You Jae Kim

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.

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.

Mortality in patients with rheumatoid arthritis-associated interstitial lung disease treated with an anti-tumor necrosis factor agent.

Background/Aims To evaluate the impact on mortality of anti-tumor necrosis factor (anti-TNF) treatment of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Methods We retrospectively reviewed the medical records of 100 RA-ILD patients who visited our tertiary care medical center between 2004 and 2011, identified those treated with an anti-TNF agent, divided patients into non-survivor and survivor groups and evaluated their clinical characteristics and causes of death. Results A total of 24 RA-ILD patients received anti-TNF therapy, of whom six died (25%). Mean age at initiation of anti-TNF therapy was significantly higher in the nonsurvivor versus survivor group (76 years [range, 66 to 85] vs. 64 years [range, 50 to 81], respectively; p = 0.043). The mean duration of anti-TNF treatment in the non-survivor group was shorter (7 months [range, 2 to 14] vs. 23 months [range, 2 to 58], respectively; p = 0.030). The duration of anti-TNF therapy in all nonsurviving patients was < 12 months. Pulmonary function test results at ILD diagnosis, and cumulative doses of disease-modifying drugs and steroids, did not differ between groups. Five of the six deaths (83%) were related to lung disease, including two diffuse alveolar hemorrhages, two cases of acute exacerbation of ILD, and one of pneumonia. The sixth patient died of septic shock following septic arthritis of the knee. Conclusions Lung complications can occur within months of initial anti-TNF treatment in older RA-ILD patients; therefore, anti-TNF therapy should be used with caution in these patients.

Lupus enteritis: clinical characteristics and predictive factors for recurrence.

Objectives To compare the clinical characteristics of lupus enteritis (LE) and non-enteric lupus (non-LE) patients and identify predictors of LE recurrence. Methods We retrospectively reviewed the medical records of 62 systemic lupus erythematosus (SLE) patients in a tertiary hospital who experienced enteric symptoms and underwent abdominal computed tomography scanning between January 1997 and December 2013. We compared the clinical characteristics between LE and non-LE patients and between recurrent LE and non-recurrent LE cases. Results Out of 62 SLE patients with enteric symptoms, 46 cases (74%) were compatible with LE based on computed tomography findings. The C4 level was decreased in the LE group compared with the non-LE group (9.0 ± 5.6 vs. 12.3 ± 6.2, p = 0.032). Recurrence of LE was observed in 14 patients (28%). Initial involvement at the colon (79% vs. 41%, p = 0.026) and bladder with/without the ureter was more common in the recurrent group (57% vs. 25%, p = 0.048). By multivariate analysis, the hazard ratios of variables associated with recurrence were 4.689 for colon involvement (95% confidence interval: 1.245–17.659, p = 0.0220] and 5.468 for cystitis with/without ureteritis (95% confidence interval: 1.629–18.360, p = 0.006). Conclusion Colon and urinary tract involvement in LE patients may be associated with the recurrence of LE.

AB0154 Pathogenic Role of Irhom2 in Seropositive Rheumatoid Arthritis

Background Tumor necrosis factor (TNF)-α is a major pathologic cytokine in rheumatoid arthritis (RA) and the current target of RA treatment has been on blocking the TNF-α. iRHOM2 is a regulator of TNF-α convertase that mediate the release of TNF-α from immune cells. Moreover, immune complexes (ICs) are known to induce expression of iRHOM2 via Fc receptors (FcλRIIIa/CD16) in monocytes, regulating the production of TNF-α. Objectives We hypothesized that the expression of iRHOM2 and Fc receptors are up regulated in seropositive RA patients, that is mediated by immune complex. Methods The level of TNF-α was measured in the serum of seropositive (+) and seronegative (−) RA patients by ELISA. Messenger RNA expression of iRHOM2 and CD16 was evaluated on peripheral blood mononuclear cells of (+) RA, (−) RA patients, and healthy controls. ICs were extracted from serum of RA patients by adding polyethylene glycol. Isolated ICs were added to THP1-cell cultures to examine the induction of iRHOM2 and CD16. Results Serum level of TNF-α was similar between (+) RA patients and (−) RA patients (3.23±(5.97) pg/ml vs. 1.99±(1.93) pg/ml). Increased iRHOM2 and CD16 mRNA expression was found on PBMC in (+) RA patients compared to those in (−) RA patients (figure). IC isolated from (+) RA patient could enhance the expression of iRHOM2 as well as CD16 from THP-1 cells. Conclusions iRHOM2, highly expressed in (+) RA monocytes, might be regulated by immune complex containing anti-cyclic citrullinated peptides antibody, although serum TNF-α level was not different in (+) and (−) RA patient. References Lichtenthaler SF. iRHOM2 takes control of rheumatoid arthritis. J Clin Invest 2013;123:560-2. Issuree PD, Maretzky T, McIlwain DR et al. iRHOM2 is a critical pathogenic mediator of inflammatory arthritis. J Clin Invest 2013;123:928-32. Cooper DL, Martin SG, Robinson JI et al. FcgammaRIIIa expression on monocytes in rheumatoid arthritis: role in immune-complex stimulated TNF production and non-response to methotrexate therapy. PLoS One 2012;7:e28918. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3199

SAT0522 The Association between Uric Acid Level and Urolithiasis on Ultrasonography

Background Previous studies have suggested that gout increases the risk for the development of urolithiasis (uric acid stone or calcium-containing stone). However, the association between the prevalence of clinical or subclinical urinary stone disease and uric acid (UA) level has not been evaluated. Objectives The purpose of this study is to evaluate the association between the rate of urinary stone on ultrasonography (USG) and UA level. Methods We retrospectively reviewed radiographic and laboratory data from a tertiary hospital in Korea from 2010 to 2013. We included 13964 adult (≥20 years old) cases in which both abdominal or kidney ultrasonography and laboratory test have been performed for any purpose during these periods. We used calculated mean serum UA and creatinine levels for each case and stratified all cases by UA level and age. The risk of urinary stone on USG was analysed in association with uric acid level by multiple logistic regression analysis with adjustment for age, sex, body mass index, creatinine and known underlying diseases including diabetes mellitus and hypertension. Results Among 6743 men (48%) and 7221 women (52%), mean age was 51.3±13.5 (range, 20-95), mean uric acid level was 4.5±2.1 mg/dL (range, 0.4-21.8), and mean creatinine level was 2.1±2.2 mg/dL (range, 0.4-18.9). Hyperuricemia (UA level above 7.0 mg/dL in men or 6.0 mg/dL in women) was found in 1750 cases (13%). Urinary stone on USG was detected in 608 cases (4.4%). The detection rates of urolithiasis in individuals with hyperuricemia and normal UA level were 5.9% and 4.1%, respectively (P=0.001). The overall detection rate of urolithiasis increased proportionally to serum UA level (Fig. 1A). In multiple logistic regression analysis, individuals with higher serum UA level had significantly higher risk of urolithiasis (adjusted odds ratio (OR)=1.136, 95% confidence interval (CI), 1.087-1.188, P<0.001), and these relationship was more prominent in men (OR=1.174, 95% CI, 1.108-1.243, P<0.001 in men; OR=1.106, CI, 1.023-1.196, P=0.011 in women) (Fig. 1B). Conclusions This study suggested that individuals with higher serum uric acid level had higher risk of clinical or subclinical urolithiasis, especially in men. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3639