Doo-Ho Lim

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.

Outcome of Takayasu Arteritis with Inactive Disease at Diagnosis: The Extent of Vascular Involvement As a Predictor of Activation

Objective. Some patients with Takayasu arteritis (TA) have inactive disease at the time of diagnosis. The objective of our study was to investigate the clinical outcomes and factors that predict disease activation in patients with clinically inactive TA. Methods. The medical records of patients diagnosed with TA between 1990 and 2012 were reviewed. At the time of diagnosis, patients were identified as having inactive disease according to the National Institutes of Health definition. Patients who went on to develop active disease during followup were classified as the “activation group”. The pattern of vascular involvement was classified according to the International Conference on TA, 1994. Results. A total of 59 patients with TA were classified as having inactive disease at the time of diagnosis. During the followup, 13 (22.0%) of these experienced TA activation (median followup, 37.0 mos; activation group). The remaining 46 (78.0%) did not experience disease activation (stable group). Renovascular hypertension was more common in the activation group than in the stable group (5/13, 38.5% vs 4/46, 8.7%, p = 0.019). Further, type V, which is the most extensive, was more common in the activation group (12/13, 92.3%) than in the stable group (18/46, 39.1%, p = 0.008). Multivariate analysis identified type V disease (OR 10.969, 95% CI 1.144–105.182, p = 0.038) as being significantly associated with an increased risk of disease activation. Conclusion. Substantial portions of patients with clinically inactive TA at the time of diagnosis experienced disease activation during followup. Type V disease may be an important predictive factor for disease activation in patients with clinically inactive TA.

Factors related to outcomes in lupus-related protein-losing enteropathy

Background/Aims: Protein-losing enteropathy (PLE), characterized by severe hypoalbuminemia and peripheral edema, is a rare manifestation of systemic lupus erythematosus. This present study aimed to identify the distinctive features of lupus-related PLE and evaluate the factors related to the treatment response. Methods: From March 1998 to March 2014, the clinical data of 14 patients with lupus PLE and seven patients with idiopathic PLE from a tertiary center were reviewed. PLE was defined as a demonstration of protein leakage from the gastrointestinal tract by either technetium 99m-labelled human albumin scanning or fecal α1-antitrypsin clearance. A positive steroid response was defined as a return of serum albumin to ≥ 3.0 g/dL within 4 weeks after initial steroid monotherapy, and remission as maintenance of serum albumin ≥ 3.0 g/dL for at least 3 months. A high serum total cholesterol level was defined as a level of ≥ 240 mg/dL. Results: The mean age of the lupus-related PLE patients was 37.0 years, and the mean follow-up duration was 55.8 months. Significantly higher erythrocyte sedimentation rate and serum total cholesterol levels were found for lupus PLE than for idiopathic PLE. Among the 14 patients with lupus PLE, eight experienced a positive steroid response, and the serum total cholesterol level was significantly higher in the positive steroid response group. A positive steroid response was associated with an initial high serum total cholesterol level and achievement of remission within 6 months. Conclusions: In lupus-related PLE, a high serum total cholesterol level could be a predictive factor for the initial steroid response, indicating a good response to steroid therapy alone.

The risk of herpes zoster in patients with ankylosing spondylitis: Analysis of the Korean National Health Insurance Service – Sample cohort database

Abstract Objectives: The aims of our study were to determine whether the use of conventional disease-modifying antirheumatic drugs (cDMARDs) or tumor necrosis factor α (TNFα) inhibitors increase the risk of herpes zoster (HZ) in patients with ankylosing spondylitis (AS). Methods: We searched the South Korean National Health Insurance Service – National Sample Cohort Database for relevant patient records between 2002 and 2013. We evaluated the incidence of HZ by categorizing patients into in three treatment groups: disease-modifying antirheumatic drug (DMARD) nonusers, cDMARD users and TNFα inhibitor users. Results: Incidence rates of HZ was 11.0 per 1000 person-years in patients with AS. The adjusted hazard ratio of HZ was higher in cDMARD and TNFα inhibitor users than in DMARD nonusers. In subgroup analyses, current treatment with a TNFα inhibitor increased the risk of HZ significantly both in female patients and in patients aged 50 years or older, but not in patients taking steroids, compared to DMARD nonusers. Conclusions: Treatment with either TNFα inhibitors or cDMARDs is associated with a higher risk of HZ, especially in female patients and older patients, and these two patient groups could therefore benefit from HZ vaccination.

Nontuberculous mycobacterial infection in rheumatoid arthritis patients: a single-center experience in South Korea

Background/Aims Nontuberculous mycobacteria (NTM) infection has been increasing worldwide in both general population and immunocompromised patients, which has also been reported in rheumatoid arthritis (RA) patients. This study aimed to identify the incidence and clinical characteristics of NTM infection in RA patients living in tuberculosis (TB) infection endemic area. Methods We performed a retrospective analysis of NTM infection cases in our RA registry at a tertiary referral center from January 1995 to December 2013. The clinical features of them were compared to those of 52 TB infection patients from same registry. Results Among 1,397 patients with RA, NTM infection was newly developed in 26 patients and the incidence of NTM infection was 164.8 per 100,000 patient-years. The Mycobacterium avium complex was the most frequent isolate (76.9%). None of the NTM infections had extrapulmonary involvement, which was rather common in TB infection (26.9%). Patients with NTM infection were older, received higher cumulative steroid doses, and had higher rates of past TB infection history and concomitant interstitial lung disease (ILD) than cases with TB infection. Conclusions In South Korea, NTM infection is not rare in RA patients, and infection rates are growing. Physicians should be cautious about NTM infection in patients with a history of TB infection or concomitant ILD, even living in TB endemic area.

Immunoglobulin G Levels as a Prognostic Factor for Autoimmune Hepatitis Combined With Systemic Lupus Erythematosus.

Autoimmune hepatitis (AIH) is a chronic progressive liver disease characterized by circulating autoantibodies and hyperglobulinemia. This study was conducted to identify the features of AIH accompanied by systemic lupus erythematosus (SLE‐AIH) that differ from those of primary AIH (P‐AIH), and to evaluate factors that affect the outcome for SLE‐AIH patients.

Clinical features and prognoses of acute transverse myelitis in patients with systemic lupus erythematosus

Background/Aims Acute transverse myelitis (ATM) is a severe complication of systemic lupus erythematosus (SLE). This study evaluated the clinical factors related to outcome in patients with SLE-associated ATM. Methods The medical records of patients diagnosed with SLE-associated ATM between January 1995 and January 2015 were reviewed. The patients were divided into two groups based on improvement of neurological deficits after treatment: favorable response group and unfavorable response group. During follow-up, the recurrence of ATM was also analyzed. Results ATM was identified in 16 patients with SLE. All of the patients were treated with high doses of methylprednisolone (≥ 1 mg/kg daily). Although 12 patients (75%) recovered (favorable response group), four (25%) had persistent neurologic deficits (unfavorable response group) after the treatment. Compared to the favorable response group, significantly higher Systemic Lupus Erythematosus Disease Activity Index-2000, lower complement levels and initial severe neurologic deficits were found in the unfavorable response group. Among the 12 favorable response patients, five (41.7%) experienced recurrence of ATM during the followup. Patients (n = 5) who experienced relapse had a shorter duration of high-dose corticosteroid treatment (13.2 days vs. 32.9 days, p = 0.01) compared to patients who did not relapse. The mean duration of tapering-off the corticosteroid until 10 mg per day was significantly longer in non-relapse group (151.3 ± 60.8 days) than in relapse group (63.6 ± 39.4 days, p = 0.013). Conclusions Higher disease activity in SLE and initial severe neurologic deficits might be associated with the poor outcome of ATM. Corticosteroid slowly tapering-off therapy might be helpful in preventing the recurrence of ATM.

Invasive Thyroid Gland Aspergillosis in a Patient with Systemic Lupus Erythematosus

https://jkms.org A 29-year-old woman who was diagnosed with lupus nephritis and treated with steroid pulse therapy and cyclophosphamide two months ago, readmitted to our hospital because of fever. A computed tomography (CT) scan showed multiple cystic lesions in the thyroid gland and necrotic cervical and mediastinal lymphadenopathies. However, no parenchymal abnormalities were noted in either of the lungs (Fig. 1). We underwent an ultrasonographyJ Korean Med Sci. 2018 May 14;33(20):e153 https://doi.org/10.3346/jkms.2018.33.e153 eISSN 1598-6357·pISSN 1011-8934

Ileocolonoscopic findings in patients with ankylosing spondylitis: a single center retrospectivestudy

Background/Aims In some Western countries, up to 50% of patients with ankylosing spondylitis (AS) have subclinical gut inflammation. This study was conducted to evaluate the prevalence and severity of gut inflammation and to determine clinical factors associated with colonic inflammation in Korean AS patients who performed ileocolonoscopy without evidence of established inf lammatory bowel diseases before. Methods One hundred and eight AS patients who underwent ileocolonoscopy were included in this study. Patients were divided into two groups based on gross ileocolonoscopic findings; patients with inflammatory lesions, and patients without inflammatory lesions. Results Inf lammatory lesions in ileocolonoscopic findings were found in 40 patients. The Ankylosing Spondylitis Disease Activity Score C-reactive protein was higher in the group with inflammatory lesions and gut lesions were found often in the terminal ileum. The risk of inflammatory lesions was higher for AS patients whose symptoms required ileocolonoscopy than for AS patients who underwent routine ileocolonoscopy screening (odds ratio, 3.96). However, abnormal lesions were detected also in 17.6% of the patients who underwent ileocolonoscopy for routine screening and most of them were erosion and ulcer. Among patients with inflammatory lesions (n = 40), 23 showed subclinical gut inflammation associated with AS and 17 were diagnosed finally as Crohn’s disease (n = 12), intestinal tuberculosis (n = 4), and ulcerative colitis (n = 1). Conclusions Our findings suggest that ileocolonoscopy might be recommended regularly in AS patients even without gastrointestinal symptoms, especially in the patients with high AS activity.

Safety of tumor necrosis factor inhibitor therapy in patients with a prior malignancy.

There is insufficient evidence to determine whether tumor necrosis factor inhibitor (TNFi) therapy is safe in patients with a recent history of cancer. The purpose of our study was to explore the influence of TNFi therapy on cancer‐related outcomes in patients who had undergone curative cancer treatment.