journal of rheumatic diseases · 2018-04-04 · pppp journal of rheumatic diseases (2010. 1....

Official Journal of Korean College of Rheumatology

Journal of Rheumatic Diseases

일자 I

장소 I

제32차 세계내과학회학술대회World Congress of Internal Medicine

대한류마티스학회 제34차 추계학술대회 심포지엄Korean College Rheumatology 34th Annual Scientific Meeting

Vol. 21, Suppl. 2, November, 2014

2014년 10월 27일(월)

COEX (4층 컨퍼런스룸 401호, 402호)

pISSN 2093-940XeISSN 2233-4718

pp

JOURNAL OF RHEUMATIC DISEASES

(2010. 1. 1∼2010. 12. 31)

임 원 명 단

자문위원 김 기 용 (울산의대) 김 동 수 (연세의대) 김 동 집 (가톨릭의대)김 목 현 (한양의대) 김 신 규 (한양의대) 김 중 곤 (서울의대)김 호 연 (건국의대) 문 명 상 (제주한라병원) 민 헌 기 (서울의대)박 병 문 (광명성애병원) 송 영 욱 (서울의대) 유 대 현 (한양의대)유 명 철 (경희의대) 이 윤 우 (위더스내과) 정 덕 환 (경희의대)최 영 길 (강남차병원) 최 일 용 (한양의대)

회 장 이 수 곤 (연세의대)이 사 장 고 은 미 (성균관의대)기획이사 박 성 환 (가톨릭의대) 최 정 윤 (대구가톨릭의대)총무이사 김 태 환 (한양의대)재무이사 이 상 헌 (건국의대)편집이사 전 재 범 (한양의대)학술이사 차 훈 석 (성균관의대)국제이사 김 완 욱 (가톨릭의대)보험이사 김 현 아 (한림의대)홍보이사 심 승 철 (충남의대)교육연구이사 유 빈 (울산의대)임상연구이사 이 신 석 (전남의대)정보이사 송 정 수 (중앙의대)무임소이사 문 영 완 (성균관의대) 박 용 범 (연세의대) 송 관 규 (고려의대)

유 태 석 (유태석내과) 이 은 봉 (서울의대)이 사 강 성 욱 (충남의대) 강 영 모 (경북의대) 공 현 식 (서울의대)

김 광 남 (한림의대) 김 진 석 (제주의대) 류 완 희 (전북의대)민 준 기 (가톨릭의대) 박 시 복 (한양의대) 백 한 주 (가천의대)서 창 희 (아주의대) 이 영 호 (고려의대) 이 지 수 (이화의대)이 창 근 (울산의대) 임 군 일 (동국의대) 정 원 태 (동아의대)홍 승 재 (경희의대)

감 사 박 원 (인하의대) 배상철 (한양의대)(가나다순)

pppp


(2010. 1. 1∼2010. 12. 31)

위 원 회 명 단

총무이사 김 태 환 (한양의대)총무위원 김 성 규 (대구가톨릭의대) 이 은 영 (서울의대) 최 성 재 (고려의대)재무이사 이 상 헌 (건국의대)재무위원 박 경 수 (가톨릭의대) 서 영 일 (한림의대) 주 지 현 (가톨릭의대)편집이사 전 재 범 (한양의대)편집간사 김 용 길 (울산의대)편집위원 강 성 욱 (충남의대) 민 준 기 (가톨릭의대) 박 민 찬 (연세의대) 박 성 훈 (대구가톨릭의대)

박 용 욱 (전남의대) 이 영 호 (고려의대) 이 재 준 (성균관의대) 최 찬 범 (한양의대)학술이사 차 훈 석 (성균관의대)학술간사 곽 승 기 (가톨릭의대)학술위원 문 영 완 (성균관의대) 성 윤 경 (한양의대) 이 명 수 (원광의대) 이 상 원 (연세의대)

이 상 일 (경상의대) 이 윤 종 (서울의대) 이 창 근 (울산의대)국제이사 김 완 욱 (가톨릭의대)국제간사 김 인 제 (이화의대)국제위원 김 기 조 (가톨릭의대) 김 성 수 (울산의대) 박 용 욱 (전남의대) 이 상 훈 (경희의대)

이 은 봉 (서울의대) 정 영 옥 (한림의대) 보험이사 김 현 아 (한림의대)

보험간사 윤 보 영 (인제의대) 홍 승 재 (경희의대)보험위원 강 태 영 (연세대원주의대) 김 태 종 (전남의대) 김 현 숙 (순천향의대) 민 도 준 (민도준내과)

박 민 찬 (연세의대) 박 성 환 (가톨릭의대) 서 영 일 (한림의대) 심 승 철 (충남의대)엄 완 식 (한양류마엄완식내과) 윤 종 현 (가톨릭의대) 이 성 원 (동아의대) 장 대 국 (장대국내과)주 지 현 (가톨릭의대)

홍보이사 심 승 철 (충남의대)홍보간사 최 찬 범 (한양의대)홍보위원 강 은 하 (서울의대) 김 상 현 (계명의대) 박 경 수 (가톨릭의대) 박 동 진 (전남의대)

신 기 철 (서울의대) 이 명 수 (원광의대) 허 진 욱 (을지의대) 홍 승 재 (경희의대)교육연구이사 유 빈 (울산의대)교육연구간사 윤 종 현 (가톨릭의대)교육연구위원 김 근 태 (고신의대) 김 상 현 (계명의대) 이 창 훈 (원광의대) 서 창 희 (아주의대)

송 정 수 (중앙의대) 이 상 일 (경상의대) 차 훈 석 (성균관의대)임상연구이사 이 신 석 (전남의대)임상연구간사 최 성 재 (고려의대)임상연구위원 강 성 욱 (충남의대) 곽 승 기 (가톨릭의대) 김 성 규 (대구가톨릭의대)김 현 아 (아주의대)

남 언 정 (경북의대) 박 용 범 (연세의대) 성 윤 경 (한양의대) 신 기 철 (서울의대)이 재 준 (성균관의대) 이 창 훈 (원광의대) 전 찬 홍 (순천향의대)

정보이사 송 정 수 (중앙의대)정보간사 권 성 렬 (인하의대)정보위원 고 혁 재 (가톨릭의대) 김 성 수 (울산의대) 나 성 수 (순천향의대) 안 중 경 (성균관의대)

이 상 원 (연세의대) 이 승 근 (부산의대) 이 은 영 (서울의대) 이 창 근 (울산의대)채 지 영 (분당제생병원) 최 상 태 (중앙의대) 허 진 욱 (을지의대)

(가나다순)

pp


(2010. 1. 1∼2010. 12. 31)

List of Korean College of Rheumatology Executive Directors

Advisory Board

President

Chairman of the Board

Director of Planning

Executive Secretary

Director of Finance

Director of Editorial Board

Director of Academic Affairs

Director of International Cooperation

Director of Insurance

Director of Public Relation

Director of Education & Research

Director of Clinical Trials

Director of Medical Information

Director at Large

Board Members

Auditor

pppp


(2010. 1. 1∼2010. 12. 31)

List of Korean College of Rheumatology Executive Directors

Executive Secretary Committee

Finance Committee

Editorial Committee

Academic Affairs Committee

International Cooperation Committee

Insurance Committee

Public Relation Committee

Education & Research Committee

Clinical Trials Committee

Medical Information Committee

JOURNAL OF RHEUMATIC DISEASESVol. 21, Suppl. 2, November, 2014

PROGRAM

일 자: 2014년 10월 27일(월)장 소: 코엑스

[ COEX Conference Room 401호 ]

08∶30~08∶40 Opening Remarks 회 장 이수곤

Welcome Address 이사장 고은미

08∶40~10∶30 WCIM 2014 Symposium 17. Rheumatologic Disease in Internist's PerspectivesChair: Ho-Youn Kim (Konkuk Univ., Korea), Hyon K. Choi (Boston Univ., USA)

08∶40~09∶05 Approach for Evaluation of Joint Disease or Connective Tissue Disease

Seung Cheol Shim (Chungnam National Univ., Korea)

09∶05~09∶35 Current Concepts in the Management of Rheumatoid Arthritis

Yoshiya Tanaka (Univ. of Occupational, Japan)

09∶35~10∶05 Treatment Update of Gouty Arthritis Hyon K. Choi (Boston Univ., USA)

10∶05~10∶30 Two-edged Sword: Corticosteroid Hyun Ah Kim (Hallym Univ., Korea)

10∶30~11∶00 Coffee Break

11∶00~12∶40 WCIM 2014 Symposium 19. Right Approaches to Understanding Rheumatic PainChair: Chung-Tei Chou (Veterans General Hospital Taipei, Taiwan)

Young-Wook Song (Seoul National Univ., Korea)

11∶00~11∶30 Is It Rheumatoid Arthritis? the Difference Between Spondyloarthritis (+/- Osteoarthritis)

and Rheumatoid Arthritis Chung-Tei Chou (Veterans General Hospital Taipei, Taiwan)

11∶30~12∶00 Low Back Pain: Delineating Inflammatory and Mechanical Sub-types

Xenofon Baraliakos (Ruhr-University Bochum, Germany)

12∶00~12∶20 Clinical Approach to Soft Tissue Rheumatism: a Path Out of Pain

Shin-Seok Lee (Chonnam National Univ., Korea)

12∶20~12∶40 How to Recognize Arthralgia Associated with Other Medical Conditions

Jisoo Lee (Ewha Womans Univ., Korea)

12∶40~14∶00 Luncheon Symposium (Pfizer)Chair: Choongki Lee (Yeungnam Univ., Korea),

Sung-Hwan Park (Catholic Univ., Korea)

Learnings from Clinical Development Program: Tofacitinib from

Discovery to Approval and Beyond Tamas Koncz (Pfizer Inc.)

Tofactinib in Rheumatoid Arthritis, Clinical Perspective

Eun Bong Lee (Seoul National University Hospital)

14∶00~15∶30 Non-scientific ProgramChair: 이수곤 (연세의대), 최정윤 (대구가톨릭의대)

14∶00~14∶50 융복합창조시대-소통과 협업의 리더십 윤은기 (한국협업진흥협회 회장)

14∶50~15∶30 선택진료비 사례로 본 보건의료정책 결정과정 손영래 (보건복지부 보험급여과장)

15∶30~15∶50 논문상 수상 및 대한류마티스학회 논문상 수상자 강연

15∶50~16∶30 Closing Remarks 회 장 이수곤

16∶30~18∶00 WCIM Plenary Lecture: Non-communicable Disease (Auditorium, 3F)

18∶00~ Dinner (COEX Conference Room South 402)

[COEX Conference Room South 402호]

09∶00~10∶30 Stem Cells for Rheumatologists: from Bench to BedsideChair: 고은미 (성균관의대), 김완욱 (가톨릭의대)

09∶00~09∶30 Stem Cells: From Basics to Applications 한명관 (전북의대)

09∶30~10∶00 Immune Modulation Property of Human Mesenchymal Stem Cells 박용범 (연세의대)

10∶00~10∶30 Induced Pluripotent Stem Cells for Rheumatic Diseases 주지현 (가톨릭의대)

10∶30~11∶00 Coffee Break

11∶00~12∶30 What is New?Chair: 유대현 (한양의대), 문영완 (성균관의대)

11∶00~11∶30 Update of Foot and Ankle Surgery in Rheumatoid Arthritis 안재훈 (가톨릭의대 정형외과)

11∶30~12∶00 Inflammatory Myopathy 남언정 (경북의대 류마티스내과)

12∶00~12∶30 Juvenile Idiopathic Arthritis 정대철 (가톨릭의대 소아청소년과)

JOURNAL OF RHEUMATIC DISEASESVol. 21, Suppl. 2, November, 2014

목 차

WCIM 2014 Symposium 17. Rheumatologic Disease in Internist's Perspectives

　1. Approach for Evaluation of Joint Disease or Connective Tissue Disease Seung Cheol Shim ··· S3

　2. Current Concepts in the Management of Rheumatoid Arthritis Yoshiya Tanaka ··· S5

　3. Treatment Update of Gouty Arthritis Hyon K. Choi ··· S6

　4. Two-edged SWORD: CORTICOSTEROID Hyun Ah Kim ··· S8

WCIM 2014 Symposium 19. Right Approaches to Understanding Rheumatic Pain

　1. Is it Rheumatoid Arthritis? The Difference between Spondyloarthritis (+/- Osteoarthritis) and Rheumatoid Arthritis Chung-Tei Chou ··· S11

2. Low Back Pain: Delineating Inflammatory and Mechanical Sub-Types Xenofon Baraliakos ··· S12

3. Clinical Approach to Soft Tissue Rheumatism: A Path Out of Pain Shin-Seok Lee ··· S13

4. How to Recognize Arthralgia Associated with Other Medical Conditions Jisoo Lee ··· S14

Luncheon Symposium (Pfizer)

　1. Learnings from Clinical Development Program: Tofacitinib from Discovery to Approval and Beyond Tamas Koncz ··· S17

　2. Tofactinib in Rheumatoid Arthritis, Clinical Perspective Eun Bong Lee ··· S18

Non-scientific Program

　1. 융복합창조시대 - 협업에 길이 있다! 윤은기 ··· S21

　2. 선택진료비 사례에서 본 보건의료정책 결정과정 손영래 ··· S28

Stem Cells for Rheumatologists: from Bench to Bedside

　1. Stem Cells: Basics to Applications 한명관 ··· S31

　2. Immune Modulation Property of Mesenchymal Stem Cell 박용범 ··· S32

　3. Induced Pluripotent Stem Cells for Rheumatic Diseases 주지현 ··· S33

What is New?

　1. Update of Foot and Ankle Surgery in Rheumatoid Arthritis 안재훈 ··· S37

2. Inflammatory Myopathy 남언정 ··· S39

3. 소아특발관절염(Juvenile Idiopathic Arthritis) 정대철 ··· S47

(2010. 1. 1∼2010. 12. 31)

대한류마티스학회 제34차 추계학술심포지엄

WCIM 2014 Symposium 17. Rheumatologic Disease in

Internist's Perspectives

Journal of Rheumat ic DiseasesVol. 21, Suppl. 2, November, 2014

S3

Approach for Evaluation of Joint Disease or Connective Tissue Disease

Chungnam National Univ., Korea

Seung Cheol Shim

Musculoskeletal complaints are among the most common symptoms, and their cause and effect need to be

established. Physicians evaluating such patients need to characterize the problem and its impact, establish the

cause, and develop a management plan. When the patient is reviewed, the physician must be able to assess

response to treatment and be able to recognize the lack of expected response. Musculoskeletal conditions are

also frequent comorbid conditions that need to be identified and treated.

The history and physical examination are the two most important components of the diagnostic process for

patients complaining of any symptoms. History taking is the most important skill in rheumatology. Taking an

accurate and comprehensive history of a patient’s musculoskeletal symptoms is crucial for making the correct

diagnosis. This history must include a precise understanding of what the patient means by the description of

symptoms. The physician must obtain a detailed account of symptom onset, location, patterns of progression,

and severity, as well as exacerbating and alleviating factors and associated symptoms. The relationship of the

symptoms to psychosocial stressors is important and should be determined. The impact of the symptoms on all

aspects of the patient’s functioning must be assessed to guide therapy.

The effects of current or previous therapy on the course of the illness are helpful in efforts to understand

current symptoms. Response to anti-inflammatory or glucocorticoid medications may suggest an inflammatory

origin. Such responses are not specific to inflammatory rheumatic diseases, however, and must be considered

in light of the entire history and physical examination. The physician must assess compliance with therapies for

musculoskeletal diseases. Noncompliance with the recommended treatment must be differentiated from treatment

failure as the explanation for the patient’s lack of improvement. The physician must appreciate the patient’s

understanding of the illness and attitudes toward it to begin effective treatment.

The physical examination is pivotal in confirming the cause and effect of musculoskeletal problems. Assessment

of the musculoskeletal system should form part of any general medical examination. The consultation involves

a patient-centered phase for the patient’s story; a physician-centered phase to clarify the story by interrogation

and examination; and an interactive phase during which the patient and physician discuss their concerns, findings,

conclusions, and plans. The consultation must meet the expectations of the patient.

Musculoskeletal conditions cause a broad range of problems that need to be assessed by a multidisciplinary

team to develop an appropriate plan of management. Clinical judgment in interpreting the findings elicited from

the history and physical examination should allow the physician to answer several key questions:

1. Do the symptoms originate in the musculoskeletal system or in other systems (e.g., neurologic disorders, vas-

cular disease, Pancoast syndrome)?

2. Is it an articular or nonarticular process? A substantial number of patients will have localized mechanical prob-

lems or nonspecific soft tissue conditions. Muscular syndromes or pain originating in periarticular foci can often

mimic an articular origin (sometimes affecting more than one site). Examples are unilateral or bilateral anserine

S4 Seung Cheol Shim: Approach for Evaluation of Joint Disease or Connective Tissue Disease

bursitis resembling an intraarticular knee joint disorder and extensor tendinitis of the thumb (de Quervain teno-

synovitis) mimicking wrist involvement. Primary bone conditions (e.g., Paget disease, osteoid osteoma, osteo-

malacia), as well as infiltrative (e.g., lymphomas) and lytic (e.g., metastatic disease, osteitis fibrosa cystica)

lesions, may also provoke pain referred to a joint.

3. Does the patient have arthralgia or arthritis? Arthralgia refers to pain localized to a joint, whereas arthritis

refers to objective evidence of an inflammatory change in the joint. Arthritis is a much more specific sign

of an articular disorder.

4. Is evidence of other organ involvement present (e.g., systemic connective tissue disorders), or does it appear

to be a disorder restricted to the musculoskeletal system (e.g., osteoarthritis)?

5. Is the articular problem inflammatory, mechanical, degenerative, or something else?

6. Does the disease affect axial or appendicular structures, or both?

Once the physician has established that the disorder originates in the joints, several other aspects of the history and

physical examination should be considered to delineate a diagnostic pattern of arthropathy. In addition, other characteristics

of the patient should be taken into account (extraarticular features of disease) normally contributing to diagnostic certainty.

A general examination of the patient should be done to look for any signs of systemic illness. This should include an

examination of the skin, noting signs of pallor (which may suggest anemia), nodules (which may suggest rheumatoid arthritis

or gout), or rashes (which may suggest lupus, vasculitis, or dermatomyositis). The physician should assess gait by asking

the patient to walk in the examining room or down the hallway, because an antalgic gait may be seen in various muscu-

loskeletal disorders of the spine or lower extremities, and various gait disorders may occur in neuromuscular diseases. The

ability of the patient to arise and transfer to the examining table should also be evaluated, as this will provide information

on pain, proximal muscle strength, and overall physical function. The patient should be assessed for appearance of the mus-

cles, including bulk, tone, and tenderness. Muscle bulk should be compared on one side of the body with the other to look

for any asymmetry, hypertrophy, or atrophy. The patient’s manner and body language may provide information on his or

her mood and anxiety level, which merits consideration in evaluating pain and tenderness.

Laboratory tests are commonly used that are relevant to major disorders seen by rheumatologists. Because laboratory

test results are commonly part of the classification and diagnostic criteria, it is important to understand some key conceptual

issues before using these tests in making diagnostic and treatment decisions.

1. In rheumatic diseases laboratory tests contribute significantly to diagnosis, which should always be based on clinical findings.

Measurement of biomarkers can also be useful for monitoring of treatment efficacy and safety as well as for stratification

of patients to predict prognosis and treatment response.

2. Sensitivity and specificity of virtually all biomarkers is limited, and therefore the laboratory diagnostics should be guided

by the clinical picture.

3. Laboratory markers provide different positive or negative predictive values; thus they can be used to exclude a disease

in cases of a normal result or to support the clinical diagnosis in cases of a pathogenic result.

Synovial fluid examination is indispensible in the diagnosis of rheumatic diseases. Normal synovial fluid is a hypocellular,

avascular connective tissue. In disease, synovial fluid increases in volume and can be aspirated. Changes in synovial fluid

cells, noncellular particles, and molecular biomarkers reflect the pathogenesis of the arthropathy. Synovial fluid microscopy,

which identifies cells and particles, is a simple, cheap, and accurate test that yields information of diagnostic and prognostic

significance. Cellular and molecular biomarkers of disease processes involving SF are increasingly being studied and may

bring about a revolution in understanding and recognizing joint disease.

In conclusion, physicians could go wrong by touching only one leg of an elephant like focusing only on joint pain. Accurate

diagnosis can be made by seeing the whole body of the elephant.


S5

Current Concepts in the Management of Rheumatoid Arthritis

Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan

Yoshiya Tanaka

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by inflammation and joint destruction, resulting

in significant morbidity and mortality. To control disease activity and prevent joint damage, synthetic disease-modifying an-

ti-rheumatic drugs (sDMARDs) such as methotrexate (MTX) should be started after patients are diagnosed according to 2010

RA classification criteria. However, sDMARDs often do not provide sufficient control of disease activity or joint destruction.

Recent progress in immunity and autoimmunity clarified that TNF and IL-6 are pleiotropic cytokines with diverse activities

and plays a central role in the pathogenesis of RA. The introduction of biologic DMARDs (bDMARDs) targeting TNF and IL-6

has enabled markedly efficient control of disease activity in patients with RA has revolutionized the treatment of RA.

Accordingly, clinical remission as well as low disease activity (LDA) in patients with long-standing RA becomes perceived

as a realistic primary goal and treat-to-target has been strongly recommended for RA. Furthermore, accumulated evidence

has shown that the maintenance of remission leads to structural and functional remission.

After the sustained remission by bDMARD and MTX, discontinuation of bDMARD is emerging from the risk/benefit point

of view, including safety and economical issues. Half of early RA could discontinue TNF-targeted bDMARDs without clinical

flare after obtaining remission by bDMARDs with MTX by several studies. However, for established RA, deep remission at

the discontinuation was a key factor to keep the treatment holiday of bDMARDs in established RA patients from the HONOR

study and RRR study.

Such a progress in the treatment of RA with bDMARDs will stretch our expectation on biosimilar infliximab. Furthermore,

orally available kinase inhibitors, including tofacitinib targeting JAK-mediated signals, are expected to be a new option for

RA treatment. However, because such intensive treatments sometimes bring drug-induced adverse effects and medical costs,

any treatments of RA should be considered with careful screening and monitoring in each patient.


S6

Treatment Update of Gouty Arthritis

Boston University School of Medicine, USA

Hyon K. Choi

Gout is a common and excruciatingly painful inflammatory arthritis caused by hyperuricemia. Gout is further complicated

by a high level of cardiovascular (CV)-metabolic comorbidities and their sequelae (e.g., premature death). In the modern

era with abundantly available foods and a strong tendency toward a sedentary lifestyle, gout has changed its epidemiology

from a “disease of kings” to a “disease of commoners”. To that effect, studies from a diverse range of countries have con-

sistently shown that the prevalence and incidence of gout has increased during the past several decades such that it is

now the most common inflammatory arthritis in many developed countries (e.g., 3.9% in the US and 2.5% in the UK).

Gout diagnosis is confirmed by urate crystal identification from the joint fluid or tophus; however, it sensitivity varies

according to the presence of symptoms (84% during acute gout and 70% during intercritical gout) and observer skills. Aside

from the crystal confirmation, classic podagra and presence of tophi have the highest clinical diagnostic value for gout

(likelihood ratios = 31 and 40, respectively). Hyperuricaemia, the causal risk factor, also helps to diagnose gout (likelihood

ratio= 10, when defined by the normal range of the local population), although some gout patients have normal serum uric

acid (SUA) levels at the time of investigation, particularly during acute flares. While plain radiographs are generally not sensi-

tive for the diagnosis of gout, ultrasound and dual energy CT scans have emerged as a potentially useful tool for the diagnosis

and management of gout, where available.

The 2012 American College of Rheumatology (ACR) gout management guidelines (established through international collabo-

ration) endorses patient education on diet, lifestyle, treatment objectives, and management of comorbidities as a core ther-

apeutic measure in gout. Purine loading and insulin resistance are two key mediating mechanisms underlying the action of

many modifiable lifestyle risk factors for hyperuricemia and gout. Nevertheless, lifestyle recommendations for gout patients

should consider both the associated benefits and risks in a holistic manner, since gout is often associated with many CV-met-

abolic comorbidities and their sequelae. To that effect, reducing obesity (with daily exercise and a healthy diet) and limiting

intake of red meat and sugary (fructose-rich) beverages are recommended to help reduce SUA levels, the risk of gout, insulin

resistance, and CV-metabolic comorbidities collectively. Conversely, dairy products, vegetables, nuts, legumes, fruits (less

sugary ones), and whole grains are healthy dietary choices for gout patients. Xanthine oxidase inhibitor therapy (allopurinol,

febuxostat) is recommended as the first-line pharmacologic urate-lowering therapy (ULT) approach in gout for the indications

of frequent or advanced (tophaceous) gout, or gout with urolithiasis or chronic kidney disease (CKD) > stage 2. The patient’s SUA level should be lowered sufficiently and durably to improve signs and symptoms of gout, with the target <6 mg/dl at

a minimum, and often < 5 mg/dl. The starting dosage of allopurinol should be no greater than 100 mg/day (and 50mg/day

in moderate to severe CKD) followed by gradual upward titration to treat to target; the required dose can exceed 300 mg

daily, even in patients with CKD. Furthermore, a recent prospective study has demonstrated that treating gout effectively

is not just a matter of initiating ULT, but rather of implementing a proper approach that combines patient education, in-

Journal of Rheumatic Diseases Vol. 21, Suppl. 2, November, 2014 S

dividualized lifestyle advice, and appropriate use of ULTs to achieve and sustain treatment targets (eg, SUA level <6 or <5

mg/dL). Over the 1-year trial period, this approach led to more than 90% of patients achieving the primary treatment target

of SUA <6 mg/dL as recommended by the ACR and the European League Against Rheumatism (EULAR), and to 85% achieving

an SUA of <5 mg/dL, the target level recommended by the British Society for Rheumatology. Further, prior to initiation of

allopurinol, HLA–B*5801 screening should be considered in populations where the HLA–B*5801 allele frequency is high (e.g.,

Koreans, Han Chinese, and those of Thai descent), as HLA–B*5801 positive subjects have a very high risk for severe allopurinol

hypersensitivity reaction.

A gout flare should be treated with pharmacologic therapy, initiated as early as possible, preferably within 24 hours of

onset to help abort the attack and reduce flare severity and duration. Established pharmacologic ULT should be continued,

without interruption, during an acute gout attack. Nonsteroidal antiinflammatory drugs (NSAIDs), corticosteroids, and oral

colchicine are all appropriate first-line options for treatment of acute gout, and certain combinations can be employed for

severe or refractory attacks. Pharmacologic antiinflammatory prophylaxis is recommended for all gout patients when pharma-

cologic urate lowering is initiated, and should be continued if there is any clinical evidence of continuing gout disease activity

and/or the SUA target has not yet been achieved.

Despite these recommendations, there are a wide variety of practical barriers to effective gout care, which is a

‘curable’ inflammatory arthritis. These barriers are likely due to commonly held negative stereotypes of gout patients

and a lack of knowledge and interest in gout among doctors. Thus, appropriate education of patients and treating

physicians should substantially improve the standard of gout care.


S8

Two-edged SWORD: CORTICOSTEROID

Department of Internal Medicine, Hallym University, Korea

Hyun Ah Kim

Corticosteroids are widely used in the treatment of allergic, immunologic and malignant diseases; however, the effectiveness

and safety of systemic corticosteroids for non-life threatening conditions, such as rheumatic diseases is still a matter of

debate.

The use of corticosteroids in rheumatoid arthritis(RA) is supported by extensive literature and their efficacy is reflected

in the recommendation for its use in treatment guidelines for RA. Low- to medium-dose corticosteroids have been shown

to have disease-modifying effect as well as potent anti-inflammatory effect especially in early RA. The indication for using

corticosteroids, and when and how to taper them, are lingering questions for clinicians with weak evidence base, however.

Although concerns about long tern use of corticosteroids have been unduly extrapolated from studies with higher-dose treat-

ment, many studies exploring the use of low- to medium-dose corticosteroid regimens have relevant methodological flaws.

International guidelines help to optimize the management of patients with RA by using updated literature from clinical

trials or research data with a thorough evidence-based format. The American College of Rheumatology currently does not

have recommendations specifically on corticosteroids use, but the European League Against Rheumatism and The Canadian

Rheumatology Association did develop specific recommendations, that corticosteroids (oral, intramuscular or intra-articular)

can be added to disease modifying anti-rheumatic drug therapy as part of the initial treatment strategy for patients with

RA.

On the other hand, the lack of randomized clinical trial data leads to failure to establish the true risk of adverse effects

of corticosteroids because several negative effects attributed to these drugs have also been associated with RA itself, espe-

cially with severe disease. As a result, patients may be unduly deprived of benefits from corticosteroids due to fears of

toxicity. The risk and benefit of corticosteroids in RA need, thus, to be regularly revisited.

In this perspectives lecture, the efficacy for radiological and clinical outcomes for corticosteroids in the treatment of RA

is systemically reviewed. New strategies aimed at improving safety without compromising efficacy is presented, such as the

employment of delayed-release corticosteroids formulations or corticosteroids with altered structure, as well. Lastly, the place

of corticosteroids in the International Guidelines for the management of RA, including the indication of corticosteroids, doses

and duration of treatment, and tapering strategies, is reviewed.

(2010. 1. 1∼2010. 12. 31)


WCIM 2014 Symposium 19. Right Approaches to

Understanding Rheumatic Pain


S11

Is it Rheumatoid Arthritis? The Difference between Spondyloarthritis (+/- Osteoarthritis) and Rheumatoid Arthritis

Veterans General Hospital Taipei, Taiwan

Chung-Tei Chou

Rheumatoid arthritis (RA) is an autoimmune disease, usually occurs in the middle age (40-50) woman, which is interbetween

ankylosing spondylitis (AS) (20-30) and osteoarthritis (OA) (>60). RA is an inflammatory joint disease with the typical clinical

manifestations of symmetrical polyarthritis but small percentage may present monarthritis (e.g, knee) or oligoarthritis at

the disease onset. OA frequently occurs in DIPS and PIPS of finger joints with Heberden’s or Bouchard's nodes. In contrast,

RA involves more freqenctly in PIPs, MCPs and wrist but present no bony formation. Knee OA on x-ray usually cause narrow-

ing of medial compartment after cartilage loss but knee RA usually cause symmetrical joint space narrowing. Laboratory

tests show positive RF or anti-CCP, high ESR or CRP in RA but none of the test positive or high in OA. Synovial fluid analysis

is useful at least it can help clinician to differentiate inflammatory (e.g, RA, AS, PsA) from noninflammatory (e.g, OA) joint

disease.

The main skeletal features in AS are axial involvement with low back pain, enthesitis and dactylitis. Peripheral arthritis

can occur in 30% to 50% of AS patients and it usually involves lower limbs including hip, knee or ankle but less in finger

joints or wrist, which is common for RA. When compare to AS, psoriatic arthritis (PsA) present more enthesitis and dactylitis,

those features are really uncommon in RA. Five clinical patterns of PsA initially were described by Moll and wright and one

of them is polyarthritis which mimics RA. The differential diagnosis of PsA from RA is either by means of typical psoriasis

lesions or unique radiologic features, for instance, remarkable bone resorption with “pencil-in-cup” or abnormal bone remod-

eling with syndesmophyte formation on spine, etc.

To early recognize the arthritis, the new classification criteria for SpA and RA was established in 2009, 2010 respectively.

Many new therapies for arthritis have been used in the past 10 years, therefore, the early diagnosis of inflammatory joint

diseases is becoming an important issue.


S12

Low Back Pain: Delineating Inflammatory and Mechanical Sub-Types

Ruhr-University Bochum, Germany

Xenofon Baraliakos

The term spondyloarthritis (SpA) covers a heterogeneous group of rheumatic diseases characterised by common clinical

symptoms such as inflammatory back pain (IBP) which is considered the leading symptom in patients with the condition.

Patients with SpA have been divided into two subgroups according to the predominant symptoms, which can either be localised

in the spine (axial SpA) or in the peripheral joints (peripheral SpA). Ankylosing spondylitis (AS), the prototype of axial SpA,

is characterised by spinal stiffness. The other common differentiations used to diagnose or classify patients with SpA are

the presence of a disease-defining feature such as psoriasis, inflammatory bowel disease (IBD, Crohn’s disease or ulcerative colitis) or the history of a triggering infection in the enteral or urogenital tract (reactive arthritis). In the absence of these

features, the term ‘undifferentiated SpA’ (uSpA) has been used while, for patients with IBP but without structural changes

in the sacroiliac joints and the spine, the term ‘non-radiographicaxial SpA’ (nrSpA) is used. Not all patients with SpA

will develop AS. A significant delay in diagnosing AS has been reported. The new Assessment of SpondyloArthritis international

Society (ASAS) classification criteria are a step forward in making an earlier diagnosis of patients with axial SpA, but it

is unclear whether they work in primary care. Possible screening tools for axial SpA including IBP and HLA B27 were pro-

posed some years ago in patients with chronic back pain.8 Some of the proposed items were tested in a referral9 and a

cohort study.

The major clinical item in SpA is IBP, first defined in 1977. IBP has long been a central part of the classification criteria

for AS and SpA. Novel definitions for IBP have recently been proposed. In a population-based study, many false positive

answers to questions on IBP were found in controls. Chronic back pain is a common symptom of patients presenting in

the office of general practitioners (GPs) and orthopaedic surgeons. There is limited knowledge on the prevalence of IBP due

to SpA in primary care, but one study reported a prevalence of 5% among patients with chronic BP —a percentage similar

to that recently reported from chiropractitioners’ offices. The aim of this talk is to show the main differences in different IBP-related clinical items in primary care and discuss

the therapeutic implications of these clinical differences.


S13

Clinical Approach to Soft Tissue Rheumatism: A Path Out of Pain

Department of Internal Medicine, Chonnam National University, Gwangju, Korea

Shin-Seok Lee

Soft tissue rheumatic disorders refer to nonsystemic, focal pathologic syndromes involving the periarticular tissues, including

muscle, tendon, ligament, fascia, aponeurosis, retinaculum, bursa, and subcutaneous tissue. These disorders are extremely

common. The archaic term “rheumatism” is sometimes used to refer to these manifestations. These soft tissue disorders

may be divided into several broad categories and include regional myofascial pain disorder, fasciitis, tendinitis, bursitis, en-

thesitis, structural disorders, neurovascular entrapment disorders, complex regional pain syndrome, and generalized pain

disorders. Many of these disorders occur in the absence of systemic disease, and some are a consequence of chronic repetitive

low grade trauma and overuse. Many are self-limiting and respond to conservative measures. Six points of management

can often be initiated during the first visit in a patient with a suspected soft tissue rheumatic disorder, even before the

results of appropriate laboratory or radiologic tests are available. These are excluding systemic disease, eliminating aggravat-

ing factors, explaining the illness, explaining self-help strategies, providing pain relief, and explaining the prognosis.

1. In regional myofascial pain, hyperirritable spots, often in just one body region, and usually within a taut band of skeletal

muscle or in the muscle's fascia, can give rise to characteristic referred pain. There are usually one or more trigger (pain)

points; these are typically indurated and painful on compression. Myofascial trigger points may result from acute trauma,

repeated minor microtrauma of daily living, or from a chronic strain of sedentary work or living habits.

2. Fasciitis includes Dupuytren’s palmar contracture, fascia lata fasciitis, and plantar fasciitis. They have discrete and dis-

parate pathologies, which include proliferation and degeneration of fascia.

3. Tendinitis, which often results from overuse, is a disorder with common features of local pain and dysfunction, inflammation,

and degeneration. It typically involves the area of the tendon near its point of insertion into the bone or its point of

muscular origin.

4. Bursitis is inflammation of the small fluid-filled pads, called bursae. Bursitis may result from direct trauma or repetitive

injury, infection, or it may be a manifestation of a systemic disease such as rheumatoid arthritis or gout.

5. Enthesitis, which is an inflammation of the site of the insertion of the tendon to the bone, is often seen in

spondyloarthritides. Common sites are the insertion of the plantar fascia and the Achilles tendon region.

6. Musculoskeletal structural disorders are relatively common, sometimes subtle, and often contribute to pain syndromes

and to injury in sports participants. Body asymmetry is a common cause for many regional pain disorders.

7. Neurovascular entrapment disorders may occur within the spinal canal (foraminal or central spinal stenosis) or along the

course of a peripheral nerve. The diagnostic triad of peripheral neurovascular entrapment includes a sensation of swelling

and pain in the involved region, paresthesias distal to the site of entrapment, and weakness.

8. A diagnosis of complex regional pain syndrome requires the presence of regional pain and sensory changes following

a noxious event. The pain is of a severity greater than that expected from the inciting injury, and is associated with

characteristic clinical findings.

9. Generalized pain disorders include the hypermobility syndrome, fibromyalgia, the clencher syndrome, polymyalgia rheuma-

tica, and somatoform disorders. These disorders all may cause widespread pain and in some cases disability.


S14

How to Recognize Arthralgia Associated with Other Medical Conditions

Department of Internal Medicine, Ewha Womans University, Seoul, Korea

Jisoo Lee

Joint pain (arthralgia) is a symptom reflective of problems in structures within or adjacent to the joint such as joint capsule,

periosteum, ligaments, subchondral bone, cartilage, tendons, and ligaments. However, alterations in pain perceptions as in

complex regional pain syndrome or fibromyalgia can also induce arthralgia. Arthralgia can have multiple causes. Most common

etiologies of arthralgia are joint diseases arising from inflammation, cartilage degeneration, infection, crystal deposition, and

trauma which require rheumatologic or orthopedic care. However, during the internal medicine clinical practice, we often

encounter arthralgia associated with common medical conditions other than rheumatic diseases. In this session, I would like

to discuss arthralgia associated with endocrine diseases such as diabetes mellitus, thyroid disorders, chemotherapy and cancer

related arthralgia, and neuropathic arthropathy. How we could recognize these conditions in daily practice will also be

discussed.

(2010. 1. 1∼2010. 12. 31)


Luncheon Symposium (Pfizer)


S17

Learnings from Clinical Development Program: Tofacitinib from Discovery to Approval and Beyond

Pfizer Inc.

Tamas Koncz

The objective of the clinical phases of drug development is to gather detailed safety and efficacy data for an agent of

interest. Clinical drug development typically lasts many years and requires collaboration between the pharmaceutical industry,

regulatory bodies, physicians, healthy volunteers and patients.

The first step, following pre-clinical studies run in vitro in animal models, is Phase 1, which established the basic pharmaco-

kinetic parameters of an agent in humans, evidence of short term safety and tolerability (typically in health volunteers) and

evidence of pharmacologic effect. If Phase 1 demonstrates a favorable pharmacodynamics/pharmacokinetic profile without

unacceptable/unmanageable safety issues, the agent can move into Phase 2. Phase 2 typically begins with proof of concept

studies, which allow the efficacy and safety of a new therapy to be evaluate in the target population of interest, with the

maximum dose tested based on Phase 1 data and learnings from the pre-clinical program. Later Phase 2 studies (sometimes

referred to as phase 2b) provide critical information by establishing the dose range and regimen for phase 3 studies and

by demonstrating efficacy and safety over a longer duration of therapy.

Provided Phase 2 demonstrates sufficient efficacy with acceptable safety, the agent can move into Phase 3. Phase 3 clinical

trials are required to address the needs of regulators, but are also designed to address many of the needs of the practicing

physician. Phase 3 clinical trials typically encompass a global population in order to take into account differences that arise

regionally, such as risk factors, co-morbidities and genetic differences. In order to test and confirm the efficacy and safety

profiles that emerge from Phase 2 and to provide reasonable power to detect adverse events, large numbers of patients

are enrolled in these studies.

Upon completion of Phase 3, and the accumulated data demonstrate a favorable benefit:risk profile, the data are then

submitted to regulatory authorities around the world to request marketing authorization of the agent. The regulators will

make a decision based on their own evaluation of the benefit:risk profile.

If the agent is granted marketing authorization, it can be prescribed depending on additional decision made by reimburse-

ment authorities. However, further understanding of the benefit:risk of the agent remains imperative, and as part of the

registration/approval process the manufacturers propose and work with the regulatory agencies to establish the appropriate

post-marketing data collection, including pharmacovigilance to continue to monitor the benefit:risk of the agent.

The presentation will cover the various stages of clinical trials during drug development using tofacitinib as an example to

highlight the journey through a clinical development for Rheumatoid Arthritis and the follow-on indications and approval

process with implications highlighted for ongoing and future research.


S18

Tofactinib in Rheumatoid Arthritis, Clinical Perspective

Department of Internal Medicine, Seoul National University College of Medicine

Eun Bong Lee, M.D., Ph.D.

Rheumatoid arthritis (RA) is a chronic inflammatory polyarthritis, causing deformity of multiple joints, poor quality of life

and even reduced life expectancy in the affected patients. Despite recent development of several biologic disease modifying

anti-rheumatic drugs (DMRARD), newer drugs are still needed due to limited efficacy and tolerability of currently used drugs.

Tofacitinib, an oral synthetic molecular drug targeting janus kinase, was recently applied to treatment of RA. Tofacitinib

showed robust clinical efficacy in broad spectrum of RA patients, which include patients who showed inadequate response

(IR) to methotrexate, disease modifying anti-rheumatic drugs or tumor necrosis factor inhibitors. In methotrexate (MTX) naïve RA patients, head to head comparison with MTX also showed superior efficacy of tofacitinib monotherapy to MTX, current

gold standard DMARD for RA treatment. In addition to its clinical efficacy, tofacitinib was shown to prevent joint destruction

significantly better than MTX in MTX-IR and MTX-naïve RA patients. Tofacitinib showed comparable safety profile as that

of biologic DMARDs. The incidences of serious infection and malignancy were comparable to those of biologic DMARDs.

Incidence of Herpes zoster infection was increased but serious multi-dermatomal infection was rare. Some laboratory abnor-

malities, which include neutropenia, lymphopenia and increase of serum Cr and low density lipoprotein cholesterol were stabi-

lized after initial change.

In conclusion, tofacitinib is a novel oral small molecule inhibitor for treatment of RA, which opened new era of targeted

synthetic DMARD (tsDMARD). It showed superior clinical efficacy in broad-spectrum of RA patients with manageable safety

profile.

(2010. 1. 1∼2010. 12. 31)


Non-scientific Program


S21

융복합창조시대 - 협업에 길이 있다!

(사)한국협업진흥협회 회장, 중앙공무원교육원 원장(전), 서울과학종합대학원 총장(전), 대한민국 백강포럼 회장

윤 은 기

S22 윤은기: 융복합창조시대 - 협업에 길이 있다!

Journal of Rheumatic Diseases Vol. 21, Suppl. 2, November, 2014 S23


S28

선택진료비 사례에서 본 보건의료정책 결정과정

보건복지부 보험급여과

손 영 래

보건의료정책은 그 정책의 성격과 규모, 형식에 따라 다양한 입안과정을 거치게 된다. 이러한 과정에서 정부 뿐만 아니라 국회, 시민사회,

언론, 이해관계자 등의 참여가 필수적이다. 특히, 정책의 영향이 크고 자원 소요가 큰 정책일수록 정책 입안과정은 어려우며, 정책창

(Policy-Window)을 열기 위한 과정은 복잡하다. 또한 보건의료 정책은 현실에서의 문제를 해소하기 위한 목적을 가지고 입안되나 한편으로

다양한 이해관계의 상충을 조정하는 과정을 거치게 된다. 이러한 과정에서 당초의 정책목적 이외에도 해당 정책으로 인한 변화가 보건의료의

다른 부문, 또는 문제점에 대하여 영향을 끼치게 되는 가능성을 평가하게 되며, 이러한 과정에서 가급적 상호 긍정적인 작용을 하기 위한

정책 변형을 거치게 되거나, 다른 부문의 부작용을 최소화할 수 있는 보완과정을 거치게 된다. 이러한 보건의료정책의 복잡한 입안과정과

조정, 변형 과정을 선택진료비 개편과정을 통해 설명하고자 한다.

(2010. 1. 1∼2010. 12. 31)


Stem Cells for Rheumatologists:

from Bench to Bedside


S31

Stem Cells: Basics to Applications

Department of Microbiology, Chonbuk National University Medical Shool, Jeonju 561-182, Korea

Myung-Kwan Han

Stem cells are unspecialized cells capable of renewing themselves through cell division, and, under certain physiologic or

experimental conditions, they can be induced to become tissue- or organ-specific cells with special functions. Recent re-

searchers primarily worked with two kinds of stem cells: embryonic and somatic stem cells. Embryonic stem cells from mouse

was derived from early mouse embryos nearly 30 years ago, in 1981. The detailed study of the biology of mouse stem cells

led to the derivation of human embryonic stem cells from human embryo in 1998. In 2006, it has been shown that the

transduction of some allow some specialized adult cells to be "reprogrammed" genetically to assume an embryonic stem

cell-like state, called induced pluripotent stem cells (iPSCs). Because of their unique regenerative abilities, stem cells have

many potentials for treating diseases such as diabetes, and heart disease. However, much work remains to be done in the

laboratory and the clinic to understand how to use these cells for cell-based therapies to treat disease, which is also referred

to as regenerative or reparative medicine. Here, the basic characteristics of embryonic and somatic stem cells and, their

applications will be concisely introduced.


S32

Immune Modulation Property of Mesenchymal Stem Cell

연세대학교 의과대학 내과

박 용 범

중간엽줄기세포(mesenchymal stromal cell, mesenchymal stem cell, MSC)는 중간엽 유래의 인체 조직에서 유래된 기질세포로 연골,

골세포 등으로 분화가 가능하다. 기존의 대부분 연구들은 이러한 분화기능을 이용한 재생치료를 다루었다.

MSC의 다른 중요한 기능은 면역조절기능으로 중간엽줄기세포가 면역반응의 각 단계에 작용하여 면역조절 작용을 나타내며, 그 결과는

면역반응의 억제 및 항염증반응으로 나타난다.

중간엽줄기세포는 항염효과 및 면역능을 조절할 수 있음이 알려지면서 그것이 분비하는 여러 싸이토카인(cytokine)에 의한 paracrine

효과가 증명되고 있다. 특히 골수, 제대혈, 지방 등으로부터 비교적 쉽게 수득이 가능하여, 자가세포 치료제로 재생의학 측면에서 임상적용이

많이 된 세포이다.

중간엽줄기세포의 재생효과(regeneration) 성질은 잘 알려져 있고 많은 연구가 진행되고 있는 반면, 중간엽줄기세포가 생체 내에 들어가

면 숙주의 면역 반응을 일으키는 것은 당연히 예견되는 일임에도 불구하고, 생체 내 반응에 대한 면역학적 기전(면역조절 및 항염증 기능)은

많이 연구되어 있지 않다.

최근 중간엽줄기세포의 면역조절 기능을 이용하여 몇몇 염증질환에서 중간엽줄기세포 치료가 시도되고 있다. 다발성 경화증(multiple

sclerosis), 전신홍반루푸스(systemic lupus erythematosus), 크론병(Crohn's disease)이나 궤양성 대장염(ulcerative colitis)과 같은 염증

성 장질환, 그리고 이식편대숙주질환(graft-versus-host disease) 등이 있으며, 현재 임상 실험들이 진행되고 있는 상황이다.

류마티스 관절염에서 중간엽줄기세포를 이용하여 류마티스 관절염의 염증을 조절한다면, 기존의 항류마티스약제나 생물학적 제제보다 훨씬

안전하고 효과적인, 획기적이고 근본적인 새로운 치료법이 될 것으로 기대된다.

본 강의에서는 중간엽줄기세포의 수지상세포에 대한 면역조절 기능과, 중간엽줄기세포의 T 세포에 대한 면역조절 기능, 그리고, 콜라겐

유발 관절염(CIA) 모델에서 최상의 치료 효과를 위한 최적의 중간엽줄기세포군, 세포수 및 그 기전 등을 이야기하고자 한다.


S33

Induced Pluripotent Stem Cells for Rheumatic Diseases

The Catholic University of Korea

Ji Hyeon Ju

Patient-derived induced pluripotent stem cells (PD-iPSC) are spotlighted for its potential application in molecular diagnosis

and self-tolerant cell source for cell therapy. We established PD-iPSC bank (Catholic Repositories of iPSC: CRiPS) and a

comprehensive registry (Catholic Arthritis Registry: CARe) of patients with autoimmune diseases such as rheumatoid arthritis,

systemic lupus erythematosus, Sjogren syndrome, Behcet disease, vasculitis, inflammatory myopathy and so on. PD-iPSCs

of 10 different autoimmune diseases were generated and more than 100 clones were established. We think that established

autoimmune iPSCs can be a good platform for disease modeling, drug screening and relevant research tool in a dish.

Recent progress in gene editing using Zinc Finger Nuclease (ZFN), Transcription activator-like effector nuclease (TALEN)

and CRISPR (clustered regularly interspaced short palindromic repeats) techniques makes it possible to directly modulate genes

in stem cell. We applied CRISPR method to edit stem cell gene. Several target genes were successfully inhibited by gRNA.

Suppression of TAP1 protein using CRISPR down-regulated the expression of HLA class I molecule. Down regulated HLA

Class I molecule was shown by FACS analysis and immunofluorescence staining. It might mean that immunogenicity of stem

cell could be overcome by diminished HLA molecule.

Gene editing will be common process for acquiring good quality stem cell and immunologically tolerant cells in future.

Furthermore, more precise disease simulation will be feasible if we could target the specific gene and modulate it.

(2010. 1. 1∼2010. 12. 31)


What is New?


S37

Update of Foot and Ankle Surgery in Rheumatoid Arthritis

가톨릭의대 서울성모병원 정형외과

안 재 훈

류마티스 관절염은 발과 발목을 종종 침범하는 전신 질환으로 약 20%의 환자들에서는 발 부위에서 그 증상이 처음 나타난다고 한다.

시간이 지나면 대부분의 환자들에서 발과 발목 부위의 증상이 발생하는 데, 투약이나 깔창, 보조기 등의 비수술적인 방법으로 치료를 충분히

했는데도 불구하고 증상이 완화되지 않을 경우는 수술이 필요하게 된다.

전족부의 류마티스 관절염

류마티스 관절염에 의한 전족부의 침범은 발 부위 중에서 가장 많이 일어나며 처음에는 중족-족지 관절의 활막염에 의한 동통 및 부종이

주된 증상이나 시간이 지남에 따라 관절 변형으로 인한 증상이 발생하게 된다. 대표적인 변형은 족무지의 외반 변형이며 보통의 무지외반증

환자에 비해 그 정도가 심하다. 소족지에서는 활막염이 진행하면서 중족-족지 관절의 아탈구 또는 탈구가 일어나게 되고 이는 다시 이차적으

로 망치 족지, 갈퀴 족지 등의 변형으로 이어지며 결국 족저부의 중족골 두 위치에서 피부 못이 발생하여 환자는 보행시 동통 및 피부

궤양 등을 호소하게 된다.

치료의 주 목적은 통증의 경감 및 보행 기능의 향상으로서 수술 방법으로는 활막 절제술, 절제 관절성형술, 관절고정술, 인공관절 치환술

등이 있다. 초기의 염증기에는 침범된 관절의 활막 절제술만을 시행할 수도 있으나, 진행된 심한 변형에 대한 가장 정통적인 재건 수술

방법은 족무지 관절에는 관절고정술을 시행하고 소족지 관절은 절제 관절성형술을 시행하는 술식이다. 족무지에서 관절고정술을 시행하는

이유는 술후 동통의 감소가 확실하고, 안정성을 제공하여 재발을 최소화하며, 보행 시 충분한 체중 부하를 가능하게 하는 점 등이다. 고정술을

시행할 때는 그 위치가 중요하며 외반 15~30도, 신전 15도 정도에서 고정될 때 지면이나 신발에 의한 자극이 최소화되므로 이상적이라고

알려져 있다. 술자에 따라 족무지의 관절고정술 대신에 절제 관절성형술을 시행하여 관절 운동을 보존하는 경우도 있으나 재발의 가능성이

높고 족지가 위로 올라가는 변형이 발생할 수 있는 단점이 있다. 최근 들어 중족-족지 관절의 파괴가 심하지 않은 무지 외반 변형이 류마티스

관절염 환자에서 발생한 경우 관절고정술 대신에 일반적인 무지 외반증 술식인 중족골 절골술 등을 이용하여 치료하는 경우도 보고되고

있으며, 이는 관절 운동을 보존하는 장점이 있는 반면 관절고정술에 비해 변형이 재발할 가능성이 높다는 점을 고려하여 수술 전에 환자와

충분히 상의한 후 시행되어야 한다. 소족지 관절이 침범된 경우 시행되는 절제 관절성형술은 중족골 두를 절제하여 탈구된 관절이 제

위치로 오게 하는 술식으로서 충분한 길이의 골을 제거하고 체중 부하가 되는 족저 부위에 원위 족지골이나 남은 골 조각 등이 튀어나오지

않도록 주의를 기울이면 수술 결과가 좋은 것으로 보고되고 있다. 모든 소족지 관절을 동시에 수술하는 경우에는 제2 중족골에서 제5

중족골로 갈수록 조금씩 더 짧아지게 하여 중족골 경사(metatarsal break)를 유지하는 것이 중요하다. 소족지에서도 아탈구된 중족-족지

관절의 파괴가 심하지 않은 경우 관절을 절제하지 않고 단순히 정복하면서 중족골 절골술을 통하여 단축함으로써 관절을 보존하는 술식이

시도되고 있으나 장기적인 결과는 아직 발표되지 않고 있다.

중족부의 류마티스 관절염

류마티스 관절염에서 중족부인 중족-족근 관절을 침범하는 경우는 흔하지 않으며, 방사선 사진상의 변화에 비해서 임상 증상은 심하지

않은 경우도 많다. 하지만 방사선 사진상 관절의 파괴와 함께 심한 동통이나 변형 등이 발생할 경우는 중족-족근 관절의 관절고정술을

이용하여 주로 치료하게 된다. 관절고정술은 족배부로 종 절개를 가한 후 나사나 금속판 등을 이용하여 고정하게 된다.

S38 안재훈: Update of Foot and Ankle Surgery in Rheumatoid Arthritis

후족부의 류마티스 관절염

후족부에서는 거골하 관절과 거주상 관절이 주로 침범되며 거골하 관절의 진행성 활막염과 함께 후경골 건의 파열이나 부전 등에 의해

외반 변형 및 편평족 변형이 발생하게 된다. 거골하 관절이나 거주상 관절이 침범된 경우 환자는 발목이 아프다고 호소하는 경우가 많으므로

그 감별 진단에 주의해야 한다.

후족부에 대한 수술적 치료는 병변의 정도에 따라서 활막 절제술, 관절고정술 등이 시행될 수 있다. 거골하 관절에 대하여 단독으로

활막 절제술을 시행하는 경우는 흔하지 않으나 후경골건의 활막염(tenosynovitis)이 심한 경우는 건활막절제술(tenosynovectomy)을 시행

하는 경우도 있다. 거골하 관절이나 중족근 관절에서 관절의 침범 및 변형이 심한 경우는 거골하 관절이나 거주상 관절만의 단독 관절고정술

이나 거골하 관절 및 중족근 관절을 같이 고정하는 삼중 관절고정술을 시행하게 된다. 최근에는 후족부를 침범한 류마티스 관절염에서

단일 광자 방출형 CT-CT (SPECT-CT)를 이용하여 거골하 관절 및 중족근 관절의 침범 정도를 확인하고 선택적으로 관절고정술을 시행하여

좋은 결과를 얻었다는 보고도 나오고 있다.

발목 관절의 류마티스 관절염

류마티스 관절염에서 발목 관절을 침범하는 경우는 다른 부위에 비해 그 빈도가 높지는 않으며 다발성 관절염의 약 9% 정도에서 발생한다

는 보고가 있다. 임상적으로 발목 부위의 부종과 압통 등을 관찰할 수 있으며 환자는 보행시 통증을 호소하게 된다. 발목 주위 관절인

거주상 관절이나 거골하 관절의 병변과 감별이 중요하며 기립 상태에서 방사선 사진을 찍으면 관절 간격의 협소 및 변형의 정도 등을

쉽게 파악할 수 있다.

수술적 치료는 먼저 중등도 이상의 활막염이 비수술적인 치료에도 6개월 이상 반응을 하지 않는 경우 활막 절제술을 고려하는 데, 최근

추세는 크게 절개하여 시행하는 것보다는 관절경술을 이용하여 최소침습적인 방법으로 절제술을 시행함으로써 환자의 빠른 회복을 돕는

것으로 바뀌고 있다. 관절의 파괴나 변형이 심한 경우는 발목의 관절고정술이 일차적인 수술 방법이며 전통적으로는 관혈적 방법으로 큰

절개를 통하여 시행하였으나 근래에는 역시 관절경적 관절고정술을 통하여 환자의 동통이나 불편감을 줄이면서 더 빠른 관절 유합을 기대할

수 있다. 고정의 위치는 외반 5도, 중립 굴곡 및 외회전 5도의 위치가 가장 기능적이라고 보고되고 있다. 한편 발목 관절의 인공관절

치환술은 최근 들어 그 적용이 늘어나고 있으며 어떤 의미에서는 류마티스 관절염 환자가 가장 적절한 수술 대상이라고 할 수 있는 데

이는 류마티스 관절염의 경우 발목 및 후족부의 여러 관절을 동시에 침범하면서도 그 변형이 큰 경우가 많지 않으며, 수술 후 관리의

측면에서도 환자들의 활동 정도가 심하지 않아 인공관절의 수명이 길어질 수 있는 이점이 있기 때문이다.

결론

발 및 발목 부위의 류마티스 관절염은 환자의 삶의 질에 심각한 장애를 초래하는 질환으로 상당 기간의 비수술적인 치료에도 반응을

하지 않는 경우는 그 부위 및 정도에 따른 적절한 수술을 시행함으로써 좋은 결과를 기대할 수 있다. 하지만 류마치스 관절염 자체의

특성과 강력한 항류마티스 제제의 사용으로 인해 술후 창상 치유나 골유합에 지장이 초래될 수 있다는 점은 수술의 결정 및 술후 관리에서

항상 주의를 기울여야 한다. 최근에는 전통적인 관절고정술과 절제 관절성형술 외의 방법을 이용하여 환자의 관절을 되도록 보존하려는

술식이 조심스럽게 시도되고 있으나 이러한 방법이 널리 받아들여지기 위해서는 좀 더 장기적인 결과의 뒷받침이 필요한 상태이다.

참고문헌

1. Abdo RV, Iorio LJ. Rheumatoid Arthritis of the Foot and Ankle. J Am Acad Orthop Surg. 1994;2:326-32. 2. Ahn JH. Operative treatment - Rheumatoid arthritis in foot and ankle. Pract Rheumatology. 2014;8:32-36.3. Jaakkola JT, Mann RA. A review of rheumatoid arthritis affecting the foot and ankle. Foot Ankle Int. 2004;25:866-74.4. Nassar J, Cracchiolo A. Complications in surgery of the foot and ankle in patients with rheumatoid arthritis. Clin Orthop.

2001;391:140-52.5. Trieb K. Management of the foot in rheumatoid arthritis. J Bone Joint Surg-Br. 2005;87:1171-7.


S39

Inflammatory Myopathy

Department of Internal Medicine (Rheumatology), Kyungpook National University School of Medicine, Daegu, Korea

Eon Jeong Nam

S40 Eon Jeong Nam: Inflammatory Myopathy


소아특발관절염(Juvenile Idiopathic Arthritis)

가톨릭대학교 의과대학 소아과학교실

정 대 철

소아특발관절염 (juvenile idiopathic arthritis, JIA)는 16세 이하의 소아 청소년 연령의 환자에서 뚜렷한 원인 없이 6주 이상이 지속되는

관절염으로서 한 가지 질환으로서 언급할 수 없다. 선진국에서는 10만명당 2-20명의 발생빈도와 16-150명의 유병률을 보이고 있다. 전신형

(systemic JIA, sJIA)는 남녀간의 차이가 없으나 다른 JIA는 여아가 남아보다 2배정도 많다. 아직 정확한 원인과 발생기전이 알려져 있지

않다. 발병기전과 유전적 원인으로는 HLA유전자와 HLA와 연관없는 싸이토카인과 연계된 유전자가 관련하여 환경적 요인에 의해 면역관용

과 염증의 불균형으로 발생한다고 생각된다. sJIA는 자가면역으로 발생하는 다른 JIA와 달리 자가염증 (autoinflammatory)으로 나타난다.

현재 JIA는 국제류마티스학회 (international league of association for Rheumatology)에서 제안된 합의에 따라 분류하여 진단하고

있다. 전신형 (sJIA), 소수관절형 (oligoarticular), 다수관절형 (polyarticular), 피부병변과 관련된 건선형 (Psoriatic), HLAB27양성의 인대

염증 연관형 (enthesitis-related), 비분류형 관절염으로 분류하고 있다. 증상이 발현되어 첫 6개월에 4개이하의 관절을 침범하는 경우

소수관절형으로 진단하고 첫 6개월이내에 4개이하의 관절로 국한된 경우는 지속형 소수관절형 (persistent oligoarticular)으로, 4개이상의

관절로 변화되면 확대형 소수관절형 (extended oligoarticular)으로 진단한다. 4개이상의 관절을 침범한 경우를 다수관절형으로 진단하며

rheumatoid factor (RF)의 양성에 따라 분류한다. RF양성 다수관절형은 성인과 매우 유사하지만, 전체 JIA 중 10%이내로서 대부분의

JIA는 RF가 음성이다. 관절과 관계없이 포도막염 (uveitis)가 동반되는 경우가 많으며 소수관절형에서 약 30%, RF-음성 다수관절형과

건선형 JIA에서 각각 10%정도 확인된다. 또한, ANA양성은 소수관절형에서 약 60%, 다수관절형에서 40%, 건선형에서 50%에서 확인된다.

JIA의 치료에 평가 및 질병활성도는 환자와 의사의 평가, 침범된 관절수와 혈액검사 지표를 기준으로 ACR30을 일반적으로 사용한다.

JIA에서 사용되는 대표적인 기능적 평가인 childhood health assessment questionnaire (CHAQ)은 성인의 HAQ과 유사하지만 성장과

발달에 따라 모든 연령에서 할 수 있는 항목을 추가하여 7세 이상에서 평가한다. 성인의 질환 활성도로 가장 많이 사용되는 DAS28는

소아연령에 부합하지 않는 경우가 많아 유럽의 PRINTO에서 제시한 JADAS (juvenile arthritis disease activity score)가 사용되고 있으며

JADAS는 의사의 평가, 환자 및 보호자의 평가, 활동성 관절의 개수와 급성염증지표를 이용한다. 관찰하는 관절수에 따라 JADAS-27,

JADAS-10, JADAS-71으로 구분하여 평가하며 성인의 DAS28이나 CDAI보다 유용한 것으로 알려져 있다.

JIA가 진단된 이후 약물 치료는 성인과 유사하여 비스테로이드 항염증약물 투여를 기본으로 하고 DMARD로서 저용량의 methotrexate를

사용하고 있다. 이러한 약제투여에도 증상이나 징후가 지속될 경우 생물학적 제제 (biological agents)를 사용하게 되며 항 TNF 제제가

흔하게 사용된다.

JIA환자의 약 1/3 정도가 사춘기를 지나 성인에 이르면서도 지속적인 면역억제치료를 하면서 성장한다. 특히, JIA는 합병증으로서 성장

지연과 국소적인 성장의 불균형이 올 수 있다. 따라서 JIA의 관리를 철저하게 하여야 하며 성인이 되는 과정에서 이행 관리 (transitional

care)가 필요하다. 이행 관리는 사춘기 초기부터 시작하여 류마티스 내과와 소아과가 협진하면서 통합된 진료가 이루어지도록 하여야 한다.

JIA에 대한 진단에 따른 경과 및 치료의 반응에서 차이가 있어 최근 JIA에 대한 새로운 진단 분류에 대한 논의가 계속되고 있다. 특히,

sJIA의 진단의 경우 관절염이 없어도 증상이 현저하게 나타나는 경우가 많아 adult onset Still disease의 상대적인 의미로서 Still disease로

분류하자는 의견들이 있다. ANA양성이면서 어린 시기에 발생한 관절염의 경우 침범된 관절수나 건선과 무관하게 질환이 경과하기에 ANA에

따른 새로운 분류에 대한 의견도 있다.

S48 정대철: 소아특발관절염(Juvenile Idiopathic Arthritis)

참고문헌

1. Cassidy JT, Petty RE, Laxer RM, Lindsley CB. Textbook of Pediatric Rheumatology. 6th ed, p. 211-35, Philadelphia, Saunders, 2011.

2. Petty RE, Southwood TR, Manners P, Baum J, Glass DN, Goldenberg J, et al: International League of Associations for Rheumatology. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001, J Rheumatol 2004;31:390-2.

3. Ravelli A, Martini A: Juvenilie idiopathic arhtiris. Lancet 2007;369:767-8.4. Brunner HI, Ravelli A: Developing outcome measures for paediatric rheumatic disease. Best Prat Res Clin Rheumatol

2009;23:609-24.5. Ruperto N, Pistorrio A, Ravelli A, et al: Criteria to define response to therapy in paediatric rheumatic disease. Eur J

Clin Pharmacol 2011;67(suppl 1):S125-31.6. Gianninin EH, Ruperto N, Ravelli A, Lovell DJ, Felson DT, Martini A: Preliminary definition of improvement in juvenile

arthritis. Arthritis Rheum 1997;40:1202-9.7. Consolaro A, Ruperyto N, Bazso A, Pistorio A, Magni-Manzoni S, Filocamo G, et al. Development and validation of a

composite disease activity score for juvenile idiopathic arthritis. Arthritis Rheum 2009;61:658-66.8. Singh G, Athreva BH, Fries JF, Goldsmith DP: Measurement of health status in children with juvenile idiopathic arthritis.

Arthritis Rheum 1994;37:1761-9.9. MaEriane F, Beresford MW, Baildam EM, Thomson W, Hyrich KL: Recent developments in disease activity indices and

outcome measures for juvenile idiopathic arthritis. Rheumatology (Oxford) 2013;52:1941-51.10. Duffy CM: Measurement of health status, functional status, and quality of life in children with juvenile idiopathic arthritis:

clinical science for the pediatrician. Rheum Dis Clin North Am 2007;33:389-402.11. Prakken B, Albani S, Martini A: Juvenile idiopathic arthritis. 2011;377:2138-49.12. Martini A: It is time to rethink juvenile idiopathic arthritis classification and nomenclature. Ann Rheum Dis 2012;71:1437-9.13. Coulson EJ, Hanson HJ, Foster HE: What does an adult rheumatologist need to know about juvenile idiopathic arthritis?

Rheumatology (Oxford) 2014;pii:keu257. [Epub ahead of print].

pp


(2010. 1. 1∼2010. 12. 31)

Journa l o f R heum atic D iseases

Vol. 21, Suppl. 2, November, 2014

2014년 10월 21일 인쇄 2014년 10월 27일 발행

발행인：이 수 곤 편집인：전 재 범 기획인：차 훈 석

발 행： 대한류마티스학회140-012, 서울시 용산구 한강로 2가 2-36번지 한강 현대하이엘 803호Tel: 02-794-2630, Fax: 02-794-2631E-mail : [email protected] : www.rheum.or.kr

편집제작：WITHIN(위드인)153-803 서울시 금천구 가산디지털 1로 137(가산동 371-16) IT캐슬 2차 401호Tel : 02-6959-5333, Fax : 070-8677-6333E-mail : [email protected]

＜pISSN 2093-940X＞＜eISSN 2233-4718＞

Publisher：Soo-Kon Lee Editor in Chief：Jae-Bum Jun

Published byKorean College of Rheumatology

Office of Executive Secretary#803 Hangang Hyundai Hiel, 2-36 Hangangno

2-ga, Yongsan-gu, Seoul 140-012, Korea Tel：82-2-794-2630, Fax：82-2-794-2631 E-mail : [email protected] Homepage : www.rheum.or.kr

이 발표논문집은 2014년도 정부재원으로 한국과학기술단체총연합회의 지원을 받아 발간되었음

This work was supported by the Korean Federation of Science and

Technology Societies Grant funded by the Korean Government.

journal of rheumatic diseases · 2018-04-04 · pppp journal of rheumatic diseases (2010. 1....

Documents