Young Sun Suh

Safe Re-administration of Tumor Necrosis Factor-alpha (TNFα) Inhibitors in Patients with Rheumatoid Arthritis or Ankylosing Spondylitis Who Developed Active Tuberculosis on Previous Anti-TNFα Therapy

There is no consensus on whether it is safe to re-administer tumor necrosis factor-alpha (TNFα) inhibitors in patients with rheumatoid arthritis (RA) or ankylosing spondylitis (AS) flared after withdrawal of TNFα inhibitors due to active tuberculosis (TB). We evaluated the safety of restarting anti-TNFα therapy in patients with TNFα-associated TB. We used data of 1,012 patients with RA or AS treated with TNFα inhibitors at Seoul St. Marys Hospital between January 2003 and July 2013 to identify patients who developed active TB. Demographic and clinical data including the results of tuberculin skin tests (TST) and interferon-γ releasing assays (IGRA) were collected. Fifteen patients developed active TB. Five cases were occurred in RA and 10 cases in AS. Nine of 15 patients had a negative TST or IGRA and 6 TST-positive patients had received prophylaxis prior to initiating anti-TNFα therapy. All patients discontinued TNFα inhibitors with starting the treatment of TB. Eight patients were re-administered TNFα inhibitors due to disease flares and promptly improved without recurrence of TB. TNFα inhibitors could be safely resumed after starting anti-TB regimen in patients with RA or AS.

The effect of targeted decolonization on methicillin-resistant Staphylococcus aureus colonization or infection in a surgical intensive care unit.

BACKGROUND The effect of decolonization on the control of methicillin-resistant Staphylococcus aureus (MRSA) may differ depending on intensive care unit (ICU) settings and the prevalence of antiseptic resistance in MRSA. METHODS This study was conducted in a 14-bed surgical ICU over a 40-month period. The baseline period featured active surveillance for MRSA and institution of contact precautions. MRSA decolonization via chlorhexidine baths and intranasal mupirocin was implemented during a subsequent 20-month intervention period. Pre-post and interrupted time series analysis were used to evaluate changes in the clinical incidence of hospital-acquired MRSA colonization or infection. MRSA isolates were tested for the presence of qacA/B genes and mupirocin resistance. RESULTS In pre-post analysis, the clinical incidence of MRSA significantly decreased by 61.6% after implementation of decolonization (P < .001). Meanwhile, interrupted time series analysis showed decreases in both the level (β = -0.686; P = .210) and trend (β = -0.011; P = .819) of clinical MRSA incidence, but these changes were not statistically significant. Of 169 MRSA isolates, 64 (37.8%) carried the qacA/B genes, and 22 (13.0%) showed either low- (n = 20) or high-level (n = 2) resistance to mupirocin. Low-level mupirocin resistance significantly increased from 0%-19.4% during the study period. CONCLUSION Although decolonization using antiseptic agents was helpful to decrease hospital-acquired MRSA rates, the emergence of antiseptic resistance should be monitored.

The risk of osteoporotic fractures according to the FRAX model in Korean patients with rheumatoid arthritis.

The aim of the current study is to identify patients without osteoporosis who met the criteria of the fracture risk assessment tool (FRAX) of the National Osteoporosis Foundation (NOF) only. The incidence of fractures was investigated in patients who met only the FRAX criteria of the NOF and patients who presented osteoporosis. Five hundred and forty five patients with rheumatoid arthritis who visited a single center were recruited in Korea. In the follow-up period of median 30 months, the new onset of fractures was investigated. Of 223 patients who have no osteoporosis, 39 (17.4%) satisfied the FRAX criteria for pharmacological intervention. During the follow-up period, 2 new onset fractures occurred in patients who met only the FRAX criteria and 22 new onset fractures did in patients with osteoporosis by bone mineral density. The incidence rate for new onset fractures of patients who met only the FRAX criteria was with 295.93 per 10,000 person-years higher than in the general population with 114.99 per 10,000 person-years. Patients who met the FRAX criteria of the NOF only need pharmacological intervention because their numbers of incidence for new onset fractures are similar to those of patients with osteoporosis by BMD. Graphical Abstract

Medication nonadherence in Korean patients with rheumatoid arthritis: the importance of beliefabout medication and illness perception

Background/Aims To investigate medication nonadherence in Korean patients with rheumatoid arthritis (RA) and analyze related factors. Methods A total of 292 patients with RA participated in this study. Medication nonadherence, intentional or unintentional, was gauged via self-reported questionnaire. Patient perceptions of illness, treatment beliefs, and moods were measured via Brief Illness Perception Questionnaire, Beliefs about Medicines Questionnaire, and Patient Health Questionnaire-2, respectively. Demographic and clinical data were also collected. Multinomial regression analysis was used to assess the impact of demographic, clinical, and psychological factors on medication nonadherence. Results The medication nonadherence rate was 54.1% (intentional, 21.6%; unintentional, 32.5%). Intentional nonadherence was reported most often in patients treated daily drugs (nonsteroidal anti-inflammatory drugs and/or disease-modifying antirheumatic drugs) (24.2%), and unintentional nonadherence was highest in patients receiving methotrexate (33.3%) (p = 0.872). In univariate analysis, beliefs in necessity and concerns of medication differed significantly in adherent and nonadherent patients (intentional or unintentional). When controlling for other factors that may impact medication nonadherence, less belief in necessity of medication (odds ratio [OR], 0.81; 95% confidence interval [CI], 0.68 to 0.95) and greater emotional response to disease (OR, 1.19; 95% CI, 1.01 to 1.40) were important predictors of intentional nonadherence. Conclusions Medication nonadherence is common in Korean patients with RA. Less belief in necessity of medication and greater emotional response to disease were identified as key factors prompting intentional nonadherence. These factors may be strategically targeted to improve medication adherence rates and subsequent clinical outcomes.

Usefulness of plain radiography for assessing hypouricemic treatment response in patients with tophaceous gout.

To investigate whether plain radiography is useful for assessing the changes in gouty tophi size following hypouricemic therapy.

The association of disease activity, pro-inflammatory cytokines, and neurotrophic factors with depression in patients with rheumatoid arthritis

Inflammation and trophic factors (brain-derived neurotrophic factor [BDNF], vascular endothelial growth factor, glial cell line-derived neurotrophic factor, and insulin-like growth factor-1) are associated with depression in the general population. Rheumatoid arthritis (RA) is a chronic representative inflammatory autoimmune disease; however, the association of disease activity, pro-inflammatory cytokines, and neurotrophic factors with depression has not been sufficiently investigated. Therefore, we determined the prevalence of depression and risk factors for depression and deterioration of depressive symptoms in RA patients. In addition, we analyzed the association between disease activity, pro-inflammatory cytokines, trophic factors, and depression in RA (N = 474). Demographic and laboratory data were examined, and routine assessment of patient index data 3 (RAPID 3) and disease activity score 28-joint count C-reactive protein (DAS 28-CRP) was performed to assess disease activity of RA. Depression was measured using the Korean version of the Beck Depression Inventory-second edition (K-BDI II). A K-BDI score ≥18 was considered the cut-off for depression in accordance with a previous validation study. The serum level of pro-inflammatory cytokines and neurotrophic factors was assessed by enzyme-linked immune sorbent assay. The prevalence of depression was 32.4% in patients with RA. The severity of disease activity of RA (RAPID 3 score [OR 2.34; 95% confidence interval, CI 1.22-4.51], DAS 28-CRP [≥3.2] [OR 1.60, 95% CI 1.01-2.53]) and severity of fatigue (OR 1.26 95% CI 1.15-1.38) were associated with depression and deterioration of depressive symptoms in the multivariate analysis. Among the components of RAPID 3 and DAS 28-CRP, patient assessment for global health and abilities for daily performance were more related to depression. The level of pro-inflammatory cytokines (IL-1β, IL-6, TNF-alpha) was not related to depression. The level of BDNF was significantly lower in RA patients with depression and was negatively correlated with K-BDI II score. Depression was related with the level of fatigue, low expression of BDNF, and high RA disease activity, which was associated with impaired ability to perform activities of daily life. Strict control of fatigue and disease activity to improve ones capacity to perform daily life activities would be important to regulate depression. The level of BDNF might be one of the possible biomarkers to predict or monitor depression in patients with RA.

Ankylosing spondylitis associated with primary aldosteronism in a middle-aged woman.

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Relationship between decreased lower extremity muscle mass and knee pain severity in both the general population and patients with knee osteoarthritis: Findings from the KNHANES V 1-2

Objective To identify the prevalence of and risk factors for knee pain and radiographic knee osteoarthritis (RKOA) and to investigate the relationship between decreased lower extremity muscle mass (DLEM) and knee pain severity. Methods Using data from the Korea National Health and Nutrition Examination Survey, 3,278 participants who were ≥50 years old and who underwent dual x-ray absorptiometry, plain knee radiographs and completed a knee pain questionnaire were enrolled. Lower extremity muscle mass (LEM) was defined as the sum of the fat-free soft tissue mass of the legs, and lower extremity muscle mass index (LMI) was calculated as LEM/body weight (%). DLEM was defined as an LMI more than two standard deviations below the mean of a gender-matched young reference group. Categorical variables were presented as numbers (weighted %). Results The prevalence of knee pain and RKOA were 22% (n = 721) and 34.7% (n = 1,234), respectively. Multivariate logistic regression analysis showed being female (OR 2.15, 95% CI 1.67–2.79), older (OR 1.03, 95% CI 1.01–1.04), less educated (OR 1.72, 95% CI 1.09–2.71), stiffness (OR 16.15, 95% CI 12.04–21.66), bed rest (OR 2.49, 95% CI 1.81–3.43), RKOA (OR 2.20, 95% CI 1.78–2.74) and DLEM (OR 1.54, 95% CI 1.09–2.17) were associated with knee pain. Participants with simultaneous RKOA and DLEM complained of more severe pain (pain score 7.18 ± 2.48) than those with knee pain without RKOA or DLEM (5.02 ± 2.44), those with only RKOA (6.29 ± 2.50), or those with only DLEM (6.78 ± 2.18) (P<0.001). These results remained after multivariate analyses of variance (MANOVAs). Conclusion The prevalence of knee pain and RKOA were 22% and 34.7%, respectively, in the general Korean population. DLEM was an independent risk factor for knee pain and it was associated with increased pain severity, regardless of RKOA.

AB0144 Generation of Disease-Specific Induced Pluripotent Stem Cells from Patients with Rheumatoid Arthritis and Osteoarthritis

Background Since the concept of reprogramming mature somatic cells to generate induced pluripotent stem cells (iPSCs) was demonstrated in 2006, iPSCs have become a potential substitute for embryonic stem cells (ESCs) given their pluripotency and “stemness” characteristics, which resemble those of ESCs. Objectives We investigated to reprogram fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) to generate iPSCs using a 4-in-1 lentiviral vector system. Methods A 4-in-1 lentiviral vector containing Oct4, Sox2, Klf4, and c-Myc was transduced into RA and OA FLSs isolated from the synovia of two RA patients and two OA patients. Immunohistochemical staining and real-time PCR studies were performed to demonstrate the pluripotency of iPSCs. Chromosomal abnormalities were determined based on the karyotype. SCID-biege mice were injected with iPSCs and sacrificed to test for teratoma formation. Results After 14 days of transduction using the 4-in-1 lentiviral vector, RA FLSs and OA FLSs were transformed into spherical shapes that resembled embryonic stem cell colonies. Colonies were picked and cultivated on matrigel plates to produce iPSC lines. Real-time PCR of RA and OA iPSCs detected positive markers of pluripotency. Immunohistochemical staining tests with Nanog, Oct4, Sox2, Tra-1-80, Tra-1-60, and SSEA-4 were also positive. Teratomas that comprised three compartments of ectoderm, mesoderm, and endoderm were formed at the injection sites of iPSCs. Established iPSCs were shown to be compatible by karyotyping. Finally, we confirmed that the patient-derived iPSCs were able to differentiate into osteoblast, which was shown by an osteoimage mineralization assay. Conclusions FLSs derived from RA and OA could be cell resources for iPSC reprogramming. Disease- and patient-specific iPSCs have the potential to be applied in clinical settings as source materials for molecular diagnosis and regenerative therapy. References Takahashi K, Yamanaka S: Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006, 126:663-76. Tiscornia G, Vivas EL, Izpisúa Belmonte JC: Diseases in a dish: modeling human genetic disorders using induced pluripotent cells. Nat Med 2011, 17:1570-6. Grskovic M, Javaherian A, Strulovici B, Daley GQ: Induced pluripotent stem cells–opportunities for disease modelling and drug discovery. Nat Rev Drug Discov 2011, 10:915-29. Acknowledgements This work was supported by a grant from the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (A092258). Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4862

Sjögren's Syndrome Accompanied by Prolactinoma: a case report and literature review

Dear Editor, Sj€ ogren’s syndrome (SS) is an autoimmune disease characterized by dryness of the eyes and mouth, which is because of the destruction of salivary and lacrimal glands by infiltrating lymphocytes. Patients with SS have an increased risk of developing malignancies, particularly non-Hodgkin B cell lymphoma and solid cancers such as breast cancer or thymoma. However, there have been no previous reports of prolactinoma in a patient with SS. Prolactin might play a role in the pathogenesis of some rheumatic diseases, including SS. Several cases of prolactinoma have been reported with concomitant systemic lupus erythematosus (SLE), which generated much interest in the possibility that prolactin influences SLE disease activity. Here we report the first case of SS associated with prolactinoma in which SS-related symptoms of dryness were relieved by a dopaminergic agonist. A 21-year-old woman was initially diagnosed with conjunctivitis sicca at a local ophthalmic clinic. She had used artificial tears more than three times per day. She had also suffered from mouth dryness from the age of 26 years and recurrent lymphadenopathy behind both ears from the age of 28 years. She did not use any medication that would cause dryness. Her blood test results were positive for anti-nuclear antibodies (ANA, 1:320, speckled and cytoplasmic pattern), anti-Ro/ SSA, anti-La/SSB, and anti-thyroglobulin antibodies (Abs, > 4000 IU/mL). Tests for double-stranded DNA, Sm, anti-phospholipids and anti-cyclic citrullinated peptide Abs were negative. However, a Schirmer test was positive. A Tc-99 m pertechnetate salivary scan revealed decreased absorption and excretion in both the parotid and submental glands (Fig. 1). Mild focal perivascular lymphocytic infiltration was observed in a minor salivary gland biopsy. The diagnosis of SS was confirmed according to the American European Consensus Criteria. The patient was also diagnosed with Hashimoto’s thyroiditis and began undergoing synthyroid and pilocarpine treatment. The patient revisited our hospital at the age of 33 years because of galactorrhea and oligomenorrhea. At that time, her blood test results revealed an increase in prolactin to 221.9 ng/mL (normal range; 4.79–23.3 ng/mL). Sellar magnetic resonance imaging identified a focal lesion on the right pituitary gland (Fig. 2). Based on these findings, she was diagnosed with prolactinoma and began undergoing treatment with the dopaminergic agonist bromocriptine mesylate. Bromocriptine treatment improved her symptoms of dryness, allowing her to reduce the use of artificial tears and pilocarpine as her prolactin level decreased (3.27 ng/mL). However, after ceasing bromocriptine treatment for 2 weeks, she suffered from severe mouth and eye dryness and a rebound in prolactin levels (60.57 ng/mL). These symptoms again improved after restarting bromocriptine treatment. At present, the patient has been treated with synthyroid and bromocriptine for 6 months and has had no recurrence of severe dryness during follow-up. Prolactin, which stimulates diverse cell types such as macrophages, dendritic cells, T cells and B cells, has been considered both a pathogenic and protective factor in autoimmune inflammation; however, the role of prolactin in autoimmune disease remains controversial. A recent study revealed that the detrimental effects of prolactin in the context of autoimmune disease prevailed in B cell-dominated diseases such as SLE, by inducing the production of autoantibodies and mature B cells. Although the pathogenic role of prolactin in SS has not yet been revealed, prolactin might also be related to B lymphocyte hyper-reactivity in patients with SS. In addition, prolactin-like proteins are synthetized and overexpressed in the glandular epithelial cells of labial salivary glands and the acinar cells of lacrimal glands, and these proteins exert important bioactive effects on immune function. Prolactin, which inhibits the apoptosis of transitional B cells and increases antibody secretion, contributes to the onset of SS through its immunostimulatory effects. Taken