Burden and management of gout in a multi-ethnic Asian cohort.

Gout has significant impact on the quality of life with over-utilisation of health resources. While lowering serum urate (SU) to ≤ 360 µmol/L improves clinical outcomes, this is usually not achieved. We describe the burden of gout and determine predictors of achieving SU target in gout patients in Singapore. This was a cross-sectional study of 282 gout patients from a Singapore hospital rheumatology service. Sociodemographic and lifestyle factors, co-existing medical conditions and medications, gout history and severity, SU levels and treatment were obtained. Patients with SU ≤ 360 µmol/L were compared with those > 360 µmol/L to determine factors associated with achieving SU target. Descriptive statistics and multivariate model were used. Severe disease was reported in 50%, with emergency attendances and hospitalisations in 33% and 19% respectively, and unemployment in 32%. Only 22% were at SU target and 67% on urate-lowering therapy (ULT) at recruitment. Hypertension, dyslipidaemia, chronic kidney disease and diabetes were prevalent in 56.7%, 48.2%, 32.3% and 18.8%, respectively. Malays had more comorbidities compared to Chinese participants. In multivariate analysis, ULT prescription and ≥ 2 comorbidities were associated with reaching SU target with odds ratios of 3.92 [95% confidence interval (CI) (1.75-8.71)] and 2.65 [95% CI (1.59-4.43)] respectively, independent of age, tophi, disease duration, body mass index, alcohol and diuretic use. Patients with gout have high disease burden resulting in significant healthcare utilisation. SU control is sub-optimal hence the use of ULT remains key in achieving SU target. Patients with other comorbidities are more likely to reach target than those with only gout as a single diagnosis.

Efficacy and safety of pulsed intravenous methylprednisolone in early active thyroid eye disease.

Introduction: The mainstay of therapy for active inflammatory phase of thyroid eye disease (TED) is immunosuppression. Patients in our centre with early active TED are treated with pulsed intravenous methylprednisolone (IVMP). Two different protocols are offered in our centre: High dose (1g/day for 3 days, monthly for 6 months), or EUGOGO protocol (500 mg weekly for six weeks, followed by 250 mg weekly for the next 6 weeks). Methods: A prospective cohort study of patients undergoing the two IVMP protocols was performed from January 2009 to May 2015. Main outcome measures were improvement of Clinical Activity Score (CAS) and International Thyroid Eye Disease (ITEDS) - VISA Inflammatory Index. Results: We had a total of 63 patients. Mean age was 43.1 ± 13.1years, females comprised 49.2% (n = 31), and 31 (49.2%) had a positive smoking history. Following IVMP, 65.0% (n = 41) had good response, 31.7% (n = 20) partial, and 3.3% (n = 2) poor. There were significant differences (p < 0.001) in CAS and ITEDS scores between pre-IVMP and post-IVMP visits, for both protocols. A higher proportion of patients receiving the modified EUGOGO protocol (58.3%) had persistent activity and required additional immunosuppression compared to those who underwent the high dose protocol (33.3%). Mild side effects were experienced by 5 (7.9%) and 3 (4.8%) patients at 3 and 6 months, respectively. There were no severe side effects, cardiovascular events or liver failure. Conclusion: With adequate screening and follow-up, six repeated cycles of high dose pulsed IVMP is an effective treatment for TED and can significantly reduce the morbidity associated with this debilitating condition. None of the 51 patients from the high dose protocol met with any serious side effects.

A randomized controlled trial for improving patient self-assessment of synovitis in rheumatoid arthritis with education by ultrasonography: the RAEUS Study.

OBJECTIVE: Patients can potentially monitor disease activity of RA through self-assessed swollen joints (clinical synovitis), but reliability is poor. The objective is to evaluate the use of education by US feedback on the ability of patients to assess for clinical synovitis in RA. METHODS: We performed a 6 month, single-centre, randomized controlled trial on patients with established RA to study the effect of education on self-assessment of joints that included initial brief patient training on tender (TJC) and swollen (SJC) joint counts followed by US feedback every 3 months vs standard care without education. Patient and physician independently performed 28-joint counts at each visit. Outcome variables included the percentage of patients with good agreement with physician-derived swollen joints [prevalence-adjusted bias-adjusted kappa (PABAK) >0.6] as well as agreement in the SJC (Bland and Altman 95% limits of agreement), feasibility/patient satisfaction survey and disease activity at 6 months. RESULTS: Of the 101 randomized patients, 95 were included (51 in the education arm and 44 in the standard care arm). At 6 months there was a significant difference in the proportion of patients with swollen joint PABAK >0.6 in the education arm compared with standard care (98 vs 85%, P = 0.02). Limits of agreement for the SJC difference between physician and patients were reduced only in the education arm. The training method is considered feasible, with 94% of patients reporting it as useful. A trend of higher rates of disease remission (28-joint DAS <2.6) in the education arm vs standard care (47% vs 29%, P = 0.07) was seen. CONCLUSION: A short course of education with US feedback may be helpful in educating patients to assess for clinical synovitis. TRIAL REGISTRATION: Clinical trials.gov, https://clinicaltrials.gov, NCT02351401.

Neurosjögren: early therapy is associated with successful outcomes.

BACKGROUND: Primary Sjögren syndrome (PSS) is a systemic autoimmune condition with an estimated prevalence of 0.6%. The frequency of neurologic manifestations in PSS varies widely from 0% to 60%. METHODS: We report the characteristics of PSS patients with neurologic involvement seen at a single tertiary hospital in Singapore. Eight consecutive women (median age, 51 years [range, 38-67 years]) with neurologic manifestations of PSS seen between March 2009 to June 2011 were followed up for a mean duration of 19 months from the onset of neurologic manifestations. RESULTS: Six of 8 patients with neurosjögren had their neurologic manifestation at time of PSS diagnosis. The lag times of neurologic manifestations from PSS diagnosis for the remaining 2 patients were 9 and 30 years, respectively. Sicca symptoms were not readily volunteered as a presenting complaint in the majority of patients. All our patients received early aggressive therapy with pulse corticosteroids and intravenously administered cyclophosphamide. The mean duration from initial presentation to initiation of treatment was 11 days (1-26 days). All achieved good recovery regardless of the type or site of neurologic involvement, initial erythrocyte sedimentation rate, immunoglobulin and complement levels. CONCLUSIONS: Neurologic disease, when present, is a strong contributor to disease activity and damage. Confirmatory tests should be conducted early regardless of the presence of sicca symptoms. Vigilance for the development of new neurologic symptoms is imperative even in chronic, apparently stable patients. It is likely that early initiation of treatment contributed to good recovery in our patients.

A nurse-led, rheumatologist-assisted telemedicine intervention for dose escalation of urate-lowering therapy in gout.

AIMS: Urate-lowering therapy (ULT) is effective in gout, but suboptimal management with wide variability in dose escalation remains widespread. We protocolized dose escalation of ULT to improve gout management. The aim was to reduce time to achieve target serum urate (SU) <360 µmol/L. METHODS: Process improvement tools were used to identify underlying causes of prolonged time to target SU. We designed a nurse-led telemedicine intervention for dose escalation of ULT. Patients with gout with SU ≥360 µmol/L meeting indications for ULT at a single institution were recruited. Exclusion criteria were estimated glomerular filtration rate <30 mL/min, pregnancy, cognitive impairment and poor mobility. A nurse-led telemedicine clinic was set up to perform patient education, monitoring of adverse events and drug escalation. We partnered with primary healthcare centers for routine blood tests. RESULTS: From July 2016 to December 2017, 127 patients were recruited. Median time to target SU was 19.0 weeks (interquartile range [IQR] 11.0-31.0). Median dose of allopurinol was 300 mg/d (IQR 200-400) in normal renal function and lower in renal impairment. Median telemedicine calls required to achieve target SU was 2 (IQR 1-3). No patient was hospitalized for gout flares. Two patients had adverse drug reactions, one required cessation of allopurinol for rash with eosinophilia, the other had self-resolving ulcers and allopurinol was continued. Lower baseline SU and number of gout flares were associated with attainment of target SU. CONCLUSION: A nurse-led telemedicine for gout care is effective and safe. Our results affirm the utility of telemedicine in increasing access to care and lower healthcare utilization.

Singapore chapter of rheumatologists' updated consensus statement on the eligibility for government subsidization of biologic and targeted therapy for the treatment of psoriatic arthritis.

AIM: There have been major advances in biologic treatment options for psoriatic arthritis (PsA) since the publication of the 2015 consensus recommendations by the Chapter of Rheumatologists, College of Physicians, Academy of Medicine, Singapore, for government-assisted funding, thus warranting a revision of this guideline. METHODS: Recent trials and nine published guidelines on the use of biologic therapy for PsA were reviewed. Based on the synthesized evidence, a task force panel (TFP), consisting of 10 practicing rheumatologists in Singapore, rated the statements pertaining to the use of biologic therapy, using a modified Delphi approach. Consensus was obtained if >70% agreed on a statement. RESULTS: The TFP agreed on 10 recommendations pertaining to the initiation, choice and continuation of biologic therapy. A biologic is indicated in patients with PsA: (a) with at least three swollen and tender joints, digits or entheses; and (b) who have failed at least two conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) strategies for a minimum of 3 months each. Any approved drug class including tumor necrosis factor inhibitors, interleukin-17 inhibitors (IL-17i), IL-12/23i or targeted synthetic DMARDs may be considered as first-line treatment, and continued only if a response is achieved by 6 months. CONCLUSION: These recommendations developed through a formal consensus method may be useful to guide funding considerations for appropriate and equitable use of biologic therapy for eligible patients with PsA.

Validity and reliability of the Gout Impact Scale in a multi-ethnic Asian population.

OBJECTIVES: The emphasis on capturing patient-reported outcomes (PRO) is increasing, but gout-specific PRO are lacking. We evaluated the reliability and validity of the 24-item Gout Impact Scale (GIS) of the Gout Assessment Questionnaire 2.0 (GAQ2.0) in a multi-ethnic Asian population. METHODS: Participants with gout in an academic medical center in Singapore completed the GIS which comprises five scales. Confirmatory factor analyses (CFA) were performed. Known-groups validity, divergent validity and internal consistency were evaluated. RESULTS: We analyzed data of 267 participants (mean [SD] age 52.2 [16.08] years, 92.1% men and 76.0% Chinese). CFA based on the original GIS factor structure had good model fit based on Tucker-Lewis Index (TLI) of 0.946 but not when based on Root Mean Square Error Of Approximation (RMSEA), which was 0.123 (90% CI: 0.116-0.130). Internal consistency of GIS exceeded 0.7 in all except one scale, consistent with previous studies. Hypotheses related to known-groups validity were largely supported. Scores were significantly higher (ie greater impact) for participants reporting at least some problem on the EQ-5D-3L anxiety/ depression item across all GIS scales. Correlations between RAND-36 Physical Functioning (PF) scale and all five scales in the GIS were poor (Spearman rank correlation coefficients: -0.2355 to 0.0426), implying that GIS does not measure impact of gout on physical health. CONCLUSION: The GIS is valid and reliable for assessing gout-specific psychosocial functioning in a multi-ethnic Asian population.

Angioedema and systemic lupus erythematosus--a complementary association?

INTRODUCTION: We report angioedema as a rare presentation leading to a diagnosis of systemic lupus erythematosus (SLE). CLINICAL PICTURE: A diagnosis of angioedema was delayed in a patient presenting with limb and facial swelling until she developed acute upper airway compromise. After excluding allergic and hereditary angioedema, acquired angioedema (AAE) was suspected, possibly precipitated by respiratory tract infection. Associated clinical and laboratory features led to a diagnosis of SLE. TREATMENT: Management proved challenging and included high dose steroids and immunosuppressants. OUTCOME: The patient responded to treatment and remains in remission without recurrence of the angioedema. CONCLUSION: AAE occurs due to the acquired deficiency of inhibitor of C1 component of complement (C1 INH). Lymphoproliferative disorders and anti-C1 INH antibodies are well-described associations. However, one should also consider the possibility of SLE.

Case reports of transient loss of vision and systemic lupus erythematosus.

INTRODUCTION: Neuropsychiatric manifestations can occur in up to two-thirds of patients with systemic lupus erythematosus (SLE). The presentations as well as the underlying immunopathogenic mechanisms can be heterogeneous and therefore have an enormous impact on therapeutic options. CLINICAL PICTURE: We describe 2 patients who presented similarly with acute onset binocular reversible visual loss. The first patient had anti-phospholipid syndrome and optic neuritis, while the second patient suffered from posterior reversible leukoencephalopathy syndrome. TREATMENT: Patient one was treated with anti-coagulation and immunosuppression while the second patient required the withdrawal of immunosuppression and supportive therapy. OUTCOME: Both patients responded favourably and had complete visual recovery. CONCLUSIONS: Different management strategies have to be employed for similar presentations having different aetiologies, underscoring the need for constant clinical vigilance.

Patient satisfaction with rheumatology practitioner clinics: can we achieve concordance by meeting patients' information needs and encouraging participatory decision making?

INTRODUCTION: The objective of this study was to determine if patient information needs are being met and the level of patient satisfaction with rheumatology practitioners in participatory decision-making and thereby indirectly explore whether concordance was achieved. MATERIALS AND METHODS: The design was a cross-sectional postal questionnaire survey of 420 patients attending outpatient clinics at the Norfolk and Norwich University Hospital who were taking disease modifying anti-rheumatic drugs (DMARDs) or a biological treatment. The population served is ethnically homogeneous and predominantly Caucasian. RESULTS: The response rate was 76%. Most respondents (79%) had inflammatory arthritis while 66% had rheumatoid arthritis. Seventy-seven per cent of patients reported that the rationale behind commencing treatment was explained and that they were given ample opportunities to ask questions. Eighty-two per cent said they were given an appropriate amount of information. Sixty-four per cent of patients were satisfied with their level of participation in the decision-making process, although a substantial number (25%) said that information from different sources was conflicting. There was no correlation between concern about side effects and patients' perceptions of the effectiveness of medication. Females were more concerned than males about possible side effects; P =0.009, using the Mann-Whitney U test. One third of the patients altered their medication in response to whether their arthritis felt better or worse. CONCLUSION: The majority of patients were satisfied that their information needs were met and with the care provided in the practitioner clinic. Participatory decision-making was sub-optimal despite patient satisfaction with the amount of time allocated to meeting their information needs. We found that patients exercise autonomy in managing their arthritis by regulating their medications through an active decision-making process, which is informed by their previous experience of medication, and how well controlled they felt their arthritis was. Research into this decision-making process may hold the key to achieving concordance.

Catastrophic subarachnoid hemorrhage in eosinophilic granulomatosis with polyangiitis without asthma.

Eosinophilic granulomatosis with polyangiitis (EGPA) is characterized by eosinophilic vasculitis. Patients rarely present without asthma. Cases developing subarachnoid hemorrhage from central nervous system vasculitis are rarely reported. We report a 48-year-old woman with rapidly evolving and progressive multi-system eosinophilic vasculitis in the absence of asthma. Tissue eosinophilia was apparent in a breast lump biopsy. Prior otitis media and prominent lymphoid tissue in the postnasal spaces hinted at otolaryngological disease. She had rapid disease progression with mononeuritis multiplex and eventually succumbed to complications of intracranial hemorrhage secondary to central nervous system vasculitis. This case demonstrates the diagnostic dilemma and treatment considerations in EGPA without asthma. It also raises the question if a reliable biomarker can aid diagnosis in atypical presentations of disease.

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.

The value of referral letter information in predicting inflammatory arthritis--factors important for effective triaging.

The aim of this study is to identify factors from referral information predictive of patients with inflammatory arthritis (IA) requiring early review. Four hundred twenty-six consecutive rheumatologist-triaged referrals from February to June 2012 were retrospectively reviewed to identify patients with rheumatologist-diagnosed IA correctly triaged for review within 2 weeks from referral date. Information from referral was analyzed descriptively followed by univariate logistic regression adjusted for age and sex to identify predictors of IA. Of the 108 patients with rheumatologist-confirmed diagnoses seen within 2 weeks, 76 patients (70.4%) were correctly triaged with 44.7% having rheumatoid arthritis (RA); 9.2%, psoriatic arthritis; 9.2%, spondyloarthritis; and 18.4%, undifferentiated inflammatory arthritis. The majority were females (63.2%), with median age of 52.8 years (Q1; Q3 38.4; 61.3) with referrers indicating presence of morning stiffness in 71.4% and symmetrical distribution in 74.6%. Five or more joints were involved in 65.7% with suspected metacarpophalangeal joint (MCPJ) (44.7%) or proximal interphalangeal joint (PIPJ) (59.6%) involvement. Of the referrals with laboratory results, erythrocyte sedimentation rate (ESR) was raised with median 43.5 mm/h (Q1; Q3 24.8; 77.5) and normal median uric acid of 312.5 µmol/L (Q1; Q3 249.5; 363.5). Univariate analysis revealed that presence of ≥5 joints affected (p = 0.001), symmetrical distribution (p = 0.006), MCPJ (p = 0.003), PIPJ (p = 0.003), and elevated ESR (p = 0.001) were predictive of IA after adjustment for age and sex. Specific information including number, pattern, and location of joint involvement with relevant laboratory investigations should be included in referral letters to assist with effective triaging of patients with IA.

What of guidelines for osteoarthritis?

Osteoarthritis (OA) is by far the most common joint disease and a major cause of pain and disability. The prevalence and impact of OA will increase in the next decades in the Asia-Pacific region due to increased longevity, increasing urbanization and a parallel increase in obesity. The three main types of evidence to inform evidence-based practice are research evidence, expert experience and patient opinion--all three of these are equally weighted. Guideline development groups vary in terms of process and structure of guideline production and in how much integration there is between research, expert and patient evidence. Nevertheless, guidelines on OA concur in recommending: holistic assessment of the patient and individualizing the management plan; patient information access; weight loss if overweight or obese, and prescription of exercise. Additional adjunctive non-pharmacological and pharmacological interventions, including surgery, may be added to this core set as required. However, when audited, it appears that management of OA is often suboptimal, with a major focus on oral analgesics, especially non-steroidal anti-inflammatory drugs. A number of barriers to implementation are evident and appropriate audit of care is necessary to improve delivery of service and to plan healthcare resources. For OA, the effect size of placebo in clinical trials is usually far greater than the additional specific effect of individual treatments, emphasizing the importance of contextual ('meaning') response in this chronic painful condition. This has important implications for clinical care in that optimization of the contextual response can lead to improvements in patient outcomes even in the absence of very effective treatments.

The autoimmunity conundrum: clotting or inflammation.

Antiphospholipid syndrome (APS) is an autoimmune condition with a myriad of clinical manifestations ranging from cardiovascular, neurologic, renal involvement to cutaneous manifestations and thrombocytopenia. We describe a young woman who presented with fever, cough and dyspnea. She had a history of recurrent pregnancy losses and her antiphospholipid antibodies and lupus serologies were positive. Echocardiography showed mobile mitral and aortic valve vegetations. She was treated as for infective endocarditis and diagnosed with primary APS with lupus-like disease. Vigilance is required to establish if there is an underlying rheumatological condition in a patient who presents with presumptive infective endocarditis in the absence of risk factors. Treatment for systemic lupus erythematosus and primary APS are distinct.

Pulmonary complications of infliximab therapy in patients with rheumatoid arthritis.

We describe 5 patients with rheumatoid arthritis (RA) who developed pulmonary complications following infliximab therapy; 4 patients had preexisting usual interstitial pneumonia. As the pathophysiology of the pulmonary insult is unknown, we advise caution in the use of anti-tumor necrosis factor-alpha therapy in patients with RA with underlying lung disease of sufficient severity to withhold methotrexate treatment.