2. Many systemic diseases, disorders, and conditions
have been implicated as risk indicators or risk factors
in periodontal disease.
Evidence also suggests that 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.
4. ENDOCRINE DISORDERS
During pregnancy, your progesterone hormone
levels are high. This increase makes you more
susceptible to developing the bacterial plaque that
can attack your gums.
Symptoms of gingivitis include:
tender, puffy gums
5. Fig. 1 Periodontal condition in patients with diabetes. (A) Adult with diabetes. (B)
The same patient. (C)Adult patient with uncontrolled diabetes. (D) The same patient
as shown in C. (E)Adult patient with uncontrolled diabetes.
6. Severe gingival inflammation, deep periodontal pockets, rapid bone
loss, and frequent periodontal abscesses often occur in patients with
poorly controlled diabetes and poor oral hygiene (Figs. 2 and 3).
Children with type I diabetes tend to have more destruction
around the first molars and incisors, but this destruction becomes
more generalized at older ages.
In patients with juvenile diabetes, extensive periodontal destruction
often occurs as a consequence of having more severe disease at a
7. Fig. 2 patient with a long-term history of
type 2 diabetes
Severe gingival inflammation, deep periodontal pockets, rapid bone loss, and
frequent periodontal abscesses often occur in patients with poorly controlled
diabetes and poor oral hygiene (Figs. 2 and 3).
Fig. 3 Periodontal abscess in type 1 diabetes.
8. The glucose content of gingival fluid and blood is higher in individuals
with diabetes than in those without diabetes with similar plaque and
gingival index scores.
The increased glucose in the gingival fluid and blood of patients with diabetes
could change the environment of the microflora, thereby inducing qualitative
changes in bacteria that may contribute to the severity of periodontal disease
observed in those with poorly controlled diabetes.
9. It has been reported that the prevalence of periodontal disease in diabetic patients is >85% (27.3% of
patients had gingivitis and 59.5% had periodontitis) whereas the prevalence of periodontitis in the general
population is 46% (1,7).
Epidemiological data confirm that diabetes is a major risk factor for periodontitis; susceptibility to
periodontitis is increased by approximately threefold in people with diabetes
Source: Diabetologia. 2012; 55(1): 21–31.
Published online 2011 Nov 6. doi: 10.1007/s00125-011-2342-y
There is emerging evidence to support the existence of a two-way relationship between diabetes and periodontitis, with
diabetes increasing the risk for periodontitis, and periodontal inflammation negatively affecting glycaemic control.
Incidences of macroalbuminuria and end-stage renal disease are increased twofold and threefold, respectively, in diabetic
individuals who also have severe periodontitis compared to diabetic individuals without severe periodontitis.
Furthermore, the risk of cardiorenal mortality (ischaemic heart disease and diabetic nephropathy combined) is three
times higher in diabetic people with severe periodontitis than in diabetic people without severe periodontitis. Treatment
of periodontitis is associated with HbA1c reductions of approximately 0.4%. Oral and periodontal health should be
promoted as integral components of diabetes management.
10. POLYMORPHONUCLEAR LEUKOCYTE FUNCTION
In patients with poorly controlled diabetes, the functions of
PMNs, monocytes, and macrophages are impaired.
As a result, the primary defense mounted by PMNs against
periodontal pathogens is diminished, and bacterial proliferation
is more likely.
No alteration of immunoglobulinA(IgA), G (IgG), or M (IgM)
has been found in patients with diabetes.
11. ALTERED COLLAGEN METABOLISM
Chronic hyperglycemia impairs collagen structure and
function, which may directly impact the integrity of the
Collagen in the tissues of patients with poorly controlled
diabetes is older and more susceptible to pathogenic
breakdown (i.e., less resistant to destruction by periodontal
12. INTERACTION BETWEEN DIABETES & PERIODONTAL DISEASE
Figure 3. Illustration of the mechanisms of interaction between diabetes and periodontal diseases. The most
widely accepted hypothesis is that diabetes increases inflammatory responses of the peridontal tissues. Exacerbated
and dysregulated inflammatory responses are the key to the proposed two-way relationship between diabetes and
periodontal diseases. AGE: advanced glycosylation end-products; MMP: extracellular matrix metalloproteinases;
PMN: polymorphonuclear leukocytes; RAGE: receptor of advanced glycosylation end-products.
Obesity is associated with increased cytokine production as well as T-
cell and monocyte/macrophage dysfunction, factors known to contribute
Female Sex Hormones
Gingival alterations during puberty, pregnancy, and menopause are
associated with physiologic hormonal changes in the female patient.
Oral changes during menopause may include thinning of the oral
mucosa, gingival recession, xerostomia, altered taste, and burning
14. HEMATOLOGIC DISORDERS
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.
Petechiae (Fig. 4) and ecchymosis (Fig. 5), observed most often
in the soft palate area, are signs of an underlying bleeding
It is essential to diagnose the specific etiology to appropriately
address any bleeding or immunologic disorder.
15. Fig. 4 Petechiae evident on the soft palate of a patient with an underlying bleeding
16. Fig. 5 Ecchymosis that is evident on the lateral aspects of the soft palate and
tonsillar pillars of a patient with chemotherapy-induced thrombocytopenia.
17. Disorders that affect the production or function of leukocytes may result in severe
A quantitative deficiency of leukocytes (e.g., neutropenia, agranulocytosis) is
typically associated with a more generalized periodontal destruction that affects
18. 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
Severe periodontitis has been observed in individuals with primary neutrophil disorders such as cyclic
neutropenia (Fig. 6), agranulocytosis, Chédiak–Higashi syndrome, and lazy leukocyte syndrome, secondary
neutrophil impairment, such as those with Down syndrome, Papillon– Lefèvre syndrome, and
inflammatory bowel disease.
19. Fig. 6 Aggressive periodontitis with cyclic neutropenia and agammaglobulinemia.
(A) Clinical presentation of the periodontal condition. (B) Panoramic radiograph
demonstrating severe bone.
The leukemias are malignant neoplasias of WBC
precursors. According to their evolution,
leukemias can be acute (which is rapidly fatal),
subacute, or chronic.
Oral and periodontal manifestations of leukemia
may include leukemic infiltration, bleeding, oral
ulcerations, and infections.
21. Fig. 7. Spontaneous bleeding from the gingival sulcus in a patient with thrombocytopenia. Normal
coagulation is evident by the appearance of the large clot that forms in the mouth. However, platelets
are inadequate to establish hemostasis at the site of hemorrhage.
Thrombocytopenia leads to bleeding tendency, which can occur in any
tissue but which in particular affects the oral cavity, especially the gingival
22. LEUKEMIC INFILTRATION
It consists of a basic infiltration of the gingival corium by leukemic cells that
increases the gingival thickness and creates gingival pockets in which bacterial
plaque accumulates, thereby initiating a secondary inflammatory lesion that
contributes to the enlargement of the gingiva.
23. Fig. 8 Leukemic infiltration that causes localized gingival
swelling of the interdental papillae between the maxillary
lateral and central incisors. Note the tense induration of
Fig. 9 Adult male with acute myelocytic leukemia. (A) A view of
the patient’s face.(B) Close-up view of skin lesions. (C) Gingival
enlargements of the entire gingival margin and interdental papilla
areas of both arches. (D) Occlusal view of the maxillary anterior
Gingival haemorrhage is a common finding in leukemic patients even in
the absence of clinically detectable gingivitis. Bleeding gingiva can be
an early sign of leukemia.
25. ORAL ULCERATION AND INFECTION
Acute gingivitis and lesions that resemble necrotizing
ulcerative gingivitis are more frequent and more severe in
patients with terminal cases of acute leukemia (Figs. 10).
This greatly altered and degenerated tissue is extremely
susceptible to bacterial infection, which can be so severe as to
cause acute gingival necrosis with pseudo-membrane formation
or bone exposure.
26. Fig. 10Adult female with acute myelocytic leukemia. (A)Anterior view of a patient
with acute myelocytic leukemia. (B) Palatal view demonstrating extensive necrosis
of the interdental and palatal tissues behind the maxillary incisors.
27. Individuals under stress may have poorer oral hygiene; they may start or
increase the clenching and grinding of their teeth; and they may smoke more
All of these behavioral changes increase their susceptibility to periodontal
disease destruction. Likewise, individuals who are under stress may be less
likely to seek professional care.
Bisphosphonate medications are primarily used to treat cancer and
osteoporosis or bone thinning—which occurs when the bones lose
calcium and other minerals that help keep them strong and compact.
They act by inhibiting osteoclastic activity, which leads to less bone
resorption, less bone remodeling, and less bone turnover.
During the treatment of osteoporosis, the goal is simply to harness
osteoclastic activity to minimize or prevent bone loss and, in many cases,
to increase bone mass by creating an advantage for osteoblastic activity.
29. Bisphosphonate-induced osteonecrosis of the jaws (BIONJ) refers to a
condition characterized by exposure of bone in mandible or maxilla
persisting for more than 8 weeks in patient who has taken or is currently
taking bisphosphonate and who has no radiation therapy to the jaws.
Among cancer patients receiving high-dose
intravenous bisphosphonates, osteonecrosis of
the jaw is dependent on dose and duration of
therapy,17–20 and has an estimated incidence
of 1% to 12%. Fig. 11 exposed bone of the maxilla with
bisphosphonate-induced osteonecrosis of the bone
30. Radiographic evidence of treatment with bisphosphonates
Panoramic radiograph of osteoporotic patient treated with bisphosphonates,
demonstrating marked increase in depth and density of mandibular inferior
border, periapical osteosclerosis, and increased number and density of
trabeculae in the body and symphaseal areas of the mandible
Panoramic radiograph: Patient: 77 years old, male, metastatic
prostate cancer, ibandronic acid & later another antiresorptive drug:
denosumab. Red arrows point to the necrotic area. Artefact due to
Bisphosphonate-induced osteonecrosis of the jaws (BIONJ)
31. The systemic administration of cortisone and adreno- corticotropic
hormone appears to have no effect on the incidence or severity of
gingival and periodontal disease.
However, renal transplantation patients receiving immunosuppressive
therapy have significantly less gingival inflammation than control subjects
with similar amounts of plaque.
Earlier literature review showed that chronic periodontitis is an independent
clinical high-risk profile for head and neck squamous cell carcinoma (HNSCC),
especially in the oral cavity, followed by the oropharynx and larynx.[In a
prospective cohort study by Michaud et al., a significant association was found
between the history of periodontitis and risk of developing lung, kidney,
pancreas, and hematological cancers. These associations are said to persist in a
number of studies, after adjustment for major risk factors, including cigarette
smoking and socioeconomic status. However, the most consistent increased risk
was noted in the studies of oral and esophageal cancers and periodontal disease.
Reference: Med Oral Patol Oral Cir Bucal. 2021 Jul; 26(4): e430–e436. Published online 2020 Dec 19. doi: 10.4317/medoral.24270
PMCID: PMC8254889 PMID: 33340075 Periodontitis as a risk factor for head and neck cancer
Letícia Miquelitto Gasparoni,1 Fábio Abreu Alves,1,2 Marinella Holzhausen,1 Cláudio Mendes Pannuti,1 and Marianna Sampaio Serpacorresponding author2
Gastric and pancreatic cancers had an association in most, but not all studies.
Lung, hematological, and other cancers were less consistently associated or did
not have sufficient studies to determine a predictable pattern. Furthermore,
Tezal et al. reported that patients with periodontal disease were more likely to
have poorly differentiated oral cavity squamous cell carcinoma (SCC) than those
without periodontitis. These findings were said to have implications for practical
and safe strategies for prevention, diagnosis, and treatment of HNSCC . The
possible link between periodontitis and malignancy is not clear, but lifetime
cumulative infection exposure is being queried.
What causes puberty gingivitis?
Puberty gingivitis is most common in preadolescent boys and girls between the ages of 11 and 13. It is typically the result of a combination of elevated hormone levels, which increase the response of gingival tissues to accumulated dental plaque, and poor oral hygiene habits.
Symptoms of puberty gingivitis are most commonly bleeding and inflammation of the gums. The gum tissue may also become swollen, red, and less firm to the touch. The production of sex hormones (oestrogen and progesterone) increases, then remains relatively constant during the remainder of the reproductive phase.1 Kronman and Loesch2 postulated that anaerobic organisms may use ovarian hormone as a substitute for vitamin K growth factor. During puberty, periodontal tissues may have an exaggerated response to local factors. A hyperplastic reaction of the gingiva may occur in areas where food debris, material alba, plaque and calculus are deposited. The inflamed tissues becomes erythematous, lobulated and retractable.1 During puberty, education of the parent or care giver is a part of successful periodontal therapy. Preventive care, including a vigorous program of oral hygiene, is also vital. Milder gingivitis cases respond well to scaling and root planning, with frequent oral hygiene reinforcement. Severe cases of gingivitis may require microbial culturing, antimicrobial mouthwashes and local site delivery or antibiotic therapy. Periodontal maintenance appointments may need to be more frequent when periodontal instability is noted.3
You will probably not be too surprised to learn that the best treatment for puberty gingivitis is prevention!
As your child gets older, he or she may be less inclined to listen to mom and dad about good oral hygiene practices. However, it’s important to remain firm on this theme to prevent gum disease from developing.
Make sure your teen is brushing thoroughly for 2 full minutes at least twice a day, and flossing carefully at least once a day.
If a child has already developed gingivitis, it’s best to get it under control as soon as possible, by way of periodontal therapy in the form of scaling and root planing. Mouthwashes containing chlorhexidine can be used to control the infection as well.
Pregnancy gingivitis most commonly develops between months 2 and 8. It may reach a peak during the third trimester. Pregnant women also face an increased risk of both tooth decay and loose teeth. More than 50% of all pregnant women experience some form of pregnancy gingivitis. Pregnancy gingivitis is an hyperplastic reaction to microbial plaque. Elevated estrogen or progesterone levels resulting from hormonal shifts enhance tissue vascularity, which permits an exaggerated inflammatory reaction to plaque. Pregnancy gingivitis produces fiery red, swollen and tender marginal gingiva and compressible and swollen interdental papilla. If pregnancy gingivitis progresses to periodontal disease, it can increase your risk of going into preterm labor.
Fig. 2 patient with a long-term history of type 2 diabetes. (A) Anterior view of the patient’s dental and periodontal condition. (B) Periapical radiographs of the remaining teeth. (C) Clinical photograph of the maxillary premolar area presenting with abscess. (D) Periapical radiograph of the maxillary premolar showing extensive bone loss associated with abscess. Fig. 3 Periodontal abscess in type 1 diabetes. (A) The patient presented with pain and abscess a few weeks after scaling and root planning of the area. (B) severe localized destruction of bone in the area of periodontal abscess. (C) Radiograph of the mandibular right premolar area taken 2 months before the presentation of the abscess.
How does diabetes mellitus cause periodontitis?
If diabetes isn't controlled well, higher blood sugar levels in saliva will help bacteria grow. This can cause gum disease. Poor blood sugar control makes it harder for the immune system to fight gum disease. And gum disease may make it harder to control the diabetes.
It has been reported that the prevalence of periodontal disease in diabetic patients is >85% (27.3% of patients had gingivitis and 59.5% had periodontitis) whereas the prevalence of periodontitis in the general population is 46% (1,7).
Figure 3 illustrates schematically the mechanisms of interaction between DM and periodontitis.
it is well known that diabetic patients present defects in polymorphonuclear leukocyte (PMNL) activity, including chemotaxis, phagocytosis and bactericidal function disorders. Shetty et al. studied PMN functions in 15 diabetic patients with chronic generalized periodontitis, and found that chemotaxis, superoxide production, phagocytosis and killing of Porphy- romonas gingivalis by diabetic PMNs were impaired significantly in comparison with healthy control subjects  . Similarly, other studies have shown that diabetic patients with severe periodontitis present reduced chemotaxis in comparison with diabetic subjects with only slight periodontitis, as well as defective apoptosis, which can lead to an increase in PMN retention in the periodontal tissues, which will be accompanied by greater tissue destruction due to continuous MMP and reactive oxygen species (ROS) secretion   .
A second element for consideration in this two-way relationship is the role of Ad- vanced Glycation End-products (AGEs). AGEs are composites derived from the non- enzymatic, irreversible glycosylation of proteins and lipids that accumulate in plasma, on the walls of blood vessels and tissues in diabetic patients, which are the main element responsible for the development of the micro and macrovascular complications characteristic of DM  . It is known that gingival macrophages present receptors with high affinity for AGEs (RAGE), so that they accumulate in the periodontal tissues of diabetics. A study by Schmidt et al.  showed that the gingival tissue of adult patients diagnosed with DM who were subjected to surgical periodontal treatment, presented higher quantities of AGEs than that of non-diabetic subjects. This finding is important as the accumulation of AGEs in the periodontal tissues of diabetic patients favors frequent pro-inflammatory episodes. When AGE binds to its receptor, this produces an overproduction of inflammatory mediators such as IL-1b, TNF-a and IL-6    . The formation of these molecules provokes ROS production, which increases oxidative stress, and the consequent cellular changes that take place contribute to the vascular damage involved in many DM complications  -  . AGEs also increase the respiratory burst of PMNs, which has the potential to increase tissue damage localized in the periodontium. In addition, AGEs have a harmful effect on bone metabolism, producing an alteration to the bone formation and repair mechanisms, together with reduced production of extracellular matrix. Apoptosis may play a role in the increased susceptibility to periodontal diseases among diabetics, and the death of matrix-pro- ducing cells could limit the possibility of repair in inflamed tissues; it is known that AGEs have harmful effects on extracellular matrix formation, in relation to apoptosis of the cells most involved in its formation such as fibroblasts  .
A third element for consideration is the changes that DM may cause in the composition of subgingival microbiota. Compared with the large number of studies that have investigated the role of inflammatory mechanisms in the relation between DM and periodontal diseases, relatively few have focused on the changes triggered by changes to oral microbiota. The few that exist indicate that in general there are more similarities than differences between diabetic and non-diabetic subjects. Nevertheless, some significant differences have been detected, such as the greater prevalence of Porphyromonas gingivalis  and Prevotella intermedia   in diabetic subjects. These studies indicate that there are probably subtle differences between diabetics and non-diabetics, although the clinical relevance of these differences is not clear. The origins of these differences could lie in the previously observed effects on periodontal tissues that could favor the growth of more pathogenic species.
Cytokines are regulators of host responses to infection, immune responses, inflammation, and trauma. Some cytokines act to make disease worse (proinflammatory), whereas others serve to reduce inflammation and promote healing (anti-inflammatory). Cytokines are produced in response to invading pathogens to stimulate, recruit, and proliferate immune cells. Cytokines includes interleukins (IL), chemokines, interferons, and tumor necrosis factors (TNF). Cytokines play an important role in normal immune responses, but having a large amount of them released in the body all at once can be harmful. This so-called CYTOKINE STORM happens when the immune system produces too many inflammatory signals. This can can cause serious symptoms that in some cases can lead to organ failure and death
Can bleeding gums be a sign of leukemia?
Yes. Your blood platelets help your body stop bleeding. If you have Leukemia, a type of cancer, your platelet count will be low. This makes it harder for you to stop bleeding in different parts of your body, including your gums.
Make an appointment with your doctor if your notice symptoms including unusual bleeding of your gums or nosebleeds.
It may be localized to the interdental papilla area (Fig. 8), or it may expand to include the marginal gingiva and partially cover the crowns of the teeth (Fig. 9C and D). GINGIVAL LEUKEMIC INFILTRATION AS THE FIRST MANIFESTATION OF ACUTE MYELOID LEUKEMIA. The leukemic infiltration of the gingival tissue associated or not with gingival enlargement could be the first manifestation of acute leukemia, and it has rarely been reported in the literature.
The Modifiable Risk factors for periodontitis and cancer: Modifiable (smoking, diabetes mellitus, psychological factors, and lifestyle factors - such as diet and alcoholism) and non-modifiable risk factors are host response and genetic factors.
Therefore, patients should be encouraged to change their lifestyle and adopt healthy habits (healthy eating, regular physical exercise), eliminate risk factors that may predispose them to cancer (smoking and alcohol), practice good oral hygiene, and visit regularly health professionals. Thus, the health multidisciplinary team must act together to reduce or eliminate potential risks that may affect the oral and systemic overall health of patients.