J.-M. Kim

Meningitis in Korean patients with systemic lupus erythematosus: analysis of demographics, clinical features and outcomes; experience from affiliated hospitals of the Catholic University of Korea

Meningitis is a rare complication of systemic lupus erythematosus (SLE), potentially leading to a fatal outcome. The demographic, clinical, and laboratory features, and the outcomes of meningitis were evaluated in Korean patients with SLE. In a retrospective medical record review of 1420 SLE patients, 20 patients who had developed septic or aseptic meningitis were identified. In 11 patients, the causative microorganisms were identified (‘septic meningitis’), and Cryptococcus neoformans was the major pathogen. The other nine patients were diagnosed with aseptic meningitis. The patients with septic meningitis were older than those with aseptic meningitis (p = 0.025) and displayed mental changes more often (p = 0.005). Leukocyte counts in the cerebrospinal fluid (CSF) were higher (p = 0.044) and the levels of CSF glucose were lower in the septic meningitis group (p = 0.036). Plasma leukocyte counts and neutrophil counts were higher in patients with septic meningitis (p = 0.037 and p = 0.020, respectively). Meningitis was observed in 1.4% of Korean patients with SLE and, in 55% of the meningitis patients, microorganisms were isolated and Cryptococcus neoformans was most commonly identified. Altered mental status, plasma leukocytosis, neutrophilia, and CSF pleocytosis and hypoglycemia were more prominent in patients with septic meningitis.

Idiopathic intracranial hypertension as a significant cause of intractable headache in patients with systemic lupus erythematosus: a 15-year experience:

Objective: To evaluate the occurrence of idiopathic intracranial hypertension (IIH) in patients with systemic lupus erythematosus (SLE) and to describe the manifestations, treatments and outcomes in these patients. Methods: We reviewed the medical records of 1084 patients with SLE followed up from January 1997 to June 2011 in our unit. We identified patients with IIH and analyzed the demographic, clinical and laboratory characteristics of these patients. Results: Among the 1084 SLE patients, 47 underwent cerebrospinal fluid studies because of their intractable headache and eight (17%) of these were diagnosed as IIH. All were females aged 14 to 32 years. Nobody belonged to the obesity group. Headache, nausea, vomiting and blurred vision were the most common presenting symptoms. All patients had active SLE at the time of admission (SLE disease activity index ≥6). Five patients had lupus nephritis. In eight patients, there were two with antiphospholipid antibodies, two with anti-ribosomal P antibodies and six with anti-Ro antibodies. All subjects recovered without any complication after high dose steroid therapy. Conclusions: IIH accounts for a considerable part of the causes of intractable headache in SLE patients and steroids should be considered as a first-line treatment.

Magnesium sulphate attenuates tourniquet-induced hypertension and spinal c-fos mRNA expression: a comparison with ketamine.

Magnesium and ketamine are well-known N-methyl-d-aspartic acid receptor antagonists. The aim of this study was to determine whether magnesium, in comparison with ketamine, attenuates tourniquet-induced hypertension and spinal c-fos mRNA expression. Rats were divided into four treatment groups: normal (baseline for c-fos mRNA expression); control (saline injection); magnesium injection; and ketamine injection. Arterial blood pressure and c-fos mRNA expression at 60 min were higher in the control than in the magnesium and ketamine groups. Human patients under sevoflurane–oxygen/nitrous oxide anaesthesia were also assigned to receive similar treatments. In humans, arterial blood pressure was increased in the control group at 50 min and thereafter compared with the magnesium and ketamine groups; the magnesium and ketamine groups did not differ. Magnesium and ketamine are equally effective in attenuating tourniquet-induced hypertension and spinal c-fos mRNA expression, suggesting that this effect may be due to reduced pain transmission.

Use of laryngeal mask airway and its removal in a deeply anaesthetized state reduces emergence agitation after sevoflurane anaesthesia in children.

This study investigated the effect of laryngeal mask airway (LMA) and removal while in a deeply anaesthetized state (deep removal) compared with endotracheal tube and extubation when awake or deeply anaesthetized on the incidence of emergence agitation in children after sevoflurane anaesthesia for subumbilical surgery. Patients (2 – 7 years) were randomly assigned to one of three groups: ET-A group (n = 56, endotracheal tube and extubation whilst awake); ET-D group (n = 56, endotracheal tube and deep extubation); LMA-D group (n = 56, experienced LMA and deep removal). The incidence of postoperative emergence agitation was significantly lower in the LMA-D patients compared with patients in the ET-A group (21.4% and 41.1%, respectively). Patients in the LMA-D group required a significantly shorter stay in the postanaesthetic care unit (PACU) than ET-A patients. There were no significant differences in the incidence of postoperative emergence agitation or length of stay in the PACU between the ETA and ET-D groups, or between the ET-D and LMA-D groups. In conclusion, using an LMA and deep removal decreased postoperative emergence agitation compared with using an endotracheal tube and awake extubation after paediatric sevoflurane anaesthesia.

Pain, xerostomia, and younger age are major determinants of fatigue in Korean patients with primary Sjögren’s syndrome: a cohort study

Objectives: Fatigue is a common clinical manifestation in patients with primary Sjögren’s syndrome (pSS). The aims of this study were to investigate the association between fatigue severity and other clinical characteristics in pSS patients and to determine the factors contributing to fatigue. Method: We analysed 257 participants from the Korean Initiative of pSS (KISS), a prospective pSS cohort. Fatigue was assessed according to the fatigue domain of the European League Against Rheumatism (EULAR) Sjögren’s Syndrome Patient-Reported Index (ESSPRI). Health-related quality of life (HRQoL) was evaluated using the EuroQol-5 dimensions (EQ-5D) questionnaire. Multiple linear regression analysis was used to estimate the effect of each variable on fatigue severity. Results: The median total ESSPRI score was 5 [interquartile range (IQR) 4–6]. Thirty-four per cent of patients reported a fatigue score > 5. Younger and premenopausal patients presented with more fatigue (p = 0.013 and p < 0.001, respectively). Higher Xerostomia Inventory (XI) scale (p < 0.001) and Ocular Surface Dryness Index (OSDI) (p < 0.001) scores were observed in patients with a fatigue score > 5. Pain, xerostomia, and age were determined to be significantly associated with fatigue severity after adjusting for depression/anxiety, OSDI score, and the presence of fibromyalgia using a multivariate general linear model. The ESSPRI fatigue score was correlated with the EQ-5D by time trade-off (TTO) values and visual analogue scale (VAS) scores. Conclusions: In Korean patients with pSS, younger age, xerostomia, and pain were correlated significantly with fatigue, and fatigue was associated with HRQoL.

Simultaneous presentation of acute disseminated encephalomyelitis (ADEM) and systemic lupus erythematosus (SLE) after enteroviral infection: can ADEM present as the first manifestation of SLE?

Central Nervous System (CNS) involvement of Systemic Lupus Erythematosus (SLE) includes a broad range of neuropsychiatric syndromes. Acute Disseminated Encephalomyelitis (ADEM) is a demyelinating CNS disorder characterized by encephalopathy and multifocal lesions predominantly involving the white matter on brain magnetic resonance imaging. ADEM associated with SLE has been only rarely reported. We report an unusual case of a 17-year-old girl who developed ADEM after enteroviral infection as the first manifestation of SLE. The authors emphasize that the patient’s illness was preceded by enteroviral infection and that ADEM occurred before any other symptoms of SLE, which makes this case unique.

AB0211 The relationship between the elevated serum immunoglobulin g4 level and disease activity in patients with rheumatoid arthritis

Background High levels of serum immunoglobulin G4 (IgG4) would comprise a useful diagnostic tool in IgG4-related disease, but little information is available about IgG4 in conditions other than IgG4-related disease, including rheumatic diseases. Previous studies indicate that the elevated serum IgG4 in rheumatoid arthritis (RA) is common and disproportional to total IgG. Objectives The aim of study is to evaluate the level of serum IgG4 and IgG4/total IgG ratio in patients with RA. Methods Ninety-six patients with RA and one hundred and thirty-five non-RA controls were enrolled between March 2014 and July 2017. All samples were collected before the treatments. The levels of Serum total IgG and IgG4 were determined by nephelometric assay. The cut-off value of serum IgG4 was 135 mg/dL. Data on clinical variables and disease activity markers, such as numbers of tender and swollen joints, levels of acute phase reactants and disease activity score 28 (DAS28) were recorded in RA patients. We compared the levels of serum IgG4 and the ratio of IgG4/total IgG in rheumatoid arthritis with healthy controls and other rheumatic diseases. This study also investigated the difference the relationship between levels of serum IgG4 and disease activity in RA. Results Among 96 RA patients, the mean of serum IgG4 was 48.0±45.4 mg/dL and 6.3% had elevated serum IgG4. The mean serum IgG4/IgG ratio of RA patients was 3.5%±2.8% (range 0.2%∼16.9%). There was no patient with elevated serum IgG4 in ankylosing spondylitis, systemic lupus erythematosus, Sjogren’s syndrome, and inflammatory myositis. When the patients were divided according to clinical activity, the percentages of the positive serum IgG4 were 25% in active disease group and 4% in low activity group. However, the serum IgG4 levels of the RA patients with active disease activity were not significantly higher than those of the RA patients with low disease activity (58.3±44.3 mg/dL vs. 39.9±30.1 mg/dL). No significant relationship was observed between the ratio of IgG4/total IgG and disease activity. The IgG4 concentrations and total IgG/IgG4 ratios were similar between RA and the other autoimmune diseases (p>0.05). Conclusions Our results showed that elevated serum IgG4 in RA is relatively common. However the presence of the elevated serum IgG4 was not associated with disease activity of RA. Further investigations are needed to explore the clinical significance in a larger study population. References [1] Lin G, et al. Elevation of serum IgG subclass concentration in patients with rheumatoid arthritis. Rheumatol Int2010;30:837–40. [2] Yamamoto M, et al. Value of serum IgG4 in the diagnosis of IgG4-related disease and in differentiation from rheumatic diseases and other diseases. Mod Rheumatol2012;22:419–25. [3] Chen LF, et al. Elevated Serum IgG4 Defines Specific Clinical Phenotype of Rheumatoid Arthritis. Mediators Inflamm2014;2014:635293. Disclosure of Interest None declared

72 Implications of autophagy for functinal changes of rheumatoid arthritis fibroblast-like synoviocytes

Background and aims Rheumatoid arthritis (RA) is characterised by exaggerated synovial proliferation in which interleukin-17A (IL-17A) plays a key role. Recently several evidences support the implication of autophagy in the pathogenesis of RA. The aims of this study are (1) to evaluate whether IL-17A influences on autophagic flux in RA synovium and (2) to investigate whether the modulation of autophagy can regulate migration and proliferation of fibroblast-like synoviocytes (FLS) from the patients with RA (RA-FLS) under inflammatory milieu. Methods FLS from the patients with RA or osteoarthritis (OA) were cultured with IL-17A and/or autophagy regulators. The expression of marker proteins for autophagic flux or the formation of autophagolysosome was analysed by western blot or immunofluorescence study. A migration scratch assay was used to assess FLS migration. Proliferation of FLS was determined by the viable cell count using trypan blue. Results LC3 conversion from LC3-I to LC3-II was increased in RA-FLS than in OA-FLS. IL-17A upregulated the expression of LC3B, Atg5, Beclin1, LAMP1 in RA-FLS. The accumulation of p62 was also prominent in RA-FLS. Migration and proliferation of FLS stimulated by IL-17A was suppressed by Bafilomycin A1 which prevented the formation of autophagolysosomes. P62-silencing enhanced IL-17A-induced autophagy activation in RA-FLS. Conclusions This study reveals that IL-17A stimulates autophagy and that intervention of autophagy can control IL-17A-induced migration and proliferation of FLS. Our results also provide additional evidence for a significant role of autophagy in the pathogenesis of RA. Thus, we suggest that autophagy might be a potential therapeutic target for the management of RA.

369 A case of hemophatocytic syndrome developed in a korean female patient with dermatomyositis

Background and aims Dermatomyositis (DM) is characterised by chronic inflammation of striated muscle and characteristic cutaneous manifestations. Hemophagocytic syndrome (HPS) is a rare life-threatening condition caused by uncontrolled activation of histiocytes resulting in prominent hemophagocytosis. Particularly, occurrence of HPS in the patients with DM is extremely rare. Methods We report the first case of HPS in a patient with DM successfully treated in Korea. Results A 56-year-old female visited our hospital, complaining of general weakness with whole body skin rash for 2 months. She had symmetric proximal muscle weakness and characteristic skin lesions including heliotrope rash, gottron’s papules and V sign. She also had swallowing difficulty proven by abnormal videofluoroscopic swallowing test. Laboratory findings showed anaemia, thrombocytopenia, elevated muscle enzymes, hyperferritinemia and hypertriglyceridemia. The autoimmune profile revealed positive antinuclear antibody (1:160, homogenous pattern) and negative anti-Jo-1 antibody. In addition to electromyography and skeletal muscle biopsy, bone marrow biopsy was performed to find the cause of microangiopathic hemolytic anaemia and thrombocytopenia. Numerous CD68-positive macrophages engulfing erythrocytes and platelets were revealed in bone marrow study. She was finally diagnosed as DM with secondary HPS. After steroid pulse therapy for 3 days, we continued high dose steroid therapy for 1 month. Thereafter, we gradually tapered the steroid and started methotrexate. After 1 year of treatment, she was completely recovered from muscle weakness, swallowing difficulty, skin lesions and cytopenia. Conclusions With this unique case, we would like to assert that HPS should be considered when cytopenia is observed in the patients with DM and that early aggressive therapy is needed.

AB0139 Interleukin-21 Is Overexpressed in Kidney Tissue from Lupus Nephritis Patients and Its Serum Levels Are Correlated with Systemic Lupus Erythematosus Disease Activity

Background Interleukin-21 (IL-21) has various effects on a number of immune cells including B cells, T cells, natural killer (NK) and NKT cells. One of the essential roles of IL-21 is to contribute to autoantibody production as a result of promoting hyperactivity of B cells. Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by pathogenic autoantibody production and systemic organ damage. A few studies have been conducted for investigating the contribution of IL-21 to the pathogenesis of murine SLE. However, only limited studies have been performed concerning the role of IL-21 in human SLE and the results are still controversial. Objectives The aim of this study was to evaluate whether IL-21 participates in the pathogenesis of human SLE. Methods Serum IL-21 levels were measured in SLE, osteoarthritis (OA) patients and healthy controls (HC). Serum IL-21 levels were analyzed for revealing the correlation with laboratory data or a disease activity index for SLE. Kidney tissues from patients with lupus nephritis and controls were used for evaluating the expression of IL-21 and IL-21R. Normal portions of human kidneys removed for renal carcinoma were used as normal controls. Results Serum levels of IL-21 were increased in the patients with SLE as compared to the patients with OA or HC. Serum IL-21 levels of the patients with SLE were positively correlated with serum levels of IgG, the titers of anti–double-stranded DNA antibodies and the scores of SLE Disease Activity Index. SLE patients with low C4 concentrations had higher serum IL-21 levels than those with normal C4 concentrations. The expression of IL-21 was higher in renal tubular epithelial cells of the patients with lupus nephritis than in those of controls. Conclusions This study reveals the association between IL-21 and disease activity in the patients with SLE. We also first demonstrate IL-21 expression in renal tissue of the patients with lupus nephritis. These findings suggest that IL-21 is critically implicated in the pathogenesis of SLE. References Ettinger R, Kuchen S, Lipsky PE: Interleukin 21 as a target of intervention in autoimmune disease. Annals of the rheumatic diseases 2008, 67 Suppl 3:iii83–86. Herber D, Brown TP, Liang S, Young DA, Collins M, Dunussi-Joannopoulos K: IL-21 has a pathogenic role in a lupus-prone mouse model and its blockade with IL-21R.Fc reduces disease progression. Journal of immunology 2007, 178(6):3822–3830. Disclosure of Interest None declared