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1 대한내과학회지 : 제 85 권제 5 호 특집 (Special Review) - 알레르기비염 알레르기비염의동반질환 한림대학교의과대학내과학교실 최정희 Allergic Rhinitis and Comorbidities Jeong-Hee Choi Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea Allergic rhinitis (AR) is a symptomatic disorder of the nose based on chronic allergic inflammation. AR is a global health problem that causes major illness and disability and inadequately treated, of which prevalence is about 20% of general population. In general, AR is rarely found in isolation and has been associated with numerous comorbidities, including bronchial asthma, allergic conjunctivitis, otitis media with effusion, sinusitis with polyp, chronic cough, adenoid hypertrophy and consequent sleep disturbance. In particular, coexistence of AR and asthma is a common feature, suggesting the concept of one airway, one disease. Poorly controlled AR can develop or trigger exacerbations of these comorbidities because they often share pathophysiologic pathways in common with AR. Thus, AR should be regarded as a spectrum of systemic disease and treatment requires a systemic approach with considering its comorbidities. (Korean J Med 2013;85: ) Keywords: Allergic rhinitis; Asthma; Comorbidity 서론알레르기비염은성인과소아모두에서가장흔한만성질환중의하나이며그유병률은대략 20% 정도이다 [1]. 알레르기비염은그저성가신증상정도로만여겨져치료를소홀히하는경우가많은데, 심하지않은경우치료하지않거나증상이있더라도일반의약품으로스스로해결하는경우가많다. 그러나알레르기비염에의한삶의질저하는상당한것으로보고되고있다. 알레르기비염은흔히기관지천식, 알레르기결막염, 부비동염, 중이염, 수면장애등의여러 가지질환들을동반하는데 (Table 1) [1,2] 알레르기비염의악화는동반질환들을악화또는발생시키며이는단순히알레르기비염치료만으로호전되지않는다. 따라서알레르기비염을별개의질환이아니라알레르기염증성전신질환으로이해하여야하며알레르기비염을진단하고치료할때흔한동반질환을같이평가하고치료하는것은필수적이다. 이에저자는여기에서표 1에나열한흔한알레르기비염의동반질환들에대해서요약하고그임상적인의의에대해서정리하고자한다. Correspondence to Jeong-Hee Choi, M.D., Ph.D. Department of Pulmonology and Allergy, Hallym University Dongtan Sacred Heart Hospital, 7 Keunjaebong-gil, Hwaseong , Korea Tel: , Fax: , mdqueen@hallym.or.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.

- The Korean Journal of Medicine: Vol. 85, No. 5, 2013 - Table 1.

2 - The Korean Journal of Medicine: Vol. 85, No. 5, Table 1. Allergic rhinitis and its comorbidities Asthma Allergic conjunctivitis Sinusitis with or without nasal polyp Otitis media with effusion Adenoid hypertrophy Sleep disturbance/obstructive sleep apnea Chronic cough 기관지천식 천식과비염은모두만성염증성기도질환으로역학, 병태생리, 임상적으로밀접한관련성이있어두질환이별개의질환이라기보다는표적기관을달리하여표현되는동일한염증반응에의한 하나의기도질환 (one airway, one disease) 으로인식하고있다 [1]. 역학비염은천식발병의중요한독립적인위험인자이다 [3]. 일반적인천식의유병률이 5% 정도인데반해서비염환자의 10-40% 에서천식이있고천식환자의 70-80% 에서비염을동반한다 [1,2]. 통년성비염에서계절성비염보다중등증-중증지속성비염환자에서경증또는간헐성비염에비해서천식의유병률이높았다 [4,5]. 또한알레르기비염환자에서 IgE 항체치가높을수록, 비특이적기도과민성이존재할수록천식의발병위험이높았다 [6,7]. 비염은이미천식을동반한환자에서는천식악화인자의하나이다. 비염의악화는천식의악화를유발하며비염과천식의중증도는매우밀접하게연관되어있다. 비염을동반한천식환자에서는더많은천식악화와이에따른응급실방문을경험하였다 [8]. 이러한결과는비염을잘치료하는것이천식조절에중요함을보여준다 [9]. 병인기전천식과비염에서코점막과기관지점막은조직병리학적으로매우유사하나다른점도있다. 기관지에는기도평활근이있어기관지수축을유발하는반면에비강에는혈관네트워크가발달하여세혈관확장에의한코막힘을유발한다 [1]. 천식과비염의인과관계를설명하는기전은다양하다. 1) 비강-기관지반사 (nasobronchial reflex) 로코의감각세포가자극 Figure 1. Diagnosis of asthma in patients with rhinitis. This flow chart is recommended by ARIA guideline. 을받아반사궁을통해기관지수축을일으킨다는가설, 2) 비염에의한코막힘으로구강호흡이증가하여기관지가알레르겐에과다노출되어기도염증이증가한다는가설, 3) 비염의염증매체들이후비루을통해기관지로흡인되어기도수축및기도염증을유발한다는가설, 4) 비강과기관지가전신면역반응으로서로연결되어알레르기염증반응을공유한다는가설등이제시되었다 [1,2]. 치료 비염과천식이동반되어있는경우는두질환의치료지침을각각참고하여같이치료하여야한다 [1,10]. 항히스타민제는천식의치료에추천되지않는다. 비강내스테로이드제는알레르기비염뿐만아니라천식으로인한입원과응급실방문같은천식의악화를예방하는효과가있다. 그러나흡입스테로이드보다천식치료에효과적이지않다. 류코트리엔조절제는천식과비염의치료에모두효과적이다. 천식을동반한알레르기비염의치료에단독으로사용할수있다. 그러나천식과비염의중증도를고려하여타약제와의병합여부를결정하여야한다. 알레르기면역치료는알레르기질환을완치시킬수있는유일한치료로서천식과비염의치료에모두효과있다. 특히꽃가루, 집먼지진드기, 개, 고양이비듬이원인항원일경우효과적이다. 최근에중증천식에서사용이증가하고있는항 IgE 항체도천식과비염의치료에모두효과있다. 결론적으로알레르기비염환자를진료할때반드시천식에대한평가가동시에이루어져야한다. 이는문진, 신체검

3 - Jeong-Hee Choi. Allergic rhinitis and comorbidities - 사, 폐기능검사등으로시행되어질수있다 (Fig. 1). 마찬가지로천식환자에서도비염의동반유무에대한평가가이루어져야한다. 천식과비염이동반되어있는경우에는두질환을함께치료하여야하며두질환이동반되어있지않다면향후발병할위험성을염두에두고진료에임하여야한다. 알레르기결막염알레르기안질환은주로결막염으로나타난다. 알레르기결막염은여러가지형태로나타나는데, 대부분은증상이경미한계절성또는통년성알레르기결막염 (seasonal or perennial allergic conjunctivitis) 이고그외아토피피부염과동반된아토피각결막염 (atopic keratoconjuctivitis), 주로아이들에게나타나는봄철각결막염 (vernal keratoconjuctivitis) 그리고콘택트렌즈사용자들에서나타나는거대유두결막염 (giant papillary conjunctivitis) 등이있다 [11,12]. 여기서는내과의들 의흔히접할수있는계절성또는통년성알레르기결막염에대해서만상술하고나머지질환들은표 2에간략히나타내었다 (Table 2) [1]. 계절성또는통년성알레르기결막염흔히말하는알레르기결막염으로결막이공기중의알레르겐에노출되었을때알레르겐이결막의 IgE 항체와결합하여비만세포로부터히스타민등의여러가지매체가분비되어발생한다. 대부분의경우알레르기비염과동반되어발견되며알레르기비염의진단없이알레르기결막염으로만진단되는경우는드물다. 약 80% 의환자에서눈및코증상을같이호소한다. 꽃가루등의실외항원에의한계절성알레르기결막염이집먼지진드기등의실외항원에의한통년성보다더흔하며증상도심하다. 진단은대부분에서자세한병력청취와진찰로가능하다. 병력에서알레르기비염, 천식, 아토피피부염등의알레르기질환의유무가중요하다. 주로양안모두에증상이있으 Table 2. Symptoms and signs of allergic eye diseases Symptoms Signs Allergic conjuctivitis Tearing Mild hyperemia Burning Mild edema Itching Mild papillary reaction (often absent) Atopic keratoconjunctivitis Itching Hyperemia Burning Eczematous lesions of eyelids Tearing Coneal ulcers Cataracts Pannus Keratoconus Retinal detatchment Vernal keratoconjunctivitis Intense itching Cobblestone papillae Intense hyperemia Tearing Mucous discharge Photophobia Milky conjuctiva Sensation of foreign body Punctate keratopathy Trantas dots Togby's ulcer Giant papillary conjunctivitis Itching Giant papillae Pain Excessive mucous production Sensation of foreign body Corneal lesions Lens intolerance

4 - 대한내과학회지 : 제 85 권제 5 호통권제 639 호 며, 눈의충혈, 소양감, 눈물흘림, 작열감이나타난다. 눈부심증상은드물다. 치료는원인물질을제거하거나회피하는것이원칙이며약물치료로는항히스타민제를점안액으로주로사용하며심한경우부신피질호르몬제를사용할수있으나녹내장이나백내장등의부작용이있어주의가필요하다. 인공눈물은알레르기항원이나염증매체를희석시키고씻어내주어증상을다소완화시킬수있으며차갑게보관된경우에보다효과적이다. 냉찜질또한부종을줄이고증상을완화시킬수있다. 경구항히스타민제는알레르기비염등전신적인알레르기질환이동반된경우에효과적이다. 부비동염및비용종알레르기와부비동염및비용종과의상관관계는아직까지명확하게밝혀지지않았지만많은연구에서알레르기비염이부비동염및비용종의발생에관여할것으로보고하였다. 꽃가루알레르기비염환자에서비유발시험후또는꽃가루계절에부비동염이발생하였으며 [13,14] 혈청총 IgE 항체치와부비동의점막두께와유의한상관관계가있었다 [15]. 만성비부비동염 (chronic rhinosinusitis) 환자에서아토피유병률이높았는데, 한연구에서는비부비동염으로수술을시행받은환자의 84% 에서흔한흡입항원에감작되었으며집먼지진드기등의통년성항원에대한감작률이꽃가루등의계절성항원보다높았다고보고하였다 [16]. 만성비부비동염에서진균에대한감작과만성비부비동염의연관성은아직까지잘모른다. 만성비부비동염의주된내과적치료는항생제와비강내스테로이드제이다 [11]. 항히스타민제는추천되지않지만동반된알레르기질환이나비부비동염의증상을경감시키는데도움이될수있다. 반복적이고심한만성비부비동염에서부비동내시경수술이널리시행되고있다. 삼출성중이염알레르기와삼출성중이염 (otitis media with effusion) 의연관성에대해서는이견이많은데, 많은연구에서일반모집단의알레르기유병률에비해서삼출성중이염환자에서알레르기의유병률이높다고보고하여알레르기가삼출성중이염의중요한원인인자중하나일것으로생각한다 [17]. 그기전으로는중이점막이알레르기에대한표적장기로직접작 용하거나코나비인두의알레르기염증세포에서유리되는사이토카인과염증매체들에의해이관기능장애에등이있다. 실제로알레르기환자의중이저류액에서알레르기염증세포들과염증매체들이증명되었으며중이점막에서호산구와 IL-4와 IL-5의 mrna 양성세포들의증가가보고되어알레르기염증반응이삼출성중이염의발생에기여함을보였다 [18]. 아데노이드비대증아데노이드는비인두에위치하는림프조직으로편도와함께구강및비강을통해침입하는병균이나바이러스에대해서방어작용을하는면역기관으로아데노이드비대증은소아에서흔하다 [19]. 아데노이드가비대해지면코막힘, 비음, 구강호흡, 코골이등의증상을유발하며심하면항상입으로호흡하기때문에얼굴의발달이상과부정교합을유발할수도있다 (adenoid face). 아데노이드비대증에서알레르기의역할은명확하지않지만알레르기환자의아데노이드에서 CD1a+ Langerhans 세포와호산구, IL-4 와 IL-5 mrna 양성세포들이증가하였다고보고되어알레르기염증이아데노이드비대증에관여함을알수있다 [18,20]. 아데노이드비대증환자에서항히스타민제의효과는불분명하나비강내스테로이드제는아데노이드의크기를줄이고관련증상을호전시키는데도움이된다. 수면장애알레르기비염환자에서수면장애는매우흔한증상이다. ARIA (allergic rhinitis and its impact on asthma) 지침에서는수면장애유무를알레르기비염을경증또는증등증- 중증으로분류하는하나의인자로제시하였다 [1]. 알레르기비염에의한코막힘은수면장애를유발할수있는데, 코막힘이전체기도저항을증가시키고구강호흡을유발하여하악과설근부의후하방전위를일으키며분당환기량의감소를일으켜이산화탄소배출에영향을미치는등의기전으로수면호흡장애와연관되는것으로생각된다 [21]. 성인을대상으로한조사에서알레르기비염환자에서정상대조군에비해서수면유도장애를호소하는경우가 3배 (24% vs. 8%), 수면유지장애를호소하는경우가두배로높았다 (31% vs. 13%). 수면

5 - 최정희. 알레르기비염의동반질환 - 호흡장애환자에서알레르기비염치료가중요한이유는코막힘및기도저항을감소시켜주관적인증상의호전과함께삶의질을개선할수있기때문이다 [21]. 한편, 소아알레르기비염환아의경우흔히동반되는편도아데노이드비대증이폐쇄성수면무호흡증을유발할수있다. 편도비대증이있는학동기아동들에서그렇지않은아동들에비해서알레르기비염의유병률이높았고 (29.7% vs. 8%) [22] 습관적으로코골이를하는학동전기아동들에서대조군에비해서유의하게흡입알레르겐에대한감작률이높았으며이들흡입알레르겐에대해양성반응을보인환아에서폐쇄성수면무호흡증의유병률이높았다 [23]. 이런환아들에서주간졸림증, 집중력장애등이문제가되기도한다. 따라서코골이가있는알레르기비염환아에서편도아데노이드비대증을반드시고려하여야한다. 만성기침 8주이상지속되는기침을만성기침이라고한다 [11]. 상기도기침증후군 (upper airway cough syndrome) 은만성기침의가장흔한원인으로이는기저질환에상관없이비강이나부비동의자극또는후비루때문에기침이발생하는경우를통칭한다. 알레르기비염은상기도기침증후군의흔한기저질환으로실제로알레르기비염환자의약 30% 에서기침을호소한다 [21]. 알레르기비염에서의기침은비염을치료함으로써치유된다. 만성기침의원인으로알레르기비염을간과하는경우기침이형천식이나천식조절실패로오인하여불필요하게천식치료약제를증량하게되는경우가있으므로항시주의를요한다. 결론알레르기비염은천식, 알레르기결막염, 부비동염, 중이염, 아데노이드비대증등의다양한질환들을동반한다. 알레르기비염은단순한코질환이아니라알레르기염증을바탕으로하는전신질환으로이해되어야하며알레르기비염을진료할때반드시그동반질환에대한평가가이루어져야한다. 알레르기비염과함께동반질환까지치료함으로써환자의만족도를충족시키고더나아가삶의질을향상시킬수있을것이다. 중심단어 : 알레르기비염 ; 천식 ; 동반질환 REFERENCES 1. 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 Aller Gen). Allergy 2008;63(Suppl 86): Lack G. Pediatric allergic rhinitis and comorbid disorders. J Allergy Clin Immunol 2001;108(1 Suppl):S Guerra S, Sherrill DL, Martinez FD, Barbee RA. Rhinitis as an independent risk factor for adult-onset asthma. J Allergy Clin Immunol 2002;109: Leynaert B, Neukirch C, Kony S, et al. Association between asthma and rhinitis according to atopic sensitization in a population-based study. J Allergy Clin Immunol 2004;113: Bousquet J, Annesi-Maesano I, Carat F, et al. Characteristics of intermittent and persistent allergic rhinitis: DREAMS Study Group. Clin Exp Allergy 2005;35: Ferdousi HA, Zetterström O, Dreborg S. Bronchial hyperresponsiveness predicts the development of mild clinical asthma within 2 yr in school children with hay-fever. Pediatr Allergy Immunol 2005;16: Settipane RJ, Settipane GA. IgE and the allergy-asthma connection in the 23-year follow-up of Brown University students. Allergy Asthma Proc 2000;21: Bousquet J, Gaugris S, Kocevar VS, et al. Increased risk of asthma attacks and emergency visits among asthma patients with allergic rhinitis: a subgroup analysis of the investigation of montelukast as a partner agent for complementary therapy [corrected]. Clin Exp Allergy 2005;35: Corren J, Manning BE, Thompson SF, Hennessy S, Strom BL. Rhinitis therapy and the prevention of hospital care for asthma: a case-control study. J Allergy Clin Immunol 2004; 113: Brozek JL, Bousquet J, Baena-Cagnani CE, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines: 2010 revision. J Allergy Clin Immunol 2010;126: The Korean Academy of Asthma, Allergy and Clinical Immunology. Asthma and Allergic Diseases. 2nd ed. Seoul: Yeomoongak, Ono SJ, Abelson MB. Allergic conjunctivitis: update on pathophysiology and prospects for future treatment. J Allergy Clin Immunol 2005;115: Naclerio RM, detineo ML, Baroody FM. Ragweed allergic rhinitis and the paranasal sinuses: a computed tomographic study. Arch Otolaryngol Head Neck Surg 1997;123: Piette V, Bousquet C, Kvedariene V, et al. Sinus CT scans and mediator release in nasal secretions after nasal cha

6 - The Korean Journal of Medicine: Vol. 85, No. 5, llenge with cypress pollens. Allergy 2004;59: Baroody FM, Suh SH, Naclerio RM. Total IgE serum levels correlate with sinus mucosal thickness on computerized tomography scans. J Allergy Clin Immunol 1997;100: Emanuel IA, Shah SB. Chronic rhinosinusitis: allergy and sinus computed tomography relationships. Otolaryngol Head Neck Surg 2000;123: Yeo SG, Park DC, Eun YG, Cha CI. The role of allergic rhinitis in the development of otitis media with effusion: effect on eustachian tube function. Am J Otolaryngol 2007;28: Nguyen LH, Manoukian JJ, Sobol SE, et al. Similar allergic inflammation in the middle ear and the upper airway: evidence linking otitis media with effusion to the united airways concept. J Allergy Clin Immunol 2004;114: Huang SW, Giannoni C. The risk of adenoid hypertrophy in children with allergic rhinitis. Ann Allergy Asthma Immunol 2001;87: Vinke JG, KleinJan A, Severijnen LW, Hoeve LJ, Fokkens WJ. Differences in nasal cellular infiltrates between allergic children and age-matched controls. Eur Respir J 1999;13: Hadley JA, Derebery MJ, Marple BF. Comorbidities and allergic rhinitis: not just a runny nose. J Fam Pract 2012; 61(2 Suppl):S Yumoto E, Kozawa T, Yanagihara N. Influence of tonsillar hypertrophy to physical growth and diseases of the nose and ear in school-age children. Nihon Jibiinkoka Gakkai Kaiho 1991;94: McColley SA, Carroll JL, Curtis S, Loughlin GM, Sampson HA. High prevalence of allergic sensitization in children with habitual snoring and obstructive sleep apnea. Chest 1997;111:

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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