口腔病理科口腔病理科 systemic diseases and oral cavity...

口腔病理科

Systemic diseases andoral cavity

全身性疾病與口腔之關係

陳玉昆副教授 : 高雄醫學大學口腔病理科 07-3121101~2755 [email protected]

學習目標1. Relationships between chronic oral infectious diseases & systemic diseases

2. Systemic diseases manifested in oral cavity

參考資料參考資料References1. 董醒任口腔疾病與全身健康的關係 Happy Teeth 2000 年 9 月 15 日 p.5-102. Okuda K & Ebihara Y. Relationships between chronic oral infectious diseases & systemic

diseases. Bull Tokyo Dent Coll 1998;39:165-743. Scannapieco FA. Role of oral bacteria in respiratory infection. J Periodontol 1999;70:793-8024. Sakane T et al. Behcet’s disease. New Eng Med J 1999;341:1284-915. Kaohsiung Medical University, Oral Pathology Department6. O’Brien SJ & Dean M. In search of AIDS-resistance genes. Sci Am 1997;177:44-537. Mann JM & Tarantola DJM. Improving HIV therapy. Sci Am 1998;279:64-678. Regezi JA et al. Oral Kaposi’s sarcoma: Biopsy accessions as an indication of declining

incidence. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002;94:3999. Sharquie KE. et al. Oral pathergy test in Behcet's disease. Br J Dermatol 2002;168-910. Crispian Scully Handbook of oral disease diagnosis & management Chapter 4, p.148-911. Cawson RA et al. Oral Disease 3rd edition, p.14.1412. Jin LJ et al. Are periodontal diseases risk factors for certain systemic disorders- what matters

to medical practitioners? Hong Kong Med J 2003;9:31-713. Chen YK et al. Intra-oral HIV-associated Burkitt’s lymphoma with mandible involvement: a

case report. Oral Oncol 2005; 41: 249-5214. Zhang Y et al. The emerging landscape of salivary diagnostics. OHDM 2014;13:200-1015. Woo VL. Oral manifestations of Crohn’s disease: A case report & review of the literature.

Case Rep in Dent 2015, Article ID 830472.

Subtopics Relationships between chronic oral infectious diseases & systemic diseases

Systemic diseases manifested in oral cavity

Systemic Diseases & Oral Cavity

Oral cavity

Systemicdiseases

bacteria


1. Oral bacteria causing bacterial endocarditis 1. Oral bacteria causing bacterial endocarditis

Bacterial endocarditis

bacteremia

Blood smear of sepsis Ref: 2


2. Relationships of periodontobacteria and cardiovascular diseases

2. Relationships of periodontobacteria and cardiovascular diseases 牙周感染與心臟血管疾病的關係

Ref: 1


3. Pathogens for bacterial pneumonia in oral cavity (epidemiological view)

3. Pathogens for bacterial pneumonia in oral cavity (epidemiological view)

LCL: lower confidence limitUCL: upper confidence limit

LCL: lower confidence limitUCL: upper confidence limit OHI: Oral Hygiene IndexOHI: Oral Hygiene Index

PercentilePercentile OHI valueOHI value Estimate of odd ratio

Estimate of odd ratio LCL UCL LCL UCL

Ref: 3


Silent aspiration

Colonization

3. Pathogens for bacterial pneumonia in oral cavity (pathway)

3. Pathogens for bacterial pneumonia in oral cavity (pathway)

Ref: 2


3. Pathogens for bacterial pneumonia in oral cavity (cytokine)

3. Pathogens for bacterial pneumonia in oral cavity (cytokine)

Trachea

Bronchus

IL: interleukin

TNF: tissue necrosis factor

Cytokine ( 細胞素 )

Ref: 3


P. gingivalis

H. influenzaeProtease

3. Pathogens for bacterial pneumonia in oral cavity (four mechanisms)


(Dental pathogen)

(Respiratory pathogen)(Enzyme)

1. Mucosal surface receptor alteration by protease 2. Aspiration into lung

Mechanism (1)

Ref: 3


P. gingivalis

H. influenzae

2. Salivary pellicle



Mechanism (2)

degradation by protease

1. Salivary pellicle prevents respiratory pathogen adhere to mucosal surface

3. Respiratory pathogenadhere to mucosal surface

Ref: 3


H. influenzae

P. gingivalis

Mucous layer



Mechanism (3)

1. Salivary pellicledegradation by protease

Salivary pellicle

2. Exposure of adhesionreceptor for respiratorypathogen

Ref: 3




Mechanism (4)

H. influenzae

Salivary cytokines (IL, TNF)

1. Upregulation of adhesion receptor on mucosal surface by cytokines

2. Promotion of respiratory pathogens colonization

Ref: 3


Ref: 14

Biomolecules & fluids from different sources constitute the saliva

Biomolecules & fluids from different sources constitute the saliva

Source 2Oral mucosacells

Source 1Salivarygland

Source 3Oral microbiota& viruses

Source 4Blood

Source 5Gingivalcrevicular fluid

Source 6Food

SALIVAA complete mixture of

DNAs, RNAs & proteinsoriginated

from several sources


Nephritis Arthritis

4. Oral chronic infectious diseases cause secondary diseases


Refs: 2, 5


Metastatic infection from oral cavity

EndocarditisBrain abscessSinusitisLudwig’s anginaOrbital cellulitisOsteomyelitisSkin ulcerPustulosis palmaris et plantaris




Metabolic injury by oral bacterial toxin

Coronary heart diseaseAbnormal pregnancy outcomePersistent pyrexiaIdiopathic trigeminal neuralgiaAtypical facial painAcute myocardial infarction






Metastatic inflamma- tion by oral bacteria

Bechet’s diseaseCrohn’s diseaseInflammatory bowel diseaseUveitis


4. Oral chronic infectious diseases cause secondary diseases - Bechet’s disease


Criteria: recurrent oral ulceration + ≥ 2 others findings

Ref: 4

Criteria for diagnosisFindings Definitions

Recurrent oralulceration

Eye lesions

Skin lesions

Positive pathergy test

Recurrent genitalulceration

Minor aphthous, major aphthous, or hepetiform ulcers observed by the physicians or patients, which have occurred at least three times over a 12 month period

Aphthous ulceration or scarring observed by the physician or patient

Erythema nodosum observed by the physician or patient, pseudofolliculitis, or papulopustular lesions or acneriform observed by the physician in a postadolescent patient who is not receiving corticosterioids

Anterior uveitis, posterior uveitis or cells in the vitreous on slite lamp examination or retinal vasculitis detected by an ophthalmologist

Test interpreted as positive by the physician at 24 to 48 hours




Ref: 9

Pricking a sterile needle into the patient’s forearm or lower lip. The results are judged to be positive when the puncture causes an aseptic erythematous nodule/pustule that is > 2mm in diameter at 24 to 48 hours. At the reaction site there is initially an accumulation of neutrophils, followed by the accumulation of mononuclear cells

Skin test Oral test

Forearm Lower lip




Erythema/Papule/Pustule--Diameter

Definition of different grades of skin pathergy testGrade of test Clinical characteristic of the test at 48 h

Negative (-)Suspect (+/-)

Positive (+)

Only erythema <2 mmOnly erythema > 3 mm or papule 1-2 mm + erythema < 2 mm1+ Papule 2-3 mm + erythema > 3 mm2+ Papule > 3 mm + erythema > 3 mm3+ Pustule 1-2 mm + erythema > 3 mm4+ Pustule > 2 mm + erythema > 3 mm

Ref: 9


Hypopyon Erythema nodosum

A horizontal layer of inflammatory cells



Oral ulcer Genital ulcer

Ref: 4


4. Oral chronic infectious diseases cause secondary diseases – Crohn’s disease


Ref: 15

Lesion Site(s) Characteristics

Persistent mucosal swelling Lips, buccal mucosa Labial enlargement, firm to palpation, typically painless

Cobblestoning of mucosa Buccal mucosa, vestibule

Mucosal edema with or without fissuring

Mucogingivitis Attached gingiva, alveolar mucosa

Patchy erythematous macules or plaques with or without hyperplasia

Linear ulcerations Vestibule, buccal mucosa, tongue, palate

Deep ulcerations with or without hyperplastic margins

Mucosal tags or polyps Buccal mucosa, vestibule

Hyperplasia of mucosa, firm or boggy to palpation

Oral manifestations of Crohn’s diseaseOral manifestations of Crohn’s disease




Labial swelling& fissuring

Mucosal tag

Ulceration

Cobblesing stonemucosa

Ref: 4




Ref: 15

Mild mucosal erythema of the right anterior maxillary gingivaMild mucosal erythema of the right anterior maxillary gingiva




Ref: 15

1. Nodular swellings of the interdental papillae between the right permanent mandibular central and lateral incisors and primary canine2. An ulceration of the free gingival margin between the incisors is seen3. Linear ulceration with hyperplasticmargins involving the alveolar mucosa

1. Nodular swellings of the interdental papillae between the right permanent mandibular central and lateral incisors and primary canine2. An ulceration of the free gingival margin between the incisors is seen3. Linear ulceration with hyperplasticmargins involving the alveolar mucosa

11

22

33




Ref: 15

A demarcated area of mucosal erythema involving the left anterior maxillary alveolar mucosa

A demarcated area of mucosal erythema involving the left anterior maxillary alveolar mucosa




Ref: 15

Low-power view showing stratified squamous epithelium with scatteredintraepithelial lymphocytes. The underlying fibrous connective tissues are characterized by a patchy chronic inflammatory cell infiltrate & an isolated granuloma (arrow)

Low-power view showing stratified squamous epithelium with scatteredintraepithelial lymphocytes. The underlying fibrous connective tissues are characterized by a patchy chronic inflammatory cell infiltrate & an isolated granuloma (arrow)

High-power view showing a well-defined, noncaseating granuloma composed predominantly of epithelioid histiocytes & lymphocytes

High-power view showing a well-defined, noncaseating granuloma composed predominantly of epithelioid histiocytes & lymphocytes


Dermatitis

5. Heat shock proteins producing by oral bacteria may induce dermal diseases

5. Heat shock proteins producing by oral bacteria may induce dermal diseases

Ref: 2


Prevotella intermediaPorphyromonas gingivalis

Toxin:lipopolysaccharide

Estrogen

6. Gingivitis pathogens cause pregnancy disorders


Ref: 2




Ref: 1


牙周病糖尿病 7. Periodontitis and diabetic mellitus 7. Periodontitis and diabetic mellitus

Ref: 1


Periodontal infection & systemic conditions -potential linkage & possible pathogenic mechanisms

Periodontal infection & systemic conditions -potential linkage & possible pathogenic mechanisms

Periodontalinfection

Cardiovascular diseases

Diabetes mellitus

Adverse pregnancy outcomes Pulmonary infections

Ref: 12

Systemic diseases manifested in oral cavity

Ref: 5

Virus ( 病毒 )

Uncoating

Replication

ReleaseAttachmentHIV

gp

120

gp 41 CCR5

Life cycle Attachment Penetration translocate endocytosis fusion

Ref: 6

Host cell Host cell

CC

R5

gp 120

CD

4

gp 120

AttachmentH I V

gp

41

H I V

gp

41

Gp120 能與 CD4 受體結合，但無法直接引導 HIV 進入host cell

CCR5 將 gp120 拉開後，gp41 引導 HIV 進入host cell

Ref: 5

Host cellHost cell

Life - Cycle Possible ways of HIV therapy Drugs block binding (attachment & fusion) Drugs inhibit reverse transcriptase Drugs under study would inhibit integrase Some existing drugs inhibit protease

CC

R5

脂質套膜

套膜蛋白

gp

41

Attachment

Nucleus

Nucleus

Integration

蛋白質外殼

Budding

CD

4

H I V

HIV RNA

CytoplasmCytoplasm

H I V

gp

41

Attachment

Reverse-transcription

Uncoating

Reverse-transcriptase

Integrase

HIV mRNAProtease

Infected otherhost cells

CytoplasmCytoplasm Caspid

Fusion

Oth

er

Ho

st c

ell

Oth

er

Ho

st c

ell

gp 120

Reverse transcriptase

Integrase

Protease

Ref: 5

受體

CD4

CCR5

Macrophage

T-cell

CCR5

Early stage

Late stage

Ref: 5

Virus ( 病毒 )

CD4 T-cellcount

Viral load

Acutephase Chronic phase AIDS

Ref: 7

Oral Manifestations of AIDS

Candidiasis (thrush)

Candidiasis (atrophic)

Kaposi sarcoma

Necrotizing gingivitis

Ref: 10

Hairy leukoplakia

Hairy leukoplakia

Hairy leukoplakia

Hairy leukoplakia

H&E

EBV


Ref: 11

Twenty-year incidence of KS at the University of California San Francisco

Oral KS cases/yearN = 203

Oral Kaposi’s sarcoma: Biopsy accessions as an indication of declining incidence

No

. o

f ca

ses

0

203

1981 200219971991

Due to highly activeantiretroviraltherapy in 1995


Ref: 8

至 2013 年底，國內愛滋感染者的服藥人數為 1 萬 4983人，其中有 8成體內測不到病毒量，目前在雞尾酒療法及規律服藥下，感染愛滋病毒已被視為一種慢性病，台灣最年長的愛滋感染者 >90 歲

至 2013 年底，國內愛滋感染者的服藥人數為 1 萬 4983人，其中有 8成體內測不到病毒量，目前在雞尾酒療法及規律服藥下，感染愛滋病毒已被視為一種慢性病，台灣最年長的愛滋感染者 >90 歲


Hairy leukoplakia

Oral candidiasis

Our Collected Case

Ref: 5

疾管署統計 2013年國內新增愛滋感染者2244人， 757人已發病 (34%)；已發病者約 53% 在 6個月內發病

疾管署統計 2013年國內新增愛滋感染者2244人， 757人已發病 (34%)；已發病者約 53% 在 6個月內發病


Our Collected Case –Burkitt’slymphoma

Refs: 5, 13


Our Collected Case – Burkitt’slymphoma

Oral Oncol Extra2005:41:249-52.

CD-20 c-myc Ki-67 p53

Refs: 5, 13

Oral Manifestations of TB

0

1

2

3

4

5

Freq

uenc

y

1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

YearOralHead & Neck

Ref: 5


Ref: 5

A B


Ref: 5

A

B C

Summaries

1. Relationships between chronic oral infectious diseases & systemic diseases

2. Systemic diseases manifested in oral cavity - AIDS, TB

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