Relationship Between Inflammation and Metabolism in Patients With Newly Presenting Rheumatoid Arthritis.

Background: Systemic inflammation in rheumatoid arthritis (RA) is associated with metabolic changes. We used nuclear magnetic resonance (NMR) spectroscopy-based metabolomics to assess the relationship between an objective measure of systemic inflammation [C-reactive protein (CRP)] and both the serum and urinary metabolome in patients with newly presenting RA. Methods: Serum (n=126) and urine (n=83) samples were collected at initial presentation from disease modifying anti-rheumatic drug naïve RA patients for metabolomic profile assessment using 1-dimensional 1H-NMR spectroscopy. Metabolomics data were analysed using partial least square regression (PLS-R) and orthogonal projections to latent structure discriminant analysis (OPLS-DA) with cross validation. Results: Using PLS-R analysis, a relationship between the level of inflammation, as assessed by CRP, and the serum (p=0.001) and urinary (p<0.001) metabolome was detectable. Likewise, following categorisation of CRP into tertiles, patients in the lowest CRP tertile and the highest CRP tertile were statistically discriminated using OPLS-DA analysis of both serum (p=0.033) and urinary (p<0.001) metabolome. The most highly weighted metabolites for these models included glucose, amino acids, lactate, and citrate. These findings suggest increased glycolysis, perturbation in the citrate cycle, oxidative stress, protein catabolism and increased urea cycle activity are key characteristics of newly presenting RA patients with elevated CRP. Conclusions: This study consolidates our understanding of a previously identified relationship between serum metabolite profile and inflammation and provides novel evidence that there is a relationship between urinary metabolite profile and inflammation as measured by CRP. Identification of these metabolic perturbations provides insights into the pathogenesis of RA and may help in the identification of therapeutic targets.

Symptoms in individuals at risk of rheumatoid arthritis.

An increasing interest in treating individuals at risk of rheumatoid arthritis (RA) to prevent the development of this chronic condition has focussed attention on the identification of risk factors of this disease. Most patients who develop RA progress through a preceding symptomatic phase that may take the form of arthralgia, palindromic rheumatism or unclassified arthritis before a disease currently classifiable as RA is established. An understanding of symptoms that identify individuals as being at risk of RA is a critical issue. Constellations of relevant symptoms could (1) form the basis of public health campaigns to encourage rapid consultation, (2) inform primary health care providers regarding which patients to perform additional tests in or whom to refer to a rheumatologist and (3) be included in algorithms to predict RA development. In this review, we present qualitative and quantitative data summarising current understanding of the symptoms experienced by individuals at risk of RA.

Metabolomics to identify biomarkers and as a predictive tool in inflammatory diseases.

There is an overwhelming need for a simple, reliable tool that aids clinicians in diagnosing, assessing disease activity and treating rheumatic conditions. Identification of biomarkers in partially understood inflammatory disorders has long been sought after as the Holy Grail of Rheumatology. Given the complex nature of inflammatory conditions, it has been difficult to earmark the potential biomarkers. Metabolomics, however, is promising in providing new insights into inflammatory conditions and also identifying such biomarkers. Metabolomic studies have generally revealed increased energy requirements for by-products of a hypoxic environment, leading to a characteristic metabolic fingerprint. Here, we discuss the significance of such studies and their potential as a biomarker.

Systematic review of randomized controlled trials on interventions for melasma: an abridged Cochrane review.

BACKGROUND: Multiple treatments exist for melasma; they are often substandard and associated with side effects. OBJECTIVES: We sought to assess the effectiveness of interventions used in the management of all types of melasma. METHODS: We undertook a systematic review using the methodology of the Cochrane Collaboration. RESULTS: We included 20 studies with a total of 2125 participants covering 23 different treatments. A meta-analysis was not possible because of the heterogeneity of treatments. Triple-combination cream (hydroquinone, tretinoin, and fluocinolone acetonide) was more effective at lightening melasma than hydroquinone alone (relative risk 1.58, 95% confidence interval 1.26-1.97) or any of the agents in a dual-combination cream. Azelaic acid (20%) was significantly more effective than 2% hydroquinone (relative risk 1.25, 95% confidence interval 1.06-1.48) at lightening melasma. In 2 studies where tretinoin was compared with placebo, objective measures demonstrated significant reductions in the severity. However, only in 1 study did participants rate a significant improvement (relative risk 13, 95% confidence interval 1.88-89.74). LIMITATIONS: There was poor methodology, a lack of standardized outcome assessments, and short duration of studies. CONCLUSIONS: The current limited evidence supports the efficacy of multiple interventions. Randomized controlled trials on well-defined participants with long-term outcomes are needed.