대한내과학회지 : 제 83 권제 1 호 2012 http://dx.doi.org/10.3904/kjm.2012.83.1.150 피하낭종과관절염의형태로나타난 Sweet 증후군 1 예 조선대학교의과대학내과학교실 기영재 조주연 정유진 김윤성 김현숙 A Case of Sweet s Syndrome Presenting as Subdermal Cystic Lesions and Arthritis Young Jae Ki, Ju Yeon Cho, Yu-Jin Jeong, Yun Sung Kim, and Hyun-Sook Kim Department of Internal Medicine, Chosun University College of Medicine, Gwangju, Korea Sweet s syndrome is characterized by a combination of clinical and pathologic findings including fever, neutrophilia, tender erythematous skin lesions, and a diffuse infiltration of mature neutrophils in the upper dermis. Numerous diseases and clinical manifestations have been associated with the disease; however, Sweet s syndrome associated with subdermal cystic skin lesions and arthritis is rare. A 71-year-old female patient presented with fever, erythematous plaques, multiple hypoglossal ulcers, and arthritis in both ankles. The skin lesions were variously sized areas of erythematous swelling on the forehead, back, and left shoulder. Musculoskeletal sonography revealed hypervascularity and a subdermal cyst in the erythematous plaque on her back. The results of a skin biopsy indicated the presence of mature neutrophilic infiltration in the dermis and thus led to the diagnosis of Sweet s syndrome. We herein present an unusual case of Sweet s syndrome presenting as erythematous subdermal cystic lesions, multiple hypoglossal ulcers, and bilateral ankle arthritis with a literature review. (Korean J Med 2012;83:150-155) Keywords: Sweet s syndrome; Subdermal cyst; Arthritis 서론 Sweet 증후군은급성열성호중구성피부질환 (acute febrile neutrophilic dermatosis) 으로발열, 호중구성백혈구증가증, 압통을동반한홍반성부종성판, 구진의임상증상과성숙한호중구의진피침윤과같은조직학적특징을가지며 1964년 Sweet에의해처음보고되었다 [1]. 발병원인은세균, 바이러스및종양항원의과민반응, 내인성사이토카인의부적절 한분비, 호중구에대한항체의발현, 그리고종양과관련된과립구콜로니자극인자 (Granulocyte-colony stimulating factor) 의형성등이라는주장들이있다 [2,3]. Sweet 증후군은피부이외에도심장, 간, 폐, 비장, 중추신경계및근골격계에도다양한임상양상을가지나관절염과의동반은비교적드물다. 저자들은 71세여자에서양측발목의관절염, 구강궤양과피하낭종의형태를동반한피부병변의 Sweet 증후군 1예를경험하고성공적으로치료하였기에문헌고찰과함께 Received: 2011. 7. 27 Revised: 2011. 10. 14 Accepted: 2011. 12. 2 Correspondence to Hyun-Sook Kim. M.D, Ph.D. Department of Internal Medicine, Chosun University Hospital, 365 Pilmun-daero, Dong-gu, Gwangju 501-717, Korea Tel: +82-62-220-3249, Fax: +82-62-234-9653, E-mail: healthyra@chosun.ac.kr - 150 -
- Young Jae Ki, et al. Sweet s syndrome with arthritis - 증례보고한다. 증례환자 : 여자, 71세주소 : 발열, 양측발목의열감을동반한부종, 얼굴과등의피부병변현병력 : 내원 4일전부터얼굴, 등, 왼쪽어깨, 오른쪽발목의다양한크기의홍반성판및구강내궤양이발생하였고, 내원 2일전부터는고열, 전신의근육통및양측발목의심해지는관절통이발생하여내원하였다. 과거력 : 환자는내원 10년전왼쪽갑상선절제술을시행 받았으며, 동시에당뇨병진단되어내원당시외래에서 Glimepiride (amaryl ) 6 mg, Metformin (Glupa ) 1,700 mg 경구투여중이다. 내원 3개월전에는왼쪽가슴흉통으로우관상동맥 (Right coronary artery) 의 80% 협착으로경피적관상동맥중재술을시행받은후 aspirin, clopidogrel 복용하면서별다른증상없이지냈다. 가족력과사회력 : 특이사항없음. 진찰소견 : 내원당시혈압 130/80 mmhg, 맥박수분당 78 회, 체온 38.8, 호흡수분당 20회였으며, 경부림프절이나편도비대등의특이소견은관찰되지않았다. 흉부및복부에서는특이사항이없었다. 피부소견은얼굴, 등, 왼쪽어깨, 오른쪽발목에경계가명확하고다양한크기의융기된홍반 A B C D Figure 1. (A) The patient had an erythematous plaque with a pseudovesicular appearance on her forehead (arrowheads). (B) The forehead plaque improved after corticosteroid therapy (arrowheads). (C) Multiple small aphthous hypoglossal ulcers were observed. (D) The hypoglossal ulcers improved after corticosteroid therapy. - 151 -
- 대한내과학회지 : 제 83 권제 1 호통권제 623 호 2012 - 성판이있었으며 (Fig. 1A), 병변부위의통증을호소하지는않았지만, 압통이있었다. 구강내설하에는다수의다양한크기의통증성궤양이있었다 (Fig. 1C). 검사실소견 : 혈액검사에서헤모글로빈 11.2 g/dl (12.0-16.0 g/dl), 백혈구 6,100/uL (4-8 10 3 /ul), 혈소판 163,000/uL (150-450 10 3 /ul) 이었으며, 적혈구침강속도 (ESR) 는 34 mm/hr (0-10 mm/hr), 단백면역화학검사에서 C 반응성단백질 (C-reactive protein) 은 14.30 mg/dl (0-5 mg/dl) 로상승되었다. 혈청생화학검사에서는혈당 202 mg/dl로증가되었으며, 요침사검사에서당이 3+ 확인되었고당화혈색소 (HbA1c) 는 10.2% 였다. VDRL, 항HIV항체, 항핵항체, 류마티스인자, PT/aPTT, 항핵항체, 항호중구세포질항체, HLA-B51은음성혹은정상 범위였다. 거대세포바이러스 (Cytomegalovirus), 엡스타인바바이러스 (Epstein-Barr virus) viral capsid antigen/early antigen, 리켓치아쯔쯔가무시 (Orientia tsutsugamushi), 렙토스피라인터로간스 (Leptospira interrogans), 한타바이러스 (Hantaan virus) 등에대한혈청항체도모두음성이었다. Alpha-fetoprotein (a-fp) 은 2.1 ng/ml (0.0-7.0 ng/ml), carcinoembryonic antigen (CEA) 는 2.7 ng/ml (0.0-5.0 ng/ml), cancer antigen 125 (CA-125) 는 14.21 U/mL (0.0-35 U/mL) 였다. 말초혈액도말검사상독성과립이관찰되었으며, 호중구의좌방이동 (shift-to-left) 소견이확인되었으나비정형골수모세포는관찰되지않았다. 갑상선기능검사결과 T3 43.2 ng/dl (60-190 ng/dl), ft4 1.28 ng/dl (0.70-1.80 ng/dl), 그리고 TSH 2.62 uiu/ml (0.25-4.0 A B C D Figure 2. (A) Ultrasound showed synovial effusion of the tibiotarsal joint (arrowheads). (B) The effusion of the tibiotarsal joint improved after intra-articular corticosteroid therapy (arrowheads). (C) An erythematous plaque was present on the right lower part of the back (arrowhead). (D) Sonography revealed a subdermal cystic lesion (arrowhead). - 152 -
- 기영재외 4 인. 피하낭종과관절염을동반한 Sweet 증후군 - A B Figure 3. (A) Diffuse neutrophilic infiltration in a skin biopsy of the back (HE stain, 40). (B) Perivascular and dermal neutrophilic aggregation (HE stain, 200). uiu/ml) 이었다. 이상초과민검사 (pathergy test) 는음성이었다. 방사선학적소견 : 흉부컴퓨터촬영상양측폐내다발성소결절이관찰되었으나림프절비대및흉수는없었으며, 복부컴퓨터촬영에서는특이소견없었다. 양측발목은경거 (tibio-talar joint) 관절초음파상관절액의저류가관찰되었으며 (Fig. 2A), 등의구진성판 (Fig. 2C) 에대한초음파검사상고혈류의비전형적침윤과동반된낭종성병변이확인되었다 (Fig. 2D). 피부생검조직의병리학적소견 : 압통을동반한전신의다양한크기의홍반성판이있어, 피하의농양가능성고려하여등의병변에서흡인시행하였으나농성물질은배출되지않았다. 홍반성판하부낭종주위에서시행한생검조직검사결과진피내염증소견과함께성숙한호중구침윤된것이확인되었다 (Fig. 3). 치료및임상경과 : 고열으로내원하였고, 흉부컴퓨터촬영상양측폐내다발성소결절이관찰되어폐렴에의한감염고려하여전신적항생제 amoxicillin/clavulanate 3,600 mg/day 을투여하였다. 항생제투여 4일째에도 38.1 의발열이지속되었으며흉부방사선상변화가없었다. 급성열성질환과홍반성피부병변을동반하였으며, 복부의홍반성판에서시행한조직검사결과 Sweet 증후군으로진단하여항생제는중단하고고용량스테로이드 (prednisol 62.5 mg/day) 를정주하였다. 또한, 양측발목의활액의저류에대하여초음파유도하흡인을하여관절낭내활액의흡인검사결과 WBC 7,000/mm 3 (Poly 90%, Monocytes 10%) 으로확인되었으며그람염색결과음성, 배양검사결과동정되는균은없어서화농성관절염은배제할수있었다. 이에스테로이드를관절강내정주하였다. 일주일후이마및등의피부병변에도병변내스테로이드주사요법을시행하였다. 투여 3일후발열소실되었으며, 7일후이마와등의피부병변, 구강내궤양이뚜렷하게호전되었다 (Fig. 1B, 1D). 관절강내주사후추적관찰한관절초음파에서경거관절의관절액저류또한호전되었다 (Fig. 2B). 이후경구스테로이드용량을점차적으로감량하여현재외래에서재발없이추적관찰중이다. 고찰 Sweet 증후군은주로얼굴, 목, 상체및사지에통증이동반된홍반성판및구진이발생하는임상적인특징을지니고있다. 1986년 Su와 Liu에의해진단기준이제시된이후, 1994년 von den Driesch 에의해조정되었다 [1]. Sweet 증후군은 1) 압통을동반한홍반성판또는결절의발생, 2) 혈관염의증거없이성숙한호중구의진피침윤의두가지주진단기준을만족하면서, 1) 38 C 이상의발열, 2) 기저의혈액학적또는고형암종, 염증성질환, 임신또는선행하는상기도감염, 위장관감염, 또는예방접종의존재, 3) 스테로이드나 KI (potassium iodide) 로치료후빠른호전, 4) 검사실소견상백혈구증가증 (>8,000/mm 3 ), 호중구증가증 (>70%), ESR - 153 -
- The Korean Journal of Medicine: Vol. 83, No. 1, 2012 - 증가 (>20 mm/hr), CRP 양성의네가지부진단기준중두가지이상을충족할때에진단된다. 피부증상은다양한크기의판의형태이나드물게낭종이나농포또는실제액체가채워지지않은형태의낭포화된형태 (pseudovesiculation) 로도보일수있다 [1]. Sweet 증후군에서관절통이동반되는경우는 32-62% 로흔하지만, 관절염이동반되는경우는약 10-15% 로비교적드물다 [1,2]. 관절증상은피부병변이발생하기전또는후에발생할수있다. 대부분의보고에서관절염은주로비대칭적으로무릎, 어깨, 엉덩이, 발목, 손목관절과같은대관절을주로침범하였으나, 손과발의소관절을침범함경우도있다 [2]. 방사선학적사진의경우에대부분정상이며, 관절낭활액의경우염증성변화를보일수있다. 본증례의환자에서는초음파결과오른쪽발목의관절낭내활액의저류, 동통을동반한열감, 부종으로인하여관절염이동반되었다. 또한환자의이마, 등, 왼쪽어깨, 오른쪽발목에서관찰된홍반성융기판과조직학적으로확인된호중구의진피침윤으로인하여 Sweet 증후군의피부증상에합당하였다. 환자의임상증상과병력, 혈액검사결과를바탕으로주진단기준두가지와부진단기준세가지를만족하여 Sweet 증후군으로진단하였으며과거력상 Sweet 증후군과관절염이동반될수있는기저질환인 myelodysplastic syndrome, 간경화및약물노출력은없었다 [3,4]. 관절염및구강궤양은 고용량스테로이드및병변내주입치료이후모두호전을보여 Sweet 증후군과연관된피부외소견으로보인다. 아프타성궤양 (aphthous-like ulceration), 궤양구내염 (ulcerative stomiatitis) 은 Sweet 증후군에서관찰될수있는구강내병변으로, 재발하는구강내궤양이특징인베체트병과감별이필요하다. 베체트병과비교하여 Sweet 증후군은피부병변이주이며, 구강궤양은약 3-30% 의경우에만보고되어있으며, 연관된성기궤양의발생은매우드물게보고되어있다 [5-6]. Sweet 증후군의국내보고는이등이국내에서발생한 Sweet 증후군 23예를연구한것이있고, 여기에서연관된전신질환으로는만성염증성장질환 (6예) 이가장흔하였으며다음으로급성골수성백혈병등의혈액종양은 5예, 고형종양은 1예였다 [7]. 질환별로좀더자세히보면궤양성대장염, 골수이형성증후군, 임균감염및간암등과같은전신질환및약제와연관된 Sweet 증후군이보고되었으며 [8-13], Jung 등 [14] 은의식혼탁으로내원한 Neuro-sweet 환자증례를보고하였으나, 피하낭종의피부병변및관절염이확인된국내보고는없었다. 이상의국내에보고된증례의임상적특징을표로정리하여보았다 (Table 1). Sweet 증후군은치료를하지않을경우수개월간증상이지속될수있다. 치료는스테로이드의전신적투여이며, 치료반응은비교적효과적이다. 스테로이드에반응이불충분할경우요오드화칼륨 (potassiumiodide), 콜히친 (Colchine), Table 1. Review of Sweet s syndrome cases that reported in Korea Case Age/Sex Arthritis Site of Skin Lesion Associated Disease WBC (/mm 3 ) ESR (mm/hr) Treatment Reference 1 68/M - Face, U/E, L/E UC 12,000 50 Prednisolone [8] 2 53/M - Forearm MDS 9,050 Unchecked Prednisolone [9] 3 75/M - Neck Hand MDS 2,700 39 Prednisolone [10] 4 35/M - U/E, L/E Trunk 5 56/M - U/E, L/E Trunk Back 6 46/M - Neck Hand Disseminated Gonococcal Infection - 154-28,690 56 Prednisolone Ciprofloxacin [11] HCC 8,340 105 Prednisolone [12] None 12,300 38 Prednisolone [13] 7 79/F - L/E Pul. TB 6,290 46 Prednisolone [14] UC, ulcerative colitis; MDS, myelodysplastic syndrome; U/E, upper extremity; L/E, lower extremity; HCC, hepatocellular carcinoma; TB, tuberculosis.
- Young Jae Ki, et al. Sweet s syndrome with subdermal cyst and arthritis - 인도메타신 (indomethacin), 클로파지민 (clofazimine), 사이클로스포린 (cyclosporine), 답손 (dapsone) 등을병용투여할수있다 [15]. 또한고령에서재발을반복하는경우는반드시악성종양의동반여부를확인하고필요시면역억제제를추가하여야한다. 작은크기의단독병변일경우에는외용스테로이드의사용이나스테로이드 (triamcinolone acetonide) 의병변내주입으로호전을보인사례들도보고되었다 [16]. 본증례에서는병변내스테로이드주사및전신투여로피하낭종을포함하는피부병변, 관절염및구강내궤양이치료후호전되었고, 용량을점차적으로감량하여재발없이치료되었다. 요 Sweet 증후군은급성열성호중구성피부질환으로다양한임상양상을보일수있다. 피하낭종을포함하는피부병변, 관절염및구강내궤양을동반한 Sweet 증후군은국내보고가드물며저자들은초음파와조직생검을통해진단후스테로이드전신투여로호전된환자 1예를경험하였기에문헌고찰과함께보고하는바이다. 약 중심단어 : Sweet 증후군 ; 피하낭종 ; 관절염 REFERENCES 1. Levin J, Werth VP. Skin disorders with arthritis. Best Pract Res Clin Rheumatol 2006;20:809-826. 2. Moreland LW, Brick JE, Kovach RE, DiBartolomeo AG, Mullins MC. Acute febrile neutrophilic dermatosis (Sweet syndrome): a review of the literature with emphasis on musculoskeletal manifestations. Semin Arthritis Rheum 1988; 17:143-153. 3. Kaiser R, Connolly K, Linker C, Maldonado J, Fye K. Stem cell transplant for myelodysplastic syndrome-associated histiocytoid Sweet's syndrome in a patient with arthritis and myalgias. Arthritis Rheum 2008;59:1832-1834. 4. Ambrose NL, Tobin AM, Howard D. Etanercept treatment in Sweet's syndrome with inflammatory arthritis. J Rheumatol 2009;36:1348-1349. 5. Hassikou H, Tabache F, Baaj M, Safi S, Hadri L. Sweet's syndrome in Behçet's disease. Joint Bone Spine 2007;74: 495-496. 6. Delke I, Veridiano NP, Tancer ML, Gomez L, Diamond I. Sweet syndrome with involvement of the female genital tract. Obstet Gynecol 1981;58:394-396. 7. Lee KS, Lee YJ, Lee WS, et al. Sweet's syndrome in Korea. Korean J Med 1996;51:340-350. 8. Lee JH, Kim HY, Kim HS, et al. A case of Sweet's syndrome associated with ulcerative colitis. Korean J Med 2005;69: 313-317. 9. Kang MR, Park EH, Jung HW, et al. A case of Sweet syndrome involving small bowel. Korean J Med 2004;67: 809-813. 10. Ko GB, Lee HK, Lee HS, et al. Case of Sweet s syndrome with pulmonary infiltration and pleural effusion in myelodysplastic syndrome. Korean J Med 2011;80:216-220. 11. Kim JW, Song R, Im CH, et al. Disseminated gonococcal infection presenting as Sweet syndrome. Korean J Med 2011;80:486-489. 12. Choe YJ, Park WB, Bang JW, et al. A case of Sweet's syndrome with pulmonary involvement. Korean J Med 2002;62:284-288. 13. Kim MK, Kim GH, Jang EJ, et al. A case of the Sweet s syndrome associated with anti tuberculous medication. Korean J Med 2011;80(Suppl 2):S188-S193. 14. Jung HY, Kim SK, Park KW, et al. A case of Sweet syndrome involving the central nervous system. Korean J Med 2008;75:463-466. 15. Cohen PR, Kurzrock R. Sweet's syndrome: a review of current treatment options. Am J Clin Dermatol 2002;3: 117-131. 16. Imanaga T, Hayashi T, Yoshii C, Suzuki S, Yatera K, Kido M. Pulmonary involvement in acute febrile neutrophilic dermatosis (Sweet's syndrome). Nihon Kokyuki Gakkai Zasshi 2000;38:206-210. - 155 -