pissn: eissn: Allergy Asthma Respir Dis 3(1):22-29, January ORIGINAL ARTICLE 계란알레르

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1 pissn: eissn: ():22-29, January 5 ORIGINAL ARTICLE 계란알레르기에서열처리한계란을이용한피부단자시험의진단적유용성 전진, 이경은,2,3, 김미나,2,3, 홍정연,2,3, 김민정,2,3, 김윤희,2,3, 박현빈,2,3, 한윤기,2,3, 이희선,2,3, 김경원,2,3, 손명현,2,3, 박중원 2,3,4, 김규언,2,3 연세대학교의과대학 소아과학교실, 2 알레르기연구소, 3 BK2 플러스의과학사업단, 4 내과학교실 Diagnostic utility of skin prick test to cooked egg in children with egg allergy Jin Jhon, Kyung Eun Lee,2,3, Mi Na Kim,2,3, Jung Yeon Hong,2,3, Min Jung Kim,2,3, Yoon Hee Kim,2,3, Hyun Bin Park,2,3, Yoon Ki Han,2,3, Hee Seon Lee,2,3, Kyung Won Kim,2,3, Myung Hyun Sohn,2,3, Jung-Won Park 2,3,4, Kyu-Earn Kim,2,3 Department of Pediatrics, 2 Institute of Allergy, 3 Brain Korea 2 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul; 4 Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea Purpose: Reliable predictors of tolerance to cooked egg in an egg allergic population are not established. We investigated the usefulness of the skin prick test to cooked egg in children with egg allergy. Methods: We studied 36 children with egg allergy. Skin prick tests (SPTs) for the uncooked or cooked form of egg white and egg yolk, whole egg, ovomucoid (OVM), and ovalbumin (OVA) were performed at diagnosis. The reagents of cooked egg for SPT were prepared by baking for 25 minutes in degree oven. We also examined specific IgE levels to whole egg, egg white, egg yolk, OVM, and OVA. Results: Patients with history of allergic reaction to extensively heated egg showed significantly increased wheal size for cooked egg white (median [interquartile range]),.5 [7. 4.6] vs. 4.2 [. 5.6], P<.) and OVM (9.6 [ ] vs. 5.6 [. 7.8], P=.) than those without the history. The strongest positive correlation was found between wheal size for cooked egg white and OVM (r=.788, P<.). SPT wheal size for cooked egg white were positively correlated with serum OVM-specific IgE levels (r=.69, P<.). Cutoff value was 7. mm in SPT wheal size for cooked egg white, the sensitivity was 73.% and specificity was 99.%. SPT for cooked egg white showed significantly higher area under curve than serum egg white specific IgE. Conclusion: Our results suggest that SPT to cooked egg white may be useful predictor of allergic reaction to cooked egg. Further investigations will be needed. ( 5;3:22-29) Keywords: Egg hypersensitivity, Skin tests, Egg proteins 서론계란알레르기는가장흔한식품알레르기중하나로주로영아와어린소아에서나타나며, 전세계적으로유병률이약.5% 2.5% 일것으로추측되고있다.,2) 우리나라에서는계란이식품알레르기를유발하는가장흔한원인식품으로알려져있으며, 3) 다양한요리의재료로쓰이고제조식품에폭넓게포함되어있어계란섭취를회피하는것이매우어렵기때문에계란알레르기가더욱중요 하게여겨지고있다. 임상적으로계란알레르기는주로영유아시기에증상이시작되며, 다른식품알레르기와마찬가지로섭취후수분에서수시간이내에일어나는 IgE 매개반응이주로나타난다. 4) 증상은두드러기, 혈관부종, 후두부종, 아나필락시스등이발생할수있으며이중피부증상이가장흔하게나타나고, 생명을위협하는심각한알레르기반응이일어나기도한다. 4-6) 또한아토피피부염의발생및악화와긴밀한연관성이있으며, 계란에감작된환자들이좀더증상이심하고지속되는아토피피부염을보인다고보 Correspondence to: Hee Seon Lee Department of Pediatrics, Institute of Allergy, Severance Hospital, Yonsei University College of Medicine, 5 Yonsei-ro, Seodaemun-gu, Seoul -752, Korea Tel: , Fax: , heeseon7@naver.com Received: April 24, 4 Revised: October, 4 Accepted: October 27, 4 5 The Korean Academy of Pediatric Allergy and Respiratory Disease The Korean Academy of Asthma, Allergy and Clinical Immunology This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( 22

2 전진외 열처리한계란을이용한피부단자시험 고된바있다. 7,8) 알레르기증상을유발하는계란의주요항원으로는난백에포함되어있는 ovomucoid (OVM, Gal d ), ovalbumin (OVA, Gal d 2), ovotransferrin (Gal d 3), lysozyme (Gal d 4) 와난황에포함되어있는 alpha-livetin (Gal d 5) 이있으며, 이들중대표적인항원인 OVM 와 OVA에대한연구가주로이루어지고있다. 9) OVA는 54% 로성분항원들중에서가장높은비중을차지하고있지만열을가하거나소화효소처리를하면변성되어항원성이감소하는반면, OVM는열처리와소화효소에도안정적으로항원성을유지하는특성이있어보다중요한성분항원으로생각되고있다.,) 계란에포함되어있는이러한주요성분항원들은환자의임상양상과관련이있다. 2) 특히 OVM 특이 IgE 항체 (OVM-sIgE) 가높은환자는지속적인계란알레르기를보이는경우가많으며열처리한계란을섭취하였을때알레르기증상이나타날가능성이높다고보고되었다. 3-5) 여러연구들에의하면약 6% 8% 의계란알레르기환자들이익힌계란을섭취하였을때에증상을보이지않으며, 5-) 익힌계란에대한증상이나타나지않을확률은환자가나이가들수록점차증가하고그속도는익히지않은계란에비해더빠르다고알려져있다. 7) 따라서환자들에게무조건계란이들어간모든음식을제한하게하는것이불필요하다는주장들이제기되고있으며, 5,8) 오히려충분히익힌계란을지속적으로섭취하는것이계란알레르기를더빨리호전시킬수있다는근거들도있다. 7,2) 이와관련하여 OVM 등의성분항원에대한특이 IgE를측정하는방법을통해서계란알레르기환자가익힌계란을섭취하였을때알레르기반응이나타나는지여부를예측할수있다는주장이설득력을얻고있다. 3-5) 하지만가열한계란을이용하여피부시험을시행하고이를성분항원과연관시킨연구는현재많지않으며아직이러한검사의표준화가이루어지지않은상태이다. 22,23) 본연구에서는계란알레르기를진단받은환아들을대상으로난백과난황을열처리하여직접제조한시약과계란의주요성분항원인 OVM와 OVA으로피부단자시험 (skin prick test, SPT) 을시행하고결과를분석하여혈청특이 IgE 결과및임상증상과의연관성을확인하고진단적유용성에대해알아보고자하였다. 대상및방법. 연구대상본연구는 년 4월부터 2년 월까지세브란스어린이병원알레르기클리닉을방문한환아들중병력상계란에알레르기증상을보였거나중등증이상의아토피피부염을보인환자들중계란알레르기가진단된 36명의환아들을대상으로분석하였다. 아토피피부염의진단은 Hanifin의기준 24) 에따라이루어졌다. 계란알레르기의진단은병력상계란섭취후 2시간이내에두드러기나 혈관부종등의알레르기증상이나타났거나계란섭취후 48시간이내에아토피피부염증상의악화를보이는환아들에게서시행한난백특이 IgE 항체가양성 (>.35 kua/l) 인경우로하였다. 계란섭취와관련된병력에대해서는피부단자시험시행당일전문의가문진을통해조사하여식품알레르기기록지를작성하였다. 생계란또는반숙이나계란프라이등조리후에도덜익혀진계란을섭취했을때의증상과계란을완전히익혀서조리한후섭취했을때의증상을모두확인하였으며, 병력이확실하지않은경우대상에서제외하였다. 본연구에서는병력으로확인된익힌계란에대한증상유무에따라두군으로분류하였으며, 이때익힌계란 (cooked egg) 은완숙으로삶은계란이나완전히익힌상태로요리재료로쓰인경우로정의하였다. 피부시험결과에영향을줄수있는항히스타민제제나스테로이드를 2주이내에복용한환자들은제외하였다. 본연구는대상환아들의보호자에게연구의목적과방법을설명하고동의서를받은후시행되었으며, 세브란스임상시험윤리위원회의심의를통과하였다. 2. 연구방법 ) 조항원제조및구입시중에서판매되고있는계란을구입하여 C 오븐에서 25분간가열하였다. 25) 생계란 (uncooked egg) 과오븐에서열처리한계란 (cooked egg) 은각각난백 (egg white, EW) 과난황 (egg yolk) 으로나누어 phosphate buffered saline (ph 7.4) 과 :4 ( 가열처리하지않은것 [vol/vol], 가열처리한것 [wt/vol]) 비율로섞어균질화시키고 4 C 에서 24시간동안교반시켰다. 이용액을 4 C, 2, rpm에서 분간원심분리하여상층액을분리한후여과지를통과시켜부유물질을제거하였다. 이렇게얻은단백질용액은투석막 (dialysis membrane) 을사용하여 2일동안투석시켰다. 투석을마친용액을다시한번 4 C, 2, rpm에서 분간원심분리하여상층액을동결건조하고사용전까지 C에서보관하였다. Purified 된 OVA (Sigma-Aldrich, St. Louis, MO, USA) 와 OVM (Sigma-Aldrich) 단백은사용전까지 C에서보관하였다. 2) 피부단자시험시약제조 Buffer에녹아있는실험실제조조항원과구입조항원을 bradford assay를통해단백정량을한후 glycerine 과 : (vol:vol) 로섞어 SPT 시약의농도가 3.5 mg/ml ( 실험실제조항원 ) 또는 2.5 mg/ml ( 구입항원 ) 가되도록각각제조하였다. 만들어진시약은 C에보관하였다. 3) 피부단자시험및혈청특이 IgE 측정생계란 (raw whole egg), 생난백 (raw egg white), 생난황 (raw egg yolk), 그리고열처리한난백 (cooked egg white) 과난황 (cooked egg 23

3 Jhon J, et al. Skin prick test to cooked egg in egg allergy yolk) 으로제조한시약과구입한항원인 OVA, OVM로제조한시약으로피부단자시험을시행하였다. 히스타민 ( mg/ml) 과생리식염수를각각양성및음성대조로사용하였다. 검사대상자의등에항원용액을점적한후주사침을이용하였으며, 결과는검사 5분후에팽진의크기를측정하였다. 아토피피부염이있는환아의경우병변이없는피부에시행하였다. 모든환아들의혈액을채취하였고 UniCAP (Pharmacia and Upjohn, Uppsala, Sweden) 을이용하여혈청총 IgE와 OVM, OVA, 난백, 난황, 그리고 whole egg에대한특이 IgE 항체를측정하였다. 수는로그변환하여분석에이용하였으며, 상관관계분석은 Pearson correlation test를사용하였다. MedCalc software (MedCalc, Mariakerke, Belgium) 을이용하여수용자작업특성곡선 (receiver operating characteristic [ROC] curve) 을구하였고곡선하면적 (area under curve, AUC) 을비교하였으며각각의변수에대해 AUC가최대가되는절단값을 Youden 방법으로구하였다. P 값의유의성검증은.5 미만일때통계적으로유의한것으로평가하였다. 결과 3. 통계방법 통계적검정은 IBM SPSS Statistics ver.. (IBM Co., Armonk, NY, USA) 을이용하였다. 연속형변수는 independent t-test 또는 Mann-Whitney test 를이용하였다. 정규분포를만족하지않는변 Table. Baseline characteristics of subjects Characteristic Reaction to cooked egg (+) (n= 26) Reaction to cooked egg ( ) (n= ) P-value Age.33 Median (range), mo (2 72) 8 ( 64) < 2 yr yr > 5 yr.928 Age at symptom onset (mo).464 Median (range) 2 (6 8) 3 (6 8) Male sex 8.84 Onset time of symptoms to raw egg (min) Median (range) (3 ) 5 ( 8).354 Family history of allergic disease Clinical diagnosis Urticaria Atopic dermatitis Bronchiolitis Asthma Allergic rhinitis 4.95 Other food allergy Anaphylaxis.65 Symptoms Skin Ocular Upper respiratory Lower respiratory Oral Gastrointestinal Cardiovascular.65 Reaction to cooked egg positive or negative group included patients who had reacted or not reacted (respectively) to extensively heated egg by cooking in the patients history.. 임상적특성 총 36 명의환아중남아는 28 명 (77.8%), 여아는 8 명 (22.2%) 이었 고내원당시연령의중앙값 (median value) 은 9 개월이고연령분포 는 72 개월이었으며, 증상이처음나타난연령의중앙값은 2 개 월이고연령분포는 6 8 개월이었다. 이들중아토피피부염으로진 단받은환자는 28 명 (77.8%) 이었으며, 우유나밀등의다른식품알 레르기를동반한환자는 24 명 (66.7%) 이었다. 알레르기반응이두드 러기등의피부증상으로나타난경우가 29 명 (8.5%) 으로가장많 았으며, 아나필락시스병력이있는환자는익힌계란에도반응을 보인환자군중 명이었다. 병력상익힌계란에알레르기증상이있 었던군과없었던군으로나누었을때, 두군은성별과나이를비롯 한여러특성에서유의한차이가없었다 (Table ). Table 2. Comparison of skin prick test (SPT) and serum specific IgE between patients with and without history of allergic reaction to cooked egg Allergen SPT wheal size (mm) Reaction to cooked egg (+) (n= 26) Reaction to cooked egg ( ) (n= ) P-value Ovomucoid 9.6 ( ) 5.6 (. 7.8).* Ovalbumin 9. (6.5.9) 5.6 (4. 7.6).63 Raw egg white 2. ( ) 6. ( ).* Cooked egg white.5 (7. 4.6) 4.2 (. 5.6) <.* Raw egg yolk 6.8 ( ) 3. (. 4.4).37* Cooked egg yolk 4.5 (2.6 6.).5 (. 2.9).7* Raw whole egg 6.5 (4.5 8.) 5. ( ).4* Total IgE 2. (. 67.) 5. ( ).355 Serum sige (kua/l) Ovomucoid 3.8 ( ).3 (. 8.5).45* Ovalbumin 8. (2. 3.7) 4.2 ( ).32 Egg white 6.2 ( ) 9.5 ( ) Egg yolk 3.4 (.5 6.3) 2.8 (.3 5.5).876 Whole egg.7 ( ) 9.3 ( ).76 Reaction to cooked egg positive or negative group included patients who had reacted or not reacted (respectively) to extensively heated egg by cooking in the patients history. Values are presented as median (interquartile range). *P<.5, statistically significant differences. 24

4 전진외 열처리한계란을이용한피부단자시험 2. 익힌계란에대한알레르기반응병력에따른피부단자시험과혈청특이 IgE 결과비교병력상익힌계란에알레르기증상이있었던군과없었던군의피부단자시험에서의반응을팽진의크기로비교하였다 (Table 2). 생난백과생난황및열처리한난백과난황에대한피부반응이모두두군사이에유의한차이를보였으며, 익힌계란에알레르기증상이있었던환자군이없었던환자군에비해열처리한난백에대한팽진의크기가통계적으로유의하게큰결과를보였다 (median [interquartile range, IQR],.5 [7. 4.6] vs. 4.2 [. 5.6], P<.). 익힌난황에대해서도익힌계란에알레르기증상이있었던군이유의하게더큰팽진의크기를보였으나익힌난백에비해통계적유의성은낮았다 (P =.7). 반면 OVA 에대한피부시험결과는두군사이에유의한차이를보이지않았고, OVM에대해서는난백과유사한결과를보여익힌계란에증상이있었던환자군이없었던군에비해팽진이크게나타났다 (median [IQR], 9.6 [ ] vs. 5.6 [. 7.8], P =.). 한편, 혈청특이 IgE 농도를비교한결과 (Table 2) 두환자군의난백, 난황, whole egg, 그리고 OVA에대한특이 IgE 농도는모두유의한차이가없었으며, 유일하게 OVM-sIgE 농도에있어두군사이에차이를보였다. 익힌계란에증상이없었던환자 군의 OVM-sIgE 농도가 (median [IQR],.3 [. 8.5] kua/l) 증상이있었던군에비해서 (median [IQR], 3.8 [ ] kua/l) 유의하게낮은결과를나타내었다 (P =.45). 3. 피부단자시험에서열처리한계란과성분항원에대한피부반응의연관성열처리에따른난백에대한피부반응과 OVA 및 OVM에대한피부반응의상관관계를알아보았다. 생난백에대한팽진의크기와 OVA (r =.536, P =.) 및 OVM (r =.547, P =.) 에대한팽진의크기가양의상관관계를보였고, 열처리한난백에대해서도 OVA (r =.763, P<.) 및 OVM (r =.788, P<.) 모두통계적으로유의한양의상관관계를나타내었으며, 이들중열처리한난백과 OVM에대한팽진의크기가서로가장강한상관관계를보였다 (Fig. ). 4. 열처리한계란에대한피부시험결과와혈청특이 IgE 항체농도의연관성열처리에따른난백에대한피부반응과 OVA 및 OVM에대한혈청특이 IgE 농도의관계를알아보았다. 생난백에대한팽진의크기 3 r=.536 P=. 3 r=.547 P=. SPT wheal size to OVA (mm) SPT wheal size to OVM (mm) 3 SPT wheal size to raw egg white (mm) A 3 SPT wheal size to raw egg white (mm) B 3 r=.763 P=. 3 r=.788 P=. SPT wheal size to OVA (mm) SPT wheal size to OVM (mm) 3 SPT wheal size to cooked egg white (mm) C 3 SPT wheal size to cooked egg white (mm) D Fig.. Correlation of skin prick test wheal size for raw egg white with OVA (A) and OVM (B), correlation of skin prick test wheal size for cooked egg white with OVA (C) and OVM (D). SPT, skin prick test; OVA, ovalbumin; OVM, ovomucoid. 25

5 Jhon J, et al. Skin prick test to cooked egg in egg allergy OVA-sIgE (log, kua/l) - r=.353 P=.35 OVA-sIgE (log, kua/l) - r=.638 P< SPT wheal size to raw egg white (mm) A -2 3 SPT wheal size to raw egg white (mm) B OVA-sIgE (log, kua/l) - r=.245 P=.49 OVA-sIgE (log, kua/l) - r=.69 P< SPT wheal size to cooked egg white (mm) C -2 3 SPT wheal size to cooked egg white (mm) D Fig. 2. Correlation of skin prick test wheal size for raw egg white with serum OVA-sIgE (A) and OVM-sIgE (B), correlation of skin prick test wheal size for cooked egg white with OVA-sIgE (C) and OVM-sIgE (D). SPT, skin prick test; OVA, ovalbumin; OVM, ovomucoid. 는 OVA-sIgE (r =.353, P =.35) 및 OVM-sIgE (r =.638, P<.) 의농도와양의상관관계를나타내었다. 열처리한난백에대한팽진의크기는 OVA-sIgE 와는유의한관련성을보이지않았던반면 (r =.245, P =.49), OVM-sIgE의농도와는비교적강한양의상관관계를보였다 (r =.69, P<.) (Fig. 2). 5. 익힌난백섭취후알레르기반응예측에대한피부반응검사의 ROC 곡선분석익힌계란에대한알레르기반응을예측하는도구로서열처리한난백과난황, 생난백, 생난황, OVM, OVA, raw whole egg 피부반응검사에대한 ROC 곡선을구하였을때, 열처리한난백에대한피부반응이 AUC.89 (95% confidence interval [CI],.73.97) 로다른항원을이용한피부반응에비해큰값을나타내었다. AUC가최대가되는절단값을구하였을때 7. mm였고이때민감도 73.%, 특이도 99.% 로나타났다. 열처리한난백에대한피부반응검사의 AUC 값은생난백 (P =.284), 열처리한난황 (P =.8), 생난황 (P =.98), OVM (P =.466), OVA (P =.37), raw whole egg (P =.64) 를이용한피부반응검사들과통계적으로의미가있는차이를 보이지않았다 (Table 3). 6. 익힌난백섭취후알레르기반응예측에대한혈청특이 IgE의 ROC 곡선분석익힌계란에대한알레르기반응을예측하는도구로서 OVM, OVA, 난백, 난황, whole egg에대한혈청특이 IgE의 ROC 곡선을구하였다. OVM-sIgE 가 AUC.72 (95% CI,.53.85) 로가장큰값을나타내었다. AUC가최대가되는절단값을구하였을때.37 kua/l 이었고이때민감도 92.3%, 특이도 6.% 로나타났다. OVM-sIgE 의 AUC 값은 OVA (P =.58), 난황 (P =.76), whole egg (P =.48) 에대한특이 IgE의 AUC와통계적으로의미있는차이를보이지는않았으며, 난백특이 IgE보다통계적으로의미있게높은 AUC를나타내었다 (P=.6) (Table 4). 7. 열처리한난백에대한피부반응과혈청특이 IgE의 ROC 비교분석열처리한난백피부반응검사의 AUC 는난백, 난황, OVA, OVM, whole egg에대한특이 IgE와비교하였을때가장높았다. 이중 26

6 전진외 열처리한계란을이용한피부단자시험 Table 3. Skin prick test wheal size in predicting response to cooked egg Allergen AUC (95% CI) Cutoff value (mm) Sensitivity (%) Specificity (%) Cooked egg white.89 (.73.97) P-value Raw egg white.83 (.67.94) Ovomucoid.84 (.68.94) Ovalbumin.7 (.53.84) Cooked egg yolk.76 (.59.88) Raw egg yolk.73 (.56.86) Raw whole egg.74 (.56.87) P-values were determined by pairwise comparison of receiver operating characteristic curves of cooked egg white with that of other allergens. AUC, area under curve; CI, confidence interval. Table 4. Serum specific IgE in predicting response to cooked egg Allergen AUC (95% CI) Cutoff value (kua/l) Sensitivity (%) Specificity (%) Ovomucoid.72 (.53.85) P-value Ovalbumin.6 (.42.76) Egg white.5 (.33.68) * Egg yolk.53 (.36.7) Whole egg.54 (.36.7) P-values were determined by pairwise comparison of receiver operating characteristic curves of ovomucoid-sige with that of serum specific IgE to other allergens. AUC, area under curve; CI, confidence interval. *P<.5, statistically significant differences. Sensitivily SPT to cooked egg white (AUC,.89) Egg white-slge (.5) P <. Egg yolk-slge (.53) P=.2 OVA-slgE (.6) P=.35 OVM-slgE (.72) P=.9 Whole egg-slge (.54) P= Specificity Fig. 3. Comparison of receiver operating characteristic (ROC) curves among skin prick test to cooked egg white, serum specific IgE to egg white, egg yolk, ovalbumin, ovomucoid, and whole egg. The area under curve (AUC) of SPT to cooked egg white was.89 (95% confidence interval,.73.97). The AUC was.5 (.33.68) for egg white-sige,.53 (.36.7) for egg yolk-sige,.6 (.42.76) for OVA-sIgE,.72 (.53.85) for OVM-sIgE, and.54 (.36.7) for whole egg-sige. SPT to cooked egg white showed significantly higher AUC than egg white-sige (P<.), egg yolk-sige (P=.2), OVA-sIgE (P=.35), and whole egg (P=.6). SPT, skin prick test; OVA, ovalbumin; OVM, ovomucoid. OVM-sIgE 와는통계적으로의미가없었고 (P =.88), 난백특이 IgE (P <.), 난황특이 IgE (P =.2), Whole egg-sige (P =.6), OVA-sIgE (P =.36) 와통계적으로의미있는차이를보였다 (Fig. 3). 고찰많은계란알레르기환자들이가열한계란에대해서는증상을나타내지않는다는최근보고들이있으며, 광범위하게열처리한계란을면역요법으로활용하는연구들이이루어지고있다. 5,7,8,2) 따라서계란알레르기환자들의익힌계란에대한관용여부를예측할수있는도구의필요성이중요하게인식되고있지만아직까지그방법이정립되지못한상황이다. 예전부터시행해오던계란전체추출물또는난백에대한피부시험이나혈청난백특이 IgE 항체는가열한계란에대한관용여부를예측하기에는유용성이떨어진다고알려져있다. 5,9,) 직접익힌계란으로경구유발검사를시행하는것이최선의방법이지만, 검사에소요되는시간과노동력, 편의성및위험성측면에서어려움이있다. 26) 본연구에서는계란을 C 오븐에서 25분간가열한후난백과난황으로나누어시약을제조하고환자에게피부단자시험을시행하여, 이시약에대한피부 반응이환자의임상병력과관련이있는지를확인하였다. 시약제조에사용한조리방법은광범위하게가열한난백에대한관용을연구한여러논문들에서피부시험이나경구유발시험에사용한바있으며, 5-7,9-2) 최근연구들에의하면오븐으로계란을가열하여피부단자시험을시행하였을때실제가열한난백에대한알레르기반응을간접적으로예측하기에유용하다고밝히고있다. 22,23) 경구면역요법에가열한계란을적용한연구에서는머핀으로제조한계란을일정기간동안지속적으로섭취하도록하였다. 2) 본연구에서병력상가열한계란에대해증상이있었던환자들과없었던환자들간의피부시험결과를비교해본결과, 열처리한난백에대한팽진의크기가증상이있었던환자들에서유의하게크게측정되었다. 계란알레르기에서가장중요한항원이며난백에존재하는 OVM 는환자가계란항원에대한관용에도달하는데에영향을미치는중요한인자들중하나로, 가열한난백에대한알레르기반응과관련이높은것으로알려져있다. 3,4) OVM는 C에서 시간동안가열하여도항원성이유지되며, ) 한연구에서는가열한난백에알레르기증상이있었던환자들중대부분이난백에서 OVM만제외시키고섭취하였을때에는증상이없었다고보고하였다. 27) 본연구에서도열처리여부와상관없이난백에대한피부시험결과가 OVM에대한팽진크기및혈청 OVM-sIgE 와강한상관관계를보임으로써, 27

7 Jhon J, et al. Skin prick test to cooked egg in egg allergy OVM가계란알레르기에서주요한항원임을뒷받침하였다. 또한혈청특이 IgE를 ROC 분석한결과에서 OVM-sIgE 가가장높은 AUC 를보여 OVM가다른항원들에비해익힌계란섭취후의반응과가장밀접한관계가있음을나타내었으며, 이는이전연구들과도유사한결과이다.,3,4,27) 최근알레르기질환진단의특이도를높이기위한방법으로써관심이증가하고있는단일성분항원검사법 (component-resolved diagnosis) 은임상적으로의미있는알레르기를구별하는데있어유용한도구로그잠재성을인정받고있다. 28) 특히땅콩알레르기에서대표적항원인 Ara h 2을비롯한땅콩의특정성분항원과임상적연관성에대해서는비교적많은연구들이이루어져있다. 29) 계란의경우단일성분항원으로서 OVA, OVM 등이중요한연구대상이며, 여러보고들을통해서난백전체에대한혈청특이 IgE 보다 OVM-sIgE 가익힌계란에대한반응여부를예측하기에더유용하다는주장들이설득력을얻고있다. 2-4) 따라서환자에게 OVM-sIgE 를측정함으로써경구유발검사를시행할지여부를결정하는데도움이될수있다. 2) 본연구에서는병력상익힌계란에증상이없었던환자군이증상이있었던군에비해 OVM 피부시험반응및 OVM-sIgE 농도가통계적으로유의하게낮은결과를보여, 익힌계란에대한알레르기반응과 OVM가관련이높음을시사하였다. 또한 OVM와는달리두환자군사이 OVA에대한피부시험결과및 OVA-sIgE 농도는유의한차이를보이지않아열에취약한 OVA는상대적으로그역할이미미하다는사실을뒷받침하였다. 직접제조한생난백및열처리한난백에대한피부반응과 OVA, OVM 에대한피부반응이서로연관성을가지는지살펴본결과에서는, 계란알레르기환아에서 OVM에대한피부반응이클수록열처리한난백에대한피부반응도유의하게커지는높은관련성을보였다. 또한열처리한난백에대한피부반응은 OVM-sIgE 와도비교적강한양의상관관계를나타내었다. 따라서본연구에서실제가열한난백을이용하여시행한피부시험은익힌계란에대한알레르기와관련이높은 OVM와밀접한연관성을가짐을알수있으며, 단일성분항원검사법과더불어임상적으로응용할만한가치가있음을시사하고있다. 이전에보고된연구에서는 23) 경구유발시험과함께피부시험의유용성을확인한결과, 갓구운머핀을이용하여피부시험을시행하였을때팽진의크기가 2 mm 미만일경우높은음성예측도를나타내었다. 본연구에서는열처리한난백에대한피부반응검사의 AUC 는.89로다른결과들과비교하였을때가장높은결과를보여진단도구적가치가있음을시사하였으며, AUC가최대가되는절단값은 7 mm이였다. 생난백에대해서는절단값이 9 mm로측정되었으며현재일반적으로계란알레르기를진단할때의기준에비해상당히높은결과를나타내었다. 따라서일반적으로시행되고있는난백피부반응검사의기준을높여익힌계란에대한알레르기증상을예측할수있을것으로생각된다. OVM의경우에는익 힌난백과유사한결과를보였으나민감도와특이도가다소낮았 고, OVA 는특이도가낮아진단적가치면에서떨어지는결과를나 타내었다. 하지만모든피부검사들은 AUC 값이통계적으로유의 한차이를보이지는않았다. 따라서열처리한난백에대한피부반 응검사가민감도와특이도면에서가장높은결과를나타내었음에 도불구하고생난백에비해진단도구로서의가치가높다고단정짓 기는어려우며이에대한연구가더필요할것으로보인다. 혈청특 이 IgE 결과와비교하였을때에는익힌난백피부반응검사가모든 혈청특이 IgE 보다높은 AUC 를보였고 EW-sIgE 와는통계적으로 의미있게차이가나타났으므로, 혈청특이 IgE 검사에비해서익 힌계란에대한알레르기여부를예측하는데더도움이될것으로 생각된다. 특히 2 세미만의영유아에서는혈청특이 IgE 보다피부 시험이더민감하다고알려져있기때문에, 26,3) 비교적어린나이에 높은분포를보이는계란알레르기환자들에게더유용할것으로 생각된다. 본연구는익힌계란에대한증상여부를직접유발검사를시행 하지않고병력청취에근거하였다는점에서한계가있다. 가열처리 과정및시간의차이에따라계란단백의항원성및알레르기성에 차이가있으므로, 표준화하여가열한계란으로실제경구유발검 사를시행하여피부시험의유용성을분석하는것이필요하겠으며 좀더많은환자들을대상으로연구가진행되어야할것이다. 결론적으로, 열처리한계란을이용한조제항원피부시험은성분 항원검사와높은연관성을보이며, 보다편리한도구로서계란알 레르기환아에서임상양상및예후를예측하기위한진단적유용 성을가질것으로생각되므로, 이에대한전향적인연구가필요할 것으로보인다. REFERENCES. Rona RJ, Keil T, Summers C, Gislason D, Zuidmeer L, Sodergren E, et al. The prevalence of food allergy: a meta-analysis. J Allergy Clin Immunol 7;: Heine RG, Laske N, Hill DJ. The diagnosis and management of egg allergy. Curr Allergy Asthma Rep 6;6: Hong SJ, Ahn KM, Lee SY, Kim KE. The prevalences of asthma and allergic diseases in Korean children. Korean J Pediatr 8;5: Boyano Martinez T, Garcia-Ara C, Diaz-Pena JM, Munoz FM, Garcia Sanchez G, Esteban MM. Validity of specific IgE antibodies in children with egg allergy. Clin Exp Allergy ;3: Colver AF, Nevantaus H, Macdougall CF, Cant AJ. Severe food-allergic reactions in children across the UK and Ireland, Acta Paediatr 5;94: Sampson HA, Mendelson L, Rosen JP. Fatal and near-fatal anaphylactic reactions to food in children and adolescents. N Engl J Med 992;327: Hill DJ, Hosking CS, de Benedictis FM, Oranje AP, Diepgen TL, Bauchau V, et al. Confirmation of the association between high levels of immunoglobulin E food sensitization and eczema in infancy: an international study. 28

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012임수진 Received : 2012. 11. 27 Reviewed : 2012. 12. 10 Accepted : 2012. 12. 12 A Clinical Study on Effect of Electro-acupuncture Treatment for Low Back Pain and Radicular Pain in Patients Diagnosed with Lumbar