ROLE OF SYSTEMIC FACTORS IN ETIOLOGY OF PERIODONTAL DISEASE

Presented by: Sonia Sachdeva MDS II Prof

INTRODUCTION

Need for assessment of systemic factors

To identify high-risk individuals in prior so that preventive and treatment procedures can be tailored to these individuals.

Only a subpopulation suffers from severe periodontal disease, systemic and other risk factors that are associated with the severe periodontal disease in this subpopulation to be identified public health measures can be rendered to prevent periodontal disease in a cost-effective manner.

CLASSIFICATION
Systemic conditions & Systemic disorders Various systemic factors that play role in etiology of periodontal disease are as follows:

Endocrine Influences

Nutritional Influences

Hematologic Disorders

Genetic Disorders

Effect of systemic drug therapy

Collagen Vascular Diseases

Immunodeficiency Disorders

Cardiovascular Diseases

Psychosomatic Disorders

Other Systemic Conditions-Metal Intoxication

ENDOCRINE DISORDERS

ENDOCRINE DISORDERS
Diabetes Hormonal fluctuations associated with puberty and pregnancy Osteoporosis

Hyperparathyroidism

Endocrine disturbances and hormone fluctuations affect the periodontal tissues directly, modify the tissue response to local factors, and produce anatomic changes in the gingiva that may favor plaque accumulation and disease progression

DIABETES MELLITUS
2 main types:

Diabetes & Periodontitis:

Considered the sixth complication of diabetes More likely to occur in diabetic patients Poorly controlled type 2 diabetics more likely to develop periodontal disease than well-controlled diabetics

Study on Pima Indian population (Arizona) population with highest prevalence of type 2 DM, the prevalence of attachment loss and bone loss was greater among DM patients than non DM patients in all age groups DM subjects aged 15-34 years had mean attachment loss and bone loss scores approx. twice as high as similarly aged non DM subjects. Mean %age of sites with >15% bone loss - 28% in well controlled type 1 diabetes mellitus subjects 44% in poorly controlled diabetics.

Mechanism of interaction in DM
i) ii) Changes in subgingival environment Altered microbiota Change in GCF composition

i) ii) iii) iv)

i) ii)

Altered tissue homeostasis and wound healing collagen production- alterations in wound healing MMP activity Accumulation of AGEs tissue turnover

Changes in host immunoinflammatory response PMNL chemotaxis, adherance and phagocytosis pro-inflammatory cytokines response from monocyte / macrophage iii) tissue oxidant stress

Response to Periodontal treatment in patients with diabetes

In well controlled DM, similar response to treatment is seen (non DM).

In poorly controlled DM, less favourable response to treatment. In these, initial response to scaling and root planing is good, but chances of recurrence within 12 months was greater
Animal studies suggest decreased bone to implant contact in DM. the survival rate for implant was 90%, with failure rate of 7.8% (DM) compared to 6.8% (Non DM) patients

PUBERTY
Increased testosterone (in males) and increased estradiol (in females) is seen. increased no. of Prevotella Intermedia sp. seen , as they substitute Progesterone & estrogen for menadione (Vitamin K) as an essential nutrient. increase in no. of Capnocytophaga species is seen, responsible for the increased bleeding tendency observed during puberty . Oral manifestations: Gingivitis, Recurrent apthous ulcers, Aggressive periodontitis (0.1% to 0.4%)

Clinical features of puberty induced gingivitis,

i)

Marginal & interdental gingival enlargement found primarily on the facial surfaces, with lingual surfaces remaining relatively unaltered. increased gingival bleeding tendency

ii)

iii) increased inflammation with relative less amounts of plaque i) When puberty is passed, the inflammation tends to subside but does not disappear until adequate plaque control is achieved.

MENSTRUATION

i)

During menstruation, changes seen are:

Gingivitis

ii)

Increase in GCF flow

iii) Enlarged hemorrhagic gingiva in days preceding menstrual flow iv) Minor increase in Tooth mobility

 Muhlemann observed a case of bright red hemorrhagic lesions of interproximal papilla prior to menstruation.

In addition to gingival inflammation

intraoral recurrent apthous ulceration herpes labialis lesions infections with Candida Albicans are seen in some women and seem to be associated with increased Progesterone levels during reproductive cycle.

PREGNANCY
During pregnancy, increased levels of sex steroid hormones-in implantation of embryo, until parturition.

During pregnancy large quantities of Estradiol (20mg/day), Estriol (80mg/day) and Progesterone (300mg/day) are produced.
Direct relationship between Gingivitis and sustained, raised levels of gestational hormones during pregnancy, with regression during the post partum period.

You lose a tooth for every pregnancy Babies drain the calcium from your teeth Every time you are pregnant your gums bleed and you have problems with them

False to all: Meticulous oral hygiene with fluoride regimen will help to prevent all tooth and gum problems experienced during pregnancy

Effects on Microbiota

Selective growth of periodontal pathogens i.e. P.Intermedia in subgingival plaque is seen during onset of pregnancy gingivitis at 3 or 4 month of pregnancy- 55 fold increase Gestational hormones act as growth factors, by satisfying the napthoquinone requirement for bacteria.

Kornmann & Losche reported that during 2nd trimester, plaque levels remain constant, but gingivitis an gingival bleeding increases in severity
Bacteroides melaninogenicus sp. also increases in pregnancy (55 fold) and in those taking contraceptives (16 fold)

Effect on Tissues & Host response Estrogen - sex steroid hormone responsible for alteration in blood vessels in target tissues in females. Increased Circulatory levels of Progesterone enhances capillary permeability and dilatation, resulting in increased gingival exudate Increased Leakage of leukocytes and plasma proteins from post capillary venules by affecting the endothelial lining, contributing to enhanced gingival inflammation.

Increased Progesterone levels the degree of keratinization of gingival epithelium and alter the connective tissue ground substance.
Keratinization alongwith increased in epithelial glycogen results in decreased effectiveness of the epithelial barrier

 Neutrophil chemotaxis and phagocytosis, alongwith T-cell responses further causes the suppression of immune system to plaque.

Progesterone in particular stimulates the production of inflammatory mediator PGE2 & increased accumulation of PMNL in the gingival sulcus
IL-6 production by human gingival fibroblasts (upto 50%)

levels of Plasminogen activator inhibitor type 2 (PAI-2), an important inhibitor of tissue proteolysis
CD3, CD4 and B lymphocytes during pregnancy, thus CD4/CD8 ratio also decreases, leading to an immunodeficient state.

Peripheral blood lymphocytes showed a decreased response to bacterial antigens, in vitro, including extracts from P.intermedia

Hormonal influences on cells of periodontium

Sex steroid hormones directly or indirectly exert influence on cellular proliferation & differentiation growth in target tissues, including keratinocytes and fibroblasts in gingiva. By altering collagen turnover, estrogens stimulate proliferation of gingival fibroblasts, and synthesis and maturation of the gingival CT.

 These hormones also increase rate of folate metabolism in oral mucosa.

Since folate is required for tissue maintenance, increased metabolism could deplete folate stores and inhibit tissue repair. During 3rd trimester, synthesis of GAGs a major constituent of CT matrix of gingiva, is reported. In certain cases, estrogen and progesterone inhibited collagen synthesis by influencing the PDL fibroblasts in vitro.

OSTEOPOROSIS
Osteoporosis means literally _porous bone, a condition where there is too little bone to provide mechanical support. Osteopenia- reduction in bone mineral density below what is required for mechanical support.

WHO Diagnostic Guidelines for Interpretation of Bone Mass Measurements in Caucasian Women
Severe Osteoporosis BMD more than 2.5 standard deviations (SD) below the mean value of peak bone mass in young normal women and the presence of fractures. Osteoporosis BMD more than 2.5 SD below the mean value of peak bone mass in young normal women. Low bone mass (Osteopenia) BMD within 1 SD and 2.5 SD of the mean value of peak bone mass in normal young women Normal BMD not more than 1SD below mean value of peak bone mass in young normal women.

Classification of Osteoporosis
Primary Idiopathic Juvenile Adult

Secondary Endocrine disorders-Diabetes mellitus Gastrointestinal and malabsorption syndromes Myeloproliferative disorders Multiple myeloma Connective tissue diseases Marfan syndrome Ehlers-Danlos syndrome Chronic Obstructive Pulmonary disease

Common Risk Factors Hereditary/genetics Osteoporosis Female gender Caucasian or Asian race Family history Menopause Petite body build Suboptimal peak bone mass Low intake calcium Low intake vitamin D High intake caffeine, protein, salt, phosphate Smoking Alcohol Physical inactivity Diabetes mellitus Multiple myeloma Periodontal Disease Age Race Familial aggregation IL-1 polymorphism

Dietary factors

Low intake calcium Low intake vitamins C, E

Environment

Systemic factors

Smoking Alcohol Stress Diabetes mellitus Osteoporosis

Periodontal disease and osteoporosis

Relationship of tooth loss and BMD has been studied.
Several reports find a correlation between tooth loss and diminished systemic BMD.Other reports fail to find this correlation. The use of tooth loss as a surrogate for periodontal disease extent has several limitations. Underlying reason for the loss of the teeth is often unknown. The extent of the disease around the remaining teeth is not taken into account in these analyses.

HORMONAL CONTRACEPTIVES
Contraceptives utilize synthetic gestational hormones (estrogen and progesterone), to reduce the likelihood of ovulation/implantation (Guyton 1987). Less dramatic but similar effects to pregnancy are sometimes observed in the gingivae of hormonal contraceptive users.
The most common oral manifestation of elevated levels of ovarian hormones is an increase in gingival inflammation with an accompanying increase in gingival exudate (Mariotti 1994).

Effect on tissue response Both estrogen and progesterone increase gingival exudate, associated with inflammatory edema (Lindhe & Bjorn 1967). A 53% increase in crevicular fluid volume has been demonstrated in hormonal contraceptive users compared with controls. Human gingiva has receptors for progesterone and estrogen (Vittek et al. 1982; Staffolani et al. 1989), providing evidence that gingiva is a target tissue for both gestational hormones. Progesterone causes increased vascular permeability, resulting in the infiltration of polymorphonuclear leukocytes and raised levels of PGE2 in the sulcular fluid (Miyagi et al. 1993). Increased capillary permeability may be induced by estrogen by stimulating the release of mediators such as bradykinin, prostaglandins, and histamine. However, the main effects of estrogen are in controlling blood flow. Hence the combination of estrogen and progesterone in the contraceptive pill can contribute to vascular changes in the gingivae. The resultant gingivitis can be minimized by establishing low plaque levels at the beginning of oral contraceptive therapy (Zachariasen 1993).

HYPERPARATHYROIDISM
Osteitis fibrosa cystica or von Recklinghausen's bone disease Generalized demineralization of the skeleton increased osteoclasis with proliferation of the connective tissue in the enlarged marrow spaces formation of bone cysts and giant cell tumors.

Oral changes malocclusion and tooth mobility radiographic evidence of alveolar osteoporosis with closely meshed trabeculae widening of the pdl space absence of the lamina dura radiolucent cyst like spaces- brown tumors

Different investigators report that 25%, 45%, and 50% of patients with hyperparathyroidism have associated oral changes.

NUTRITIONAL INFLUENCES

i)

Nutritional deficiencies that produce changes in the oral cavity. These changes include alterations of the lips, oral mucosa and bone as well as of the periodontal tissues.
These changes are considered to be periodontal or oral manifestations of nutritional disease.

ii)

iii) There are no nutritional deficiencies that by themselves can cause gingivitis or periodontal pockets.

Nutritional influences
Physical character of diet

Effect on microbes
distribution of types of organisms metabolic activity & pathogenic potential,

Effect on oral microbes

Sources of nutrients:
Endogenous Exogenous

Deficiency of specific components

FAT-SOLUBLE VITAMIN DEFICIENCY

VITAMIN A DEFICIENCY. Dermatologic, mucosal, and ocular manifestations. Degenerative changes occur in epithelial tissues keratinizing metaplasia. Periodontal changes Animal studies: Hyperplasia and hyperkeratinization of the gingival epithelium with proliferation of the junctional epithelium and retardation of gingival wound healing. In the presence of local factors, vitamin A-deficient rats develop deep periodontal pockets.
Humans: No relation between this vitamin and periodontal disease.

 VITAMIN D DEFICIENCY. Animal studies (young dogs): osteoporosis of alveolar bone osteoid that forms at a normal rate but remains uncalcified failure of osteoid to resorb reduction in the width of the periodontal ligament space a normal rate of cementum formation, but defective calcification and some cementum resorption Distortion of the growth pattern of alveolar bone. Osteomalacic animals: Rapid, generalized, severe osteoclastic resorption of alveolar bone, proliferation of fibroblasts that replace bone and marrow, and new bone formation around the remnants of unresorbed bony trabeculae. Radiographically: generalized partial to complete disappearance of the lamina dura, loss of trabeculae, increased radiolucence of the trabecular interstices, and increased prominence of the remaining trabeculae.

WATER-SOLUBLE VITAMIN DEFICIENCY

B-COMPLEX DEFICIENCY. Oral changes common to B-complex deficiencies
Gingivitis- non-specific, as it is caused by bacterial plaque rather than by the deficiency. Glossitis Glossodynia Angular cheilitis Inflammation of the entire oral mucosa.

VITAMIN B1
Oral disturbances: Hypersensitivity of the oral mucosa Minute vesicles (simulating herpes) on the buccal mucosa, under the tongue, or on the palate. Erosion of the oral mucosa

 Glossitis; angular cheilitis; seborrheic dermatitis; and superficial vascular keratitis. Glossitis is characterized by a magenta discoloration and atrophy of the papilla.

VITAMIN B2

In mild to moderate cases, dorsum exhibits a patchy atrophy of the lingual papilla and engorged fungiform papilla, which project as pebble like elevations.
In severe deficiency, the entire dorsum is flat, with a dry and often fissured surface.

FISSURED TONGUE

 Angular cheilitis, begins as an inflammation of the commisure of the lips, followed by erosion, ulceration and fissuring.

D/D Angular Cheilitis due to decreased VD in dentures Candidiasis (Perleche)

ORAL ULCERATION

Supplemental riboflavin is ineffective to resolve cases of glossitis and angular cheilitis that are not caused by vitamin deficiency.

ANGULAR CHEILOSIS

VITAMIN B3
Pellagra : diarrhea, dermatitis and dementia. Glossitis and stomatitis may be the earliest signs of niacin deficiency. The gingiva may be involved in ANIACINOSIS with or without tongue changes. Most common finding is NUG usually in areas of local irritation. Oral manifestations in experimental animals :

Black tongue Gingival inflammation with destruction of gingival, periodontal ligament and alveolar bone. Necrosis of the gingiva and other oral tissues and leucopenia are the terminal features of niacin deficiency.

BIOTIN DEFICIENCY
Oral signs of biotin deficiency are

pallor of the tongue, and patchy atrophy of the lingual papilla. Although the pattern resembles geographic tongue, it is confined to the lateral margins or is generalized to the entire dorsum.

FOLIC ACID DEFICIENCY

Macrocytic anemia with megaloblastic erythropoeisis, accompanied by oral changes , gastrointestinal changes, diarrhea and intestinal malabsorption. Folic acid deficient animals demonstrate necrosis of gingiva, periodontal ligament and alveolar bone without inflammation. The absence of inflammation is due to deficiency induced granulocytopenia.

In humans with sprue and other folic acid deficient states, generalized stomatitis occur, accompanied by ulcerated glossitis and cheilitis.

Fiery red tongue completely Devoid of papilla

Folic acid deficiency

VITAMIN B12 DEFICIENCY

A deficiency of vitamin B12 is rarely caused by insufficient dietary sources unless strict vegan diets are followed.

Lack of intrinsic factor is the primary cause of deficiency.

Pernicious anemia (a megaloblastic anemia) occurs frequently in the elderly relative to achlorhydria and decreased synthesis of intrinsic factor by the parietal cells. Deficiency symptoms develop very slowly.

 Initial oral symptoms develop with Glossopyrosis followed by swelling and pallor with eventual disappearance of the filiform and fungiform papilla. The tongue may be completely smooth, shiny and deeply reddened with loss or distortion of taste. Bright red, diffuse, excruciating painful lesions may occur in the buccal and pharyngeal mucosa and undersurface of the tongue. stomatitis or a pale or yellowish mucosa, xerostomia, cheilosis, hemorrhagic gingival and bone loss. Neurological symptoms like numbness or tingling, occur as a consequence of demyelination of nerves.

VITAMIN C
Vitamin C deficiency in humans result in scurvy, a disease characterized by hemorrhagic diathesis and retardation of wound healing. Clinical manifestations

Increased susceptibility of infections Impaired wound healing Bleeding and swollen gums Mobile teeth Hemorrhagic lesions into the muscles of extremities, joints and sometimes nail beds Petechial hemorrhages often around hair follicles

Possible etiologic relationships between ascorbic acid and periodontal disease

Low levels of ascorbic acid influences the metabolism of collagen within the periodontium, thereby affecting the ability of the tissue to regenerate & repair by itself. It interferes with bone formation leading to the loss of alveolar bone. Increases the permeability of oral mucosa to tritiated endotoxin and tritiated inulin and of normal crevicular epithelium to tritiated dextran. Optimal levels of ascorbic acid is required to maintain the integrity of the periodontal microvasculature as well as the vascular response to bacterial irritation and wound healing. Depletion of vitamin C may interfere with the ecologic equilibirium of bacteria in plaque and increase its pathogenicity.

 Histopathological features
Defective formation and maintenance of collagen Retardation or cessation of osteoid formation & impaired osteoblastic function Increased capillary permeability Susceptibility to traumatic hemorrhages Hyporeactivity of contractile elements of the peripheral blood vessels Sluggishness of blood flow PMNs affected

GINGIVITIS IN VIT.C DEFICIENCY

Gingivitis with enlarged, hemorrhagic, bluish red gingiva is described as one of the classic signs of vitamin C deficiency, Gingivitis is not caused by vitamin C deficiency.

Vitamin C deficiency may aggravate the gingival response to plaque and worsen the edema, enlargement and bleeding.

 Periodontal manifestations
Involve the free gingiva and alveolar mucosa. In severe cases, the gingiva becomes brilliant red, tender and grossly swollen. The spongy tissues are extremely hyperemic and bleed spontaneously. In long standing cases, tissues attain a dark blue or purple hue. Alveolar bone resorption with increased tooth mobility is also been reported

PROTEIN DEFICIENCY
Hypoproteinemia- muscular atrophy, weakness, weight loss, anemia, leucopenia, edema, impaired lactation, decreased resistance to infection slow wound healing, lymphoid depletion and reduced ability to form certain hormones and enzyme systems. Changes in periodontium In the periodontium of experimental animals: Degeneration of the connective tissue of the gingiva and periodontal ligament, osteoporosis of alveolar bone retardation in the deposition of cementum, delayed wound healing.

STARVATION
In a study of controlled semistaravation in young adults there were no changes in the oral cavity or skeletal system despite a 24% loss of body weight. Another study showed a reduction in plaque index scores and a considerable increase in gingival index scores as the fasting period lengthened. In experimental animals, acute starvation results in osteoporosis of alveolar bone and other bones, reduction in the height of alveolar bone and accentuated bone loss associated with gingival inflammation.

HEMATOLOGIC DISORDERS

RED BLOOD CELL DISORDERS

Anemia

Pernicious anemia- Tongue changes in 75% of cases. Tongue appears red, smooth, and shiny, owing to atrophy of the papillae. Marked pallor of the gingiva.
Iron deficiency anemia induces similar tongue and gingival changes- Plummer-Vinson syndrome Sickle cell anemia - Oral changes include generalized osteoporosis of the jaws, with a peculiar stepladder alignment of the trabeculae of the interdental septa, along with pallor and yellowish discoloration of the oral mucosa. Periodontal infections may precipitate sickle cell crisis. Aplastic anemias - Oral changes include pale discoloration of the oral mucosa and increased susceptibility to infection, owing to the concomitant neutropenia.

Acatalasia or acatalasemia
Rare, inherited (autosomal recessive) disorder caused by the lack of catalase in cells, especially red and white blood cells. The neutralisation of catalase protects these cells from harmful oxidising agents which could denature haemoglobin and produce local hypoxia and necrosis of the gingiva. A report by Delgado and Calderon(1979) indicated severe periodontal destruction and gingival necrosis is likely in these patients.

While patients with acatalasia are not generally prone to infections, approximately 2550% suffer an oral condition called Takaharas disease, characterized by painful ulcerations of the gingiva and tonsillar lacunae.

WHITE BLOOD CELLS

Quantitative leucocyte disorders
Neutropenia: Neutrophil count falls below 1,000 cells/ml. An absolute neutrophil count less than 200 cells/ml corresponds with an inability to mount an inflammatory response. Cyclic neutropenia: Periodontal manifestations- inflamed gingiva, gingival ulceration, periodontal attachment and bone loss. Familial neutropenia: Periodontal manifestations- fiery red oedematous gingivitis, which is often hyperplastic and accompanied by periodontal bone loss. Kirstila et al (1993) described a Finnish family with three adolescent siblings affected by neutropenia. Two of the siblings had severe periodontitis and the other sibling presented with oral ulceration.

Leukaemia
Gingival tissues are considered more susceptible to leukaemic cell infiltration. Gingival bleeding is also a common sign in both acute and chronic leukaemia. In some cases there is rapid loss of alveolar bone, usually due to exacerbation of pre-existing periodontitis or as a result of chemotherapy or radiotherapy treatment regimes. Clinical periodontal features include anaemic pallor of the gingivae, bleeding due to platelet deficiency and reduced resistance to infection due to decreased immune and inflammatory cell numbers.

Periodontium in Leukemic Patients

Oral and periodontal manifestations of leukemia consist of Leukemic infiltration Bleeding Oral ulcerations & infections.

Leukemic Infiltration of Periodontium

Leukemic cells can infiltrate the gingiva and, less frequently, the alveolar bone. Gingival infiltration often results in leukemic gingival enlargement. Leukemic gingival enlargement consists of a basic infiltration of the gingival corium by leukemic cells that creates gingival pockets where bacterial plaque accumulates, initiating a secondary inflammatory lesion that contributes also to the enlargement of the gingiva. Gingiva appears initially bluish red and cyanotic, with a rounding and tenseness of the gingival margin; then it increases in size, most often in the interdental papilla and partially covering the crowns of the teeth.

 Bleeding.

Bleeding gingiva can be an early sign of leukemia.

Due to the thrombocytopenia that results from replacement of the bone marrow cells by leukemic cells and also from the inhibition of normal stem cell function by leukemic cells or their products. This bleeding tendency can also manifest itself in the skin and throughout the oral mucosa, where petechiae are often found, with or without leukemic infiltrates. Oral bleeding has been reported as a presenting sign in 17.7% of patients with acute leukemia and in 4.4% of patients with chronic leukemia.

Oral Ulceration and Infection. Granulocytopenia resulting from the replacement of bone marrow cells by leukemic cells reduces the tissue resistance to opportunistic microorganisms and leads to ulcerations and infections.
These lesions occur in sites of trauma such as the buccal mucosa in relation to the line of occlusion or the palate. Acute gingivitis and lesions of necrotizing ulcerative gingivitis are more frequent and severe in terminal cases of acute. The inflamed gingiva differs clinically from inflamed gingiva in nonleukemic individuals. It is a peculiar bluish red, is markedly sponge like and friable, and bleeds persistently on the slightest provocation or even spontaneously. This markedly altered and degenerated tissue is extremely susceptible to bacterial infection, which can be so severe as to cause acute gingival necrosis and pseudomembrane formation.

Classification for the aetiology of gingival lesions in leukaemic patients has been proposed by Barrett.(1984) .
Category 1 is concerned with lesions caused by direct leukaemic infiltration and includes gingival enlargement.

Category 2 deals with direct drug toxicity caused by chemotherapeutic agents.

Category 3 comprises the detrimental effects of graft-versushost reactions. In this disease, the transplanted lymphocytes react against host antigens. Category 4 involves secondary effects from the depression of marrow/lymphoid tissue and includes haemorrhage, neutropenic ulceration and an increased susceptibility to microbial infections.

Qualitative disorders
Neutrophil dysfunction

Qualitative disorders of neutrophil function also increase the hosts susceptibility to infection.
Classification of neutrophil disorders corresponds with the major neutrophil processes: margination (rolling and adhesion), chemotaxis and migration, phagocytosis, degranulation and killing. Defects in the process of margination: LAD I &LAD II Defects in intracellular killing: Chediak Higashi Syndrome

PLATELETS
Thrombocytopenia Thrombocytopenic purpura - Low platelet count, a prolonged clot retraction and bleeding time, and a normal or slightly prolonged clotting time. There is spontaneous bleeding into the skin or from mucous membranes. Petechiae and hemorrhagic vesicles occur in the oral cavity, particularly in the palate, tonsillar pillars, and the buccal mucosa. The gingivae are swollen, soft, and friable. Bleeding occurs spontaneously or on the slightest provocation and is difficult to control. Gingival changes represent an abnormal response to local irritation; the severity of the gingival condition is dramatically alleviated by removal of the local factors.

IMMUNODEFICIENCY DISORDERS
Agranulocytosis.
Ulceration in the oral cavity, oropharynx, and throat is characteristic. The mucosa exhibits isolated necrotic patches that are black and gray and are sharply demarcated from the adjacent uninvolved areas. The absence of a notable inflammatory reaction due to lack of granulocytes is a striking feature.

The gingival margin may or may not be involved. Gingival hemorrhage, necrosis, increased salivation, and fetid odor are accompanying clinical features. The occurrence of rapidly destructive periodontitis has been described in cyclic neutropenia.

 ANTIBODY DEFICIENCY DISORDERS Agammaglobulinemia. Agammaglobulinemia results from a deficiency in B cells; T-cell function remains normal. It can be congenital (X-linked or Bruton's agammaglobulinemia) or acquired. The disease is characterized by recurrent infections, including destructive periodontitis in children

ACQUIRED IMMUNODEFICIENCY SYNDROME. Acquired immunodeficiency syndrome (AIDS) is caused by the human immunodeficiency virus (HIV) and is characterized by destruction of lymphocytes, rendering the patient susceptible to opportunistic infections, including destructive periodontal lesions and malignancies.

CARDIOVASCULAR DISEASE

CARDIOVASCULAR DISEASES
Congenital Heart Disease

Arteriosclerosis

Tetralogy of Fallot

Eisenmengers Syndrome

ARTERIOSCLEROSIS Both periodontal disease and arteriosclerosis increase with age.

Circulatory impairment induced by vascular changes may increase the patient's susceptibility to periodontal disease.
Conversely, there is recent evidence to suggest that individuals with periodontal disease may be at greater risk for heart disease as a result of chronic periodontal infections and inflammation. In experimental animals, partial ischemia of more than 10 hours' duration created by arteriolar occlusion produces changes in the oxidative enzymes and acid phosphatase activity and in the glycogen and lipid content of the gingival epithelium. Focal necrosis, followed by ulceration, occurs in the epithelium, with the junctional epithelium least affected. Changes typical of periodontal disease do not occur. Ischemia is followed by hyperemia, which is accompanied by metabolic changes and increased DNA synthesis in the epithelium. The gingival response to arteriolar occlusion is epithelial proliferation and thickening.

 Tetralogy of Fallot 1. Ventricular septal defect 2. pulmonary stenosis 3. malposition of the aorta to the right 4. Compensatory right ventricular enlargement. The oral changes include a purplish red discoloration of the lips and gingiva and sometimes severe marginal gingivitis and periodontal destruction. The discoloration of the lips and gingivae corresponds to the general degree of cyanosis and returns to normal after corrective heart surgery. The tongue appears coated, fissured, and edematous, and there is extreme reddening of the fungiform and filiform papillae.

 Eisenmengers Syndrome Among patients with ventricular septal defects, about half with large defects (>1.5 cm in diameter) develop Eisenmenger syndrome. This syndrome is distinguished by a greater blood flow from stronger left ventricle to the right ventricle (backward flow) through the septal defect causing increased pulmonary blood flow, which in turn leads to progressive pulmonary fibrosis, small vessel occlusion, and high pulmonary vascular resistance. The natural history of a patient with untreated Eisenmengers syndrome is a gradual increase in cyanosis over many years, eventually leading to cardiac failure. In cases of Eisenmenger syndrome, the lips, cheeks, and buccal mucous membranes are cyanotic, but markedly less so than in tetralogy of Fallot. Severe generalized marginal gingivitis may be found.

GENETIC DISORDERS

GENETIC DISORDERS
Marfan syndrome Connective tissue alterations: Ehler-Danlos syndrome. severe congenital neutropenia infantile genetic agranulocytosis or Kostmann syndrome (IGA) Chediak-Higiashi syndrome Immune alterations Down syndrome

Papillon-Lefvre syndrome

hyperimmunoglobulinemia E syndrome

CONNECTIVE TISSUE ALTERATIONS

Ehlers-Danlos Syndrome (EDS)
Covers a group of connective tissue disorders that are characterized by defective defective collagen synthesis.
Autosomal dominant Mainly affect the joints and skin. Types IV and VIII have an increased susceptibility to periodontitis. Type VIII- in particular is associated with fragile oral mucosa and blood vessels and severe generalized periodontitis with the clinical appearance of generalized early-onset periodontitis. In EDS type VIII - there is considerable interfamilial variability but the distinguishing finding is periodontitis, resembling clinically the early-onset form, leading to premature loss of permanent teeth.

2.Marfan Syndrome
Generalized disorder of connective tissue with skeletal, ocular, and cardiovascular malformations. Characteristically these patients are tall and thin with arachnodactyly and joint hypermobility. In the case of Marfan syndrome, periodontitis manifests in a chronic and severe form with patterns of both horizontal and vertical bone resorption, and in accordance to the presence of bacterial plaque. Dental mobility has been shown to be due to periodontitis, and is not attributable to the primary condition of the syndrome.

GENETIC DISORDERS RESULTING IN IMMUNE

ALTERATIONS

1. Downs Syndrome
Periodontal disease is characterized by a generalized early periodontitis, which commences in the deciduous dentition and continues into the adult dentition. Even though oral hygiene of these patients is poor the periodontal destruction in these patients exceeds that explainable by local factors alone. Periodontal disease is characterized by Deep periodontal pocket moderate gingivitis Commonly seen in lower anterior region Marked recession associated with high frenal attachment Acute necrotizing lesion is a frequent finding

 The high prevalence of periodontitis in down syndrome patients is explained by a. Reduced resistance due to poor circulation especially in those area of terminal vascularization such as gingival tissue and defect in T cell maturation and PMN chemotaxis b. Increase in number of P. intermedia in mouths of children with down syndrome

2. Leukocyte Adhesion Deficiency Syndrome

Autosomal recessive disease.

Deficiencies in expression of the Leucocyte Function Adhesion family of adhesins.

Children with deficiencies in expression of the Leucocyte Function Adhesion family of adhesins have been reported as suffering from severe periodontal infections, data relating adult periodontitis to this condition are not available.

3. Papillon-Lefevre syndrome
An autosomal recessive disease due to mutation in the cathepsin C gene
Etiology is variable --deficits in chemotaxis, phagocytosis and intra cellular killing. Hyperkeratosis of palms and soles Generalised rapid destruction of the periodontal attachment apparatus, resulting in premature loss of both the dentitions. Other findings: Ectopic calcification of falx ceribri and choriod plexus. Increased susceptibility to infections Mental retardation Endocrine disorders Aggressive periodontitis

4. Chediak Higashi Syndrome

Rare autosomal recessive disorder affecting neutrophils, due to mutation in the vesicle trafficking regulatory gene. Manifests early in life as Occulo cutanous albinism Photophobia Pyogenic infections and lymph adenopathy Oral findings include 1. Gingivitis 2. Ulcerations of both tongue and buccal mucosa 3. Early onset periodontitis leading to loss of both the dentitions. Hallmark -large Azurophilic granules in the cytoplasm of the neutrophils.- impair neutrophil migration which causes neutrophils unable to phagocytose microbes.

5. Hypophosphatasia
Patients with this condition have a decreased serum alkaline phosphatase and severe loss of alveolar bone and premature loss of the deciduous teeth, particularly anteriorly. Microscopically, the teeth show either complete loss of cementum or isolated areas of cementum resorption.

6. Congenital neutropenia (Kostmann syndrome)

Inherited hematologic disorder manifesting in the first year of life and characterized by severe bacterial infections.

Absolute neutrophil count of less than 2,000/ml and an arrest of neutrophil hematopoiesis at the promyelocyte/myelocyte stage.
While most of the originally reported cases died in infancy, aggressive treatment with antibiotics has more recently prolonged the lifespan of children suffering from this disease.

7. Feltys syndrome
Uncommon complication of rheumatoid arthritis, in which splenomegaly and leukopenia are the major additional features. leukopenia noted in Feltys syndrome - due to a lack of circulating neutrophils. Breedveld et al. monitored a variety of hematologic parameters in a group
of 15 patients at 3-month intervals for 3 years. Relating the presence of infections in these patients to laboratory values, the authors determined that the risk of infection was best correlated with neutrophil counts <1,000/ml, rather than some functional deficiency of neutrophil cells.

8. Lazy leukocyte syndrome

An extremely rare disorder that manifests in both quantitative and qualitative neutrophil defects.

Recurrent infections due to both a deficiency in neutrophil chemotaxis and a systemic neutropenia.
Impaired random and directional motility leads to a diminished in vivo migration of neutrophils into the tissue and to sites of inflammation.

9. Chronic Granulomatous Disease

Rare disease with 2 genetic forms, autosomal recessive and Xlinked recessive. The defect in this disease is in the ability of phagocytic cells to perform killing by the oxidative pathway after ingestion. Kinane (1990) described a family with the X-linked recessive form of chronic granulomatous disease. Erythema of the gingiva and oral mucosa with occasional ulceration were seen, no periodontal manifestations were attributable to this condition.

10. Glycogen storage disease type 1b

Autosomal recessive disorder caused by a defect in the glucose6-phosphate transporter protein. Clinical features :dolllike facial appearance, stunted growth, hypoglycemia, ketosis, lactic acidosis, hyperlipidemia, gout, and bleeding episodes brought on by impaired platelet function secondary to metabolic disorders. Additional distinguishing features of glycogen storage disease type 1b are neutropenia, neutrophil dysfunction, and an increased susceptibility to infection. Defects in both random and directed PMN migration.

Reports of oral disease in glycogen storage disease type 1b patients are common & include: Oral Ulceration Candidiasis Gingivitis And Periodontitis. Dougherty & Gataletto described a case of generalized aggressive periodontitis in a child with glycogen storage disease type 1b.

EFFECT OF SYSTEMIC DRUG THERAPY

Membrane Ion-Channel Blockers

Influence gingival fibroblasts to overproduce collagen matrix and ground substance when stimulated by gingival inflammation following plaque build-up unfavorable gingival form and false pocketing may be plaque retentive and thus might be local modifiers of periodontitis.

Anti-epileptic drugs
Gingival overgrowth occurs in about half of all individuals who ingest phenytoin on a chronic regimen. prevalence higher than it is when phenytoin is taken in combination with other antiepileptic agents.

Cyclosporine
exerts its effect by selective suppression of specific subpopulation s of T lymphocytes, interfering with production of lymphokines and IL 1 and 2.

No evidence linking the use of these medicines with periodontitis.

gingival lesions are often clinically and histologically indistinguishable from those elicited by phenytoin.

PHENYTOIN INDUCED ENLARGEMENT

COLLAGEN VASCULAR DISORDERS

SJOGRENS SYNDROME
Primary -sicca syndrome Secondary form Study by Najera et al (1997)
dryness of the eyes and mouth.

triad of dry eyes with keratoconjunctivitis sicca, xerostomia and an associated autoimmune disease, usually rheumatoid arthritis

2.2 higher risk of having adult periodontitis.

RHEUMATOID ARTHRITIS
Occurrence of Sjogrens syndrome in approx. 15% of such patients. More than 50% of Sjogrens patients are affected by rheumatoid arthritis.

deterioration of TMJ
loss of vertical dimension of the condyle anterior open bite.

excessive occlusal forces in the molar regions

lost bone support from extrusion of the anterior teeth.

LUPUS ERYTHEMATOSUS
chronic autoimmune disease that affects the connective tissue and multiple organ systems. An increased incidence of infection in systemic lupus erythematosus patients is an often-reported finding. It is estimated that at least 50% of systemic lupus erythematosus patients will suffer an infection during the course of the disease. Hematologic disorders that may explain this increased incidence of infection are a tendency to neutropenia and various neutrophil abnormalities. oral manifestation - formation of multiple white plaques with dark, reddish or purple margins with a tendency to form telangiectasia and ulceration.

 little information on the periodontal status of systemic lupus erythematosus patients. In an uncontrolled study of 16 women with systemic lupus erythematosus, Rhodus & Johnson found periodontitis in all but one of them. Novo et al. observed periodontitis in 60% of 30 systemic lupus erythematosus patients compared to 50% in a control group with rheumatoid arthritis.

In a comparison of the periodontal status of systemic lupus erythematosus patients with age and sex-matched controls, Mutlu et al. found that the SLE patients had significantly shallower probing depths than the control group.

PROGRESSIVE SYSTEMIC SCLEROSIS AND CREST SYNDROME

Most conspicuous oral manifestation - fibrosis of the facial skin to affect 35% of Sjogrens syndrome patients. 39% of patients complained of dysphagia and 28% reported limited mouth opening as a consequence of the sclerosis. The advanced progression of facial tissue fibrosis has been described as the cause for resorption of the mandibular bone in the area of the mandibular angles . A relatively characteristic oral manifestation of progressive systemic sclerosis is the radiographic demonstration of apparent widening of the periodontal ligament space. This typically affects posterior teeth and the pdl space may be increased as much as 3-4 times the normal thickness.

Uniform widening of pdl space in systemic sclerosis

PSYCHOSOMATIC DISORDERS
Harmful effects that result from psychic influences on the organic control of tissues are known as psychosomatic disorders

2 ways in which psychosomatic disorders may be induced in the oral cavity are: 1. through the development of habits that are injurious to the periodontium. 1. by the direct effect of the autonomic nervous system on the physiologic tissue balance.

 PSYCHIATRIC INFLUENCE OF SELF INFLICTED INJURY

under conditions of mental and emotional stress, the mouth may subconsciously become an outlet for the gratification of basic drives in the adult. Gratification may be derived from neurotic habits, such as grinding or clenching the teeth; nibbling on foreign objects (e.g., pencils or pipes); nail biting; or excessive use of tobacco, which are all potentially injurious to the periodontium.
Self-inflicted gingival injuries such as gingival recession have been described in both children and adults.

SELF INFLICTED INJURY ON GINGIVA DUE TO SCRATCHING OF AREA

GINGIVITIS
Stress diminishes saliva flow and increases dental plaque formation. Emotional stress modifies the saliva pH and its chemical composition like the IgA secretion. Deinzer et al. (1999-2001)- examined the impact of academic stress by students at university during their examination period on periodontal health. Academic stress was shown to be a risk factor for gingival inflammation with increasing crevicular interleukin-1 levels and a diminution of the quality of the oral hygiene. In a pilot study in 1998, Axtelius showed the presence of cortical in gingival crevicular fluid. A study by Johanssen (2006) confirm the fact that the concentration of cortisol in the gingival crevicular fluid is higher by person showing depression signs.

NECROTIZING PERIODONTAL DISEASES

The first reports were written about mouth pain among the soldiers of Alexander the Great. The first studies showing this influence were made by Pindborg (1951) (higher number of necrotic periodontitis during military service) and in 19631964 by Giddon (more necrotic periodontitis in college during examination period). The presence of NUG in soldiers stressed by war time conditions in the trenches lead to one of the early diagnostic terms used to describe this condition, trench mouth.

The main risk factors for necrotic periodontitis and previous episode are: past episode of necrotic periodontitis, bad oral hygiene, bad sleep, unusual emotional stress, tobacco, alcohol, bad alimentation and recent illness. Many of those factors are often related to stress.

CHRONIC PERIODONTITIS
Linden et al. predicted the future attachment loss depending on the following criteria: age, socio-economical level, a less satisfactory professional life and a passive and dependant character. Axtelius (1998) has suggested that patients with psychosocial strain and passive dependent traits did not respond as well as patients with less stressful psychosocial situation and with a rigid personality to periodontal treatment.

The real relationship between stress and chronic periodontal disease is difficult to establish and more research needs to be done.

AGGRESSIVE PERIODONTITIS

Page et al. (1983)

Monteira da Silva (1996)
Kamma and Baehni

established link existing between aggressive periodontitis and psycho-social factors and loss of appetite.

showed that people with aggressive periodontitis were more depressed and more socially isolated people than people with chronic periodontitis or a control group.

evaluated the clinical and microbiological status of patients with early onset periodontitis who had received supportive periodontal care every 36 months for a period of 5 years following active periodontal treatment. Results showed that supportive periodontal care was effective, but some sites in some patients were still progressive. These variables were related to the progression of the disease: Bacterial load, number of acute episodes, number of teeth lost, smoking and stress.

These studies show the relationship existing between aggressive periodontitis and psychosocial stress.

PERIODONTAL TREATMENT
Kamma and Baehni- supportive periodontal care was more effective in patients with aggressive periodontitis harbouring less stress. Wimmer et al. explain the influence of coping with stress on periodontal therapy and conclude that patients with maladaptative coping strategies have more advanced disease and poor response to a non-surgical periodontal treatment. Thus maladaptative behaviors, especially in association with other risk factors (like smoking) are of great importance in the medical history, treatment and maintenance of patients with periodontal disease. Gamboa et al. (2005), show the influence of Emotional Intelligence (a measure of the coping mechanisms) on the initial responses to periodontal treatment in patients with chronic periodontitis. Reductions of dental plaque and gingival bleeding were positively correlated in patients having an active coping

OTHER SYSTEMIC CONDITIONS

METAL INTOXICATION

Bismuth Intoxication
Chronic
GI disturbances, nausea, vomiting Jaundice Ulcerative gingivostomatitis, generally with pigmentation and accompanied by a metallic taste and burning sensation of the oral mucosa. Tongue may be sore and inflamed.
Urticaria, exanthematous eruptions , herpes zoster like eruptions and pigmentation of the skin and mucous membranes

Acute
Methemoglobin formation

Cyanosis

Dyspnea.

Bismuth pigmentation in the oral cavity

narrow, bluish-black discoloration of the gingival margin in areas of preexistent gingival inflammation. Such pigmentation results from the precipitation of particles of bismuth sulfide associated with vascular changes in inflammation. It is not evidence of intoxication but simply indicates the presence of bismuth in the bloodstream.

Bismuth pigmentation in the oral cavity also occurs in cases of intoxication. It assumes a linear form if the marginal gingiva is inflamed.

Lead Intoxication.
Pallor of the face and lips and gastrointestinal symptoms consisting of nausea, vomiting, loss of appetite, and abdominal colic. Peripheral neuritis, psychologic disorders, and encephalitis have been reported. Oral signs- salivation, coated tongue, a peculiar sweetish taste, gingival pigmentation, and ulceration. The pigmentation of the gingiva is linear (burtonian line), steel gray, and associated with local irritation. Oral signs may occur without toxic symptoms.

Mercury Intoxication
Headache, insomnia, cardiovascular symptoms, pronounced salivation (ptyalism), and a metallic taste.

Gingival pigmentation in linear form results from the deposition of mercuric sulfide.
The chemical also acts as an irritant, which accentuates the preexistent inflammation and commonly leads to notable ulceration of the gingiva and adjacent mucosa and destruction of the underlying bone. Mercurial pigmentation of the gingiva also occurs in areas of local irritation in patients without symptoms of intoxication.

TOBACCO USE

Vascular
constriction of the blood vessels of the gingiva

Immune
deleterious effects on leukocyte function.

Direct effects on tissues

cytotoxic substances can penetrate the epithelium and may exert deleterious effects on fibroblasts.

Bone
decreases intestinal absorption of calcium and may thereby affect osteoblast function and increase bone loss in otherwise healthy postmenopau sal women.

Healing
Postsurgical healing may be interfered with by absorption of the toxic substances in tobacco smoke by the root surfaces.

suppress serum antibody levels to certain periodontal bacteria.

suppresses production of the IgG2 both in patients with periodontitis and in those with normal periodontium.

 1983, Ismail and co-workers analyzed smoking and periodontal disease and found that smoking remained a major risk indicator for periodontal disease after adjusting for potential confounding variables, such as age, oral hygiene, and socioeconomic status. Grossi and co-workers also found a direct and linear dose response between level of smoking (pack years) and destructive periodontitis, supporting the contention that smoking is a risk factor for periodontal disease. Longitudinal studies have confirmed that current smokers exhibited greater disease progression as compared with nonsmokers. Attachment loss is also directly related to serum cotinine levels.

 While there is no evidence that the use of smokeless tobacco increases susceptibility to periodontal disease, smokeless tobacco may affect gingival inflammation by affecting levels of IL-1 and PGE2 in gingival tissues. Although there is no direct evidence, it is likely that cigar and pipe smoking will have effects similar to cigarette smoking if the exposures are comparable.

CONCLUSION