Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
23610010 The beneficial effect of total glucosides of paeony on psoriatic arthritis links to circul 2014 Mar Total glycosides of peony (TGP) is a natural immuno-modulatory drug extracted from traditional Chinese herb peony. It has been approved by State Food and Drug Administration for the treatment of rheumatoid arthritis. However, data of TGP effect on psoriatic arthritis (PsA) is still scarce. In this study, 19 patients with PsA received 12-week treatment of TGP, and clinical efficacy in joint manifestations was evaluated by DAS28 at weeks 0, 4, 8 and 12. Peripheral percentages of Tregs, Th1, Th2 and NK cells were analyzed, and serum Th1-type cytokines (IL-12, IFN-γ and TNF-α), Th2-type cytokines (IL-4, IL-5 and IL-10) as well as pro-inflammatory factors (IL-2, IL-6 and IL-8) were concomitantly examined. Six patients (32%) exhibited ≥25% decrease of DAS28 (responders). Interestingly, all responders displayed a continuous decrease in Treg and Th1 numbers during TGP treatment, concomitant with significant decreases in Th1-type cytokine levels. Serum IL-6 also showed a significant decline in responders. Non-responders lacked these sequential alterations. Thus, TGP merits further consideration as a promising therapeutic option for PsA. The result indicated that recovery of Tregs and Th1 may serve as prognostic markers to assess responsiveness to TGP treatment in PsA.
23762133 Chinese Herbal Formula Huo-Luo-Xiao-Ling Dan Protects against Bone Damage in Adjuvant Arth 2013 Huo-luo-xiao-ling dan (HLXL) is an herbal mixture that has long been used in traditional Chinese medicine for the treatment of rheumatoid arthritis (RA) and other inflammatory disorders. Despite the availability of potent conventionally used drugs for RA, their limited efficacy in a proportion of patients coupled with their high cost and severe adverse effects has necessitated the search for novel therapeutics for this debilitating disease. Further, the control of both inflammation and bone damage is essential for effective management of arthritis. The aim of our study was to evaluate the efficacy of HLXL against arthritic bone damage in adjuvant arthritis (AA) model of RA. Our results show that HLXL treatment suppressed inflammatory arthritis and reduced bone and cartilage damage in the joints of arthritic Lewis rats. HLXL-induced protection against bone damage was mediated primarily via inhibition of mediators of osteoclastic bone remodeling (e.g., receptor activator of nuclear factor kappa-B ligand; RANKL), skewing of RANKL/osteoprotegerin (OPG) ratio in favor of antiosteoclastic activity, reduction in the number of osteoclasts in the arthrodial joint's bone, and inhibition of cytokine production and MMP activity. Our results suggest that HLXL might offer a promising alternative/adjunct treatment for both inflammation and bone damage in RA.
25770637 Raynaud syndrome. 2014 Dec Raynaud syndrome (RS) was first described by the French physician Maurice Raynaud in 1862 with the characteristic tricolor change featuring pallor (ischemic phase), cyanosis (deoxygenation phase), and erythema (reperfusion phase) induced by cold or stress. Although the underlying pathophysiological mechanism is unclear, alterations in activity of the peripheral adrenoceptor have been implicated, specifically an enhanced smooth muscle contraction due to overexpression or hyperactivity of postsynaptic alpha 2 receptors. There are 2 ways that RS can appear clinically; isolated, formerly referred as Raynaud disease or now primary RS and in association with other conditions, usually connective tissue disorders (eg, Sjögren syndrome, systemic lupus erythematosus, scleroderma, and rheumatoid arthritis), frequently called Raynaud phenomenon or secondary RS. The estimated prevalence in the general population is 3%-5%, with a higher prevalence in women than in men. The diagnosis is mainly clinical, based on patient descriptions of skin changes. Upper extremity pulse-volume recording is used to rule out proximal arterial obstruction. The differentiation between a vasospastic vs and obstructive mechanism is made using digital pressures and photoplethysmography, where an obstructive mechanism has decreased pressures and blunted waveforms. Cold challenge testing, such as ice water immersion with temperature recovery, is highly sensitive but lack specificity. Serologic screening (antinuclear antibody and rheumatoid factor) is advocated to rule out associated connective tissue disorders. Most patients with RS can be managed conservatively, with avoidance of cold exposure or hand warming. For those in whom conservative management is inadequate, a number of pharmacologic and surgical therapies have been used. Owing to lack of complete understanding of the underlying pathophysiology, targeted therapy has not been possible; rather, therapy has been focused on the use of general vasodilation strategies. In this review, the diagnosis, natural history, and current medical and invasive therapy are summarized.
25488787 Treatment of spondyloarthritis beyond TNF-alpha blockade. 2014 Oct The advent of biologics targeting tumor necrosis factor-alpha (TNF-alpha) has revolutionized the field of rheumatology in general and the treatment of spondyloarthritis (SpA) in particular, since - apart from non-steroidal anti-inflammatory agents - no disease modifying treatments are available for this frequent, inflammatory rheumatic condition. The significant improvements in signs and symptoms observed with TNF-blockers in this group of diseases, have raised the bar with regard to treatment goals, including clinical remission. Even if treatment failure with TNF-blocking agents may be a relatively rare phenomenon, cases of primary non-responders, secondary loss-of-efficacy and intolerance, have been described. Results with abatacept, rituximab and tocilizumab - all effective in the treatment of rheumatoid arthritis - were disappointing, especially in patients that had previously failed anti-TNF therapy. On the other hand, there is increasing evidence that targeting the cytokines of the Th-17 axis is associated with major improvements of skin psoriasis and its associated arthritis. In axial spondyloarthritis, preliminary proof-of-concept studies with ustekinumab and interleukin-17 targeting therapies suggest that these agents could become the first new treatment options, not targeting TNF. Finally, the advent of small molecules targeting inflammatory, intracellular signalling pathways, may further change our future therapeutic approach.
24470663 mTOR Signaling Cascade in Psoriatic Disease: Double Kinase mTOR Inhibitor a Novel Therapeu 2014 Jan In this short communication we are providing insight about the regulatory role of the phosphatidylinositol 3-kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) kinase system in psoriatic disease. This is an upcoming active research field in respect to elucidating the inflammatory and proliferative cascades of psoriatic disease. To provide a new dimension to the understandings of the molecular principles of the pathogenesis of autoimmune diseases, we hypothesized that (i) dysregulation of cytokines and growth factors in autoimmune diseases activate the mTOR signaling system and (ii) the activated mTOR kinase system is a key regulator of the inflammatory/proliferative cascades of the disease process. In support of this hypothesis we have earlier reported that growth factors (nerve growth factor (NGF) and platelet-derived growth factor (PDGF)) and relevant cytokines (interleukin (IL)-17, IL-22) known to be critical for psoriasis, psoriatic arthritis, and rheumatoid arthritis activate the mTOR signaling system. Here, we are providing our latest observations that the mTOR signaling proteins are upregulated in psoriatic skin and further we observed that proliferation of keratinocytes (KC) and synovial cells (synovial fibroblasts (FLS)) of psoriatic arthritis are dependent on the PI3K-AKT-mTOR kinase system. To our knowledge, we are the first to explore whether a double kinase inhibitor of mTOR signal proteins has a therapeutic potential for psoriatic disease. Here we will be sharing our views, our research work in this field and as well we will provide evidences how a double kinase inhibitor of mTOR signal proteins can be an effective therapeutic agent for psoriatic disease.
24167401 Thermal damage during humeral reaming in total shoulder resurfacing. 2013 Jul INTRODUCTION: Total shoulder resurfacing (TSR) provides a reliable solution for the treatment of glenohumeral arthritis. It confers a number of advantages over traditional joint replacement with stemmed humeral components, in terms of bone preservation and improved joint kinematics. This study aimed to determine if humeral reaming instruments produce a thermal insult to subchondral bone during TSR. PATIENTS AND METHODS: This was tested in vivo on 13 patients (8 with rheumatoid arthritis and 5 with osteoarthritis) with a single reaming system and in vitro with three different humeral reaming systems on saw bone models. Real-time infrared thermal video imaging was used to assess the temperatures generated. RESULTS: Synthes (Epoca) instruments generated average temperatures of 40.7°C (SD 0.9°C) in the rheumatoid group and 56.5°C (SD 0.87°C) in the osteoarthritis group (P = 0.001). Irrigation with room temperature saline cooled the humeral head to 30°C (SD 1.2°C). Saw bone analysis generated temperatures of 58.2°C (SD 0.79°C) in the Synthes (Epoca) 59.9°C (SD 0.81°C) in Biomet (Copeland) and 58.4°C (SD 0.88°C) in the Depuy Conservative Anatomic Prosthesis (CAP) reamers (P = 0.12). CONCLUSION: Humeral reaming with power driven instruments generates considerable temperatures both in vivo and in vitro. This paper demonstrates that a significant thermal effect beyond the 47°C threshold needed to induce osteonecrosis is observed with humeral reamers, with little variation seen between manufacturers. Irrigation with room temperature saline cools the reamed bone to physiological levels and should be performed regularly during this step in TSR.
25988057 Secondary Sjogren's syndrome presenting with hypokalemic periodic paralysis. 2014 Nov Renal tubular acidosis (RTA) may develop in a large population of patients with Sjogren's syndrome (SS), but most of the subjects are asymptomatic. Here, we report a patient with known rheumatoid arthritis and symptoms of xerostomia, xerophthalmia and periodic paralysis. SS should be considered as a cause of RTA. The treatment of the underlying disorder may ameliorate the symptoms.
25378850 Bilateral pleural effusion with APLA positivity in a case of rhupus syndrome. 2014 Oct Rhupus syndrome is a rare syndrome characterized by overlap of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Our patient was a diagnosed case of RA and developed SLE 2 years after. She was a middle-aged woman, presented with bilateral pleural effusion with exacerbation of skin and joint symptoms of SLE. We diagnosed the case as tubercular pleural effusion by positive Mycobacterium tuberculosis in bactec 460 culture. She had also anti-phospholipid antibody positivity without any symptoms and signs of thrombosis.
24619529 [Cheilitis granulomatosa and Melkersson-Rosenthal syndrome. Intralymphatic histiocytosis a 2014 Mar Intravascular and/or intralymphatic cell aggregations can occur in malignant tumors as well as in benign reactive conditions, such as chronic inflammatory diseases. This article discusses the valuable histomorphological aspects of intralymphatic histiocytosis (or granuloma) in the differential diagnostics to other entities exemplified by a case report on juvenile cheilitis granulomatosa. In addition other benign entities sometimes presenting with the phenomenon of intravascular histiocytosis (e.g. rheumatoid arthritis, orthopedic metal implants and Rosai-Dorfman disease) are discussed.
24381786 The enigmatic cytokine oncostatin m and roles in disease. 2013 Dec 8 Oncostatin M is a secreted cytokine involved in homeostasis and in diseases involving chronic inflammation. It is a member of the gp130 family of cytokines that have pleiotropic functions in differentiation, cell proliferation, and hematopoetic, immunologic, and inflammatory networks. However, Oncostatin M also has activities novel to mediators of this cytokine family and others and may have fundamental roles in mechanisms of inflammation in pathology. Studies have explored Oncostatin M functions in cancer, bone metabolism, liver regeneration, and conditions with chronic inflammation including rheumatoid arthritis, lung and skin inflammatory disease, atherosclerosis, and cardiovascular disease. This paper will review Oncostatin M biology in a historical fashion and focus on its unique activities, in vitro and in vivo, that differentiate it from other cytokines and inspire further study or consideration in therapeutic approaches.
23374958 Unilateral lower leg purpura. 2013 Jan 15 We present a case of an extensive, purpuric eruption on the lower leg with peculiar clinical findings in 55-year-old woman with rheumatoid arthritis. The purpuric lesions were present unilaterally on the left lower leg, where prominent varices and telangiectasia were noted. Histological examination revealed a perivascular infiltration of lymphocytic cells and eosinophils and extravasation of erythrocytes in the upper and middle dermis. There was no evidence of vasculitis. The eruption responded well to treatment with hemostatic agents and elastic stockings. Based on the clinical and histological findings, we concluded that the main pathophysiology of the purpuric eruption is an extravasation of erythrocytes related to increased venous pressure secondary to venous stasis.
26516498 Failed back surgery syndrome - definition, epidemiology and demographics. 2013 Feb Failed back surgery syndrome is an unhelpful term that hides the true issues concerning the mechanism of pain and subsequent therapies that patients with chronic radicular neuropathic pain are exposed to. Patients with chronic radicular neuropathic pain who have had previous spinal surgery are numerous and comparable in prevalence and incidence to other pain associated diseases such as rheumatoid arthritis but with higher annual costs. Better recognition of this patient group with the effective recognition and multi-disciplinary care aimed at achieving best patient and societal outcomes is required.
24348567 Rheumatoid factor positivity is associated with increased joint destruction and upregulati 2013 We evaluated changes in gene expression of mTOR, p21, caspase-3, ULK1, TNF α , matrix metalloproteinase (MMP)-9, and cathepsin K in the whole blood of rheumatoid arthritic (RA) patients treated with methotrexate (MTX) in relation to their rheumatoid factor status, clinical, immunological, and radiological parameters, and therapeutic response after a 24-month follow-up. The study group consisted of 35 control subjects and 33 RA patients without previous history of MTX treatment. Gene expression was measured using real-time RT-PCR. Decreased disease activity in patients at the end of the study was associated with significant downregulation of TNF α expression. Downregulation of mTOR was observed in seronegative patients, while no significant changes in the expression of p21, ULK1, or caspase-3 were noted in any RA patients at the end of the study. The increase in erosion numbers observed in the seropositive patients at the end of the follow-up was accompanied by upregulation of MMP-9 and cathepsin K, while seronegative patients demonstrated an absence of significant changes in MMP-9 and cathepsin K expression and no increase in the erosion score. Our results suggest that increased expression of MMP-9 and cathepsin K genes in the peripheral blood might indicate higher bone tissue destruction activity in RA patients treated with methotrexate. The clinical study registration number is 0120.0810610.
25289650 Role of hyperbaric medicine for intractable leg ulcers: a case report. 2014 Oct We present a case report of intractable multifactorial leg ulcer that was treated successfully with multiple approaches including hyperbaric oxygen treatment (HBOT) to prepare for skin grafting. A 66-year-old female with a history of rheumatoid arthritis and Felty's syndrome presented with a non-healing ulcer on her left leg that was caused by a trauma. She failed multiple treatment options including debridement, different wound dressings, antibiotics, anti-inflammatories and vein closure procedure. She finally healed with skin graft following HBOT that prepared the wound bed before the procedure.
25207178 Spontaneous Rupture of the Extensor Pollicis Longus Tendon due to Unusual Etiology. 2014 Mar BACKGROUND: The etiology of spontaneous rupture of the extensor pollicis longus tendon includes systemic or local steroid injections, wrist fracture, tenosynovitis, synovitis, rheumatoid arthritis, and repetitive wrist motions. CASE REPORT: We encountered a case of extensor pollicis longus tendon rupture with an unusual etiology, cow milking. In this case, transfer of the extensor indicis proprius tendon was performed successfully. At 1 year after surgery, extension of the thumb was sufficient. CONCLUSION: It appears that patients with occupations involving repetitive motions are at a high risk of closed tendon ruptures.
24242190 Non-steroidal anti-inflammatory drugs and hypertension. 2014 Jun Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently used to alleviate pain of the patients who suffer from inflammatory conditions like rheumatoid arthritis, osteoarthritis, and other painful conditions like gout. This class of drugs works by blocking cyclooxgenases which in turn block the prostaglandin production in the body. Most often, NSAIDs and antihypertensive drugs are used at the same time, and their use increases with increasing age. Moreover, hypertension and arthritis are common in the elderly patients requiring pharmacological managements. An ample amount of studies put forth evidence that NSAIDs reduce the efficiency of antihypertensive drugs plus aggravate pre-existing hypertension or make the individuals prone to develop high blood pressure through renal dysfunction. This review will help doctors to consider the effects and risk factors of concomitant prescription of NSAIDs and hypertensive drugs.
24953920 Systemic aspects of soft tissue rheumatic disorders (STRDs). 2014 Jun OBJECTIVE: To determine the markers of systemic inflammation in soft tissue rheumatic disorders (STRDs). STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY: Rheumatology Clinic, Yazd, Iran, from November 2010 to December 2011. METHODOLOGY: Patients aged 20 years or above with known diagnosis of STRD according to clinical criteria and/ or paraclinical investigations for at least 3 weeks duration were longitudinally followed. Patients with diagnosis of rheumatoid arthritis, hypothyroidism, or any other known systemic conditions (other than diabetes mellitus) were excluded. After careful and detailed history taking, laboratory tests indicating systemic inflammation including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and routine screening rheumatologic tests were assessed. RESULTS: Of the 90 patients, 75% were female and 25% were male and 28 (31.1%) of patients had diabetes mellitus. Fifty six (62%) and 49 (54%) of all studies cases had some degrees of morning stiffness and remarkable fatigue respectively. Twenty two (24%) had elevated CRP and 5 (5.5%) had abnormal ESR. Rheumatoid factor (RF) and anti-CCP was positive in 5 (5.5%) and 12 (13.3%) of patients accordingly. Three (3.3%) patients suffered from anemia of chronic disease. Mean ESR was 48 ± 7.34 (hl) and mean CRP was 10.06 ± 1.96 mg/dl. Mean RF was 10.8 ± 1.64 U/ml and mean anti- CCP was 18.5 ± 2.71 U/ml. Mean hemoglobin was between 10.4 ± 1.01 g/dl. CONCLUSION: Features of subtle systemic inflammation are positive in some cases of soft tissue rheumatism.
24809277 PET imaging of inflammation. 2014 May 9 Inflammatory diseases are common place and often chronic. Most inflammatory cells have increased uptake of glucose which is enhanced in the presence of local cytokines. Therefore, imaging glucose metabolism by the means of [18] F-fluro-de-oxy glucose (FDG) positron emission tomography (PET) holds significant promise in imaging focal inflammation. Most of the work published involved small series of patients with either vasculitis, sarcoid or rheumatoid arthritis. It would appear that FDG PET is a simple and effective technique to identify inflammatory tissue in these conditions. There is even some work to suggest that by comparing baseline and early post therapy scans clinical outcome can be predicted. This would appear to be true with vasculitis as well as retroperitoneal fibrosis. The number of patients in each study is small but the evidence is compelling enough to recommend FDG PET imaging in the routine care of these patients.
25356316 Rothia prosthetic knee joint infection: report and mini-review. 2013 Oct Rothia spp. are gram-positive pleomorphic bacteria that are part of the normal oral microflora. They are associated with dental and periodontal disease, although systemic infections have also been reported. We describe the case of a 75-year-old lady with rheumatoid arthritis who presented with prosthetic knee joint infection due to Rothia aeria. We discuss its identification and the evidence regarding association of dental disease with Rothia spp. joint infections based on available literature.
23691417 An unusual complication after shoulder hemiarthroplasty. 2013 Hemiarthroplasty of the shoulder can be a safe and an effective treatment for pain in patients with rheumatoid arthritis. Many complications have been previously described in the literature; the most common of which are dislocation, loosening, periprosthetic fractures, and infection. We report a patient who presented with a discharging sinus over the tip of the acromium which was created by the displacement of the prosthesis and erosion of the AC joint and distal clavicle. The erosion of the distal clavicle and AC joint caused the remaining proximal clavicle to become mobile and displaced posteriorly; this spike of clavicle was then able to penetrate the trapezius muscle and eventually the skin causing an aseptic sinus. This was successfully treated with the exploration and excision of the distal 2 cm of the clavicle.