Faith Li-Ann Chia

Severe cutaneous adverse reactions to drugs.

Purpose of reviewThis paper updates the treatment of Stevens–Johnson syndrome and toxic epidermal necrolysis supported by relevant views about the pathogenesis. Recent findingsBuilding on the thesis that Stevens–Johnson syndrome and toxic epidermal necrolysis are due to dermal cell apoptosis, molecular pathways that may lead to this have been proposed. Intravenous immunoglobulin is postulated to block apoptosis via the Fas pathway. Most series on the use of intravenous immunoglobulin in toxic epidermal necrolysis have been favourable. Tumour necrosis factor is also thought to be an important mediator of cell death in toxic epidermal necrolysis. There was impressive control of the progression of toxic epidermal necrolysis with intravenous anti-tumour necrosis factor antibody infliximab in two cases. Strong associations between human leukocyte antigen subtypes and severe cutaneous reactions due to allopurinol and carbamazepine have been described. SummaryTo date, there is no established treatment of Stevens–Johnson syndrome/toxic epidermal necrolysis. With advancing knowledge of the pathogenesis, it is hoped that better forms of treatment may result.

APLAR rheumatoid arthritis treatment recommendations

Rheumatoid arthritis is a chronic inflammatory condition that affects approximately 1% of the worlds population. There are a wide number of guidelines and recommendations available to support the treatment of rheumatoid arthritis; however, the evidence used for these guidelines is predominantly based on studies in Caucasian subjects and may not be relevant for rheumatoid arthritis patients in the Asia‐Pacific region. Therefore, the Asia Pacific League of Associations for Rheumatology established a Steering Committee in 2013 to address this issue.

Sphingosine kinase and sphingosine-1-phosphate receptors: novel therapeutic targets of rheumatoid arthritis?

Rheumatoid arthritis (RA) is a chronic, destructive, autoimmune joint disease characterized by elevated levels of proinflammatory cytokine production. Sphingosine kinase (SphK) phosphorylates sphingosine into sphingosine-1-phosphate. Synovial fluid of RA patients exhibits significantly higher levels of S1P than their non-inflammatory osteoarthritis counterparts. SphK blockade suppresses cytokines and MMP-9 release in RA peripheral blood mononuclear cells. In addition, downregulation of SphK1 either through a specific siRNA approach or transgenic human TNF-α SphK1-deficient mice (hTNF-α/SphK1(-/-)) exhibit significantly less synovial inflammation and joint pathology. By contrast, SphK2 modulation leads to disease exacerbation. These results clearly demonstrate that such anti- and proinflammatory potential of SphK1/2 modulation may alter the outcome in RA synovitis and raises the possibility that drugs that specifically target SphK1 activity may play a beneficial role in the treatment of RA and other autoimmune rheumatic diseases.

Achieving consensus in ultrasonography synovitis scoring in rheumatoid arthritis

Ultrasonography is sensitive for synovitis detection but interobserver variation in both acquisition and image interpretation is still a concern. The objective was to assess if a short collegiate consensus would improve inter‐observer reliability in scoring of synovitis.

Urine sVCAM‐1 and sICAM‐1 levels are elevated in lupus nephritis

We sought to evaluate the relationship of urine levels of soluble cellular adhesion molecules sVCAM‐1 (vascular) and sICAM‐1 (intercellular) in systemic lupus erythematosus (SLE) patients with or without lupus nephritis, and to explore their correlation with renal disease activity.

Consensus development on eligibility of government subsidisation of biologic disease modifying anti-rheumatic agents for treatment of ankylosing spondylitis: The Singapore experience

The beneficial effects of biologic disease‐modifying anti‐rheumatic drugs (bDMARDs), such as tumour necrosis factor inhibitors (anti‐TNF) in active ankylosing spondylitis (AS) are well established. The significant costs on patients in the absence of financial subsidization can limit their use. The objective was to describe a consensus development process on recommendations for government‐assisted funding of biologic therapy for AS patients in Singapore.

A 62‐Year‐Old Man With Progressive Weakness, Multiple Neurologic Deficits, and Hypernatremia

History of the presenting symptom The patient had a 6-month history of unsteady gait and generalized weakness with constitutional symptoms of loss of weight and appetite. He consulted his general practitioner 2 months later. Laboratory investigations then showed normal complete blood count and liver and thyroid function tests. Magnetic resonance imaging (MRI) of the brain with contrast fluid-attenuated inversion recovery (FLAIR) sequences and diffusion-weighted imaging showed multiple nonspecific foci of an abnormal signal seen in the white matter of both cerebral hemispheres. VDRL serology was nonreactive. The only abnormal investigation was an elevated serum sodium level at 148 mmoles/liter (reference interval 135–145). He was referred to a neurologist, who made a diagnosis of multiple system atrophy based on features of cerebellar dysfunction and dysautonomia, which included orthostatic hypotension and erectile dysfunction. His serum vitamin E level was 11.3 mg/liter (reference interval 5.5–18.0). He was commenced on highdose oral vitamin E therapy as an antioxidant for multiple system atrophy. He subsequently presented to the general medicine department and was admitted for progression of symptoms. Medical history He had been attending long-term followup visits with his general practitioner for hyperlipidemia and type 2 diabetes mellitus for 10 years. Glycosylated hemoglobin (HbA1c) 2 months prior to admission was 11.8%. His regular medications included lovastatin, glipizide, and vitamin E tablets. He had no recent exposure to anyone with tuberculosis or history of pulmonary tuberculosis.

SAT0511 Achieving Consensus in Ultrasonography Synovitis Scoring in Rheumatoid Arthritis

Background Ultrasonography (US) is a sensitive method for synovitis detection in clinical practice but interobserver variation in both acquisition and image intepretation is still a key concern [1]. Various semiquantitative synovitis scoring methods have been proposed in the past for B-mode and PDUS. Recently, the OMERACT US Task Force also proposed the EULAR-OMERACT PDUS composite scoring which had moderate to excellent reliability [2]. However, this has not been tested formally outside of the steering group. Objectives The objective was to evaluate if a collegiate small group consensus would improve US synovitis assessment and scoring in patients with rheumatoid arthritis, in both still images and in image acquisition. Methods Eight rheumatologists from Singapore participated in a 1 day consensus meeting in November 2012, divided into (i) still-image interpretation and consensus followed by (ii) image acquisition and interpretation, according to definitions and synovitis scoring rules endorsed by OMERACT and TUI (Targeted Ultrasound Initiative). Interobserver reliability of semiquantitative scoring in B-mode, Power Doppler (PDUS) and EULAR-OMERACT PDUS composite score was assessed by intraclass correlation co-efficient (ICC). Agreement at the joint region level was calculated using prevalence-adjusted-biased-adjusted-kappa (PABAK). Results For B-mode still images, ICC was good at 0.75 (95%CI 0.66-0.82) while for PDUS images this was excellent; ICC=0.88 (95%CI 0.83-0.92). During image acquisition and interpretation, B-mode scoring showed ICC=0.75 (95%CI 0.66-0.84) while for PDUS the ICC was lower at 0.59 (95%CI 0.48-0.72). The ICC for EULAR-OMERACT PDUS composite synovitis scoring was good at 0.77 (95%CI 0.68-0.85). At the joint level, agreement varied with PABAK being excellent in the small joints of the hands but poor to fair in the wrists, elbows, ankles and MTP, and no agreement at the knees (PABAK range -0.34 to 0.85). Conclusions A consensus meeting between colleagues was useful in improving interobserver variation in synovitis scoring by ultrasonography, but agreement in non-hand joints is still a problem, requiring further standardisation. References Cheung PP, Dougados M, Gossec L. Reliability of ultrasonography to detect synovitis in rheumatoid arthritis: a systematic literature review of 35 studies (1415 patients). Arthritis Care Res (Hoboken) 2010; 62:323-34. Naredo E, Wakefield R, Iagnocco A, et al. The OMERACT Ultrasound Task Force - Perspectives. J Rheumatol 2011;38:2063-7. Disclosure of Interest None Declared

Singapore Chapter of Rheumatologists consensus statement on the eligibility for government subsidy of biologic disease modifying anti-rheumatic agents for the treatment of psoriatic arthritis

In Singapore, patients with psoriatic arthritis (PsA) constitute a significant disease burden. There is good evidence for the efficacy of anti‐tumor necrosis factor (anti‐TNF) in PsA; however cost remains a limiting factor. Non‐biologic disease modifying anti‐rheumatic drugs (nbDMARDs) hence remain the first‐line treatment option in PsA in spite of limited evidence. The Singapore Chapter of Rheumatologists aims to develop national guidelines for clinical eligibility for government‐assisted funding of biologic disease modifying anti‐ rheumatic drugs (bDMARDs) for PsA patients in Singapore.

Associations of B cell-activating factor (BAFF) and anti-BAFF autoantibodies with disease activity in multi-ethnic Asian systemic lupus erythematosus patients in Singapore

To measure the levels of B cell‐activating factor (BAFF) and endogenous anti‐BAFF autoantibodies in a cohort of multi‐ethnic Asian systemic lupus erythematosus (SLE) patients in Singapore, to determine their correlation with disease activity. Serum samples from 121 SLE patients and 24 age‐ and sex‐matched healthy controls were assayed for BAFF and anti‐BAFF immunoglobulin (Ig)G antibody levels by enzyme‐linked immunosorbent assay (ELISA). The lowest reliable detection limit for anti‐BAFF‐IgG antibody levels was defined as 2 standard deviations (s.d.) from blank. Correlation of serum BAFF and anti‐BAFF IgG levels with disease activity [scored by SLE Activity Measure revised (SLAM‐R)], and disease manifestations were determined in these 121 patients. SLE patients had elevated BAFF levels compared to controls; mean 820 ± 40 pg/ml and 152 pg ± 45/ml, respectively [mean ± standard error of the mean (s.e.m.), P < 0·01], which were correlated positively with anti‐dsDNA antibody levels (r = 0·253, P < 0·03), and SLAM‐R scores (r = 0·627, P < 0·01). In addition, SLE patients had significantly higher levels of anti‐BAFF IgG, which were correlated negatively with disease activity (r = –0·436, P < 0·01), levels of anti‐dsDNA antibody (r = –0·347, P < 0·02) and BAFF (r = –0·459, P < 0·01). The majority of patients in this multi‐ethnic Asian SLE cohort had elevated levels of BAFF and anti‐BAFF antibodies. Anti‐BAFF autoantibody levels correlated negatively with clinical disease activity, anti‐dsDNA and BAFF levels, suggesting that they may be disease‐modifying. Our results provide further information about the complexity of BAFF pathophysiology in different SLE disease populations and phenotypes, and suggest that studies of the influence of anti‐cytokine antibodies in different SLE populations will be required when selecting patients for trials using targeted anti‐cytokine therapies.