CASE REPORT http://dx.doi.org/10.5371/hp.2012.24.4.328 Print ISSN 2287-3260 Online ISSN 2287-3279 Acute Phase of Sero-negative Rheumatoid Arthritis Misdiagnosed as Pyogenic Arthritis - A Case Report - Cheol Hee Park, MD, Joo Hyun Lee, MD, Tae Jin Kim, MD, Dong Hurr, MD, Young Soo Chun, MD, Kee Hyung Rhyu, MD, Yoon Je Cho, MD, PhD Department of Orthopedic Surgery, College of Medicine, Kyung Hee University, Seoul, Korea In cases of sero-negative rheumatoid arthritis (RA), no abnormal findings are observed on blood tests and its clinical course is favorable, compared to sero-positive RA. In the acute phase of sero-negative RA, infiltration of neutrophils may be the only pathologic finding on frozen section biopsy. Thus, it might be misdiagnosed as pyogenic arthritis. We report on a case of acute sero-negative RA misdiagnosed as pyogenic arthritis during hip surgery with review of the literature. Key Words: Hip, Seronegative rheumatoid arthritis, Pyogenic arthritis 서 론 류마티스인자를포함한혈청학적이상소견이보이지않는류마티스관절염을혈청음성류마티스관절염이라지칭하며 (sero-negative rheumatoid arthritis) 류마티스인자가존재하는혈청양성류마티스관절염과구분하게된다. 혈청음성류마티스질환은경과가양호하며방사선학적으로도변화가적어혈청양성류마티스관절염에비해진단이어렵다 1). 류마티스관절염에서나타나는전형적인병리학적인소견은림프구침착과림프소포 (lymphoid follicle) 형성, 판누스형성등이지만급성기의류마티스질환에서는오히려호중구의침착이관찰될수있으며이는류마티스관절염의진단에익숙한병리소견이아니다 2). 본저자들은고관절수술시시행한동결생검상다수의호중구침착이보여, 화농성관절염으로오진된급성기의혈청음성류마티스관절염의증례를경험하였으며이를보고하고자한다. 증 례 Submitted: October 14, 2012 1st revision: October 23, 2012 2nd revision: October 29, 2012 3rd revision: November 15, 2012 Final acceptance: November 16, 2012 Address reprint request to Yoon Je Cho, MD, PhD Department of Orthopaedic Surgery, College of Medicine, Kyung Hee University, #1 Hoegi-dong, Dongdaemun-gu, Seoul 130-702, Korea TEL: +82-2-958-8346 FAX: +82-2-964-3865 E-mail: yjcho@khmc.or.kr 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. 52 세여자환자가양측고관절의심한통증을주소로내원하였다. 환자는 4 년전부터양측서혜부의통증이경미하게시작되었고 2 년전부터증상이악화되어개인의원에서경구용스테로이드를처방받아지속적으로복용하였다. 외래방문시시행한신체학적검사에서양측고관절의심한운동제한과관절운동시통증이더심해지는양상이관찰되었다. 통증으로인한심한파행소견이관찰되었고, 양측고관절의 Patrick 검사와 log roll 검사는모두양성소견이었다. 환자의 Harris 고관절점수와 UCLA 점수는각각 38 점, 3 점이었다. 방사선학적검사에서양측고관절에비구이형성증의소견이보였고관절간격의협소화와 328 Copyright c 2012 by Korean Hip Society
Cheol Hee Park et al.: Acute Phase of Sero-negative Rheumatoid Arthritis Misdiagnosed as Pyogenic Arthritis 연골하골의골흡수및낭종형성소견을관찰할수있었다 (Fig. 1). 정밀한평가를위해 MRI 를촬영하였으며 T1 에서명확하지않은양측대퇴골두의저신호강도의띠와함께연골하골의흡수및다량의골낭종을확인할수있었고 (Fig. 2A), T2 에서는대퇴골두무혈성괴사의전형적인소견인이중선징후는관찰되지않았으나양측고관절의관절액은증가되어있었고활액막의증식소견이관찰되었다 (Fig. 2B). 임상적으로고관절외타부위의통증이없고, 스테로이드를꾸준히복용한과거력이있다는점에서대퇴골두무혈성괴사의가능성이있었으나, 방사선학적검사에서양측대퇴골두의심한변형없이관절간격이좁아진점, MRI 상 T1 에서저신호강도의띠가명확하게보이지않았던점등고관절의무혈성괴사에서보이는전형적인소견과맞지않는부분이있었다. 원발성및속발성관절염의가능성 도고려하였으나일반적인관절염소견에비해대퇴골두의파괴와활액막의증식이심한양상이었다. 이에다른질환의감별을위해혈액학적검사를진행하였으며백혈구수치는 6000/uL (segmented neutrophil count 68.7%) 으로정상수치였으나, ESR (erythrocyte sedimentation rate) 과 CRP (C-reactive protein) 는각각 100 mm/hr, 10.67 mg/dl 로정상에비해높았으며, 혈청요산수치는 3.9 mg/dl, 류마티스인자는 10.4 IU/mL 이하로정상이었다. 환자는과거및현재고관절외에타부위의불편한증상을크게호소하지않았으며류마티스인자및요산수치가정상이었다는점에서류마티스관절염및통풍성관절염의가능성은낮은것으로판단하였다. 화농성관절염에서보이는고체온및환부의발적, 열감등의소견은관찰되지않았으나혈청학적검사에서 ESR 과 CRP 의수치가높고환부의관절운동시고관절통증이심하였으며, 타부위감 A B Fig. 1. Preoperative radiographs of the hip joint showing sclerotic change of both femoral head, subchondral bone cysts & fracture, joint destructive change. (A) AP view, (B) Frogleg view. A B Fig. 2. MRI view showing joint fluid collection, synovial hypertrophy, subchondral bone cyst & fracture. (A) T1 weighted coronal view (B) T2 weighted coronal view. www.hipandpelvis.or.kr 329
염을감별하기위해시행한흉부방사선학적검사와소변검사등에서특이소견이나타나지않아고관절의저독성의화농성관절염 (low virulence pyogenic arthritis) 에무게를두고무혈성괴사등타질환을감별하기로결정하였다. 우선관절천자를통해고관절의관절액을채취하려하였으나충분한양의관절액을얻을수없어체액검사및도말, 배양등의검사를시행할수없었다. 이에술전항생제를사용할수없었으며수술적치료를진행하며동시에생검및균배양검사를진행하여질병을감별후항생제를사용하기로결정하였고, 우측고관절의파괴및통증이좌측보다심하여우측부터수술을시행하였다. 우측고관절의육안적수술소견상고관절의활액막증식및대퇴골두파괴외에심각한이상소견은관찰되지않았으나, 화농성관절염및면역성질환을감별하기위한동결생검상 HPF (high power field) 에서 20 개이상의호중구가관찰되는급, 만성의염증소견이있어화농성관절염으로진단하였다. 고관절의파괴가심하게진행되어있어단순한변연절제및세척술로는적절한치료가이루어질수없다고판단되어파괴가진행된대퇴골두를제거후대퇴경부에 4 개 Fig. 3. Postoperative radiographs showing antibiotics pregnated cement spacer insertion of the right hip joint. 의해면골나사 (cancellous screw) 를고정하여지주를만들고그위에 vancomycin 과 1 세대 cepha 계열의항생제를혼합한골시멘트로대퇴골두모양을만들어고관절에삽입후수술을종료하였다 (Fig. 3). 술후지속적인 1 세대항생제사용에도불구하고염증의혈청학적지표인 ESR/CRP 수치는호전되지않았으며이에고관절에염증을일으키는다른원인들에대해서도재평가하게되었다. 균배양검사에서특별한균은배양되지않았으며최종병리소견은다량의호중구가관찰되는급, 만성의염증소견으로확인되었다. 다른질환을감별하기위해시행한혈청학적검사인류마티스인자및 procalcitonin, anti-ccp (anti-cyclic citrullinated peptide) 와 HLA-B27 에서는모두정상소견이관찰되었다. 다른원인을밝혀내지못한채감염에대한치료를지속하던중, 술후 4 주째환자가 수술받은고관절의통증이일부호전되니손목과손이뻐근하다 고표현하였다. 다시시행한자세한문진상경부에서나타나는 1 시간이상의미약한조조강직과양측손목과수부의관절의종창이동반되지않은 6 주이상의미약한통증이중수지관절과근위지관절에있음을확인할수있었다. 이에다시류마티스관절염을의심하게되었고, 수부와무릎, 천장관절, 족부의방사선사진을추가적으로촬영후수부초음파검사를진행하였다. 추가촬영된방사선학적사진들은정상이었으나초음파상에서양측손목과양측 2, 3, 4 번째중수지관절에미약한미란소견과함께활액막염소견이확인되었다. 이에병리과에생검조직의세밀한재평가를요청하였고, 그결과류마티스관절염에서전형적으로관찰되는림프형질세포 (lymphoplasmacyte) 의침착이나림프소포의소견은없으나, 다량으로관찰되는호중구가일부분연골하에침착되는양상과검체의한부위에서연골에침입하는작은판누스 (pannus) 조직이확인되었다 (Fig. 4). 이는림프구가침착되지않은채다량의호중구가나타나는급성기의류마티스관절염으로해석할수있었고혈액학적 A B C Fig. 4. (A) Histologic examination of hematoxyline and eosin stained specimen showed of neutrophils infiltration in the tissues around the hip joint and did not show the lymphoid follicle ( 100). (B) The same findings above figure ( 400), (C) Small pannus (dark arrow) formation ingrowing cartilage ( 100). 330 www.hipandpelvis.or.kr
Cheol Hee Park et al.: Acute Phase of Sero-negative Rheumatoid Arthritis Misdiagnosed as Pyogenic Arthritis 으로특별한이상소견이없는혈청음성류마티스관절염으로진단할수있었다. 환자는항생제를중단하고 NSAID 와스테로이드, 면역억제제 (mizorbine), DMARD (methotrexate) 를복용하였으며, 이후수부와손목의미약한증상과혈중 ESR/CRP 가호전되었고고관절의통증도더완화되었다. 이후환자는고관절의원활한기능을위해양측의고관절전치환술을시행받았으며통증의호소및보행의장애없이퇴원하였다. 고 찰 류마티스관절염은전신적인만성염증성질환으로진단시에임상증상과함께혈액학및방사선학적소견을모두고려하여야한다 3). 이러한류마티스관절염의정확한병리기전및원인은완전히이해되지않았으나호중구, 대식세포, 활액섬유아세포와 T 림프구, B 림프구등이류마티스질환의시작에중요한역할을담당한다고알려져있으며최근의연구결과에따르면호중구가다른혈액세포와반응하여류마티스관절염의초기시작과전반적인진행과정에있어서중요한역할을담당하고있는것으로밝혀졌다 4). 류마티스관절염의병리소견으로는다량의림프구침착및림프소포형성이일반적인것으로알려져있지만이는주로만성기의소견이며, 급성기에는오히려다량의호중구가침착되는소견이관찰될수있다. 만약급성기에림프구가관절조직에침범하기전에호중구가먼저활액으로들어와염증반응을시작하는단계인경우, 본증례와같이림프구침착과림프소포등의전형적인소견없이호중구의침착만이병리소견에서관찰수있으며이는화농성관절염으로오인될수있다 2). 류마티스인자는류마티스관절염의모든환자에서나타나지않으며질환의발생에꼭필요한것은아니나, 높은류마티스인자의역가는질환의중증도와악화, 류마티스결절, 관절외증상과관련이있다 5,6). 그외특이도가높은 Anti-CCP 7) 와 ANA (antinuclear antibody), 면역글로불린검사또한진단에도움이되는혈청학적검사이다. 상기혈청학적인검사가음성으로나타나는류마티스관절염을혈청음성류마티스관절염이라하며진단시손목과수부의주로나타나는임상적인증상과함께골미란과활액막염등의영상의학적확인이필요하나경과가미약하기때문에진단이어렵다 1). 본증례에서는류마티스관절염에서나타나는일반적인혈액학적소견들 (rheumatoid factor, Anti-CCP) 이음성으로나타나면서질병의진단을어렵게만들었으며수부, 손 목등고관절외의타부위관절통이매우미약하고특히수부의외형상의변형및염증소견이관찰되지않았다는점들도류마티스관절염의진단을지연시키는요인이되었다. 또한혈청음성류마티스관절염자체의미약한경과외에도타병원에서처방받아복용하고있던스테로이드와진통소염제가류마티스관절염의증세를약화시켜이의진단을더욱어렵게한것으로사료된다. 동결생검상일반적으로알려진류마티스관절염의전형적인특징소견들이보이지않았던점은진단을방해한가장큰요인이다. 혈청음성류마티스관절염은혈액학적인검사에서이상소견이나타나지않고그진행과정이일반적인류마티스관절염보다양호하기때문에진단이어려우며, 특히급성기의병리소견에서호중구의침착만관찰될수있어, 환자가지닌병의정확한진단과올바른치료를저해하는요소가될수있으며본증례처럼화농성관절염으로오인하여필요없는수술적치료가시행될수있으므로주의해야한다. 따라서화농성관절염이의심되기는하나임상적으로명확한증거가미약한경우에는혈청음성류마티스관절염의가능성을생각해보아야하며정확한진단과치료를위해서는세심한병력청취와신체학적검사, 방사선검사및초음파등의정밀한영상의학적검사가필요할것으로사료된다. REFERENCES 01.Rozin AP, Hasin T, Toledano K, Guralnik L Balbir- Gurman A. Seronegative polyarthritis as severe systemic disease. Neth J Med. 2010;68:236-41. 02. Bullough PG. Orthopaedic pathology. 4th ed. Edinburgh: Mosby; 2004. 286-97. 03.Arnet FC, Edworthy SM, Bloch DA, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988;31:315-24. 04.Cascão R, Rosário HS, Souto-Carneiro MM, Fonseca JE. Neurtophils in rheumatoid arthritis: More than simple final effectors. Autoimmun Rev. 2010;9:531-5. 05.Morel J, Combe B. How to predict prognosis in early rheumatoid arthritis. Best Pract Res Clin Rheumatol. 2005;19:137-46. 06.van Zeben D, Hazes JM, Zwinderman AH, Cats A, van der Voort EA, Breedveld FC. Clinical significance of rheumatoid factors in early rheumatoid arthritis: results of a follow up study. Ann Rheum Dis. 1992;51:1029-35. 07. Nishimura K, Sugiyama D, Kogata Y, et al. Meta-analysis: diagnostic accuracy of anti-cyclic citrullinated peptide antibody and rheumatoid factor for rheumatoid arthritis. Ann Intern Med. 2007;146:797-808. www.hipandpelvis.or.kr 331
국문초록 고관절의화농성관절염으로오진된급성기혈청음성류마티스관절염 - 증례보고 - 박철희 이주현 김태진 허 @ 동 전영수 유기형 조윤제경희대학교의과대학정형외과학교실 혈청음성류마티스관절염은혈액검사에서이상소견이나타나지않는자가면역성질환으로임상경과가혈청양성류마티스관절염에비해양호하다. 급성기에는수술중시행한동결생검에서호중구의침착만관찰될수있어서화농성관절염으로오진될수있다. 저자들은고관절수술시화농성관절염으로오진된급성기의혈청음성류마티스관절염환자를경험하였기에이를문헌고찰과함께보고하고자한다. 색인단어 : 고관절, 혈청음성류마티스관절염, 세균성관절염 332 www.hipandpelvis.or.kr