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1 대한내과학회지 : 제 85 권제 5 호 특집 (Special Review) - 알레르기비염 알레르기비염의치료 고려대학교의과대학내과학교실 허규영 Treatment of Allergic Rhinitis Gyu-Young Hur Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea Allergic rhinitis (AR) is defined as chronic inflammatory reactions to common allergens in the nasal mucosa with at least two AR symptoms including rhinorrhea, nasal congestion, sneezing, nasal/ocular pruritus, and postnasal drainage. AR is a common health problem, and it affects around 10-25% of general population. Its prevalence is increasing according to the environmental changes. AR and asthma frequently coexist in the same patient, therefore we should consider it and check for asthma to diagnose AR. Antihistamines and nasal corticosteroids are recommended as the 1st line treatment of AR. Decongestants may be effective for nasal congestion, and leukotrienes are helpful to improve both nasal and bronchial inflammations in patients with AR and asthma. Allergen specific immunotherapy is useful in IgE mediated AR and can prevent the progression to asthma and new sensitizations. Appropriate AR treatment including medications and immunotherapy can improve symptoms and reduce medications. Finally improvement of quality of life can be achieved. (Korean J Med 2013;85: ) Keywords: Allergic rhinitis; Treatment; Asthma 서론알레르기비염은비강내염증반응으로콧물, 코막힘, 재채기, 코가려움등의증상이발생하는질환이다. 원인에따라코점막에서일어나는 IgE 매개성염증반응에의한알레르기비염과이와관련이없는비알레르기비염으로구분된다. 알레르기비염의유병률은전체인구의약 10-25% 에달하며최근알레르기질환이급증하면서증가추세를보이고있다. 이러한높은유병률로인하여비염에따른삶의질저 하와의료비지출이앞으로사회경제적인문제가될수있다. 또한천식환자의약 60-80% 가알레르기비염이있으며 [1,2] 알레르기비염환자의약 20-40% 가량이천식을동반하고있다 [3]. 따라서비염환자에서천식의동반여부를확인하고적절한치료를하는것이매우중요하다. 환경조절여러가지흡입알레르겐중에서도집먼지진드기가알레 Correspondence to Gyu Young Hur, M.D., Ph.D. Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, 148 Gurodong-ro, Guro-gu, Seoul , Korea Tel: , Fax: , gyhur@korea.ac.kr Copyright c 2013 The Korean Association of Internal Medicine This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

2 - The Korean Journal of Medicine: Vol. 85, No. 5, 르기비염에서가장중요한항원으로알려져있다 [4]. 그러나대부분비염환자를대상으로한연구에서는집먼지진드기알레르겐회피만으로임상적인호전을유발할정도로의미있는알레르겐수치감소를보이지않고있으며 [5] 비염증상을호전시키지않고있다 [6]. 그러나여러비염치료지침에서는알레르겐의회피를권장하고있다 [7,8]. 천식의경우에서도질병조절및약물사용량을감소시키기위해알레르겐회피및환경조절을권장하고있다. 그러나천식의경우는환경조절을통해알레르겐수치를감소시켜특히소아에서는임상적호전을기대할수있다 [5,9]. 약물치료비염치료에사용되는약제는대부분경구용혹은비강내로투여한다. 비강내투여방식은약제가비강내에직접전달되어높은농도를유지할수있고전신부작용을최소화한다는장점이있다. 대부분의알레르기비염환자들은알레르기결막염혹은천식을동반하는경우가많으므로이를고려하여약제를선택하도록한다 (Table 1). 항히스타민제항히스타민제는 H1수용체길항제로, 표적세포의히스타민수용체에경쟁적으로작용하여히스타민의결합을막는역할을한다. 비염에서의항히스타민제는콧물, 재채기, 코가려움에효과적이다. 1세대항히스타민제 1세대항히스타민제는중추신경계의 H1수용체에작용하여졸림, 어지러움, 무력감등부작용이나타날수있다. 변비, 설사, 메스꺼움, 구토등의소화장애가발생할수있으며항콜린, 항무스카린성효과에따라다양한정도의점막건조, 시력흐려짐, 변비, 배뇨곤란, 빈맥, 발기부전등이나타날수있다. 그러므로 1세대항히스타민제를당뇨병, 녹내장, 전립선비대, 심장질환이있는환자에게처방하는것은주의를요한다. 항히스타민제는중추신경억제제인알코올, barbiturates, 기타진정제와의병용시주의를요하고 MAO 억제제인 iproniazid, phenelzine를투여하는환자에서는금기이다. 2세대항히스타민제 2세대항히스타민제는 blood brain barrier (BBB) 를쉽게통과하지않아중추신경계의 H1 수용체에대한결합력이약하여 1세대항히스타민제에비하여진정작용이적은편이다. 하지만 fexofenadine 을제외한모든약물에서 BBB를통과할수는있으므로환자에따라서진정작용을보이기도하며 cetirizine의경우 11-14% 환자에서진정작용을보이는것으로알려져있다. 항콜린성효과가적으므로당뇨병, 녹내장, 전립선비대, 심장질환이있는환자에서도비교적안전하게사용할수있다. 따라서 2세대항히스타민제를 1세대항히스타민제보다먼저사용할것을권장하고있다 [10]. 비강용항히스타민제비강용항히스타민제는경구용항히스타민제와달리코막힘에도효과가있다. 흔한부작용으로쓴맛이나고 (19.7%) Table 1. Advantages and disadvantages of intranasal administration Advantages of intranasal administration High concentrations can be delivered directly into the target organ avoiding or minimizing systemic effects. Some of the drugs (eg. Cromones) should be administered only via the intranasal routes as they are not adequately absorbed when given orally. Some drugs have systemic effects when administered orally (e.g. intranasal glucocorticosteroids are also effective in allergic conjunctivitis) [11]. The onset of action is faster than that of an oral drug. Problems of intranasal administration Some patients experience side effects of crusting and bleeding. Some local side effects may be occurred. (e.g. rhinitis medicamentosa, nasal dryness, nasal bleeding and so on.) Intranasal medication cannot be given when the nose is completely blocked. Especially if multiple target organs should be treated, oral drugs may be preferred

3 - Gyu-Young Hur. Treatment of allergic rhinitis - 체내로도흡수되어진정작용 (11.5%) 을나타낼수있다. 치료지침에서는계절성알레르기비염환자에서경구용 2세대항히스타민제를비강내항히스타민제보다추천한다 [10]. 비강용스테로이드제비강내스테로이드제사용은전신부작용의발생가능성을최소화하면서비강점막의약물농도를높게유지할수있는방법이다. 이는알레르기비염증상뿐만아니라안구증상도같이호전시킬수있다 [11]. 코막힘증상을호전시키는데비강내스테로이드제제가일차약제로서다른약제보다효과적이다. 비강내스테로이드제는부작용이상대적으로적고장기적으로사용하더라도비강점막의위축을유발하지않으며경구스테로이드제를사용할때고려해야하는부작용이거의없어안전하게사용할수있다. 소아에서사용하는흡입용스테로이드가최종적으로성장지연을일으킨다는보고가최근에있었다 [12]. 그러나비강내스테로이드에서는 1년간단기연구이지만성장지연이없었다는연구결과가있었다 [13]. 따라서치료지침에서는성인알레르기비염의치료제로비강내스테로이드를강력히추천하며경구류코트리엔억제제보다권장한다 [10]. 류코트리엔억제제류코트리엔억제제는알레르기비염및결막염증상개선에효과가있다. 류코트리엔억제제와항히스타민제의병합요법과류코트리엔억제제단일요법에비해추가적인이득이별로없어계절성알레르기비염환자에서는항히스타민제단독요법이일차적으로권장된다. 또한알레르기비염과천식이동시에있는환자에서류코트리엔억제제를사용하면코증상뿐만아니라기관지증상을호전시킨다. 일부가이드라인에서는비염이동반된경한천식환자에서일차약제로류코트리엔억제제단독사용을권유하기도한다 [14]. 그러나 2010년개정된 ARIA 지침에서는천식치료목적의단일제제로는흡입스테로이드제가경구용류코트리엔제보다우월하다고권고하고있다 [10]. 혈관수축제알레르기혹은비알레르기비염에서코막힘의치료를위 해서단기간비강내혈관수축제를사용하는것은효과적이다. 그러나코가려움이나, 재채기, 콧물에는효과가없다. 비강내혈관수축제를장기간 (10일이상 ) 사용할경우에는반동성비강점막부종을일으킬수있다 (rhinitis mediamentosa, drug-induced rhinitis, rebound rhinitis) [15]. 경구용혈관수축제로는 ephedrine, phenylephrine, phenylpropanolamine 등이있으며특히 pseudoephedrine이경구혈관수축제로가장많이쓰이고있다. 전신적인부작용은드물지않으며불안, 어지러움, 두통, 손떨림, 불면, 심계항진, 고혈압등이있다. 녹내장이나갑상선항진증이있는환자, 전립선비대증으로소변저류가있는고령환자에서는주의하여야한다. 경구용혈관수축제와항히스타민제복합제제는많이사용되고있으며특히 pseudoephedrine이항히스타민과복합제제로흔히사용되고있다. 이는재채기, 콧물외에도코막힘을호전시킬수있다. 또한 ibuprofen과 pseudoephedrine, chlorpheniramine 복합사용이알레르기비염의증상개선에부가적인효과가있음이보고되었다 [16]. 면역요법알레르기면역요법은알레르기환자에게원인알레르겐을점진적으로투여하여알레르겐에대한내성을유발하여질환의경과를변경시키는방법이다. 알레르기비염환자에서면역요법은 3년이상충분한기간동안치료하면중단후에도치료효과가지속되며 [17] 향후천식으로진행되는위험을줄여주고 [18] 새로운알레르겐에감작되는것을예방할수있다 [19]. 알레르기비염에사용되는면역요법은투여경로에따라피하면역요법과설하면역요법으로나뉜다. 면역요법대상환자선정면역요법은원인알레르겐에의한 IgE 반응과임상증상과의연관성이확실한환자를대상으로한다 [20]. 원인알레르겐은피부단자시험또는혈청내특이 IgE 항체측정으로판단하나실제증상과의연관성이없는경우도많으므로임상적판단이중요하다. 면역요법의절대적금기증으로는 1 심한전신면역질환이나악성종양을앓고있는경우, 2 부작용발생시응급처

4 - 대한내과학회지 : 제 85 권제 5 호통권제 639 호 치로사용되는에피네프린을사용할수없는환자, 예를들어관상동맥질환이나심한고혈압으로베타차단제를매일복용해야하는경우, 3 환자의순응도가나쁜경우이다. 상대적금기증으로는 1 5세미만의영유아환자, 2 중증천식환자, 3 임신중에면역요법을시작하는것등이있다 [20]. 면역요법대상알레르겐선정최근까지이중맹검대조연구를통하여면역요법의효능이명확하게입증된알레르겐으로는꽃가루 ( 잔디, 돼지풀류, 자작나무, 쑥, 개잎갈나무 ) 와집먼지진드기, 바퀴, 곤충독, 그리고곰팡이 (Alternaria, Cladosporium) 에서유의한효과가입증되었으며, 동물알레르겐의경우에는고양이털, 개비듬이있다. 따라서알레르기피부단자시험및혈청특이 IgE 검사결과와함께병력상환자에게임상적으로의미를가지는한종류혹은가능한소수의알레르겐으로면역요법을실시하는것이바람직하다. 또한여러종류의꽃가루에동시에감작된경우는항원간의교차항원성을고려하여항원을선택하도록한다. 우리나라에서중요한알레르겐우리나라환경에서중요한흡입알레르겐으로는집먼지진드기 (D. farinae, D. pteronyssinus), 잡초꽃가루, 수목꽃가루, 잔디꽃가루등이있으며 [21] 면역요법에포함할수있다 [22-24]. 집먼지진드기는국내연구에서가장많이면역요법의효과가보고된알레르겐이며다음으로는꽃가루알레르겐이있다. 국내에서는계절에따라 3-5월에수목류 ( 참나무, 오리나무, 자작나무 ), 5-9월잔디류, 8-10월잡초류 ( 쑥, 돼지풀 ) 꽃가루가주로관찰된다 [25]. 또한최근애완동물에의한알레르기질환이큰문제로대두되고있어회피가어려울경우 동물알레르겐도면역요법에포함시키는것이좋겠다. 따라서우리나라에서는집먼지진드기, 꽃가루및동물알레르겐등이면역요법을시행하는중요한알레르겐이되겠다 [26]. 설하면역요법최적용량 ( 고용량 ) 의설하면역요법은성인과소아의알레르기비염에효과적이다 [27-31]. 설하면역요법은혀밑에알레르겐추출액을 1-2분동안머금고있다가삼키는방법이일반적이며초기에알레르겐의용량을올리는증량단계를거쳐적절한유지용량으로유지한다. 설하면역요법은고용량이더라도안전하며중대한부작용이적다 [32-34]. 또한설하면역요법은환자가스스로집에서투여하므로, 처방하는의사는부작용발생시대처방법이나투여를못했을때의용량조정등에대한환자교육을미리시행하여야한다. 항 IgE 치료항 IgE (recombinant, humanized, monoclonal anti-ige; Omalizumab) 항체는유리 IgE와복합체를만들어비만세포및호염기구와 IgE 의결합을방해하고유리 IgE를낮추는작용을한다 [35]. omalizumab 은혈청내유리 IgE 수치를낮추어주증상을줄여주고삶의질을향상시킨다 [36]. 특히천식과비염이동시에있는환자에서 omalizumab 을사용하면코증상및기관지증상을모두개선시키며천식악화를예방할수 Table 2. Indications for surgical interventions Drug-resistant inferiour turbinate hypertrophy Anatomical variations of the septum with functional relevance Anatomical variations of the bony pyramid with functional relevance Secondary or independently developing chronic sinusitis Different forms of nasal unilateral polyposis or therapy-resistant bilateral nasal polyp Fungal sinus disease Figure 1. Updated ARIA recommendations

5 - 허규영. 알레르기비염의치료 - Table 3. Stepwise medical treatment proposed in the ARIA Step Recommended treatment Mild IAR Oral H1-antihistamines Moderate/severe IAR Intranasal glucocorticosteroids (equivalent beclomethasone μg) If needed, after 1wkk of treatment, oral H1-antihistamines and oral glucocorticosteroids should be added Mild PER Oral H1-antihistmines or a low dose of intranasal glucocorticosteroids (equivalent beclomethasone μg) Moderate/severe PER High dose of intranasal glucocorticosteroids (equivalent beclomethasone μg) If symptoms are severe, add oral H1-antihistamines and oral glucocorticosteroids at the beginning of the treatment IAR, intermittent allergic rhinitis; PER, persistent allergic rhinitis. 있다 [37]. 그러나우리나라에서는중증천식환자에서만 omalizumab 치료가인정되고있으며알레르기비염의치료로는권장되지않는다. 하지만천식과비염이모두있고명백한 IgE 관련성이있으며적절한천식치료에도조절이잘되지않는경우에는천식의치료목적으로 Omalizumab 치료를고려할수있으며 [10] 부가적인비염증상개선에도효과를기대할수있겠다. 수술적치료수술은알레르기질환자체를치료하는데는도움이되지않으나비갑개비후, 연골혹은뼈에의한상기도폐쇄등을치료하는데수술이도움이되기도한다 (Table 2). 치료지침비염치료지침인 ARIA (Allergic Rhinitis and its Impact on Asthma) 에서는치료방침을다음과같이제시하고있다 (Fig. 1). 알레르기비염의진단시에특히중증지속성비염일경우에는천식동반여부를반드시확인하여야한다. ARIA 에서제시하는단계별약물치료는다음과같다 (Table 3) [7]. 결론알레르기비염은원인알레르겐을규명하여환경조절을통하여회피하고약물치료를통해상기도염증을완화시켜치료하는내과적질환이다. 알레르기비염환자에서천식을동반하고있는경우가많으므로천식여부를확인하는것이치료에중요하며적절한약물치료및면역치료등을통하여 증상개선및약물사용량을감소시켜삶의질을개선시킬수있다. 중심단어 : 알레르기비염 ; 치료 ; 천식 REFERENCES 1. Vignola AM, Chanez P, Godard P, Bousquet J. Relationships between rhinitis and asthma. Allergy 1998;53: Matsuno O, Miyazaki E, Takenaka R, et al. Links between bronchial asthma and allergic rhinitis in the Oita Prefecture, Japan. J Asthma 2006;43: Lundbäck B. Epidemiology of rhinitis and asthma. Clin Exp Allergy 1998;28(Suppl 2): Bush RK. Does allergen avoidance work? Immunol Allergy Clin North Am 2011;31: Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, revised Available from: ch13.pdf. 6. Sheikh A, Hurwitz B, Shehata Y. House dust mite avoidance measures for perennial allergic rhinitis. Cochrane Database Syst Rev 2007;(1):CD Bousquet J, Khaltaev N, Cruz AA, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen). Allergy 2008;63(Suppl 86): Roberts G, Xatzipsalti M, Borrego LM, et al. Paediatric rhinitis: position paper of the European Academy of Allergy and Clinical Immunology. Eur J Allergy Clin Immunol 2013;68: Matsui EC. Role of environmental control in the management of asthma and allergy. J Allergy Clin Immunol 2012; 129:271.e Brozek JL, Bousquet J, Baena-Cagnani CE, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines:

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ÀÇÇÐ°�ÁÂc00Ì»óÀÏ˘ Common Allergic Diseases in Children Sang - Il Lee, M.D. Department of pediatrics Sungkyunkwan University School of Medicine, Samsung Medical Center E - mail : silee@smc.samsung.co.kr Abstract Allergy