Genetic Biomarkers as Predictors of Response to Tocilizumab in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis

Rheumatoid arthritis (RA) is a lifelong, debilitating disease which incredibly impacts a patient’s quality of life if not treated to the optimal target. The clinical response of tocilizumab, an interleukin-6 (IL-6) inhibitor, is associated with several gene polymorphisms, particularly targeting the IL-6 pathway. This systematic review and meta-analysis seeks to investigate genetic biomarkers that predict the treatment outcome of tocilizumab therapy in RA patients. After evaluating the quality of retrieved records, five studies were chosen to carry out a quantitative synthesis involving 591 participants. We analysed genetic markers of IL-6R single nucleotide polymorphism (SNP)s rs12083537, rs2228145 and rs4329505, FCGR3A, CD69, GALNT18 and FCGR2A. A plausible finding based on meta-analysis revealed that RA patients with homozygous AA genotype for rs12083537 polymorphism of the IL-6R gene demonstrate a better response to TCZ treatment as opposed to homozygous and heterozygous patients with the G allele. Nonetheless, limitations in evaluating the available studies by meta-analysis include a lack of studies with dissimilarities in study design and outcome definitions, small sample sizes with low statistical power and heterogeneity of cohorts, a restricted the number of tested SNPs and small effects for the selected variants. Inconsistent finding remains as a great challenge to forge ahead towards personalised medicine for RA management

Necrotizing autoimmune myopathy: a case series

Necrotizing autoimmune myopathy (NAM) is considered a new subgroup of a rare autoimmune idiopathic inflammatory myopathies. Classically, NAM presented with sub-acute onset of proximal muscle loss of power with raised creatinine kinase and characteristic muscle biopsy showing muscle necrosis and regeneration with little inflammation. Statin use, connective tissue diseases, malignancy and HIV infection are the identified risk factors for NAM. The autoantibodies expected to be presented in NAM are anti-signal recognition particle (SRP) and anti-hydroxymethylglutaryl-coenzyme A reductase (anti-HMGCR) antibodies. In this article, we present three cases of NAM with different risk factors and autoantibodies which we believe to have impact on the clinical course and outcome of our patients

Successful febuxostat desensitization in a patient with febuxostat hypersensitivity: A Malaysian experience

Over the years, allopurinol has been widely used as the preferred choice of urate lowering therapy in patients with gout. However, its role in patients with renal impairment is limited; and adverse reactions are well documented. Febuxostat, a newer oral non-purine xanthine oxidase inhibitor has been proven in several trials to be more effective and tolerable compared to allopurinol and may be used in patients with renal impairment. Here, we describe a case of successful febuxostat desensitization in a patient with a history of allopurinol- and febuxostat-induced adverse cutaneous reaction, as well as the protocol utilized

Anti-MDA5 dermatomyositis after COVID-19 vaccination:a case-based review

Anti-MDA5 (Melanoma differentiation-associated protein 5) myositis is a rare subtype of dermatomyositis (DM) characterized by distinct ulcerative, erythematous cutaneous lesions and a high risk of rapidly progressive interstitial lung disease (RP-ILD). It has been shown that SARS-CoV-2 (COVID-19) replicates rapidly in lung and skin epithelial cells, which is sensed by the cytosolic RNA-sensor MDA5. MDA5 then triggers type 1 interferon (IFN) production, and thus downstream inflammatory mediators (EMBO J 40(15):e107826, 2021); (J Virol, 2021, https://doi.org/10.1128/JVI.00862-21); (Cell Rep 34(2):108628, 2021); (Sci Rep 11(1):13638, 2021); (Trends Microbiol 27(1):75–85, 2019). It has also been shown that MDA5 is triggered by the mRNA COVID-19 vaccine with resultant activated dendritic cells (Nat Rev Immunol 21(4):195–197, 2021). Our literature review identified one reported case of MDA5-DM from the COVID-19 vaccine (Chest J, 2021, https://doi.org/10.1016/j.chest.2021.07.646). We present six additional cases of MDA5-DM that developed shortly after the administration of different kinds of COVID-19 vaccines. A review of other similar cases of myositis developing from the COVID-19 vaccine was also done. We aim to explore and discuss the evidence around recent speculations of a possible relation of MDA5-DM to COVID-19 infection and vaccine. The importance of vaccination during a worldwide pandemic should be maintained and our findings are not intended to discourage individuals from receiving the COVID-19 vaccine

Preliminary report: April 2009 - August 2010 National Inflammatory Arthritis Registry (NIAR)

Rheumatoid Arthritis (RA) is the most common form of infl ammatory arthritis. It is estimated to affect about 1% of the population. Of unknown aetiology, it typically affects many joints, causing acute inflammation, in most cases leading to joint erosions and joint damage (1). The NIAR, initiated in 2008, was set up with the aim of obtaining information about patients with Rheumatoid Arthritis. Information about patients with the other inflammatory arthritides will be collected in the future