대한안과학회지 2018 년제 59 권제 7 호 J Korean Ophthalmol Soc 2018;59(7):697-701 ISSN 0378-6471 (Print) ISSN 2092-9374 (Online) https://doi.org/10.3341/jkos.2018.59.7.697 Case Report 매독에동반된양안긴장동공의치료 Treatment of Bilateral Tonic Pupil Associated with Syphilis 문용석 양희경 황정민 Yong Seok Mun, MD, Hee Kyung Yang, MD, Jeong-Min Hwang, MD, PhD 서울대학교의과대학분당서울대학교병원안과학교실 Department of Ophthalmology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea Purpose: We report a case of a male with bilateral tonic pupils associated with syphilis, that partially improved after syphilis treatment. Case summary: A 27-year-old male presented with a 2-month history of near vision impairment. The right and left pupils were 5.5 mm and 6.5 mm in diameter, respectively, in the dark and 5.3 mm and 6.1 mm, respectively, in the light. Both pupils demonstrated light-near dissociation, slow constriction and redilation when looking at near, and constriction after instillation of 0.0625% pilocarpine. Serological tests were positive for syphilis, while cerebrospinal fluid testing was negative. Two months after treatment with intramuscular injection of benzathine penicillin G, his near vision subjectively improved and the right and left pupils were 5.9 mm and 6.4 mm, respectively, in the dark and 4.8 mm and 5.3 mm, respectively, in the light. The size of both pupils decreased and the pupillary light responses partially improved in both eyes. Conclusions: Patients with bilateral tonic pupils should have serological tests for syphilis. Recovery of tonic pupils can be expected after early treatment with effective antibiotics. J Korean Ophthalmol Soc 2018;59(7):697-701 Keywords: Syphilis, Tonic pupil 매독에동반되는대표적동공운동장애인아르길로버트슨 (Argyll-Robertson) 동공은대개양안의축동과함께대광반사소실, 대광-근접반사해리를특징으로한다. 1,2 긴장동공은아르길로버트슨동공과달리매독에동반되는경우는적다고알려져있다. 2-10 기존에보고된증례들은대부분뇌척수액 venereal diseases research laboratory (VDRL) 검사 Received: 2018. 3. 23. Revised: 2018. 4. 30. Accepted: 2018. 6. 21. Address reprint requests to Hee Kyung Yang, MD Department of Ophthalmology, Seoul National University Bundang Hospital, #82 Gumi-ro 173beon-gil, Bundang-gu, Seongnam 13620, Korea Tel: 82-31-787-7379, Fax: 82-31-787-4057 E-mail: eye@snubh.org * Conflicts of Interest: The authors have no conflicts to disclose. 를통해신경매독을진단받았으며, 외국의보고에서신경매독치료후단안을침범한긴장동공이호전된예는있으나동공반응과그호전양상에대해자세히기술한경우는없었다. 3-12 한편, 중추신경계침범이없는매독환자에서발생한양안의긴장동공이매독치료후호전을보인경우는국내외에보고된적이없다. 이에저자들은양안의긴장동공으로내원하여중추신경계침범이없는매독으로진단된환자에서, 매독치료후긴장동공의호전을보인 1예를경험하였기에이를보고하고자한다. 증례보고 27세남자환자가 2개월전부터서서히시작된근거리시력저하를주소로내원하였다. 눈부심이함께동반되었고두통, 안통은동반하지않았다. 4년전뇌진탕및좌측안면마 c2018 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. 697
- 대한안과학회지 2018 년제 59 권제 7 호 - A B C D Figure 1. Pupil sizes before and after instillation of 0.0625% pilocarpine. (A) On initial examination, the minimal pupil sizes were 5.3 mm on the right and 6.1 mm on the left. (B) After instillation of 0.0625% pilocarpine, both pupils showed significant constriction, suggesting cholinergic denervation supersensitivity. (C) Results of digital pupillometry on initial examination showing decreased constriction (CON) to light. (D) Results of digital pupillometry after instillation of 0.0625% pilocarpine showing decreased pupil sizes in both eyes. MAX = maximum pupil diameter; MIN = minimum pupil diameter; CON = (MAX-MIN)/MAX; LAT = latency; ACV = average constriction velocity; MCV = maximum constriction velocity; ADV = average dilation velocity; T75 = time to reach 75% recovery. 비의과거력이있었으며, 같은해양안레이저각막상피절삭성형술 (laser epithelial keratomileusis, LASEK) 을시행받았다. 그외당뇨병, 고혈압과같은전신질환이나안외상, 안 과수술의과거력은없었다. 원거리나안시력은우안 1.2, 좌안 1.2였으며, 근거리나안시력은우안 0.5, 좌안 1.0이었다. 자동굴절검사상우안 698
- 문용석외 : 매독에동반된긴장동공 - A B Figure 2. Pupil sizes after treatment with benzathine penicillin G. (A) Two months after treatment with benzathine penicillin G, minimal pupil sizes decreased to 4.8 mm on the right and 5.3 mm on the left. (B) Results of digital pupillometer two months after treatment show partially improved pupillary light responses (CON, MCV, ACV) in both eyes. MAX = maximum pupil diameter; MIN = minimum pupil diameter; CON = (MAX-MIN)/MAX; LAT = latency; ACV = average constriction velocity; MCV = maximum constriction velocity; ADV = average dilation velocity; T75 = time to reach 75% recovery. +0.50 Dsph. -0.50 Dcyl. 180, 좌안 0.00 Dsph. -0.25 Dcyl. 180 였고, 안압은우안 8 mmhg, 좌안 9 mmhg 였다. 반대눈을가리고시표를원거리에서근거리로옮길때시표가흐려보이기시작하는지점을조절근점으로정의하였으며, 우안의조절근점은 35 cm로조절력이저하되었고, 근거리시력은 +2.50 D의볼록렌즈를대면 1.0으로교정되었다. 교대가림검사상원거리와근거리모두정위였고, 눈운동은정상이며눈을움직일때동반되는통증은없었다. 세극등현미경검사상각결막및수정체에이상소견이없었고, 전방에염증세포및홍채의부분마비는관찰되지않았다. 자동동공측정계 (PLR-200, NeurOptics Inc., Irvine, CA, USA) 를이용하여측정한양안의동공크기는원거리를주시한상태에서실내등을껐을때 (dark) 우안 5.5 mm, 좌안 6.5 mm, 실내등을켰을때 (light) 우안 5.3 mm, 좌안 6.1 mm로동공수축비율이우안 3%, 좌안 8% 로양안대광반사가저하되었고, 근접반사에서는느린동공의수축과확대를보이는대광-근접반사해리를보였다. 0.0625% 필로카르핀을점안했을때동공크기는양안모두감소하였다 (Fig. 1). 양안의긴장동공진단하에전신질환을감별하기위해시행한혈액검사에서 rapid plasma reagin (RPR) 양성, fluorescent treponemal antibody absorption (FTA-ABS) 양성으로 매독이확진되었다. 피부병변이나기타중추신경계이상은동반되지않았고, 뇌척수액검사에서 VDRL 음성, 뇌척수액백혈구증가증은보이지않았으며동반된신경학적징후는없었다. 후천성면역결핍증후군동반을감별하기위해실시한항체검사는음성이었다. Benzathine penicillin 240만단위를 1주간격으로 3회근주하였으며, 치료 2개월후환자의주관적인근거리시력저하증상은호전되었다. 동공크기는원거리를주시한상태에서실내등을껐을때 (dark) 우안 5.9 mm, 좌안 6.4 mm, 실내등을켰을때 (light) 우안 4.8 mm, 좌안 5.3 mm로동공수축비율이우안 18%, 좌안 16% 로호전되었고, 치료전에비해대광반사와평균동공수축속도가호전되었다 (Fig. 2). 13 고찰 신경매독에서나타나는전형적인동공운동장애는양안의동공축동과대광 -근접반사해리를보이는아르길- 로버트슨동공이다. 1 한편, 긴장동공은대광-근접반사해리를보이는점에서아르길- 로버트슨동공과유사하나, 연령, 성별, 동공크기, 양측이환율등에서아르길-로버트슨동공과다르며, 80% 이상이단안에발생하고, 근접반사시느리고과도 699
- 대한안과학회지 2018 년제 59 권제 7 호 - 한축동, 홍채의부분마비로인한벌레모양운동 (vermiform movement), 저농도의부교감신경자극제에대한과민반응등을특징적으로보인다. 2,4 Sakai et al 4 은신경매독에동반된양안긴장동공총 4예를보고하였다. 이중 2예는양안시신경병증, 1예는보행장애와건반사소실, 1예는눈운동장애를동반하고있었으며, 4예모두매독치료후에도동공운동장애는호전되지않았다. Fletcher and Sharpe 3 도신경매독에동반된양안긴장동공 4예와잠복매독에동반된양안긴장동공 1예를보고하였으며, 5예모두매독치료후에도긴장동공은호전되지않았다. Englestein et al 5 이보고한신경매독에동반된양안긴장동공 1예또한치료후에도호전되지않았다. Gu et al 11 은신경매독에동반된좌안의긴장동공을보고하였며, 매독치료 9개월후조명하에좌안동공크기는치료전보다 5 mm 감소하였으나대광반사는회복되지않았다. Takata et al 12 은신경매독에동반된좌안의긴장동공 1예를보고하였으며, 매독치료 6개월후대광반사가회복되고좌안동공크기는치료전보다 2 mm 감소하였다. 이처럼대부분의보고에서매독치료후동공반응의호전을보이지않았으며, 치료후호전을보인기존보고 2예는신경매독에동반되어단안에발생하였으며, 동공반응의회복양상에대한자세한기술이없다. 11,12 긴장동공은섬모체신경절 (ciliary ganglion) 또는신경절후부교감신경 (postganglionic parasympathetic fibers) 의손상에의해유발되는것으로알려져있다. 6,14,15 긴장동공의발생원인은대부분불명인경우가많으나외상, 종양, 수술에의한신경손상, 안와연조직염, 바이러스감염, 매독감염, 자율신경병증등에의해발생할수있으며, 바이러스감염의경우혈청검사에서역가가상승되어있지않은경우가많다. 3,16 특히양안에동시에발생한긴장동공의경우매독외에라임병, 편두통, 쇼그렌증후군, 밀러-피셔증후군, 신경사르코이드증, 신경모세포종, 히르슈슈프룽병등의가능성이있으므로관련된검사를해야한다. 17-23 매독감염에의한긴장동공은명확한병태생리가알려져있지않으며, 일부문헌에서매독이섬모체신경절또는신경절후부교감신경에염증이나허혈을유발하여손상시켰을것으로추측하고있다. 3,4 대부분의보고에서매독치료후동공반응의호전을보이지않았으나, 3-10 증상발생후 1 개월만에시행한매독치료후긴장동공이회복되었다고보고한외국의두증례와 2개월만에치료하여부분적인호전을보인이증례를통해, 매독에의해직접또는간접적인섬모체신경절또는신경절후부교감신경에가역적인손상이발생하여, 이를조기에치료하면회복될수있음을시사한다. 11,12 매독에의한긴장동공의경우, 80% 이상이단안에발생하는특발성긴장동공과달리대부분양안에발생하여, 이증례와앞서보고된 10예모두양안을침범하였고단안침범은 2예뿐이었다. 3-5,11,12 일반적인긴장동공의경우반대안이환율이매년 4% 정도로낮은것을감안하면, 매독에의한긴장동공은양안의섬모체신경절또는신경절후부교감신경을침범하는전신적인병태생리학적기전을추측해볼수있다. 24 다만이증례는앞선보고들과달리뇌척수액검사를통해신경매독이음성이고다른신경학적증상이나징후를동반하지않았기에, 긴장동공이매독에의한직접적인중추신경계침범뿐아니라간접적인말초신경병증의가능성이있음을시사한다. 결론적으로양안에동시에발생한긴장동공이관찰되었을때, 매독을포함한전신질환의가능성을염두에두고혈액검사를시행해야하고, 뇌척수액검사를통해신경매독을감별해야한다. 또한매독의진단과동시에조기에적절한항생제를투여하면긴장동공의부분적인회복을기대할수있다. REFERENCES 1) Loewenfeld IE. The Argyll Robertson pupil 1869-1969. A critical survey of the literature. Surv Ophthalmol 1969;14:199-299. 2) Thompson HS, Kardon RH. The argyll robertson pupil. J Neuroophthalmol 2006;26:134-8. 3) Fletcher WA, Sharpe JA. Tonic pupils in neurosyphilis. Neurology 1986;36:188-92. 4) Sakai T, Shikishima K, Mizobuchi T, et al. Bilateral tonic pupils associated with neurosyphilis. Jpn J Ophthalmol 2003;47:368-71. 5) Englestein ES, Ruderman MI, Troiano RA, Digiovanni VJ. Dilated tonic pupils in neurosyphilis. J Neurol Neurosurg Psychiatry 1986;49:1455-7. 6) Thompson HS. Adie's syndrome: some new observations. Trans Am Ophthalmol Soc 1977;75:587-626. 7) Bowsher D, Lahuerta J. A case of tabes dorsalis with tonic pupils and lightning pains relieved by sodium valproate. J Neurol Neurosurg Psychiatry 1987;50:239-41. 8) Yasaki S, Ohshima J, Yonekura J, et al. A case of early syphilis presenting general paresis-like symptoms and bilateral tonic pupils. Rinsho shinkeigaku 1992;32:994-9. 9) Ohya Y, Matsumura T, Kojima S, et al. Bilateral internal carotid artery stenoses in a patient with meningovascular neurosyphilis. Rinsho shinkeigaku 1993;33:875-9. 10) Kim HB, Kwon OW, Chun GH. Bilateral tonic pupil in syphilis. J Korean Ophthalmol Soc 1983;24:877-81. 11) Gu X, Guan Z, Chai Z, Zhou P. Unilateral mydriasis as the primary sign of neurosyphilis. Infection 2014;42:215-7. 12) Takata T, Kamada M, Ikeda K, et al. Unilateral mydriatic tonic pupil as an early isolated symptom of neurosyphilis. J Neurol Sci 2014;344:219-20. 13) Bak E, Yoo YJ, Yang HK, Hwang JM. Quantitative pupillometry of 700
- 문용석외 : 매독에동반된긴장동공 - the pupillary light reflex in Koreans. J Korean Ophthalmol Soc 2017;58:712-7. 14) Loewenfeld IE, Thompson HS. The tonic pupil: a re-evaluation. Am J Ophthalmol 1967;63:46-87. 15) Miller NR, Walsh FB, Hoyt WF. Walsh and Hoyt's clinical neuro-ophthalmology, 6th ed. Vol. 1. Philadelphia: Lippincott Williams & Wilkins, 2005; 761-4. 16) Wabbels BK, Elflein H, Lorenz B, Kolling G. Bilateral tonic pupils with evidence of anti-hu antibodies as a paraneoplastic manifestation of small cell lung cancer. Ophthalmologica 2004;218:141-3. 17) Fugimoto F, Ghanem RC, Monteiro ML. Bilateral tonic pupil as the only remaining ophthalmic sign of Lyme disease: case report. Arq Bras Oftalmol 2005;68:381-4. 18) Millar E, Habib M, Gnanaraj L. Bilateral tonic pupil secondary to migraine in a child. J Pediatr Ophthalmol Strabismus 2010;47 Online:e1-2. 19) Vetrugno R, Liguori R, Cevoli S, et al. Adie's tonic pupil as a manifestation of Sjögren's syndrome. Ital J Neurol Sci 1997;18:293-5. 20) Bae JS, Kim JK, Kim SH, Kim OK. Bilateral internal ophthalmoplegia as an initial sole manifestation of Miller Fisher syndrome. J Clin Neurosci 2009;16:963-4. 21) Sevketoglu E, Tatlı B, Tuğcu B, et al. An unusual cause of fulminant Guillain-Barré syndrome: angel's trumpet. Pediatr Neurol 2010;43:368-70. 22) Heuser K, Kerty E. Neuro-ophthalmological findings in sarcoidosis. Acta Ophthalmol Scand 2004;82:723-9. 23) Lambert SR, Yang LL, Stone C. Tonic pupil associated with congenital neuroblastoma, Hirschsprung disease, and central hypoventilation syndrome. Am J Ophthalmol 2000;130:238-40. 24) Holmes G. Partial iridoplegia associated with symptoms of other disease of the nervous system. Tran Ophthal Soc UK 1931;51: 209-28. = 국문초록 = 매독에동반된양안긴장동공의치료 목적 : 매독환자에서발현된양안의긴장동공이매독치료후부분적인호전을보인 1 예를경험하였기에이를보고하고자한다. 증례요약 : 27 세남자가 2 개월전부터시작된근거리시력저하를주소로내원하였다. 양안의동공크기는실내등을껐을때우안 5.5 mm, 좌안 6.5 mm, 실내등을켰을때우안 5.3 mm, 좌안 6.1 mm 였으며동공반응은대광 - 근접반사해리를보이며근거리주시때느린동공의수축과확대, 그리고 0.0625% 필로카르핀점안후양안의동공이축동되었다. 혈청검사상매독이확진되었다. Benzathine penicillin G 를근주하고 2 개월경과후주관적인근거리시력저하증상이호전되었으며, 동공크기는실내등을껐을때우안 5.9 mm, 좌안 6.4 mm, 실내등을켰을때우안 4.8 mm, 좌안 5.3 mm 로일부호전되었고, 양안대광반사도부분적으로호전되었다. 결론 : 양안긴장동공관찰시혈청검사를통해매독여부를확인해야하며, 조기에적절한항생제를투여하면긴장동공의상대적으로빠른회복을기대할수있다. < 대한안과학회지 2018;59(7):697-701> 701