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1 대한한방내과학회지제 37 권 6 호 (2016 년 12 월 ) J. Int. Korean Med. 2016;37(6): 구강작열감증후군환자에서심상유두수측정의진단적가치 이엄지, 박재우, 김진성경희대학교대학원임상한의학과 Diagnostic Values of the Measurement of Fungiform Papillae in Patients with Burning Mouth Syndrome Eom-jee Lee, Jae-woo Park, Jin-sung Kim Dept. of Clinical Korean Medicine, Graduate School, Kyung-Hee University ABSTRACT Objectives: This study evaluated the diagnostic values of measuring the number of fungiform papillae in patients with burning mouth syndrome (BMS). Methods: Seventy participants (35 BMS patients and 35 Healthy control) participated in this study. The number of fungiform papillae (FP) was measured on the anterior part of the tongue within an area of 9 mm 2 using a digital camera. The subjects were evaluated on their yin deficiency and blood stasis conditions using the Yin-Deficiency Questionnaire (YDQ) and Blood Stasis Questionnaire (BSQ). Moreover, the severities of subjective tongue pain in the BMS patients were assessed using Visual Analog Scale. Results: There were significant differences in the number of FP and the YDQ and BSQ scores between the two groups. The number of FP and the YDQ scores in the BMS group showed statistically significant correlations with the VAS score of tongue pain. In the bivariate logistic regression analysis, the factor that most strongly contributed to BMS was the number of FP. The optimal cut-off value of the number of fungiform papillae was calculated as 5.5 with 71.4% sensitivity and 82.9% specificity. There was no statistically significant correlation between the number of FP and the YDQ or BSQ score. Conclusions: According to these findings, measuring the number of FP could be a valuable evaluation indicator of BMS. Key words: burning mouth syndrome, fungiform papillae, Yin-deficiency Ⅰ. 서론 구강작열감증후군 (burning mouth syndrome, BMS) 은임상적으로증상을유발할수있는구강점막의이상소견이없음에도작열감양상의불편감이 투고일 : , 심사일 : , 게재확정일 : 교신저자 : 김진성서울시동대문구경희대로 26 경희대학교대학원임상한의학과 TEL: oridoc@khu.ac.kr 본논문은제 1 저자의석사학위논문을수정, 보완한것임. 나통증이나타나는질환이다 1. 만성적구강통증과함께미각기능이상이나구강건조감이흔히동반되며 2, 증상으로인한불편함이외에도삶의질을현저히저하시킨다 3. BMS의병인에대해서는명확히밝혀진바는없으나신경학적기능장애, 스트레스축과호르몬의기능장애, 정신적인요인들을비롯하여구강의이상습관과치아문제와같은국소적원인, 당뇨, 갑상선기능저하증, 쇼그렌증후군, 칸디다증과같은다양한요인이있으며, 병인이구체적으로밝혀져 978

2 이엄지 박재우 김진성 있지않고복합적인요인이작용하기때문에, 표준적인진단과치료가확립되어있지않은실정이다 4,5. 심상유두 (fungiform papillae) 는미각과체성감각과관련된신경이분지하고있어서혀에서수용하는감각들과연관이깊은데, BMS에서통증및미각이상등의증상이나타나기때문에심상유두와 BMS의관계에대해서도여러연구들이시행되었으나, 연구들마다결과에차이를보인다 6,7. 혀에존재하는설유두 (lingual papillae) 와한의학적변증유형간의상관성에대한연구도보고되었으나 8 BMS 환자를대상으로한연구는아직보고된바없다. 한의학적으로는 BMS를주로陰虛, 心火上炎, 瘀血, 脾虛, 肝鬱등으로변증하여치료하지만특히음허로인한허화를기본병리로보고있으며 9,10, 通則不痛, 不通則痛 의관점에서보았을때어혈증도 BMS의주요변증유형으로볼수있다 11,12. 본연구에서는환자군과건강대조군에서심상유두의수를비교해보고, BMS 환자의특정유형에서심상유두수가밀접한관계가있을수있다는가정하에심상유두의수와음허증 어혈증에대한상관성을조사함으로써심상유두의수가 BMS 의한의학적변증과 BMS의객관적진단지표로활용될수있는가능성을탐색하고자하였다. Ⅱ. 연구대상자및연구방법 1. 대상본연구는 BMS 환자를대상으로, 구강점막에서느끼는감각과관계되는심상유두의수를 BMS 환자군과건강대조군간비교분석하고음허및어혈변증유형별로비교분석함으로써, 심상유두수측정의유용성을검증하고자한연구이다. 본연구는 2014년 12월 1일부터 2015년 6월 15일까지경희대학교한방병원한방소화기내과구강병클리닉에내원한 BMS 환자중포함기준및제외기준 (Table 1) 을적용하여적합하다고선정된 35명을대상으로하였다. 대조군으로는구강내점막이상과같은뚜렷한비정상적소견이없으면서구강내의작열감및통증이없는동일한연령대의건강인을 35명모집하여진행하였다. 연구대상자전원은연구목적및과정등에대하여연구자로부터충분한설명을들었으며, 자발적으로동의서를작성하였다. 본연구는의학연구윤리에대한헬싱키선언을준수하였으며, 경희대학교한방병원임상시험심사위원회 (institutional review board, IRB) 의승인 (IRB No. KOMCIRB HR-027) 을받은후진행되었다. Table 1. Inclusion and Exclusion Criteria Inclusion criteria Burning mouth syndrome group 1. Over the age of No difficulty in communication; such as reading, writing, seeing, hearing, etc. 3. Subjects who complain about burning sensation of pain in oral cavity without any abnormal features like abnormality of oral mucosa or tooth 4. Subjects who sign a written informed consent spontaneously Healthy control group 1. Over the age of No difficulty in communication; such as reading, writing, seeing, hearing, etc. 3. Subjects who don t have burning sensation of pain in oral cavity and any abnormal features like abnormality of oral mucosa or tooth 4. Subjects who sign a written informed consent spontaneously 979

3 구강작열감증후군환자에서심상유두수측정의진단적가치 Exclusion criteria 1. A history of diseases like diabetes mellitus, thyroid diseases, oral diseases, dental and periodontal diseases, otorhinolaryngological diseases, gastrointestinal diseases which can induce burning sensation 2. A history of craniocervical radiation therapy 3. Subjects who cannot maintain the state of sticking their tongue out 4. Subjects who have excessively increased filiform papillae, which disturb observations of fungiform papillae 5. Subjects unable to limit oral activities (eating, gargling, etc.) at least 4 hours 2. 연구방법 1) 인구학적조사전체연구대상자 60명에게설문지를이용한면담을실시하여성별, 연령 ( 년 ), 이환기간 ( 개월 ), 신장 (cm), 체중 (kg), 체질량지수 (body mass index, BMI)(kg/m 2 ), 흡연력, 음주력등을조사하였다. 2) 구강작열감에대한 VAS 측정시각적상사척도 (visual analog scale, VAS) 는환자가호소하는주관적인증상을객관화하기위해임상적으로다용하는방법중의하나로서 13, 본연구에서는환자군에서의주관적인구강작열감정도를평가하기위하여시행하였다. 측정방법은 mm의직선을이용하여 0 mm 지점을 없음 으로, 100 mm 지점을 매우심함 으로설정하여대상자스스로느끼는증상의정도를가로선위에직접표시하게하였으며, 0 mm 지점에서표시된지점까지의거리를자로측정하여점수화하였다. 3) 단위면적당심상유두수의측정심상유두 (fungiform papillae) 관찰에영향을줄수있는요소를배제하기위하여측정 4시간전에일체의구강활동을금하도록한상태에서촬영을진행하였다. 심상유두수의측정방법과관련하여혀표면일부에분포하는심상유두의수로혀전체의심상유두수를유추할수있으며 18, 그중에서도혀를구역별로나누었을때설첨부에서 1 cm 떨어진구역에서측정할때가장높은상관관계를보였다는선행연구결과 18,19 를참고하여측정부위를설정하였다 (Fig. 1). 또한, 청색식용색소로혀를염색할경우심상유두는염색이되지않아분홍색으로관 찰되거나연하게염색되고심상유두를제외한부위는진한푸른색으로염색되어심상유두를선명히관찰할수있다는것을이용하여 20, 촬영에앞서청색 1호식용색소를이용해측정부위를염색하였고혀에남아있는색소는물로입을헹구어내어제거하였다. 염색후혀를전방으로내밀게하여미리지름 6 mm의구멍을뚫어놓은눈금종이를설첨부와설배면의중앙선좌측에완전히밀착시키고혀를내민상태로유지하면서사진을촬영하는동안가능한움직이지않게한후사진을 3~4회연속촬영하였다 (Fig. 2). 이중에서심상유두를가장선명하게관찰할수있는사진을택하여지름 6 mm의단위면적내에분포하는심상유두의수를측정하였다. 촬영도구로는디지털카메라 (SAMSUNG NX300M, Korea) 를이용하였다. Fig. 1. Measuring area on the anterior part of the tongue. 980

4 이엄지 박재우 김진성 A B Fig. 2. (A-B) Measurement of fungiform papillae in a human tongue. (A) A tongue is stained with blue food dye and a graph paper with a perforation of 6 mm diameter is placed on the anterior part of the tongue. (B) Arrows indicate typical lingual fungiform papillae. 4) 음허증설문지를이용한음허증판정연구대상자의음허증 ( 陰虛證 ) 여부를진단하기위하여이 14 등에의해신뢰성과타당성이입증된음허증설문지 (Yin-deficiency questionnaire, YDQ) 를이용하였다. 본설문지는음허증을구성하는증상 ( 五心煩熱, 午後觀紅, 潮熱, 口乾咽燥, 盜汗, 形體消瘦, 眩暈, 失眠, 尿少色黃, 大便秘結 ) 에대한 10개문항으로구성되어있으며, 각증상의심한정도를 mm의직선을이용하여 0 mm 지점을 없음 으로, 100 mm 지점을 매우심함 으로설정하여대상자스스로느끼는증상의정도를가로선위에직접표시하게하였다. 0 mm 지점에서표시된지점까지의거리를자로측정하여점수화하였고, 최종합산점수를구한후장등 15 의연구를통해산 출된최적절단값인 304점을기준으로하여이를초과한경우에는음허증으로진단하고, 이하인경우에는음허증이아닌것으로진단하였다. 5) 어혈증설문지를이용한어혈증판정연구대상자의어혈증 ( 瘀血證 ) 여부를진단하기위하여양등 16 에의해개발되고박등 17 에의해신뢰성과타당성이입증된어혈증설문지 (blood stasis questionnaire, BSQ) 를이용하였다. 본설문지는어혈증과관련된총 12개문항으로구성되어있으며, 각항목에 전혀그렇지않다 (1점), 그렇지않다 (2점), 그렇지않은편이다 (3점), 보통이다 (4점)', 그런편이다 (5점), 그렇다 (6점), 매우그렇다 (7 점 ) 의 7점 Likert 척도로대상자스스로응답할수있도록하였다. 선행연구 17 를통해마련된최적절단값은각항목의점수가 1-4점일경우에는 0점, 5-7점일경우에는 1점 으로이분척도를이용해환산하여더했을때, 3점을기준으로 3점이상일경우에는어혈증으로, 미만일경우에는어혈증이아닌것으로판정하였다. 3. 통계분석수집된모든자료는 mean±standard deviation (S.D.) 또는 number(%) 로나타내었다. 환자군과건강대조군의일반적특성, 심상유두수, YDQ 점수및 BSQ 점수는 Independent t-test를이용하였고, 환자군에서구강작열감의정도를평가한 VAS 와심상유두수, YDQ 점수, BSQ 점수간의상관관계는 Pearson s correlation analysis 를이용하였다. 심상유두수, 음허 어혈점수가 BMS 발생에미치는영향은 Bivariate logistic regression analysis 를이용하여분석하였고, 환자군및건강대조군을대상으로심상유두수의 ROC(receiver operating characteristic) curve를이용하여 BMS 유무에대한심상유두수의최적절단값 (optimal cut-off value) 를도출하였다. 최적절단값과 BMS 진단여부에따른민감도, 특이도, 양성예측도및음성예측도는 2 2 table을이용하여산출하였다. 음허증및어혈증설문지를 981

5 구강작열감증후군환자에서심상유두수측정의진단적가치 이용한환자군, 건강대조군의음허증, 어혈증판정여부에대한분석은 Chi-square test를이용하였으며, 음허증, 어혈증판정결과에따른심상유두수분석은 Mann-Whitney U-test 를이용하였다. 음허 어혈점수와심상유두수간의상관관계는 Pearson s correlation analysis를이용하였다. 연구에사용된자료의분석및통계처리는 PASW Statistics 18(SPSS Inc., Chicago, IL, USA) 프로그램을이용하였고, 유의수준은 P-value<0.05로하였다. Ⅲ. 결과 1. 일반적특성 70명의연구대상자중환자군이 35명, 대조군이 35명이었고, 평균연령은환자군은 58.77±13.05세, 대조군은 55.69±10.38 세로통계적으로유의한차이가없었으며 (p=0.277), 남녀성비는같았다. BMI 평균은환자군에서 22.88±3.05, 대조군에서 23.74±2.85 로통계적으로유의한차이가없었다 (p=0.229)(table 2). Table 2. General Characteristics of Subjects BMS HC p N Age (year) 58.77± ± Gender, male:female 1:34 1:34 1 BMI 22.88± ± BMS : burning mouth syndrome, HC : healthy control, BMI : body mass index Values are the mean±standard deviation. P-value is calculated by independent t-test. * : statistically significant difference (p<0.05) 2. 환자군과건강대조군의평가지표비교심상유두수의경우환자군이단위면적당평균 6.20±2.04개, 대조군이평균 3.63±2.18개로환자군에서더많았으며통계적으로유의한차이가있었다 (p=0.000). YDQ를통한음허점수는환자군이평균 ±141.19점, 대조군이 ±112.42점으로 환자군에서더높았고통계적으로유의한차이가있었다 (p=0.000). BSQ를통한어혈점수는환자군이 32.00±11.68점, 대조군이 26.09±9.04점으로환자군에서더높았고통계적으로유의한차이가있었다 (p=0.021)(table 3). Table 3. Comparisons of Number of Fungiform Papillae, Total Score of Yin-deficiency Questionnaire and Blood Stasis Questionnaire between BMS and HC Group BMS HC p Number of fungiform papillae ±2.04 ± * Total score of YDQ ± ± * Total score of BSQ ±11.68 ± * BMS : burning mouth syndrome, HC : healthy control, YDQ : Yin-deficiency questionnaire, BSQ : blood stasis questionnaire Values are the mean±standard deviation. P-value is calculated by independent t-test. * : statistically significant difference (p<0.05) 3. 환자군에서구강작열감의정도와평가지표간의상관성환자군에서심상유두수는구강작열감의 VAS 점수와통계적으로유의한양의상관관계를보였으며 (r=0.399, p=0.018), 음허점수도구강작열감의 VAS 점수와통계적으로유의한양의상관관계를보였다 (r=0.424, p=0.011). 어혈점수는통계적으로유의한상관관계를보이지않았다 (r=0.009, p=0.959)(table 4). 4. 심상유두수, 음허증및어혈증이구강작열감증후군발생에미치는영향환자군의심상유두수, 음허증및어혈증이 BMS 발생에미치는영향을이변량로지스틱회귀분석을이용하여분석하였다 (Table 5). 회귀모형의독립변수는나이, BMI, 심상유두수, 음허및어혈 982

6 이엄지 박재우 김진성 점수였고, 종속변수는 BMS 유무였다. Hosmer and Lemeshow test의 P-value는 1단계에서 0.552, 2단계에서 0.113으로적합한모형이었고, 모형의설명력은 47.9% 였으며 (R²=479), 최종결과에서독립변수중심상유두수와음허점수가유의한위험요인이었다 (for number of fungiform papillae, OR: 1.665, 95%CI: , p=0.002, for total score of YDQ, OR: 1.007, 95%CI: , p=0.005). Table 4. Correlation Analysis between VAS of Tongue Pain and Total Score of YDQ and BSQ VAS of tongue pain r p Number of fungiform papillae * Total score of YDQ * Total score of BSQ VAS : visual analog scale, YDQ : Yin-deficiency questionnaire, BSQ : blood stasis questionnaire r : pearson's correlation coefficient P-value is calculated by Pearson's correlation. : statistically significant correlation * : statistically significant (p<0.05) Table 5. Results of the Bivariate Logistic Regression Analysis for BMS Variable Odd ratio 95% CI Lower Upper p Age BMI Step 1 Number of fungiform papillae * Total score of YDQ * Total score of BSQ Age Step 2 BMI Number of fungiform papillae * Total score of YDQ * BMS : burning mouth syndrome, CI : Confidence Interval, BMI : body mass index, YDQ : Yin-deficiency questionnaire, BSQ : blood stasis questionnaire P-value is calculated by bivariate logistic regression analysis. * : statistically significant (p<0.05) 5. 심상유두수의최적절단값및타당도 (Validity) 평가환자군과건강대조군의심상유두수의 ROC 곡선및최적절단값을도출한결과 ROC 곡선아래의면적 (area under the ROC curve, AUC) 은 (p=0.000) 이었고, 최적절단값은 5.5로산출되었으며이때의민감도와특이도는각 71.4% 와 82.9% 였다 (Fig. 3). ROC 곡선에의해도출된최적절단값들을근거로 2 2 table을작성하여분석한결과, 민감도는 0.714(25/35), 특이도는 0.829(29/35), 양성예측도는 0.806(25/31), 그리고음성예측도는 0.744(29/39) 이었다 (Table 6). 983

7 구강작열감증후군환자에서심상유두수측정의진단적가치 Fig. 3. ROC curve of the number of fungiform papillae. ROC curve : Receiver operating characteristic curve Table 6. Two-by-two Table Using the Number of Fungiform Papillae BMS HC Number of fungiform papillae Sensitivity 71.4% Specificity 82.9% Positive predictive value 80.6% Negative predictive value 74.4% BMS : burning mouth syndrome, HC : healthy control 6. 음허증, 어혈증판정결과및판정결과에따른심상유두수분석 1) 음허증및어혈증판정결과전체연구대상자에서음허증설문지를시행하여최적절단값인 304점를기준으로음허증을판정하였다. 건강대조군에비해환자군에서음허증으로진단된비율이통계적으로유의한차이가있었고 (χ 2 =10.769, p=0.001), 건강대조군에비해환자군에서어혈증으로진단된비율도통계적으로유의한차이가있었다 (χ 2 =5.851, p=0.016)(table 7). 2) 음허증, 어혈증판정결과에따른심상유두수분석음허증판정결과에따른심상유두수는전체에서만통계적으로유의한차이가있었고 (p=0.001), 환자군및건강대조군으로나누었을때에는통계적으로유의한차이가없었으며. 어혈증판정결과에따른심상유두수는모든군에서유의한차이가없었다 (Table 8). Table 7. Yin-deficiency Pattern and Blood Stasis Pattern According to BMS and HC Group Yin-deficiency pattern Blood stasis pattern Yes n (%) No n (%) χ 2 p Yes n (%) No n (%) χ 2 p Total 18 (25.71) 52 (74.29) 19 (27.14) 51 (72.86) BMS 15 (42.86) 20 (57.14) 14 (40.00) 21 (60.00) * HC 3 (8.57) 32 (91.43) 5 (14.28) 30 (85.71) * BMS : burning mouth syndrome, HC : healthy control P-value is calculated by chi-square test. * : statistically significant (p<0.05) 984

8 이엄지 박재우 김진성 Table 8. Comparisons of the Number of Fungiform Papillae between Two Groups Evaluated by Yin-deficiency Questionnaire and Blood Stasis Questionnaire Number of Yin-deficiency pattern Blood stasis pattern p fungiform papillae Yes No Yes No p Total 6.67± ± * 5.42± ± BMS 6.87± ± ± ± HC 5.67± ± ± ± BMS : burning mouth syndrome, HC : healthy control Values are the mean±standard deviation. P-value are calculated by Mann-Whitney U-test. * : statistically significant difference (p<0.05) 7. 심상유두수와음허점수, 어혈점수와의상관성전체연구대상자에서심상유두수는음허점수와통계적으로유의한양의상관관계를보였고 (r=0.380, p=0.001), 환자군에서심상유두수는음허점수와약한양의상관관계를보였지만통계적으로유의하지않았으며 (r=0.308, p=0.072), 건강대조군에서심상유두수와음허점수는유의한상관관계를보이지않았다 (r=-0.006, p=0.973). 또한전체, 환자군, 건강대조군모두에서심상유두수는어혈점수와유의한상관관계를보이지않았다 (Table 9). Table 9. Correlation Analysis between the Number of Fungiform Papillae and Total Score of YDQ and BSQ Total score of Total score of Number of YDQ BSQ fungiform papillae r p r p Total * BMS HC YDQ : Yin-deficiency questionnaire, BSQ : blood stasis questionnaire, BMS : burning mouth syndrome, HC : healthy control r : pearson's correlation coefficient P-value is calculated by Pearson's correlation. : statistically significant correlation * : statistically significant (p<0.05) Ⅳ. 고찰 BMS는구강내점막이상및치아병변과같은뚜렷한비정상적소견이없음에도불구하고구강내의타는듯한작열감또는통증을주증상으로호소하는질환으로, 특징적인육안적 조직학적소견이존재하지않는다. 따라서 BMS의진단은구강점막의상태및환자의진술에의존하게되며, 이와같은특성으로인해진단및치료에어려움이많다 21. 설진 ( 舌診 ) 은한의학의 4가지진단방법인망문문절 ( 望聞問切 ) 의사진 ( 四診 ) 중망진 ( 望診 ) 에속하는진단법으로, 설질과설태의색택, 형태의변화를살펴서장부 기혈 진액의상태를관찰하고병사의성질, 경중등을판단할수있어중요한진단방법중하나이다 22. 설진에서는주로설질과설태의상태및변화에초점을맞추고있으나, 최근에는혀에존재하는설유두의한종류인심상유두와한의학적변증유형중비기허증간의상관성을분석해보고자한연구가이루어지기도하였다 8. 설유두는혀의배면에존재하며, 심상유두 (fungiform papilla), 사상유두 (filiform papilla), 엽상유두 (foliate papilla), 유곽유두 (circumvallate papilla) 의 4종류로구성된다. 이중심상유두에는안면신경에서분지되어나온고삭신경과, 삼차신경의분지인하악신경에서분지되는설신경이분포되어 985

9 구강작열감증후군환자에서심상유두수측정의진단적가치 있는데, 고삭신경은혀에서느끼는미각과관련되며설신경은통증 온도감각을느끼는체성감각과관련이있다. 말초에서받아들이는미각과체성감각을중추로전달하는신경전달과정은상호작용을일으켜서, 미각의자극이있을경우삼차신경에서중추로전해지는감각전달을억제한다 23. 따라서미각을수용 전달하는고삭신경의기능이저하될경우미각인지가저하됨으로써설신경에서중추로전해지는통증경로를차단하지못하여구강내자극에대한과감각으로 BMS의증상인구강내작열감및통증이발생할수있다 6,24. 이와같은고삭신경의기능저하를동반한신경퇴행성의과정 6 이외에 BMS의병태생리로알려진기전에는구강내점막의말초세섬유소실및신경염증물질방출로인해감각수용체의민감화, 신경퇴행성질환인파킨슨병과유사하게도파민의분비가줄어들면서도파민을매개로하는하향성통증조절이저하되는중추성장애, 폐경후호르몬변화로인한점막의변성 위축, 불안감및스트레스등으로타액내코티솔분비가증가하는것으로인한구강점막신경섬유들의퇴행성변화가있다 4. Supertaster 는미뢰가많이분포되어있는심상유두의수가일반인에비해많고, 6-n-propylthiouracil (PROP) 의쓴맛을평균이상으로민감하게느끼는사람을일컫는다 24. 이 supertaster 에서의심상유두수가 supertaster 가아닌사람에비해많이측정되었고혀의체성감각기능과공간에대한예민도또한높다는연구결과가있었으며 24,25, BMS 환자에서 supertaster 의비율이높고 11 supertaster와같이심상유두가많은사람에서신경분포가많아져서 BMS 발생이더쉬울것이라는가설이제시되기도하였다 26. 하지만 Nasri-Heir 등 6 에의하면 BMS 환자와정상인에서심상유두수의차이를보이지않기도하였다. 종합하면, BMS 환자에서의심상유두수에대한견해에는차이가있으나 BMS의병태생리와관련하여심상유두의역할을배제할수는어려울것으로보인다. 음허증은腎水不足으로遺精, 盜汗, 消渴, 骨蒸潮熱, 手足心熱, 小便頻數, 舌紅등의증상이나타나는변증유형으로, 東醫寶鑑 辨證 27 에서는 陰虛生內熱者, 有所勞倦, 形氣衰少, 穀氣不盛, 上焦不行, 下脘不通, 胃氣熱, 熱氣熏胸中, 故內熱 이라하여陰虛로몸에熱證이나타날수있다고하였다. BMS의주증상은화끈거리거나얼얼한작열감양상의통증으로熱證의증상이나, 앞서설명한 BMS 의주요병태생리들이대부분신경퇴행성변화라는점과주로중년층이상에서호발하는질환이라는점에서 BMS는음허증에서나타나는허열증상으로볼수있다. 중의학에서는 BMS를주로陰虛火旺證, 陰虛傷津證, 心火上炎證, 脾虛血少證, 肝熱鬱蒸證의여러변증유형으로나누지만 28, BMS가내분비기능의저하가나타나는폐경기전후의여성및고령자에서다발하는역학적특성과병발하는증상을고려했을때특히음허로인한허화를기본병리로보고있다 9,10,29. 어혈증은氣血의運行阻滯로인해나타나며 素問擧痛論 에서 經脈流行不止, 環周不休, 寒氣入經而稽遲, 泣而不行, 客於脈中則氣不通, 故卒然而痛, 類經 에서 通則不痛, 不通則痛 라하여, 어혈이있을때통증이발생한다고설명하고있다. BMS의질환특성을고려하였을때는음허의병리를생각할수있으나, 통증이주증상이라는것을중점적으로본다면어혈증도 BMS의주요변증유형의하나로생각할수있으며, 실제중의치료에서도 BMS 환자들을어혈로변증하여치료해효과가있었던증례를보고하고있다 11,12. 본연구에서는설진의일환으로서심상유두수의측정이 BMS의음허 어혈변증유형진단및 BMS의객관적진단지표로활용될수있는가능성에대해최적절단값의조사와타당도검정을통해분석하였다. 심상유두의수와 BMS와의관련성을평가하기위해환자군과건강대조군의심상유두수를비교하고, 심상유두수와증상의상관성및 BMS 발생 986

10 이엄지 박재우 김진성 에미치는영향을분석하였다. 환자군의평균심상유두의수는 6.20개로건강대조군의평균심상유두의수인 3.63개에비해유의하게많았는데 (Table 3), 이는기존연구들의결과와유사하다. 또한심상유두의수와구강작열감의 VAS는유의한양의상관관계를보였고 (Table 4), BMS의발생요인분석시심상유두의수가 BMS의발생에가장큰영향을미치는요인으로나타났다 (Table 5). 한편, 심상유두의수가 BMS의객관적진단지표로서활용될수있는가를평가하기위하여 ROC curve를이용해최적절단값을도출한후이를기준으로민감도와특이도를산출하여심상유두수측정의타당도를평가하였다. 그결과심상유두수의최적절단값은 5.5였으며통계적인유의성을나타내어, 심상유두수가 BMS의진단지표로서활용될수있는가능성을제시하였다. 진단의정확도는 ROC curve 아래의면적인 AUC에의해서측정될수있는데, 심상유두수의 ROC 곡선의경우 AUC가 0.813으로중등도의정확성을나타내었고, 이때의민감도가 71.4%, 특이도가 82.9% 으로각각중등도수준을보여심상유두수측정이 BMS에대한정량적진단법으로서의유용할가능성을보여주었다 (Fig. 2, Table 6). 심상유두수가 BMS의한의학적변증유형진단에지표로서활용될수있는지를살펴보기위해심상유두수와음허, 어혈점수와의상관성을분석한결과를종합해보았을때심상유두의수가음허 어혈변증유형과관계된다고결론내리기는힘들다. 그러나, 환자군과건강대조군을대상으로한경우는각각의대상자수가 35명으로다소적기때문에이러한결과를일반화하는것은어려움이있으며, 이러한결과를보인것은변증여부를판정하는방법과도관련된것으로보인다. 본연구에서는음허증및어혈증설문지를이용하여음허 어혈변증여부를판정하였는데, 두설문지는모두대상자의자각증상에대해 VAS 또는 likert 척도로주관적으로표현한기록만을반영한다는한계 가있다. 보다신뢰성있는판정결과를얻기위해서는임상의가직접환자를대하여망문문절을시행하는과정이필요하기때문에후속연구에서는임상한의사의변증을포함시킬필요가있다고판단되며, 이에따라결과도달라질수있을것이다. 더불어본연구에서사용한음허증설문은 BMS와음허증의상관성에대한선행연구에서사용한설문 30 으로, 장등 15 이분석한최적절단값은구강건조증의 VAS가 4점이상인구강건조증환자를대상으로하여도출된것으로향후더욱보편적으로활용될수있는설문을이용하는것이보다바람직할것으로본다. 연구수행결과, 심상유두수는독립변수로서 BMS 발생에영향을주고증상의정도와도관련이있었으며, 심상유두수의측정이유의한최적절단값이존재하는타당한방법이될수있음을보여주어 BMS와관련된지표로서의유용성을확인할수있었다. 또한, 심상유두의수가음허증및어혈증과직접적으로관련된다고보기에는어려움이있었으나, 주관적증상과의상관성과 BMS 발생에미치는영향을분석하였을때 BMS의변증으로음허증이보다적합하였다. Ⅴ. 결론본연구에서는 BMS 환자와건강대조군을대상으로심상유두수가 BMS의음허 어혈변증유형진단및 BMS의객관적진단지표로의활용될수있는가능성을최적절단값의조사와타당도검정을통해분석하여다음과같은결론을얻었다. 1. 환자군에서건강대조군에비해심상유두의수가유의하게많았고, 심상유두의수는주관적구강작열감의 VAS와유의한상관관계를보였으며, BMS의발생요인분석시심상유두의수가 BMS의발생에가장큰영향을미치는요인이었다. 987

11 구강작열감증후군환자에서심상유두수측정의진단적가치 2. ROC curve를이용해도출한심상유두의수의최적절단값은 5.5였으며통계적으로유의하였고, 이때의 AUC는 0.813으로중등도의정확성을나타내었다. 이때의민감도는 71.4%, 특이도는 82.9% 로나타났다. 3. 심상유두의수가음허증 어혈증변증유형진단에지표로서활용될수있는지확인하기위해심상유두수와음허증, 어혈점수와의상관성을분석한결과유의한상관관계가없었다. 참고문헌 1. Lewis AK, Prime SS, Cohen SN. An overview of burning mouth syndrome for the dermatologist. Clin Exp Dermatol 2016;41(2): Kolkka-Palomaa M, Jӓӓskelӓinen SK, Laine MA, Teerijoki-Oksa T, Sandell M, Forssell H. Pathophysiology of primary burning mouth syndrome with special focus on taste dysfunction: a review. Oral Dis 2015;21(8): Lopez-Jornet P, Camacho-Alonso F, Lucero-Berdugo M. Quality of life in patients with burning mouth syndrome. J Oral Pathol Med 2008;37(7): Ducasse D, Courtet P, Olie E. Burning mouth syndrome: current clinical, physiopathologic, and therapeutic data. Reg Anesth Pain Med 2013; 38(5): Gurvits GE, Tan A. Burning mouth syndrome. World J Gastroenterol 2013;19(5): Nasri-Heir C, Gomes J, Heir GM, Ananthan S, Benoliel R, Teich S, et al. The role of sensory input of the chorda tympani nerve and the number of fungiform papillae in burning mouth syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2011;112(1): Bartoshuk LM, Duffy VB, Reed D, Williams A. Supertasting, earaches and head injury: genetics and pathology alter our taste worlds. Neurosci Biobehav Rev 1996;20(1): Choi J, Kim JS. Fungiform papillae and its correlation with rome Ⅲ classification and spleen qi deficiency in functional dyspepsia. J Int Korean Med 2015;36(3): 周兵, 周杰. 灼口汤治疗阴虚型灼口综合征观察. 临床口腔医学杂志 2012;28(4): 郭宏奇. 中药辨证治疗灼口综合征临床观察. 疾病监测与控制杂志 2009;8: 韩芳, 张智靖. 血府逐瘀口服液治疗舌痛症 20 例. 实用诊断与治疗杂志 2003;17(4): 韩晓虹. 桃红四物汤治疗舌痛症 30 例的疗效观察. 中国医药导报 2007;4(06X): Wewers ME, Lowe NK. A critical review of visual analogue scales in the measurement of clinical phenomena. Res Nurs Health 1990;13: Lee SJ, Park JB, Lee SS, Kim KH. Development of yin-deficiency questionnaire and examine the reliability and validity. Korean J Orient Physiology & Pathology 2004;18(2): Jang SW, Kim JS. Development cut-off value for yin-deficiency questionnaire and diagnostic ability of yin-deficiency in xerostomia. J Int Korean Med 2014;35(4): Yang DH, Park YJ, Park YB, Lee SC. Development of questionnaires for blood stasis pattern. J Korean Inst Orient Med Diagn 2006;10(1): Park YJ, Yang DH, Lee JM, Park YB. Development of a valid and reliable blood stasis questionnaire and its relationship to heart rate variability. Complement Ther Med 2013;21(6): Shahbake M, Hutchinson I, Laing DG, Jinks AL. Rapid quantitative assessment of fungiform papillae density in the human tongue. Brain Res 2005;1052(2): Correa M, Hutchinson I, Laing DG, Jinks AL. 988

12 이엄지 박재우 김진성 Changes in fungiform papillae density during development in humans. Chem Senses 2013; 38(6): Cruickshanks KJ, Schubert CR, Snyder DJ, Bartoshuk LM, Huang GH, Klein BE, et al. Measuring taste impairment in epidemiologic studies: the Beaver Dam Offspring Study. Ann N Y Acad Sci 2009;1170: Eliav E, Kamran B, Schaham R, Czerninski R, Gracely RH, Benoliel R. Evidence of chorda tympani dysfunction in patients with burning mouth syndrome. J Am Dent Assoc 2007;138(5): Dept. of Diagnostics & Biofunctional Medicine in Colleges of Korean Medicine. Biofunctional medicine. 1st ed. Seoul: Koonja Pub; 2008, p Bartoshuk LM, Snyder DJ, Grushka M, Berger AM, Duffy VB, Kveton JF. Taste damage: previously unsuspected consequences. Chem Senses 2005;30(Suppl1): Essick GK, Chopra A, Guest S, McGlone F. Lingual tactile acuity, taste perception, and the density and diameter of fungiform papillae in female subjects. Physiol Behav 2003;80(2-3): Yackinous C, Guinard JX. Relation between PROP taster status and fat perception, touch, and olfaction. Physiol Behav 2001;72(3): Grushka M, Bartoshuk L. Burning mouth syndrome and oral dysesthesias. Can J Diagn 2000: Heo J. Yoon SH, Kim JM, Kim HJ, Choi CH, Jeon JH, et al. trans. Dongui Bogam. 1st ed. Hadong: Dongui bogam Pub; p 何园, 林梅, 李秉琦. 灼口综合征的治疗方案. 现代口腔医学杂志 2003;17(6): 赵继鹏, 李凤和. 从肝肾阴虚论治灼口综合症的初步研究. 口腔医学研究 2011;27(12): Seon JK, Kim JS, Han GJJ, Oh SW, Son JH, Kang K, et al. Clinical characteristics and evaluation of yin-deficiency syndrome in patients with burning mouth syndrome. J Int Korean Med 2011;32(4):

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