excisional biopsy.

Foreign-Body Reactions
Foreign-body reactions lead to localized inflammatory conditions of
the gingiva and are caused by the introduction of foreign material
into the gingival connective tissues through breaks in the
epithelium.20 Common examples are the introduction of amalgam
into the gingiva during the placement of a restoration, the
extraction of a tooth, or an endodontic apicoectomy with retrofill
leaving an amalgam tattoo (Fig. 5.14A), with resultant metal
fragments observed during biopsies (Fig. 5.14B); abrasives may also
be introduced during polishing procedures.

FIG. 5.14 (A) Gingival pigmentation associated with

previous apicoectomy and amalgam retro-fill. (B)
Biopsy depicts metal fragments.

Periodontitis
Periodontitis is defined as “an inflammatory disease of the
supporting tissues of the teeth caused by specific microorganisms
or groups of specific microorganisms, resulting in progressive
destruction of the periodontal ligament and alveolar bone with
increased probing depth formation, recession, or both.”51 The
clinical feature that distinguishes periodontitis from gingivitis is the
presence of clinically detectable attachment loss as a result of

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inflammatory destruction of the periodontal ligament and alveolar
bone. This loss is often accompanied by periodontal pocket
formation and changes in the density and height of the subjacent
alveolar bone. In some cases, recession of the marginal gingiva may
accompany attachment loss, thereby masking ongoing disease
progression if only probing depth measurements are taken without
measurements of clinical attachment levels.

Key Fact
Probing depth measurement alone is inadequate for an assessment
of periodontitis. Clinical attachment loss is usually assessed by
adding the extent of gingival recession to the probing depth
measurement to estimate the total extent of tissue loss from the
cementoenamel junction (CEJ) of the tooth. However, when
recession is not visible, it is essential that height of the marginal
gingiva coronal to the CEJ be determined and that measurement
subtracted from the probing depth to establish the extent of clinical
attachment loss. The measurement of clinical attachment around a
tooth provides insights on the history and extent of periodontal
destruction around the tooth. One common pitfall of clinical
periodontal examination is the direct translation of probing depths
as clinical attachment levels when the gingival margin lies above
the cementoenamel junction, leading to an overestimation of
attachment levels.

Clinical signs of inflammation—such as changes in color,

contour, and consistency as well as bleeding with probing—may
not always be positive indicators of ongoing attachment loss.
However, the presence of continued bleeding with probing during
sequential visits has proved to be a reliable indicator of the
presence of inflammation and an increased risk for subsequent
attachment loss at the bleeding site. The attachment loss associated
with periodontitis may occur in a cyclic fashion, with attachment
loss progressing either continuously or in episodic bursts of disease
activity. However, the available clinical instruments for detecting
disease are not sensitive enough to capture the cycles of attachment
loss and repair that occur during disease activity and remission,

347
respectively (i.e., the periodontal probe is graded in 1-mm
increments).

Key Fact
In the AAP/EFP 2018 classification of periodontal diseases, a
multidimensional staging and grading system will be introduced
to subclassify periodontitis disease entities. The severity of
periodontal disease at the time of presentation and the complexity
of disease management will dictate the staging, while grading
offers additional information, including the rate of past
progression of the disease and the risk for future progression.

Although many classifications of the different clinical

manifestations of periodontitis have been presented since the late
1990s, consensus workshops in North America in 19898 and in
Europe in 19936 identified that periodontitis may present in early-
onset, adult-onset, and necrotizing forms (Table 5.1). In addition,
the AAP consensus concluded that periodontitis may be associated
with systemic conditions (e.g., diabetes, HIV) and that some forms
of periodontitis may be refractory to conventional therapy. Early-
onset disease was distinguished from adult-onset disease by the age
of onset (< 35 years of age was set as an arbitrary separation of
diseases), the rate of disease progression, and the presence of
alterations in host defenses. The early-onset diseases were more
aggressive, occurred in individuals younger than 35 years old, and
were associated with defects in host defenses. Adult forms of
disease were slowly progressive, became clinically more evident
during the fourth decade of life, and were not associated with
defects in host defenses. In addition, early-onset periodontitis was
subclassified into prepubertal, juvenile, and rapidly progressive
forms with localized or generalized disease distributions.

TABLE 5.1
Classification of the Various Forms of Periodontitis

Classification Forms of Periodontitis Disease Characteristics

AAP World Workshop in Adult periodontitis Age of onset >35 years

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 Clinical Periodontics, 19895 Slow rate of disease
progression
No defects in host defenses

Early-onset periodontitis Age of onset <35 years

(may be prepubertal, Rapid rate of disease
juvenile, or rapidly progression
progressive) Defects in host defenses
Associated with specific
microflora
Periodontitis associated with Systemic diseases that predispose
systemic disease to rapid rates of periodontitis
Diseases: diabetes, Down
syndrome, HIV infection,
Papillon–Lefèvre syndrome
Necrotizing ulcerative Similar to acute necrotizing
periodontitis ulcerative gingivitis but with
associated clinical attachment loss
Refractory periodontitis Recurrent periodontitis that does
not respond to treatment
European Workshop in Adult periodontitis Age of onset: fourth decade of life
Periodontology, 19933 Slow rate of disease progression
No defects in host response
Early-onset periodontitis Age of onset: before fourth decade
of life
Rapid rate of disease progression
Defects in host defense
Necrotizing periodontitis Tissue necrosis with attachment
and bone loss
AAP International Chronic periodontitis See Box 5.3
Workshop for Classification Aggressive periodontitis
of Periodontal Diseases, Periodontitis as a
19992 manifestation of systemic
diseases
AAP, American Academy of Periodontology; HIV, human immunodeficiency virus.

Extensive clinical and basic scientific research involving these

disease entities has been performed in many countries, and
emerging information has provided support for the unification of
many of the preexisting disease categories.13,23,49 In particular,
supporting evidence was lacking for the distinct classifications of
adult periodontitis, refractory periodontitis, and the various
different forms of early-onset periodontitis as outlined by the AAP
Workshop for the International Classification of Periodontal
Diseases in 19995 (see Table 5.1). It has been observed that chronic
periodontal destruction caused by the accumulation of local factors
(e.g., plaque, calculus) can occur before the age of 35 years and that
the aggressive disease seen in young patients may be independent
of age and instead have a familial (genetic) association. With

349
respect to refractory periodontitis, little evidence supports the
theory that this condition is indeed a distinct clinical entity. The
causes of continued loss of clinical attachment and alveolar bone
after periodontal therapy are currently poorly defined and apply to
many disease entities. In addition, clinical data from the medical
community emerged to support the belief that forms of
periodontitis that were collectively referred to as prepubertal
periodontitis were in fact representing periodontitis as a
manifestation of distinct systemic diseases, such as in leukocyte
adhesion deficiency syndromes. As a result, the AAP held an
International Workshop for the Classification of Periodontal
Diseases in 1999 to further refine the classification system with the
use of current clinical and scientific data.5 The resulting
classification of the different forms of periodontitis was simplified
to describe three general disease forms: chronic periodontitis,
aggressive periodontitis, and periodontitis as a manifestation of
systemic disease (Table 5.1 and Box 5.3).

Box 5.3
Periodontitis
The disease periodontitis can be subclassified into the following
three major types based on clinical, radiographic, historical, and
laboratory characteristics.
Chronic Periodontitis
The following characteristics are common to patients with chronic
periodontitis:

• Prevalent in adults but can occur in children

• Amount of destruction consistent with local factors
• Associated with a variable microbial pattern
• Subgingival calculus frequently found
• Slow-to-moderate rate of progression with possible periods of
rapid progression
• Possibly modified by or associated with the following:

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 • Systemic diseases such as diabetes mellitus and
human immunodeficiency virus (HIV) infection
• Local factors predisposing to periodontitis
• Environmental factors such as cigarette smoking and
emotional stress

Chronic periodontitis may be further subclassified into localized

and generalized forms and characterized as mild, moderate, or
severe based on the common features described previously and the
following specific features:

• Localized form: <30% of teeth involved

• Generalized form: >30% of teeth involved
• Mild: 1 to 2 mm clinical attachment loss (CAL)
• Moderate: 3 to 4 mm CAL
• Severe: ≥5 mm CAL

Aggressive Periodontitis
The following characteristics are common to patients with
aggressive periodontitis:

• Otherwise clinically healthy patient (note the distinction with

periodontitis as a manifestation of systemic disease)
• Rapid attachment loss and bone destruction
• Familial aggregation of diseased individuals

The following characteristics are common but not universal:

• Amount of microbial deposits inconsistent with disease

severity
• Increased levels of Actinobacillus actinomycetemcomitans
• Abnormalities in phagocyte function
• Hyper-responsive macrophages, producing increased
prostaglandin E2 (PGE2) and interleukin-1β (IL-1β)
• In some cases, self-arresting disease progression

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 Aggressive periodontitis may be further classified into localized
and generalized forms based on the common features described
here and the following specific features.
Localized Form

• Circumpubertal onset of disease

• Localized first molar or incisor disease with proximal
attachment loss on at least two permanent teeth, one of which
is a first molar
• Robust serum antibody response to infecting agents

Generalized Form

• Usually affecting persons under 30 years of age (however, may

be older)
• Generalized proximal attachment loss affecting at least three
teeth other than first molars and incisors
• Pronounced episodic nature of periodontal destruction
• Poor serum antibody response to infecting agents

Periodontitis as a Manifestation of Systemic Diseases

Periodontitis may be observed as a manifestation of the following
systemic diseases:

1. Hematologic disorders
a. Acquired neutropenia
b. Leukemias
c. Other
2. Genetic disorders
a. Familial and cyclic neutropenia
b. Down syndrome
c. Leukocyte adhesion deficiency syndromes
d. Papillon–Lefèvre syndrome
e. Chédiak–Higashi syndrome
f. Histiocytosis syndromes
g. Glycogen storage disease

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 h. Infantile genetic agranulocytosis
i. Cohen syndrome
j. Ehlers-Danlos syndrome (types IV and VIII autosomal
dominant [AD])
k. Hypophosphatasia
l. Other
3. Not otherwise specified

Data from Flemmig TF: Periodontitis. Ann Periodontol 4:32, 1999; Kinane DF: Periodontitis
modified by systemic factors. Ann Periodontol 4:54, 1999; and Tonetti MS, Mombelli A:
Early-onset periodontitis. Ann Periodontol 4:39, 1999.

Since the establishment of the currently accepted 1999

classification, a taskforce commissioned by the AAP proposed an
update to the existing classification scheme in 2015.3 The update
focused on suggestions to address the challenges in clinical
documentation of attachment level changes and the distinction
between chronic and aggressive periodontitis. In particular, the
AAP task force recommended the consideration of probing depth
levels, in addition to attachment levels, in determining the severity
of periodontitis to avoid overestimation. The classification of
diseases and conditions of the periodontium discussed in this
chapter will focus on the currently accepted 1999 classification with
references to the AAP update when appropriate.

Chronic Periodontitis
Chronic periodontitis is the most common form of periodontitis13;
Box 5.3 includes the characteristics of this form of periodontitis.
Chronic periodontitis is most prevalent in adults, but it can also be
observed in children. Different classification schemes have
confirmed or discarded the age range of more than 35 years to
separate chronic versus aggressive periodontitis. According to the
existing definition, persons younger than 35 years may exhibit a
rate of progression of disease consistent with the definition of
chronic periodontitis. Nonetheless, epidemiologic evidence
supports the suggestion that persons younger than 25 years at
disease onset are likely to exhibit aggressive periodontitis. Intraoral
radiographs along with periodontal charting records are of

353
paramount importance to the documentation of disease onset and
rate of progression.
Chronic periodontitis is associated with the accumulation of
plaque and calculus. It generally has a slow to moderate rate of
disease progression, but periods of more rapid destruction may also
be observed. Increases in the rate of disease progression may be
caused by the impact of local, systemic, or environmental factors
that may influence the normal host–bacteria interaction. Local
factors may influence plaque accumulation (Box 5.4), whereas
systemic diseases (e.g., diabetes mellitus, HIV) may influence the
host's defenses, and environmental factors (e.g., cigarette smoking,
stress) may influence the response of the host to plaque
accumulation. Chronic periodontitis may occur as a localized
disease in which less than 30% of evaluated teeth demonstrate
attachment and bone loss, or it may occur as generalized when
more than 30% of teeth are affected.

Box 5.4
Developmental or Acquired Deformities and
Conditions
Localized Tooth-Related Factors That Modify or
Predispose to Plaque-Induced Gingival Diseases or
Periodontitis

1. Tooth anatomic factors

2. Dental restorations or appliances
3. Root fractures
4. Cervical root resorption and cemental tears

Mucogingival Deformities and Conditions Around Teeth

1. Gingival or soft tissue recession

a. Facial or lingual surfaces
b. Interproximal (papillary)
2. Lack of keratinized gingiva

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 3. Decreased vestibular depth
4. Aberrant frenum or muscle position
5. Gingival excess
a. Pseudopocket
b. Inconsistent gingival margin
c. Excessive gingival display
d. Gingival enlargement (see Box 5.2)
e. Abnormal color

Mucogingival Deformities and Conditions on

Edentulous Edges

1. Vertical and/or horizontal ridge deficiency

2. Lack of gingiva or keratinized tissue
3. Gingival or soft tissue enlargements
4. Aberrant frenum or muscle position
5. Decreased vestibular depth
6. Abnormal color

Occlusal Trauma

1. Primary occlusal trauma

2. Secondary occlusal trauma

Data from Blieden TM: Tooth-related issues. Ann Periodontol 4:91, 1999; Halmon WW:
Occlusal trauma: effect and impact on the periodontium. Ann Periodontol 4:102, 1999; and
Pini Prato GP: Mucogingival deformities. Ann Periodontol 4:98, 1999.

Key Fact
Chronic periodontitis is classified by extent and severity of disease,
such as generalized (extent), moderate (severity) chronic
periodontitis.

Chronic periodontitis can be further classified on the basis of its

extent and severity. The severity of disease has been traditionally
determined as either slight/mild (1 to 2 mm of loss; Fig. 5.15),
moderate (3 to 4 mm of loss; Fig. 5.16), or severe (≥5 mm of loss; Fig.

355
5.17) on the basis of the amount of clinical attachment loss (see Box
5.3). Clinical attachment levels provide important benefits over
probing depth alone to monitor disease progression using the CEJ
as a fixed reference point. In fact, probing depth levels only have
poor to moderate sensitivity for predicting attachment level
changes overtime. Nonetheless, clinical experience has revealed
that oftentimes measurement of clinical attachment levels in
practice may prove to be erroneous. The most common error occurs
in the case of sites without gingival recession, whereby the location
of the gingival margin is coronal to the CEJ. If the clinician in such a
case only records the probing depth without charting the location of
the CEJ (often charted as “positive recession” in electronic
periodontal charts), the resulting attachment levels will be
erroneously recorded as being equal to the probing depth. To
prevent such an overestimate of disease, it has been suggested that
clinicians consider that mild periodontitis be associated with
probing depths of <4 mm, moderate periodontitis with probing
depths of 5 to 6 mm, and severe periodontitis with probing depths
of ≥7 mm. However, probing depths alone should not be used to
classify periodontitis without simultaneous consideration of clinical
attachment levels and radiographic bone loss.

356
 FIG. 5.15 (A) Clinical image of plaque-related
slight/early chronic periodontitis with 1- to 2-mm clinical
attachment loss in 40-year-old female. (B)
Radiographic images of the patient.

357
 FIG. 5.16 (A) Clinical image of plaque-related
moderate chronic periodontitis with 3- to 4-mm clinical
attachment loss in a 53-year-old male smoker. (B)
Radiographic images of the patient.

FIG. 5.17 (A) Clinical image of plaque-related

severe/advanced chronic periodontitis with >5 mm
clinical attachment loss in a 47-year-old female. (B)
Radiographic images of the patient.

Key Fact
In the AAP/EFP 2018 classification of periodontal diseases, one of
the major changes that will be implemented is avoidance of a
separate category of “aggressive periodontitis.” Both chronic and
aggressive periodontitis disease entities will be grouped together
and will be simply called periodontitis.

Aggressive Periodontitis

358
Aggressive periodontitis differs from the chronic form primarily by
the rapid rate of disease progression seen in an otherwise healthy
individual (Figs. 5.18 and 5.19). The absence of large accumulations
of plaque and calculus, with a positive family history of aggressive
disease, is suggestive of a genetic trait34,49 (see Box 5.3). This form of
periodontitis was previously classified as early-onset periodontitis
(see Table 5.1) and therefore still includes many of the
characteristics previously identified with the localized and
generalized forms of early-onset periodontitis. Although the clinical
presentation of aggressive disease appears to be universal, the
causative factors involved are not always consistent. Box 5.3
outlines additional clinical, microbiologic, and immunologic
characteristics of aggressive disease that may be present. As was
previously described for early-onset disease, aggressive forms of
periodontitis usually affect young individuals during or shortly
after puberty and may be observed during the second and third
decades of life (i.e., 10 to 30 years of age). The disease may be
localized, as previously described for localized juvenile
periodontitis, or generalized, as previously described for
generalized juvenile periodontitis and rapidly progressive
periodontitis (see Table 5.1). Box 5.3 describes the common features
of the localized and generalized forms of aggressive periodontitis.

359
 FIG. 5.18 (A) Clinical image of plaque-related
aggressive moderate periodontitis with 1- to 7-mm PD
and 3- to 4-mm clinical attachment loss in a 31-year-
old male. (B) Radiographic images of the patient.

360
 FIG. 5.19 (A) Clinical image of plaque-related
aggressive severe periodontitis with 3- to 13-mm PD
and 7- to 15-mm clinical attachment loss in a 32-year-
old male. (B) Radiographic images of the patient.

Flash Back
Recall that chronic periodontitis is also categorized by the extent of
localized or generalized disease according to the percentage of teeth
involved with 30% of teeth being the cutoff between the two
categories. Importantly, there is a distinct difference in the use of
these definitions in the context of aggressive periodontitis. For
aggressive periodontitis, the localized form is recognized to have a
specific clinical phenotype, which is typically limited to incisor and
first molar teeth.

Periodontitis as a Manifestation of Systemic

Disease
Several hematologic and genetic disorders have been associated

361
with the development of periodontitis in affected individuals22,23
(see Box 5.3). The majority of existing publications are case reports,
whereas only a few research studies have been performed to
investigate the exact nature of the effect of the specific condition on
the tissues of the periodontium primarily because of the rare
occurrence of many of these diseases. It is speculated that the major
effect of these disorders is through alterations in immune response,
such as in the case of interleukin-17 overexpression in leukocyte
adhesion deficiency30 or due to tissue metabolic disorders such as in
some forms of Ehlers–Danlos syndrome.2 The clinical manifestation
of many of these disorders appears at an early age and may be
confused with aggressive forms of periodontitis depicting rapid
attachment loss and the potential for early tooth loss. This was one
of the drivers for the transition from the term early-onset
periodontitis, which characterized a heterogeneous group of
diseases, to the definitions of aggressive periodontitis and
periodontitis as a manifestation of systemic diseases. With the
introduction of this form of periodontitis (see Table 5.1), the
potential exists for overlap and confusion between periodontitis as
a manifestation of systemic disease in both the aggressive and the
chronic forms of disease when a systemic component is suspected.
At present, periodontitis as a manifestation of systemic disease is the
diagnosis to be used when the systemic condition is the major
predisposing factor and when local factors (e.g., large quantities of
plaque and calculus) are not clearly evident or their presence alone
does not justify the severity or progression of disease. This
definition is reserved for a specific group of diseases and
syndromes that have been documented to have a profound
destructive effect on the periodontium. The removal of local factors
as part of conventional periodontal therapy in such cases is often
inadequate to arrest the periodontal destruction due to the systemic
effect. When periodontal destruction is clearly the result of local
factors but has been exacerbated by the onset of conditions such as
diabetes mellitus (Figs. 5.20 and 5.21) or HIV infection, the
diagnosis should be chronic periodontitis modified by the systemic
condition.

362
FIG. 5.20 (A) Clinical image of plaque-related severe
aggressive periodontitis in a 53-year-old male, smoker
with diabetes and hemoglobin A1c (HbA1c) = 10.7. (B)
Radiographic images of the patient.

363
 FIG. 5.21 Selective probing depths of the same 53-
year-old diabetic patient shown in Fig. 5.20 with severe
aggressive periodontitis.

Papillon–Lefèvre syndrome (PLS) is one example of a condition

that causes severe periodontitis as one of its manifestations. PLS is
an autosomal-recessive disorder caused by mutations in the
cathepsin C gene located on chromosome 11q14.17 The clinical
manifestations of the syndrome include severe aggressive
periodontitis and diffuse keratoderma on the palms, the soles, the
knees, or all three16 (Figs. 5.22 and 5.23). The consanguinity of the
parents is a common finding in approximately one-third of the
cases.31

FIG. 5.22 Panoramic radiograph and clinical photos of

a 13-year-old female with Papillon–Lefèvre syndrome
(PLS). PLS is an autosomal recessive disorder caused
by mutations in the cathepsin C gene located on
chromosome 11q14. The clinical manifestations of the
syndrome are severe aggressive periodontitis as well
as diffuse keratoderma on the palms, soles, or knees.

364
 In PLS patients by the age of 4 to 5 years, the primary
teeth have typically exfoliated or been extracted due to
severe periodontal destruction. Subsequently, an
edentulous phase occurs during which a reduction in
the oral microbial load is noted and gingival health is
restored. Following eruption of the permanent
dentition, a similar cycle of severe periodontal
inflammation is repeated that generally does not
respond to conventional periodontal therapy. An
increase in tooth mobility and periodontal abscesses is
frequently observed shortly after the eruption of
permanent teeth. (Courtesy Dr. Georgios Kotsakis, Seattle, Washington.)

FIG. 5.23 Patient with Papillon-Lefèvre (PLS)

syndrome exhibiting hyperkeratosis on palms of the
hand and soles of the feet. PLS clinically affects both
the primary and permanent dentition. Signs of
palmoplantar keratoderma usually appear
simultaneously with the eruption of the first primary
teeth (5–6 months), but may appear as early as 1
month of age. (Courtesy Dr. Georgios Kotsakis, Seattle, Washington.)

365
 Clinical Correlation
When monogenic diseases are encountered, consanguinity can be a
common finding particularly in certain ethnic cultures where it is
socially acceptable. Appropriate genetic counseling is advisable. In
addition, when the diagnosis for the proband (the first offspring
for whom disease is noted) is established, it is crucial that the
siblings are carefully examined for prompt diagnosis of additional
cases.

Impaired neutrophil function is considered to be the primary

cause of PLS and to eventually result in the deregulation of the
polymorphonuclear leukocyte response to microbial infection.11
Although the subgingival microbiota associated with PLS is
diverse, opportunistic periodontal pathogens such as
Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis,
Tannerella forsythia, Fusobacterium nucleatum, and Prevotella
intermedia are frequently identified among plaque samples from
PLS patients.1,50 Serum immunoglobulin G titers against Aa are
typically elevated in individuals with PLS, thereby implicating Aa
as a significant causative factor.50 Individuals with PLS are often
initially screened by a dermatologist or a pediatrician, and the
phenotype of the syndrome may be mistaken for atopic dermatitis
(eczema) or palmoplantar keratoderma.35 The case presented in
Figs. 5.22 and 5.23 was treated for several years by a dermatologist
as atopic dermatitis with occasional cauterization of misdiagnosed
“plantar warts.” The diagnosis of PLS was established in a
periodontal office. A multidisciplinary treatment approach for these
patients including referral to a periodontist cannot be
overemphasized. After a diagnosis of PLS has been established, it is
important to collect a complete family history and to construct a
pedigree to help identify undiagnosed or misdiagnosed siblings
(Fig. 5.24). In 1979 Haneke proposed palmoplantar hyperkeratosis,
the loss of primary and permanent teeth, and an autosomal-
recessive pattern of inheritance as being essential criteria to verify a
diagnosis of PLS.16 Secondary manifestations of PLS may include
ectopic intracranial calcifications and increased susceptibility to
infections, including pyogenic liver abscesses that can be fatal.9

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 FIG. 5.24 No history of consanguinity was reported in
this case. However, approximately one-third of the
diagnosed Papillon-Lefèvre (PLS) cases descend from
same ancestor. Offsprings III1, III3, and III4 display a
PLS phenotype. All siblings should be thoroughly
examined by a periodontist once a case of PLS has
been diagnosed.

PLS clinically affects both the primary and permanent dentition.

Signs of palmoplantar keratoderma usually appear simultaneously
with the eruption of the first primary teeth (i.e., 5 to 6 months of
age), but they may appear as early as the age of 1 month. By the age
of 4 to 5 years, the primary teeth have typically exfoliated or been
extracted as a result of severe periodontal destruction.
Subsequently, an edentulous phase occurs during which a
reduction in the oral microbial load is noted and gingival health is
restored. After the eruption of the permanent dentition, a similar
cycle of severe periodontal inflammation is repeated that generally
does not respond to conventional periodontal therapy.11 An
increase in tooth mobility and periodontal abscesses is frequently
observed shortly after the eruption of the permanent teeth.
The periodontal prognosis for patients with PLS has significantly
improved in response to an increase in the prompt and accurate
diagnosis of the syndrome, the better understanding of its
pathogenesis, and more efficient professional supervision. There
appears to be a consensus among clinicians that the successful
treatment of periodontitis among individuals with PLS requires the

367
eradication of Aa.10,12,43 Treatment of the primary dentition includes
frequent prophylaxis appointments to ensure that the patient
maintains adequate masticatory function and nutrition during early
childhood. To create a healthy environment for the permanent teeth
to erupt into, it has been advocated that a course of antibiotics
effective against Aa be systemically administered along with the
extraction of all primary teeth 6 to 12 months before the eruption of
the first permanent tooth. However, culture and sensitivity testing
of the subgingival plaque may enhance the selection of the most
effective antibiotic regimen. De Vree and colleagues described two
patients with PLS.10 Aa was eradicated from one individual, who
was able to retain most of his teeth over a 15-year period; the
second individual's Aa was found to be resistant to the antibiotics
combination, and he lost all of his teeth despite intensive treatment.
The combination of trimethoprim and sulfamethoxazole (i.e.,
cotrimoxazole) has also been shown to be effective against Aa and
to lead to a significant improvement in neutrophilic function
against Aa.24 A stringent periodontal maintenance schedule is of
utmost importance to efficaciously monitor the patient's oral
hygiene and to be able to intercede promptly if signs of
inflammation reoccur.32 Retinoids, which are synthetic analogues of
vitamin A, a treatment modality against PLS skin manifestations,
have also been considered as immunomodulatory adjuncts for the
treatment of PLS-associated periodontitis.12,24
Sarcoidosis is a chronic disease that is expressed as a cell-
mediated, delayed-type hypersensitivity that primarily affects the
lungs, lymph nodes, skin, eyes, liver, spleen, and small bones of the
hands and feet.36 Sarcoidosis rarely affects the oral cavity, with
incidence of occurrence in descending order noted in the lymph
nodes, lips, soft palate, buccal mucosa, gingiva, tongue, and bone.36
Fig. 5.25 depicts the pretreatment pattern of bone loss and recession
associated with sarcoidosis, with pulmonary parenchymal fibrous
infiltrate noted in the lungs as depicted by a white lacy pattern on a
chest radiograph (Fig. 5.25C). Histologic features of sarcoidosis
include the presence of an intense chronic inflammatory infiltrate
with focal areas of noncaseating granulomas and a positive Kveim
test (Fig. 5.26C). The remineralization of alveolar bone is noted on
radiographs obtained 1 year after the systemic administration of

368
steroids (e.g., prednisone) (Fig. 5.26A).

FIG. 5.25 Sarcoidosis pretreatment. (A) Intraoral x-

rays depict more extensive bone loss for anterior teeth
than clinical attachment loss. (B) Extensive recession
plus clinical attachment loss. (C) Pulmonary
parenchymal fibrous infiltrate.

369
 FIG. 5.26 Sarcoidosis after treatment with prednisone.
(A) Intraoral x-rays depict remineralization of bone. (B)
Reduction in gingival inflammation while extensive
recession and clinical attachment loss persist. (C)
Pretreatment biopsy.

Medication-Related Osteonecrosis of
the Jaw
Medication-related osteonecrosis of the jaw (MRONJ) is an updated
term that has replaced the phrase bisphosphonate-related
osteonecrosis of the jaw (BRONJ). Bisphosphonates (BPs) are
pyrophosphate analogues with a high affinity for hydroxyapatite
crystals. They inhibit osteoclast-mediated bone resorption and play
a key role in the management of osteolytic bone disorders,
including osteoporosis, Paget disease, bone metastasis, and
multiple myeloma.44 However, their prolonged use is associated
with MRONJ.18
The American Association of Oral and Maxillofacial Surgeons
defined MRONJ as “exposed bone in the maxillofacial area

370