オスラー病(遺伝性出血性末梢血管拡張症)の鼻出血
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- なつき いんそん
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1 endoglin 1 12 ALK1 2 1/3 Curaao criteria Sutton Babington 2 5 Legg Chiari 1887Chauffadin1896 Rendu Osler Weber Osler Osler Hanes hereditary hemorrhagic telangiectasia HHT McDonald 10 9q3433 McAllister 11 Johnson 12 Vincent
2 523 1 OWR1 9q endoglintype III TGFβ OWR2 12q1114 ALK1type I TGFβ 5q p14 HHTjuvenile polyposis coli 18q21.1 MADH4 or SMAD4 HHT IIprimary pulmonary 2q33 BMPR II hypertension 12q Johnson activin receptorlike kinasealk q3334 endoglin q13 ALK hetero homo 15 vasculogenesis angiogenesis 2 4 TGFβ TGFβ TGFβ Smad Smad ALK1 ALK5 endoglin 180 kd 2 TGFβ TGFβ TGFβ13 ALK 1 TGFβ TGFβ1 TGFβ BMPbone morphogenetic protein9 16 ALK1 endoglin ALK1 ALK1 ALK5 ALK 5 HHT endoglin 328 ALK1 271 HHT Mutation Database http //hhtmutation.org/ HHT 139 9
3 /1331 Antilles, Holland Westermann et al, /2351 French Department of Ain Plauchu & Bideau /3375 French Department of Ain Bideau et al, /2300 Jura Valley, France Bideau et al, /5062 Jura Valley, France Bideau et al, /4287 DeuxSèvres,France Bideau et al, /3500 Island of Funen,Denmark Vase & Grove, /5155 Leeward Islands Jessurun et al, / Dakeishi et al, /6400 County of Fyn, Denmark Kjeldsen et al, /16,500 Vermont,US Guttmacher et al, /39,216 Northern England Porteus et al, phenotype 4 1 a b c Braverman IM, et al, J Invest Dermatol, Braverman arteriovenous malformationavm3 AVM arteriovenous fistulaavffistulous type AVM nidus type small nidus type AVMmicro AVM
4 AVM 1530 POM CT AVM 831 CT AVM 1144 AVMAVF 522 MRIMRA AVM 1 MRIMRA AVM 3 22 Mahoney & Shapshay AVM White 25 simple type AVM complex type HHT 1020 nidus 1cm micro AVM MR 1cm nidus type AVM MR AVF 30micro AVM 40nidus type AVM
5 523 4 HHT1 HHT y y /21 12/4 4/14 Grade AVM AVM Kjeldsen et al, 2005 HHT1 HHT y /219 53/75 28/48 AVM AVM AVM Letteboer TG et al, 2006 HHT1 HHT AVM AVM AVM Lesca et al, AVM HHT AVM AVM AVM 2 AVM / AVM CT AVM AVM AVM
6 523 5 Curaao criteria 7 AVM Type Mahoney & Shapshay, I F T AlDean & BachmannHarildstad, 2008 AVM 8 Curaao criteria 35) HHT AVM CT CT MR AVM CT Rebeiz AlDean & BachmannHarildstad TNM Iintensity Ffrequency Ttransfusion I5F3T1 6 Mahoney & Shapshay 41 7 Rebeiz
7 HHT FernandezL 49 ALK1 endoglin ALK1/endoglin in vitro 1 12g 2 41 Mahoney & Shapshay 41 3 NdYAG
8 mm 41 NdYAG 1 23 KTP defocus A 40 facial degloving 2000 degloving ,000ml 300ml B 63.5cm
9 523 5 Saunders C QOL QOL
10 耳展 オスラー病の鼻出血 52 3 b 2 型 びまん性連結血管 a 1 型 孤立性 点状血管拡張 d 4 型 連 結 型動静 脈 奇 形 c 3 型 孤立性動静脈奇形 図 2 鼻粘膜血管病変の分類 a 口蓋と舌の血管拡張 b 舌と口唇の血管拡張 図 3 口腔粘膜での血管拡張像 口蓋では分枝状を 口唇では丘疹状をとりやすい 舌では両型ともみられる 図 4 アルゴンプラズマ凝固 図 5 植皮片の鼻腔内挿入と縫合 鼻翼を翻転し 移植皮膚を鼻腔内に挿入し 前方を縫 合している
11 523 a 6 32 b a b a58 4 b
12 AVM HHT micro AVM AVM 3mm mm AVF AVM 11 HHT 10 AVFAVM 63 1 Sutton HGFamilial epistaxis. Medical Mirror , 1864., London. 2 Babington BGHereditary epistaxis. Lancet , Legg JWHaemophilia complicated with multiple naevi. Lancet , Rendu HJLMEpistaxis repetees chez un sujet porteur de petits angiomes cutanes et muquez. Gaz de Hop Civils et MilitairesParis491322, Osler WOn a family form of recurring epistaxis, associated with multiple telangiectases of the skin and mucous membranes. Bull Johns Hopkins Hosp , Weber FMultiple hereditary developmental angiomatatelangiectasesof the skin and mucous membranes associated with recurring hemorrhages. Lancet , Hanes FMMultiple hereditary telangiectases causing hemorrhagehereditary hemorrhagic telangiectasia. Bull Johns Hopkins Hosp , OSLER McDonald MT, Papenberg KA, Ghosh S, Glatfelter AA, Biesecker BB, et ala disease locus for hereditary hemorrhagic telangiectasia maps to chromosome 9q3334. Nat Genet , McAllister KA, Grogg KM, Johnson DW, Gallione CJ, Baldwin MA, et alendoglin, a TGFβ binding protein of endothelial cells, is the gene for hereditary hemorrhagic telangiectasia type 1. Nat Genet , Johnson DW, Berg JN, Gallione CJ, McAlister KA, Warner JP, et ala second locus for hereditary hemorrhagic telangiectasia maps to chromosome 12 : Genome Res 52128, Vincent P, Plauchu H, Hazan J, Fauré S, Weissenbach J, et ala third locus for hereditary hemorrhagic telangiectasia maps to chromosome 12q. Hum Mol Genet , Johnson DW, Berg JN, Baldwin MA, Gallione CJ, Marondel I, et almutations in the activin receptorlike kinase 1 gene in hereditary hemorrhagic telangiectasia type 2. Nat Genet , Begbie ME, Wallace GMF, Sholvlin CLHereditary hemorrhagic telangiectasiaoslerweber Rendu syndromea viewfromthe21 st century. Postgrad Med J , TGFβ Bideau A, Brunet GH, Heyer E, Plauchu H, Robert JMAn abnormal concentration of cases
13 523 of RenduOsler disease in Valserine valley of the French Jura : a genealogical and demographic study. Ann Hum Biol , Guttmacher AE, Mckinnon WC, Upton MDHereditary hemorrhagic telangiectasiaa disorder in search of the genetic community. Am J Med Genet , Kjeldsen AD, Vase P, Gren AHereditary hemorrhagic telangiectasia a population based study of prevalence and mortality in Danish patients. J Intern Med , Dakeishi M, Shioya T, Wada Y, Shindo T, Otaka K,et algenetic epidemiology of hereditary hemorrhagic telangiectasia in a local community in the northern part of Japan. Hum Mutat , Braverman IM, Keh A, Jacobson BSUltrastructure and threedimensional organization of the telangiectases of hereditary hemorrhagic telangiectasia. J Invest Dermatol , Folz BJ, Wollstein AC, Lippert BM, Werner JA. Morphology and distribution of nasal telangiectasia in HHTpatients with epistaxis. Am J Rhinol , Mahoney EJ, Shapshay SMNew classification of nasal vasculature patterns in hereditary hemorrhagic telangiectasia. Am J Rhinol , Haitjema T, Westerman CJJ, Overtoom TTC, Timmer R, Disch F, et alhereditary hemorrhagic telangiectasiaoslerweberrendu diseasenew insights in pathogenesis, complications and treatment. Arch Intern Med , White RI Jr, Mitchell SE, Barth KH, Kaufman SL, Kadir S, et alangioarchitecture of pulmonary arteriovenous malformationsan important consideration before embolotherapy. AJR Am J Roentgenol , Krings T, Ozanne A, Chng SM, Alvarez H, Rodesch G, et alneurovascular phenotypes in hereditary haemorrhagic telangiectasia patients according to age. Review of 50 consecutive patients aged 1 day60 years. Neuroradiology , Berg J, Porteous M, Reinhardt D, Gallione C, Holloway S, et alhereditary hemorrhagic telangiectasia : a questionnaire based study to delineate the different phenotypes caused by endoglin and ALK1 mutations. J Med Genet , Kjeldsen AD, Mo/ller TR, Brusgaard K, Vase P, Andersen PEClinical symptoms according to genotype amongst patients with hereditary hemorrhagic telangiectasia. J Intern Med , Letteboer TG, Mager JJ, Snijder RJ, Koeleman BP, Lindhout D, et algenotypephenotype relationship in hereditary haemorrhagic telangiectasia. J Med Genet , Lesca G, Olivieri C, Burnichon N, Pagella F, Carette MF, et algenotypephenotype correlations in hereditary hemorrhagic telangiectasia Data from the French Italian HHT network. Genet Med 91422, Aassar OS, Friedman CM, White RIThe natural history of epistaxis in hereditary hemorrhagic telangiectasia. Laryngoscope , Folz BJ, Tennie J, Lippert BM, Werner JA Natural history and control of epistaxis in a group of German patients with RenduOslerWeber disease. Rhinology , Sadick H, Sadick M, Götte K, Naim R, Riedel F, et alhereditary hemorrhagic telangiectasiaan update on clinical manifestations and diagnostic measures. Wien Klin Wochenschr , Ianola AA, Memeo M, Sabba C, Cirulli A, Rotondo A, et alhereditary hemorrhagic telangiectasiamultidetector row CT assessment of hepatic involvement. Radiology , Shovlin CL, Guttmacher AE, Buscarini E, Faughnan ME, Hyland RH, et aldiagnostic criteria for hereditary hemorrhagic telangiectasia RenduOslerWeber syndrome. Am J Med Genet , Rebeiz EE, Bryan DJ, Ehrlichman RJ, Shapshay SMSurgical management of life threatening epistaxis in OslerWeberRendu disease. Ann Plast Surg , Lund V, Howard DJA treatment algorithm for the management of epistaxis in hereditary hemorrhagic telangiectasia. Am J Rhinol ,
14 Bergler W, Sadick H, Götte K, Riedel F, Hörmann KTopical estrogens combined with argon plasma coagulation in the management of epistaxis in hereditary hemorrhagic telangiectasia. Ann Otol Rhinol laryngol , Pagella F, Semino L, Olivieri C, Corno S, Dore R, et altreatment of epistaxis in hereditary hemorrhagic telangiectasia patients by argon plasma coagulation with local anesthesia. Am J Rhinol , AlDeen S, BachmannHarildstad GA grading scale for epistaxis in hereditary hemorrhagic telangiectasia. Rhinology , Mahoney EJ, Shapshay SMNdYAG laser photocoagulation for epistaxis associated with hereditary hemorrhagic telangiectasia. Laryngoscope , Sadick H, Naim R, Oulmi J, Hörmenn K, Bergler W, et alplasma surgery and topical estrioleffects on the nasal mucosa and longterm results in patients with Osler s disease. Otolaryngol Head Neck Surg , Sadick H, Bergler WF, Oulmi Kagermann J, Naim R, Sadick M, et al Estriol induced squamous metaplasia on the nasal mucosa in patients with hereditary hemorrhagic telangiectasia. Arch Med Res , Vase PEstrogen treatment of hereditary hemorrhagic telangiectasia. A double blind controlled clinical trial. Acta Med Scand , Jameson JJ, Cave DRHormonal and antihormonal therapy for epistaxis in hereditary hemorrhagic telangiectasia. Laryngoscope , Yaniv E, Preis M, Hadar T, Shvero J, Haddad MAntiestrogen therapy for hereditary hemorrhagic telangiectasiaa double blind placebo controlled clinical trial. Laryngoscope , Sabba C, Gallitelli M, Palasciano GEfficacy of unusually high dose of tranexamic acid for the treatment of epistaxis in hereditary hemorrhagic telangiectasia. N Engl J Med , MoralesAngulo C, Pérez del Molino A, Zarrabeitia R, Fernández A, SanzRodriguez F, et al Treatment of epistaxis in hereditary hemorrhagic telangiectasia Rendu Osler Weber disease with tranexamic acid. Acta Otorhinolaringol Esp , FernandezL A, GarridoMartin EM, SanzRodriguez F, Ramirez JR, MoralesAngulo C, et altherapeutic action of tranexamic acid in hereditary hemorrhagic telangiectasia HHT : regulation of ALK1/endoglin pathway in endothelial cells. Thromb Haemost , Fiorella ML, Ross D, Henderson KJ, White RI JrOutcome of septal dermoplasty in patients with hereditary hemorrhagic telangiectasia. Laryngoscope , Stankiewicz JANasal endoscopy and control of epistaxis. Curr Opin Otolaryngol Head Neck Surg , Bublik M, Sargi Z, Casiano RRUse of the microdebridder in selective excision of hereditary hemorrhagic telangiectasia a new approach. Otolaryngol Head Neck Surg , Saunders WHSeptal dermoplasty for control of nosebleeds caused by hereditary hemorrhagic telangiectasia or septal perforations. Trans Am Acad Ophthalmol Otolaryngol , Saunders WHSeptal dermoplastya new procedure for control of nose bleeds in patients with hereditary haemorrhagic telangiectasia. J LaryngolOtol776976, Saunders WHereditary hemorrhagic telangiectasia. Effective treatment of epistaxis by septal dermoplasty. Acta Otolaryngol , Saunders WHSeptal dermoplastyten years experience. Trans Am Acad Ophthalmol Otolaryngol , Brooker DS, Cinnamond MJYoung s procedure in the treatment of epistaxis. J Laryngol Otol , Gluckman JL, Poortugal LGModified Young s procedure for refractory epistaxis due to hereditary hemorrhagic telangiectasia. Laryngoscope , Lund VJ, Howard DJClosure of the nasal cavities in the treatment of refractory hereditary
15 523 hemorrhagic telangiectasia. J Laryngol Otol , Hitchings AE, Lennox PA, Lund VJ, Howard DJThe effect of treatment for epistaxis secondary to hereditary hemorrhagic telangiectasia. Am J Rhinol , Pollak JS, Saluja S, Thabet A, Henderson KJ, Denbow N, et alclinical and anatomic outcomes after embolotherapy of pulmonary arteriovenous malformations abstract. J Vasc Intrv Radiol , Brady AP, Murphy MM, O Connor TMHereditary hemorrhagic telangiectasia : a cause of preventable morbidity and mortality. Ir J Med Sci Published online16, October, Summary ISSUES OF EPISTAXES IN CASES OF HEREDITARY HEMORRHAGIC TELANGIECTASIA Keiichi Ichimura, MD Department of Otolaryngology Head and Neck Surgery, Jichi Medical University School of Medicine Hereditary hemorrhagic telangiectasiahhtis an autosomal dominant inherited disorder affecting blood vessels of the skin, mucous membrane and viscera. Epidemiologic studies have revealed a wide range of incidences, with agreement in Europe and Japan at rates between and Mutations in at least five genes can cause HHT, with the two major disease genes on chromosome 9endoglinand chromosome 12ALK1responsible for HHT. HHT patients vary greatly in course and severity of epistaxes. Most patients have selflimiting nasal bleeding and do not require hospitalization, but about one third have severe hemorrhage necessitating admission and treatment. Clinical diagnosis of HHT is made according to the four Curaao criteria. A variety of treatment strategies have been employed. These include LASER coagulation, hormonal therapy, embolization, nasal dermoplastyndand nostril closure. It is difficult to make specific treatment recommendations for a disease that may have a wide spectrum of clinical manifestations including minimal to life threatening degrees of epistaxis. The LASER has been used as first line therapy or as additional therapy after more conventional therapies have failed. Our study demonstrated ND to be an effective procedure for HHT patients with moderate or severe nasal bleeding. The nasal mucosa of the anterior part of the septum, nasal floor and the lateral wall are removed. A split skin graft is usually used to cover the denuded area. ND can offer patients reduced frequency of bleeding. In severe and intractable cases, modified Young s procedurenostril closurehas been shown to be most effective. Key wordshereditary hemorrhagic telangiectasia, epistaxis, nasal dermoplasty, nostril closure, LASER coagulation
無水エタノールによる硬化療法および鼻粘膜癒着処置を施行したオスラー病による難治性鼻出血の1例
119 874 2016 : 0 1cc : : : : : :WBC3 640/μl RBC 247 10 /μl PLT 22 9 10 /μl Hb 7 9g/dl PT APTT : : : 1ml 30G absolute ethanol Et 0 1 0 2ml 2mm 119 875 1 000mg/day Et 0 3ml Al Deen endoglin ALK1 1 3 a b
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