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ID PMID Title PublicationDate abstract
25527879 Risks of in-hospital death and complications after fusion surgery in patients with atlanto 2015 Apr OBJECTIVE: To examine in-hospital mortality and postoperative major complications in patients undergoing fusion surgery for atlantoaxial subluxation (AAS) and to examine whether the risk of perioperative complications varies between patients with and without rheumatoid arthritis (RA). METHODS: A retrospective analysis of data from the Diagnosis Procedure Combination database, a nationwide administrative impatient database in Japan, identified 1090 patients who underwent spinal fusion surgery for AAS during 2007-2012. Patients' clinical characteristics were extracted, including age, sex, use of homologous blood transfusion, length of stay, and type of hospital. Clinical outcomes included in-hospital death and major complications, including surgical-site infection, sepsis, cardiac events, respiratory disorders, acute renal failure, pulmonary embolism, perioperative stroke, and vertebral injury. Massive blood transfusion was defined as at least 6 units of red blood cells. RESULTS: Four hundred sixty-five patients (42.7%) were classified as the RA group. In-hospital mortality after fusion surgery for AAS was 0.5% (5/1090), and major complications occurred in 5% (55/1090). Multivariate analyses showed that patients with RA were more likely to have major complications after surgery than patients without RA (odds ratio: 1.69; 95% confidence interval: 0.96-2.97; P = 0.07), and the rate of massive blood transfusion was significantly greater in patients with RA than in patients without RA (odds ratio: 2.29; 95% confidence interval: 1.12-4.68; P = 0.02). CONCLUSIONS: The in-hospital mortality after fusion surgery for AAS was relatively low. However, patients with RA had an increased risk of postoperative complications and massive blood transfusion compared with patients without RA.
24013646 The JAK inhibitor, tofacitinib, reduces the T cell stimulatory capacity of human monocyte- 2014 Dec OBJECTIVE: Tofacitinib, which is a Janus kinase (JAK) inhibitor, has shown clinical effects in the treatment of rheumatoid arthritis. JAKs are important kinases in lymphocyte differentiation; however, their function in dendritic cells (DCs) is unknown. In this study, the function of JAKs in DCs was investigated with tofacitinib. METHODS: The effects of tofacitinib on the maturation of human monocyte-derived DCs induced by lipopolysaccharide (LPS) stimulation were investigated. In addition, its effects on T cell stimulatory capability was investigated by coculturing with naïve CD45RA-positive T cells. RESULTS: Tofacitinib decreased expression of CD80/CD86 in a concentration-dependent manner in LPS-stimulated DCs; however, it did not affect HLA-DR expression. Tofacitinib suppressed tumour necrosis factor, interleukin (IL)-6 and IL-1β production without affecting transforming growth factor (TGF)-β and IL-10 production. Meanwhile, CD80/CD86 expression in DCs was enhanced by type I interferon (IFN) stimulation, and the LPS-induced CD80/CD86 expression was inhibited by an antibody to type I IFN receptor. Furthermore, tofacitinib suppressed production of type I IFN and activation of interferon regulatory factor (IRF)-7, which is a transcription factor involved in CD80/CD86 and type I IFN expression. Tofacitinib also decreased the T cell stimulatory capability of DCs and increased expression of indoleamine 2,3-dioxygenase (IDO)-1 and IDO-2. CONCLUSIONS: Tofacitinib, a JAK1/JAK3 inhibitor, affected the activities of human DCs. It decreased CD80/CD86 expression and T cell stimulatory capability through suppression of type I IFN signalling. These results suggest a novel mode of action for tofacitinib and a pivotal role for JAKs in the differentiation of DCs.
24855454 Differential regulation of anti-inflammatory genes by p38 MAP kinase and MAP kinase kinase 2014 BACKGROUND: Conventional p38α inhibitors have limited efficacy in rheumatoid arthritis, possibly because p38 blockade suppresses the counter-regulatory mechanisms that limit inflammation. In contrast, targeting the upstream MAP kinase kinases, MKK3 and MKK6, partially maintains p38-mediated anti-inflammatory responses in bone marrow-derived macrophages (BMDM). In this study, we explored the mechanisms that preserve anti-inflammatory gene expression by evaluating differential regulation of IL-10 and p38-dependent anti-inflammatory genes in MKK3-/-, MKK6-/-, and p38 inhibitor-treated wildtype cells. METHODS: BMDM from wild type (WT), MKK3-/-, and MKK6-/- mice were pre-treated with p38 inhibitor SB203580 (SB), JNK inhibitor SP600125 (SP), and/or ERK inhibitor PD98059 (PD) and stimulated with LPS. Supernatant protein levels were measured by multiplex bead immunoassay. mRNA expression was determined by qPCR and protein expression by Western blot analysis. De novo IL-10 mRNA synthesis was quantified in cells treated with ethynyl-uridine and LPS followed by reverse transcription and qPCR. mRNA half-life was measured in LPS-treated cells that were then incubated with actinomycin D ± SB203580. RESULTS: Pre-treatment of WT BMDM with p38 inhibitor significantly reduced IL-10 production in the three groups, while ERK and JNK inhibitors had minimal effects. IL-10 production was significantly decreased in MKK3-/- BMDM compared with either WT or MKK6-/- cells. IL-10 mRNA expression was modestly reduced in MKK3-/- BMDM but was preserved in MKK6-/- cells compared with WT. De novo IL-10 mRNA synthesis was inhibited in MKK3-/- and p38 inhibitor pre-treated cells, but not MKK6-/- cells compared with WT. IL-10 mRNA half-life was markedly reduced in p38 inhibitor-treated WT cells while MKK-deficiency had minimal effect. DUSP1 mRNA levels were preserved in MKK-deficient cells but not in p38 inhibitor-treated WT cells. Tristetraprolin mRNA and protein levels were reduced in p38 inhibitor-treated WT cells compared with MKK6-/- cells. CONCLUSION: Unlike p38-inhibition, the absence of MKK6 mostly preserves IL-10 and TTP protein expression in BMDM. MKK6-deficiency also spares DUSP1 and IL-1RA, which are key negative regulators of the inflammatory response. Together, these data suggest that MKK6 is a potential therapeutic target in RA.
23576060 Rationale for treating primary Sjögren's syndrome patients with an anti-CD6 monoclonal an 2013 Jul CD6 is a cell surface receptor expressed on the majority of T cells and a subset of B cells. When expressed, CD6 contributes to lymphocyte activation through its extracellular domain 1, while adhesion and cellular migration are related to the extracellular scavenger receptor cysteine-rich domain (SRCR-D)-3 of CD6. Itolizumab, clone T1h, is a newly developed humanized IgG1 monoclonal antibody that targets CD6 SRCR-D1 and blocks immune activation. Itolizumab has been proposed to be effective in autoimmune diseases such as rheumatoid arthritis, Sjögren's syndrome and multiple sclerosis. In Sjögren's syndrome, the utilization of itolizumab as therapeutic option is reinforced by our recent observation that ALCAM, the CD6 ligand, is overexpressed and that CD6-positive T and B cells are detected within salivary glands from Sjögren's syndrome patients. In this study, itolizumab-positive target cells were characterized within both peripheral blood and salivary glands in order to provide rational for anti-CD6 treatment in Sjögren's syndrome.
25433530 Patient-reported joint count in juvenile idiopathic arthritis: the reliability of a maniki 2015 Mar OBJECTIVE: To evaluate the reliability of a manikin format, patient-reported joint count in juvenile idiopathic arthritis (JIA), and to detect changes in agreement at a second visit. METHODS: Patients with JIA aged 12-21 were asked to mark joints with active arthritis on a manikin before their regular clinic visit. The physician then performed a joint count without having seen the patient's assessment. Agreement between scores of physician-reported and patient-reported joint counts was assessed using ICC. Kappa statistics were used to assess reliability of scoring individual joints. RESULTS: The study included 75 patients with JIA. In general, patients had a low number of active joints (median 1 joint, indicated by the physician). ICC was moderate (0.61) and κ ranged from 0.3-0.7. At the second visit, κ were similar; the ICC was 0.19. When a patient scored 0 joints, the physician confirmed this 93%-100% of the time. When the patient marked ≥ 1 joints, the physician confirmed arthritis 59%-76% of the time. Sensitivity to change was moderate. CONCLUSION: Agreement between physician and patient on the number of joints with active arthritis was reasonable. Untrained patients tended to overestimate the presence of arthritis when they marked active joints on a manikin-format joint count. When the patient indicated absence of arthritis, the physician usually confirmed this. As the agreement did not improve at followup, future research should focus on the possibility of achieving this through training. For now, the patient-reported joint count cannot replace the physicians' joint count in clinical practice; it may be used in epidemiological studies with caution.
24736907 Growth of children with juvenile idiopathic arthritis. 2014 Mar OBJECTIVE: To evaluate the growth pattern in children with juvenile idiopathic arthritis and its subtypes in comparison with age, sex and temporally matched controls. STUDY DESIGN: Prospective study. SETTING: Pediatric rheumatology clinic of a tertiary care hospital in Eastern part of India. PARTICIPANTS: Seventy-five children (2-12 years) diagnosed as juvenile idiopathic erthritis by International League of Associations for Rheumatology criteria and 75 age- and sex- matched controls. INTERVENTION: Weight, height and body mass index were recorded at six monthly interval in both groups over a period of 3 years. MAIN OUTCOME MEASURES: weight, height and body mass index. RESULTS: Subtype distribution of juvenile idiopathic arthritis was: oligoarthritis (49%, n=37), rheumatoid factor negative polyarthritis (27%, n=20), rheumatoid factor positive polyarthritis (8%, n=6), systemic onset (15%, n=11) and enthesitis related arthritis (1.3%, n=1). Anthropometric parameters in children with juvenile idiopathic arthritis were not significant different from controls. Comparison between the subtypes showed significant differences in height (P=0.011), weight (P=0.005), and growth velocity (P=0.005), but not in body mass index. Systemic onset disease led to significant restriction in height (P=0.018; 95% CI 2.13-33.77) and weight (P=0.008; 95% CI 1.47-14.43) compared to controls. Growth velocity was significantly affected in rheumatoid factor positive polyarthritis (P=0.003; 95% CIO. 46-3.14). CONCLUSIONS: Children with juvenile idiopathic arthritis do not have significantly lower values of anthropometric parameters compared to controls. Significant restriction in height and weight is seen in systemic onset disease, and growth velocity is significantly reduced in rheumatoid factor positive subjects.
24669664 Antiarthritic activity of Cynodon dactylon (L.) Pers. 2014 Mar Cynodon dactylon (L.) (Poaceae) is traditionally used herb to treat fevers, skin diseases and rheumatic affections. The ethanolic extract of C. dactylon was found to be safe at all the dose levels (100, 200 and 400 mg/kg, orally) and there was no mortality up to the dose of 5000 mg/kg of extract when administered orally. C. dactylon showed significant antiarthritic activity against Freund's complete adjuvant induced arthritis in rats. Treatment with C. dactylon significantly reduced the mean percentage change in injected and non injected paw, ankle diameter, clinical severity and significantly increased body weight. Results were confirmed using biochemical parameters; there was a significant improvement in the levels of Hb and RBC in C. dactylon treated rats. The increased levels of WBC, ESR, C- reactive protein (CRP) and TNFalpha were significantly suppressed in C. dactylon treated rats. C. dactylon showed protective effect in arthritic joints but it has been supported by an improvement in bone lesions rather than in cartilage lesions. It can be concluded that ethanolic extract of C. dactylon at a dose of 400 mg/kg is effective in improving haematological level, CRP and reducing TNFalpha level. Phytochemical screening showed the presence of alkaloids, flavonoids and glycosides in ethanolic extract. All the above results support the traditional uses of the plant in the treatment of rheumatoid arthritis.
24797159 Apremilast: first global approval. 2014 May Apremilast (Otezla(®)), an oral small molecule inhibitor of type-4 cyclic nucleotide phosphodiesterase (PDE-4), is under development with Celgene Corporation for the treatment of psoriatic arthritis, psoriasis, ankylosing spondylitis, Behçet's syndrome, atopic dermatitis, and rheumatoid arthritis. Apremilast is indicated for the treatment of active psoriatic arthritis in adults. Apremilast has received its first global approval for this indication in the USA. Regulatory submissions for approval in this indication are under review in Canada and Europe. Regulatory filings have also been submitted for apremilast in the treatment of plaque psoriasis in the USA and Europe. This article summarizes the milestones in the development of apremilast leading to its first approval for the treatment of psoriatic arthritis.
24403693 Wait times for physical and occupational therapy in the public system for people with arth 2013 Summer PURPOSE: Although arthritis is the leading cause of pain and disability in Canada, and physical therapy (PT) and occupational therapy (OT) are beneficial both for chronic osteoarthritis (OA) and for inflammatory arthritis such as rheumatoid arthritis (RA), there appear to be problems with access to such services. The aim of this study was to document wait times from referral by physician to consultation with PT or OT in the public health care system for people with arthritis in Quebec, Canada. METHOD: Appointments were requested by telephone, using hypothetical case scenarios; wait times were defined as the time between initial request and appointment date. Descriptive statistics were used to examine the wait times in relation to diagnosis, service provider and geographic area. RESULTS: For both scenarios (OA and RA) combined, 13% were offered an appointment within 6 months, 13% offered given an appointment within 6-12 months, 24% were told they would need to wait longer than 12 months, and 22% were refused services. The remaining 28% were told they would require an evaluation appointment for functional assessment before being given an appointment for therapy. No difference was found between RA and OA diagnoses. CONCLUSIONS: Our study suggests that most people with arthritis living in the province of Quebec are not receiving publicly accessible PT or OT intervention in a timely manner.
25351383 [Spondyloarthritis: new names for old acquaintances]. 2014 After rheumatoid arthritis, ankylosing spondylitis (AS) is one of the most common rheumatic diseases. AS belongs to the spondyloarthritis group which is characterised by inflammation of the spine and has a strong genetic association with the HLA-B27 antigen. Recently, the Assessment of SpondyloArthritis International Society has introduced new international classification criteria for spondyloarthritis, i.e. axial and peripheral manifestations AS is one of the known axial spondyloarthritides but it is also a type of axial spondyloarthritis that does not show radiographic abnormalities, but has the same symptoms and risk factors that characterise axial spondylarthritis. This form is known as non-radiographic axial spondylarthritis. Peripheral spondyloarthritis is characterised by peripheral arthritis, enthesitis and dactylitis. Examples of peripheral spondyloarthritides are psoriatic arthritis and reactive arthritis, previously known as Reiter's syndrome.
25033485 Granuloma annularis revealing Wegener's granulomatosis. 2014 Apr Skin manifestations are often associated with systemic autoimmune diseases (SAD). Some SAD, such as systemic lupus erythematosus, psoriatic arthritis and scleroderma display pathognomonic dermatological features, whereas other systemic diseases such as sarcoidosis, vasculitis and rheumatoid arthritis can present with non-specific skin manifestations that range from erythema nodosum to necrotic lesions. Here we report the case of a 25-year-old man with uveitis, polyarthrirtis, pulmonary involvement, nephrotic syndrome, cutaneous granuloma and pneumonia by E. coli.
24095939 Role of vascular channels as a novel mechanism for subchondral bone damage at cruciate lig 2015 Jan OBJECTIVES: The purpose of this work was to test whether normal peri-entheseal vascular anatomy at anterior and posterior cruciate ligaments (ACL and PCL) was associated with distribution of peri-entheseal bone erosion/bone marrow lesions (BMLs) in inflammatory arthritis (IA) and osteoarthritis (OA). METHODS: Normal microanatomy was defined histologically in mice and by 3 T MRI and histology in 21 cadaveric knees. MRI of 89 patients from the Osteoarthritis Initiative and 27 patients with IA was evaluated for BMLs at ACL and PCL entheses. Antigen-induced arthritis (AIA) in mice was evaluated to ascertain whether putative peri-entheseal vascular regions influenced osteitis and bone erosion. RESULTS: Vascular channels penetrating cortical bone were identified in knees of non-arthritic mice adjacent to the cruciate ligaments. On MRI of normal cadavers, vascular channels adjacent to the ACL (64% of cases) and PCL (71%) entheses were observed. Histology of 10 macroscopically normal cadaveric specimens confirmed the location of vascular channels and associated subclinical changes including subchondral bone damage (80% of cases) and micro-cyst formation (50%). In the AIA model, vascular channels clearly provided a site for inflammatory tissue entry and osteoclast activation. MRI showed BMLs in the same topographic locations in both patients with early OA (41% ACL, 59% PCL) and IA (44%, 33%). CONCLUSION: The findings show that normal ACL and PCL entheses have immediately adjacent vascular channels which are common sites of subtle bone marrow pathology in non-arthritic joints. These channels appear to be key determinants in bone damage in inflammatory and degenerative arthritis.
23840476 Identification of the tyrosine-protein phosphatase non-receptor type 2 as a rheumatoid art 2013 OBJECTIVES: Genome-wide association studies have facilitated the identification of over 30 susceptibility loci for rheumatoid arthritis (RA). However, evidence for a number of potential susceptibility genes have not so far reached genome-wide significance in studies of Caucasian RA. METHODS: A cohort of 4286 RA patients from across Europe and 5642 population matched controls were genotyped for 25 SNPs, then combined in a meta-analysis with previously published data. RESULTS: Significant evidence of association was detected for nine SNPs within the European samples. When meta-analysed with previously published data, 21 SNPs were associated with RA susceptibility. Although SNPs in the PTPN2 gene were previously reported to be associated with RA in both Japanese and European populations, we show genome-wide evidence for a different SNP within this gene associated with RA susceptibility in an independent European population (rs7234029, P = 4.4×10(-9)). CONCLUSIONS: This study provides further genome-wide evidence for the association of the PTPN2 locus (encoding the T cell protein tyrosine phosphastase) with Caucasian RA susceptibility. This finding adds to the growing evidence for PTPN2 being a pan-autoimmune susceptibility gene.
24781133 [Dental implantation and prosthetics in Sjögren's syndrome]. 2014 The author discusses the methods and conditions for the successful outcome of implantation in patients with Sjögren's syndrome. Considers it no alternative orthopedic and psychological rehabilitation of the patient with objective xerostomia. Examines implantation in patients with Sjögren's syndrome as a specialized form of surgical care.
24574234 Genome-wide DNA methylation patterns in naive CD4+ T cells from patients with primary Sjö 2014 Mar OBJECTIVE: Primary Sjögren's syndrome (SS) is a systemic autoimmune disease with incompletely understood etiology. This study was undertaken to investigate the role of epigenetic dysregulation in the pathogenesis of primary SS. METHODS: A genome-wide DNA methylation study was performed in naive CD4+ T cells from 11 patients with primary SS compared to age-, sex-, and ethnicity-matched healthy controls. Cytosine methylation was quantified using the Illumina Infinium HumanMethylation450 BeadChip array, and the data were validated using bisulfite sequencing. RESULTS: Genome-wide analyses identified 553 hypomethylated CpG sites and 200 hypermethylated CpG sites in naive CD4+ T cells from patients with primary SS as compared to healthy controls, representing 311 hypomethylated and 115 hypermethylated gene regions. The hypomethylated genes in patients with primary SS included LTA (encoding lymphotoxin α). Other relevant genes, such as CD247, TNFRSF25, PTPRC, GSTM1, and PDCD1, were also hypomethylated. The interferon signature pathway was represented by hypomethylation of STAT1, IFI44L, USP18, and IFITM1. A group of genes encoding members of the solute carrier proteins were differentially methylated. In addition, the transcription factor gene RUNX1 was hypermethylated in patients with primary SS, suggesting a possible connection to lymphoma predisposition. Gene ontology (GO) analysis of hypomethylated genes demonstrated enrichment of genes involved in lymphocyte activation and immune response. GO terms for hypermethylated genes included antigen processing and presentation. CONCLUSION: This is the first epigenome-wide DNA methylation study in patients with primary SS. These findings highlight a role for DNA methylation in primary SS and identify disease-associated DNA methylation changes in several genes and pathways in naive CD4+ T cells from patients with primary SS that may be involved in the pathogenesis of this disease.
24480435 Role of vacuolar ATPase and Skp1 in Sjögren's syndrome. 2014 Mar Immune mechanisms alone cannot directly account for exocrine gland dysfunction and extraglandular features such as renal tubular acidosis, neuropathy, hearing loss and fatigue in Sjögren's syndrome (SS). Absence of Vacuolar ATPase (V-ATPase) has been reported in SS related renal tubular acidosis (RTA). We hypothesise how defect in V-ATPase could account for decreased neurotransmitter release leading onto exocrine dysfunction, neuroendocrine manifestations and hearing loss which are well described manifestations in SS. S-phase-kinase-associated protein-1 (Skp1) is a constituent of RAVE which is involved in V-ATPase assembly. It is also a component of SCF ligase which is crucial in NFκB signalling. SKP1 also interacts with TRIM 21/Ro 52 which is an autoantigen in SS. By virtue of these interactions, we postulate how a defective skp1 could fit into the existing pathogenesis of SS and also account for increased risk of lymphoma in SS as well as congenital heart block in fetus of mothers with SS.
24224588 CT findings of thoracic manifestations of primary Sjögren syndrome: radiologic-pathologic 2013 Nov Primary Sjögren syndrome is an immune-mediated exocrinopathy characterized by lymphoplasmacytic infiltration of the salivary and lacrimal glands. Various systemic extraglandular disorders are associated with primary Sjögren syndrome, and the thorax is commonly affected. The pulmonary manifestations of primary Sjögren syndrome may be categorized as airway abnormalities, interstitial pneumonias, and lymphoproliferative disorders; in each category, bronchiectasis or centrilobular nodules, nonspecific interstitial pneumonia, and lymphoid interstitial pneumonia are common. These manifestations do not usually occur in isolation; they are concomitantly seen with other types of lesions. Mucosa-associated lymphoid tissue (MALT) lymphoma and amyloidosis are key components of lymphoproliferative disorders, and MALT lymphoma should always be considered because its morphologic characteristics are similar to those of benign lymphoproliferative disorders. Amyloidosis is rare but important because it carries a risk for underlying MALT lymphoma or plasmacytoma, and it may lead to hemoptysis during biopsy. In addition, thin-walled air cysts are characteristic of primary Sjögren syndrome, irrespective of the main pulmonary manifestations. Lymphadenopathy and multilocular thymic cysts may be seen in the mediastinum. During the follow-up period, there is a risk for acute exacerbation of interstitial pneumonia and development of malignant lymphoma. Often, primary Sjögren syndrome is subclinical, but there are various underlying risks. Thus, imaging findings are important. In addition to the various types of interstitial pneumonia and airway abnormalities, air cysts and mediastinal manifestations may help diagnose primary Sjögren syndrome.
24913964 Myelitis transverse in Sjögren's syndrome and systemic lupus erythematosus: presentation 2015 Jan Transverse myelitis is a rare focal inflammation of the spinal cord. Multiple etiologies have been identified including autoimmune diseases, mainly systemic lupus erythematosus and Sjögren' syndrome. It can occur in an acute or subacute clinical onset, with the acute presentation having a worse prognosis. An early diagnosis and intensive treatment are important features recommended in these patients. We present three cases with transverse myelitis associated with autoimmune diseases. We discuss different clinical manifestations, association with autoantobodies, radiologic findings, and therapeutic and prognostic issues.
24464153 SLE and dental erosion: a lethal cocktail. 2014 Apr A 13-year-old Pacific Island girl presented complaining of fever, joint pain and dry mouth. She was using limes to relieve her dry mouth. On examination, the most striking clinical finding was severe dental erosion and caries. Autoimmune serology confirmed a diagnosis of systemic lupus erythematosus (SLE) with possible Sjögren's syndrome. The case illustrates the devastating consequence of excessive consumption of acidic citrus juice in sicca syndrome.
23329715 An unexpected diagnosis in a dyspnoeic patient with primary Sjogren syndrome. 2013 Jan 17 We describe a case of a 50-year-old lady with newly diagnosed primary Sjogren syndrome who presented with severe pulmonary artery hypertension and pericardial effusion. She was managed by immunosuppressive agents and a combination of standard therapy for pulmonary hypertension. Our patient had a clinically significant involvement of cardio-pulmonary system that is atypical of this disease. Prompt recognition and management of this condition are extremely crucial as untreated cases carry a grave prognosis. However, the ideal treatment strategy is yet to be defined for this condition.