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Arthritis, general [keywords]
- Protein kinase small molecule inhibitors for rheumatoid arthritis: Medicinal chemistry/clinical perspectives. [Journal Article, Review]
- World J Orthop 2014 Sep 18; 5(4):496-503.
Medicinal chemistry strategies have contributed to the development, experimental study of and clinical trials assessment of the first type of protein kinase small molecule inhibitor to target the Janus kinase/Signal Transducers and Activators of Transcription (JAK/STAT) signaling pathway. The orally administered small molecule inhibitor, tofacitinib, is the first drug to target the JAK/STAT pathway for entry into the armamentarium of the medical therapy of rheumatoid arthritis. The introduction of tofacitinib into general rheumatologic practice coupled with increasing understanding that additional cellular signal transduction pathways including the mitogen-activated protein kinase and phosphatidylinositide-3-kinase/Akt/mammalian target of rapamycin pathways as well as spleen tyrosine kinase also contribute to immune-mediated inflammatory in rheumatoid arthritis makes it likely that further development of orally administered protein kinase small molecule inhibitors for rheumatoid arthritis will occur in the near future.
- Association of Metabolic Syndrome and Hidradenitis Suppurativa. [JOURNAL ARTICLE]
- JAMA Dermatol 2014 Sep 17.
An association between the metabolic syndrome (MetS) and chronic inflammatory diseases, such as psoriasis or rheumatoid arthritis, has been suggested. Hidradenitis suppurativa (HS), a more localized chronic inflammation of the skin, has been speculated to have a similar association. Hidradenitis suppurativa is a substantial burden for the individual and a socioeconomic burden globally. Information about the burden of possible comorbidities is scarce.To investigate the possibility of an association between HS and MetS.Cross-sectional population- and hospital-based study of HS and MetS. We identified 32 patients with physician-verified HS from the outpatient clinic at the Department of Dermatology, Roskilde Hospital, and 326 patients with HS and 14 851 individuals without HS from the general population. Individuals with HS were younger, predominantly female, and more often smokers compared with the non-HS group.Hidradenitis suppurativa.Metabolic syndrome and its components of diabetes mellitus, hypertension, dyslipidemia, and obesity.When compared with the non-HS group, the odds ratios (ORs) for the hospital HS and population HS groups were 3.89 (95% CI, 1.90-7.98) and 2.08 (95% CI, 1.61-2.69), respectively, for MetS; 5.74 (95% CI, 1.91-17.24) and 2.44 (95% CI, 1.55-3.83), respectively, for diabetes mellitus; 6.38 (95% CI, 2.99-13.62) and 2.56 (95% CI, 2.00-3.28), respectively, for general obesity; and 3.62 (95% CI, 1.73-7.60) and 2.24 (95% CI, 1.78-2.82), respectively, for abdominal obesity. With regard to dyslipidemia, significant results were found for decreased levels of high-density lipoprotein cholesterol, with ORs of 2.97 (95% CI, 1.45-6.08) and 1.94 (95% CI, 1.52-2.48) for the hospital HS and general population HS groups, respectively, when compared with the non-HS group. With regard to increased triglyceride levels, only the result for the population HS group compared with the non-HS group was significant, with an OR of 1.49 (95% CI, 1.18-1.87). The OR for hypertension, which was only significant for the hospital HS group compared with the non-HS group, was 2.14 (95% CI, 1.01-4.53). Obesity and inflammation acted as possible confounders. The ORs were higher for the hospital HS group compared with the population HS group. The association between HS and MetS was not influenced by the degree of HS severity.As with more systemic inflammatory diseases, HS appears to be associated with MetS, indicating substantial comorbidities. Because this study is cross-sectional, causality remains to be explored.
- Rheumatoid arthritis and the risk of bipolar disorder: a nationwide population-based study. [Journal Article]
- PLoS One 2014; 9(9):e107512.
Studies have suggested that chronic inflammation plays an essential role in the pathophysiology of both rheumatoid arthritis (RA) and bipolar disorder. The most common clinical features associated with RA are anxiety and depression. The risk of bipolar disorder among patients with RA has not been characterized adequately.To determine the association between RA and the subsequent development of bipolar disorder and examine the risk factors for bipolar disorder among patients with RA.We identified patients who were diagnosed with RA in the Taiwan National Health Insurance Research Database. A comparison cohort was created by matching patients without RA with those with RA according to age, sex, and comorbidities. The occurrence of bipolar disorder was evaluated in both cohorts.The RA cohort consisted of 2,570 patients, and the comparison cohort consisted of 2,570 matched control patients without RA. The incidence of bipolar disorder (incidence rate ratio = 2.13, 95% confidence interval [CI] = 1.12-4.24, P = .013) was higher among patients with RA than among control patients. Multivariate, matched regression models revealed that asthma (hazard ratio [HR] = 2.76, 95% CI 1.27-5.96, P = .010), liver cirrhosis (HR = 3.81, 95% CI = 1.04-14.02, P = .044), and alcohol use disorders (HR = 5.29, 95% CI = 1.71-16.37, P = .004) were independent risk factors for the development of bipolar disorder among patients with RA.RA might increase the incidence of bipolar disorder development. Based on our data, we suggest that, following RA diagnosis, greater attention be focused on women with asthma, liver cirrhosis, and alcohol use disorder. Prospective clinical studies of the relationship between RA and bipolar disorder are warranted.
- 5-Lipoxygenase Inhibitors Attenuate TNF-α-Induced Inflammation in Human Synovial Fibroblasts. [Journal Article]
- PLoS One 2014; 9(9):e107890.
The lipoxygenase isoform of 5-lipoxygenase (5-LOX) is reported to be overexpressed in human rheumatoid arthritis synovial tissue and involved in the progress of inflammatory arthritis. However, the detailed mechanism of how 5-lipoxygenase regulates the inflammatory response in arthritis synovial tissue is still unclear. The aim of this study was to investigate the involvement of lipoxygenase pathways in TNF-α-induced production of cytokines and chemokines. Human synovial fibroblasts from rheumatoid patients were used in this study. 5-LOX inhibitors and shRNA were used to examine the involvement of 5-LOX in TNF-α-induced cytokines and chemokines expression. The signaling pathways were examined by Western Blotting or immunofluorescence staining. The effect of 5-LOX inhibitor on TNF-α-induced chemokine expression and paw edema was also explored in vivo in C57BL/6 mice. Treatment with 5-LOX inhibitors significantly decreased TNF-α-induced pro-inflammatory mediators including interleukin-6 (IL-6) and monocyte chemo-attractant protein-1 (MCP-1) in human synovial fibroblasts. Knockdown of 5-LOX using shRNA exerted similar inhibitory effects. The abrogation of NF-κB activation was involved in the antagonizing effects of these inhibitors. Furthermore, 5-LOX inhibitor decreased TNF-α-induced up-regulation of serum MCP-1 level and paw edema in mouse model. Our results provide the evidence that the administration of 5-LOX inhibitors is able to ameliorate TNF-α-induced cytokine/chemokine release and paw edema, indicating that 5-LOX inhibitors may be developed for therapeutic treatment of inflammatory arthritis.
- Septic arthritis of the pubic symphysis: an atypical abdominal pain. [JOURNAL ARTICLE]
- Acta Clin Belg 2014 Sep 16.:2295333714Y0000000067.
Septic arthritis of the pubic symphysis is a rare infection mostly caused by Staphylococcus aureus, and is traditionally associated with risk factors (sports, female incontinence surgery). Typical features of pubic symphysis infection include abdominal, pelvic, or groin pain that increases upon standing and walking, causing limping to occur. Acute onset of fever is often associated. It is important to distinguish septic arthritis of the pubic symphysis from its aseptic homologue, improperly called 'osteitis pubis' in English literature. This general term is mostly used to designate a mechanical pubic pain and has several aetiological meanings (joint stress, postoperative pain, rheumatic diseases). However, some authors consider the infection of the pubic symphysis as a variant of osteitis pubis, placing the two diseases in the continuum of the same entity. This confusion in pubic pathology related to its rarity and its atypical presentation, may in some cases lead to diagnostic and therapeutic delay. In this article, we would like to make practitioners aware of this uncommon and often ignored anatomical site, so that it can recover its place in the differential diagnosis of abdominal pain.
- Glucocorticoids in Juvenile Idiopathic Arthritis. [JOURNAL ARTICLE]
- Neuroimmunomodulation 2014 Sep 12; 22(1-2):112-118.
Glucocorticoid (GC) drugs are a potent and rapidly effective therapeutic option for the treatment of juvenile idiopathic arthritis (JIA). These medications are mainly used for the management of the extra-articular features of systemic-onset disease. A course of low-dose prednisone may be considered for achieving a rapid disease control in patients with severe polyarthritis refractory to other therapies or while awaiting the full therapeutic effect of a recently initiated disease-modifying antirheumatic drug or biologic agent. Short-term systemic GC administration may also be indicated for chronic iridocyclitis unresponsive to topical therapy. The general objective of GC therapy is to limit the maximum dose and exposure to the highest doses to what is needed to achieve disease control, and then to gradually taper the dose until the minimum level sufficient to maintain disease quiescence over time is reached. High-dose intravenous 'pulse' methylprednisolone administration is sometimes chosen to treat the most severe or acute disease manifestations of systemic JIA, particularly macrophage activation syndrome. Intra-articular GC injection is a safe and rapidly effective treatment for synovitis in children with chronic arthritis. Triamcinolone hexacetonide is the optimal GC preparation for pediatric patients. Local injection therapy is used most frequently to treat oligoarthritis, but the strategy of performing multiple injections to induce disease remission, while simultaneously initiating therapy with second-line or biologic agents, has also been proposed for children with polyarticular JIA. Administration of GCs is associated with potentially deleterious adverse effects, some of which can be irreversible. This highlights the need of a judicious use of these medications and careful monitoring of their toxicity. The recently published recommendations for the management of JIA provide useful guidance to the clinicians for the administration of GCs in children with chronic arthritis. © 2014 S. Karger AG, Basel.
- Risk of Developing Depressive Disorders following Rheumatoid Arthritis: A Nationwide Population-Based Study. [JOURNAL ARTICLE]
- PLoS One 2014; 9(9):e107791.
To evaluate the risk of depressive disorders among rheumatoid arthritis (RA) by using the Taiwan National Health Insurance Research Database (NHIRD).We conducted a retrospective study of a matched cohort of 18 285 participants (3 657 RA patients and 14 628 control patients) who were selected from the NHIRD. Patients were observed for a maximum of 10 years to determine the rates of newly diagnosed depressive disorders, and Cox regression was used to identify the risk factors associated with depressive disorders in RA patients.During the 10-year follow-up period, 205 (11.2 per 1000 person-years) RA patients and 384 (5.1 per 1000 person-years) control patients were diagnosed with depressive disorders. In RA patients, most depressive disorders (n = 163, 80%) developed with five years of being diagnosed with RA. The incidence risk ratio of depressive disorders between RA patients and control patients was 2.20 (95% confidence interval [CI], 1.84-2.61, P<.001). After adjusting for age, sex, and comorbidities, RA patients were 2.06 times more likely to develop depressive disorders (95% CI, 1.73-2.44, P<.001) compared with the control patients. Hyperthyroidism (HR = 1.67) was an independent risk factor for depressive disorders in patients with RA.The likelihood of developing depressive disorders is greater among RA patients than among patients without RA. Symptoms of depression should be sought in patients with RA.
- Altered cellular and humoral immunity to varicella-zoster virus in patients with autoimmune diseases. [JOURNAL ARTICLE]
- Arthritis Rheumatol 2014 Sep 15.
Objective Patients with autoimmune diseases such as systemic lupus erythematosus (SLE) and granulomatosis with polyangiitis (GPA) have a 3-20-fold increased risk of herpes zoster compared to the general population. Aim of this study is to evaluate if susceptibility is due to decreased levels of cellular and/or humoral immunity to varicella-zoster virus (VZV). Methods A cross-sectional study on VZV-specific immunity was performed in 38 SLE patients, 33 GPA patients and 51 healthy controls (HC). IgG and IgM antibody levels to VZV were measured by an in-house glycoprotein enzyme-linked immunosorbent assay (gpELISA). Cellular responses to VZV were determined by interferon (IFN)-γ enzyme-linked immunosorbent spot (ELISpot) assay and carboxyfluorescein succinimidyl ester (CFSE)-dye dilution proliferation assay. Results IgG antibodies, but not IgM antibodies, to VZV were increased in SLE patients compared to levels in HC. Antibodies in GPA patients did not differ significantly from levels in HC. SLE patients, not GPA patients, had a decreased number of IFN-γ spot forming cells in response to stimulation with VZV compared to HC. Proliferation of CD4(+) T cells in response to stimulation with VZV was decreased in SLE patients and not in GPA patients. Conclusion SLE patients have increased IgG antibody levels against VZV, while cellular immunity is decreased. In GPA patients, antibody levels as well as cellular responses to VZV were comparable to those in HC. These data suggest that increased prevalence of HZ in SLE patients is due to a poor cellular response. Vaccination strategies should aim to boost cellular immunity against VZV. © 2014 American College of Rheumatology.
- High-Spatial-Resolution Bone Densitometry with Dual-Energy X-ray Absorptiometric Region-free Analysis. [JOURNAL ARTICLE]
- Radiology 2014 Sep 15.:140636.
Purpose To outline the conceptual development of dual-energy absorptiometric (DXA) region-free analysis, quantify its precision, and evaluate its application to quantify the change in longitudinal femoral periprosthetic bone mineral density (BMD) in patients during the 12 months after total hip arthroplasty. Materials and Methods All subjects had undergone total hip arthroplasty for idiopathic arthritis, and the scans were collected as part of previous ethically approved studies (1998-2005) for which informed consent was provided. Contemporary image processing approaches were used to develop a region of interest-free DXA analysis method with increased spatial resolution for assessment of proximal femoral BMD. The method was calibrated, and its accuracy relative to a proprietary algorithm was assessed by using a hip phantom. The precision of the method was examined by using repeat DXA acquisitions in 29 patients, and its ability to allow spatial resolution of localized periprosthetic BMD change at the hip was assessed in an independent group of 19 patients who were measured throughout a 12-month period. Differences were evaluated with t tests (P < .05). Results The method allowed spatial resolution of more than 10 000 individual BMD data points on a typical archived prosthetic hip scan. The median data point-level error of the method after calibration was -1.9% (interquartile range, -7.2% to 3.5%) relative to a proprietary algorithm. The median data point-level precision, expressed as a coefficient of variation, was 1.4% (interquartile range, 1.2%-1.6%). Evaluation of BMD change in a model of periprosthetic bone loss demonstrated large but highly focal changes in BMD that would not be resolved by using traditional region of interest-based analysis approaches. Conclusion The proposed approach provides a quantitative, precise method for extracting high-spatial-resolution BMD data from existing DXA datasets without the limitations imposed by region of interest-based analysis. © RSNA, 2014.
- Imaging of hidradenitis suppurativa and its complications. [Journal Article]
- Case Rep Radiol 2014.:294753.
We present a 56-year-old man with known diabetes mellitus and a 10-year history of hidradenitis suppurativa (HS) and highlight, through MR imaging findings, the relentless natural progression of the disease, characterized by recurrent exacerbations of abscesses and fistulae and complications of perianal fistulae and sacral osteomyelitis. We also demonstrate the appearance of this condition on PET-CT with F-18 FDG, which was performed for staging after postexcision tissue specimen revealed well-differentiated squamous cell carcinoma. The association of arthritis and possible dactylitis was also manifested in our patient. Discussion of HS in the radiology literature is limited and, to our knowledge, there has been no case report describing these imaging findings in the same patient.