Post-mRNA vaccine flares in autoimmune inflammatory rheumatic diseases: Results from the COronavirus National Vaccine registry for ImmuNe diseases SINGapore (CONVIN-SING).

BACKGROUND: Studies of flares of autoimmune inflammatory rheumatic diseases (AIIRD) after COVID-19 mRNA vaccination are limited by small sample size, short follow up or at risk of selection bias. METHODS: A national retrospective cohort study of consecutive AIIRD patients ≥12 years old, across 8 hospitals who received at least one dose of a COVID-19 mRNA vaccine. Patients were included from the date of 1st vaccine dose and censored at the time of flare or on the date of the clinic visit at least 3 months from cohort entry, whichever came first. Predictors of flare were determined by Cox proportional hazards analysis. FINDINGS: 4627 patients (73% Chinese, 71% female) of median (IQR) age 61 (48, 70) years were included; 42% Rheumatoid arthritis, 14% Systemic lupus erythematosus and 11% Psoriatic arthritis. 47% were in remission, 41% low disease activity, 10% moderate disease activity and 1% in high disease activity. 18% patients flared, of which 11.7% were within the 3-month period of interest. 11.8% patients improved. Median (IQR) time-to-flare was 60 (30, 114) days. 25% flares were self-limiting, 61% mild-moderate and 14% severe. Older patients (53-65 years and >66 years) had a lower risk of flare [HR 0.6 (95% CI 0.5-0.8) and 0.7 (0.6-0.8) respectively]. Patients with inflammatory arthritis and with active disease had a higher risk of flare [HR 1.5 (1.2-2.0) and 1.4 (1.2-1.6), respectively]. Treatment with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), immunosuppression and prednisolone was also associated with an increased risk of flare [HR 1.5 (1.1-2), 1.2 (1.1-1.4) and 1.5 (1.2-1.8) for prednisolone ≤7.5 mg respectively]. INTERPRETATION: There was a moderately high rate of AIIRD flares after mRNA vaccination but also improvement in several patients. Severe flares and hospitalisation were rare. Thus, vaccination remains safe and highly recommended.

Proton pump inhibitor induced subacute cutaneous lupus erythematosus: Clinical characteristics and outcomes.

BACKGROUND: There is a growing literature reporting the association between proton pump inhibitor (PPI) use and subacute cutaneous lupus erythematosus (SCLE). AIMS: To compare the clinical characteristics of a cohort of patients with PPI-induced SCLE, their clinical course and treatment with a control group of primary SCLE patients not exposed to PPI. METHODS: We conducted a matched case-control study in a tertiary referral setting at the Louise Coote Lupus Unit. There were 64 SCLE patients: 36 with PPI-induced SCLE and 28 patients with primary SCLE. RESULTS: Twenty-six patients (72%) had pre-existing SLE in the PPI-induced SCLE group. Lower limb skin lesions were significantly more prevalent in the PPI group (p < 0.0001). The prevalence of anti-Ro and anti-Ro-52 antibodies was numerically higher in the PPI group (64% and 60%), respectively, compared with 46% and 42% in the primary SCLE group. Peripheral blood eosinophils were normal in all patients in the PPI group. Thirteen patients underwent skin biopsy in the PPI group and 12 had histology in keeping with SCLE. The median time to presentation was 8 months with a median resolution period of 6 weeks. PPIs were stopped in 34 patients, while 2 patients continued treatment for other clinical indications. Twelve patients received concurrent oral corticosteroids. Two patients had severe SCLE in the form of Toxic Epidermal Necrolysis requiring critical care admission and were managed with corticosteroids, IV immunoglobulin and/or belimumab. CONCLUSION: Lower limb involvement is a pointer to PPI-induced SCLE which is likely a class effect with all PPI.

Development of a novel gout treatment patient decision aid by patient and physician: A qualitative research study.

BACKGROUND: Gout treatment is not optimized globally, often due to therapeutic inertia by physicians or poor adherence to urate-lowering medications by patients. A patient decision aid (PDA) to facilitate shared decision making (SDM) in gout treatment may overcome these physician-patient barriers. OBJECTIVE: The study explored the views of physicians and patients on a novel locally designed gout treatment PDA prototype. DESIGN: Qualitative descriptive design was used to gather data from in-depth-interviews (IDI) and focus group discussions (FGD). Data analysis was via thematic analysis. Emergent themes shaped a revised version of the PDA. SETTING AND PARTICIPANTS: Adult Asian patients with recent acute gout exacerbations and local Primary Care Physicians (PCP) in Singapore were purposefully chosen. 15 patients with gout and 11 PCPs participated across three IDIs and six FGDs, with the investigators exploring their views of a prototype gout treatment PDA. RESULTS: Patients and physicians generally concurred with the content and design of the PDA prototype. However, while patients preferred fewer treatment details, the PCPs desired more information. Patients preferred the display of statistics, while PCPs felt that numbers were not relevant to patients. The latter were hesitant to include treatment options that were unavailable in primary care. Both stakeholders indicated that they would use the PDA during a consultation. PCPs would need further training in SDM, given a lack of understanding of it. CONCLUSION AND PATIENT CONTRIBUTION: Patients will be the prime users of the PDA. While their views differed partially from the physicians, both have jointly developed the novel gout treatment PDA.

Relapsing polychondritis - A single Centre study in the United Kingdom.

INTRODUCTION AND OBJECTIVES: Relapsing Polychondritis (RP) is a rare immune mediated inflammatory disorder that may result in damage and destruction of cartilaginous tissues. PATIENTS AND METHODS: We retrospectively analysed patients with a clinical diagnosis of RP. Patients were investigated using pulmonary function tests, dynamic high-resolution CT scans, bronchoscopy, laryngoscopy and/or PET-CT scans along with autoimmune serology. Patients had other specialist reviews when indicated. RESULTS: We identified 68 patients with a diagnosis of RP, 55 (81%) were Caucasian, 8 (12%) Afro Caribbean, 4 (6%) Asian and 1 patient had Mixed Ethnicity. Twenty-nine (43%) had pulmonary involvement and in 16, pulmonary involvement was the initial presentation. The mean age at onset was 44 years (range 17-74). There was a mean diagnostic delay of 55 weeks. Sixty-six (97%) patients received a combination of oral Prednisolone and disease modifying anti-rheumatic drugs. Twelve of 19 (63%) received biologics, with an initial good response, and 10 remain on treatment. Eleven patients with respiratory collapse required CPAP to maintain airway patency. Twelve (18%) patients died due to RP and 9 had respiratory complications. Two patients developed myelodysplasia and one had lung carcinoma. In a multivariate regression analysis, the prognostic variables were ethnicity, nasal chondritis, laryngotracheal stricture and elevated serum creatinine. CONCLUSION: RP is a rare autoimmune condition often associated with significant delays in diagnosis and initiation of treatment. Pulmonary involvement in RP may cause significant morbidity and mortality due to organ damage. Disease modifying anti rheumatic drugs and biologics should be considered early in the disease course to minimise adverse effects of long-term corticosteroid therapy and organ damage.

Prevalence and factors associated with flares following COVID-19 mRNA vaccination in patients with rheumatoid arthritis, psoriatic arthritis and spondyloarthritis: a national cohort study.

OBJECTIVE: To determine prevalence and factors associated with flares post Coronavirus disease 2019 (COVID-19) mRNA vaccination in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and spondyloarthritis (SpA). METHODS: A retrospective multi-centre study was conducted (January 2021 to February 2022). Data were collected during index visit, defined as first post-vaccine visit in which the patient had a physician-defined flare, or if at least 3 months had elapsed since first vaccine dose, whichever came first. Factors associated with flares were identified using mixed effects Cox regression and expressed as hazard ratio (HR) and 95% confidence interval (CI). RESULTS: Total of 2377 patients were included (1563 RA, 415 PsA and 399 SpA). Among patients with RA, PsA and SpA, 21.3%, 24.1% and 21.8% experienced a flare respectively. Of those who experienced a flare, only 10.2%, 11.0% and 14.9% were severe in patients with RA, PsA and SpA respectively. Patients with low or moderate/high disease were more likely to flare compared to those in remission in patients with RA only (HR: 1.68, 95% CI 1.22-2.31; HR: 2.28, 95% CI 1.50-3.48, respectively). Receiving the Moderna vaccine was associated with a higher HR of flare compared to the Pfizer vaccine in patients with PsA only (HR: 2.21, 95% CI 1.20-4.08). Patients who had two vaccine doses were found to be less likely to flare (HR: 0.08, 95% CI 0.06-0.10). HRs of flares were not significantly different among RA, PsA and SpA. CONCLUSION: About one-fifth of patients experienced a disease flare post COVID-19 mRNA vaccination, but most flares were non-severe. Patients with active disease prior to vaccination should be monitored closely for disease flares, especially in patients with RA.

Latent Class Analysis Identifies Distinct Phenotypes of Systemic Lupus Erythematosus Predictive of Flares after mRNA COVID-19 Vaccination: Results from the Coronavirus National Vaccine Registry for ImmuNe Diseases SINGapore (CONVIN-SING).

We recently reported that messenger ribonucleic acid (mRNA) coronavirus disease 2019 (COVID-19) vaccination was associated with flares in 9% of patients with systemic lupus erythematosus (SLE). Herein, we focused our analysis on patients from a multi-ethnic Southeast Asian lupus cohort with the intention of identifying distinct phenotypes associated with increased flares after mRNA COVID-19 vaccination. METHODS: Six hundred and thirty-three SLE patients from eight public healthcare institutions were divided into test and validation cohorts based on healthcare clusters. Latent class analysis was performed based on age, ethnicity, gender, vaccine type, past COVID-19 infection, interruption of immunomodulatory/immunosuppressive treatment for vaccination, disease activity and background immunomodulatory/immunosuppressive treatment as input variables. Data from both cohorts were then combined for mixed effect Cox regression to determine which phenotypic cluster had a higher risk for time to first SLE flare, adjusted for the number of vaccine doses. RESULTS: Two clusters were identified in the test (C1 vs. C2), validation (C1' vs. C2') and combined (C1″ vs. C2″) cohorts, with corresponding clusters sharing similar characteristics. Of 633 SLE patients, 88.6% were female and there was multi-ethnic representation with 74.9% Chinese, 14.2% Malay and 4.6% Indian. The second cluster (C2, C2' and C2″) was smaller compared to the first. SLE patients in the second cluster (C2 and C2') were more likely to be male, non-Chinese and younger, with higher baseline disease activity. The second cluster (C2″) had more incident flares (hazard ratio = 1.4, 95% confidence interval 1.1-1.9, p = 0.014) after vaccination. A higher proportion of patients in C2″ had immunomodulatory/immunosuppressive treatment interruption for vaccination as compared to patients in C1″ (6.6% vs. 0.2%) (p < 0.001). CONCLUSION: We identified two distinct phenotypic clusters of SLE with different patterns of flares following mRNA COVID-19 vaccination. Caution has to be exercised in monitoring for post-vaccination flares in patients with risk factors for flares such as non-Chinese ethnicity, young age, male gender and suboptimal disease control at the time of vaccination.

Maternal and Fetal Outcomes in Systemic Lupus Erythematosus Pregnancies.

INTRODUCTION: To describe the maternal and fetal outcomes in systemic lupus erythematosus (SLE) pregnancies followed-up in a single tertiary referral centre. METHODS: We performed a retrospective cohort study of 75 SLE pregnancies who were followed up in Singapore General Hospital over a 16-year period from 2000 to 2016. Adverse fetal and maternal outcomes including preterm delivery, miscarriages, fetal growth restriction, congenital heart block, neonatal lupus, pre-eclampsia and SLE flares were obtained from the medical records. RESULTS: The mean age at conception was 32 years old (SD 3.8). The mean SLE disease duration was 5.9 years (SD 5.2). The majority (88%) had quiescent SLE disease activity at baseline. Most pregnancies resulted in a live birth (74.7%). The mean gestational age at birth was 37.4 weeks (SD 3.4). Adverse fetal outcomes occurred in 53.3%. Preterm delivery (33.9%), miscarriages (20%) and fetal growth restriction (17.3%) were the most frequent adverse fetal outcomes. There was 1 neonatal death and SLE flares occurred in a third (33%). In the subgroup of SLE pregnancies with antiphospholipid syndrome, there were higher SLE flare rates (40%) and adverse fetal outcomes occurred in 8 pregnancies (80%). There were no predictive factors identified for all adverse fetal and maternal outcomes. In the subgroup analysis of preterm delivery, anti-Ro (SS-A) antibody positivity and hydroxychloroquine treatment were associated with a lower risk of preterm delivery. CONCLUSION: Although the majority had quiescent SLE disease activity at baseline, SLE pregnancies were associated with high rates of adverse fetal and maternal outcomes.

Prevalence and factors associated with flares following COVID-19 mRNA vaccination in patients with rheumatoid arthritis, psoriatic arthritis and spondyloarthritis: a national cohort study

Abstract Objective To determine prevalence and factors associated with flares post Coronavirus disease 2019 (COVID-19) mRNA vaccination in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and spondyloarthritis (SpA). Methods A retrospective multi-centre study was conducted (January 2021 to February 2022). Data were collected during index visit, defined as first post-vaccine visit in which the patient had a physician-defined flare, or if at least 3 months had elapsed since first vaccine dose, whichever came first. Factors associated with flares were identified using mixed effects Cox regression and expressed as hazard ratio (HR) and 95% confidence interval (CI). Results Total of 2377 patients were included (1563 RA, 415 PsA and 399 SpA). Among patients with RA, PsA and SpA, 21.3%, 24.1% and 21.8% experienced a flare respectively. Of those who experienced a flare, only 10.2%, 11.0% and 14.9% were severe in patients with RA, PsA and SpA respectively. Patients with low or moderate/high disease were more likely to flare compared to those in remission in patients with RA only (HR: 1.68, 95% CI 1.22-2.31; HR: 2.28, 95% CI 1.50-3.48, respectively). Receiving the Moderna vaccine was associated with a higher HR of flare compared to the Pfizer vaccine in patients with PsA only (HR: 2.21, 95% CI 1.20-4.08). Patients who had two vaccine doses were found to be less likely to flare (HR: 0.08, 95% CI 0.06-0.10). HRs of flares were not significantly different among RA, PsA and SpA. Conclusion About one-fifth of patients experienced a disease flare post COVID-19 mRNA vaccination, but most flares were non-severe. Patients with active disease prior to vaccination should be monitored closely for disease flares, especially in patients with RA.

Magnetic resonance imaging bone edema is not a major feature of gout unless there is concomitant osteomyelitis: 10-year findings from a high-prevalence population.

OBJECTIVE: Magnetic resonance imaging (MRI) is commonly used in autoimmune inflammatory arthritis to define disease activity and damage, but its role in gout remains unclear. The aim of our study was to identify and describe the MRI features of gout. METHODS: Over a 10-year period we identified patients with gout who underwent MRI scanning of the hands or feet. Scans were reviewed for erosions, synovitis, tenosynovitis, tendinosis, bone edema, and tophi by a musculoskeletal radiologist and 2 rheumatologists in a blinded manner. MRI features in patients with uncomplicated gout were compared with features where concomitant osteomyelitis was diagnosed. RESULTS: A total of 47 patients with gout (51 scans) were included: 33 (70%) had uncomplicated gout and 14 (30%) had gout complicated by osteomyelitis. MRI features included tophi in 36 scans (71%), erosions in 35 (69%), bone edema in 27 (53%), synovitis in 15 (29%), tenosynovitis in 8 (16%), and tendinosis in 2 (4%). Uncomplicated gout and gout plus osteomyelitis did not differ for most MRI features. However, "severe bone marrow edema" was much more common in gout plus osteomyelitis, occurring in 14/15 scans (93%) compared with 3/36 scans (8%) in uncomplicated gout (OR 154.0, 95% CI 14.7-1612, p < 0.0001). Sensitivity and specificity of "severe bone edema" for concomitant osteomyelitis were 0.93 (95% CI 0.68-0.99) and 0.92 (95% CI 0.78-0.98), respectively. CONCLUSION: MRI reveals that gout affects the joints, bones, and tendons. Bone edema in patients with chronic tophaceous gout is frequently mild and this contrasts with the "severe bone edema" observed in patients with concomitant osteomyelitis.