SECTION III: ETIOLOGY OF PERIODONTAL DISEASES
CHAPTER 5
Periodontal Pathogenesis
Philip M. Preshaw
CHAPTER OUTLINE
Histopathology of Periodontal Linking Pathogenesis to Clinical
Disease Signs of Disease
Inflammatory Responses in the Resolution of Inflammation
Periodontium
Understanding periodontal pathogenesis is key to improving man-
agement strategies for this common, complex disease. The first
challenge is to understand exactly what is meant by the term patho-
genesis. According to Merriam Webster ’s Collegiate Dictionary,
the word pathogenesis is defined as “the origination and develop-
ment of a disease.” Essentially, this refers to the step-by-step pro-
cesses that lead to the development of a disease and that result in
a series of changes in the structure and function of, in this case,
the periodontium. In broad terms, the pathogenesis of a disease
is the mechanism by which a causative factor or factors causes
the disease. The word itself is derived from the Greek roots
pathos (meaning “suffering”) and genesis (meaning “generation or
creation”).
Our knowledge of periodontal pathogenesis has evolved over
the years. It is important to be aware of this, because treatment
philosophies have similarly changed in parallel with our improving
understanding of the disease processes. For example, during the
late 1800s, Willoughby D. Miller (an eminent dental researcher
who established the important causal role of oral bacteria for dental
caries) asserted that “during the last few years the conviction has
grown continually stronger, among physicians as well as dentists,
that the human mouth, as a gathering-place and incubator of diverse
pathogenic germs, performs a significant role in the production of
varied disorders of the body, and that if many diseases whose origin
is enveloped in mystery could be traced to their source, they would
be found to have originated in the oral cavity.”116 This marked the
beginning of an era of dental treatment strategies that aimed to treat
systemic diseases by eliminating the so-called “foci of infection”
in the mouth. As a result, many patients underwent unnecessary
dental clearances to manage their systemic diseases.
By the 1930s, such approaches were beginning to be questioned
as evidenced by a clinical study of 200 patients with rheumatoid
arthritis of whom 92 had their tonsils removed as treatment for the
arthritis (even though only about 15% gave any history of tonsillitis
or sore throat) and of whom 52 had some or all of their teeth
removed.28 Of the 92 who had their tonsils removed, there was no
impact on the arthritis in 86 patients (although 2 got worse); of the
52 who had teeth removed, there was no benefit in 47 cases (and
3 reported a worsening of their arthritis after the extractions). The
authors wrote that “focal infection is a splendid example of a
plausible medical theory which is in danger of being converted by
76
Immune Responses in Periodontal
Pathogenesis
Concept of Host Susceptibility
its too enthusiastic supporters into the status of an accepted fact.”28
The end of the focal infection era was signaled by an editorial in
the Journal of the American Medical Association in 1952, which
stated that “many patients with diseases presumably caused by foci
of infection have not been relieved of their symptoms by removal
of the foci, many patients with these same systemic diseases have
no evident focus of infection, foci of infection are as common in
apparently healthy persons as in those with disease.”165
Advances in the management of periodontitis have been driven
by improved knowledge of the epidemiology, causation, and patho-
genesis of the disease.195 During the 1970s, the role of plaque as
the sole causative factor for periodontitis was unquestioned. In
those days, nonsurgical treatment was in its infancy, and most
treatment options involved surgery (e.g., gingivectomy for the
treatment of shallower pockets, access flap surgery for the treat-
ment of deeper sites). When looking back, it becomes clear that
the treatment strategies used during a given time period are entirely
dependent on the prevailing understanding of pathogenesis at
that particular point in time. It is therefore very likely that the
management options that we take for granted now will change
again in the future. This is to be welcomed, because a progressive
clinical discipline such as periodontology that is well founded
in science and with patient benefit as its primary value should
strive to improve therapeutic strategies in the light of continued
discovery.
Periodontal disease results from a complex interplay between
the subgingival biofilm and the host immune–inflammatory events
that develop in the gingival and periodontal tissues in response to
the challenge presented by the bacteria. It is generally accepted that
gingivitis precedes periodontitis, but it is clear that not all cases of
gingivitis progress to periodontitis. With gingivitis, the inflamma-
tory lesion is confined to the gingiva; however, with periodontitis,
the inflammatory processes extend to additionally affect the peri-
odontal ligament and the alveolar bone. The net result of these
inflammatory changes is the breakdown of the fibers of the peri-
odontal ligament, resulting in clinical loss of attachment together
with resorption of the alveolar bone.
During the 1970s and 1980s, bacterial plaque was generally
considered to be preeminent as the cause of periodontitis. At that
time, it was accepted that poor oral hygiene resulted in increased
plaque accumulation, which in turn resulted in periodontal disease.
 CHAPTER 5 Periodontal Pathogenesis 77

However, this model failed to take into account observations such and causing tissue damage. Our current understanding of suscep-
as the fact that there are many individuals with poor oral hygiene tibility to periodontitis suggests that individuals who are more
who do not develop advanced periodontal disease and, conversely, susceptible to the disease mount an excessive or dysregulated
that there are unfortunate individuals who, despite good oral immune–inflammatory response for a given bacterial challenge,
hygiene and compliance with periodontal treatment protocols, con- which leads to increased tissue breakdown as compared with those
tinue to experience progressive periodontal breakdown and who individuals who have a more normal inflammatory response.
would be considered to have aggressive periodontitis. These find-
ings were confirmed by the work of Löe and colleagues, who Clinically Healthy Gingival Tissues
studied Sri Lankan tea laborers who had no access to dental care Clinically healthy gingival tissues (e.g., those observed in patients
and who could be divided into three main categories: (1) individu- with excellent oral hygiene and no visible plaque deposits who
als (≈8% of the population studied) who had a rapid progression typically have received regular and meticulous professional clean-
of periodontal disease; (2) those (≈81%) who had a moderate pro- ing) are pink in appearance, not swollen, not inflamed, and firmly
gression of such disease; and (3) those (≈11%) who demonstrated attached to the underlying tooth and bone, with minimal bleeding
no progression of periodontal disease beyond gingivitis.107 All on probing. The dentogingival junction is a unique anatomic
patients in this population displayed abundant plaque and calculus feature that functions to attach the gingiva to the tooth. It comprises
deposits. The causative role of plaque bacteria is clear in that the an epithelial portion and a connective tissue portion, both of which
bacteria initiate and perpetuate the inflammatory responses that are of fundamental importance for periodontal pathogenesis. The
develop in the gingival tissues. However, the major determinant of epithelial portion can be divided into three distinct epithelial struc-
susceptibility to disease is the nature of the immune–inflammatory tures: the gingival epithelium, the sulcular epithelium, and the
responses themselves. It is paradoxical that these defensive pro- junctional epithelium (Figure 5-1). These epithelial structures are
cesses, which are protective by intent (i.e., to prevent the ingress in continuity with each other, but they have distinct structures and
of the bacteria and their products into the tissues), result in the functions as indicated in Box 5-1.
majority of tissue damage that leads to the clinical manifestations The junctional epithelium is a particularly unique epithelial
of disease. structure, because the surface cells are specialized for the purpose
Periodontal disease is therefore a unique clinical entity. It is of attachment to the tooth.11 Therefore, unlike other epithelial
not an infection in the classic sense of the word. With most infec- tissues elsewhere in the body, there is no opportunity for the
tions, a single infective organism causes the disease (e.g., human sloughing of cells from the surface. Instead, cells at the basal layer
immunodeficiency virus/acquired immunodeficiency syndrome,
syphilis, tuberculosis), and the identification of that organism pro-
vides the basis for the diagnosis. With periodontal disease, a large
number of species are identifiable in the periodontal pocket, and
many more are as yet unknown because they have not been cul-
tured. It is impossible to conclude that a single species or even a
group of species causes periodontal disease. Many of the species
that are considered important in periodontal pathogenesis may
simply reside in deep pockets because the pocket is a favorable
environment in which they can survive (i.e., it is warm, moist, and
anaerobic, with a ready supply of nutrients). Many of the unique
features of periodontitis are derived from the anatomy of the peri-
odontium, in which a hard, nonshedding surface (the tooth) is
partly embedded within the body (within connective tissue),
crosses an epithelial surface, and is partly exposed to the outside
world (within the confines of the mouth). The bacteria that colo-
nize this surface are effectively outside of the body (although they
are in the subgingival crevice), yet the inflammatory response that
develops is located within the body. These factors add complexity
to our understanding of the role of the biofilm and the immune–
inflammatory responses that are part of periodontal tissue
breakdown.

Histopathology of Periodontal Disease

To better understand periodontal pathogenesis, it is important to
have an appreciation of the histologic appearance of clinically
healthy tissues as well as of inflamed gingival and periodontal
tissues. It is important to note that, even in gingival tissues that
clinically would be considered to be noninflamed and healthy, there
is always evidence of inflammatory responses occurring if they are
examined microscopically. This is normal given that there is a
chronic low-grade challenge presented by the subgingival plaque
bacteria. The low-grade inflammatory response that results is not
detectable macroscopically at the clinical level, but it is an essential
protective mechanism for combating the microbial challenge and
for preventing bacteria and their products from infiltrating tissues
Figure 5-1 Histologic appearance of healthy gingiva. A photomi-
crograph of a demineralized tooth with the gingival tissues in situ
(hematoxylin and eosin staining, low magnification). Ameloce-
mental junction (A). Enamel space (ES). Gingival health is charac-
terized by the organization of the epithelium into distinct zones;
junctional epithelium (A and B), sulcular epithelium (B and C), free
gingiva (C and D), and attached gingiva (D and E). The gingival
connective tissue is composed of densely packed, organized, and
interlacing collagen bundles. There are a few scattered inflamma-
tory cells but no significant inflammatory cell infiltrate.