潰瘍類七年制(2017)

1、口腔黏膜病種類口腔黏膜感染性疾病 口腔黏膜潰瘍類疾病口腔黏膜大皰類疾病口腔黏膜斑紋類疾病口腔變態(tài)反應(yīng)性疾病唇 舌 疾 病ContentsRecurrent aphthous ulcer, RAU Behets diseaseTraumatic ulceration/mucosal hematomaOral mucositisUlcerative Lesions of Oral Mucosa (Chapter 4) 以潰瘍?yōu)橹饕R床表現(xiàn)的一類疾病黏膜上皮完整性的連續(xù)性破壞上皮全層的缺失可深達(dá)肌層Diseases at a glanceAfter this class, you should:Cl

2、early understand the characteristics, clinical classification therapeutic principles of recurrent aphthous ulcerDifferentiate pemphigus and pemphigoid and their therapeutic principles Ulcerative Lesions of Oral Mucosa Ulcer - a discontinuity of the mucosa exhibiting COMPLETE loss of the epitheliumRe

3、current aphthous ulcer(RAU)one of the most common oral ulcerative diseaseunclear etiologyperiodical recurrencehigh prevalence (20%60% of the population)Recurrent aphthous ulcerEtiology & MechanismUnknown, every reason is possible: immunity, hereditary, infection, environment, endocrine, trauma, mood

4、(p.59-p.61, self-study)Recurrent aphthous ulcer2. Clinical Features self-limited periodical recurrence Characteristics: red/yellow/hollow/sore Recurrent aphthous ulcer3. Clinical types Minor: 10 mm, single, scarring Herpetiform: more than 10 small lesionsRAU(minor)Ulcer with classic featuresSmall le

5、sion (diameter less than 0.5 cm)Occurs on freely movable mucosa with low keratinization (labial mucosa, buccal, tongue, floor of mouth, soft palate)RAU(major)Single, major and deep ulcer, and cause scarringLarge lesion (diameter more than 1 cm)Often occur in posterior oral cavityRAU(Herpetiform)Mult

6、iple, small, diffuse, painful, superficial May occur on some keratinizing surfacesOften involve in tongue ventral or floor of mouthRecurrent aphthous ulcer4. Diagnosis History (self-limited, periodical recurrence) Clinical features (red, yellow, hollow, sore) Biopsy -Major RAURecurrent aphthous ulce

7、r5. Differential diagnosisRAU (major)TuberculosisOral cancerMajor RAUMalignant tumor TB-ulcerRecurrent & self-limited YesNoNoUlcerCrater-formCrater or cauliflower-form indent-formInfiltrationNoYesNoPathologyInflammationMalignancy TB noduleDifferential diagnosisDifferential diagnosis among Major RAU,

8、 Malignant tumor and TB-ulcer (also refer to textbook P.63)Recurrent aphthous ulcer6. TherapyPrinciples:-Try to find out the cause (etiological treatment vs. symptomatic treatment)-Individualize treatment plan-Reduce the drug toxin and side effect Recurrent aphthous ulcerb) Topical medication Sympto

9、matic treatment* Any regimen that can relieving pain, diminish inflammation, promote wound healing is helpfule.g. oral paste/gel/ ointment, chlorhexidine mouthwashRecurrent aphthous ulcerc) Systemic medicationControl recurrence, try to etiological treatmentCorticosteroids: 控制RAU癥狀的首選藥物其代表為強(qiáng)的松中小劑量(約1

10、525mg/d)口服34周地塞米松等可換算成相同劑量后應(yīng)用(地塞米松0.75mg=強(qiáng)的松5mg)Recurrent aphthous ulcerImmunosuppressor:用于激素療效不理想或不耐受的患者環(huán)磷酰胺(Cyclophosphamide)等：療效和骨髓抑制等毒副作 用均明顯，只宜短期應(yīng)用雷公藤：男性不育、肝毒，慎用中成藥：昆明山海棠、火把花根片、帕芙林 副作用較輕，可酌情長期應(yīng)用* 具有非特異免疫抑制作用的藥物反應(yīng)停(Thalidomide)25-50mg p.o. qn 1- 2 month能迅速減輕癥狀、明顯縮短發(fā)作期美國FDA已批準(zhǔn)用于治療AIDS的口腔潰瘍損害需注意其致

11、畸作用，孕婦禁用，育齡婦女慎用Recurrent aphthous ulcer海豹胎事件20世紀(jì)50至60年代初期反應(yīng)停在全世界廣泛使用，它能夠有效地阻止女性懷孕早期的嘔吐，對(duì)胚胎的毒性，有明顯的時(shí)間性，即在不同的孕期服用反應(yīng)停，可引起不同的畸形。1959年12月，西德兒科醫(yī)生Weidenbach首先報(bào)告了一例女嬰的罕見畸形?；螊雰簺]有臂和腿，手和腳直接連在身體上，很像海豹的肢體，故稱為海豹肢畸形兒及海豹胎。西德、美國、荷蘭和日本等國，由于服用該藥物而誕生了12000多名有一個(gè)國家一直沒有允許其上市，也鮮有受害者, 這個(gè)國家是？為何如此幸運(yùn)？朗西絲奧爾德姆凱爾西（Frances Oldham

12、 Kelsey）女士優(yōu)異聯(lián)邦公民服務(wù)總統(tǒng)獎(jiǎng)Recurrent aphthous ulcerImmunomodulator:副作用小、停藥后無反跳現(xiàn)象Thymosin (胸腺素), Transfer Factor (轉(zhuǎn)移因子), Levamisole (左旋咪唑), Polyresistin A (多抗甲素), etc.Bacille Calmette Guerin (BCG) - Polysaccharide Nucleic Acid (卡介菌多糖核酸) Sig: 1mL i.m. qod 30dRecurrent aphthous ulcerOthersVitamins and microe

13、lementsVitamin B, C; zinc sulfate regimenTraditional Chinese medicine口炎清等中成藥Recurrent aphthous ulcerd) Life habitsDiet control: eat healthily, reduce the fried foodsSound mindPlenty of sleep* LOHAS: lifestyles of health and sustainability治療方案設(shè)計(jì)方案1：一般的局部用藥，合用營養(yǎng)因子、 中成藥或中醫(yī)辨證施治 (基礎(chǔ)用藥,低發(fā))方案2：皮質(zhì)激素?fù)p害下局部注射

14、(重型)方案3：中小劑量皮質(zhì)激素的全身應(yīng)用 (各型,頻發(fā)) 方案4：免疫調(diào)節(jié)劑的全身應(yīng)用 (各型,頻發(fā)) 方案5：反應(yīng)停等非特異免疫抑制藥物的全 身應(yīng)用 (各型,頻發(fā)) 方案6：免疫抑制劑的全身應(yīng)用 (各型,頻發(fā)) 治療方案選擇 根據(jù)：RAU病損的發(fā)作頻率高：間歇期4周發(fā)作頻率 臨床分型 治療方案高、中、低 各型 方案1（基礎(chǔ)用藥）高 各型 首選方案3或方案5，必要時(shí)合 用方案6，如無效改用方案4中 輕型 首選方案4 重型 方案2和方案4低 輕型 選擇方案1 重型 選擇方案2；無效改用方案4高、中、低 皰疹樣型 方案3或方案5Behets Diseasea multisystem inflam

15、matory illnessoral and genital mucosa ulcerations, skin lesions, intraocular (eye) inflammationa variety of other disorders involving multiple organs in the bodyBehets DiseaseEtiology & PathogenesisUnclear immunity, hereditary, infection(p.68-p.69, self-study)Behets Disease2. Clinical manifestations

16、Oral: RAUEye: Iridocyclitis (虹膜睫狀體炎), hypopyon (前房積膿), choroiditis (脈絡(luò)膜炎), etc.Genital: RAUSkin: erythema nodosum (結(jié)節(jié)性紅斑), folliculitis (毛囊炎), skin pricked reactionskin pricked reaction* 0.1 mL saline is intracutaneous injected into the front arm with a sterile needle. 1 to 2 days after the test, oc

17、currence of a small red bump or pustule at the site of needle insertion, constitutes a positive test. at least 95% BDpatientsMainly by minor type The first systemic manifestation (about 70% cases) Oral lesion: RAUGenital lesions:RAUSimilar to major RAUMale - scrotum and penisFemale - vulva or vagina

18、Characteristic skin lesions:Left: Erythema nodosum-like lesions (結(jié)節(jié)性紅斑)Right: folliculitis (毛囊炎)Behets DiseaseOther lesionsJoint lesion (arthritis, etc.)Cardiovascular diseasesDigestive tract diseasesNerve system diseasesRespiratory system diseases Behets Disease3. Diagnosis Oral RAU (at least three

19、 times in 12 months)+ any two of:Recurring genital sores/ulcersEye inflammationCharacteristic skin lesionsPositive pathergy (skin prick test)Behets Disease4. TherapyThere is no cure for Behcets disease however spontaneous regression may occurTreatment is aimed at limiting and preventing complication

20、s from symptoms Treatment includes medications, rest, and exerciseMeditationOral lesion: similar to RAUSpecialized treatment for multiple organ disorders should be transfer to relative departments (dermatology, ophthalmology, etc.)Traumatic mucosal hematoma & traumatic ulcerationa hematoma or ulcer

21、localized on the oral mucosa in which the surface epithelium has been destroyed by topical physical and chemical irritationsTraumatic hematoma & ulcerEtiologyPhysical factors-denture irritation, biting injuries, burn, friction irritation from sharp or fractured teethChemical factors-medical factors,

22、 strong acid/alkali injuryTraumatic hematoma & ulcer2. Clinical features of traumatic ulcerPhysical injury Ulcer-associated factors in oral cavity (e.g. denture, sharp and fractured teeth, etc.)The shape of ulcer match the irritationUlcer will heal after removing the irritation factors for 23 weeksT

23、raumatic ulcerTraumatic hematoma & ulcerChemical injury Topical medications existedMucosa hyperaemiaErosionYellow-white pyogenic membrane or necrosis on localized areaTraumatic hematoma & ulcer2. Clinical features of traumatic hematomaOften occur on buccal, soft palate mucosaPurple blister, with var

24、ious shape and sizeWell-demarcated red lesion after hematoma brokenExudates center with surrounding erythematous flareBurning painTraumatic hematoma & ulcer3. Differential DiagnosisTB ulcer squamous carcinomamajor RAU Key points: Recurrence / Self-limited / Local irritating factor / Shape of the ulc

25、erTraumatic hematoma & ulcer4. TreatmentRemove the local irritating factorsPain relief, anti-inflammation, and healing promotion (refer to RAU therapy)Localized corticosteroid injectionOral mucositisMucositis is the painful inflammation and ulceration of the mucous membranes lining the digestive tra

26、ctan adverse effect of chemotherapy and radiotherapy treatment for cancerOral mucositis refers to the particular inflammation and ulceration that occurs in the moutha common and often debilitating complication of cancer treatment1. Signs and symptomsTime courseDay 0Day 4-5Day 10slowly improvingFew w

27、eeks laterSymptomaticPeakRadiation start2 weeks afterslowly improving6-8 weeks laterSymptomaticPeakRadiation endChemotherapy induced mucositisRadiotherapy induced mucositisOral mucositisMucosal changes: thinred, inflamed ulceratedcovered with pseudomembraneSymptoms:Peripheral erythema Ulcers may ran

28、ge from 0.5cm- 4cmSeverely painful (trouble speaking, eating, or even opening the mouth)Conventional Pharmacology High Turnover Rate of Mucosal Cells Makes Them Susceptible to Damage During Cytotoxic TherapyNormal mucosa provides an effective protective barrierHigh epithelial turnoverReduced turnove

29、rReduced epithelial turnover leads to mucosal breakdownMucosal injuryDNA damageNonDNA damageGeneration of ROSMucosa becomes susceptible to injuryAdapted from Sonis ST. Nat Rev. 2004;4:277-284.ROS = reactive oxygen speciesEverolimus(依維莫司) plus exemestane(依西美坦 ): A novel therapeutic strategyActivation

30、 of the mTOR pathway is an important factor driving disease progression and endocrine resistance Vilarreal-Garza C et al. Ann Oncol 2012.23(10):2526-35; 19. Miller TW et al. Breast Cancer Res 2011;13:224-35; 20. Di Cosimo S, Baselga J. Nat Rev Clin Oncol 2010;7:139-47Adapted from reference mTOR Inhi

31、bitorsaffect the inflammatory processinvolve T-Cell infiltrationMainly CD8 and cytotoxic T-Cellsresults in increased production of pro-inflammatory cytokines eg. TNF-, IL-1, IL-2, IL-6results in decreased epithelial proliferation Due to lower levels of IL-10This combination of events leads to the fo

32、rmation of oral ulcers Martins, F. et al. (2013). A reivew of oral toxicity associated with mTOR inhibitor therapy in cancer patients. Oral Oncology , 1-6.Tyrosine Kinase Inhibitors target the capillary endothelium Blocks VEGFR 1/2/3, PDGFR, c-KIT, FMS like tyrosine kinase 3.c-KIT is present in the

33、acini and ducts of salivary glands and in human keratinocytesVEGFR 1 is present in the epidermal layer of unwounded skin Once damage to the oral mucosa is sustained, would healing is impaired as VEGF regulates the wound repair mechanismMignogna, M. D. et al. (2009). Sunitinib Adverse Event: Oral Bul

34、lous and Lichenoid Mucositis. The Annals of Pharmacotherapy, 546-547.Recently approved targeted therapies associated with Oral Mucositis (any grade)mTOR Inhibitors EU approvalEverolimus44% 2009, 2012Temsirolimus41% 2007Tyrosine Kinase InhibitorsErlotinib17% 2005Sunitinib38% 2006Sorafenib 28% 2005Paz

35、opanib4% 2009Source: SmPC and Boers-Doets et al, The Oncologist 2012;17:135-144Oral mucositis3. DiagnosisHistory of chemotherapy, bone marrow transplants or radiotherapyClinical symptomsOral mucositis4. Treatment Supportive therapyOral hygiene -the mainstay of treatmentEpithelium regeneration promotion: keratinocyte growth factor (金因肽)Pain relief: mouth wash with lidocaine, oral gelSecondary infection control: anti virus, bacteria or fungus Oral mucositisExperimental therapies:Anti-inflammation: cytokines mo