CHAPTER 6 RELATIONSHIP BETWEEN

PERIODONTAL DISEASE AND SYSTEMIC HEATH - Influence of Systemic Conditions

Endocrine disorders and hormonal changes
1. Diabetes mellitus: metabolic disorder characterized by hyperglycemia due to defective secretion
or activity of insulin
① Types of diabetes
A. Type 1
a. Cell-mediated autoimmune destruction of the insulin-producing beta cells of the
islets of Langerhans in the pancreas, resulting in insulin deficiency.
b. Young adult or children. Unstable and difficult to control marked tendency to ketosis
and coma.
c. S/sy: including polyphagia, polydipsia, polyuria, and predisposition to infections
B. Type 2
a. Caused by peripheral resistance to insulin action, impaired insulin secretion, and
increased glucose production in the liver.
b. Typically begins as insulin resistance, which leads to the reduced pancreas
production of insulin as the demand increases.
c. Most common form. Generally in obese individuals and can be controlled by diet
and oral hypoglycemic agents.
d. Ketosis and coma are uncommon. Less severe signs and symptoms than type1
C. Hyperglycemia secondary to other diseases or condition
a. Gestational diabetes: disappear after delivery but with increased risk of dev. type 2
diabetes.
b. Endocrinopathies
c. Other genetic syndromes associated with diabetes – Down’s syndrome,
Klinefelter’s syndrome, Turner’s syndrome, Wolfram’s syndrome
② Diagnosis
American Diabetes Association criteria for the diagnosis of diabetes mellitus, impaired
glucose tolerance (IGT), and impaired fasting glucose (IFG).

A. The actual diagnosis of gestational diabetes mellitus is usually based on a 3-h oral
glucose tolerance test in which a fasting blood sample is drawn after 8–14 h of fasting.
B. This is immediately followed by giving a 100-g glucose load orally and then drawing
blood samples again at 1, 2, and 3 h time-points.
C. If two or more of the threshold glucose levels are exceeded the diagnosis is made.
③ Oral manifestation
A. Include cheilosis, mucosal drying and cracking, burning mouth and tongue, diminished
salivary low, and alterations in the lora of the oral cavity, with greater predominance of
Candida albicans, hemolytic streptococci, and staphylococci.
B. Increased rate of dental caries in patients with poorly controlled diabetes
C. Individuals with controlled diabetes have a normal tissue response, a normally
developed dentition, a normal defense against infections, and no increase in the
incidence of caries
D. Effect of diabetes on the periodontium: diabetes alters the response of the periodontal
tissues to local factors (dental plaque)
a. Periodontal disease is considered to be the 6 th complication of diabetes, and
diabetes is one of the risk factor of periodontitis. (peripheral neuropathy, retinal
degeneration, renal insufficiency, atherosclerosis including coronary disease,
micro-angiopathy.)
b. Changes include enlarged gingiva, sessile or pedunculated gingival polyps,
polypoid gingival proliferations, abscess formation, periodontitis, and loosened
teeth
c. Children with type 1 diabetes tend to have more destruction around the 1 st molars
and incisors (molar-incisor form) but becomes more generalized at older ages.

④ Mechanism of diabetes as a risk factor of periodontitis

A. Altered polymorphonuclear leukocyte function
a. In patients with poorly controlled diabetes, the functions of PMNs, monocytes and
macrophages are impaired.
b. As a result, the primary defense mounted by PMNs against periodontal pathogens
is diminished, and bacterial proliferation is more likely
B. Altered collagen metabolism.
a. Chronic hyperglycemia impairs collagen structure and function, which may directly
impact the integrity of the periodontium
b. Numerous proteins and matrix molecules undergo a nonenzymatic glycosylation,
thereby resulting in accumulated glycation end-product (AGEs). Collagen is cross-
linked by AGE formation, which makes the collagen less soluble and less likely to
be normally repaired or replaced.
 c.
AGEs and receptors for AGEs (RAGEs) play a central role in the classic
complications of diabetes, and will also play sig. role in periodontal disease
progression as well.
C. Hyper-inflammatory response
a. Gingival IL-1β and TNF-α levels are significantly higher in poorly controlled
diabetes.
b. High serum levels of the acute phase reactants fibrinogen and C-reactive protein.
⑤ Complications of diabetes mellitus
A. Acute complications
a. Diabetic ketoacidosis
b. Hyperglycemic hyperosmolar state
c. Hypoglycemia
B. Uncontrolled diabetes/ chronic hyperglycemia
a. Micovascular disease: retinopathy, nephropathy, or neuropathy
b. Macrovascular disease: cardiovascular and cerebrovascular condition
c. Increased susceptibility to infection, poor wound healing.
⑥ Management of periodontal diseases in diabetic patients.
A. Periodontal therapy including nonsurgical or surgical
B. Systemic antibiotics
C. Insulin therapy and oral hypoglycemic drugs.

2. Metabolic syndrome: a condition of abdominal obesity combined with 2 or more of the following
metabolic disturbances: hypertenstion, dyslipidemia, and hyperglycemia.
① Individuals with metabolic syndrome are at increased risk for dev. type 2 D.m. and CVS
disease.
② Condition of excess adipose tissue contributes to an increased systemic proinflammatory
response in these individuals.
③ Subjects who are overweight and obese had a higher risk of dev. periodontitis when
compared with those who did not.
④ TNF-a and IL-6 are increased as well as T-cell and monocyte/macrophage dysfunction may
contribute to periodontitis.

3. Female sex hormone

① During puberty and pregnancy, these changes are characterized by nonspecific inflammatory
reactions with a predominant vascular component, which leads clinically to a marked
 hemorrhagic tendency.
② Oral changes during menopause may include thinning of the oral mucosa, gingival recession,
xerostomia, altered taste, and burning mouth.

③ Puberty
A. Clinical features Pronounced inflammation, bluish red discoloration and edema are
seen.
B. Site: Pubertal gingivitis manifests as marginal and interdental gingival enlargement
primarily on facial surfaces and rarely on lingual surfaces.
C. As adulthood approaches, the severity of the gingival reaction diminishes, even when
local factors persist.
D. With good oral hygiene (removing local factor), it can be prevented.

④ Menstruation
A. Some patients may complain of bleeding gums or a bloated, tense feeling in the gums
during the days preceding menstrual flow.
B. Increased gingival bleeding, swollen gingiva, increased gingival exudate. GCF flow rate
is unaltered.
C. Pre-existing gingivitis is aggravated by menstruation.
D. Tooth mobility does not change sig. during the menstrual cycle.
⑤ Pregnancy
A. Affects the severity of previously inflamed areas, but it does not alter healthy gingiva.
B. Impressions of increased incidence may be created by the aggravation of previously
inflamed but unnoticed areas.
C. Tooth mobility, pocket depth, and gingival fluid are also increased during pregnancy
D. Severity is increased beginning in the 2nd or 3rd month it becomes more severe by the 8 th
month and decreases during the 9th month of pregnancy.
 E. Partial reduction in the severity of gingivitis occurs by 2 months postpartum, and after 1
year, the condition of the gingiva is comparable to who have not been pregnant.
F. The 2 peaks of accentuation of gingivitis (during 1 st trimester when there is an
overproduction of gonadotropins and during the 3rd trimester, when estrogen and
progesterone levels are highest), the destruction of gingival mast cells by the increased
sex hormones and the resultant release of histamine and proteolytic enzymes may also
contribute to the exaggerated inflammatory response to local factors.
G. Clinical feature
a. Pronounced ease of bleeding, tooth mobility and GCF secretion are seen
b. Inflamed gingiva with variety of color from bright red to bluish red.
c. Painless unless complicated by acute infections
d. Marginal and interdental gingivae are edematous; they pit on pressure, appear
smooth and shiny, are soft and pliable, and sometimes have a raspberry-like
appearance.
e. In some cases the gingiva forms discrete tumor-like masses which are referred to
as pregnancy tumors. (Mostly seen in interproximal sites of maxillary anteriors)

H. Microscopically
a. Marked inflammatory cellular infiltration occurs, with edema and degeneration of
the gingival epithelium and connective tissue.
b. The epithelium is hyperplastic, with accentuated rete pegs, induced surface
keratinization and various degrees of intercellular and extracellular edema and
infiltration by leukocytes with numerous newly-formed engorged capillaries.
E. Microbiologically
a. Subgingival flora changes to more anaerobic flora as pregnancy progresses
b. Sig. increased numbers of P.intermedia. (which is associated with the elevation in
systemic levels of estradiol and progesterone)
⑥ Menopause.
A. Concentration of circulating estrogen decreases leading to compromised anti-
inflammatory effects on the periodontium.
B. As a result, women can develop a gingivostomatitis/ senile atrophic gingivitis
C. Can occur during menopause or during the postmenopausal period, it is not a common
condition.
D. Gingiva and oral mucosa are dry, shiny, varied color (paleness to redness), easy
tendency to bleed. Dryness and burning sensation
E. Abnormal taste sensations described as “salty,” “peppery,” or “sour”; and dificulty with
removable partial prostheses.
F. Microscopically, the gingiva exhibits atrophy of the germinal and prickle cell layers of the
peihtelium and, in some patients, areas of ulceration.
 ⑦ Contraceptives
A. Aggravate the gingival response to local factors in a manner similar to that seen during
pregnancy.
B. Increase in periodontal destruction when these drugs are taken for longer than 1.5
years.

4. Hyperparathyroid.
① Osteitis fibrosa cystica/ vonRecklinghausen bone disease: Produces generalized
demineralization of the skeleton, increased osteoclasts with proliferation of the connective
tissue in the enlarged marrow spaces and the formation of bone cysts and giant cell tumors.
② Oral changes include malocclusion and tooth mobility, radiographic evidence of alveolar
osteoporosis with closely meshed trabeculae, widening of the periodontal ligament space,
absence of the lamina dura, and radiolucent cystlike spaces.
③ Brown tumors: bone cyst that is filled with fibrous tissue with abundant hemosiderin-laden
macrophages and giant cells, are actually reparative cellular process, and it is histologically
identical to giant cell tumor

Hematologic disorders
1. Hemorrhagic tendencies occur when the normal hemostatic mechanisms are disturbed. Abnormal
bleeding from the gingiva or other areas of the oral mucosa that is difficult to control is an
important clinical sign that suggests a hematologic disorder.

2. Petechiae and ecchymosis observed most often in the soft palate area are signs of an underlying
bleeding disorder.

3. Leukocyte disorders: quantitative deficiency of leukocytes (e.g., neutropenia, agranulocytosis) is

typically associated with a more generalized periodontal destruction that affects all teeth.
① Neutropenia
A. May be caused by diseases, medications, chemicals, infections, idiopathic conditons or
hereditary conditions.
B. An absolute neutrophil count (ANC) of 1000 to 1500 cells/µL is diagnostic for mild
neutropenia. An ANC of 500 to 1000 cells/µL is considered moderate neutropenia, and
 an ANC of <500 cells/µL indicates a severe neutropenia.
C. In severe neutropenia, infections are difficult to manage and may be life threatening.
② Agranulocytosis
A. More severe neutropenia that involves neutrophils, basophils and eosinophils.
B. Defined as an ANC of <100 cells/µL.
C. Reduction in the number of circulating granulocytes, and it results in severe infections,
including ulcerative necrotizing lesions of the oral mucosa, the skin, and the
gastrointestinal and genitourinary tracts.
D. Less severe forms of the disease are called neutropenia or granulocytopenia.
E. Drug idiosynerasy is the most common cause of agranulocyosis. (Drugs include
aminopyrine, barbiturates and their derivatives, benzene ring derivatives, sulfonamides,
gold salts and arsenical agents).
F. Generally occurs as an acute disease may be chronic or periodic, with recurring
neutropenic cycles (such as cyclic neutropenia).
G. Clinical features
a. Onset of disease is accompanied by fever, malaise, general weakness and sore
throat.
b. Ulceration in the oral cavity, oropharynx and the throat is characteristic
c. Mucosa exhibits isolated necrotic patches that are black and gray and that are
sharply demarcated from the adjacent uninvolved areas.
d. Absence of notable inflammatory reaction caused by a lack of granulocytes is a
striking feature.
e. Gingival hemorrhage, necrosis, increased salivation, and fetid odor are
accompanying clinical features.
f. Patients with cyclic neutropenia has generalized aggressive periodontitis and recur
with recurrent exacerbation of the disease.
H. DD: noma, NUG, acute necrotizing inflammation of the tonsils and diphtheria. Definitive
diagnosis is made by hematologic findings of pronounced leukopenia and almost
complete absence of neutrophils.

4. Leukemia
① Characterized by the following
A. Diffuse replacement of the bone marrow with proliferating leukemic cells.
B. Abnormal numbers and forms of immature WBCs in the circulating blood
C. Widespread infiltrates in the liver, spleen, lymph nodes, and other body sites.
② Classified as
A. Lymphocytic: malignant change occurs in cells that normally form lymphocytes.
B. Myelogenous: malignant change occurs in cells that normally form RBC, some times of
WBCs and platelets. Includes monocytic leukemias
③ As leukemia tend to displace normal components of the bone marrow element with leukemic
cells, thereby resulting in anemia, leukopenia, and thrombocytopenia.
 A. Anemia: poor tissue oxygenation which makes tissue more friable and susceptible to
breakdown.
B. Leukopenia: poor cellular defense and increased susceptibility to infections.
C. Thrombocytopenia leads to bleeding tendency, which can occur in any tissue but which
in particular affects the oral cavity, especially the gingival sulcus
④ Periodontium in leukemic patients
A. Oral manifestation may include leukemic infiltration, bleeding, oral ulceration and
infections. Expression of these signs is more common in acute than chronic
B. Leukemic infiltration
a. Leukemic cells can infiltrate the gingiva, and gingival infiltration often result in
leukemic gingival enlargement.
b. Highest incidence with acute monocytic leukemia > acute myelocytic-monocytic
leukemia > acute myelocytic leukemia.
c. Not found in edentulous patients and with chronic leukemia, suggesting that it
represents the accumulation of immature leukemic blast cell in the gingiva adjacent
to tooth surfaces with bacterial plaque.
d. Clinical features
- May be localized to the interdental papilla or it may expand to include the
marginal gingival and partially cover the crowns of the teeth. (left pic)
- Gingiva appears bluish red and cyanotic, with a rounding and tenseness of the
gingival margin.
- Abnormal accumulation of leukemic cells in the dermal and subcutaneous
connective tissue is called leukemia cutis, and it forms elevated and flat
macules and papules.

e. Microscopically
- The gingiva exhibits, a dense, diffuse infiltration of predominantly immature
leukocytes in the attached and marginal gingiva.
- The normal connective tissue components of the gingiva are displaced by the
leukemic cells
- Cellular accumulation is denser in the reticular layer and in papillary layer
contains comparatively few leukocytes.
- Common findings include degeneration associated with intercellular and
intracellular edema and leukocytic infiltration with diminished surface
 keratinization
- Marginal gingiva differs from that of other gingival location In that it usually
exhibits a notable inflammatory component. Scattered foci of plasma cells and
lymphocytes with edema and degeneration and marginal necrosis with
pseudomembrane formation may be seen.

C. Bleeding
a. Bleeding gingiva can be an early sign of leukemia which is caused by
thrombocytopenia
b. Bleeding can be manifest in the skin and throughout the oral mucosa, where
petechiae are often found.
c. Bleeding can also be a side effect of the chemotherapeutic agents used to treat
leukemia.
D. Oral Ulceration and Infection
a. Normal inflammatory response may be diminished
b. Granulocytopenia increase host susceptibility to opportunistic microorgansisms and
leads to ulceration and infections.
c. Discrete, punched-out ulcers that penetrate deeply into the submucosa and are
covered by a firmly attached white slough can be found on the oral mucosa. These
lesions occur in sites of trauma (such as buccla mucosa in line of occlusion)
d. Patients with previous herpes virus infection may develop recurrent herpetic oral
ulcers (multiple sites) in large, atypical forms.
e. Acute gingivitis and lesions that resemble NUG are more frequent and more severe
in patients with terminal cases of acute leukemia.

f. The inflamed gingiva in patients with leukemia differs clinically from that found in
nonleukemic individuals The gingiva is a peculiar bluish red, it is spongelike and
friable, and it bleeds persistenly on the slightest provocation or even spontaneously.
g. Altered and degenerated tissues are extremely more susceptible to bacterial
infection which results in acute gingival necrosis with pseudomembrane formation or
bone exposure.
 ⑤ Eliminating or reducing local factors (bacterial plaque) can minimize the severe oral changes
associated with leukemia. (with severe leukemia, symptoms can only be alleviated with
treatment of leukemia).
Some patients may have normal blood counts while leukemic cells reside primarily in the bone
marrow. This type of disease is called aleukemic leukemia.

5. Anemia
Classified according to cellular morphology and hemoglobin content
① Macrocytic hyperchromic anemia. (pernicious anemia)
A. Result in tongue changes in 75% of patients.
B. Tongue appears red, smooth, and shiny as a result of atrophy of the papillae.
C. Marked pallor of the gingiva.
② Microcytic hypochromic anemia (iron-deficiency anemia)
A. Induces similar tongue and gingival changes.
B. Plummer-Vinson syndrome: with glossitis and ulceration of the oral mucosa and
oropharynx and that induces dysphagia.
③ Sickle cell anemia
A. Characterized by pallor, jaundice, weakness, rheumatoid manifestation and leg ulcers.
B. Oral change include generalized osteoporosis of the jaws, peculiar stepladder alignment
of the trabeculae of the interdental septa, along with pallor and yellowish discoloration of
oral mucosa.
C. Periodontal infections may precipitate sickle cell crisis
④ Normocytic normochromic anemia (hemolytic or aplastic anemia).
A. Aplastic anemia results from a failure of the bone marrow to produce erythrocytes.
B. Usually the effect of toxic drugs on the marrow or the displacement of RBCs by leukemic
cells.
C. Oral changes include pale discoloration of the oral mucosa and increased susceptibility
to infection because of the concomitant neutropenia

6. Thrombocytopenia
① Purpura: purplish appearance of the skin or mucous membrane where bleeding has occurred
as a result of decreased platelets.
② Etiology: may be idiopathic or as secondary to some known etiologic factors
③ Petechiae and hemorrhagic vesicles occur in the oral cavity, particularly in the palate, the
tonsillar pillars, and the buccal mucosa.
④ The gingivae are swollen, soft, and friable. Bleeding occurs spontaneously or with the
slightest provocation, and it is difficult to control.
⑤ The severity of the gingival condition is dramatically alleviated by removal of the local factor

7. Antibody deficiency disorders.

 ① Agammaglobulinemia, or hypogammaglobulinemia, is an immune deficiency that results
from inadequate antibody production caused by a deficiency in B cells.
② Aggressive periodontitis is a common finding in children who are diagnosed with
agammaglobulinemia
③ Congenital (X-linked or Bruton agammaglobulinemia)
A. Caused by X-linked, recessive gene (Bruton tyrosine kinase).
B. Only males have the disease.
C. In the absence of mature B cells, patients lack lymphoid tissue and fail to develop
plasma cells. Thus, the production of antibodies is deficient.
D. Germinal centers where B cells proliferate and differentiate are poorly developed in all
lymphoid tissues
④ Acquired or late-onset agammaglobulinemia is most often known as common variable
immunodeiciency disease (CVID)
A. Characterized by the onset of recurrent bacterial infections during the second and third
decades of life as a result of drastic decreases in immunoglobulin and antibody levels.
B. Cause: unkown failure of B-lymphocyte differentiation into plasma cells.
C. In contrast to patients with the X-linked form of the disease, patients with CVID typically
have an enlarged spleen and swollen glands or lymph nodes.
D. Develops autoantibodies against their blood cells.

Genetic disorders
1. Systemic conditions that are associated with or that predispose an individual to periodontal
destruction include genetic disorders that result in an inadequate number or reduced function of
circulating neutrophils.

2. Chédiak–Higashi Syndrome
① Rare disease that affects the production of organelles found in almost every cell
② It affects mostly the melanocytes, platelets, and phagocytes. It causes partial albinism, mild
bleeding disorders, and recurrent bacterial infections.
③ Neutrophils contain abnormal, giant lysosomes that can fuse with the phagosome, but their
ability to release their contents is impaired, thus the killing of ingested microorganisms is
delayed.
④ Patients with Chédiak– Higashi syndrome are susceptible to repeated infections that can be
serious and life threatening.
⑤ Aggressive periodontitis has been described.

3. Lazy Leukocyte Syndrome

① Characterized by susceptibility to severe microbial infections, neutropenia, defective
chemotactic response by neutrophils, and an abnormal inflammatory response.
② Those who are diagnosed with lazy leukocyte syndrome are susceptible to aggressive
periodontitis with destruction of bone and early tooth loss

4. Leukocyte adhesion deficiency (LAD): primary immunodeficiency often diagnosed at birth.

① Many children with LAD do not survive.
② LAD results from an inability to produce or a failure to normally express an important cell
surface integrin (CD18), which is necessary for leukocytes to adhere to the vessel wall at the
site of infection.
③ Without adhering to the vessel wall they can’t migrate to the infection site.
④ They begin during or immediately after the eruption of the primary teeth. Extremely acute
inflammation and proliferation of the gingival tissues with rapid destruction of the bone are
found.
5. Papillon–Lefèvre Syndrome
① Rare cases of adult onset of this syndrome, with only mild periodontal lesions, have also
been described.
② The syndrome is characterized by hyperkeratotic skin lesions, severe destruction of the
periodontium, and, in some cases, calcification of the dura.
③ Symptoms of Papillon–Lefèvre syndrome diminish with age and that teeth that erupt later
may not be lost.
④ The microscopic changes reported include marked chronic inlammation of the lateral wall of
the pocket with a predominantly plasma cell iniltrate, considerable osteoclastic activity with
an apparent lack of osteoblastic activity, and an extremely thin cementum.

6. Down syndrome
① The prevalence of periodontal disease in patients with Down syndrome is high, occurring in
almost 100% of patients who are younger than 30 years of age.
② Periodontal disease in those with Down syndrome is characterized by the formation of deep
periodontal pockets associated with substantial plaque accumulation and moderate gingivitis
③ Generalized but tend to be more severe in the lower anterior region.
④ May be associated with poor PMN chemotaxis, phagocytosis, and intracellular killing.

Stress and psychosomatic disorders.

1. Psychologic conditions, particularly psychosocial stress, have been implicated as risk indicators
for periodontal disease
There is well-known association between stress and NUG

2. Although stress may predispose an individual to more destruction from periodontitis, the presence
of periodontal pathogens remains as the essential etiologic factor. In other words, stress alone
does not cause or lead to periodontitis in the absence of periodontal pathogens.

3. Stress and depression have a negative effect on periodontal treatment outcomes.

Nutritional influence
1. Data suggest that diets that contain foods rich in antioxidants are beneficial, whereas foods that
contain high levels o refined carbohydrates are detrimental to the inflammatory process.

2. Fat soluble vitamin deficiency

① Vit.A deficiency
A. Major function of Vit.A is to maintain the health of the epithelial cells of the skin and
mucous membrane.
B. In the absence of Vit.A degenerative changes occur in epithelial, thereby resulting in a
keratinizing metaplasia.
C. may lead to hyperkeratosis, hyperplasia of the gingiva and increased periodontal pocket
formation.
② Vit. D/ calciferol deficiency
A. A deficiency of vitamin D and an imbalance in calcium–phosphorus intake result in
rickets in young children and osteomalacia in adults.
B. No studies have demonstrated a relationship between vitamin D deiciency and
periodontal disease, but vit. D deficiency effects the alveolar bone.
③ Vit. E deficiency
A. Vitamin E serves as an antioxidant to limit free-radical reactions and to protect cells from
lipid peroxidation.
B. No relationship between vit. E deficiencies and oral disease but Vit.E accelerate gingival
wound healing.
 ④ Vit K deficiency: increased bleeding tendency

3. Water soluble vitamin deficiency

① B-complex
A. Oral changes that are common to B-complex deficiencies are gingivitis, glossitis,
glossodynia, angular cheilitis, and inflammation of the entire oral mucosa.
B. Thiamin deficiency, called beriberi
a. Are characterized by paralysis; cardiovascular symptoms, including edema; and loss
of appetite.
b. Oral disturbances associated with thiamin deficiency include hypersensitivity of the
oral mucosa; minute vesicles (simulating herpes) on the buccal mucosa, under the
tongue, or on the palate; and erosion of the oral mucosa
C. Riboflavin deficiency
a. include glossitis, angular cheilitis, seborrheic dermatitis, and a supericial
vascularizing keratitis
b. Glossitis is characterized by a magenta discoloration and atrophy of the papillae. In
mild to moderate cases, the dorsum exhibits a patchy atrophy of the lingual papillae
and engorged fungiform papillae, which project as pebble-like elevations.
c. With severe deficiency, the entire dorsum is flat, with a dry and often fissured
surface.
d. Angular cheilitis begins as an inflammation of the commissure of the lips, and this is
followed by erosion, ulceration, and fissuring.
Candidiasis may develop in the commissures of debilitated persons, which is known as perleche.
D. Niacin deficiency results in pellagra
a. Symptoms of dermatitis, GI disturbances, neurologic and mental disturbances
(dermatitis, diarrhea or dementia), glossitis, gingivitis and generalized stomatitis.
b. Glossitis and stomatitis may be the earliest clinical signs of niacin deficiency.
c. Most common finding is necrotizing ulcerative gingivitis usually in areas of local
irritation.
E. Folic acid deficiency
a. Results in macrocytic anemia with megaloblastic erythropoiesis accompanied by
oral changes, GI lesions, diarrhea, and intestinal malabsorption.
b. Generalized stomatitis occurs, which may be accompanied by ulcerated glossitis
and cheilitis.
c. Ulcerative stomatitis is an early indication of the toxic effect of the folic acid
antagonists (e.g., methotrexate) used for the treatment of leukemia
② Vitamin C deficiency/ scurvy
A. Characterized by hemorrhagic diathesis and delayed wound healing
B. Scurvy results in the defective formation and maintenance of collagen, the impairment or
cessation of osteoid formation, and impaired osteoblastic function.
C. Clinical manifestations of scurvy include hemorrhagic lesions into the muscles of the
extremities, the joints, and sometimes the nailbeds; petechial hemorrhages, often
around the hair follicles; increased susceptibility to infections; and impaired wound
healing. Bleeding, swollen gingiva, and loosened teeth are common features of scurvy
D. Gingivitis with enlarged, hemorrhagic, bluish-red gingiva is described as one of the
classic signs of vitamin C deficiency, but gingivitis is not caused by vitamin C deficiency,
rather it is caused by bacterial plaque, with vit C deficiency it may aggravate (가속) the
gingival response to plaque and worsen the edema, enlargement and bleeding. (same
for periodontitis)
E. The periodontal fibers that are least affected by vitamin C deficiency are those just
below the junctional epithelium and above the alveolar crest, which explains the
 infrequent apical downgrowth of the epithelium.

4. Protein deficiency
① Hypoproteinemia are characterized by muscular atrophy, weakness, weight loss, anemia,
leukopenia, edema, impaired lactation, decreased resistance to infection, slow wound
healing, lymphoid depletion, and reduced ability to form certain hormones and enzyme
systems.
② Accentuates the destructive effects of bacterial plaque and occlusal trauma on the
periodontal tissues but the initiation and severity still depend on the bacterial plaque.
In other words, protein deprivation results in periodontal tissues that lack integrity and that,
as a result, are more vulnerable to breakdown when challenged by bacteria.

Medication
1. Bisphosphonates
① Bisphosphonate medications are primarily used to treat cancer (via intravenous [IV]
administration) and osteoporosis (via oral administration).
② The effects of bisphosphonates on oral hard and soft tissue cells share the common
mechanism of interference with products of the mevalonate pathway The inhibition of
farnesyl pyrophosphate synthase leads to the inhibition of the mevalonate pathway end
product, geranylgeranyl pyrophosphate
③ The strength of binding and the ease of release of bisphosphonates with hydroxyapatite
make these drugs more or less potent
④ Bisphosphonate have 2 side chains R1, and R2. E2 side chain infleunces the mode of action
and det. the strength or potency of the medication.
⑤ Bisphosphonates inhibit osteoclast by 2 mechanism that depend on whether the R2 side
chain contains nitrogen.
A. Nonaminobisphosphonates are metabolized by osteoclasts to form an adenosine
triphosphate analog that interferes with energy production and causes osteoclast
apoptosis.
B. Aminobisphosphonates (i.e., risedronate, zoledronate, ibandronate, and alendronate)
are more potent and have multiple effects on osteoclasts, including the following:
a. Inactivation of adenosine triphosphate
b. Osteoclast cytoskeletal disruption
c. impairment of osteoclast recruitment
d. induction of osteoblasts to produce osteoclast-inhibiting factor
⑥ Bisphosphonate may act on oral keratinocytes to impair wound healing by inhibiting
epithelial migration and wound closure.
⑦ Bisphosphonates have a high affinity for hydroxyapatite. They are rapidly absorbed in bone,
especially in areas of high activity, which may help to explain why bisphosphonate-induced
osteonecrosis is found only in the jaws.
⑧ Definition of BRONJ: exposure and necrosis of portions of the jaw bone in patients who have
been exposed to bisphosphonates that has persisted for longer than 8 weeks with no history
of radiation therapy to the jaws
⑨ Stages
A. Stage 0 patients are patients at risk who have been treated with IV or oral
bisphosphonates but who have no apparent exposed or necrotic bone.
B. Stage 1 involves exposed or necrotic bone in patients who are asymptomatic with no
infection.
C. Stage 2 involves exposed or necrotic bone in patients with pain and clinical evidence of
infection.
D. Stage 3 involves exposed or necrotic bone in patients with pain, infection, and one or
more of the following: pathologic fracture, extraoral fistula, or osteolysis that extends to
 the inferior border.
⑩ Clinical features
A. BRONJ manifest as exposed alveolar bone that occurs spontaneously or after a
traumatic event such as a dental procedure.
B. The sites may be painful, with surrounding soft tissue induration and inlammation.
Infection with drainage may be present. Radiographically, lesions appear radiolucent,
with sclerosis of the lamina dura, a loss of the lamina dura, or a widening of the
periodontal ligament in areas where teeth are present.
C. Histologically, bone appears necrotic, with empty lacunae demonstrating a lack of living
osteocytes.
D. BRONJ occur most often in areas with dense bone and thin overlying mucosa, such as
tori, bony exostoses, and the mylohyoid ridge.
E. More common in the mandible than in the maxilla.

⑪ Potential risk factors that may contribute to BRONJ include systemic corticosteroid therapy,
smoking, alcohol, poor oral hygiene, chemotherapy, radiotherapy, diabetes, and hematologic
disease.

2. Corticosteroids.
① The systemic administration of cortisone and adrenocorticotropic hormone appears to have
no effect on the incidence or severity of gingival and periodontal disease.
② Renal transplantation patients receiving immunosuppressive therapy (either prednisone or
methylprednisone combined with either azathioprine or cyclophosphamide) have
significantly less gingival inflammation than control subjects with similar amounts of plaque
Other systemic conditions.
1. Osteoporosis
① T-score between +1 and −1 is considered normal, whereas a T-score between −1 and −2.5
indicates low bone density or osteopenia and a T-score of less than −2.5 (i.e., more than 2.5
standard deviations below normal) is diagnostic for osteoporosis.
② Women with higher skeletal BMD were more likely to retain their teeth in the presence of
periodontitis (i.e., deep periodontal pockets) compared with women with osteoporosis.
③ Less risk for tooth loss and improved oral health among postmenopausal women receiving
hormone replacement therapy
2. Congenital heart disease
① Chronic hypoxia causes impaired development, compensatory polycythemia (i.e., an
increase in RBCs and hemoglobin), and clubbing edema of toes and fingers
② Patients with congenital heart defects are often at risk for infective endocarditis as a result of
turbulent blood low in the heart and the associated cardiovascular defects.
③ Oral abnormalities associated with cyanotic congenital heart disease include delayed
eruption of both primary and permanent dentitions, increased positional abnormalities, and
enamel hypoplasia
④ Tetralogy of fallot
A. Tetralogy of Fallot is characterized by four cardiac defects: (1) ventricular septal defect,
(2) pulmonary stenosis, (3) malposition of the aorta to the right, and (4) compensatory
right ventricular enlargement.
B. Clinical features include severe cyanosis, audible heart murmurs, and breathlessness.
Cyanosis and breathlessness cause cerebral anoxia and syncope.
C. Oral changes include a purplish-red discoloration of the lips and the gingiva. Severe
marginal gingivitis and periodontal destruction have been reported
⑤ Eisenmenger syndrome
A. This syndrome is distinguished by a greater blood low from the stronger left ventricle to
the right ventricle (backward low) through the septal defect. This causes increased
pulmonary blood low, which in turn leads to progressive pulmonary ibrosis, small vessel
occlusion, and high pulmonary vascular resistance.
B. With increasing pulmonary resistance, the right ventricle hypertrophies, the shunt
becomes bidirectional, and ultimately blood low is reversed (i.e., it lows from right to left).
The increased vascular resistance builds pressure in the right ventricle, thereby causing
right ventricular hypertrophy and a reversal in the direction of the blood low, which
results in a right-to-left shunt

3. Hypophosphatasia
① Hypophosphatasia is a rare familial skeletal disease that is characterized by rickets, poor
cranial bone formation, craniostenosis, and the premature loss of the primary teeth,
particularly the incisors.
② Patients have a low level of serum alkaline phosphatase, and phosphoethanolamine is
present in serum and urine.
③ Teeth are lost with no clinical evidence of gingival inlammation, and they show reduced
cementum formation.

4. Metal intoxication.
① Bismuth intoxication
A. Chronic bismuth intoxication is characterized by gastrointestinal disturbances, nausea,
vomiting, and jaundice as well as by an ulcerative gingivostomatitis, generally with
pigmentation and accompanied by a metallic taste and burning sensation of the oral
mucosa.
B. Urticaria, different types of exanthematous eruptions, bullous and purpuric lesions,
herpes zoster–like eruptions, and pigmentation of the skin and mucous membranes are
among the dermatologic lesions attributed to bismuth intoxication.
 C. Bismuth pigmentation in the oral cavity usually appears as a narrow, bluish-black
discoloration of the gingival margin in areas of preexisting gingival inflammation
② Lead intoxication
A. There is pallor of the face and lips and gastrointestinal symptoms that consist of nausea,
vomiting, loss of appetite, and abdominal colic. Peripheral neuritis, psychologic
disorders, and encephalitis
B. Oral signs include salivation, coated tongue, a peculiar sweetish taste, gingival
pigmentation, and ulceration.
C. Gingival pigmentation is linear (Burtonian line), steel gray, and associated with local
inflammation..
③ Mercury intoxication
A. Mercury intoxication is characterized by headache, insomnia, cardiovascular symptoms,
pronounced salivation (ptyalism), and a metallic taste.
B. Gingival pigmentation in linear form results from the deposition of mercuric sulfide.

CHAPTER 6 RELATIONSHIP BETWEEN

PERIODONTAL DISEASE AND SYSTEMIC HEATH – Impact of periodontal infection.

1. The organisms and their products such as LPS have ready acess to the periodontal tissues and
to the circulation via the sulcular epithelium which is frequently ulcerated and discontinuous.
Bacteremias are common after mechanical periodontal therapy, and they also occur frequently
during normal daily function and oral hygiene procedures.

2. Alveolar bone loss increased the risk of mortality more than smoking (52% increased risk due to
higher incidence of CHD-related events such as MI and unstable angina among men younger
than 60 years of age with alveolar bone loss compared with those without bone loss.
3. Periodontal infections can adversely affect systemic health with manifestations such as coronary
heart disease, stroke, diabetes, preterm labor, low-birth-weight delivery, and respiratory disease.

PERIODONTAL DISEASE, CORONARY HEART DISEASE AND ATHEROSCLEROSIS

1. Patients with poor oral hygiene, as indicated by higher debris and calculus scores, had a twofold
increased risk for CHD.
There is consistent and strong epidemiologic evidence that periodontitis imparts increased risk for
future cardiovascular disease.

2. Effects of periodontal infection.

① Systemic infections are known to induce a hypercoagulable state and increase blood
viscosity. Fibrinogen levels and WBC counts are often increased in patients with periodontal
disease. Individuals with poor oral health may also have significant elevations in coagulation
factor VIII/ von Willebrand factor antigen, thereby increasing the risk of thrombus formation.
② Increased viscosity of blood may promote major ischemic heart disease and cerebrovascular
accident (stroke) by increasing the risk of thrombus formation.

③ There is a greater risk of bacteremia after toothbrushing in patients with higher levels of
plaque, calculus, and gingivitis as compared with those with minimal plaque and gingival
inflammation.
④ Subjects with generalized gingival bleeding after brushing showed an almost eightfold
increase in their incidence of bacteremia as compared with those with minimal gingival
bleeding.
⑤ The periodontium, when affected by periodontitis, also acts as a reservoir of endotoxins
(LPSs) from gram-negative organisms. Endotoxins can pass readily into the systemic
circulation during normal daily function, thereby inducing damage to the vascular
endothelium and precipitating many negative cardiovascular effects.
⑥ Thromboembolism
A. Oral organisms may be involved in coronary thrombogenesis. Platelets selectively bind
some strains of Streptococcus sanguinis which is component of supragingival plaque
and P. gingivalis.
B. The aggregation of platelets is induced by the platelet aggregation– associated protein
(PAAP) expressed on some strains of these bacteria.
⑦ Atherosclerosis
A. The formation of atherosclerotic plaques is precipitated by damage to vascular
endothelium that results in an inflammatory response in which circulating monocytes
adhere to the vascular endothelium.
B. Damage to vascular endothelium can occur because of the presence of intravascular
microorganisms and their products; chemical damage, often resulting from elements of
tobacco and other exogenous toxins; and increased shear force along the vascular
lining, such as that occurring in hypertension.
C. The adhesions of monocyte to the damaged vascular endothelium are up-regulated by
number of factors including LPSs, prostaglandins, and proinflammatory cytokines.
D. After binding to the endothelial lining, monocytes penetrate the endothelium and migrate
under the arterial intima. The monocytes ingest circulating LDL, thereby forming the
foam cells that are characteristic of atheromatous plaque. After entering the arterial
media, monocytes may also transform to macrophages.
E. Arterial thrombosis often occurs after an atheromatous plaque ruptures. Plaque rupture
exposes circulating blood to arterial collagen and tissue factor from monocytes and
macrophages that activate platelets and the coagulation pathway.
F. Platelet and fibrin accumulation forms a thrombus that may occlude the vessel and
result in an ischemic event such as angina or MI.
G. The thrombus may separate from the vessel wall and form an embolus, which may also
occlude vessels, again leading to an acute event such as MI or cerebral infarction
(stroke).
3. Patients with an abnormally exuberant inflammatory response often have a hyperinflammatory
monocyte and macrophage phenotype (MØ+). Monocytes and macrophages from these
individuals secrete significantly increased levels of proinflammatory mediators (e.g., IL-1, TNF-α,
PGE2) in response to bacterial LPSs compared with patients with a normal monocyte and
macrophage phenotype. The presence of an MØ+ phenotype may place patients at risk for both
CHD and periodontitis.

4. Acute-phase proteins such as C-reactive protein (CRP) and fibrinogen are produced in the liver in
response to inflammatory or infectious stimuli and act as inflammatory markers. CRP induces
monocytes and macrophages to produce tissue factor, which stimulates the coagulation pathway
and increases blood coagulability. Increased fibrinogen levels may contribute to this process. CRP
also stimulates the complement cascade, further exacerbating inflammation

5. Elevations in serum CRP and fibrinogen levels are well-accepted risk factors for cardiovascular
disease, and serum CRP and fibrinogen levels are often elevated in subjects with periodontitis as
compared with subjects without periodontitis
6. After scaling and root planning with a resultant decrease in periodontal inflammation, markers of
vascular health improve significantly over time.

PERIODONTAL DISEASE AND STROKE

1. Ischemic cerebral infarction, or stroke, is often preceded by systemic bacterial or viral infection.

2. The presence of systemic infection before the stroke resulted in significantly greater ischemia and
a more severe postischemic neurologic defect than stroke not preceded by infection.

3. Nonhemorrhagic stroke, or ischemic stroke, is usually caused by thromboembolic events and

cerebrovascular atherosclerosis, whereas hemorrhagic stroke often results from a vascular bleed
such as an aneurysm. Periodontal disease has been associated primarily with an increased risk
 of nonhemorrhagic stroke.

PERIODONTAL DISEASE AND DIABETES MELLITUS

1. Complication of DM.

2. Periodontitis negatively affects glycemic control in diabetes patients. Periodntal diseases can
induce or perpetuate an elevated systemic chronic inflammatory state, which is reflected in
increased serum CRP, IL-6, and fibrinogen levels Inflammation induces insulin resistance
3. Periodontal treatment results in significant reduction in HbA1C in Type II diabetes patients
4. Periodontal therapy may have a smaller impact on glycemic control in patients with type 1
diabetes than in those with type 2 disease.
5. Systemic antibiotics may eliminate residual bacteria after scaling and root planning, thereby
further decreasing the bacterial challenge to the host. Tetracyclines are also known to suppress
the glycation of proteins and decrease the activity of tissue-degrading enzymes such as matrix
metalloproteinases.

PREGNANCY AND PERIODONTAL DISEASE

1. Maternal periodontal diseases are associated with an increased risk of various APO, including
preterm birth (PTB), fetal growth restriction (FGR), low birthweight (LBW), pre‐eclampsia (PE) and
gestational diabetes (GDM).

2. Effect of periodontal disease on pregnancy

① PRE-TERM BIRTH (PTB) and LBW
A. F. nucleatum is the most often isolated species in amniotic fluid of women with PTB.
B. Bacterial infection → Bacteria and products in amnion → Inflammatory response in
amnion →Increased amniotic prostaglandin production → Preterm labor.
② Periodontal disease may also increase the risk for preeclampsia.
A. Preeclampsia is a major cause of perinatal and maternal morbidity and mortality.
B. Preeclampsia has multiple potential etiologies

3. Scaling and root planning provided during the second and third trimesters of gestation are safe
procedures. Use of local anesthetics is acceptable during such treatment,

PERIODONTITIS AND COPD

Among nonsmokers and former smokers, even severe periodontitis did not increase the risk for
COPD. In current smokers, however, the presence of severe periodontitis was associated with an
increased risk of COPD.
COPD exacerbation is an acute event in which respiratory symptoms are worsened, usually to the
point where a change in medication is needed. Most COPD exacerbations are caused by infections.
In controlled clinical trials, scaling and root planning was associated with a decrease in the frequency
of COPD exacerbations compared with nontreatment.

Periodontal Disease and Acute Respiratory Infections

1. Community-acquired bacterial pneumonia is caused primarily by the inhalation of infectious
 aerosols or the aspiration of oropharyngeal organisms. Streptococcus pneumoniae and
Haemophilus influenzae are the most common.

2. Hospital-acquired (nosocomial) bacterial pneumonia has a very high morbidity and mortality rate.
The incidence of nosocomial pneumonia is highest among severely ill patients,
① Although nosocomial pneumonia is most often caused by gram-negative aerobic organisms,
many cases are the result of infection by anaerobic bacteria, including those that are
typically found in the subgingival environment
② The longer the hospital stay, the greater the prevalence of PRPs. PRPs are found
predominantly in the gastrointestinal tract, and they may be passed via esophageal relux
into the oropharynx, where they colonize. Subsequent aspiration may lead to pneumonia
③ Dental plaque has been shown to serve as a reservoir of PRPs; such colonization in plaque
results in a persistent source of potential aspiration.
④ Selective decontamination is a technique that combines systemic antibiotics with orally
administered nonabsorbable antibiotics in an attempt to eradicate PRPs from the digestive
tract and the oropharynx and thereby minimize the risk of nosocomial respiratory infections.
⑤ One systematic review showed that mechanical oral hygiene performed in nursing homes
and hospitals significantly decreased the occurrence and progression of respiratory tract
infections and pneumonia;