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1 대한안과학회지제 49 권제 8 호 2008 J Korean Ophthalmol Soc 49(8): , 2008 DOI : /jkos = 증례보고 = 콜라겐함유피부주입물주사후수년이지나다른부위에발생한염증성육아종 조영준 1 이덕구 1 이성복 1,2 충남대학교의과대학안과학교실 1, 충남대학교의학연구소 2 목적 : 미용목적으로이마부위에콜라겐함유피부주입물을시술받은후 7 년이지나우측안쪽눈구석아래쪽에발생한염증성육아종을경험하였기에이를보고하고자한다. 증례요약 : 7 년전이마에콜라겐함유피부주입물을주입받았던 47 세여자환자가 20 여일전에발견된우측안쪽눈구석아래부위의종괴를주소로내원하였다. 서서히크기가증가했다는종괴는비교적단단하였으나고정되어있지는않았고경한압통을보이고있었다. 안와전산화단층촬영및자기공명영상에서약 1 cm 크기의경계가명확하지않고조영증강이되는결절성음영을보였고골의미란은관찰되지않았다. 피부절개를통하여종괴를제거하였고, 생검중종괴주위에서성분을알수없는이물이발견되었다. 조직검사에서이물질에의한염증성육아종으로진단되었다. 결론 : 콜라겐함유피부주입물은미용효과가오래지속되고합병증이적어미용목적으로널리사용되고있다. 하지만콜라겐함유피부주입물을주입하고수년이경과한후에라도주입부위또는그주위의다른위치에서도염증성육아종과같은합병증이발생할수있음을유의하여야하겠다. < 한안지 49(8): , 2008> 지난 40 여년간다양한물질이피부충전물로개발되어왔으며, 주로중년여성에서눈과입주위, 이마그리고뺨부위의주름을없애기위하여사용되었다. 그중콜라겐함유피부주입물 (dermal filler) 은 1980 년대이후에미용적인목적으로널리사용되어왔다. 1 콜라겐함유피부주입물에는인체나소에서추출한순수콜라겐제품과, 피부주입물의효과를연장하기위하여인체내에서분해가되지않는물질을혼합한 Artecoll R 이나 Artefill R 같은제품이개발되어사용되고있다. 2,3 콜라겐함유피부주입물의부작용으로는주입부위의비특이성염증, 통증, 경결, 홍반, 종창, 농양형성, 국소괴사, 국소과민반응, 체액성항체형성에의한전신반응등이알려져있다. 2-4 드물게주입부위에육아 < 접수일 : 2007 년 10 월 4 일, 심사통과일 : 2008 년 3 월 25 일 > 통신저자 : 이성복대전시중구대사동 640 충남대학교병원안과 Tel: , Fax: sblee@cnu.ac.kr * 본논문의요지는 2007 년제 97 회대한안과학회춘계학술대회에서포스터로발표되었음. 종이발생할수도있는데, 일반적으로시술후한달이내에발생하며홍반, 경결, 결절등의증상이동반되고, 2-4 수년후에주입부위에서발생한육아종도매우드물게보고되어있다. 2,5,6 저자들은미용목적으로이마부위에콜라겐함유피부주입물을시술받은후 7 년이지나우측안쪽눈구석아래쪽에발생한염증성육아종을경험하였기에이를보고하고자한다. 증례보고 7 년전미간주름을없애기위하여이마에콜라겐함유피부주입물을주입받았던 47 세여자환자가내원 20 여일전에발견된우측안쪽눈구석아래부위의종괴를주소로내원하였다. 환자는정확한콜라겐함유피부주입물의명칭은알지못했으며, 이마부위이외에는피부주입물을사용하지않았다고하였다. 종괴는우측안쪽눈구석아래부위에서서서히크기가증가했다고하였다 (Fig. 1). 촉진검사에서종괴는비교적단단하였고, 고정되어있지않았으며, 경한압통을동반하고있었다. 안와전산화단층촬영에서우측내안각아래쪽으로경계가명확하지않은연부조직정도의음영을가진결절이관찰되었고주위골의미란은 1330

조영준외 : 염증성육아종 Figure 1. Preoperative photograph. The hard, non-fixed and mild tender mass is palpated on the right medial canthal area (arrows). 관찰되지않았다 (Fig. 2).

조직병리검사에서이물반응에의한만성육아종성염증소견을보이고, 진피전반에걸쳐뚜렷한경계를가진둥글고투명한공간이산재되어있었으며, 그주위에이물거대세포가관찰되어이물질에의한염증성육아종으로진단되었다 (Fig. 5). 고 찰 콜라겐은연부조직의증강을위해주로쓰이는조직충전물로서 1977 년 Knapp et al 7 이동종 ( 인체 ) 또는 Figure 2.

이후최초의우형콜라겐인 Zyderm I R 이 1981 년 FDA 의승인을얻으면서전세계적으로보급되었고, 3 짧은시술시간, 뛰어난보정효과, 안전성등의우수성을인정받음으로써전세계적으로가장널리쓰이는연부조직충전물이되었다. 8 하지만콜라겐은생체내에서콜라겐분해효소에의해분해됨으로써그지속시간이짧고, 시술전에과민반응에대한검사가필요한단점이있다.

2 조영준외 : 염증성육아종 Figure 1. Preoperative photograph. The hard, non-fixed and mild tender mass is palpated on the right medial canthal area (arrows). 관찰되지않았다 (Fig. 2). 안와자기공명영상에서는약 1 cm 크기의경계가명확하지않고조영증강이되는결절성음영을보였다 (Fig. 3). 절제생검을통하여 14 4 mm 의종괴를적출하였으며 (Fig. 4A), 성분을알수없는투명하고단단한이물이종괴주위에서함께발견되었다 (Fig. 4B). 조직병리검사에서이물반응에의한만성육아종성염증소견을보이고, 진피전반에걸쳐뚜렷한경계를가진둥글고투명한공간이산재되어있었으며, 그주위에이물거대세포가관찰되어이물질에의한염증성육아종으로진단되었다 (Fig. 5). 고 찰 콜라겐은연부조직의증강을위해주로쓰이는조직충전물로서 1977 년 Knapp et al 7 이동종 ( 인체 ) 또는 Figure 2. Preoperative orbital CT scan shows soft tissue swelling without bony erosion in the right medial canthal area (arrow). 이종 ( 소 ) 에서채취한콜라겐을 28 명의환자에게주사하면서처음소개되었다. 이후최초의우형콜라겐인 Zyderm I R 이 1981 년 FDA 의승인을얻으면서전세계적으로보급되었고, 3 짧은시술시간, 뛰어난보정효과, 안전성등의우수성을인정받음으로써전세계적으로가장널리쓰이는연부조직충전물이되었다. 8 하지만콜라겐은생체내에서콜라겐분해효소에의해분해됨으로써그지속시간이짧고, 시술전에과민반응에대한검사가필요한단점이있다. 2-4 Figure 3. Preoperative orbital MRI findings. (A) On T1-weighted axial image, about 1 cm-sized, ill defined mass appears as an isosignal intensity with extraocular muscles in the right medial canthal area (arrow). (B) The mass is well enhanced on post-contrast T1-weighted axial image (arrowhead). 1331

The mass is consisted of histiocytes, epitheloid cells and multinucleated giant cells (arrow). The mass has also numerous empty vacuoles. The mass was diagnosed as foreign body inflammatory granuloma.

3 대한안과학회지제 49 권제 8 호 2008 년 Figure 4. Gross findings of the mass. (A) The mass (14 4 mm) is not encapsulated and has irregular surface. (B) Unidentified 2 1 mm and 1 1 mm sized foreign bodies are found around the mass. These are hard and translucent. Figure 5. Histopathologic findings of the mass. The mass is consisted of histiocytes, epitheloid cells and multinucleated giant cells (arrow). The mass has also numerous empty vacuoles. The mass was diagnosed as foreign body inflammatory granuloma. (Hematoxylin and eosin stain; original magnification 400). Zyderm I R 이 3 개월정도로짧은지속기간을보여효과를연장하기위해 Zyderm I R 보다높은콜라겐농도를가진 Zyderm II R 와콜라겐분해효소에저항성을가지는 Zyplast R 가개발되었으나, 그지속기간이각각 3~6 개월, 6~12 개월로약간의연장만을보여주었다. 3,4 이후인체내에서분해가되지않는 polymethylmeth acrylate (PMMA) microsphere 를이용하여콜라겐의작용기간을연장하고자하는연구가있었다. 초기에젤라틴에 PMMA microsphere 를혼합한 Arteplast R 가개발되었으나주입부위에육아종의발생이 2.5% 정도로많아이후에는사용되지않았다. 9,10 최근에는콜라겐에매우정제된 PMMA microsphere 를혼합한 Artecoll R (Bovine-collagen 75%, PMMA 25%) 이나 Artefill R (Bovine-collagen 80%, PMMA 20%) 과같은콜라겐제품들이주로사용되고있으며, 2,3,11 2 년이상으로효과가지속되는것으로알려져있다. 12,13 콜라겐함유피부주입물의사용초기에는시술직후에시술부위에발생하는좌상, 종창, 압통, 피부변색, 주사부위의점상출혈및비특이성염증등의부작용만알려졌으나, 최근에는농양형성, 국소괴사, 혈종형성, 감염, 국소과민반응, 체액성항체형성에의한전신반응, 삽입물의피하이동, 비후성반흔, 육아종형성등의드문부작용이보고되면서그사용이감소하고있다. 2-4,14,15 특히육아종의형성은다양한피부주입물에의해발생할수있으며, 임상적으로발견가능한육아종이형성되는확률은 0.01~0.1% 정도로알려져있다 흡수성물질이비흡수성 ( 영구적 ) 물질에비하여육아종의발생율이낮으며, 비흡수성물질이더라도불규칙한표면의미립자에비해 PMMA 처럼매끈한표면의미립자를가진주입물에서육아종의발생율이낮은것으로알려져있다. 12 같은 PMMA 의경우에도초기에개발된 Arteplast R 보다, PMMA 의크기가더균등하고정전기등이발생하지않도록정제된 PMMA 를사용한 Artecoll R 이나 Artefill R 을사용한경우에육아종의발생율이낮았다. 11 콜라겐에의한육아종은일반적으로시술후한달이내에발생하며, 주입부위에홍반, 경결, 종창또는결절을동반하는것으로알려져있는데, 2 이러한동반증상은감염에의한증상과혼동될수있으므로육아종의확진을위해서는일반적으로조직학적, 미생물학적검사가요구된다. 12 시술후수년후에발생하는육아종은 1332

4 조영준외 : 염증성육아종 매우드물며시술부위의표층부및심부의근육을침범하여발생한경우가보고된바있다. 2 본증례는이마부위에콜라겐함유피부주입물을주입한후약 7 년후에주입부위가아닌우측안쪽눈구석아래쪽에육아종이발생하였다. 조직병리검사에서이물반응에의한만성육아종성염증소견을보이고, 진피전반에걸쳐뚜렷한경계를가진둥글고투명한공간이산재되어있었으며, 그주위에이물거대세포가관찰되어 Artecoll R 이나 Artefill R 과같이 PMMA 와혼합된콜라겐함유피부주입물에의한육아종의조직소견과매우유사하여, 환자에게발생한육아종이콜라겐함유피부주입물에의하여유발되었을것으로생각된다. 2,11,15 그러나 Artecoll R 또는 Artefill R 육아종은일정한크기의공포를동반하는데비하여, 11 본증례는상대적으로다양한크기의공포를보였고, 성분을알수없는이물이함께발견되어, 정제가덜된유사제품을사용하였거나다른종류의피부주입물을함께사용했을가능성이있다고생각된다. 지금까지콜라겐함유피부주입물에의한육아종은그발생위치가주입부위에국한된것만보고되었고, 5,13,15 주입 10 년후까지도발생된예가보고된바있다. 5 콜라겐함유피부주입물의부작용중의하나가주입물의피하이동인것을감안하면, 콜라겐함유피부주입물이피하이동을일으키고수년이지나서육아종을형성하는것도가능할것이라고생각된다. 저자들이아는바에의하면본증례는콜라겐함유피부주입물주입후수년후에육아종이주입부위가아닌곳에서발생한최초의보고이다. 결론적으로콜라겐함유피부주입물과같이영구적또는반영구적피부주입물을사용할때에는시술후수년이경과한후에라도주입부위또는그주위의다른위치에서도염증성육아종과같은합병증이발생할수있음을유의하여야하겠다. 참고문헌 1) Lombardi T, Samson J, Plantier F, et al. Orofacial granulomas after injection of cosmetic fillers. Histopathologic and clinical study of 11 cases. J Oral Pathol Med 2004;33: ) Zimmermann US, Clerici TJ. The histological aspects of fillers complications. Semin Cutan Med Surg 2004;23: ) Rohrer TE. Soft tissue filler substances. Current Problems in Dermatology 2001;13: ) Bergeret-Galley C. Comparison of resorbable soft tissue fillers. Aesthetic Surg J 2004;24: ) Constantinides M, Zimbler MS, Jagirdar J. An unusual late reaction to facial injections. Otolaryngol Head Neck Surg 1999;120: ) Moscona RR, Bergman R, Friedman-Birnbaum R. An unusual late reaction to Zyderm I injections: a challenge for treatment. Plast Reconstr Surg 1993;92: ) Knapp TR, Kaplan EN, Daniels JR. Injectable collagen for soft tissue augmentation. Plast Reconstr Surg 1977;60: ) Drake LA, Dinehart SM, Farmer ER, et al. Guidelines of care for soft tissue augmentation: collagen implants. J Am Acad Dermatol 1996;34: ) Lemperle G, Pietz R, Lemperle M. Plastic Surgery. Vol. 2. Amsterdam: Elsevier, 1992: ) Lemperle G, Holmes R, Larson FG. Granuloma formation and electrical surface charges after Bioplastique and Arteplast implantation. Aesthetic Plast Surg 2000;24: ) Lemperle G, Romano JJ, Busso M. Soft tissue augmentation with artecoll: 10-year history, indications, techniques, and complications. Dermatol Surg 2003;29: ) Lowe NJ, Maxwell CA, Patnaik R. Adverse reactions to dermal fillers: review. Dermatol Surg 2005;31: ) Conejo-Mir JS, Sanz Guirado S, Angel Munoz M. Adverse granulomatous reaction to Artecoll treated by intralesional 5-fluorouracil and triamcinolone injections. Dermatol Surg 2006;32: ) Haneke E. Polymethyl methacrylate microspheres in collagen. Semin Cutan Med Surg 2004;23: ) Kim KJ, Lee HW, Lee MW, et al. Artecoll granuloma: A rare adverse reaction induced by microimplant in the treatment of neck wrinkles. Dermatol Surg 2004;30: ) Rudolph CM, Soyer HP, Schuller-Petrovic S, Kerl H. Foreign body granulomas due to injectable aesthetic microimplants. Am J Surg Pathol 1999;23: ) Requena C, Izquierdo MJ, Navarro M, et al. Adverse reactions to injectable aesthetic microimplants. Am J Dermatopathol 2001;23: ) Hanke CW. Tissue Augmentation in Clinical Practice. Procedures and Techniques, Vol. 1. New York: Marcel Dekker, 1998: ) Shafir R, Amir A, Gur E. Long-term complications of facial injections with Restylane (injectable hyaluronic acid). Plast Reconstr Surg 2000;106: ) Berqeret-Galley C, Latouche X, Illouz YG. The value of new filler material in corrective and cosmetic surgery: DermaLive and DermaDeep. Aesthetic Plast Surg 2001;25:

5 대한안과학회지제 49 권제 8 호 2008 년 =ABSTRACT= Late-onset Migrated Inflammatory Granuloma After Collagen-Containing Filler Injection Young Joon Jo, M.D. 1, Deok Goo Lee, M.D. 1, Sung Bok Lee, M.D. 1,2 Department of Ophthalmology, College of Medicine, Chungnam National University 1, Daejeon, Korea Chungnam National University Research Institute for Medical Sciences 2, Daejeon, Korea Purpose: To report a case of inflammatory granuloma in the right medial canthal area which occurred seven years after a cosmetic collagen-containing dermal filler injection in the forehead. Case summary: A-47-year-old female, who had been treated with collagen-containing filler 7 years earlier, presented with a mass in the right medial canthal area discovered 20 days previously. There was mild tenderness and the mass was firm and not fixed. The patient reported that the size of the mass was slowly increasing. Orbital computed tomography and magnetic resonance imaging showed an approximate 1 cm-sized, poorly defined, enhancing nodular thickening without evidence of bony erosion. The mass was removed through a skin incision and unidentified foreign bodies were found around the mass. On histopathologic examination, it was diagnosed as inflammatory granuloma caused by foreign substances. Conclusions: Collagen-containing fillers are widely used in cosmetic surgery for their lasting effect and few complications. However some complications such as inflammatory granuloma may occur at the injection site or other sites, even several years after operation. J Korean Ophthalmol Soc 49(8): , 2008 Key Words: Collagen, Filler, Granuloma Address reprint requests to Sung Bok Lee, M.D. Department of Ophthalmology, Chungnam National University Hospital #640 Daesa-dong, Jung-gu, Daejeon , Korea Tel: , Fax: , sblee@cnu.ac.kr 1334

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