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Oral Manifestations of Systemic Diseases (II) Dr. Suhail S. Kishawi Consultant in Endocrinology and Diabetes
Oral Manifestations of Systemic
Diseases (II)
Dr. Suhail S. Kishawi
Consultant in Endocrinology and Diabetes
يواشيقلا فيرش ليهس .د
يركسلاو ءامصلا ددغلا يراشتسأ
ةينطابلا ضارملأا يراشتسأ

Oral Manifestations of Systemic Diseases

Many systemic diseases are reflected in the oral mucosa, maxilla,

and mandible.

Mucosal changes may include ulceration or mucosal bleeding.

Immunodeficiency can lead to opportunistic diseases such as infection and neoplasia.

Bone disease can affect the maxilla and mandible.

Systemic disease can cause dental and periodontal changes.

Drugs prescribed for a systemic disease can affect oral tissue.

Oral Manifestations of Systemic Diseases

Local factors may be involved in the manifestation of systemic

disease in oral mucosa.

The mucosa may be more easily injured due to a systemic disease, and mild irritation and chronic inflammation may cause lesions that otherwise would not occur.

These may include

Endocrine disorders, disorders of red and white blood cells, disorders of platelets and other bleeding and clotting disorders, and immunodeficiency disorders

Blood Disorders

Disorders of Red Blood Cells and Hemoglobin

Disorders of White Blood Cells

Bleeding Disorders

Blood Disorders

The complete blood count examines red blood cells, white blood cells, and platelets.

It provides information about the number of each type of

cell, the ratio of types, and the appearance of the cells.

Disorders of Red Blood Cells

and Hemoglobin

Iron Deficiency Anemia

Pernicious Anemia

Folic Acid and Vitamin B 12 Deficiency Anemia

Thalassemia

Sickle Cell Anemia

Celiac Sprue

Aplastic Anemia

Polycythemia

Normal CBC

Normal CBC

Anemia

A reduction in the oxygen-carrying capacity of blood

Most often related to a decrease in the number of circulating red blood cells

Nutritional anemias

A deficiency in a substance required for the normal development of red blood cells, commonly vitamins

Suppression of bone marrow stem cells

Symptoms
Symptoms

Lack of

Concentration

Infection

Irritability

Symptoms Lack of Concentration Infection Irritability Fatigue Palpitation Dizziness Weakness

Fatigue

Palpitation

Symptoms Lack of Concentration Infection Irritability Fatigue Palpitation Dizziness Weakness
Symptoms Lack of Concentration Infection Irritability Fatigue Palpitation Dizziness Weakness

Dizziness

Weakness

Symptoms Lack of Concentration Infection Irritability Fatigue Palpitation Dizziness Weakness
Clinical Features •Pallor of skin Soft ejection systolic murmur •And m/m Edema Signs Tachycardia Koilonychia
Clinical Features
•Pallor of skin
Soft ejection
systolic murmur
•And m/m
Edema
Signs
Tachycardia
Koilonychia
Glossitis
Stomatitis

Anemia

Clinical features

Pallor of skin and oral mucosa

Angular cheilitis Erythema and atrophy of oral mucosa

Loss of filiform and fungiform papillae on the dorsum of the tongue

Iron Deficiency Anemia

An insufficient amount of iron is supplied to bone marrow for red

blood cell development.

May occur as a result of deficient iron intake, blood loss from heavy menstrual bleeding or chronic gastrointestinal bleeding, poor iron absorption, or an increased requirement for iron in situations such as pregnancy or infancy

Plummer-Vinson syndrome may result from long standing iron deficiency anemia.

Includes dysphagia, atrophy of the upper alimentary tract, and a predisposition to developing oral cancer

Clinical Features and Oral Manifestations of Iron

Deficiency Anemia

Often asymptomatic, may have nonspecific symptoms such as weakness and fatigue

In severe cases may see angular cheilitis, pallor of oral tissue, and an erythematous, smooth, painful tongue

Clinical Features and Oral Manifestations of

Iron Deficiency Anemia

Clinical Features and Oral Manifestations of Iron Deficiency Anemia

Pernicious Anemia

Probably an autoimmune disorder in most situations   May be caused by removal of
Probably an autoimmune disorder in most situations   May be caused by removal of
Probably an autoimmune disorder in most situations   May be caused by removal of
Probably an autoimmune disorder in most situations
May be caused by removal of the stomach, gastric cancer,
or gastritis
Caused by a deficiency in intrinsic factor
 Intrinsic factor is secreted by parietal cells in the
stomach; it is necessary for absorption of vitamin B 12
Vitamin B 12
Vitamin B 12

There are a number of key steps in the absorption of Vitamin B 12 . The two key locations are the stomach and the terminal ilium. Dietary vitamin B 12 binds with intrinsic factor (IF) in the stomach, a transport protein produced by gastric parietal cells. The B12-IF complex then travels through the small intestine and is absorbed by special receptors in the distal ileum. This pathway is important when considering possible causes of Vitamin B 12 deficiency.

Causes of

vitamin B12

deficiency

1. Pernicious

anaemia

2. Inadequate

intake

3. Poor

absorption

•Oesophagus •Vitamin B 12 ingested •Stomach •IF Intrinsic factor •Distal ileum •Site of B 12
•Oesophagus
•Vitamin B 12
ingested
•Stomach
•IF Intrinsic factor
•Distal ileum
•Site of B 12
absorption

Vitamin B 12 deficiency can take up to two years to develop as the body has sufficient stores for this period.

Pernicious anaemia:

the leading cause of B 12 deficiency. IgG

autoantibodies

target gastric parietal cells and its product IF causing an atrophic gastritis. This results in reduced secretion of intrinsic factor and therefore reduced B 12 - IF complex for absorption in the distal ileum.

Clinical Features and Oral Manifestations of

Pernicious Anemia

Weakness, pallor, and fatigue on exertion,nausea, dizziness, diarrhea, abdominal pain, loss of appetite, and weight loss

Angular cheilitis, mucosal pallor, painful atrophic and erythematous mucosa, mucosal ulceration, loss of papillae on the dorsum of the tongue, and burning and painful tongue

Clinical Features and Oral

Manifestations of Pernicious Anemia

Clinical Features and Oral Manifestations of Pernicious Anemia
Clinical Features and Oral Manifestations of Pernicious Anemia

Folic Acid and Vitamin B 12 Deficiency Anemia

From dietary deficiencies

Can occur in association with malnutrition

May be found with alcoholism or pregnancy

Oral Manifestations of Folic Acid and Vitamin B 12 Deficiency Anemia

Oral manifestations are indistinguishable from those of pernicious anemia.

Thalassemia (Mediterranean Anemia)  A group of inherited disorders of hemoglobin synthesis  An autosomal

Thalassemia

(Mediterranean Anemia)

A group of inherited disorders of hemoglobin synthesis

An autosomal dominant inheritance pattern

The heterozygous form may be mildly symptomatic or asymptomatic.

The homozygous form is associated with severe hemolytic anemia.

Clinical Features and Oral Manifestations of

Thalassemia

Yellow skin & pallor, fever, malaise, and weakness

The face includes prominent cheekbones, depression of the bridge of the nose, a prominent maxilla, and protrusion or flaring of maxillary anterior teeth.

Radiographs of skull may show marked vertical striation (hair on end appearance)

Skull x-ray in a 5 year old boy with thalassemia major Marked vertical striations give

Skull x-ray in a 5 year old boy with thalassemia major Marked vertical striations give the appearance of hair standing on end

Sickle Cell Anemia

An inherited blood disorder

When someone is heterozygous, it is called sickle cell trait.

When someone is homozygous, they are much more severely affected.

Occurs before age 30 and is more common in women than in men

The red blood cells develop a sickle shape when there is

decreased oxygen.

This can be triggered by exercise, exertion, administration of a general anesthetic, pregnancy, or even sleep.

Clinical Features and Oral Manifestations of

Sickle Cell Anemia

The person has weakness, shortness of breath, fatigue, joint pain, and nausea.

Radiographic

There is a loss of trabeculation, and large, irregular marrow

spaces appear.

A “hair-on-end” pattern may be seen in the skull.

Clinical Features and Oral Manifestations of

Sickle Cell Anemia

Clinical Features and Oral Manifestations of Sickle Cell Anemia

Celiac Sprue

A chronic disorder due to sensitivity to wheat gluten

Ingestion causes injury to intestinal mucosa.

This injury may cause malabsorption of nutrients and a resulting

anemia.

Clinical Features and Oral Manifestations of

Celiac Sprue

Symptoms include diarrhea, nervousness, and paresthesia.

Painful, burning tongue, atrophy of papillae, and ulceration of oral

mucosa

Aplastic Anemia

A severe depression of bone marrow activity causes a decrease in all circulating blood cells. pancytopenia

Primary aplastic anemia the cause is unknown

Secondary aplastic anemia a result of a drug or chemical agent

Aplastic Anemia

Aplastic Anemia

Oral Manifestations of Aplastic Anemia

Infection, spontaneous bleeding, petechiae, and purpuric spots

 Infection, spontaneous bleeding, petechiae, and purpuric spots

Polycythemia

Characterized by an increase in the number of circulating red blood cells

May be absolute or relative

The three forms of polycythemia are

Polycythemia Vera

Secondary Polycythemia

Relative Polycythemia

Polycythemia Vera (Primary Polycythemia)

A neoplastic proliferation of bone marrow stem cells causes an abnormally high number of circulating red blood cells.

Unknown cause

More common in men than in women

Age of onset usually between 40 and 60 years of age

Clinical features

Headache, dizziness, and itching (pruritus)

Thrombi may form.

Secondary Polycythemia

The increase in red blood cells is caused by a physiologic response to decreased oxygen.

A decrease in blood oxygen causes an increase in erythropoietin by the kidneys.

May be due to pulmonary disease, heart disease, living at high altitude, or elevation in carbon monoxide

Relative Polycythemia

Caused by a decrease in plasma volume

Causes may include diuretics, vomiting, diarrhea, or excessive sweating.

Most patients are middle-aged white men under physiologic stress, mildly overweight, hypertensive, and heavy smokers.

Oral Manifestations of Polycythemia

The oral mucosa may appear deep red to purple; the gingiva may be edematous and bleed easily.

Submucosal petechiae, ecchymosis, and hematoma formation may be present.

Disorders of White Blood Cells

Agranulocytosis

Leukemia

Disorders of White Blood Cells

Three groups of white blood cells are found in

circulation.

Granulocytes

Neutrophils (PMNs), eosinophils, and basophils

Lymphocytes

Monocytes

Agranulocytosis

A significant reduction in circulating neutrophils

Leukopenia an abnormally low white blood cell count

Neutropenia a reduction in the number of circulating

neutrophils

Agranulocytosis

Can result from a problem in development of neutrophils or accelerated destruction of neutrophils

Primary the cause is unknown, may be an immunologic disorder

Secondary a result of chemicals or drugs

Clinical Features and Oral Manifestations of

Agranulocytosis

Sudden onset of fever, chills, jaundice, weakness, and sore throat

Oral infection

AGRANULOCYTOSIS

(White Blood Cell disorder)

A marked reduction in circulating neutrophils.

A sudden onset of a severe sore throat.

A marked presence of infection in the mouth:

Necrotizing ulcerations

Excessive bleeding from the gingiva

Rapid destruction of supporting tissue of the teeth

Regional lymphadenopathy

Excessive bleeding from the gingiva

Excessive bleeding from the gingiva

Necrotizing ulcerations

Necrotizing ulcerations

Regional lymphadenopathy

Regional lymphadenopathy

Leukemia

Malignant neoplasms of hematopoietic stem cells

Characterized by an excessive number of abnormal white blood cells in circulating blood

Unknown cause; may be due to oncogenic viruses

There are many different types categorized as to whether they are acute or chronic.

Acute Leukemias

Characterized by very immature cells and a rapidly fatal course if not treated

Acute lymphoblastic leukemia involves immature lymphocytes

Primarily affects children and young adults

Good prognosis

Acute myeloblastic leukemia involves immature granulocytes

Primarily affects adolescents and young adults.

Prognosis is not as good as lymphatic.

Clinical and Oral Features of Acute Leukemias

Weakness, fever, enlargement of

lymph nodes, and bleeding

Gingival enlargement

Oral infection

Bleeding gums, petechiae and ecchymosis

lymph nodes, and bleeding  Gingival enlargement  Oral infection  Bleeding gums, petechiae and ecchymosis

Chronic Leukemias

Slow onset

Primarily affect adults

Clinical Features and Oral Manifestations of Chronic

Leukemias

Easy fatigability, weakness, weight loss, anorexia

Pallor of lips and gingiva, gingival enlargement, petechiae and ecchymosis, gingival bleeding

Bleeding Disorders

Hemostasis

Purpura

Hemophilia

Hemostasis

A cessation of bleeding

Circulating platelets adhere to a damaged surface and aggregate to form a temporary clot.

Fibrin binds the platelets

Fibrin is converted from fibrinogen by a cascade of circulating proteins.

Defects may be caused by abnormalities of either platelets or coagulation factors.

These may be determined with laboratory tests.

Hemostasis

Hemostasis
Hemostasis
Coagulation Cascade
Coagulation Cascade
Coagulation Cascade

(aPTT)

(PT)

(aPTT, PT, TT)

Hemostasis

Hemostasis
Hemostasis

Platelet Count

To determine the number of platelets

Normal is 150,000 to 400,000/mm 3

Spontaneous gingival bleeding may occur if the count is less than 20,000/mm 3

Bleeding Time

The adequacy of platelet function

Normal is between 1 and 6 minutes.

Prolonged is greater than 5 or 10 minutes.

Prothrombin Time (PT)

The ability to form a clot

Normal is usually between 11 and 16 seconds.

INR is the ratio of PT to thromboplastin activity.

Values less than 3 are considered normal.

Patients on anticoagulants may have INR values of 4 to 5.

Partial Thromboplastin Time (PTT)

Measures the other way by which clot formation occurs

A normal PTT is usually 25 to 40 seconds.

Prolongation to 45 or 50 seconds may be associated with

bleeding problems.

Over 50 seconds may be severe

Purpura

A reddish-blue or purplish discoloration of skin or mucosa from spontaneous extravasation of blood

May be due to a defect or deficiency in blood platelets

Blood may ooze from gingival margins.

Thrombocytopenic Purpura

A bleeding disorder that results from a severe reduction in circulating platelets

Idiopathic thrombocytopenic purpura

If the cause is unknown

Immune thrombocytopenia

An autoimmune type of process

Secondary thrombocytopenic purpura

Often associated with drugs

Clinical and Oral Manifestations of

Thrombocytopenic Purpura

Spontaneous purpuric or hemorrhagic lesions on the skin

Patients bruise easily, may have blood in urine, and have frequent nosebleeds.

Nonthrombocytopenic Purpura

Bleeding disorders that can result from either a defect in

capillary walls or disorders of platelet function

Vitamin C deficiency and infections or chemicals and allergy may be the cause of alterations in vascular walls.

Drugs, allergy, and autoimmune disease may cause disorders of platelet function.

Von Willebrand disease is an autosomal dominant disorder of platelet function.

Oral Manifestations of Nonthrombocytopenic

Purpura

Spontaneous gingival bleeding, petechiae, ecchymoses, and hemorrhagic blisters

Hemophilia

 A disorder of blood coagulation  Results in severely prolonged clotting time  Due

A disorder of blood coagulation

Results in severely prolonged clotting time

Due to a deficiency in plasma proteins involved in coagulation

Types of Hemophilia

The two most common types are type A and type B.

Transmitted as X-linked diseases through an unaffected carrier daughter to a son

Type A

Caused by a deficiency of plasma thromboplastinogen or factor VIII

Type B

Christmas disease

Less common, the clotting defect is plasma thromboplastin or

factor IX

Oral Manifestations of Hemophilia

Spontaneous gingival bleeding, petechiae, and ecchymosis

After an injection on person with hemophilia

After an injection on person with hemophilia

Diagnosis and Treatment of Hemophilia

The bleeding time and PT in hemophilia are normal; the PTT is prolonged.

Diagnosis involves identifying the missing factor; treatment involves replacing it.

Immunodeficiency

Can involve the different parts of the immune system either alone or together

May involve a deficiency in cell-mediated or humoral immunity

May involve deficiency in phagocytosis

Divided into

Primary immunodeficiency of genetic origin

Secondary immunodeficiency from another underlying disorder

Primary Immunodeficiencies

Of genetic origin

May involve B cells, T cells, or both

Very rare

Bruton disease (X linked congenital

agammaglobulinemia)

DiGeorge syndrome (thymic hypoplasia)

Severe combined immunodeficiency

Secondary Immunodeficiencies
Secondary Immunodeficiencies
Secondary Immunodeficiencies

Secondary Immunodeficiencies

Occur as the result of an underlying disorder

May be malnutrition, viral infection, cancer, renal disease and Hodgkin’s disease

May occur with immunosuppressive drugs, drugs used

along with radiation, chemotherapy

Oral Manifestations of Therapy for Oral Cancer

Radiation Therapy

Chemotherapy

Oral Manifestations of Therapy for Oral

Cancer

Oral cancer can be treated with surgery, radiation therapy, or chemotherapy, or a combination.

Radiation Therapy

The patient often experiences mucositis during radiation therapy.

Mucositis begins about the second week of therapy and subsides a few weeks after its completion.

It is painful and appears as an erythematous and ulcerated mucosa.

The patients may have difficulty eating, pain on swallowing, and loss of taste.

erythematous and ulcerated mucosa.  The patients may have difficulty eating, pain on swallowing, and loss

Radiation Therapy

Destruction of major salivary glands may result in xerostomia

The patient is prone to rampant caries and oral candidiasis.

They also are prone to osteoradionecrosis.

 The patient is prone to rampant caries and oral candidiasis.  They also are prone

Radiation Therapy

Patients should have an oral evaluation before radiation

therapy of the head and neck.

Potential sources for oral infection and teeth with a questionable prognosis should be removed.

The hygienist can help with

Fluoride application

Patient education

Frequent follow-up appointments

Chemotherapy

Drugs used for cancer chemotherapy affect basal cells of the epithelium.

Mucositis and oral ulceration are common complications.

A decrease in all blood cells may occur

Lowered RBC counts can lead to anemia.

Lowered WBC counts can lead to infections.

Lowered platelets can lead to bleeding problems.

Hematologic diseases

Leukemia

Gingival hypertrophy

Petechiae Mucosal ulcers

Hemorrhage

Treatment of leukemia

Reactivation of herpes simplex virus oral mucosistis

Summary of oral manifestations of gastrointestinal

and hematologic diseases

Angular cheilitis

Iron-deficiency anemia

Hemorrhage

Scurvy

Ulcerative colitis

Aphthous ulcers

Crohn's disease

Pernicious anemia

Ulcerative colitis

Intraoral burning

Iron-deficiency anemia

Pernicious anemia

Candidiasis

Crohn's disease (steriod therapy)

Iron-deficiency anemia

Pyostomatitis vegetans (steriod

therapy)

Ulcerative colitis (steroid therapy

Summary of oral manifestations of gastrointestinal and hematologic diseases
Summary of oral manifestations of
gastrointestinal and hematologic diseases

Labial swelling

Glossitis

Crohn's disease

Crohn's disease

 

Iron-deficiency anemia

Erosion of enamel and dentin

Pernicious anemia

Anorexia nervosa/bulimia

Ulcerative colitis

Gastroesophageal reflux

Ulcerations and erosions

Gingivitis

Crohn's disease

Anorexia nervosa/bullimia

Iron-deficiency anemia

Crohn's disease

Pernicious anemia

Scurvy

Ulcerative colitis

Connective-tissue diseases

Sjögren syndrome

autoimmune disease

men : women - 1 : 9, 50 years and older

Main signs

sicca syndrome

keratoconjuctivitis sicca

xerostomia

Oral signs

decrease in saliva

xerostomia dry, red, wrinkled mucosa

difficulty in swalloving and eating

disturbance in taste and speech

increased dental caries

infections

atrophy of the papilae

candidiasis

disturbance in taste and speech • increased dental caries • infections • atrophy of the papilae
disturbance in taste and speech • increased dental caries • infections • atrophy of the papilae
disturbance in taste and speech • increased dental caries • infections • atrophy of the papilae

Connective-tissue diseases

Kawasaki disease

vasculitis of medium and large arteries

Oral signs

swelling of papilae on the surface of the tongue (strawbery tongue)

intense erythema of the mucosal surfaces

cracked, cherry red, swolen and hemorrhagic lips

(strawbery tongue)  intense erythema of the mucosal surfaces  cracked, cherry red, swolen and hemorrhagic
(strawbery tongue)  intense erythema of the mucosal surfaces  cracked, cherry red, swolen and hemorrhagic
(strawbery tongue)  intense erythema of the mucosal surfaces  cracked, cherry red, swolen and hemorrhagic

Connective-tissue diseases

Scleroderma

diffuse sclerosis of the skin, GIT, heart muscle, lungs, kidney

Oral signs

pursed lips dificult to open the mouth

esophafeal sclerosis gastroesophageal reflux damage of enamel

pale, rigid mucosa

teleangiectasias

decreased mobility of tongue

salivary hypofunction

 decreased mobility of tongue  salivary hypofunction Limited mouth opening and decreased tongue mobility Gingival

Limited mouth opening and decreased tongue mobility

mobility of tongue  salivary hypofunction Limited mouth opening and decreased tongue mobility Gingival retraction

Gingival retraction

Connective-tissue diseases

Connective-tissue diseases ulcer  Lupus erythematosus  autoimmune disease Oral signs  ulcerations  oral
Connective-tissue diseases ulcer  Lupus erythematosus  autoimmune disease Oral signs  ulcerations  oral

ulcer

Lupus erythematosus

autoimmune disease

Oral signs

ulcerations

oral lesions of lichen planus

petechiae

damage of salivary glands - xerostomia

 oral lesions of lichen planus –  petechiae  damage of salivary glands - xerostomia

lichen planus lesions

 oral lesions of lichen planus –  petechiae  damage of salivary glands - xerostomia

Behcet’s Disease

Vasculitis with triad

oral, genital ulcers,

uveitis or iritis

oral

aphthous-like

painful, clusters on lips, gingiva, buccal, tongue

less often palate,

oropharynx

genital

similar in appearance

, clusters on lips, gingiva, buccal, tongue • less often palate, oropharynx  genital • similar
, clusters on lips, gingiva, buccal, tongue • less often palate, oropharynx  genital • similar

Behcet’s Disease

 occular • uveitis, iritis • hypopyon  healing in days to weeks some scarring
 occular
• uveitis, iritis
• hypopyon
 healing in days to
weeks some scarring
 symptoms
simultaneously,
months apart
uveitis, iritis • hypopyon  healing in days to weeks some scarring  symptoms simultaneously, months

Pulmonary diseases

Cystic fibrosis
Cystic fibrosis
 Pulmonary diseases Cystic fibrosis  Oral signs disorder of salivary glands swelling lips  gingivitis


Oral signs disorder of salivary glands swelling lips gingivitis dryness

 
diseases Cystic fibrosis  Oral signs disorder of salivary glands swelling lips  gingivitis dryness 

Sarcoidosis

Sarcoidosis, also called sarcoid (from the Greek 'sark' and 'oid' meaning

"flesh-like")

An immune system disorder characterised by non-caseating granulomas (small inflammatory nodules) that most commonly arises in young adults.

The cause of the disease is still unknown.

Any organ can be affected; however, granulomas most often appear in the

lungs or the lymph nodes.

Symptoms can occasionally appear suddenly but usually appear gradually.

The clinical course varies and ranges from asymptomatic disease that

resolves spontaneously to a debilitating chronic condition that may lead to

death.

Pulmonary Sarcoidosis

Pulmonary Sarcoidosis Oral signs  Multiple, nodular, painles ulcerations of the gingiva, bucal mucosa, labial
Oral signs
Oral signs

Multiple, nodular, painles ulcerations of the gingiva, bucal mucosa, labial mucosa and palate

Tumor like swelling of salivary glans

Swelling of the tongue

Xerostomia

Facial nerve palsy

and palate  Tumor like swelling of salivary glans  Swelling of the tongue  Xerostomia

Cutaneous diseases

Cutaneous diseases Psoriasis  Oral signs  Fissured tongue Small white papules Red and white plagues
Psoriasis  Oral signs
Psoriasis
Oral signs
Cutaneous diseases Psoriasis  Oral signs  Fissured tongue Small white papules Red and white plagues


Fissured tongue Small white papules Red and white plagues

   Bright red patches
Bright red patches
Acantosis nigricans 
Acantosis nigricans

Hyperpigmentation, papillomatosis Oral signs Gingival hyperplasia Gingiva, tongue, lips - papilomas

 

Discussion Questions
Discussion Questions

What oral manifestations of systemic diseases

may be observed within the oral cavity?

What disorders of blood cells may be observed within the oral cavity?

What effects may immunodeficiency have upon the oral cavity?

What oral manifestations may be observed during therapy for oral cancer?

What effects of drugs may be observed within the oral cavity?

may be observed during therapy for oral cancer?  What effects of drugs may be observed
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