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Concept: Rheumatology

242

Folklore remedies for pain and inflammation in rheumatoid arthritis include the application of magnets and copper to the skin. Despite the popular use of devices containing magnets or copper for this purpose, little research has been conducted to evaluate the efficacy of such treatments.

Concepts: Inflammation, Clinical trial, Rheumatoid arthritis, Rheumatology, Pain, Non-steroidal anti-inflammatory drug, Anti-inflammatory, Acupuncture

177

Genetic diversity across different human populations can enhance understanding of the genetic basis of disease. We calculated the genetic risk of 102 diseases in 1,043 unrelated individuals across 51 populations of the Human Genome Diversity Panel. We found that genetic risk for type 2 diabetes and pancreatic cancer decreased as humans migrated toward East Asia. In addition, biliary liver cirrhosis, alopecia areata, bladder cancer, inflammatory bowel disease, membranous nephropathy, systemic lupus erythematosus, systemic sclerosis, ulcerative colitis, and vitiligo have undergone genetic risk differentiation. This analysis represents a large-scale attempt to characterize genetic risk differentiation in the context of migration. We anticipate that our findings will enable detailed analysis pertaining to the driving forces behind genetic risk differentiation.

Concepts: Human Genome Project, Rheumatology, Ulcerative colitis, Corticosteroid, Systemic lupus erythematosus, Lupus erythematosus, Autoimmune diseases, Proteinuria

173

Systemic sclerosis (scleroderma) is unique among the rheumatic diseases because it presents the challenge of managing a chronic multisystem autoimmune disease with a widespread obliterative vasculopathy of small arteries that is associated with varying degrees of tissue fibrosis. The hallmark of scleroderma is clinical heterogeneity with subsets that vary in the degree of disease expression, organ involvement, and ultimate prognosis. Thus, the term scleroderma is used to describe patients who have common manifestations that link them together, whereas a highly variable clinical course exists that spans from mild and subtle findings to aggressive, life-threatening multisystem disease. The physician needs to carefully characterize each patient to understand the specific manifestations and level of disease activity to decide appropriate treatment. This is particularly important in treating a patient with scleroderma because there is no treatment that has been proven to modify the overall disease course, although therapy that targets specific organ involvement early before irreversible damage occurs improves both quality of life and survival. This review describes our approach as defined by evidence, expert opinion, and our experience treating patients. Scleroderma is a multisystem disease with variable expression; thus, any treatment plan must be holistic, yet at the same time focus on the dominant organ disease. The goal of therapy is to improve quality of life by minimizing specific organ involvement and subsequent life-threatening disease. At the same time the many factors that alter daily function need to be addressed, including nutrition, pain, deconditioning, musculoskeletal disuse, comorbid conditions, and the emotional aspects of the disease, such as fear, depression, and the social withdrawal caused by disfigurement.

Concepts: Medicine, Diseases and disorders, Rheumatology, Autoimmune disease, Lupus erythematosus, Systemic disease, Scleroderma, Systemic scleroderma

172

The aim is to characterize subgroups or phenotypes of rheumatoid arthritis (RA) patients using a systems biology approach. The discovery of subtypes of rheumatoid arthritis patients is an essential research area for the improvement of response to therapy and the development of personalized medicine strategies.

Concepts: Medicine, Evolution, Rheumatoid arthritis, Rheumatology, Systems biology

171

Accompanying the increased use of biologic and non-biologic antirheumatic agents, patients with RA have been exposed to an increased risk of Pneumocystis jirovecii infection, which causes acute fulminant P. jirovecii pneumonia (PCP). Mortality in this population is higher than in HIV-infected individuals. Several guidelines and recommendations for HIV-infected individuals are available; however, such guidelines for RA patients remain less clear. Between 2006 and 2008 we encountered a clustering event of P. jirovecii infection among RA outpatients. Through our experience with this outbreak and a review of the recent medical literature regarding asymptomatic colonization and its clinical significance, transmission modes of infection and prophylaxis of PCP, we have learned the following lessons: PCP outbreaks among RA patients can occur through person-to-person transmission in outpatient facilities; asymptomatic carriers serve as reservoirs and sources of infection; and short-term prophylaxis for eradication of P. jirovecii is effective in controlling PCP outbreaks among RA outpatients.

Concepts: Epidemiology, Rheumatoid arthritis, Rheumatology, Methotrexate, Cyclophosphamide, Disease-modifying antirheumatic drug, Hydroxychloroquine, Sulfasalazine

170

Significant advances have been made in understanding the genetic basis of systemic sclerosis (scleroderma) in recent years. Can these discoveries lead to individualized monitoring and treatment? Besides robustly replicated genetic susceptibility loci, several genes have been recently linked to various systemic sclerosis disease manifestations. Furthermore, inclusion of genetic studies in design and analysis of drug trials could lead to development of genetic biomarkers that predict treatment response. Future genetic studies in well-characterized systemic sclerosis cohorts paired with advanced analytic approaches can lead to development of genetic biomarkers for targeted diagnostic and therapeutic interventions in systemic sclerosis.

Concepts: DNA, Medicine, Gene, Genetics, Genomics, Rheumatology, Scleroderma, Systemic scleroderma

169

BACKGROUND: Metabolic syndrome, a cluster of classical cardiovascular risk factors, including hypertension, obesity, glucose intolerance, and dyslipidemia is highly prevalent in patients with rheumatoid arthritis (RA). The aim of the study was to assess the frequency of metabolic syndrome (MS) in RA patients, and to evaluate the relationships between metabolic syndrome and RA. METHODS: The study was conducted on 120 RA patients according to the 1987 revised American College of Rheumatology classification criteria, and 100 age and sex matched apparently healthy controls. The frequency of metabolic syndrome was assessed using six Metabolic Syndrome definitions (Joint Consensus 2009, National Cholesterol Education Programme 2004 and 2001, International Diabetes Federation, World Health Organisation and European Group for Study of Insulin Resistance). Logistic regression was used to identify independent predictors of metabolic Syndrome. RESULTS: the frequency of metabolic syndrome varied from 18 to 48.6% in RA according to the definition used and was significantly higher than controls (for all definitions p<0.05). In multivariate analysis, higher ESR was independently associated with the presence of Met S (OR =1.36; CI: 1.18--2.12; p = 0.03). Glucocorticoid use, but not other disease modifying anti-rheumatic drugs (DMARDs), values remained significant independent predictors of the presence of metabolic syndrome in RA patients (OR = 1.45; CI: 1.12--2.14; p = 0.04). CONCLUSIONS: In summary, the frequency of metabolic syndrome in RA varies according to the definition used and was significantly higher compared to controls (for all definitions p<0.05). Higher systemic inflammatory marker, and glucocorticoids use were independent predictors associated with the presence of metabolic syndrome in patients with RA. These findings suggest that physicians should screen for metabolic syndrome in patients with RA to control its components and therefore reduce the risk of cardiovascular disease in these patients.

Concepts: Nutrition, Atherosclerosis, Insulin, Diabetes mellitus, Obesity, Rheumatoid arthritis, Rheumatology, Metabolic syndrome

168

Among 101 feet that presented with symptoms and signs similar to Morton’s neuroma, intermetatarsal rheumatoid nodules were found in fiveĀ feet (three patients). Two patients had bilateral involvement. Histology of the excised tissue showed the presence of a rheumatoid nodule and Morton’s neuroma in fourĀ feet and a rheumatoid nodule with unremarkable nerve bundles in one. A rheumatoid nodule can coexist with Morton’s neuroma, as seen in our patients, and the presentation is often similar to that of a Morton’s neuroma. Our patients were rendered asymptomatic with surgical treatment and went on to have appropriate management of rheumatoid arthritis. Rheumatoid nodule should be considered in the differential diagnosis of Morton’s neuroma in not only rheumatoid arthritis patients but also asymptomatic patients who have never been tested for rheumatoid antibodies.

Concepts: Medical terms, Rheumatoid arthritis, Rheumatology, Histopathology, Greek loanwords, Arthritis, Morton's neuroma, Rheumatoid nodule

159

Objective. RA and axial SpA have an important impact on patients' lives. The objective of this study was to explore the reporting of different aspects of that impact in publications, with a focus on differences between diseases and over time.Methods. A systematic literature review retrieved all articles reporting on the life impact of RA or axial radiographic SpA in adults published within the last 10 years and issued from European research. The data were classified into physical impact (including pain, functional assessment and fatigue), psychological impact (including psychological distress and coping) and social impact (including relationships, family and social life). The number of articles published over time was analysed by linear regression.Results. In all, 1352 abstracts were screened and 149 publications (40 056 patients) were analysed: 129 articles (86.5%) concerned RA and 16 (10.7%) concerned axial SpA. The mean number of articles reporting on the physical aspects of impact was 11.4 (s.d. 4.8) per 2-year period, but increased more than 2-fold (from 7 articles in 2001-3 to 15 in 2010-11), in particular due to recent publications on fatigue, whereas the number of articles on psychological aspects [mean 12.4 (s.d. 4.0)] decreased markedly after 2006. Publications reporting on social aspects [mean 8.2 (s.d. 4.1)] remained globally stable.Conclusion. In the era of biologics, there is an interest in the patient-perceived life impact of RA and axial SpA in the European literature, but the impact of RA has been the subject of greater exploration. There are clearly trends over time in the reporting of impact.

Concepts: Rheumatoid arthritis, Rheumatology, Academic publishing, Subject, Arithmetic mean, Arthritis, Publishing, Psoriatic arthritis

153

A patient with a known biopsy of polyarteritis nodosa diagnosis presented with cyclic fevers, acute kidney injury, and progression of rash from macular to pustular, worsening despite being on antibiotics, without evidence of infection on multiple cultures. The patient had a pathological diagnosis from a skin biopsy of acute generalized exanthematous pustulosis syndrome, with a total resolution of rash, fevers, and acute kidney injury on treatment with pulse steroids.

Concepts: Inflammation, Biopsy, Pathology, Rheumatology, Vasculitis, Acute kidney injury, Polyarteritis nodosa, Diseases involving the fasciae