Successful Etanercept Therapy for Refractory Sacroiliitis in a Patient with Ankylosing Spondylitis and Mixed Connective Tissue Disease

The concurrence of ankylosing spondylitis (AS) in a patient with mixed connective tissue disease (MCTD) is rarely described in the literature. Significant and sustained efficacy with tumor necrosis factor (TNF)-alpha blockers has been demonstrated in AS patients. However, evidence to date has revealed associated side effects, including antinuclear antibody induction and development of a lupus-like syndrome. Several authors have reported lupus-like manifestations in MCTD patients treated with TNF-alpha blockers used to control peripheral polyarthritis. In our case report, we demonstrate a good response to etanercept therapy for refractory sacroiliitis in a patient with coexisting AS and MCTD, without development of a lupus-like syndrome. This demonstrates that etanercept therapy may be an appropriate therapeutic agent for sacroiliitis in MCTD patients, as it is in AS alone.

Intima-media Thickness and Arterial Stiffness of Carotid Artery in Korean Patients with Behcet's Disease

Behcet's disease (BD) is a systemic vasculitis involving diverse sizes of arteries and veins. We performed this study to evaluate the vascular changes by assessment of the arterial stiffness and intima-media thickness (IMT) of carotid artery in Korean patients with BD. Forty-one patients with BD and age-, and sex-matched 53 healthy subjects were recruited in this study. Carotid arterial stiffness and IMT were assessed by using high-resolution B-mode ultrasonography. Arterial stiffness parameters such as carotid arterial distensibility coefficient, stiffness index, and incremental elastic modulus (E(inc)) were significantly increased in BD patients compared with those in healthy subjects, but not in IMT. Positive relationship was noted between age and IMT, whereas age of onset was significantly associated with arterial stiffness in BD. This finding suggests impaired endothelial function before visible structural changes of arterial wall in BD. Age and age of onset may be an independent risk factor for carotid IMT and arterial stiffness, respectively. Further studies in more large populations are required to confirm our results.

Association of Interleukin-18 Polymorphisms with Adult Onset Still's Disease in Korea / 대한류마티스학회지

OBJECTIVE: It has been suggested that overproduction of interleukin -18 (IL-18) may contribute to the pathogenesis of adult onset Still's disease (AOSD). Recently, positive association between a polymorphism in the IL-18 gene and different diseases like diabetes, sarcoidosis and asthma has been reported. The aim of the present study was to investigate the potential association of two single-nucleotide polymorphisms (SNPs) at position -137 (G/C) and -607 (C/A) in the promoter region of the IL-18 gene with susceptibility and clinical feature of AOSD in the Korean population. METHODS: We examined two SNPs of IL-18 in 70 patients with AOSD and 204 healthy control individuals. The genotyping were performed using sequence specific PCR. Haplotypes were analyzed by the estimated haplotype program. The patients with AOSD were subdivided into groups according to disease course: monocyclic systemic, polycyclic systemic, and chronic articular type. RESULTS: As for the -607 genotypes, 13 of the 69 patients had CC genotype (18.8%), 36 the CA type (52.2%) and 20 the AA type (29.0%). AOSD patients had higher frequency of A allele at -607 when compared to controls (OR 1.48, 95% CI 1.00~2.18, p=0.048). AOSD patients had significantly higher frequency of AA genotypes at -607 when compared to controls (AA vs CA& CC, OR 1.90, 95% CI 1.01~3.58, p=0.044). As for the -137 genotypes, of the 68 patients, 57 had GG genotype (83.8%), 9 the GC type (13.2%) and 2 (2.9%) had the CC type. No differences were found in allele and genotype frequencies between two groups. The haplotype frequencies of the IL-18 polymorphism were not significantly different between patients with AOSD and controls. The frequency of -137 GG genotype was significantly increased in chronic articular type compared to healthy control and systemic type of AOSD. CONCLUSION: In IL-18 gene polymorphisms, the A allele and AA genotye at position -607 might be genetic risk factors for the development of AOSD in Korean population. Further investigation in larger groups is required to provide more conclusive evidence regarding the role of the IL-18 gene polymorphism in AOSD.

Concurrence of Sjogren's Syndrome in a Patient with Chlamydia-induced Reactive Arthritis: An Unusual Finding

A 40-year-old Korean man presented with painful swelling and tenderness of both ankle joints as well as the plantar surfaces of both feet, along with inflammatory back pain, and a purulent discharge from the urethral orifice. The patient also complained of sicca-like symptoms including dry eyes and dry mouth. An immunological analysis revealed a high titer of rheumatoid factor, positive results for antinuclear antibody and anti-Ro antibody, and a positive result for HLA-B27. An antibody titer for Chlamydia was also significantly increased. Positive results of the Schirmer's test and for keratoconjunctivitis sicca were confirmed by an ophthalmologist. These clinical manifestations were compatible with Chlamydia-induced reactive arthritis (ReA) accompanied by Sjogren's syndrome (SS). This is the first report of the combination of these two distinct disease entities in the Korean population.

A Case of Behcet's Disease with Thin Glomerular Basement Membrane Disease / 대한류마티스학회지

Behcet's Disease (BD) is a chronic inflammatory disorder characterized by vasculitis of unknown cause, involving multiple organs. In the past years, renal involvement has not been regarded as a feature of BD. However, renal lesions in BD, although uncommon, have increasingly been recognized in recent years. Five categories of renal lesions associated with BD have been identified, including glomerulonephritis, amyloidosis, renal vascular involvement, interstitial nephritis, and other problems, such as complications of drug therapy or abnormalities of the genitourinary tract. On the other hand, regional differences in the disease expression of BD are well appreciated. Renal lesions accompanied by BD have rarely been reported in Korea, although it have been described occasionally in the Middle Eastern countries. Hereby, we described a 46-year-old female patient who had BD with persistent hematuria and proteinuria, whose renal biopsy specimens were consistent with thin glomerular basement membrane disease. Interestingly, some portions of her glomerular capillary walls were filled with fuchsinophilic fibrin-like materials.

Limited Polyarteritis Nodosa Presenting as Acute Appendicitis / 대한류마티스학회지

Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis of small and medium-sized muscular arteries that typically involve multiple organs, including peripheral nerve, skin, joint, muscle, gastrointestinal tract, kidney, and heart. In addition to systemic involvement of the classical PAN, localized diseases of the gallbladder, uterus, testis, and skin have been reported. In particular, a limited involvement of the appendix is an unusual manifestation of PAN and usually runs a favorable prognosis when compared with the classical PAN. We described a 13-year-old woman with a limited form of PAN presenting as acute appendicitis without other systemic manifestations. She recovered after exploratory laparotomy and appendectomy without administration of steroid or immunosuppressant.

Successful Treatment of Refractory Thrombocytopenia with Mycophenolate Mofetil in a Patient with Systemic Lupus Erythematosus

While mild thrombocytopenia in systemic lupus erythematosus (SLE) is frequently seen in the context of active disease, severe thrombocytopenia causing significant bleeding is not that common. Corticosteroids are considered the first line therapy for severe thrombocytopenia in SLE. Second-line therapeutic agents or splenectomy have been reported to be effective for patients who fail to respond to steroids or those who require moderate doses of steroids to maintain the platelet counts. Recent randomized controlled studies have shown that mycophenolate mofetil (MMF) is an efficacious and safe therapeutic agent in patients with proliferative forms of lupus nephritis. However, little information has been available regarding the role of MMF in the treatment of immune thrombocytopenia complicated with SLE. Hereby I describe a patient with SLE in whom thrombocytopenia was refractory to corticosteroids, intermittent intravenous cyclophosphamide, azathioprine, cyclosporine, intravenous gamma globulin, danazol, and splenectomy, and whose platelet counts eventually normalized during therapy with MMF. In this patient, thrombocytopenia is initially thought to be associated with active SLE involving major organ. However, after immunosuppressive agents were given, the refractory nature of thrombocytopenia seems to be an isolated phenomenon, independently of SLE activity.

A Limited Polyarteritis Nodosa of the Breast / 대한류마티스학회지

Polyarteritis nodosa (PAN) is a chronic inflammatory disorder characterized by a necrotizing vasculitis of small and medium-sized artery, which can involve several organs, such as, the kidney, skin, peripheral nerves, muscle, heart, and gastrointestinal tract. In addition to systemic involvement of the classical PAN, a localized disease of the gallbladder, uterus, testis, and skin has been reported. In particular, a limited involvement of the breast is an unusual manifestation of PAN and usually runs a favorable prognosis when compared with the classical PAN. We describe a 64-year-old female patient who had a limited disease of PAN on both the breasts. She presented with mass-like lesions on both the breasts. After surgical excision of the breast lesions, she has been doing well with only a low dosage of prednisolone.

Three Cases with Cutaneous Polyarteritis Nodosa / 대한류마티스학회지

Systemic polyarteritis nodosa is a necrotizing vasculitis that involves small and medium-sized muscular arteries in the multiple organ systems, whereas cutaneous polyarteritis nodosa (CPAN) is a localized disease characterized by necrotizing vasculitis of small and medium-sized arteries in the skin without life-threatening organ involvement. CPAN is usually limited to skin, muscle, and joints. It is chronic but takes a benign course. The most common cutaneous manifestations include nodules, ulcers and a livedo reticularis pattern on the extremities. We describe three cases with CPAN showing necrotizing vasculitis on the skin without systemic symptoms or visceral involvement. In Korea, most previously published cases with CPAN have shown a good response to a short term of corticosteroids or colchicine administration. However, two of our three patients required another immunosuppressive agent in addition to corticosteroids to manage their intractable skin lesions, and the remaining one showed a good response to a short course of prednisolone. In addition, there was one patient with CPAN having hepatitis B surface antigen, which might be associated with his refractory skin disease.

Widespread Scleredema Accompanied with a Monoclonal Gammopathy in a Patient with Advanced Ankylosing Spondylitis

Scleredema is a rare cutaneous mucinosis characterized by chronic diffuse induration of the skin, and it is occasionally associated with a monoclonal gammopathy (MG). Ankylosing spondylitis (AS) is noted to be another, chronic systemic inflammatory disorder of the axial skeleton that may accompany the MG. However, patients with scleredema and AS accompanied with a MG have not been reported in the literature. We here report a 40-yr-old man with scleredema and advanced AS accompanied with a MG of IgA-kappa protein. Widespread, long-standing scleredema has been developed over 10 yrs after the initial manifestation of AS. It is uncertain whether the coexistence of scleredema and AS is more than coincidental.

New Insights on the Pathogenesis of Behcet's Disease / 대한류마티스학회지

Behcet's disease (BD) is a chronic inflammatory disorder of unknown cause, characterized by recurrent oral ulcerations, genital ulcerations, ocular and skin lesions. Although the exact pathogenesis for BD is not completely understood, it has been suggested that the disease is triggered in genetically susceptible individuals by environmental factors, such as microbial agents. It is noted that multiple genes, including MHC and non-MHC genes, are implicated in the pathogenesis of BD. Although the HLA-B51 is known to be the candidate gene showing the strongest association with BD, it is necessary to be determined whether this HLA molecule is directly involved in the pathogenesis of BD. Cross-reactivity between microbial 65-kD and human 60-kD heat shock proteins is demonstrated to cause an increased T cell (particularly gammadelta T cell) response. The resultant overexpression of pro-inflammatory cytokines (mainly Th-1 type) from several immune cells seems to be responsible for the enhanced inflammatory reaction, and this may be associated with the genetic factors.

Vasculo-Behcet's Disease Developing in a Patient with Ebstein Anomaly / 대한류마티스학회지

Behcet's disease (BD) is a chronic inflammatory disease, involving several organs. It is well known that there are the marked regional differences in the disease expression of BD. In case of the vascular involvement in BD, the frequency rate has been described in 25~30% among the patients from the MiddLe East, whereas it has been noted in 5~15% in our country. In general, BD associated with large vessel lesions is named vasculo-BD. On the other hand, the cardiac involvement in BD has rarely been reported in the literature. Ebstein anomaly is a kind of malformation that is characterized by a downward displacement of the tricuspid valve into the right ventricle. We reported a 54-year-old male patient with vasculo-BD who had inferior vena cava obstruction and Ebstein anomaly. The association of Ebstein anomaly with vasculo-BD is considered to be coincidental. To the best of our knowledge, this is the first case of Ebstein anomaly associated with BD.

Systemic lupus erythematosus accompanied with idiopathic inflammatory myopathy: report of 2 cases / 대한내과학회지

Generalized myalgia and muscle tenderness are relatively common during exacerbations in patients with systemic lupus erythematosus (lupus), and inflammatory myositis involving the proximal muscles occurs in 5~11% of patients during the course of the disease. However, patients with overlap syndrome of lupus and idiopathic inflammatory myopathy have been not that frequent. We described 2 patients with overlap syndrome of these two diseases. Patient 1 was a 27-year-old female patient concurrently having lupus and dermatomyositis. She manifested the characteristic skin rash for dermatomyositis such as heliotrope rash. Patient 2 was a 32-year-old female patient concurrently having lupus and polymyositis, in whom the disease-specific autoantibodies for lupus or idiopathic inflammatory myopathy such as anti-ds DNA antibody, anti-Sm antibody and anti-Jo-1 antibody were positive.

A Case of Juvenile Ankylosing Spondylitis with Atlantoaxial Bony Ankylosis and Rheumatoid-like Hands / 대한류마티스학회지

Ankylosing spondylitis (AS) is a heterogeneous and systemic rheumatic disorder of unknown cause that is characterized by inflammation of the spine and sacroiliac joints. It is more common in young men. The disease is frequently associated with peripheral arthritis, enthesitis, anterior uveitis and high prevalence of HLA-B27. In some patients with AS, peripheral arthritis can occurs earlier than spinal symptom and more commonly affects the lower extremities than the upper extremities. Unlike men, women appear to have milder or atypical AS, especially at juvenile onset. However, involvement of the hands is extremely rare. Juvenile AS, defined as onset of disease prior to the age of 16 years, is considered a pediatric form of AS. On the other hand, although the atlantoaxial subluxation has been infrequently observed in patients with ankylosing spondylitis, atlantoaxial bony ankylosis has not been described in the literature. We describe a 23-year-old woman with juvenile AS who developed the atlantoaxial bony ankylosis and the hand involvement mimicking rheumatoid arthritis. Besides the rheumatoid-like hands and atlantoaxial bony ankylosis, she has shown the typical features of spondyloarthrpathy such as bilateral sacroiliitis, inflammatory spinal pain, enthesitis, severe arthritis of both hip joints, and positive HLA-B27 test.

Successful Combination Therapy of Cyclosporine and Methotrexate for Refractory Polymyositis with Anti-Jo-1 Antibody: A Case Report

Although corticosteroids have been the initial agent for the treatment of inflammatory myopathies (IM), immunosuppressive agents such as azathioprine, methotrexate, cyclophosphamide, or cyclosporine are commonly required to control the disease except mild cases. On the other hand, the efficacy of combination therapy of cyclosporine and methotrexate in severe rheumatoid arthritis has been proven without serious side effects. However, in treatment-resistant myositis, the experience of such a therapy is very limited, and has not been described in refractory polymyositis with anti-Jo-1 antibody. Here, we report a young female patient with recalcitrant polymyositis and anti-Jo-1 antibody who was successfully treated with the combination therapy of cyclosporine and methotrexate. At first, the myositis did not respond to several agents, such as corticosteroid, monthly pulse cyclophosphamide, azathioprine, or cyclosporine. Methotrexate was initially avoided as treatment regimen because of its potential pulmonary toxicity in the case with preexisting lung disease.

Survey and Validation of the Criteria for Behcet's Disease Recently Used in Korea: a Suggestion for Modification of the International Study Group Criteria

The criteria employed for Korean Behcet's disease (BD) from January 1990 to December 2000 have been investigated, and the diagnostic validity for those criteria was determined. For the generation of a modified set of preliminary criteria from the International Study Group (ISG) criteria, the diagnostic values for individual feature of BD were calculated. The criteria by the Behcet's Disease Research Committee of Japan appeared to be widely employed with the ISG criteria. However, because the ISG criteria revealed a relatively valid outcome in Korea, the application of this criteria will be needed for the universal unification until the criteria with better performance comes out. On the other hand, the modified set of preliminary criteria that consisted of the clinical items with better results seemed to improve some pitfalls of the ISG criteria. Although that criteria showed better performance than the preexisting criteria, it should be necessary to validate its effectiveness in other areas.

Treatment of Behcet's Disease / 대한류마티스학회지

Behcet's disease is a chronic inflammatory disease with various organ involvements, its pathogenesis being unclear. It runs the clinical course of unpredictable exacerbations and remissions. In addition to a triple syndrome of oral ulceration, genital ulceration, and uveitis, there may be the involvement of other systems, such as joints, gastrointestinal tract, central nervous system, vessels, heart, or lungs. Although we have more information about the agents, through the controlled studies, that have been already available to us, the considerable portions of managements have been still done empirically. In addition, the major goal of treatment is to suppress an inflammatory status of the disease and therapy should be tailored according to the disease activity and involved organ. In these days, promising data have also been accumulated in the tumor necrosis factor inhibitors, especially in Behcet's patients with severe manifestations refractory to conventional treatments.

The Clinical Significance of a Pathergy Reaction in Patients with Behcet's Disease

This study was done to evaluate the frequency, intensity, and specificity of a positive pathergy reaction (PR) in Behcet's disease (BD) patients, to clarify an association between the PR and the clinical features or disease severity, and to assess whether patients with pustule formation at the venous puncture site (PFVPS) without positive PR could be regarded as a positive reaction. The PR was tested in 64 BD patients, 74 disease controls, and 20 healthy controls. Venous PR was performed in 8 BD patients with PFVPS. Follow-up PR was done in 14 patients with positive reaction during inactive phase. The PR was positive in 35.9% of BD patients, in 1 patient among disease controls, and in none of healthy controls. The pustule formation was observed in one BD patient. There was no statistical significance between positive PR and the clinical variables. The mean clinical activity score of BD patients with positive PR was similar to patients with negative reaction. Venous PR was positive in 7 patients. The follow-up PR was positive in 2 patients during inactive phase. Conclusively the positive PR appeared to be specific for BD, and was not associated with the clinical variables or disease severity, but was usually found during active phase in cases with positive reaction. The PFVPS in patients with negative PR might be considered to be positive.

The Comparison Between Behcet's Disease and Spondyloarthritides: Does Behcet's Disease Belong to the Spondyloarthropathy Complex?

This study was to clarify whether Behcet's disease (BD) could be classified into the spondyloarthropathy (SpA) complex. It was undertaken on 58 patients with BD (BD group), 56 patients with SpA (SpA group), and 3 patients who concurrently satisfied the criteria for BD and SpA (BDSpA group). The clinical parameters and known susceptible HLA antigens were compared between BD group and SpA group. In addition, 3 patients in BDSpA group were reviewed. The prevalence of definitive sacroiliitis (SI) in BD group and SpA group was 46.4% and 5.2%, respectively. However, none had a definitive SI in healthy controls. Enthesitis was observed in 3.4% of BD group and in 50% of SpA group. The patterns of eye involvement were different between these two groups. HLA-B27 was negative in all 49 patients of BD group, whereas it was positive in 67.9% of SpA group. The prevalence of HLA-B51 was 51.7% in BD group, and that in SpA group was 21.4%. One patient in BDSpA group was considered to have concurrent BD and ankylosing spondylitis (AS). Another patient was closer to AS, and the third to BD. Conclusively, it seems that BD could not be classified into the SpA complex.

A Case of Interstitial Lung Disease Associated with Juvenile Rheumatoid Arthritis / 대한류마티스학회지

Juvenile rheumatoid arthritis (JRA) can develop the extra-articular manifestations, which are growth retardation, osteopenia, chronic uveitis, and rarely pleuropulmonary involvement. Approximately 30% of patients with JRA show abnormal pulmonary function test without pulmonary symptoms, in which the frequent abnormality is in carbon monoxide diffusing capacity, but clinically evident pulmonary parenchymal disease in JRA is extremely uncommon. We describe a 23-years-old female with JRA who presented with dyspnea due to interstitial lung disease and pulmonary hypertension. She had suffered from polyarthralgia and dyspnea since 8 years old.