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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 謝 謝