiva. basal lamina is destroyed in some areas. In the connective tissue,
collagen fibers are destroyed around the infiltrate of intact and
disrupted plasma cells, neutrophils, lymphocytes, monocytes, and
mast cells (Figure 14-9).
In histologic sections, an intense and chronic inflammatory reaction
is observed. Several detailed cytologic studies have been performed
on chronically inflamed gingiva.13-15,40,46,49,53 A key feature that dif-
ferentiates the established lesion is the increased number of plasma
cells, which become the preponderant inflammatory cell type. The predominance of plasma cells is thought to be a primary
Plasma cells invade the connective tissue not only immediately characteristic of the established lesion. However, several studies of
below the junctional epithelium but also deep into the connective human experimental gingivitis have failed to demonstrate plasma
tissue, around the blood vessels, and between the bundles of col- cell predominance in the affected connective tissues,7,8,49 including
lagen fibers.6 The junctional epithelium reveals widened intercel- one study of 6 months’ duration.1 Increases in the proportions of
lular spaces that are filled with granular cellular debris, including plasma cells were evident with longstanding gingivitis, but the time
lysosomes derived from disrupted neutrophils, lymphocytes, and for the development of the classic “established lesion” may exceed
monocytes (Figure 14-8). The lysosomes contain acid hydrolases that 6 months.
can destroy tissue components. The junctional epithelium develops An inverse relationship appears to exist between the number of
intact collagen bundles and the number of inflammatory cells.51

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222 PART 1  Biologic Basis of Periodontology

EC L

EC

Figure 14-6  Scanning electron micrograph of a leukocyte emerg-

Figure 14-3  Scanning electron micrograph showing a leukocyte
traversing the vessel wall to enter into the gingival connective ing to the pocket wall and covered with bacteria and extracellular
tissue. lysosomes. B, Bacteria; EC, epithelial cells; L, lysosomes.

Figure 14-7  Marginal supragingival plaque and gingivitis.

Figure 14-4  Early human gingivitis lesion. There is an area of

lamina propria subjacent to the crevicular epithelium that shows a
capillary with several extravascular lymphocytes and one lympho-
cyte within the lumen. The specimen also exhibits a considerable
loss of perivascular collagen density. (×2500.) (Courtesy Dr. Charles
Cobb, Kansas City, MO.)

Figure 14-8  Established gingivitis in a human subject. An area of

crevicular epithelium exhibits enlarged intercellular spaces with
numerous microvilli and desmosomal junctions. Several lympho-
cytes, both small and large, are seen migrating through the epithe-
Figure 14-5  Marginal gingivitis and irregular gingival contour. lial layer. (×3000.)

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 CHAPTER 14  Gingival Inflammation 223

Stage IV Gingival Inflammation:

The Advanced Lesion
The extension of the lesion into alveolar bone characterizes the
fourth stage, which is known as the advanced lesion40 or phase of
periodontal breakdown.26 This is described in detail in Chapters
21 and 23.

Microscopically, fibrosis of the gingiva is present, and there are

widespread manifestations of inflammatory and immunopathologic
tissue damage.36 At the advanced stage, the presence of plasma
cells dominates the connective tissue, and neutrophils continue
dominating the junctional epithelium.

Patients with experimental gingivitis had significantly more

plaque accumulation, higher interleukin-1β levels, and lower
interleukin-8 concentrations at 28 days.11
Gingivitis will progress to periodontitis only in individuals who
are susceptible. Patients who had sites with consistent bleeding
Figure 14-9  Advanced gingivitis in a human subject. This speci- (gingival index = 2) had 70% more attachment loss as compared
men from the lamina propria exhibits plasma cell degeneration,
with sites that were not inflamed consistently (gingival index = 0).
with abundant cellular debris visible. (×3000.) (Courtesy Dr. Charles
Cobb, Kansas City, MO.)
Teeth with noninflamed sites consistently had a 50-year survival
rate of 99.5%, whereas teeth with consistently inflamed gingiva
had a 63.4% survival rate over 50 years. On the basis of this lon-
gitudinal study of the natural history of periodontitis in a well-
maintained male population, persistent gingivitis represents a risk
factor for periodontal attachment loss and for tooth loss.22 However,
whether periodontitis can occur without a precursor of gingivitis is
Collagenolytic activity is increased in inflamed gingival tissue16 by not known at this time.
the enzyme collagenase. Collagenase is normally present in gingi-
val tissues5; it is produced by some oral bacteria and by PMNs. Suggested Readings
Enzyme histochemistry studies have shown that chronically Deinzer R, Weik U, Kolb-Bachofen V, et al: Comparison of experimental
inflamed gingivae have elevated levels of acid and alkaline gingivitis with persistent gingivitis: differences in clinical parameters
phosphatase,55 β-glucuronidase, β-glucosidase, β-galactosidase, and cytokine concentrations. J Periodontal Res 2(4):318–324, 2007.
esterases,29 aminopeptidase,33,42 and cytochrome oxidase.9 Neutral Lang NP, Schätzle MA, Löe H: Gingivitis as a risk factor in periodontal
mucopolysaccharide levels are decreased,53 presumably as a result disease. J Clin Periodontol 36(Suppl 10):3–8, 2009.
Listgarten MA, Hellden L: Relative distribution of bacteria at clinically
of degradation of the ground substance.
healthy and periodontal diseased sites in humans. J Clin Periodontol
Established lesions of two types appear to exist; some remain 5:115, 1978.
stable and do not progress for months or years,32,33,52 and others Lorencini M, Silva JA, de la Hoz CL, et al: Changes in MMPs and inflam-
seem to become more active and to convert to progressively matory cells in experimental gingivitis. Histol Histopathol 24(2):157–
destructive lesions. In addition, the established lesions appear to 166, 2009.
be reversible in that the sequence of events that occurs in the tissues Page RC, Schroeder HE: Pathogenesis of inflammatory periodontal disease:
as a result of successful periodontal therapy seems to be essentially a summary of current work. Lab Invest 34:235, 1976.
the reverse of the sequence of events observed as gingivitis devel-
ops. As the flora reverts from that characteristically associated with
destructive lesions to that associated with periodontal health, the References
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population increases proportionately.27,31 website www.expertconsult.com.

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 CHAPTER 14  Gingival Inflammation 223.e1

26. Lindhe J, Hamp SE, Löe H: Experimental periodontitis in the beagle

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