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口 腔 病 理 科
An Overview of the Association
of Systemic Diseases & Oral Cavity:
Oral Infection/Oral Manifestation
全身性疾病與口腔關聯之簡論：
口腔感染/口腔表徵
陳玉昆助理教授: 高雄醫學大學 口腔病理科
07-3121101~2755
[email protected]
大 綱
1. Relationships between
chronic oral infectious
diseases & systemic
diseases
2. Systemic diseases manifested
in oral cavity
參考資料
References
1. 董醒任 口腔疾病與全身健康的關係 Happy Teeth 2000年9月15日 p.5-10
2. Okuda K & Ebihara Y. Relationships between chronic oral infectious diseases & systemic
diseases. Bull Tokyo Dent Coll 1998;39:165-74
3. Scannapieco FA. Role of oral bacteris in respiratory infection. J Periodontol 1999;70:793-802
4. Sakane T et al: Behcet’s disease. New Eng Med J 1999;341:1284-91
5. Kaohsiung Medical University, Oral Pathology Department
6. O’Brien SJ & Dean M. In search of AIDS-resistance genes. Sci Am 1997;177:44-53
7. Mann JM & Tarantola DJM. Improving HIV therapy. Sci Am 1998;279:64-67
8. 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;94:399
9. Sharquie KE. et al. Oral pathergy test in Behcet's disease. Br J Dermatol 2002;168-9
10. Crispian Scully Handbook of oral disease diagnosis & management Chapter 4, p.148-9
11. Cawson RA et al. Oral Disease 3rd edition, p.14.14
12. Jin LJ et al. Are periodontal diseases risk factors for certain systemic disorders- what matters
to medical practitioners? Hong Kong Med J 2003;9:31-7
13. Chen YK et al. Intra-oral HIV-associated Burkitt’s lymphoma with mandible involvement: a
case report. Oral Oncol 2005; 41: 249-52
Systemic Diseases & Oral Cavity
Subtopics
Relationships between chronic oral
infectious diseases & systemic diseases
Systemic diseases manifested in oral cavity
Oral cavity
bacteria
Systemic
diseases
Systemic Diseases & Oral Cavity
1. Oral bacteria causing bacterial endocarditis
bacteremia
Bacterial endocarditis
Blood smear of sepsis
Ref: 2
Systemic Diseases & Oral Cavity
2. Relationships of periodontobacteria
and cardiovascular diseases
牙周感染與心臟血管疾病的關係
Ref: 1
Systemic Diseases & Oral Cavity
3. Pathogens for bacterial pneumonia in
oral cavity (epidemiological view)
Percentile
OHI value
LCL: lower confidence limit
UCL: upper confidence limit
Estimate of
odd ratio
LCL UCL
OHI: Oral Hygiene Index
Ref: 3
Systemic Diseases & Oral Cavity
3. Pathogens for bacterial pneumonia in
oral cavity (pathway)
Silent aspiration
Colonization
Ref: 2
Systemic Diseases & Oral Cavity
3. Pathogens for bacterial pneumonia in
oral cavity (cytokine)
Cytokine
(細胞素)
IL: interleukin
Trachea
TNF: tissue necrosis
factor
Bronchus
Ref: 3
Systemic Diseases & Oral Cavity
3. Pathogens for bacterial pneumonia in
oral cavity (four mechanisms)
Mechanism (1)
(Respiratory pathogen)
H. influenzae
(Enzyme)
Protease
P. gingivalis
(Dental pathogen)
1. Mucosal surface receptor
alteration by protease
2. Aspiration into lung
Ref: 3
Systemic Diseases & Oral Cavity
3. Pathogens for bacterial pneumonia in
oral cavity (four mechanisms)
Mechanism (2)
2. Salivary pellicle
degradation
by protease
P. gingivalis
H. influenzae
1. Salivary pellicle prevents
respiratory pathogen adhere
to mucosal surface
3. Respiratory pathogen
adhere to mucosal surface
Ref: 3
Systemic Diseases & Oral Cavity
3. Pathogens for bacterial pneumonia in
oral cavity (four mechanisms)
Mechanism (3)
H. influenzae
P. gingivalis
Mucous layer
1. Salivary pellicle
degradation by
protease
Salivary pellicle
2. Exposure of adhesion
receptor for respiratory
pathogen
Ref: 3
Systemic Diseases & Oral Cavity
3. Pathogens for bacterial pneumonia in
oral cavity (four mechanisms)
Mechanism (4)
Salivary cytokines
2. Promotion of respiratory
pathogens colonization
H. influenzae
1. Upregulation of adhesion receptor
on mucosal surface by cytokines
Ref: 3
Systemic Diseases & Oral Cavity
4. Oral chronic infectious diseases cause
secondary diseases
Nephritis
Arthritis
Refs: 2, 5
Systemic Diseases & Oral Cavity
4. Oral chronic infectious diseases cause
secondary diseases
Metastatic infection
from oral cavity
Endocarditis
Brain abscess
Sinusitis
Ludwig’s angina
Orbital cellulitis
Osteomyelitis
Skin ulcer
Pustulosis palmaris et plantaris
Systemic Diseases & Oral Cavity
4. Oral chronic infectious diseases cause
secondary diseases
Metabolic injury
by oral bacterial
toxin
Coronary heart disease
Abnormal pregnancy outcome
Persistent pyrexia
Idiopathic trigeminal neuralgia
Atypical facial pain
Acute myocardial infarction
Systemic Diseases & Oral Cavity
4. Oral chronic infectious diseases cause
secondary diseases
Metastatic inflammation by oral bacteria
Bechet’s disease
Crohn’s disease
Inflammatory bowel
disease
Uveitis
Systemic Diseases & Oral Cavity
4. Oral chronic infectious diseases cause
secondary diseases - Bechet’s disease
Criteria for diagnosis for Bechet’s disease
Findings
Recurrent oral
ulceration
Recurrent genital
ulceration
Eye lesions
Definitions
Skin lesions
Positive pathergy test
Criteria: recurrent oral ulceration +
≥ 2 others findings
Ref: 4
Systemic Diseases & Oral Cavity
4. Oral chronic infectious diseases cause
secondary diseases
Skin test
Oral test
Forearm
Ref: 9
Systemic Diseases & Oral Cavity
4. Oral chronic infectious diseases cause
secondary diseases
Definition of different grades of skin pathergy test
Grade of test
Clinical characteristic of the test at 48 h
Negative (-) Only erythema <2 mm
Suspect (+/-) Only erythema > 3 mm or
papule 1-2 mm + erythema < 2 mm
Positive (+) 1+ Papule 2-3 mm + erythema > 3 mm
2+ Papule > 3 mm + erythema > 3 mm
3+ Pustule 1-2 mm + erythema > 3 mm
4+ Pustule > 2 mm + erythema > 3 mm
Erythema/Papule/Pustule--Diameter
Ref: 9
Systemic Diseases & Oral Cavity
4. Oral chronic infectious diseases cause
secondary diseases
Oral ulcer
Genital
ulcer
A horizontal layer of
inflammatory cells
Hypopyon
Ref: 4
Erythema nodosum
Systemic Diseases & Oral Cavity
4. Oral chronic infectious diseases cause
secondary diseases – Crohn’s disease
Labial swelling
& fissuring
Ulceration
Mucosal tag Cobblesing stone
mucosa
Ref: 4
Systemic Diseases & Oral Cavity
5. Heat shock proteins producing by oral
bacteria may induce dermal diseases
Dermatitis
Ref: 2
Systemic Diseases & Oral Cavity
6. Gingivitis pathogens cause pregnancy
disorders
Estrogen
Prevotella intermedia
Porphyromonas
gingivalis
Toxin:
lipopolysaccharide
Ref: 2
Systemic Diseases & Oral Cavity
6. Gingivitis pathogens cause pregnancy
disorders
Ref: 1
Systemic Diseases & Oral Cavity
7. Periodontitis and diabetic mellitus
牙周 病
糖尿病
Ref: 1
Systemic Diseases & Oral Cavity
Periodontal infection & systemic conditions potential linkage & possible pathogenic mechanisms
Cardiovascular diseases
Diabetes mellitus
Periodontal
infection
Adverse pregnancy outcomes
Pulmonary infections
Ref: 12
Systemic diseases manifested in oral cavity
Ref: 5
Virus (病毒)
Life cycle
Attachment
Penetration
translocate
endocytosis
fusion
HIV
Uncoating
Replication
Release
Attachment
gp 41
CCR5
Ref: 6
HIV
HIV
Attachment
gp 41
gp 41
gp 120
Host cell
CCR5
CD4
gp 120
Host cell
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
Attachment
HIV
Reverse
transcriptase
Life - Cycle
Integrase
Possible ways of
HIV therapy
Protease
gp 41
Drugs block binding (attachment & fusion)
Infected other
Drugs inhibit reverse transcriptase
host cells
Drugs under study would
inhibit integrase
Some existing drugs
inhibit protease
脂質套膜
CD4
Attachment
CCR5
gp 120
Integration
Budding
套膜蛋白
Integrase
Nucleus
HIV RNA
HIV mRNA
Nucleus
gp 41
Fusion
Cytoplasm
Cytoplasm
HIV
Caspid
ReverseProtease
transcription
Reversetranscriptase
Uncoating
蛋白質外殼
Ref: 5
CD4
CCR5
CCR5
受體
Early stage
Macrophage
T-cell
Late stage
Ref: 5
Virus (病毒)
Acute
phase
Chronic phase
AIDS
CD4 T-cell
count
Viral load
Ref: 7
Oral Manifestations of AIDS
Candidiasis (thrush)
Kaposi sarcoma
Necrotizing gingivitis
Candidiasis (atrophic)
Ref: 10
Oral Manifestations of AIDS
Hairy leukoplakia
EBV
Hairy leukoplakia
Hairy leukoplakia
Ref: 11
H&E
Oral Manifestations of AIDS
Oral Kaposi’s sarcoma: Biopsy accessions
as an indication of declining incidence
20
No. of cases
Oral KS cases/year
N = 203
Due to highly active
antiretroviral
therapy in 1995
0
1981
1991
1997
2002
Twenty-year incidence of KS at the
University of California San Francisco
Ref: 8
Oral Manifestations of AIDS
Hairy leukoplakia
Our Collected Case
Oral candidiasis
Ref: 5
Oral Manifestations of AIDS
Our
Collected
Case –
Burkitt’s
lymphoma
Refs: 5, 13
Oral Manifestations of AIDS
Our
Collected
Case –
Burkitt’s
lymphoma
CD-20
c-myc
Ki-67
p53
Oral Oncol Extra
2005:41:249-52.
Refs: 5, 13
Oral Manifestations of TB
5
Frequency
4
3
2
1
0 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007
Oral
Head & Neck
Year
Ref: 5
Oral Manifestations of TB
A
B
Ref: 5
Oral Manifestations of TB
A
B
C
Ref: 5
Conclusion
Comprehensive & update review
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