Bon San Koo

Idiopathic Inflammatory Myopathy Associated with Malignancy: A Retrospective Cohort of 151 Korean Patients with Dermatomyositis and Polymyositis

Objective. To define the standardized incidence ratio (SIR) of malignancy and factors associated with malignancies in Korean patients with dermatomyositis (DM) and polymyositis (PM). Methods. The demographic, clinical, and laboratory features of 151 patients diagnosed with DM/PM were compared in patients with and without malignancies. Results. Malignancies were found in 23 of 98 patients with DM (23.5%) and in 2 of 53 with PM (3.8%). Lung cancer (8 patients) was the most common malignancy. Compared with the period-specific, sex-matched, and age-matched Korean population, the SIR for malignancy in patients with DM was 14.2 (95% CI 9.0–21.3). Univariate analysis showed that factors associated with malignancy included older age (p < 0.001), DM (p = 0.002), dysphagia (p < 0.001), the absence of interstitial lung disease (ILD; p = 0.001), and lower elevations in aspartate aminotransferase (p = 0.005) and lactate dehydrogenase concentrations (p < 0.001). Multivariate analysis showed that factors independently associated with malignancy included older age (per 10 years, OR 2.3, 95% CI 1.6–3.5, p < 0.001), DM (OR 5.9, 95% CI 1.3–26.2, p = 0.020), dysphagia (OR 2.6, 95% CI 1.2–6.6, p = 0.042), and the absence of ILD (OR 0.1, 95% CI 0.01–0.9, p = 0.040). Conclusion. DM was associated with a greater risk of concomitant malignancies, especially lung cancer, than PM. Independent factors associated with malignancies in patients with DM/PM were older age, the presence of dysphagia, and the absence of ILD.

Efficacy of Incentive Spirometer Exercise on Pulmonary Functions of Patients with Ankylosing Spondylitis Stabilized by Tumor Necrosis Factor Inhibitor Therapy

Objective. To evaluate the effect of combining incentive spirometer exercise (ISE) with a conventional exercise (CE) on patients with ankylosing spondylitis (AS) stabilized by tumor necrosis factor (TNF) inhibitor therapy by comparing a combination group with a CE-alone group. Methods. Forty-six patients (44 men, 2 women) were randomized to the combination group (ISE plus CE; n = 23) or the CE group (n = 23). The CE regimen of both groups consisted of 20 exercises performed for 30 min once a day. The ISE was performed once a day for 30 min. The trial duration was 16 weeks. Patients were assessed before and at the end of treatment by measuring the Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index (BASFI), chest expansion, finger to floor distance, pulmonary function measures, and 6-min walk distance. Results. Both groups improved significantly in terms of chest expansion (p < 0.01), finger to floor distance (p < 0.01), and BASFI (p < 0.05) after completing the exercise program. However, only the combination group showed significant improvements in the forced vital capacity (p < 0.05), total lung capacity (p < 0.01), and vital capacity (p < 0.05). Although this did not achieve statistical significance, the combination group was mildly superior to the CE-alone group in functional disability and pulmonary function measures. Conclusion. Combining ISE with a CE can provide positive results in patients whose AS has been clinically stabilized by TNF inhibitor therapy.

Pericentral Hydroxychloroquine Retinopathy in Korean Patients

PURPOSE A pericentral pattern of hydroxychloroquine (HCQ) retinopathy recently has been recognized in the United States in patients of Asian heritage. We report on an investigation of this pericentral retinopathy within a Korean population. DESIGN Retrospective, observational study. PARTICIPANTS Patients taking HCQ who were referred to ophthalmology for screening of HCQ retinopathy. METHODS The medical records of patients were reviewed, including spectral domain optical coherence tomography, fundus autofluorescence, and visual fields. MAIN OUTCOME MEASURES Frequency of pericentral pattern of HCQ retinopathy and features of progression. RESULTS Among 218 patients referred, 9 (4.1%) were diagnosed with toxicity. Of these, 8 had a predominantly pericentral pattern of retinal change, whereas only 1 had the classic parafoveal distribution of retinal damage. Progression of retinopathy was documented in 3 patients followed more than 12 months while taking HCQ. No progression was seen in 2 patients without retinal pigment epithelial (RPE) damage who were followed for at least 12 months after discontinuation of HCQ. CONCLUSIONS We found that a pericentral pattern of HCQ retinopathy was predominant among Korean patients, rather than the traditional (bulls eye) parafoveal pattern of damage. Retinopathy progressed while on the drug, but the progression stopped in patients with toxicity detected before RPE damage. These observations suggest the need for new approaches when screening for HCQ toxicity in Asian patients.

Safety of resuming tumour necrosis factor inhibitors in patients who developed tuberculosis as a complication of previous TNF inhibitors

OBJECTIVES There is no consensus on whether restarting TNF inhibitors (TNFis) after treatment of an active tuberculosis (TB) infection caused by previous TNFi exposure is safe. In this study we sought to determine the safety of resuming TNFis in patients following TB treatment. METHODS The medical records of all patients (n = 683) that received TNFi treatment at a single rheumatology clinic between June 2003 and December 2012 were retrospectively reviewed. Among them, data from patients who developed active TB infection were collected and patient outcomes were evaluated for those who resumed TNFis after TB treatment. RESULTS Of 683 patients, 13 patients developed an active TB infection during TNFi treatment (4 on etanercept, 4 on adalimumab and 5 on infliximab). The median duration of TNFi treatment before TB infection was 20 months. TNFi treatment was reinitiated in six patients: four within 2 months after TB treatment and two after completion of TB treatment. Four patients reinitiated with the same TNFi, whereas two patients started with another TNFi. During a mean follow-up of 30.6 months, all six patients successfully completed TB treatment with no TB infection relapses. CONCLUSION Our results suggest that resuming TNFi therapy in patients following adequate TB treatment is safe, even before completion of TB treatment.

Successful rituximab treatment of refractory hemophagocytic lymphohistiocytosis and autoimmune hemolytic anemia associated with systemic lupus erythematosus

Abstract High-dose steroids, immunosuppressants such as cyclophosphamide and cyclosporine, and high-dose intravenous immunoglobulin have all been used to control hemophagocytic lymphohistiocytosis (HLH) or autoimmune hemolytic anemia (AIHA) associated with systemic lupus erythematosus (SLE); however, some patients are refractory to treatment. Rituximab has successfully resolved many of the refractory manifestations of SLE. Here, we report a case of HLH and AIHA associated with SLE that was refractory or intolerable to conventional therapy, but was successfully treated with rituximab.

Clinicopathologic characteristics of IgG4-related retroperitoneal fibrosis among patients initially diagnosed as having idiopathic retroperitoneal fibrosis

Abstract Objective. The purpose of our study was to determine the number of IgG4-related retroperitoneal fibrosis (RPF) cases that were initially diagnosed as idiopathic RPF and to investigate clinical characteristics of IgG4-related RPF. Methods. We retrospectively reviewed the medical records of 41 RPF patients who were treated at our tertiary care medical center in South Korea between January 2000 and January 2013. We identified cases of 19 patients in which a diagnosis was made based on percutaneous biopsy or surgery and selected these cases for further analysis. Immunostaining for IgG4 and histopathologic examinations were performed for pathology specimens. Results. In the 19 RPF patients, more than 30 IgG4-positive plasma cells per specimen were identified in 9 cases with dense lymphoplasmacytic infiltrates, storiform fibrosis, or obliterative phlebitis (IgG4-related RPF group). The recurrence rate of IgG4-related RPF was significantly higher than that of idiopathic RPF (67% vs. 10%, p = 0.015). Initial and cumulative steroid dosages were not different between the two groups. Conclusions. We found that 47% of the patients initially diagnosed with idiopathic RPF showed IgG4-related RPF evidence according to the pathology and IgG4-related RPF patients showed higher recurrence rate than idiopathic RPF patients. We suggest that maintenance immunosuppressive therapy is required in IgG4-related RPF patients.

Frequency of immunoglobulin G4-related aortitis in cases with aortic resection and their clinical characteristics compared to other aortitises

To identify the frequency of immunoglobulin G4 (IgG4)‐related aortitis in patients who undergo aorta surgery and are diagnosed by pathology as having chronic aortic inflammation and to compare IgG4‐related aortitis with other non‐infectious aortitises in terms of clinical characteristics.

Neuro-behçet's disease in South Korea: clinical characteristics and treatment response

Neuro‐behçets disease (NBD) is a rare complication of Behçets disease (BD) but is still important due to its morbidity and mortality. In this study, we sought to identify the characteristics of NBD by examining the clinical characteristics, and whether there were differences in the clinical characteristics or the treatment between relapsed and non‐relapsed groups.

TNF-α confers resistance to Fas-mediated apoptosis in rheumatoid arthritis through the induction of soluble Fas

AIMS Rheumatoid arthritis (RA) is a chronic inflammatory arthritis that is characterized by hyperplastic synovial tissue containing activated synovial fibroblasts. Contradictory findings in the apoptosis of fibroblast-like synoviocytes (FLS) have been described elsewhere, showing that RA FLS have an enhanced susceptibility to Fas (also known as CD95)-mediated apoptosis in vitro in contrast to the observed lack of apoptosis in the RA synovium in vivo. However, the potential mechanisms responsible for this discrepancy remain under investigation. The soluble form of Fas (sFas) was found to inhibit Fas-induced apoptosis by binding to Fas ligand (FasL), thereby preventing the interaction between FasL and membrane-bound Fas. MAIN METHODS We determined the levels of soluble FasL (sFasL) and sFas in patients with RA and the effects of proinflammatory mediators, including TNF-α, on the induction of apoptotic mediators in RA FLS. KEY FINDINGS The levels of sFasL and sFas were significantly elevated in the synovial fluids of RA patients compared with control subjects. In addition, we found that the sFas is substantially induced in RA FLS by TNF-α, which were abundantly present in the synovial fluid of RA. SIGNIFICANCE These findings suggest that TNF-α confers resistance to Fas-mediated apoptosis through sFas induction, which could explain the apparent resistance of RA synovial cells to apoptosis in vivo.

Immunoglobulin G4-related disease with lymphoplasmacytic aortitis mimicking Takayasu arteritis.

Immunoglobulin 4 (IgG4)Yrelated systemic disease, which is defined pathologically as lymphoplasmacytic infiltration by IgG4-positive plasma cells, involves multiple organs. It may result in autoimmune pancreatitis, sclerosing cholangitis, IgG4associated nephropathy, and interstitial pneumonia, mimicking the clinical manifestations of other infectious, inflammatory, and neoplastic diseases. Aortic lesions, such as noninfectious thoracic aortitis, inflammatory abdominal aortic aneurysms/ periaortitis, and idiopathic retroperitoneal fibrosis, may also be related to IgG4-related disease. In most patients, aortitis resulting from IgG4-related diseases predominantly involves the thoracic aorta, including the aortic arch and descending aorta; however, there have been no reports of IgG4-related disease presenting as stenosis of the branch vessels of thoracic aorta, similar to Takayasu arteritis. We describe a patient with lymphoplasmacytic aortitis associated with IgG4-related disease involving the carotid and subclavian arteries.