강직성척추염환자에서대동맥박리를동반한마르팡증후군 1 예

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1 대한내과학회지 : 제 84 권제 6 호 강직성척추염환자에서대동맥박리를동반한마르팡증후군 1 예 을지대학교의과대학내과학교실 류지원 박지영 송은주 허진욱 A Case of Aortic Dissection with Marfan Syndrome and Ankylosing Spondylitis Ji Won Ryou, Ji Young Park, Eun Ju Song, and Jin-Wuk Hur Department of Internal Medicine, Eulji University College of Medicine, Seoul, Korea A 33-year-old male presented with an acute onset of back pain and abdominal pain. He was cm tall and had an arm span of 194 cm, and had mild pectus carinatum as well as arachnodactyly. Plain radiographs showed kyphoscoliosis of the lumbar spine, bamboo spine of the thoracic spine, and sacroiliitis of the pelvis. Abdominal computed tomography revealed debakey type 3 aortic dissection. We prescribed beta blockers to control his blood pressure. According to the modified New York criteria, we diagnosed him with HLA negative ankylosing spondylitis and initiated therapy with nabumetone and sulfasalazine. We later diagnosed Marfan syndrome based on the Ghent criteria and mutation screening at the fibrillin-1. After treatment, he has been followed up without symptoms or complications. (Korean J Med 2013;84: ) Keywords: Marfan syndrome; Aortic dissection; Ankylosing spondylitis INTRODUCTION Marfan syndrome is caused by a mutation of the genes encoding fibrillin-1 (FBN1) [1,2]. Aortic dissection is prevalent in patients with Marfan syndrome and is caused by the mutation of the genes encoding FBN1 and type III procollagen [3]. Ankylosing spondylitis is an HLA-B27-associated inflammatory disease that affects mainly the sacroiliac joints and axial skeleton. It may also cause extraskeletal manifestations, such as acute anterior uveitis, aortic insufficiency, and cardiac conduction disturbances. The mutation of the FBN1 gene or a cell-mediated auto-immune response in ankylosing spondylitis are common pathologic sequelae [4]. Aortic dissection is particularly prevalent in patients with Marfan syndrome and Ehlers-Danlos syndrome. Mutation of the FBN1 gene and type III procollagen have been implicated in some cases. The coexistence of Marfan syndrome and ankylosing spondylitis has been reported only twice in the literature [4,5], and furthermore, aortic dissection with coexistence of Marfan syndrome and Received: Revised: Accepted: Correspondence To Jin-Wuk Hur, M.D., Ph.D. Division of Rheumatology, Department of Internal Medicine, Eulji University College of Medicine, 14 Hangeulbiseok-gil, Nowon-gu, Seoul , Korea Tel: , Fax: , rheumatism@eulji.ac.ar Copyright c 2013 The Korean Association of Internal Medicine This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

- The Korean Journal of Medicine: Vol. 84, No. 6, 2013 - ankylosing spondylitis has never been reported. Thus, we report this rare case and review the literature.

He had limited chest expansion (2 cm), but no restriction in lumbar spine In February 2007, a 33-year-old male presented with acute back pain and abdominal pain.

9 cm tall, weighed 85 kg, and had an arm span of 194 cm. He had mild pectus carinatum and arachnodactyly.

2 - The Korean Journal of Medicine: Vol. 84, No. 6, ankylosing spondylitis has never been reported. Thus, we report this rare case and review the literature. CASE REPORT spinal pain with morning stiffness which lasted for more than an hour, and which improved with exercise. He also reported intermittent buttock pain. The Patrick s test was positive. He had limited chest expansion (2 cm), but no restriction in lumbar spine In February 2007, a 33-year-old male presented with acute back pain and abdominal pain. At admission, he had a systolic and diastolic blood pressure of 170/100 mmhg, a heart rate of 80/min, and a body temperature of On examination he was cm tall, weighed 85 kg, and had an arm span of 194 cm. He had mild pectus carinatum and arachnodactyly. Abdominal radiographs showed kyphoscoliosis of the lumbar spine and a plain anterioposterior radiograph of the pelvis showed sacroiliitis (Fig. 1). Plain anterioposterior and lateral views of the lumbar spine showed scoliosis and lordosis of the lumbar spine (Fig. 2). A plain lateral view of the thoracic spine showed kyphosis and syndesmophytes (Fig. 3) and pelvic bone computed tomography (CT) showed sacroiliitis at the sacroiliac joint (Fig. 4). He presented with a 6-month history of predominantly lumbar Figure 1. Plain anterioposterior view of the pelvis showed bilateral sacroiliitis (black arrow). A B Figure 2. Plain anterioposterior (A) and lateral views (B) of the lumbar spine revealed scoliosis and lordosis of the lumbar spine

Ji Won Ryou, et al. Marfan syndrome and AS Figure 5. Computed tomography revealed Debakey type 3 aortic dissection (white arrow). Figure 3.

Magnetic resonance imaging of both sacroiliac joints showed an irregular articular surface and mild subchondral sclerosis without a bone marrow edema pattern.

Therefore, we diagnosed him with HLA-B27 negative ankylosing Figure 4.

There is a subchondral cyst (white arrow) at the iliac side of the left inferior sacroiliac joint (bilateral grade 2 sacroiliitis according to the New York criteria).

3 Ji Won Ryou, et al. Marfan syndrome and AS Figure 5. Computed tomography revealed Debakey type 3 aortic dissection (white arrow). Figure 3. Plain lateral view of thoracic spine showed kyphosis and a syndesmophyte (black arrow). Figure 6. Magnetic resonance imaging of both sacroiliac joints showed an irregular articular surface and mild subchondral sclerosis without a bone marrow edema pattern. Also, mild erosion (white arrow) was present at the iliac side of the left inferior sacroiliac joint. at 4.19 mg/dl. Rheumatoid factor and HLA-B27 were negative. Therefore, we diagnosed him with HLA-B27 negative ankylosing Figure 4. Pelvic bone computed tomography showed narrowing of both sacroiliac joint spaces, and an irregular articular surface (white wedge). There is a subchondral cyst (white arrow) at the iliac side of the left inferior sacroiliac joint (bilateral grade 2 sacroiliitis according to the New York criteria). spondylitis based on the modified New York criteria. Computed tomography images of the abdomen and chest showed DeBakey type 3 aortic dissection (Fig. 5). We controlled the patient s blood pressure with beta blockers and started him on nabumetone and sulfasalazine to treat the ankylosing spondylitis. movement. On laboratory testing, he had an elevated erythrocyte After the first week, his CRP decreased to 1.05 mg/dl. Magnetic sedimentation rate (ESR) at 32 mm/hr, and C reactive protein (CRP) resonance imaging showed sacroiliitis of both sacroiliac joints and

4 - 대한내과학회지 : 제 84 권제 6 호통권제 634 호 dural ectasia of the lumbar vertebral bodies (Fig. 6). Symptoms of Marfan syndrome; i.e., scoliosis, pectus carinatum, dilatation of the ascending aorta without aortic regurgitation on echocardiography, and dural ectasia affecting the lumbosacral spinal canal, were present. To confirm the presence of Marfan syndrome, a molecular study of the FBN1 gene was performed and a mutation of FBN1 on Chromosome 15q21.1 was identified. Thus, we diagnosed him with Marfan syndrome based on the Ghent criteria and mutation screening of FBN1. During treatment, his abdominal pain and back pain improved, after which he was discharged and has been followed up for 1 month without symptoms or complications. DISCUSSION Marfan syndrome is a heritable connective tissue disease first described by Bernard Antoine Marfan in The syndrome affects articular and non-articular structures, and can affect the eye and ascending aorta, resulting in significant morbidity. The syndrome is diagnosed using the Ghent criteria, which our patient satisfied, so we diagnosed him with Marfan syndrome. Marfan syndrome is inherited as an autosomal dominant trait. The disease is caused by a mutation of the gene encoding fibrillin-1, which is on the long arm of chromosome 15 [1]. Fibrillin-1 is a major component of extracellular matrix structures known as microfibrils, and mutation of the gene alters the structure of fibrillin-1, which contributes to the articular and non-articular features of the disease [1]. Thus, aortic dissection is prevalent in patients with Marfan syndrome, as it results from mutation of the FBN1 genes and type III pro-collagen. However, a correlation between the genotype and the cardiovascular phenotype has not yet been established. Identification of the mutation in the FBN1 and TGFBR2 genes in family members should be conducted at preventive checkups [3]. For this patient, the mutation study of the FBN1 gene was performed to confirm a clinical diagnosis of Marfan syndrome and the mutation of FBN1 on Chromosome 15q21.1 was identified. We will screen his family members for other genetic mutations. Ankylosing spondylitis is an HLA-B27-associated inflammatory disease that mainly affects the sacroiliac joint. It may also involve peripheral joints and can manifest extra-skeletally, causing acute anterior uveitis, aortic insufficiency, and cardiac conduction disturbances. Diagnosis is achieved according to the modified New York criteria. To confirm the clinical diagnosis, a patient should have the presence of radiographic sacroiliitis plus any one of the following three criteria: a history of inflammatory back pain, limitation of motion of the lumbar spine, or limited chest expansion. Our patient was diagnosed with ankylosing spondylitis based on radiographic sacroiliitis, inflammatory back pain, and limited chest expansion. Ankylosing spondylitis begins with fibrosis and ossification of cartilage with enthesis, eventually leading to ankylosis and loss of mobility of affected joints. The coexistence of Marfan syndrome and ankylosing spondylitis has been reported only twice in the literature. Fietta, et al. [4] reported the first case, in which transthoracic echocardiography showed a prolapsed posterior mitral leaflet and mild aortic insufficiency with no aortic dilatation. Kiss C, et al. [5] reported the second case, in which echocardiography showed dilatation of the ascending aorta, mitral valve prolapse, and mild mitral insufficiency. In Marfan syndrome, cardiovascular abnormalities are a major source of morbidity and mortality. Also, ankylosing spondylitis patients may present with cardiac abnormalities. Takagi et al. [6] described the first reported case of Stanford type A (DeBakey type 1) acute aortic dissection without Marfan syndrome in HLA-B27-negative ankylosing spondylitis. Simkin, et al. [7] suggested that fibrillin-1 may be involved in the pathogenesis of spondylitic inflammation of the aorta and the eye as well as of bones and joints. Thus, the defective structure of fibrillin-1 in microfibrils or elastin fibers may account for the wide spectrum of clinical manifestations of Marfan syndrome and ankylosing spondylitis [7,8]. Additionally, the genetic mutation of fibrillin-1 in ankylosing spondylitis may cause aortic dissection. Our case may support the hypothesis proposed by Simkin, et al. [7] In conclusion, we reported here a rare case of coexistent ankylosing spondylitis and Marfan syndrome with aortic dissection. 중심단어 : 마르팡증후군 ; 강직성척추염 ; 대동맥박리

5 - 류지원외 3 인. 마르팡증후군과강직성척추염 - REFERENCES 1. Dietz HC, Cutting GR, Pyeritz RE, et al. Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene. Nature 1991;352: Pepe G, Giusti B, Evangelisti L, et al. Fibrillin-1 (FBN1) gene frameshift mutations in Marfan patients: genotypephenotype correlation. Clin Genet 2001;59: Waldmüller S, Müller M, Warnecke H, et al. Genetic testing in patients with aortic aneurysms/dissections: a novel genotype/phenotype correlation? Eur J Cardiothorac Surg 2007;31: Fietta P, Manganelli P. Coexistent Marfan's syndrome and ankylosing spondylitis: a case report. Clin Rheumatol 2001; 20: Kiss C, Jónap I, Gergely P, Poór G. Coexistent Marfan's syndrome and ankylosing spondylitis. J Rheumatol 2006; 33: Takagi H, Kato T, Matsuno Y, et al. Aortic dissection without Marfan's syndrome in ankylosing spondylitis. J Thorac Cardiovasc Surg 2004;127: Simkin PA. Acetabular osteitis in ankylosing spondylitis: does fibrillin figure in its pathogenesis? J Rheumatol 2001;28: Fietta P, Manganelli P. Is fibrillin-1 the link between ankylosing spondylitis and Marfan's syndrome? J Rheumatol 2002;29:

A growth disturbance and not a disorder with ligamentous laxity

Marfan Syndrome A growth disturbance and not a disorder with ligamentous laxity 1 in 5,000-10,000 extensive phenotypic variability Fibrillin-1 abnormality Chromsome no. 15 Different forms of mutations