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ID PMID Title PublicationDate abstract
25030429 Emerging role of epigenetics in systemic sclerosis pathogenesis. 2014 Oct Systemic sclerosis is a connective tissue disease of unknown aetiology characterised by autoimmunity, inflammation, vascular abnormalities and ultimately fibrosis. Although great advances have been made in determining the molecular mechanisms of disease pathogenesis over the last decade, aided by new genetic screens, no current specific disease-modifying treatment is yet available. Epigenetics is defined as heritable changes that are not due to changes in DNA sequence, and there is at present intense research effort to understand the basic mechanisms of epigenetic regulation and how these impact diseases. Epigenetic modifications and dysregulation are associated now with autoimmune disease, inflammatory disease and cancer. In rheumatic diseases all three epigenetic processes are associated with various diseases including rheumatoid arthritis and systemic sclerosis. In systemic sclerosis much focus has been on microRNAs; however, other modifications including DNA methylation are emerging to have a key role. This review examines the role of epigenetics in systemic sclerosis and appraises the contribution of each modification and suggests that modulators of epigenetic changes may be a novel therapeutic option.
24980932 Double arthrodesis through a medial approach for end-stage adult-acquired flatfoot. 2014 Jul Triple arthrodesis has traditionally been the procedure of choice for end-stage adult-acquired flatfoot. The results have been universally good, and it has proven to be dependable and predictable. Nonetheless, complications have been reported following triple arthrodesis in certain patients. Selective arthrodesis of the talonavicular joint and subtalar joint through a single medial approach has been developed as an alternative. The authors especially prefer this procedure with severe transverse plane deformity and often choose this approach as an alternative to triple arthrodesis in high-risk patients, including those patients with diabetes mellitus, rheumatoid arthritis, long-term steroid use, and the elderly.
25473708 2014 Jun 30 Non-steroidal anti-inflammatory drugs (NSAIDs) play an important role in the pain management in various clinical conditions such as headaches, menstrual disorders, postoperative pain, spinal and soft tissue pain, rheumatoid arthritis (RA), osteoarthritis (OA), and ankylosing spondylitis (AS) by blocking cyclooxygenase (COX) enzymes that are needed to produce prostaglandin. Ketorolac tromethamine (Toradol) is a NSAID available in Canada that is administered by either oral tablets or intramuscular injection, though this review will focus solely on oral administration. Oral Toradol has a Health Canada indication for short-term management (not to exceed 5 days for post-surgical patients or 7 days for patients with musculoskeletal pain) of moderate to moderately severe acute pain, including post-surgical pain, acute musculoskeletal trauma pain and post-partum uterine cramping pain. The recommended dose for oral administration is 10 mg every 4 to 6 hours, not exceeding 40 mg per day. Common side effects include rash, ringing in the ears, headaches, dizziness, drowsiness, abdominal pain, nausea, diarrhea, constipation, heartburn, and fluid retention. Toradol, like most NSAIDs, is commonly associated with gastrointestinal bleeding. In view of the concern regarding the potential safety risks and uncertainty of additional benefits compared with other NSAIDs, this report aims to review the clinical effectiveness of oral ketorolac for management of dental, non-dental, and non-cancer pain.
24688191 Bilateral diaphragmatic paralysis associated with the use of the tumor necrosis factor-alp 2014 Apr A 51-year-old woman was referred for evaluation of progressive dyspnea of 3 months- duration. She had received 3 doses of adalimumab for treatment of rheumatoid arthritis prior to the onset of her dyspnea. Her chest examination revealed absent diaphragmatic movement with inspiration. Spirometry showed a severe restrictive defect. Radiologic studies confirmed the diagnosis of bilateral diaphragmatic paralysis. Laboratory and radiologic workup excluded other possible causes of the diagnosis. Adalimumab was discontinued, and she was treated with bilevel positive airway pressure ventilation and intravenous immunoglobulin. Three months later, the diaphragmatic paralysis persisted. This is the second reported case of bilateral diaphragmatic paralysis occurring in a patient who had received adalimumab. Acute neuropathies are rare side effects of tumor necrosis factor-alpha inhibitors.
24600755 Selective case study describing the use of Apligraf on necrobiosis lipoidica associated wi 2014 Feb Necrobiosis lipoidica is a rare skin disease characterised by large, well-demarcated, symmetrical plaques with overlying telangiectasias and atrophic, fibrotic features. The disease is associated with diabetes mellitus (1 in 300 cases), but can also be linked to other diseases such as rheumatoid arthritis. Women are three times more likely to develop necrobiosis lipoidica compared to men. Ulcerations are the most serious type of complications in necrobiosis lipoidica, and they occur most frequently on the legs of patients. However, the aetiology of necrobiosis lipoidica still remains unclear. Although many studies have been conducted in order to determine necrobiosis lipoidica's pathophysiology, a clear and definite path to disease has not been recorded. In this case study, a patient with necrobiosis lipoidica that had been refractory to conventional therapy received treatment with Apligraf® bioengineered wound dressings. Apligraf was shown to be effective in managing the patient's multiple hard-to-heal wounds. It was more successful than previous therapies in achieving granulation tissue formation and wound volume reduction, in addition to being a more rapid form of treatment.
24529080 A brief history of ultrasound in rheumatology: where we were. 2014 Jan Ultrasonography in the '70s was a well-known and widely used method within several medical specialties but not in rheumatology. Initial development of the field was led by radiologists who mainly investigated the potential of ultrasound in the assessment of large joints. In the late '80s, the first studies supporting the role of ultrasound in the detection of soft tissue changes and bone erosions in the hands of patients with rheumatoid arthritis were published. In the '90s, the dramatic improvement of spatial resolution due to the new generation high frequency probes opened up new avenues for the exploration of otherwise undetectable anatomical details. Ultrasound research during this period was enhanced by the growing use of colour Doppler and power Doppler and by the first prototypes of three dimensional ultrasound. Over the last 10 years, the buzz words in ultrasound research in rheumatology have been standardisation, early diagnosis and therapy monitoring.
24127271 Imaging in rheumatology: reconciling radiology and rheumatology. 2013 Dec Imaging in rheumatology was in the past largely confined to radiographs of the hands and sacroiliac joints (SIJs) helping to establish the diagnosis and then monitoring disease progression. Radiographs are not very sensitive for early inflammation in inflammatory rheumatic disorders and the demand on imaging services was therefore limited. However, over the last 10-15 years new drugs and new technologies have brought new challenges and opportunities to rheumatology and radiology as specialties. New drug treatments allow more effective treatment, preventing many complications. Early diagnosis and disease monitoring has become the challenge for the rheumatologist and radiologist alike. The best possible patient outcome is only achieved if the two specialties understand each other's viewpoint. This article reviews the role of imaging-in particular radiography, magnet resonance imaging, computer tomography, ultrasound and nuclear medicine-for the diagnosis and monitoring of rheumatological disorders, concentrating on rheumatoid arthritis, inflammatory spondylarthropathies and gout. Teaching Points • New drugs for the treatment of inflammatory disorders has led to greatly improved outcomes. • Imaging often allows for earlier diagnosis of inflammatory disorders. • Early diagnosis and treatment can often prevent the development of crippling disease manifestations. • Tailored imaging examinations are best achieved by consultation of rheumatologist and radiologist.
23818030 Total elbow arthroplasty: current options. 2013 Jul Total elbow arthroplasty (TEA) has changed considerably in the past three decades. Based on the good long-term results with TEA in patients with rheumatoid arthritis, the indications expanded to include management of acute traumatic and posttraumatic conditions in young, higher-demand patients. Today, unlinked, linked semiconstrained, and convertible devices are available. The high complication rate with earlier surgeries led to surgical advances such as new cementing technique and a focus on managing the triceps. Complications such as infection, aseptic loosening, polyethylene wear, periprosthetic fracture, triceps insufficiency, wound breakdown, and ulnar nerve injury will continue to spur the evolution of surgical technique and implant design. Refinement of surgical indications and improvement in implant fixation, polyethylene design, component implantation, and pathology-specific implants will determine the future success of TEA.
23665436 Rituximab in dermatology. 2013 Jun Rituximab was introduced into clinical practice as a medication with considerable potential. Its use in patients with B-cell lymphoma and rheumatoid arthritis revealed numerous indications in autoimmune diseases, many of which involve the skin, thus requiring dermatologists to become familiar with both the characteristics of anti-CD20 antibodies and the role of B cells in multiple skin diseases. Thanks to these developments, we will be able to use rituximab more frequently and appropriately in our patients and draw up consensus guidelines based on large case series. In other words, establishing the indications for rituximab will make it possible to shorten disease course and reduce morbidity due to more specific drugs.
23431319 An important role of blood and lymphatic vessels in inflammation and allergy. 2013 Angiogenesis and lymphangiogenesis, the growth of new vessels from preexisting ones, have received increasing interest due to their role in tumor growth and metastatic spread. However, vascular remodeling, associated with vascular hyperpermeability, is also a key feature of many chronic inflammatory diseases including asthma, atopic dermatitis, psoriasis, and rheumatoid arthritis. The major drivers of angiogenesis and lymphangiogenesis are vascular endothelial growth factor- (VEGF-)A and VEGF-C, activating specific VEGF receptors on the lymphatic and blood vascular endothelium. Recent experimental studies found potent anti-inflammatory responses after targeted inhibition of activated blood vessels in models of chronic inflammatory diseases. Importantly, our recent results indicate that specific activation of lymphatic vessels reduces both acute and chronic skin inflammation. Thus, antiangiogenic and prolymphangiogenic therapies might represent a new approach to treat chronic inflammatory disorders, including those due to chronic allergic inflammation.
24342660 Association of BANK1 and cytokine gene polymorphisms with type 1 diabetes in Tunisia. 2014 Feb 25 Type 1 diabetes (T1D) is an autoimmune disease (AID) with both genetic and environmental components. We aimed to investigate the genetic association of polymorphisms in genes previously linked with other AIDs, namely BANK1, IL15 and IL2/IL21 region. A total of 76 T1D patients and 162 controls from Southern Tunisia were recruited for a case-control association study investigating the relationship between sixteen SNPs of the BANK1, IL15 and IL2/IL21 gene region and T1D. In the BANK1 gene, G allele and GG genotype of rs3733197 were significantly increased in the group of T1D patients compared to controls. In addition, in the IL15 gene, the minor allele A of rs10519613 polymorphism was significantly higher in patients than in controls. No significant association was found for SNPS in IL2/IL21 gene region. The analysis of the haplotype structure revealed the G-C-A-C-T haplotype of the IL15 gene as associated with a reduction in the risk of developing T1D, while A-T-A-C-T haplotype increased the risk of developing the disease. Furthermore, in the IL2/IL21 region, only one haplotype consisting of eight SNPs was markedly associated with T1D susceptibility. Moreover, G-C combination of the BANK1/IL15 was significantly increased in T1D patients, compared to controls. Our results establish BANK1 and IL15 as new T1D genetic susceptibility factors and replicate the association of the 4q27 region with T1D. Our data agree with the effect previously observed for other autoimmune conditions and delineate a shared underlying mechanism.
24196389 Underlying diagnosis predicts patient-reported outcomes after revision total knee arthropl 2014 Feb OBJECTIVE: To assess the association of underlying diagnosis with outcomes after revision total knee arthroplasty (TKA). METHODS: For this cohort study we used prospectively collected data from the Mayo Clinic Total Joint Registry on all revision TKA patients from 1993 to 2005 with 2- or 5-year response to a validated knee questionnaire that assesses pain and function. We used logistic regression to assess the odds of moderate-severe activities of daily living (ADL) limitations and moderate-severe index knee pain 2 and 5 years after revision TKA. Odds ratios (ORs) and 95% CIs are presented. RESULTS: The underlying diagnosis for the 2- and 5-year cohorts was loosening, wear or osteolysis in 73% and 75%; dislocation, bone or prosthesis fracture, instability or non-union in 17% and 15%; and failed prior arthroplasty with components removed or infection in 11% and 11%, respectively. In multivariable adjusted analyses that included preoperative status, compared with patients with loosening/wear/osteolysis, patients with dislocation/fracture/instability/non-union had an OR of 2.1 for moderate-severe ADL limitation (95% CI 1.3, 3.1, P < 0.001) and those with failed prior arthroplasty/infection had an OR of 1.1 (95% CI 0.6, 1.8, P = 0.4). At 5 years, differences were no longer significant. In multivariable adjusted analyses, compared with patients with loosening/wear/osteolysis, patients with dislocation/fracture/instability/non-union had an OR of 2.0 for moderate-severe pain (95% CI 1.3, 3.1, P < 0.01) at 2 years and an OR of 2.1 (95% CI 1.3, 3.8, P = 0.01) at 5 years. Failed prior arthroplasty/infection was not significantly different than the reference category. CONCLUSION: Underlying diagnosis is independently associated with ADL limitations and pain after revision TKA. This information can help patients have realistic expectations of outcomes.
24036458 Altered expression of miR-146a in myasthenia gravis. 2013 Oct 25 The purpose of this study was to analyze the expression of miR-146a in PBMCs obtained from patients with myasthenia gravis (MG) and healthy controls and to investigate the effect of the inhibition of miR-146a on the activation of AchR specific B cells obtained from mice. The expression of miR-146a levels in PBMCs obtained from patients with MG and healthy controls were determined by qRT-PCR. MiR-146a's complementary fragment, AntagomiR-146a, was synthesized as inhibitor, and the nonfunctional fragment, which has similar construction to AntagomiR-146a, was synthesized as negative control inhibitor. The expression of miR-146a, CD40, CD80 and CD86 on AchR specific B cells were analyzed by qRT-PCR and flow cytometry. Western blotting was used to detect the expression of TLR4, NF-κB and Bcl-2 .The expression of miRNA-146a in PBMCs obtained from patients with MG was significantly upregulated compared to healthy controls (P<0.01). Transfection with miR-146a inhibitor dramatically decreased expression of miR-146a, CD40, CD80, TLR4 and NF-κB on AchR specific B cells compared to mock transfected cells. We conclude that abnormal expression/regulation of miR-146a may play an important role in the regulation of AchR specific B cells and contribute to the pathogenesis of MG.
23651756 The effects of in vivo B-cell depleting therapy on ex-vivo cytokine production. 2013 Jun In renal transplantation, IL-17 production by T-cells might be dependent on the presence of B-cells. Therefore, the effect of in vivo B-cell depletion on ex-vivo IL-17 production was investigated. Twenty patients undergoing living-donor renal transplantation were recruited from a larger cohort of patients participating in a randomized, double-blind trial. All patients were allocated to a single intra-operative dose of either placebo or rituximab (375 mg/m(2)) added to the standard immunosuppressive therapy. Blood was collected at baseline, at one day, and at one month after surgery. The healthy kidney donors also gave blood at baseline. Peripheral blood mononuclear cells were stimulated ex-vivo in different manners (heat killed Candida albicans yeast, heat killed Staphylococcus aureus, or αCD3αCD28 coated beads), to address the role of B-cells in ex-vivo cytokine responses. The concentration of monocyte- and T-cell-derived cytokines (IL-1β, IL-6, TNF-α, IFN-γ, IL-17 and IL-22) was measured in supernatants. Of the 20 recruited patients, 13 received treatment with rituximab and 7 received placebo. In all patients, IL-17 was produced by CD4-positive, γδTCR-negative cells. After stimulation, there was no difference between patients and healthy controls in ex-vivo production of IL-17 or other cytokines. In all patients there was a general decrease of monocyte- and T-cell-derived cytokines after transplantation, except for IL-17. There was no difference between patients who received rituximab and patients who received placebo. A single dose of rituximab treatment added to standard immunosuppressive therapy in renal transplant patients did not influence the production of IL-17 or other monocyte- or T-cell derived cytokines after ex-vivo stimulation.
25098478 Sjögren syndrome and neuromyelitis optica spectrum disorder co-exist in a common autoimmu 2014 Aug The relationship between Sjögren's syndrome (SS) and neuromyelitis optica spectrum disorder (NMOSD) is not completely understood. We report two patients with both conditions and review 47 other previously reported cases meeting currently accepted diagnostic criteria, from 17 articles extracted from PubMed. Out of 44 patients whose gender was informed, 42 were females. Mean age at onset of neurological manifestation was 36.2 years (10-74). Serum anti-AQP4-IgG was positive in 32 patients, borderline in 1, and negative in 4. Our Case 1 was seronegative for AQP4-IgG and had no non-organ-specific autoantibodies other than anti-SSB antibodies. Our Case 2 had serum anti-AQP4, anti-SSA/SSB, anti-thyreoglobulin and anti-acethylcholine-receptor antibodies, as well as clinical hypothyreoidism, but no evidence of myasthenia gravis. Our Cases and others, as previously reported in literature, with similar heterogeneous autoimmune response to aquaporin-4, suggest that SS and NMO co-exist in a common autoimmune milieu which is not dependent on aquaporin-4 autoimmunity.
24977983 Effect of rebamipide ophthalmic suspension on signs and symptoms of keratoconjunctivitis s 2014 Aug PURPOSE: The aim of this study was to investigate the efficacy of 2% rebamipide suspension in treatment of keratoconjunctivitis sicca (KCS) in patients with Sjögren syndrome (SS) with or without punctal occlusions. METHODS: Thirty patients with SS, diagnosed based on the presence of autoantibodies and/or focus score >1 on lip biopsies, with corneal fluorescein staining scores (FSS) >3, and conjunctival lissamine green-staining scores (LSS) >3, were treated 4 times daily for 4 weeks with 2% rebamipide ocular suspension. Ocular examinations were performed before treatment and 2 and 4 weeks after treatment to evaluate FSS (0-9), LSS (0-6), and tear film break-up time (BUT). Hyaluronate and/or artificial tears were not discontinued. The patients were interviewed regarding the 5 major KCS symptoms, foreign body sensation, dry eye sensation, photophobia, ocular pain, and blurred vision, with each graded from none (0) to very severe (4). RESULTS: Of the 30 patients, 3 failed to attend all sessions, leaving 27 (25 females, 2 males, mean age 62.5 ± 10.8 years) to be studied. FSS and LSS showed improvement at week 2, but BUT showed improvement later, at week 4. All 5 symptoms improved significantly. When the patients were divided into 3 groups according to the presence of punctal occlusions, FSS and LSS were found to improve in all groups, but BUT improved only in patients with both puncta occluded at week 4. CONCLUSIONS: Rebamipide ophthalmic suspension was effective in treating KCS of patients with SS, probably by increasing mucins and suppressing inflammatory cytokines. Punctal occlusions resulted in sufficient retention of tear fluid to enhance the activities of rebamipide and improve BUT.
24602383 Specific forms of BAFF favor BAFF receptor-mediated epithelial cell survival. 2014 Jun Although B cell activating factor (BAFF) and its receptor BR3 are produced and expressed by many cells, their role has been restricted to the lymphocyte lineage. Using various techniques (RT-PCR, indirect immunofluorescence, flow cytometry analysis), we observed the expression of BR3 and the production of BAFF by the human salivary gland cell line, by epithelial cells from biopsies of Sjögren's syndrome patients and their controls, but also by salivary gland epithelial cells in culture. To decipher the role of BAFF and BR3 on epithelial cells, BAFF and BR3 were neutralized by blocking antibodies or RNA specific inhibitor (siBR3) and epithelial cell survival was analyzed. Blocking BR3 promotes epithelial cell apoptosis in vitro. This apoptosis resulted in the nuclear translocation of PKCδ. BAFF neutralization by various anti-BAFF antibodies leads to different effects depending on the antibody used suggesting that only some forms of BAFF are required for epithelial cell survival. Our study demonstrates that BR3 is involved in the survival of cultured epithelial cells due to an autocrine effect of BAFF. It also suggests that epithelial cells produce different forms of BAFF and that only some of them are responsible for this effect.
24333758 Chronic inflammation and extra-nodal marginal-zone lymphomas of MALT-type. 2014 Feb Extranodal marginal zone lymphoma of mucosa associated lymphoid tissue (MALT) is an indolent B-cell non-Hodgkin lymphoma (NHL) arising in lymphoid populations that are induced by chronic inflammation in extra nodal sites. The stomach is the most commonly affected organ, and MALT lymphoma is clearly associated with a gastroduodenitis induced by a microbial pathogen, Helicobacter pylori, thus gastric MALT lymphoma represents a paradigm for evaluating inflammatory-associated lymphomagenesis. Variable levels of evidence have indicated a possible association between other microorganisms and non-gastric MALT lymphomas. In addition to infectious etiology, chronic inflammation arising as a result of autoimmune diseases such as Sjogren's syndrome or Hashimoto thyroiditis, poses a significant risk factor for developing NHL. Recently, genetic alterations affecting the NF-κB pathway, a major signaling pathway involved in many cancers, have been identified in MALT lymphoma. This review will present MALT lymphoma as an example of the close pathogenetic link between chronic microenvironmental inflammation and tumor development, showing how these observations can be integrated into daily clinical practice, also in terms of therapeutic implications, with particular focus on the NF-κB pathway.
24176941 Immunological profiles determine neurological involvement in Sjögren's syndrome. 2014 Feb BACKGROUND: Up to 68% of patients with primary Sjögren's syndrome (pSS) undergo neurological complications, and evidence for distinct immunological subgroups is emerging. We sought to determine systemic and immunological profiles associated with neurological manifestations. METHODS: 420 patients fulfilling the 2002 American-European pSS criteria were retrospectively analyzed. Neurological manifestations were diagnosed through clinical, biological, electrophysiological, and imaging findings. Biographical, clinical, and laboratory data were compared. RESULTS: Within 93 (22%) patients with neurological manifestations, peripheral and central nervous systems were involved in 66% and 44%, respectively. Raynaud's phenomenon, cutaneous vasculitis, renal involvement, and cryoglobulinemia were associated with sensorimotor neuropathy and mononeuritis multiplex (p<0.05). Conversely, pure sensory neuropathy occurred without extraglandular manifestation, and without anti-Ro/SSA antibodies (p<0.05). All neurological manifestations were associated with increased use of corticosteroids and immunosuppressive drugs (p<0.05). CONCLUSIONS: In pSS, patients with sensorimotor neuropathies and pure sensory neuropathies have distinct extraglandular and immunological profiles.
24080911 The Hippo signaling pathway is required for salivary gland development and its dysregulati 2013 Nov Sjogren's syndrome (SS) is a complex autoimmune disease that primarily affects salivary and lacrimal glands and is associated with high morbidity. Although the prevailing dogma is that immune system pathology drives SS, increasing evidence points to structural defects, including defective E-cadherin adhesion, to be involved in its etiology. We have shown that E-cadherin has pivotal roles in the development of the mouse salivary submandibular gland (SMG) by organizing apical-basal polarity in acinar and ductal progenitors and by signaling survival for differentiating duct cells. Recently, E-cadherin junctions have been shown to interact with effectors of the Hippo signaling pathway, a core pathway regulating the organ size, cell proliferation, and differentiation. We now show that Hippo signaling is required for SMG-branching morphogenesis and is involved in the pathophysiology of SS. During SMG development, a Hippo pathway effector, TAZ, becomes increasingly phosphorylated and associated with E-cadherin and α-catenin, consistent with the activation of Hippo signaling. Inhibition of Lats2, an upstream kinase that promotes TAZ phosphorylation, results in dysmorphogenesis of the SMG and impaired duct formation. SMGs from non-obese diabetic mice, a mouse model for SS, phenocopy the Lats2-inhibited SMGs and exhibit a reduction in E-cadherin junctional components, including TAZ. Importantly, labial specimens from human SS patients display mislocalization of TAZ from junctional regions to the nucleus, coincident with accumulation of extracellular matrix components, fibronectin and connective tissue growth factor, known downstream targets of TAZ. Our studies show that Hippo signaling has a crucial role in SMG-branching morphogenesis and provide evidence that defects in this pathway are associated with SS in humans.