Research 이병민 in 외 Vestibular 5인. 돌발성난청에서 Science Vol. 메니에르병으로의 17, No. 3, September 진행 2018 빈도 O riginal A rticle pissn 2092-8882, eissn 2093-5501 https://doi.org/10.21790/rvs.2018.17.3.95 돌발성난청에서메니에르병으로의진행빈도 이병민 1, 서진현 1, 박현우 1, 이현진 2, 허동구 2, 안성기 1,3 1 경상대학교의과대학경상대학교병원이비인후과학교실, 2 창원경상대학교병원이비인후과, 3 경상대학교건강과학연구원 Incidence of Progression into Ménière Disease from Idiopathic Sudden Sensorineural Hearing Loss: Midterm Follow-up Study Byeong Min Lee 1, Jin Hyun Seo 1, Hyun Woo Park 1, Hyun Jin Lee 2, Dong Gu Hur 2, Seong Ki Ahn 1,3 1 Department of Otorhinolaryngology and Head & Neck Surgery, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, Jinju; 2 Department of Otorhinolaryngology and Head & Neck Surgery, Gyeongsang National University Changwon Hospital, Changwon; 3 Institute of Health Sciences, Gyeongsang National University, Jinju, Korea Received Jul 9, 2018 Revised Aug 16, 2018 Accepted Aug 28, 2018 Corresponding Author: Seong Ki Ahn Department of Otorhinolaryngology and Head & Neck Surgery, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, 79 Gangnam-ro, Jinju 52727, Korea Tel: +82-55-750-8178 Fax: +82-55-759-0613 E-mail: skahn@gnu.ac.kr ORCID code: https://orcid.org/0000-0002-1078-2646 Copyright c 2018 by The Korean Balance Society. All rights reserved. This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Objectives: Ménière disease is a clinical syndrome characterized by the four major symptoms of episodic vertigo, sensorineural hearing loss, tinnitus, and aural fullness. Sensorineural hearing loss, especially low frequency, is the characteristic type of audiogram in Ménière's disease. However, it is difficult to distinguish idiopathic sudden sensorineural hearing loss (ISSNHL) with vertigo from the first attack of Ménière disease. The purpose of this study was to investigate the incidence of progression into Ménière Disease from low frequency ISSNHL. Methods: Two hundred eighty-three patients were included in this study. We classified the patients with ISSNHL according to the hearing loss in audiogram and analyzed how many of them actually progressed to Ménière disease based on diagnosis criteria. Results: Among the 240 patients, 37.1% (89 patients) were confirmed low frequency ISSNHL and 14.6% (13 patients) of them were diagnosed with Meniere disease. Conclusions: This study showed that the progression from low frequency ISSNHL to Ménière disease was higher than other frequency ISSNHL, as in other studies. Res Vestib Sci 2018;17(3):95-101 Keywords: Sudden hearing loss; Sensorineural hearing loss; Ménière disease; Incidence 서론 1861년프랑스내과의사인 Prosper Ménière에의해일시적으로발생하는어지럼, 이명, 난청이내이의병변일수있음이처음보고된이후로수많은연구들이진행되어왔다 [1]. 메니에르병은어지럼, 감각신경성난청, 이명그리고이충만감과같은 4가지대표적인증상을보이는임상증후 군으로알려져있으며원인은알수없는경우가대부분이나해부학적이상이나바이러스감염, 알레르기나자가면역질환등이추정되고있다 [2]. 메니에르병에서나타나는감각신경성난청의경우주로저음역대의난청이흔함이알려져있다 [3]. 이런이유로환자가저음역대감각신경성난청이처음발생하였을때이것을돌발성난청 (sudden sensorineural hearing loss) 과구별하기는쉽지않다. 세계보 95
Res Vestib Sci Vol. 17, No. 3, Sep. 2018 건기구와유럽연합 (World Health Organization and the European Union) 에따르면돌발성난청의유병률은 100,000 당 50명이하일정도로매우드문질환이며메니에르병또한유병률이 100,000명당 190명정도로보고되어있다 [4-6]. 실제로저음역난청환자들중 10% 내외에서메니에르병으로진행한다는보고들이있으나관련된연구가많지않으며그결과가상이할뿐만아니라최신메니에르병의진단기준을적용한보고가없다. 이에저자들은최신메니에르병의진단기준을적용하여돌발성난청에서메니에르병으로진행되는빈도및난청음역에따른비교, 그리고그에따른청력호전정도를확인하고자연구를진행하였다. 대상및방법 이연구는 2013년도부터 2015년도까지돌발성난청으로내원한환자 283명을대상으로하였다. 대상군중고막천공이나외상, 소음노출등특이과거력이있는환자들은제외하였으며악성종양이나자가면역질환등다른전신적질환이있는환자또한연구에서제외하였다. 돌발성난청의진단은증상이발생한지 72시간이내순음청력검사상최소한 3개이상의연속된주파수에서 30 db 이상역치가감소한경우로정의하였다 [7]. 이에총 240명이선별되었으며남성이 137명, 여성이 103명, 평균나이는 50.5세이며 13세에서 80세까지분포되었다. 대상군의청력역치는순음청력검사를통해확인하였으며 4분법으로계산하여평균 50 db, 표준편차 27.7 db로나타났고범위는 6.3 100 db이었다. 100 db 이상의고도난청과무반응결과는 100 db로계산하였다 (Table 1). 평균추적관찰기간은 195주이며시행한순음청력검사상청력저하의양상에따라저음역 (0.25 1 khz), 중간음역 (1 4 khz), 고음역 (4 8 khz) 및전 Table 1. Demographic data (n=240) Variable Value Age (yr) Mean±SD (range) 50.5±13.8 (13 80) Sex, male:female 137:103 Laterality, right:left 119:121 F/U period (wk) Mean±SD (range) 195±41 (126 280) Pure Tone Audiometry (db) Mean±SD (range) 50±27.7 (6.3 100) SD, standard deviation; F/U, follow-up. 체음역난청으로분류하였다 (Fig. 1). 모든환자들은고용량스테로이드 (1 mg/kg, 최대 60 mg, 10 days) 치료를시행하였고, 그중저음역감각신경성난청환자들은스테로이드와동시에이뇨제 (hydrochlorothiazide 25 mg, twice a day) 도함께복용하도록하였다. 이뇨제는모든저음역감각신경성난청환자들에게 2주를기준으로처방하였으며그전에난청이호전이되면중단하도록하였다. 메니에르병으로진행된경우는 3개월을기본으로복용하였으며이후증상발현여부에따라추가또는중단하였다. 회복여부는외래환자인경우 1주일뒤에첫번째재평가를시행하였으며이후환자사정에따라 1주혹은 2주간격으로추적관찰하였고입원환자의경우주 3회순음청력검사를시행하였다. 메니에르병은미국이비인후-두경부외과학회에서 2015년에정의한명확한메니에르병의기준에준하여진단하였으며 (The 2015 report of the Committee on Hearing and Equilibrium of the American Academy of Otolaryngology- Head and Neck Surgery, definite Ménière's disease) 청력의회복은 Siegel s Criteria 에따라순음청력검사결과에서 15 db 이상호전되었을경우로정의하였다 (Tables 2, 3) [2,8,9]. 이를통해각음역대별난청에따라메니에르병으로의진행및청력회복에대해분석하였으며성별에따른분석도함께시행하였다. 범주형변수의경우빈도수와비율로결과를나타내었고, 연속형변수는평균값과표준편차를이용해표현하였다. 난청음역에따른메니에르병으로의진행률과의상관관계를확인하기위해각음역대별로나누어 Fisher exact test를사용하여통계학적유의성을확인하였으며, 성별에따른진행률및메니에르병의진행여부에따른청력호전정도를분석을보기위해 chi-square test를사용하였다. 모든통계학적검증은 IBM SPSS ver. 18.0 (IBM Co., Armonk, NY, USA) 를사용하였으며, p 값이 0.05 미만일때통계적으로유의미하다고판정하였다. 결과총 240명의환자들중에서저음역감각신경성난청환자는 89명 (37.1%), 중간음역감각신경성난청환자는 5명 (2.1%), 고음역감각신경성난청환자는 43명 (17.9%), 전음역감각신경성난청환자는 103명 (42.9%) 으로확인되었다. 증상발생후첫내원까지걸린기간은평균 8.4일, 표준편차는 10.2일이었으며 240명중 47명이타병원에서약물치 96
이병민 외 5인. 돌발성난청에서 메니에르병으로의 진행 빈도 Fig. 1. Hearing loss (HL) type. (A) High tone HL, (B) middle tone HL, (C) low tone HL, and (D) whole tone HL. 97
Res Vestib Sci Vol. 17, No. 3, Sep. 2018 Fig. 1. Continued. 98
이병민외 5 인. 돌발성난청에서메니에르병으로의진행빈도 Table 2. Amended 2015 criteria for diagnosis of Ménière disease Definite Two or more spontaneous episodes of vertigo, each lasting 20 minutes to 12 hours Audiometrically documented low- to midfrequency sensorineural hearing loss in 1 ear, defining the affected ear on at least 1 occasion before, during, or after 1 of the episodes of vertigo Fluctuating aural symptoms (hearing, tinnitus, or fullness) in the affected ear Not better accounted for by another vestibular diagnosis Probable Two or more episodes of vertigo or dizziness, each lasting 20 minutes to 12 hours Fluctuating aural symptoms (hearing, tinnitus, or fullness) in the affected ear Not better accounted for by another vestibular diagnosis 료를먼저시작하였다. 전체환자들중 14명 (5.8%) 의환자들이고용량스테로이드복용이후경과관찰중에 definite Ménière disease로진단되었으며저음역감각신경성난청환자군에서는 13명 (14.6%), 전음역감각신경성난청환자군에서는 1명 (0.97%) 으로확인되었고중음역및고음역감각신경성난청환자군에서는 definite Ménière disease로진단된환자들은없었다 (Tables 4, 5). 청력의회복여부를보았을때메니에르병으로진단된환자들에서는 14명중 10명 (70.3%) 이회복되었으며메니에르병으로진단되지않은환자들에서는 226명중 98명 (43.4%) 이회복되었으며이는 p 값이 0.04로통계적으로유의미한값을가졌다 (Fig. 2). 청력이회복된환자군에서순음청력검사상난청발생시평균은 50 db, 표준편차는 27.6 db이었며회복후평균 28.3 db, 표준편차는 18.6 db로확인되었고, 치료시작후청력회복까지걸린기간은평균 12.4일, 표준편차 11.3일로나타났다. 성별에따른차이로는남성환자들중에서메니에르병으로진행한환자는총 131명중 6명 (4.4%) 이었으며여성환자들에서는총 95명중 8명 (7.8%) 이었다 (Fig. 3). 성별에따른메니에르병으로의진행률을비교한통계분석에서위험도 (odd ratio) 는여성대비남성에서 0.56로상대적으로낮게측정되었으나, p 값은 0.28로통계적으로유의미한차이를보이지는않았다. 고 찰 돌발성난청의유병률은 100,000 명당 3 160 명으로다양 Table 3. Siegel s criteria of hearing recovery Type Hearing recovery I. Complete recovery Final hearing better than 25 db II. Partial recovery More than 15 db gain, final hearing 24 25 db III. Slight improvement More than 15 db gain, final hearing poorer than 45 db IV. No improvement Less than 15 db gain, final hearing poorer than 75 db 하게보고가되고있지만실제유병률은훨씬더높을것이라는견해가많다 [10]. 이는자연적인회복률이높아증상이발생하여도실제로병원을찾지않는환자들이많을것이라고생각되기때문이며자연회복률은 45% 65% 정도로보고되고있다 [11]. 메니에르병초기에발생하는증상들의비율을보면난청은 22%, 어지럼이 37%, 두가지모두나타나는경우가 41% 정도로보고되고있어단순히난청만있을경우에는돌발성난청과감별이어렵다고알려져있다 [12]. 이연구에서는메니에르병의주증상인난청이단일증상으로발생한경우돌발성난청으로진단될수있을것이며, 그후경과관찰중에어지럼이나이명, 이충감과같은증상이동반되면서메니에르병으로진행할수있을것이라생각했고실제그빈도를확인하였다. 이연구에서저음역감각신경성난청환자들에서 14.6% 에서메니에르병으로진행됨을확인하였으며다른음역의난청환자들보다메니에르병으로진행될가능성이높음을알수있었다. 청력회복의경우에도메니에르병으로진단된군에서 71.4%, 그렇지않은군에서 43.4% 로나타나메니에르병의증상중하나인감각신경성난청의경우일시적으로나타나는경우가많아청력의회복률이높음을마찬가지로함께설명할수있다. 메니에르병의성별에따른유병률차이는일반적으로여성에서좀더높다고알려져있다. 그차이가크지는않으나여성대남성의비가 1.3:1 4.3:1로다양하게보고되어있으며이연구에서도남녀유병률의차이가 1.8:1로여성군에서좀더높게나타났으나통계적으로유의미하지는않았다 [6]. 이런성별에서의차이는메니에르병이성호르몬에따른영향도있을것이라보는견해도있으며성별에따라사회적활동이다름에서나타나는차이라보는견해도있다 [13]. 메니에르병의발병기전은내림프수종과관련이있을것이라생각되며이로인한내이의막성미로내의내림프압력의증가로인해감각신경성난청이나어지럼, 이명및이충만감과같은증 99
Res Vestib Sci Vol. 17, No. 3, Sep. 2018 Table 4. Rate of progression to Ménière disease (MD) and hearing recovery according to hearing loss type Hearing loss type No. (%) MD progression MD nonprogression p-value High 43 (17.9) 0 (0) 43 (100) 0.68 a) Middle 5 (2.1) 0 (0) 5 (100) 0.55 a) Low 89 (37.1) 13 (14.6) 76 (85.4) 0.01 a) Whole 103 (42.9) 1 (1) 102 (99) 0.06 a) a) Person χ 2 test. Table 5. Demographic data (progression to Ménière disease) Variable Total (n=14) Age (yr) Mean±SD (range) 49.9±13.7 (32 65) Sex, male:female 6:8 Laterality, right:left 7:7 F/U period (wk) Mean±SD (range) 192±40 (132 274) Pure Tone Audiometry (db) Mean±SD (range) 38±25 (5 100) SD, standard deviation; F/U, follow-up. Fig. 3. Ratio of progression to Meniere disease was 4.4% in male and 7.8% in female (p=0.28). 을경우메니에르병과돌발성난청을감별하는것은여전히어렵다. 실제두질환을감별하기위해전정유발근전위검사를시행해보았을때유의한차이가있어감별진단에이를이용할수있다는보고도있으나임상에서난청으로내원한모든환자에게검사를시행하기에는어려움이있다 [11]. Fig. 2. In patients with progression to Meniere disease, 71.4% had hearing recovery. On the other hand, the recovery rate was 43.4% in not progression patients (p=0.04). 상이발생한다고알려져있다 [14]. 때문에내림프압력을줄이는방법으로저염식이를통한염분섭취의감소나이뇨제복용이대표적으로알려져있으며여러연구를통해실제증상완화및악화방지에효과가있음이입증되었다 [15]. 이연구는후향적분석을통해저음역감각신경성난청이다른음역대의감각신경성난청과비교하여메니에르병으로진행할가능성이높다는사실을확인하였다. 그러나환자가처음내원하여저음역감각신경성난청이확인되었 결론메니에르병환자가실제로돌발성난청으로잘못진단되었을가능성을고려해볼때, 청력의개선과관계없이지속적인경과관찰이필요하다. 특히나저음역난청환자들에게는메니에르병으로의진행가능성및치료와경과에대해추가적으로설명하도록하고특히나어지럼이나다른증상이동반될시재내원이필요함을설명하는것이바람직하다. 중심단어 : 돌발성난청, 감각신경성난청, 메니에르병, 발병률 100
이병민외 5 인. 돌발성난청에서메니에르병으로의진행빈도 이해관계 (CONFLICT OF INTEREST) 저자들은이논문과관련하여이해관계의충돌이없음을명시합니다. REFERENCES 1. Meniere P. Congestions cerebrales apoplectiformes. Gaz md Paris 1861;16:55. 2. Goebel JA. 2015 Equilibrium Committee Amendment to the 1995 AAO-HNS guidelines for the definition of Ménière's disease. Otolaryngol Head Neck Surg 2016;154:403-4. 3. Stahle J, Stahle C, Arenberg IK. Incidence of Ménière's disease. Arch Otolaryngol 1978;104:99-102. 4. Klemm E, Deutscher A, Mösges R. A present investigation of the epidemiology in idiopathic sudden sensorineural hearing loss. Laryngorhinootologie 2009;88:524-7. 5. Harris JP, Alexander TH. Current-day prevalence of Ménière's syndrome. Audiol Neurootol 2010;15:318-22. 6. A lexander TH, Harris JP. Current epidemiology of Meniere's syndrome. Otolaryngol Clin North Am 2010;43:965-70. 7. Wilson WR, Byl FM, Laird N. The efficacy of steroids in the treatment of idiopathic sudden hearing loss. A double-blind clinical study. Arch Otolaryngol 1980;106:772-6. 8. Lopez-Escamez JA, Carey J, Chung WH, Goebel JA, Magnusson M, Mandalà M, et al. Diagnostic criteria for Menière's disease. J Vestib Res 2015;25:1-7. 9. Siegel LG. The treatment of idiopathic sudden sensorineural hearing loss. Otolaryngol Clin North Am 1975;8:467-73. 10. Teranishi M, Katayama N, Uchida Y, Tominaga M, Nakashima T. Thirty-year trends in sudden deafness from four nationwide epidemiological surveys in Japan. Acta Otolaryngol 2007;127: 1259-65. 11. Chen CN, Young YH. Differentiating the cause of acute sensorineural hearing loss between Ménière's disease and sudden deafness. Acta Otolaryngol 2006;126:25-31. 12. Enander A, Stahle J. Hearing in Menière's disease. A study of pure-tone audiograms in 334 patients. Acta Otolaryngol 1967;64:543-56. 13. Watanabe I. Ménière's disease in males and females. Acta Otolaryngol 1981;91:511-4. 14. Hallpike CS, Cairns H. Observations on the pathology of Ménière's syndrome: (section of otology). Proc R Soc Med 1938;31:1317-36. 15. Park HW, Chung WH, Kim SH, Kim KS, Chung JW, Chae SW, et al. Multicenter randomized study on the efficacy of isosorbide in patients with Mèniére's disease. Res Vestib Sci 2016;15:44-50. 101