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대한안과학회지 2015 년제 56 권제 12 호 J Korean Ophthalmol Soc 2015;56(12):1979-1984 ISSN 0378-6471 (Print) ISSN 2092-9374 (Online) http://dx.doi.org/10.3341/jkos.2015.56.12.1979 Case Report 중심망막동맥폐쇄로인한갑작스런시력저하가첫증상으로나타난결절다발동맥염 1 예 A Case of Polyarteritis Nodosa with Decreased Vision as a First Symptom 김창주 1 남기엽 1 이상준 1,2 이승욱 1 Chang Zoo Kim, MD 1, Ki Yup Nam, MD, PhD 1, Sang Joon Lee, MD, PhD 1,2, Seung Uk Lee, MD, PhD 1 고신대학교의과대학안과학교실 1, 고신대학교의과대학의과학연구소 2 Department of Ophthalmology, Kosin University College of Medicine 1, Busan, Korea Institute of Medicine, Kosin University College of Medicine 2, Busan, Korea Purpose: Polyarteritis nodosa (PAN) is the necrotic vasculitis affecting middle and small-sized arteries throughout the body including ocular tissue. We report an atypical PAN case of unilateral central retinal artery occlusion in which the ocular involvement occurred before systemic symptoms. Case summary: A 58-year-old male visited the ophthalmology department due to abruptly decreased visual acuity. Best corrected visual acuity (BCVA) was 0.05 (in the right eye) and 1.0 (in the left eye) basedon the Snellen chart. He complained of acute decreased vision occurring ten days prior and intermittent migraine on the right side with no underlying diseases, such as hypertension or diabetes mellitus. Relative afferent pupillary defect was observed in the right eye. Generalized edema was found around the optic disc and fovea on fundus examination and optical coherence tomography. The patient was diagnosed with central retinal artery occlusion (CRAO) based on a fluorescein angiography. Subsequently, PAN was diagnosed based on clinical features, laboratory test results and imaging studies. The treatment was started with an immunosuppressive agent. One month later, the BCVA was 0.05 based on the Snellen chart. Conclusions: In PAN patients, decreased vision can occur as a first symptom due to CRAO. If the patient visits the ophthalmology clinic, history taking and laboratory tests for PAN can aid in early diagnosis and treatment, as well as preventing additional complications of PAN. J Korean Ophthalmol Soc 2015;56(12):1979-1984 Key Words: Central retinal artery occlusion, Polyarteritis nodosa 결절다발동맥염은눈조직을포함하여몸전체의중간, 작은크기의동맥에이환되는괴사성혈관염이다. 1 전형적 Received: 2015. 6. 19. Revised: 2015. 8. 19. Accepted: 2015. 10. 16. Address reprint requests to Seung Uk Lee, MD, PhD Department of Ophthalmology, Kosin University Gospel Hospital, #262 Gamcheon-ro, Seo-gu, Busan 49267, Korea Tel: 82-51-990-6140, Fax: 82-51-990-3026 E-mail: seung28@hanmail.net * This study was presented as an e-poster at the 111th Annual Meeting of the Korean Ophthalmological Society 2014. 으로내장, 신장, 연조직의혈관을침범하며모든장기에이환가능하지만폐는보존되는특징이있다. 2 가장흔하게는피부, 관절, 말초신경, 위장관, 신장이침범되는것으로알려져있다. 3 최근연구에서는눈에이환되는비율이약 10% 로보고되었고, 시야흐림이가장흔한증상 (31%) 이었다. 4 문헌상으로는결절다발동맥염으로진단받은환자에서갑작스런시력소실과연관하여일과성흑암시, 허혈성시신경병증, 그리고중심망막동맥폐쇄와함께나타난맥락막경색등을포함한증례들이보고되어있다. 3,5-7 그러나이러한보고들이있음에도불구하고아직결절다발동맥염에 c2015 The Korean Ophthalmological Society This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 1979

- 대한안과학회지 2015 년제 56 권제 12 호 - A D B E C F Figure 1. Photographs of fundus and optical coherence tomography (OCT). (A) Ischemic change fo the perifovea and posterior pole. (B) It shows cross section line in OCT. (C) The edema of inner retina is seen which is typical sign of central retinal artery occlusion. Each retinal layer is difficult to differentiate. (D) The other fundus of same patient looks like normal. (E) It shows cross ssection line in OCT. (F) The other eye of same patient shows normal retinal layers.retinal layers. 1980

- 김창주외 : 결절다발동맥염환자의중심망막동맥폐쇄 - 있어서눈증상은진단기준에들어있지않아눈증상을심하게호소하는환자라하더라도정확한진단이어려우며, 특히다른전신증상이전에첫증상으로중심망막동맥폐쇄로인한시력저하를나타낸결절다발동맥염의보고는없다. 저자들은결절다발동맥염을진단받기전발생한환자의일측성중심망막동맥폐쇄를경험하였고, 이는눈증상이선행된비전형적인결절다발동맥염의증례로이를보고하고자한다. 증례보고 소화기증상으로검사를위해내과에입원해있던 58세남자환자가입원 2일째발생한갑작스런우안의시력저하를주소로안과에진료의뢰되었다. 초진시현성굴절검사를통한최대교정시력우안 0.05, 좌안 1.0으로확인되었으며, 10일전갑자기발생한우안의시력저하와간헐적으로나타난우측편두통을호소하였다. 담낭암으로 2개월전수술을시행받았으며다른전신기저질환은없었다. 안과적수술과거력상양안백내장수술을받았고인공수정체삽입상태였다. 대광반사에서우안에상대적구심성동공운동장애가관찰되었으며안저검사및빛간섭단층촬영검사 상우안의시신경유두및황반주변으로안저의전반적인부종이관찰되었다 (Fig. 1). 형광안저촬영시행후우안의중심망막동맥폐쇄로진단하고치료로전방천자및방수생성억제제점안, 안구마사지등을실시하였다 (Fig. 2). 또한경동맥을통한초음파검사및혈전용해치료를권유하였으며지속적인경과관찰을시행하였다. 진료후 4일째우안의최대교정시력은 0.025, 상대적구심성동공운동장애양성소견및안저의부종이지속되었다. 12일간의지속적인경과관찰끝에결국우안최대교정시력 0.05로적극적인치료를종결하고보존적인치료를시행하였다. 환자에게발생한망막동맥폐쇄, 저작근파행, 지속되는불명열등의증상은안과, 이비인후과, 치과, 감염내과, 류마티스내과의협진을시행하였으나뚜렷한원인을찾지못하였다. 이후지속적인체중감소를포함하여고환통증, 다발신경병증이추가로발생하여신장혈관조영검사후, 적혈구침강속도 (erythrocyte sedimentation rate, ESR) 상승, 백혈구증가증, C반응성단백질 (C-reactive protein, CRP) 상승등의검사실소견과종합하여입원 29일째결절다발동맥염으로진단, 류마티스내과로전과되어면역억제치료를시작하였다 (Table 1). 8 1개월후경과관찰한우안의최대교정시력은 0.05로측정되었다 (Fig. 3). A B C Figure 2. Fluoroscein angiography. (A) Fluorescein angiography shows delayed arm-to-retina time. (B, C) At early and late phase, hypofluorescent lesions are seen the superior and inferior area of the optic disc. Table 1. Criteria for the diagnosis of polyarteritis nodosa (Lightfoot et al 8 ) At least three of the following 10 findings 1. Weight loss greater than or equal to 4 kg 2. Livedo reticularis mottling of the skin over the torso or extremities 3. Testicular pain or tenderness 4. Myalgias, weakness, or leg tenderness 5. Mononeuropathy or polyneuropathy 6. Systemic hypertension with diastolic greater than 90 mm Hg 7. Elevated blood urea nitrogen or creatinine level 8. Presence of hepatitis B surface antigen or antibody in serum 9. Arteriographic evidence of aneurysms or occlusions (nonarteriosclerotic) 10. Polymorphonuclear leukocytes or polymorphonuclear and mononuclear cells present in artery walls on biopsy of small or medium-sized arteries 1981

- 대한안과학회지 2015 년제 56 권제 12 호 - A D B E C F Figure 3. Photographs of fundus and optical coherence tomography (OCT). (A) Relative pale optic disc, but no significant ischemic area is seen. (B) It shows cross section line in OCT. (C) Shows the mildly regressed thickening of the inner retina compared with OCT image taken 1 month ago. Each retinal layer is seen more apparently. (D) The other fundus of same patient looks like normal. (E) It shows cross ssection line in OCT. (F) The other eye of same patient shows normal retinal layers. 1982

- 김창주외 : 결절다발동맥염환자의중심망막동맥폐쇄 - 고찰 결절다발동맥염은중간그리고작은크기의동맥에발생하는괴사성혈관염이특징인전신성질환으로, 이환되는경우그조직뿐만아니라생명까지도위협할수있다. 9 발생은남자가여자보다약 2배정도더많으며, 발생시평균연령은 50세정도이다. Table 1과같이 10개항목중 3개이상이포함될때결절다발동맥염으로진단한다. 8,10 어느부위든이환가능하며피부, 점막조직, 흉부, 복부, 신장, 신경계등을침범한다. 눈쪽으로는약 10% 의이환율을보이면서충혈, 시야흐림, 갑작스런시력소실, 포도막염, 망막혈관염, 삼출물, 망막출혈, 시신경병증, 동안신경마비등의증상을보일수있다. 6 그래서환자가급성염증소견을시신경부위에서보이거나, 중심망막동맥폐쇄가있을때, 혹은망막혈관들이질병의징후와함께전신증상을보이는경우라면감별진단으로결절다발동맥염을고려해야만한다. 그렇지만비슷한증상을보이는다른혈관염들과초기에감별하기는어려운데이는관련한특정한임상양상이나검사실검사가없기때문이다. 3,6 Solomon and Solomon 7 은결절다발동맥염과관련한중심성망막동맥폐쇄의증례를보고하였고, Akova et al 1 은결절다발동맥염과연관하여눈쪽염증으로인한증상들이먼저나타난 5예를통해질병의연속적인변화들을정리하였다. 눈쪽합병증으로는공막염, 변연부궤양성각막염, 비육아종성포도막염, 망막혈관염, 안와의가성종양, 측두동맥염이보고되었다. Hsu et al 6 은손발의감각저하와간헐적인시야흐림을호소하던 70세여자환자가증상발생 2주후중심망막동맥폐쇄로인한우안의시력저하를보고하였다. Schmidt et al 11 은좌안에먼저, 그리고후에우안에망막동맥폐쇄가발생한 67세결절다발동맥염남자환자의증례를보고하였다. 본증례의환자는갑자기우안의시력저하가나타났고안과에내원하였을때는이미중심망막동맥폐쇄로인한증상이진행된후였다. 4 kg 이상의체중감소, 고환의압통, 하지압통을포함한근육통, 이완기혈압의상승 (>90 mmhg), 복부혈관조영단층촬영검사상양측 kidney의 intraparenchymal artery에 multiple small aneurysm들이관찰되면서 multifocal parenchymal infarction도동반되어결절다발동맥염으로진단하고전신적스테로이드치료와함께류마티스내과로전과되었다. 치료를시작한이후에다시눈쪽증상의재발은없었으며정기적인추적관찰만시행하였다. Akova et al 1 과 Hsu et al 6 은각각측두동맥염, 손발저림증상이나타난후중심망막동맥폐쇄가나타난경우를보고하였으며, Solomon and Solomon 7 은진단후나타난중심망막동맥폐 쇄를보고하였다. 본증례는진단되기전중심망막동맥폐쇄로인한눈쪽증상이나타났다. 중심망막동맥폐쇄이외에도소수의환자들에게서 retinal vessel을침범한혈관염, 가성종양유사병변이나타나거나, 결막결절, 주변부각막염및궤양, 천공을동반한양측성의주변부각막궤양등의눈증상이보고되었다. 1,12-16 이상의보고된여러증례에서눈쪽의증상은결절다발동맥염의진단에선행하여나타나는경우결절다발동맥염을의심하는근거가되기도하며진단후나타나는증상이되기도한다. 그외진단을위한혈액검사에서는본증례의환자처럼적혈구침강속도 (ESR) 상승, 백혈구증가증, C반응성단백질 (CRP) 상승이특징적으로나타나게된다. 그렇지만 Emad et al 3 의보고와같이위항목의검사결과가정상범위인경우에도결절다발동맥염의진단및중심동맥망막폐쇄가합병될수있다. 결절다발동맥염의치료로는 corticosteroids가일차적으로사용되며, 주요내장장기를침범하였거나진행되는경우에세포독성약제를추가로사용할수있다. 치료하지않는경우의 5년생존율은 10-15% 이며, corticosteroids로치료하는경우 50%, 그리고 cyclophosphamide를추가했을때 80% 까지증가하는것으로보고되어있다. 1,17 결절다발동맥염의경우환자는눈의증상이선행하여나타나서먼저안과의사를찾아오기도하고혹은다른증상으로병원을다니다가나중에안과를찾아오기도한다. 이런경우시야흐림을포함한안과적증상의병력청취뿐아니라체중감소, 근육통, 위약감등의전신적인병력청취와함께, 필요한경우전신적인신체진찰을하는것까지시행하는것이결절다발동맥염의진단에도움이될것이다. 여기에신장기능검사, 염증수치등의실험실검사또한필요하다면시행을하고, 의심되는경우즉시내과의사에게의뢰하여진단에필요한추가적인검사를받게하는것이안과의사의역할이될것이다. 결론적으로결절다발동맥염환자에서중심망막동맥폐쇄가첫증상으로나타날수있으며안과에내원하는경우관련문진과실험실검사를추가하여빨리진단후전신적인치료를시행하는것이추가적인다른합병증을예방할수있을것이다. REFERENCES 1) Akova YA, Jabbur NS, Foster CS. Ocular presentation of polyarteritis nodosa. Clinical course and management with steroid and cytotoxic therapy. Ophthalmology 1993;100:1775-81. 2) Forbess L, Bannykh S. Polyarteritis nodosa. Rheum Dis Clin North Am 2015;41:33-46, vii. 3) Emad Y, Basaffar S, Ragab Y, et al. A case of polyarteritis nodosa 1983

- 대한안과학회지 2015 년제 56 권제 12 호 - complicated by left central retinal artery occlusion, ischemic optic neuropathy, and retinal vasculitis. Clin Rheumatol 2007;26:814-6. 4) Rothschild PR, Pagnoux C, Seror R, et al. Ophthalmologic manifestations of systemic necrotizing vasculitides at diagnosis: a retrospective study of 1286 patients and review of the literature. Semin Arthritis Rheum 2013;42:507-14. 5) Håskjold E, Frøland S, Egge K. Ocular polyarteritis nodosa. Report of a case. Acta Ophthalmol (Copenh) 1987;65:749-51. 6) Hsu CT, Kerrison JB, Miller NR, Goldberg MF. Choroidal infarction, anterior ischemic optic neuropathy, and central retinal artery occlusion from polyarteritis nodosa. Retina 2001;21:348-51. 7) Solomon SM, Solomon JH. Bilateral central retinal artery occlusions in polyarteritis nodosa. Ann Ophthalmol 1978;10:567-9. 8) Lightfoot RW Jr, Michel BA, Bloch DA, et al. The American College of Rheumatology 1990 criteria for the classification of polyarteritis nodosa. Arthritis Rheum 1990;33:1088-93. 9) Cohen RD, Conn DL, Ilstrup DM. Clinical features, prognosis, and response to treatment in polyarteritis. Mayo Clin Proc 1980;55: 146-55. 10) Raashid L. Polyarteritis Nodosa and Related Disorders. In: Gary SF, Ralph CB, Sherine EG, et al. eds. Kelley's Textbook of Rheumatology, 9th ed. Philadelphia: Saunders, 2013, chap. 90. 11) Schmidt D, Lagrèze W, Vaith P. Ophthalmoscopic findings in 3 patients with panarteritis nodosa and review of the literature. Klin Monbl Augenheilkd 2001;218:44-50. 12) Wise GN. Ocular periarteritis nodosa; report of two cases. AMA Arch Ophthalmol 1952;48:1-11. 13) Morgan CM, Foster CS, D Amico DJ, Gragoudas ES. Retinal vasculitis in polyarteritis nodosa. Retina 1986;6:205-9. 14) Vanwien S, Merz EH. Exophthalmos secondary to periarteritis nodosa. Am J Ophthalmol 1963;56:204-8. 15) Purcell JJ Jr, Birkenkamp R, Tsai CC. Conjunctival lesions in periarteritis nodosa. A clinical and immunopathologic study. Arch Ophthalmol 1984;102:736-8. 16) Moore JG, Sevel D. Corneo-scleral ulceration in periarteritis nodosa. Br J Ophthalmol 1966;50:651-5. 17) Lhote F, Cohen P, Guillevin L. Polyarteritis nodosa, microscopic polyangiitis and Churg-Strauss syndrome. Lupus 1998;7:238-58. = 국문초록 = 중심망막동맥폐쇄로인한갑작스런시력저하가첫증상으로나타난결절다발동맥염 1 예 목적 : 결절다발동맥염은눈조직을포함하여몸전체의중간, 작은크기의동맥에이환되는괴사성혈관염이다. 저자들은결절다발동맥염을진단받기전선행한환자의일측성중심망막동맥폐쇄를경험하였고이는눈증상이선행된비전형적인결절다발동맥염의증례로이를보고하고자한다. 증례요약 : 58 세남자환자가갑작스런우안의시력저하를주소로안과에내원하였다. 현성굴절검사를통한최대교정시력우안 0.05, 좌안 1.0 으로확인되었으며, 고혈압, 당뇨등의전신기저질환은없는상태로 10 일전갑자기발생한우안의시력저하와간헐적으로나타난우측편두통을호소하였다. 대광반사에서우안에상대적구심성동공운동장애가관찰되었으며안저검사및빛간섭단층촬영검사상우안의시신경유두및황반주변으로안저의전반적인부종이관찰되었다. 환자는형광안저촬영후우안의중심망막동맥폐쇄로진단받았고이후임상소견과검사실결과, 영상검사를근거로결절다발동맥염진단하에면역억제치료를시작하였다. 1 개월후우안의최대교정시력은 0.05 로확인되었다. 결론 : 결절다발동맥염환자에서중심망막동맥폐쇄로인한시력저하가첫증상으로나타날수있으며안과에내원하는경우관련문진과실험실검사를추가하여빨리진단후전신적인치료를시행하는것이추가적인다른합병증을예방할수있을것이다. < 대한안과학회지 2015;56(12):1979-1984> 1984