Severe cutaneous adverse reactions to drugs.

PURPOSE OF REVIEW: This paper updates the treatment of Stevens-Johnson syndrome and toxic epidermal necrolysis supported by relevant views about the pathogenesis. RECENT FINDINGS: Building 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. SUMMARY: To 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.

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.

AIM: 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. METHODS: Evidence synthesis was performed by reviewing seven published guidelines on use of biologics for PsA. Using the modified Research and Development/University of California at Los Angeles Appropriateness Method (RAM), rheumatologists rated indications for therapies for different clinical scenarios. Points reflecting the output from the formal group consensus were used to formulate the practice recommendations. RESULTS: Ten recommendations were formulated relating to initiation, continuation and options of bDMARD therapy. The panellists agreed that a bDMARD is indicated if a patient has active PsA with at least five swollen and tender joints, digits or entheses and has failed two nbDMARD strategies at optimal doses for at least 3 months each. Any anti-TNF may be used and therapy may be continued if an adequate PsARC response is achieved by 3 months after commencement. CONCLUSION: The recommendations developed by a formal group consensus method may be useful for clinical practice and guiding funding decisions by relevant authorities in making bDMARD usage accessible and equitable to eligible patients in Singapore.

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

INTRODUCTION: 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. METHODS: Evidence synthesis followed by a modified RAND/UCLA Appropriateness Method (RAM) was used. Eleven rheumatologists rated indications for therapies for different proposed clinical scenarios. Points reflecting the output from the formal group consensus were used to formulate 10 practice recommendations. RESULTS: It was agreed that a bDMARD (anti-TNF) is indicated if a patient has active AS with a Bath Ankylosing Spondylitis Activity Index (BASDAI) ≥ 4 and spinal pain of ≥ 4 cm on visual analogue scale (VAS) on two occasions at least 12 weeks apart, despite being on a minimum of two sequential non-steroidal anti-inflammatory drugs at maximal tolerated dose for at least 4 weeks, in addition to adherence to an appropriate physiotherapy program for at least 3 months. To qualify for continued biologic therapy, a patient must have documentation of response every 3 months and at least 50% improvement in BASDAI and reduction of spinal pain VAS ≥ 2 cm. CONCLUSION: A validated and feasible consensus process can enable pragmatic standardized recommendations to be developed for bDMARD subsidization for AS patients in a local Asian context.

Achieving consensus in ultrasonography synovitis scoring in rheumatoid arthritis.

OBJECTIVE: 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. METHODS: Eight rheumatologists (Singapore) participated in a 1-day consensus meeting divided into: (i) still-image interpretation and consensus followed by; (ii) image acquisition and interpretation, according to definitions and synovitis scoring rules endorsed by Outcome Measures in Rheumatology (OMERACT) and TUI (Targeted Ultrasound Initiative). Interobserver reliability of semiquantitative scoring in B-mode, Power Doppler (PDUS) and European League Against Rheumatism (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 at ICC = 0.88 (95% CI 0.83-0.92) with ICC improving by 12% for B-mode and 13% for PDUS respectively. 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 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 metatarsophalangeal joints, and no agreement at the knees (PABAK range -0.34 to 0.85). CONCLUSION: A consensus meeting was useful in improving interobserver variation in US synovitis scoring of still images, but image acquisition and interpretation especially in non-hand joints require further standardization.

Urine sVCAM-1 and sICAM-1 levels are elevated in lupus nephritis.

AIM: 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. METHODS: Paired serum and urine samples of 121 Asian SLE patients, and urine samples of 19 normal healthy controls were collected. Demographic data, disease activity and damage scores, and selected laboratory parameters, including levels of anti-double stranded DNA antibody, complements C3, C4, and creatinine were captured. Renal disease activity was scored with renal SLE Activity Measure revised (rSLAM-R). Serum and urine sVCAM-1 and sICAM-1 levels were assayed by enzyme-linked immunosorbent assay. RESULTS: Urinary sVCAM-1 and sICAM-1 were elevated in SLE patients compared to controls. Significantly higher levels of urine sVCAM-1 found in patients with active lupus nephritis correlated with rSLAM-R. In addtion, significantly more patients with active lupus nephritis had detectable levels of urine sICAM-1, but no correlation with renal activity was observed. CONCLUSION: Urinary sVCAM-1 may serve as a potential biomarker for early diagnosis of lupus nephritis as levels correlated with even mild abnormalities of urine sediment. In addition, both urine sVCAM-1 and sICAM-1 levels may be useful in identifying patients at risk of lupus nephritis.