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1 대한내과학회지 : 제 76 권제 3 호 2009 특집 (Special Review) - 주요알레르기질환의진단과치료 알레르기비염의진단과치료 경북대학교의학전문대학원내과학교실 이종명 Diagnosis and treatment of allergic rhinitis Jong Myung Lee, M.D. Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea The diagnosis of allergic rhinitis can generally be made on the basis of the history and physical examination. The history helps establish seasonality, potentially inciting factors, and co-morbidities including sinusitis, nasal polyps, allergic conjunctivitis, and asthma. On physical examination, the nasal mucous membranes are pale, wet, and boggy. Allergy testing is performed in order to confirm the diagnosis and which allergens are relevant to the symptoms. The management of allergic rhinitis includes allergen avoidance, pharmacologic treatment, and specific immunotherapy. Mild symptoms are easily controlled with either a second-generation antihistamine or a nasal corticosteroid alone. For patients with moderate-to-severe symptoms with nasal congestion as a predominant finding, therapy should be started with daily use of a nasal corticosteroid, which would be combined with other medications, such as antihistamines and decongestants. Specific immunotherapy is generally reserved for the selected patients whose symptoms are inadequately controlled with a pharmacotherapy and allergen avoidance. (Korean J Med 76: , 2009) Key Words: Allergic rhinitis; Skin test; Antihistamine; Corticosteroid 서론비염과천식은역학, 병태생리및임상적으로밀접한관련성이있어근래에는하나의기도질환 (one airway, one disease) 으로인식되고있다 1). 천식환자는대부분비염을동반하고있고, 비염을가진환자의반수이상은천식이나알레르기결막염을동반하고있다 2). 또한비염은천식발생의중요한위험인자이며 3, 4), 이미천식을동반한환자에서는천식악화인자의하나이다. 따라서내과의사는알레르기비염을진단하고치료하기위해필요한지식을갖추고있어야한다. 알레르기비염의진단비염은발생기전에따라알레르기성과비알레르기성으로대별할수있다 ( 표 1). 그러나실제로는이두가지형태가 혼합된경우가단독형보다더흔한것으로알려져있다 5). 알레르기비염은증상이나타나는양상에따라통년성, 계절성, 계절적악화를동반한통년성, 삽화성 (episodic) 으로구분하는데 6), 국내에서는외국에비해상대적으로통년성혹은계절적악화를동반한통년성비염이많은편이다. 한편 ARIA (Allergic Rhinitis and its Impact on Asthma) 가이드라인은이러한구분대신에증상의기간에따라간헐성및지속성, 증상의중증도에따라경증및중등증- 중증으로분류하며 ( 그림 1), 이에따른단계적치료법을권장하고있다 7). 알레르기비염의주요증상은코나목안의가려움, 발작적인재채기, 물처럼맑은콧물, 코막힘, 후각기능의감소등이며, 환자에따라서는재채기와콧물을주증상으로하기도하고 (sneezers and runners) 지속적인코막힘을주증상으로하기도한다 (blockers). 부비동염이나중이염이합병되거나천식혹은알레르기결막염이동반된환자에서는이에

2 - Jong Myung Lee. Diagnosis and treatment of allergic rhinitis - Table 1. Classification of rhinitis 1. Allergic rhinitis - seasonal, perennial, perennial with seasonal exacerbations, episodic 2. Nonallergic rhinitis - vasomotor rhinitis, infectious rhinitis, gustatory rhinitis, nonallergic rhinitis with eosinophilia syndrome (NARES) 3. Occupational rhinitis - IgE-mediated, nonimmune mechanism, work-aggravated rhinitis 4. Other rhinitis syndromes - hormonal-induced rhinitis, drug-induced rhinitis, atrophic rhinitis, rhinitis associated with inflammatory-immunologic disorders Figure 1. Classification of allergic rhinitis 7) 따른증상도나타난다. 진단을위해서는상세한병력청취가무엇보다중요하다. 환자가특정한계절에증상이반복되는경우, 알레르기결막염이나천식을동반한경우, 알레르기가족력이뚜렷한경우에는비염의원인이알레르기일가능성이매우크다. 이외에도비염의악화요인, 치료에대한반응, 직업과의연관성, 주거환경등에대한문진도포함되어야한다. 진찰에서는비점막이창백하게부어있고맑은분비물로덮여있는소견을비경으로볼수있다. 분비물이누렇고끈적끈적하면감염성비염이나부비동염을의심해야한다. 병력과진찰만으로진단이확실치않거나치료에대한반응이기대에미치지못할경우에는알레르기검사가필수적이다. 이는피부반응검사나혈청특이 IgE 검사를통해가능하며, 전자가더간편하면서도진단적가치가높다 8). 비염환자에서는천식이동반되는경우가많으므로폐기능을검사하는것이좋다. 이밖에혈청총 IgE나혈액호산구검사도도움이되지만기생충감염등에서도증가하므로특이적인소견은아니다. 코분비물도말검사는혈액보다호산구성염증반응을더직접적으로반영하며, 백혈구중호산구가차지하는비 율이 10% 이상이면의미가있다 9). 감별해야할질환은여러가지가있으며병력과진찰만으로구별이쉽지않은경우도있다. 특히혈관운동성비염 (vasomotor rhinitis) 은증상이유사하며, 콧물을주로호소하는아형과코막힘을주로호소하는아형도있어알레르기비염으로오인되기도한다. 이질환은자율신경계의이상에의해발생한다고추측되며 10) 알레르기비염과는달리성인에서주로발생한다. 기온이나기압의변화, 냄새, 연기, 술, 자극적인음식, 감정과같은비특이적인자극에의해악화하며, 진단은다른비염의배제에의해서만가능하다. 치료로는콧물이주증상일때는국소용항콜린제, 코막힘이주증상일때는국소용스테로이드, 혼합형일때는국소용항히스타민제가일차적으로권유된다. 조절이되지않으면이들을병용하거나다른약제를추가한다 11). 경구용항히스타민제는별로효과가없는것으로보고되어있으며악화인자를피하도록교육한다. 부비동염, 비용종, 비중격만곡증, 비강내종양, 비갑개비후등도알레르기비염과유사한증상을보일수있어감별되어야한다. 한편알레르기비염환자에서는부비동염과비용종이잘합병하므로치료에도불구하고코막힘이호전되지않으며이의합병가능성을고려하여야한다. 알레르기비염의치료 1. 회피요법 HEPA 필터가내장된진공청소기나진드기살충제의사용, 알러젠의통과가불가능한특수천으로침구감싸기등이집먼지진드기의실내농도와비염증상을감소시킨다는보고들이있지만아직확실한증거는부족하며 12), 여러가지방법을함께시행하는것이더효과적일것으로생각된다. 꽃가루에매우민감한계절성비염환자는원인이되는꽃가루의농도가높을때에는외출을자제하는것이좋다

3 - 대한내과학회지 : 제 76 권제 3 호통권제 583 호 Table 2. Name, type, and dose of intranasal corticosteroids Trade name Generic name Type μg/spray Adult dose Child dose Age limit (y) Beconase AQ Beclomethasone Pump 200 spray spray bid 1-2 spray bid 6 monohydrate Flonase Fluticasone Pump 120 spray 50 2 sprays qd 1-2 spray qd 4 propionate Nasarel Flunisolide Pump 200 spray 25 2 spray bid-tidd 2 spray bid 6 Nasacort AQ Triamcinolone Pump 120 spray spray qd 1-2 spray qd 6 Nasonex Mometasone Pump 120 spray 50 2 spray qd 1 spray qd 2 Rhinocort AQ Budesonide Pump 120 spray spray qd 1-2 spray qd 6 Veramyst Fluticasone Pump 120 spray 50 2 spray qd 1 spray qd 2 furoate Omnaris Ciclesonide Pump 120 spray 50 2 spray qd 12 Table 3. Effect of therapies on rhinitis symptoms Sneezing Rhinorrhea Obstruction Nasal itching Eye Sx Antihistamines oral intranasal intraocular Corticosteroids intranasal Decongestants oral intranasal Chromones intranasal intraocular Anticholinergics Antileukotrienes 약물요법 1) 항히스타민제 Chlorpheniramine, hydroxyzine, mequitazine, cyproheptadine 과같은 1세대항히스타민제는작용시간이짧고진정작용, 항콜린작용 ( 점막건조, 배뇨장애, 변비 ) 등의부작용으로인해사용에제한이많다. 2세대항히스타민제로는 astemizole, terfenadine, cetrizine, loratadine, acrivastine, fexofenadine, azelastine, ebastine 등이있으며, 이들은작용시간이길고부작용이크게개선되었다. Cetirizine이나국소용 azelastine은권장량에서도진정작용이나타날수있지만 fexofenadine, loratadine, desloratadine은권장량에서진정작용을보이지않는다 13). 그러나 astemizole과 terfenadine은 azole계항진균제 (fluconazole, itraconazole) 나 macrolide 계항생제 (erythromycin, clarithromycin) 와병용시에심각한부정맥을유발할수있으므로주의가필요하다 14). Astemizole과 azelastine은식욕을증가시켜체중을증가시킬수있다. 항히스타민제는경증알레르기비염의일차치료약제이다. 소양증, 재채기, 콧물및결막염증상에는매우효과적이지만코막힘에는별효과가없는단점이있다. 효과면에서각약제들간에유의한차이가있다는증거는아직없다. 국소용항히스타민제는경구용과효과가비슷하거나더낫다는보고가있지만 15, 16), 국소용스테로이드제보다는효과가떨어지는것으로알려져있다 17). 2) 국소용스테로이드제국소용스테로이드제가갖추어야할이상적인조건으로는 1) 스테로이드수용체친화도, 강도및특이도가높고 2)

4 - 이종명. 알레르기비염의진단과치료 - Figure 2. Treat in a stepwise approach (adolescents and adults). 전신생체이용률 (bioavailability) 이낮으며 3) 간에서의 1차통과청소율 (first-pass inactivation rate) 이높고 4) 하루한번사용하는것등이다. 현재개발된약제중에는 mometasone furoate, ciclesonide, fluticasone furoate 등이이러한특성에근접하고있다 18). 그러나비염증상의개선에어떤약제가다른종류보다더뛰어나다는것을입증할만한자료는아직없다. 용량및용법은종류에따라다소차이가있다 ( 표 2). 필요시마다투여해도효과가있는것으로알려져있지만규칙적으로사용하는것이더효과적이며, 근래에개발된제 제들은 1~2 일내에이미효과가나타나기시작하는것으로보고되고있다 19). 국소용스테로이드는알레르기비염의증상을개선하는데가장효과적인약제로서중등증- 중증알레르기비염치료의 1차선택약제로인정되고있다. 메타분석에서경구용히스타민과비교하여눈증상의개선에는비슷한효과를보인반면, 코막힘과재채기의개선에서는스테로이드제가더효과적이었다 20). 국소용스테로이드제를국소용항히스타민제와비교한연구에서도비슷한결과가관찰되었다 17). 또한대

5 - The Korean Journal of Medicine: Vol. 76, No. 3, 부분의연구에서이약제는항히스타민제와항류코트리엔제의병합치료보다더우수한성적을보였다 21). 국소부작용으로는점막건조나자극, 코피등이가끔발생한다. 부신억제나성장장애등과같은전신부작용은별로문제가없는것으로알려져있다. 3) 기타약제들류코트리엔수용체차단제는알레르기비염에효과가있지만그정도는스테로이드제에비해약한것으로보고되어있다 21). 따라서이약제는항히스타민제나국소적스테로이드, 혹은이들의병합요법에도증상이충분히조절되지않는경우에추가약제로사용하는것이권장된다. 비반세포안정제인 cromolyn은효과가스테로이드제보다약하며치료성적도일정치않다. 비충혈제거제로사용되는알파교감신경자극제는코막힘에유효하며, 대개항히스타민제와병합하여경구로사용한다. 알파교감신경자극제는관상동맥질환, 고혈압, 당뇨, 갑상선기능항진증이있거나 monoamine oxidase 저해제를투여중인환자에서는주의해서사용해야한다. 또한국소용의경우, 규칙적으로분무하면의인성비염 (rhinitis medicamentosa) 이발생하므로사용기간을 10일이내로제한해야한다. 알레르기비염에사용하는약물들의효과를요약하면표 3과같다 22). 3. 면역요법대부분의치료지침에서면역요법은항원회피와약물치료로잘조절되지않을경우에시행하기를권장하고있다 6, 7, 22). 그러나이요법은알레르기질환의자연경과를변화시킬수있는유일한방법이며 23), 비염에대한치료효과는다수의연구에서입증된바있다 24). 피하로항원을주사하는것이전통적인방법이지만근래에는유럽을중심으로설하면역요법 (sublingual immunotherapy) 도이용되고있다. 이방법은투여가간편하고, 효과에는큰차이가없으며더안전한것으로알려져있다 25). 결론현대의학은표준화된치료를강조하고있으며알레르기비염의치료에도몇가지지침들이소개되어있다 6, 7, 10, 22). 이중국내외에서널리이용되고있는 ARIA 가이드라인 7) 을소개하면그림 2와같다. 이지침은알레르기비염을간헐성과지속성으로구분하며이를다시증상의중증도에따라경증및중등증- 중증으로세분하여일차약제의선택에차이 를두고있으며, 치료에반응하거나반응하지않는경우에대한단계적인접근법을제시하고있어적용하기에편리하다. 중심단어 : 알레르기비염 ; 알레르기검사 ; 항히스타민제 ; 국소용부신피질호르몬제 REFERENCES 1) Blaiss MS. Rhinitis-asthma connection: epidemiologic and pathophysiologic basis. Allergy Asthma Proc 26:35-40, ) Bousquet J, Knani J, Hejjaoui A, Ferrando R, Cour P, Dhivert H, Michel FB. Heterogeneity of atopy. I. Clinical and immunologic characteristics of patients allergic to cypress pollen. Allergy 48: , ) Dixon AE, Kaminsky DA, Holbrook JT, Wise RA, Shade DM, Irvin CG. Allergic rhinitis and sinusitis in asthma: differential effects on symptoms and pulmonary function. Chest 130: , ) Burgess JA, Walters EH, Byrnes GB, Giles GG, Jenkins MA, Abramson MJ, Hopper JL, Dharmage SC. Childhood adiposity predicts adult-onset current asthma in females: a 25-yr prospective study. Eur Respir J 29: , ) Settipane RA, Charnock DR. Epidemiology of rhinitis: allergic and nonallergic. Clin Allergy Immunol 19:23-34, ) Wallace DV, Dykewicz MS, Bernstein DI, Blessing-Moore J, Cox L, Khan DA, Lang DM, Nicklas RA, Oppenheimer J, Portnoy JM, Randolph CC, Schuller D, Spector SL, Tilles SA. The diagnosis and management of rhinitis: An updated practice parameter documents of the Joint Task Force on Practice Parameters in Allergy, Asthma and Immunology. J Allergy Clin Immunol 122:S1-84, ) Bousquet J, Van Cauwenberge P, Khaltaev N. Allergic rhinitis and its impact on asthma. J Allergy Clin Immunol 108(5 Suppl):S , ) Petersson G, Dreborg S, Ingestad R. Clinical history, skin prick test and RAST in the diagnosis of birch and timothy pollinosis. Allergy 41: , ) Crobach M, Hermans J, Kaptein A, Ridderikhoff J, Mulder J. Nasal smear eosinophilia for the diagnosis of allergic rhinitis and eosinophilic non-allergic rhinitis. Scand J Prim Health Care 14: , ) Dykewicz MS, Fineman S, Skoner DP, Nicklas R, Lee R, Blessing-Moore J, Li JT, Bernstein IL, Berger W, Spector S, Schuller D. Diagnosis and management of rhinitis: complete guidelines of the Joint Task Force on Practice Parameters in Allergy, Asthma and Immunology. American Academy of Allergy, Asthma, and Immunology. Ann Allergy Asthma Immunol 81(5 Pt 2): , ) Wheeler PW and Wheeler SF. Vasomotor rhinitis. Am Fam Physician 72: ,

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<303220C6AFC1FD20B0EDBFB5C0CF D E687770> 대한내과학회지 : 제 85 권제 5 호 2013 http://dx.doi.org/10.3904/kjm.2013.85.5.452 특집 (Special Review) - 알레르기비염 알레르기비염의진단 전남대학교의과대학알레르기내과 고영일 Diagnosis of Allergic Rhinitis Young-Il Koh Division of Allergy, Asthma