Seminars in Arthritis and Rheumatism - Articles in Press

Neuropsychiatric Lupus: The Prevalence and Autoantibody Associations Depend on the Definition: Results from the 1000 Faces of Lupus Cohort - Corrected Proof

2012-05-17

Objectives: The (ever) prevalence of neuropsychiatric systemic lupus erythematosus (NPSLE) can vary widely depending on the definition used. We determined the prevalence of NPSLE in 1000 Faces of Lupus, a large multicenter Canadian cohort. Methods: Adults enrolled at 10 sites who satisfied the American College of Rheumatology (ACR) classification for systemic lupus erythematosus (SLE) were included. NPSLE was defined as (i) NPSLE by ACR classification criteria (seizures or psychosis), (ii) ACR, SLEDAI (seizure, psychosis, organic brain syndrome, cranial nerve disorder, headache, and cerebrovascular accident (CVA)), SLAM (CVA, seizure, cortical dysfunction, and headache), and SLICC (cognitive impairment, psychosis, seizures, CVA, cranial or peripheral neuropathy, and transverse myelitis) with and (iii) without minor nonspecific NPSLE manifestations (including mild depression, mild cognitive impairment, and electromyogram-negative neuropathies), and (iv) by ACR and SLEDAI neuropsychiatric (NP) indexes alone. Factors associated with NPSLE were explored using regression models. Results: Cohort size was 1253, with mean disease 12 ± 10 years, mean age 41 ± 16 years, and 86% female. Subgroup size was dependent on the specific definition of NPSLE. Prevalence of NPSLE was 6.4% in group (i), n = 1253 (n = 80); 38.6% in group (ii), n = 681(n = 263); 28.7% in group (iii), n = 586 (n = 168); and 10.2% in group (iv), n = 1125 (n = 115). In univariate analysis, Aboriginals had a nearly 2-fold increase in frequency of NPSLE in all groups. Education level and income were not associated with NPSLE (P = 0.32 and 0.03, respectively). As well, number of ACR criteria, SLAM, age at diagnosis, disease duration, and gender were not associated with NPSLE. Anti-Ro was significantly associated in groups (i) and (iv) and antiphospholipid antibodies (aPL) were increased in groups (i), (ii), and (iii); however, this lost significance when thromboembolic events were excluded from SLICC, SLEDAI, and SLAM indexes. In group (iv), absence of anti-Sm was significant. In multivariate analysis, anti-Ro and aPL (i) and anti-Ro+ and lack of anti-Sm (iv) were significant. NPSLE was not increased in those with +anti-DNA, La, or ribonucleoprotein (RNP), lupus anticoagulant (LAC), or anticardiolipin (aCL) antibody. Conclusions: The prevalence and factors associated with NPSLE varied depending on the definition used, was highest in Aboriginals, and may be higher if +anti-Ro or aPL are present. SLAM and SLICC include mild subjective disease manifestations, which contributed to a 10% higher prevalence of NPSLE compared to a more strict definition. NPSLE may be less in this database than other publications as its overall prevalence may be decreasing, or because of selection bias inherent to those who enter an observational cohort. NPSLE was associated with aPL and often anti-Ro and varied by ethnicity.

Can Magnetic Resonance Imaging of the Hand and Wrist Differentiate Between Rheumatoid Arthritis and Psoriatic Arthritis in the Early Stages of the Disease? - Corrected Proof

2012-05-17

Objective: To investigate whether rheumatoid arthritis (RA) and psoriatic arthritis (PsA) can be differentiated in the early stages of the disease (duration of symptoms ≤1 year) on the basis of magnetic resonance imaging (MRI) features of the hand and wrist. Material and methods: Twenty early RA and 17 early PsA patients with symptomatic involvement of the wrist and hand joints and inconclusive radiographic studies were examined prospectively with contrast-enhanced MRI. Images were evaluated in accordance with the Outcome Measures in Rheumatology Clinical Trials recommendations. Results: Certain MRI features, such as the presence of enthesitis or extensive diaphyseal bone marrow edema, were observed exclusively in PsA (P = 0.0001). These distinctive findings were present in nearly 71% (12/17) of PsA patients. Diffuse and, in some cases, pronounced soft-tissue edema spreading to the subcutis was also seen more frequently in patients with PsA (P = 0.002). There were no significant differences in the frequency of synovitis, bone erosions, subchondral bone edema, or tenosynovitis between the 2 groups. However, in RA extensor tendons were involved more often than the flexor tendons, whereas in PsA the opposite was observed (P = 0.014). With respect to the discriminatory power of the different MRI findings examined, only the presence of enthesitis or diaphyseal bone edema and, to a lesser extent, the pattern of hand tendon involvement and the presence of soft-tissue edema accurately differentiated PsA from RA (all these features achieved accuracies greater than 0.70). Conclusions: We observed significant differences in the MRI findings of the hand and wrist that can help to distinguish between RA and PsA in the early stages of disease. This imaging method could help to assist in the differential diagnostic process in selected patients in whom diagnosis cannot be unequivocally established after conventional clinical, biochemical, and radiographic examinations.

Risk of Significant Infection in Rheumatoid Arthritis Patients Switching Anti-Tumor Necrosis Factor-α Drugs - Corrected Proof

2012-05-17

Objectives: To describe rates of first significant infection of rheumatoid arthritis patients who switch between anti-tumor necrosis factor (aTNF) drugs. Methods: Subjects with rheumatoid arthritis who received only aTNF drugs were observed in an insurance claims database from January 2001 to December 2007. Nonswitchers (NS) remained on one aTNF throughout the study period (date of the first aTNF claim was the index date); switchers (S) received at least one other aTNF (claim date for the 2nd agent was the index date). Significant infections included those that required intravenous antibiotics or hospitalization. Two attributable risk periods were used: () an infection occurring ≤90 days following a claim for an aTNF (90-day) and () an infection occurring after the index date (ever-treated). Follow-up was censored at the first occurrence of a significant infection event, end of eligibility, or end of study period. Data were analyzed using Cox regression. Results: In 13,752 NS and 2293 S patients, time-stratified rates declined 2- to 3-fold between the first year versus ≥2 years. Risk of significant infection was not different for either attribution model [90-day hazard ratio (HR) = 0.93, 95CI: 0.74 to 1.17, P = 0.55; ever treated HR = 0.94, 95CI: 0.78 to 1.15, P = 0.57]. First and second year rates were similar. Predictors included age ≥50 years; history of significant or opportunistic infection, diabetes, respiratory disease; Charlson score ≥2; or prior hospitalizations. Conclusions: The risk of a significant infection was not different between NS and S patients. Regardless of switching status, the rate of infection was greater in the first year. This study was limited by the lack of clinical data to determine the reason for switching.

Sarcoidosis Triggered by Interferon-Beta Treatment of Multiple Sclerosis: A Case Report and Focused Literature Review - Corrected Proof

Soumya D. Chakravarty, Mary E. Harris, Andrew M. Schreiner, Mary K. Crow — 2012-05-09

Objectives: To report a rare case of sarcoidosis induced by chronic interferon-beta (a type I interferon) therapy of multiple sclerosis and to review previously reported cases. Methods: We describe a patient with a prior diagnosis of multiple sclerosis, who developed noncaseating granulomas in her skin and pulmonary lymph nodes, consistent with sarcoidosis, while being treated with recombinant interferon-beta. A retrospective review of the literature was performed using the PubMed database. Results: In our patient, sarcoidosis developed after 3 years of continuous recombinant interferon-beta therapy, dosed 3 times a week. The patient presented with progressive dyspnea on exertion, diffuse arthralgias, low-grade fevers, with an acute onset of rash. The diagnosis of sarcoidosis was secured by finding typical, well-formed, noncaseating granulomas on skin and endobronchial biopsies, with other possible etiologies for granulomatous conditions excluded beforehand. Following the withdrawal of recombinant interferon-beta and a course of corticosteroids combined with disease-modifying anti-rheumatic drug therapy, the patient's clinical presentation resolved. Excluding ours, only 4 additional cases of sarcoidosis developing after interferon-beta therapy have been reported, with 2 of those cases in the context of underlying multiple sclerosis. Conclusions: Developing sarcoidosis during treatment of multiple sclerosis with recombinant interferon-beta represents an exceedingly rare and paradoxical adverse event. The occurrence of sarcoidosis with the use of this agent is perhaps due to a dysregulation in the modulatory role played by interferon-beta (and more generally type I interferon) expression in chronic inflammation.

Intra-Articular Glucocorticosteroid Injection into Sternocostoclavicular Joints in Patients with SAPHO Syndrome - Corrected Proof

2012-05-07

Objective:: Painful swelling of the anterior chest wall caused by osteitis and hyperostosis in the sternocostoclavicular region are characteristically observed in patients suffering from SAPHO syndrome. Autoimmune triggering of inflammation and bacterial infection is hypothesized to be involved in the pathogenesis. Promising treatment modalities include antirheumatic and antibiotic medications. Methods:: Ten patients with SAPHO syndrome and symptomatic osteitis in the sternocostoclavicular region were treated by a single instillation of glucocorticosteroids (20 mg triamcinolone) into the sternocostoclavicular joints. The disease activity was evaluated on the basis of a questionnaire asking for osteitis activity (quantified for complains on a scale of 0-6), by Health Assessment Questionnaire (HAQ) score, erythrocyte sedimentation rate, C-reactive protein, and magnet resonance imaging (MRI) scanning of the sternocostoclavicular region (osteitis scores quantified for inflammation on a scale of 0-2 by the radiologist) prior to injection and after 12 weeks. No changes of the preexisting antirheumatic therapy were allowed during the observation interval. Results:: All patients continued the study during the follow-up. The osteitis score changed from 4.2 (mean; standard error (SE) ±0.3) to 3.2 (±0.4), [P = 0.062], the erythrocyte sedimentation rate from 19.0 (range from 12 to 30) to 19.9 (from 12 to 27), [P = 0.430], and the MRI score from 1.6 (±0.2) to 1.5 (±0.2) [P = 1.0]. One patient developed an increase of the clinical osteitis activity from 3 to 5 according the scoring system; only 2 patients showed a reduction of the MRI activity score from 2 to 1. Conclusions:: Intra-articular glucocorticosteroid instillation does not appear to reduce osteitis in the sternocostoclavicular region in patients with SAPHO syndrome.

Challenges Associated with the Management of Gouty Arthritis in Patients with Chronic Kidney Disease: A Systematic Review - Corrected Proof

Rodolfo V. Curiel, Nicolas J. Guzman — 2012-05-04

Objective: As many as half of all patients with gouty arthritis have some degree of renal impairment. The goal of this systematic review is to provide physicians with a comprehensive examination of available data on the risks and benefits of gouty arthritis treatment options when used in patients with chronic kidney disease (CKD). Methods: We conducted a systematic literature review to determine what information is available to guide treatment decisions in this patient population. PubMed was searched for English-language articles indexed through July 2011 containing the terms “gout” or “hyperuricemia” and synonyms for renal impairment in combination with drug names. Publications were deemed relevant if they reported results from clinical studies, case reports, or prescribing practices of the drug of interest in patients with gouty arthritis and CKD. Results: Nonsteroidal anti-inflammatory drugs and colchicine are oftentimes not considered appropriate in patients with CKD. Corticosteroids may be an effective alternative in this population; however, their efficacy has not been confirmed in randomized controlled trials and these agents can cause serious side effects. Allopurinol can be used for the prophylactic management of chronic hyperuricemia in patients with CKD, but the recommended decreased dosage may limit efficacy and serious hypersensitivity reactions may preclude its use. Febuxostat and pegloticase are new treatment options for chronic urate-lowering prophylaxis; however, the safety of these drugs in patients with advanced CKD has not yet been reported. Conclusions: There is currently an unmet need for additional treatment options for the management of gouty arthritis in patients with CKD.

Development of Leprosy in a Patient with Rheumatoid Arthritis During Treatment with Etanercept: A Case Report - Corrected Proof

2012-04-27

Background: Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder. There is a clear association between some disease-modifying drugs used to treat RA and infection. The introduction of the anti-tumor necrosis factor (TNF) therapies has improved the outcome of severe RA. The TNF-antagonism may increase susceptibility to granulomatous pathogens such as Mycobacterium tuberculosis, Listeria monocytogenes, and Histoplasma capsulatum. Methods: We report the case of a 37-year-old woman with RA receiving an anti-TNF agent, who developed a rash on her back and both legs, which was finally diagnosed as tuberculoid leprosy. Results: This is the first case of leprosy due to anti-TNF therapy reported in Europe. Conclusions: Clinicians should be aware of this and other types of atypical and serious infections that patients may suffer from when treated with anti-TNF agents.

Magnetic Resonance Imaging of Subchondral Bone Marrow Lesions in Association with Osteoarthritis - Corrected Proof

Li Xu, Daichi Hayashi, Frank W. Roemer, David T. Felson, Ali Guermazi — 2012-04-27

Objectives: This nonsystematic literature review provides an overview of magnetic resonance imaging (MRI) of subchondral bone marrow lesions (BMLs) in association with osteoarthritis (OA), with particular attention to the selection of MRI sequences and semiquantitative scoring systems, characteristic morphology, and differential diagnosis. Histologic basis, natural history, and clinical significance are also briefly discussed. Methods: PubMed was searched for articles published up to 2011, using the keywords bone marrow lesion, osteoarthritis, magnetic resonance imaging, bone marrow edema, histology, pain, and subchondral. Results: BMLs in association with OA correspond to fibrosis, necrosis, edema, and bleeding of fatty marrow as well as abnormal trabeculae on histopathology. Lesions may fluctuate in size within a short time and are associated with the progression of articular cartilage loss and fluctuation of pain in knee OA. The characteristic subchondral edema-like signal intensity of BMLs should be assessed using T2-weighted, proton density-weighted, intermediate-weighted fat-suppressed fast spin echo or short tau inversion recovery. Several semiquantitative scoring systems are available to characterize and grade the severity of BMLs. Quantitative approaches have also been introduced. Differential diagnoses of degenerative BMLs include a variety of traumatic or nontraumatic pathologies that may appear similar to OA-related BMLs on MRI. Conclusions: Subchondral BMLs are a common imaging feature of OA with clinical significance and typical signal alteration patterns, which can be assessed and graded by semiquantitative scoring systems using sensitive MRI sequences.

Treatment of Chronic Gouty Arthritis: It Is Not Just About Urate-Lowering Therapy - Corrected Proof

Naomi Schlesinger — 2012-04-27

Objectives: The management of gouty arthritis is focused on treating pain and inflammation associated with acute flares and preventing further acute flares and urate crystal deposition. A challenge associated with the successful management of gouty arthritis is an increased risk of acute flares during the first months after initiation of urate-lowering therapy (ULT). This increase in flare frequency can occur regardless of the choice of ULT and is linked to suboptimal patient adherence to ULT. Current treatment recommendations for the use of prophylaxis are limited. There are no definitive recommendations as to which agents should be used or for how long therapy is beneficial after starting ULT. This article aims to improve awareness of the importance of gouty arthritis flare prophylaxis when initiating ULT and to summarize current recommendations and clinical findings related to the efficacy and safety of currently available and investigational new therapies. Methods: This review discusses the pathophysiology of acute gouty arthritis flares during initiation of ULT and examines the literature on the use of anti-inflammatory prophylaxis for reduction of these flares. Results: It has recently become clear that, even when the patient is asymptomatic, chronic inflammation is often present in patients with chronic gouty arthritis. Chronic anti-inflammatory therapy should therefore be added to chronic ULT. Prophylaxis with colchicine as well as with nonsteroidal anti-inflammatory drugs (NSAIDs) during ULT initiation can reduce the incidence and severity of gouty arthritis flares substantially; however, safety concerns associated with colchicine and NSAIDs may limit their use. Conclusion: When colchicine and NSAIDs are contraindicated or poorly tolerated, rilonacept and canakinumab, interleukin-1 inhibitors in trials, may prove to be useful alternatives for flare prevention. (Of note, although both inhibit the IL-1β pathway, rilonacept also binds to IL-1α and IL-1RA, in contrast to canakinumab, which binds selectively to IL-1β.)

Potential Immunologic Targets for Treating Fibrosis in Systemic Sclerosis: A Review Focused on Leukocytes and Cytokines - Corrected Proof

Minoru Hasegawa, Kazuhiko Takehara — 2012-04-27

Objectives: Systemic sclerosis (SSc) is a connective tissue disease characterized by tissue fibrosis. Although the pathogenesis remains unclear, a variety of cells contribute to the fibrotic process via interactions with each other and production of various cytokines. Recent literature related to the immunologic pathogenesis and future strategies for treating the fibrosis of SSc are discussed and, especially, this literature-based review that includes the authors' perspective, focused on leukocytes and cytokines. Methods: A PubMed search for articles published between January 2005 and January 2012 was conducted using the following keywords: systemic sclerosis, leukocyte, cytokine, growth factor, and chemokine. The reference lists of identified articles were searched for further articles. Results: Targeting profibrogenic cytokines, including transforming growth factor-β, is still a very active area of research in SSc and most cellular studies have focused on the roles of fibroblasts in SSc. However, a growing number of recent studies indicate a role for B cells in the development of SSc and other autoimmune diseases such as systemic lupus erythematosus. Therefore, B-cell-targeted therapies, including currently available monoclonal antibodies against CD19, CD20, CD22, and B-cell-activating factor, belonging to the tumor necrosis factor family represent possible treatment options. Furthermore, the modulation of T-cell costimulatory molecules such as a recombinant fusion protein of cytotoxic T-lymphocyte antigen-4 may be as effective in SSc as it is in treating other autoimmune diseases. Approaches to antagonize interleukin (IL)-1, IL-6, or IL-17A signaling may also be attractive. Conclusions: This review describes recent advances in the treatment of fibrosis in SSc patients focused on immunologic strategies, such as leukocyte- or cytokine-targeted therapies.

The Broad Spectrum of Urate Crystal Deposition: Unusual Presentations of Gouty Tophi - Corrected Proof

Lindsy J. Forbess, Theodore R. Fields — 2012-04-23

Objectives: Gout is typically described as an inflammatory arthropathy that affects the peripheral joints. Our aim was to describe atypical and rare clinical presentations of gouty tophi to help increase physician awareness and aid in patient care. Methods: The relevant English literature of unusual gout manifestations was searched using the keywords gout, toph*, monosodium urate, uric acid, unusual, and rare. Well-described case reports, case series, and review articles were evaluated and included, if relevant, in the literature review. Results: Review of the literature revealed many unusual manifestations of gouty tophi involving the head and neck, skin, viscera, bones, tendons, ligaments, nerves, and axial skeleton. Transplant recipients, women, and elderly people are particularly susceptible to developing tophi. Furthermore, gout can cause diagnostic dilemmas, as it can be a great mimicker of and can coexist with infection, malignancy, and other connective tissue diseases. Imaging modalities can help detect tophi in atypical locations. Conclusions: Tophi can present in unexpected locations, even as the first sign of gout, and vigilance is required when unusual symptoms or signs occur in a patient with gout.

The Use of Canakinumab, a Novel IL-1β Long-Acting Inhibitor, in Refractory Adult-Onset Still's Disease - Corrected Proof

Apostolos Kontzias, Petros Efthimiou — 2012-04-18

Objectives: We describe the successful treatment of adult-onset Still's disease (AOSD) with canakinumab, a novel anti-interleukin (IL)-1β, long-acting, monoclonal antibody, on patients refractory to anakinra and rilonacept. In many cases the expected positive therapeutic effect of short-acting IL-1 inhibitors is transient or completely absent, leading to our hypothesis that their short half-life may be associated with incomplete IL-1 blockade, given the cyclic nature of the disease. Methods: We report 2 cases of AOSD resistant to short-acting IL-1 blockade, which were subsequently treated with canakinumab. A retrospective chart review was conducted of patients diagnosed with AOSD in our regional referral center. Results: Response to treatment was assessed by its effect on the systemic symptoms (resolution of fever and rash), polyarthritis (using the disease activity score 28--C-reactive protein score), and the levels of serum ferritin. Canakinumab demonstrated sustained efficacy in both patients as evidenced by clinical and laboratory parameters with minimal adverse reactions. Conclusions: This is the first documented report of successful use of canakinumab, a novel IL-1β inhibitor, in AOSD patients refractory to traditional disease-modifying antirheumatic drugs and short- to moderate-acting IL-1 blockade. Prospective comparative studies are needed to validate canakinumab's efficacy and safety.

Muckle-Wells Syndrome and Male Hypofertility: A Case Series - Corrected Proof

2012-04-18

Objectives: Muckle-Wells syndrome (MWS) is a rare autoinflammatory disorder associated with NLRP3 gene mutations, which cause excessive caspase-1 activation and processing of interleukin (IL)-1β and IL-18. Here we investigated whether MWS disease may be associated with impaired fertility in male patients. Methods: Medical records of all male MWS patients with NLRP3 mutations followed in our tertiary center for inherited autoinflammatory diseases were reviewed retrospectively for data indicating fertility problems. Results: Six of 9 patients were unable to have children despite regular sexual activity during at least 2 years; 3 succeeded in having children through in vitro fertilization. Infertility was the main reason for divorce in 1 patient. Spermiogram analyses were available in 8 of the 9 patients. Oligozoospermia was observed in 5 patients and azoospermia in 3 patients. In 3 patients, treatment with IL-1-targeting drugs for 6 months, 12 months, and 5 years, respectively, had a moderate or no effect on spermatozoa counts. In 2 patients testosterone levels were low and testosterone treatment significantly increased spermatozoa counts in 1 of them. Conclusions: MWS may be associated with subfertility and infertility in male patients. Consequently, sexual health and fertility should be assessed systematically in adolescent and adult male patients. Additional studies are required to establish the frequency of subfertility in male MWS patients, to understand when subfertility occurs in the disease natural history, and, finally, to investigate whether early management with IL-1-targeting drugs, or testosterone treatment or early sperm cryo-conservation may help to allow procreation.

Scientific Evidence of the Therapeutic Effects of Dead Sea Treatments: A Systematic Review - Corrected Proof

Uriel Katz, Yehuda Shoenfeld, Varda Zakin, Yaniv Sherer, Shaul Sukenik — 2012-04-13

Objectives: The Dead Sea, the deepest and most saline lake on earth, has been known from biblical times for its healing properties. The aim of this systematic review was to present critically the level of evidence for the claims of therapeutic effects of Dead Sea treatments in several rheumatologic diseases and psoriasis as well as to review these treatments' safety. Methods: All articles cited in MEDLINE under the query, “Dead Sea,” were reviewed. Results: We found bona fide evidence that Dead Sea treatments are especially effective in psoriasis due to both the special characteristics of solar ultraviolet radiation in the Dead Sea and the Dead Sea water balneotherapy. Dead Sea mud and Dead Sea balneotherapy have been found to be beneficial in rheumatologic diseases, including rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and knee osteoarthritis. In the safety analysis, we found no evidence for an increase in skin neoplasia, although skin actinic damage seems to be increased in patients treated in the Dead Sea. Dead Sea treatments do not lead to worsening of blood pressure. Substantial ingestion of Dead Sea water (generally in unusual near-drowning cases) is toxic and can result in cardiac rhythm disturbances because of electrolyte concentration abnormalities. Laboratory analysis of Dead Sea mud did not reveal mineral concentrations that could represent a health concern for their intended use. Conclusions: Dead Sea treatments are beneficial in several rheumatologic diseases and psoriasis and have a good safety profile.

No Increased Rate of Acute Myocardial Infarction or Stroke Among Patients with Ankylosing Spondylitis—A Retrospective Cohort Study Using Routine Data - Corrected Proof

2012-04-12

Objectives: To examine if people with ankylosing spondylitis (AS) are at higher risk of acute myocardial infarction (MI) or stroke compared to those without AS. Methods: Primary care records were linked with all hospital admissions and deaths caused by MI or stroke in Wales for the years 1999-2010. The linked data were then stratified by AS diagnosis and survival analysis was used to obtain the incidence rate of MI and separately cerebrovascular disease (CVD)/stroke. Cox regression was used to adjust for gender and age. Logistic regression was used to examine prevalence of diabetes, hypertension, or hyperlipidemia for those with AS compared to those without. Results: There were 1686 AS patients (75.9% male, average age 46.1 years) compared to 1,206,621 controls (48.9% male, average age 35.9 years). Age- and gender-adjusted hazard ratios for MI were 1.28 (95% CI: 0.93 to 1.74) P = 0.12, and for CVD/stroke 1.0 (95% CI: 0.73 to 1.39) P = 0.9, in AS compared to controls. The prevalence of diabetes and hypertension, but not hyperlipidemia/hypercholesterolemia, was higher in AS. Conclusions: There is no increase in the MI or CVD/stroke rates in patients with AS compared to those without AS, despite higher rates of hypertension, which may be related to nonsteroidal anti-inflammatory drug use.

Disease-Specific Patient Reported Outcome Tools for Systemic Lupus Erythematosus - Corrected Proof

2012-04-05

Purpose: Systemic lupus erythematosus (SLE) can significantly affect both health and non-health-related quality of life (HRQOL and non-HRQOL). However, of the existent published patient-reported outcome (PRO) tools, none were developed from US patients, an ethnically diverse population. Furthermore, these tools do not address men with SLE or assess non-HRQOL issues. Herein, we present the development and validation of the Lupus Patient-Reported Outcome tool (LupusPRO) and discuss its clinical utility and research value compared with other PRO tools currently available for SLE. Methods: Beginning with a conceptual framework, items for LupusPRO were generated using feedback from women and men with SLE. The tool underwent iterations based on patient feedback and clinimetric and psychometric analyses. Validity (content, construct, and criterion) and reliability (internal consistency and test-retest) for the 44-item LupusPRO tool are presented. Results: Consistent with the conceptual framework, items were identified that were related to HRQOL and non-HRQOL constructs. HRQOL domains included (1) lupus symptoms; (2) physical health (physical function, role physical); (3) pain–vitality; (4) emotional health (emotional function and role emotional); (5) body image; (6) cognition; (7) procreation; and (8) lupus medications. Non-HRQOL domains were (1) available social support and coping; (2) desires–goals; and (3) satisfaction with medical care. Internal consistency reliability (0.68-0.94), test-retest reliability (0.55-0.92), content, construct (r > 0.50 with SF-36), and criterion (r > −0.35 with disease activity) validity were fair to good. Conclusions: LupusPRO is a valid and reliable disease-targeted patient-reported health outcome tool that is generalizable to SLE patients in the United States of varied ethnic backgrounds and either gender.

The Effect of Tumor Necrosis Factor-α Antagonists on Arterial Stiffness in Rheumatoid Arthritis: A Literature Review - Corrected Proof

2012-04-05

Background: There is evidence that patients with rheumatoid arthritis (RA) have a higher arterial stiffness than their age-matched healthy counterparts and thus have a higher cardiovascular risk. Under National Institute for Clinical Excellence guidelines, tumor necrosis factor-α (TNF-α) antagonists are indicated clinically in patients with severe active rheumatoid disease. TNF-α antagonists have been found to reduce inflammatory markers in RA; however, it is debatable if they have favorable effects on the cardiovascular system. This review evaluates the effect of TNF-α antagonists on arterial stiffness, a predictor of cardiovascular disease, in RA patients. Search strategy: A search of Ovid MEDLINE and ISI Web of Knowledge databases was conducted to identify studies into the effect of TNF-α antagonists on arterial stiffness in RA patients. Eight studies matching the search criteria were included for analysis. Findings: Two methods were used to assess arterial stiffness: pulse wave velocity and augmentation index. Despite inconsistencies in augmentation index values, aortic pulse wave velocity in all but one study was significantly reduced following TNF-α antagonist treatment. Most studies had methodological limitations, including inadequate sample size, nonblinding of those involved in the measurements, and inadequate inclusion/exclusion criteria. Variation in results could be due to the use of different TNF-α antagonists, different outcome measures being used, and differences in follow-up. Conclusions: The balance of evidence suggests that TNF-α antagonists may have a beneficial effect on arterial stiffness and therefore cardiovascular risk. However, larger more robust longer term studies are warranted to confirm recent findings.

Rheumatoid Arthritis Is an Independent Risk Factor for an Increased Augmentation Index Regardless of the Coexistence of Traditional Cardiovascular Risk Factors - Corrected Proof

2012-04-05

Background: Rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity. It was previously shown that the augmentation index (AIx), a marker of vascular dysfunction, is higher in RA patients without traditional cardiovascular risk factors than in healthy controls. In this study we determined whether the impact of RA on the AIx is diminished in the context of coexisting, strong cardiovascular risk factors. Patients and methods: A total of 411 participants were included [203 with RA; 208 in the non-RA (n-RA) group]. Pulse-wave analysis was performed on the radial artery using applanation tonometry. The impact of RA on the AIx was determined in a single and in a multiple linear regression model. Results: The mean unadjusted AIx was 30.5 ± 9.0% for RA patients and 24.0 ± 11.0% for the n-RA group (P < 0.001). In the regression model, the following variables are statistically significant at approximately the same level (P < 0.001); the order of impact of these variables is age > diastolic blood pressure > sex > RA > height > smoking status. RA, height, and smoking had a nearly equal impact on the AIx. Conclusions: The AIx is increased in RA patients regardless of the coexistence of traditional cardiovascular risk factors, thereby reflecting vascular dysfunction in this population. The impact of RA on the vascular system is comparable to that of smoking.

Do Patients with Elderly-Onset Rheumatoid Arthritis Have Severe Functional Disability? - Corrected Proof

2012-04-02

Objective: To identify the clinical features of elderly-onset rheumatoid arthritis (EORA) and their impact on disease outcome. Methods: A total of 3169 rheumatoid arthritis (RA) patients were recruited as part of the Korean Observational Study Network for Arthritis, the nationwide cohort of South Korea. Patients were stratified according to age at disease onset: <40 years (younger age-onset RA, n = 1167), between the ages of 40 and 59 (middle-aged-onset RA, n = 1516), and ≥60 years (EORA, n = 486). To evaluate the significance of differences in clinical features among these 3 groups, we performed analysis of variance (anova) and the χ2 test. We used multivariable logistic regression analysis to examine the association of onset age with functional disability measured with Health Assessment Questionnaire-Disability Index (HAQDI). Results: EORA patients were associated with high HAQDI (≥1) in bivariable analysis [odds ratio (OR) 1.36, confidence interval (CI) 1.04-1.77]. However, in multivariable analysis, not elderly onset but patients' age, female gender, high disease activity, disease duration over 10 years, and comorbidity with cardiovascular disease were associated with high HAQDI. Only in a predefined subgroup with disease duration <10 years, elderly onset was an independent influencing factor for the functional disability of RA patients (OR 3.04, CI 1.85-5.67: disease duration of <5 years, OR 3.07, CI 1.64-5.74: disease duration of 5 to 10 years). Conclusions: Disease onset in older age was associated independently with functional disability of RA patients who have relatively short disease duration.

Treatment of Systemic Sclerosis Complications: What to Use When First-Line Treatment Fails—A Consensus of Systemic Sclerosis Experts - Corrected Proof

2012-04-01

Objectives: There is a need for standardization in systemic sclerosis (SSc) management. Methods: SSc experts (n = 117) were sent 3 surveys to gain consensus for SSc management. Results: First-line therapy for scleroderma renal crisis (SRC) was an angiotensin-converting enzyme inhibitor (ACEi). For SRC there were not many differences between treating mild or severe SRC. In general, Second-line was to add either a calcium channel blocker (CCB) or angiotensin receptor blocker (ARB) and then an alpha-blocker (66% agreed). Endothelin receptor agonists (ERAs) were the first treatment in mild pulmonary arterial hypertension (PAH) (72%), followed by adding a phosphodiesterase-5 inhibitor (PDE5i) (77%) and then a prostanoid (73%). For severe PAH, initial treatment was 1 of the following: a prostanoid (49%), combination of a ERA and a PDE5i (18%), or combination of a ERA and a prostanoid (16%) (71% agreed). For mild Raynaud's phenomenon (RF), after a CCB and adding a PDE5i (35%), trying an ARB (32%) and finally a prostanoid (23%) was suggested. For more severe RF, 54% agreed on adding a PDE5i (45%) or prostanoid (32%) to a CCB. In the prevention of digital ulcers (DU), initial treatment was a CCB (73%), then adding a PDE5i, then use of a ERA, and then a prostanoid (44% agreed). In interstitial lung disease/pulmonary fibrosis, for induction, usually intravenous cyclophosphamide and mycophenolate mofetil (MMF) or azathioprine were chosen. For maintenance, MMF was chosen by three-fourths (56% agreed). For gastroesophageal reflux disease, >50% would exceed the maximum recommended proton pump inhibitor dose if required (72% agreed). For skin involvement after methotrexate, MMF was usually chosen (37% agreement). For SSC-related inflammatory arthritis, methotrexate therapy (60%) was followed by adding corticosteroids (37%) or hydroxychloroquine (31%) (62% agreed). Conclusions: Discrepancies in drug choices occurred in treatment after first line in SSc. Not all algorithms had good agreement. This study provides some guidance for SSc management.

Differences in the Patient's and the Physician's Perspective of Disease in Psoriatic Arthritis - Corrected Proof

2012-03-19

Objective: To define the relative impact of disease components of psoriatic arthritis (PsA) on the global burden of disease and to compare physician's and patients' ratings of disease activity. Methods: PsA patients fulfilling the Classification Criteria for Psoriatic Arthritis (N = 55) were asked for an evaluation of the absolute and relative impact of general and specific rheumatic symptoms (ie, arthritis, enthesitis, spinal disease, dactylitis), general and specific psoriatic symptoms (skin disease, nail disease), and other common symptoms (eg, fatigue). Results were related to the respective physician's evaluations of disease-related symptoms based on visual analog scale (VAS) ratings and comparative measures of disease activity (ie, swollen and tender joint counts, MASES, PASI, NAPSI). Results: One-half of the global burden of disease in PsA patients was attributed to rheumatic symptoms with peripheral arthritis as the leading component, whereas the other one-half was equally distributed to psoriatic and additional common symptoms such as fatigue. In general, corresponding patient and physician ratings of global, rheumatic, and psoriatic disease activity showed good correlations when using VAS but at the same time revealed significantly lower ratings of the corresponding physician on VAS and transformed comparative measures (all P ≤ 0.02). Conclusions: Although we found good correlations of various disease activity measures, physicians usually evaluated the disease activity of PsA lower than patients. These results highlight the necessity of incorporating patient reported outcome measures into the assessment of disease activity in PsA, which can easily be visualized with the help of a spiderweb graph.

Lipid Testing in Patients with Rheumatoid Arthritis and Key Cardiovascular-Related Comorbidities: A Medicare Analysis - Corrected Proof

2012-03-19

Objective: For patients with rheumatoid arthritis (RA) and comorbid cardiovascular disease (CVD), diabetes, or hyperlipidemia, annual lipid testing is recommended to reduce morbidity and mortality from comorbidities. Given trends encouraging complex patients to receive care in “medical homes,” we examined associations between regularly seeing a primary care provider (PCP) and lipid testing in RA patients with cardiovascular-related comorbidities. Methods: We performed a retrospective cohort study examining a 5% random USA Medicare sample (2004-06) of beneficiaries over 65 years old with RA and concomitant CVD, diabetes, or hyperlipidemia (n = 16,893). We examined the relationship between receiving lipid testing in 2006 and having at least 1 PCP visit per year in 2004, 2005, and 2006 using multivariate regression. Results: Ninety percent of patients had prevalent CVD; 46% had diabetes, and 64% had hyperlipidemia. However, annual lipid testing was only performed in 63% of these RA patients. Thirty percent of patients saw a PCP less than once per year, despite frequent visits (mean >9) with other providers. Patients without at least 1 annual PCP visit were 16% less likely to have lipid testing. Increased age, complexity scores, hospitalization, and large town residence predicted decreased lipid testing. Conclusions: Despite comorbid CVD, diabetes, or hyperlipidemia, 30% of Medicare RA patients saw a PCP less than once per year, and 1 in 3 lacked annual lipid testing. Findings support advocating primary care visits at least once per year. Remaining gaps in lipid testing suggest the need for additional strategies to improve lipid testing in at-risk RA patients.

Relapsing Polychondritis in the Department of Defense Population and Review of the Literature - Corrected Proof

Stephanie D. Mathew, Daniel F. Battafarano, Michael J. Morris — 2012-03-13

Objective: The objective of this study was to characterize the clinical features of relapsing polychondritis (RPC) within the Department of Defense beneficiary population and determine the utility of echocardiography, imaging studies, and pulmonary function testing for diagnosis and monitoring disease. Methods: We performed a retrospective Electronic Medical Record chart review of all patients diagnosed with RPC within the Department of Defense between January 2004 and December 2009. Results: Thirty patients met McAdam's diagnostic criteria and an additional 13 met our criteria for partial RPC. Auricular chondritis (88%), inflammatory eye disease (57%), and arthritis (60%) were the most common clinical manifestations. Pulmonary involvement was seen in 16 (37%) patients. Methotrexate (42%) and corticosteroids (21%) were the most conventional therapies. Thirty (70%) patients had pulmonary function tests with flow volume loop abnormalities observed in 33%. Chest computed tomography was performed in 63%, with abnormalities in 48%. Abnormalities on echocardiography were observed in 12 of 25 (48%) patients. Conclusions: The incidence, demographic data, and organ involvement in our RPC patients were similar to previous studies. The diagnosis of RPC was determined primarily on physical examination and symptom-driven diagnostic testing. There was no notable pattern by rheumatologists for monitoring the progression of tracheobronchial tree or large vessel involvement. Interpreting flow volume loops is recommended with pulmonary function testing to detect early laryngotracheal involvement. Computed tomography of the chest is also recommended to monitor for vascular and tracheobronchial tree involvement.

The Role of Complement in the Antiphospholipid Syndrome: A Novel Mechanism for Pregnancy Morbidity - Corrected Proof

Michael Samarkos, Eleni Mylona, Violeta Kapsimali — 2012-03-12

Objectives: Despite the experimental research data on antiphospholipid syndrome (APS), the pathogenesis of thrombosis and fetal loss remains unknown. The objective of this study was to analyze the major advances in the field of complement activation as a possible thrombosis mechanism in the APS. Methods: The authors conducted a systemic analysis of the English literature and summarized both animal and human data that indicate the inappropriate complement activation as a mechanism causing thrombosis in the APS. Results: The important role of complement activation in the pathogenesis of fetal loss was established using mice deficient in a complement regulatory protein. Further studies have shown that the infusion of human IgG antiphospholipid antibodies (aPL) induced fetal loss in pregnant mice, an effect that was abrogated by the concurrent administration of a C3 convertase inhibitor. Further studies suggested that C5a and neutrophils were the key components responsible for fetal injury. Moreover, use of F(ab)′2 fragments of aPL suggested the complement activation occurred mainly via the classical pathway. Other studies using models of induced thrombosis suggested that antibodies against β2GPI required the presence of terminal complement components to induce thrombus formation, and mice deficient in C3 or C5 were found to be resistant to aPL-induced thrombosis. Based on the aforementioned findings, it has been suggested that heparin prevents fetal loss in patients with APS by inhibiting complement activation rather than by its anticoagulant effect. Conclusions: The studies on complement are significant because they shift the focus of research in APS from thrombosis to inflammation. However, as human data are limited, more clinical research is necessary before the above findings translate in changes in the management of APS.

Role of Interleukin-12 and - 18 in Lupus-like Syndrome Patients with Statin Use: Comment on: Association Between Statin Use and Lupus-like Syndrome Using Spontaneous Reports⁎ - Corrected Proof

Se Jin Park, Jae Il Shin — 2012-03-12

We read with great interest the recent contribution by de Jong et al. (). They assessed whether there was an association between statin use and the occurrence of lupus-like syndrome (LLS) and found that statins were associated with the reporting of LLS (reporting odds ratios 2.01; 95% confidence intervals 1.61-2.51). However, they did not explicate more detailed causality. We would like to suggest a possible pathomechanism in the development of LLS by using statin.

IL-6 Receptor Inhibition Positively Modulates Bone Balance in Rheumatoid Arthritis Patients with an Inadequate Response to Anti-Tumor Necrosis Factor Therapy: Biochemical Marker Analysis of Bone Metabolism in the Tocilizumab RADIATE Study (NCT00106522) - Corrected Proof

2012-03-09

Objective: To evaluate changes in biochemical markers of bone metabolism in response to tocilizumab in patients with anti-tumor necrosis factor—refractory rheumatoid arthritis (RA). Methods: RADIATE was a randomized, double-blind, placebo-controlled, parallel-group phase 3 trial. C-reactive protein, osteocalcin (OC), C-terminal telopeptides of type-I collagen (C-terminal telopeptides of type-1 collagen (CTX-I) and type-I collagen degradation product), and matrix metalloproteinase-3 (MMP-3) serum levels were analyzed from 299 RA patients. Patients were randomly assigned to either tocilizumab (4 or 8 mg/kg) or placebo intravenously every 4 weeks, along with concomitant stable methotrexate (10 to 25 mg weekly) in all treatment arms. The change in biochemical markers CTX-I and OC in combination was evaluated as a measure of net bone balance, a reflection of the change in equilibrium between resorption and formation. Results: Both tocilizumab doses decreased C-reactive protein levels and significantly inhibited cathepsin K–mediated bone resorption in RADIATE subjects, as measured by a decrease in CTX-I. There was a significant overall improvement in net bone balance at week 16 as measured by a decrease in the CTX-I:OC ratio (−25%, P < 0.01). Furthermore, a significant reduction in MMP-3 (43%, P < 0.001) and type-I collagen degradation product levels (18%, P < 0.001) were observed following treatment, both consistent with decreased MMP-mediated type-I collagen catabolism in joint tissue. Conclusions: In anti-tumor necrosis factor—refractory patients, tocilizumab significantly reduced the levels of biochemical markers of cathepsin K–mediated bone resorption and MMP-mediated tissue degradation and remodeling. These observations suggest that tocilizumab has a positive effect on bone balance, which could in part explain the retardation of progressive structural damage observed with tocilizumab. Clinical trial registry number: NCT00106522.

Efficacy and Safety of TNF Antagonists in Sarcoidosis: Data from the Spanish Registry of Biologics BIOBADASER and a Systematic Review - Corrected Proof

2012-03-05

Objective: To evaluate the safety, efficacy, and effectiveness of TNF antagonists in patients with sarcoidosis. Methods: A descriptive study of a case series registered in BIOBADASER and a systematic review was performed. The search strategy of articles published between 1998 and July 2011 in Medline, Embase, and the Cochrane Library included synonyms of sarcoidosis and synonyms of TNF antagonists. Results: Seven patients treated with infliximab (IFX) and 1 with etanercept (ETN) switched to IFX for inefficacy were registered in BIOBADASER 2.0. In 3, treatment is still ongoing. Reasons for discontinuation were serious adverse events in 2 cases, inefficacy in 2 cases, and complete clinical response in 2 cases. Eight serious adverse events were reported. In the selected 69 of 2262 reports and 1 abstract of the review, 232 patients (89.9%) were treated with IFX and 26 (10.0%) were treated with ETN. In 2 randomized clinical trials, favorable response of the lung disease was reported with IFX. In other randomized clinical trials, no improvement of ocular manifestations was reported with ETN. In the cases series, results were diverse. Mean weighted rates of adverse events, infections, serious infections, and malignancy were 39.9, 22.1, 5.9, and 1.0 per 100 patient-years, respectively. Conclusions: There is insufficient evidence to ensure the efficacy of TNF antagonists in sarcoidosis. Nevertheless, IFX may be effective in selected manifestations of the disease. Before starting treatment of sarcoidosis with IFX, a careful evaluation of the benefit/risk ratio must be considered on an individual basis.

Injection of Botulinum Toxin for Treatment of Chronic Lateral Epicondylitis - Corrected Proof

2012-02-16

We are pleased to read the article, “Injection of Botulinum Toxin for Treatment of Chronic Lateral Epicondylitis: Systematic Review and Meta-Analysis,” by Kalichman and coworkers in Seminars in Arthritis and Rheumatism (2011;40:532-8). The conclusions in their abstract stated that present literature provides support for use of botulinum toxin A injections into the forearm extensor muscles (60 units) for the treatment of chronic treatment-resistant lateral epicondylitis (). As they did not specify the proprietary name of the 60 units botulinum toxin type A, the readers may be misled if they only read the abstract without referring to the entire article.

Treatment of Erdheim-Chester Disease with Long-Term High-Dose Interferon-α - Corrected Proof

2012-02-10

Objectives: Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis, characterized by a foamy CD68+, CD1a− histiocyte tissue infiltration. Efficacy of standard doses of interferon-α-2a (IFNα) has been suggested in a small series but with variation, depending on the organs involved. Our aim was to report our single-center experience about the use of high-dose IFNα in ECD. Methods: Twenty-four ECD patients have received high-dose IFNα (IFNα ≥18 mIU/wk or pegylated-IFNα ≥180 μg/wk). IFNα efficacy was evaluated clinically and morphologically using a standardized protocol (median follow-up 19 months). Results: Indication for treatment was central nervous system and/or heart involvement (n = 20), exophthalmos (n = 1), and standard-dose IFNα inefficacy (n = 3). High-dose IFNα was effective in 16 patients (67%) with improvement (n = 11, 46%) and stabilization (n = 5, 21%). Late and gradual improvement was observed during prolonged follow-up in most patients. The efficacy of high-dose IFNα was dependent on the organs involved: central nervous system and heart improvement or stabilization occurred in 7/11 (64%) and 11/14 (79%) patients, respectively. Six patients (25%) worsened. High doses of IFNα were well-tolerated: 13 (54.2%) patients had side effects but treatment interruption was infrequent (n = 3, 12.5%). Conclusions: High-dose IFNα may be effective in severe ECD. Improvement may be slow, and high-dose IFNα treatment should be prolonged.

Gait Analysis of the Lower Limb in Patients with Rheumatoid Arthritis: A Systematic Review - Corrected Proof

Hetty Baan, Rosemary Dubbeldam, Anand V. Nene, Martin A.F.J. van de Laar — 2012-02-10

Introduction: In rheumatoid arthritis (RA), signs and symptoms of feet and ankle are common. To evaluate the dynamic function of feet and ankles, namely walking, a variety of gait studies have been published. In this systematic review, we provide a systematic overview of the available gait studies in RA, give a clinimetrical assignment, and review the general conclusions regarding gait in RA. Methods: A systematic literature search within the databases PubMed, CINAHL, sportdiscus, Embase, and Scopus was described and performed and delivered 78 original gait studies that were included for further data extraction. Results: The clinimetrical quality of the 78 included RA gait studies measured according a tailored QUADAS item list and proposed clinimetrical criteria by Terwee and coworkers are moderate. General conclusions regarding the walking abnormalities of RA patients point to a slower walk, longer double support time, and avoidance of extreme positions. Frequently found static features in RA are hallux valgus, pes planovalgus, and hind foot abnormalities. Conclusions: Gait studies in RA patients show moderate clinimetrical properties, but are a challenging way of expressing walking disability. Future gait research should focus on more uniformity in methodology. When this need is satisfied, more clinical applicable conclusions can be drawn.

Global Trend of Survival and Damage of Systemic Lupus Erythematosus: Meta-Analysis and Meta-Regression of Observational Studies from the 1950s to 2000s - Corrected Proof

Anselm Mak, Mike W.-L. Cheung, Hui Jin Chiew, Yang Liu, Roger Chun-man Ho — 2012-01-18

Objective: To assess systemically with meta-analysis the trend of survival and its determinants, which are hindering further improvement of survival of patients with systemic lupus erythematosus (SLE) over the past 5 decades. Methods: Retrospective, cross-sectional, and prospective observational studies addressing survival and damage in SLE patients published between 1 January 1950 and 31 July 2010 were identified in electronic databases. Using the random-effects model, effect size was calculated based on the logit of the overall 5- and 10-year survival rates. The pooled logit and its robust 95% confidence interval were transformed back into the 5- and 10-year survival rates, after adjusting for potential dependence on the data. Potential factors predicting the pooled survival rates were explored by meta-regression. Results: Seventy-seven studies involving 18,998 SLE patients were analyzed. Between the 1950s and the 2000s, their overall survival significantly increased, from 74.8% to 94.8% and 63.2% to 91.4% for the overall 5-year and 10-year survival, respectively (P < 0.001). The survival improvement, however, appeared to slow down between 1980 and 1990. Meta-regression revealed that neuropsychiatric and renal damage negatively affected the overall 5-year survival, whereas neuropsychiatric damage remained so for the 10-year survival for the past 50 years. Furthermore, the prevalence of neuropsychiatric damage has been significantly increasing over the past 5 decades. Conclusions: For the past 50 years, damage involving the renal and neuropsychiatric systems has been negatively affecting survival of SLE patients. Early detection and aggressive management of renal and neuropsychiatric involvement may potentially improve further the survival of lupus patients.

Meta-Analysis on the Performance of Sonography for the Diagnosis of Carpal Tunnel Syndrome - Corrected Proof

2012-01-13

Objective: We aimed to review and pool recent large methodological studies evaluating the diagnosis performance of ultrasonography vs electrodiagnostic testing (EDX). Methods: Using the keywords: “carpal tunnel syndrome”, “ultrasound”, and “validity”, recent articles evaluating ultrasonography compared with a reference including EDX were selected from 4 databases (PubMed, Embase, Web of science, and BDSP) and from previous review for older articles, after 2 rounds. Relevant data for different thresholds of cross-sectional area of the median nerve were extracted from the articles to calculate the pooled sensitivity, specificity, and likelihood ratios. Different analyses were also performed to study potential sources of heterogeneity, such as calculation of area under the curve, using summary receiver operating characteristic curve. Results: Among the 189 articles found, 13 articles were included. A cross-sectional area of the median nerve between 9.5 and 10.5 mm2 (study included once only), found for 11 studies, gave the pooled sensitivity as 0.84 [0.81 to 0.87] and the likelihood ratio for a negative test as 0.21 [0.17 to 0.27]. Specificity (0.78 [0.69-0.88]) and the likelihood ratio for a positive test (3.74 [2.30-6.10]) were heterogeneous. For a threshold at 7.0 to 8.5 mm2, pooled sensitivity was 0.94 [0.87 to 1.00], and for 11.5 to 13.0 mm2 specificity was 0.97 [0.91 to 1.00]. The only significant variable on potential sources of heterogeneity was the cross-sectional area of the median nerve threshold and area under the curve was 0.87 (asymmetric). Conclusions: Pooling recent articles seems to confirm that sonography using cross-sectional area of the median nerve could not be an alternative to EDX for diagnosis of carpal tunnel syndrome but could give complementary results.

NOD2/CARD15 Gene Mutations in Patients with Familial Mediterranean Fever - Corrected Proof

2012-01-13

Objective: Familial Mediterranean fever (FMF) and Crohn's disease are autoinflammatory disorders, associated with genes (MEFV and NOD2/CARD15, respectively) encoding for regulatory proteins, important in innate immunity, apoptosis, cytokine processing, and inflammation. Although mutations in the MEFV gene were shown to modify Crohn's disease, the role of NOD2/CARD15 gene mutations in the FMF disease phenotype was never studied before. Patients and methods: The cohort consisted of 103 consecutive children with FMF, followed in a single referral center. NOD2/CARD15 genotypes were analyzed in all patients and 299 ethnically matched unaffected controls. Demographic data, clinical characteristics, and disease course of FMF patients with and without NOD2/CARD15 mutation were compared. Results: A single NOD2/CARD15 mutation was detected in 10 (9.7%) FMF patients and 26 (8.7%) controls. No homozygous or compound heterozygous subjects were discovered in the 2 groups. FMF patients carrying a NOD2/CARD15 mutation had a higher rate of erysipelas-like erythema and acute scrotum attacks, a trend for a higher rate of colchicine resistance and a more severe disease as compared with patients without mutations. Conclusions: NOD2/CARD15 mutations are not associated with an increased susceptibility to develop FMF. Nevertheless, the presence of these mutations in FMF patients appears to be associated with a trend to a more severe disease.

Treatment of Systemic Sclerosis-Associated Calcinosis: A Case Report of Rituximab-Induced Regression of CREST-Related Calcinosis and Review of the Literature - Corrected Proof

2012-01-06

Objectives: Calcinosis is frequently encountered in patients with systemic sclerosis (SSc) and may be associated with significant morbidity. No treatment has shown so far an unequivocal beneficial effect. Methods: We performed an extensive internet search (MEDLINE) using the keywords calcinosis, calcification, scleroderma, systemic sclerosis, and treatment. Results: Our patient had extensive Calcinosis, Raynaud, Esophagitis, Sclerodactyly, telangiectasia (CREST)-related calcinosis, frequently ulcerating and painful. Following 2 rituximab courses (consisting of 4 weekly infusions, 375 mg/m2 each), calcinosis significantly improved and pain disappeared. Pharmacologic agents used in the treatment of SSc-associated calcinosis include diltiazem, minocycline, warfarin, biphosphonates, and intravenous immunoglobulin. Other therapeutic approaches include surgical excision, laser vaporization, and extracorporeal shock wave lithotripsy. Conclusions: Evidence for all existing therapies is weak and therefore larger scale controlled studies are needed. Rituximab appears as a promising treatment especially in view of recent evidence that this therapy may be also effective in the underlying disease.

Use of Diuretics and the Risk of Gouty Arthritis: A Systematic Review - Corrected Proof

2012-01-06

Objective: To systematically review the literature investigating the relationship between use of diuretics and the risk of gouty arthritis. Methods: PubMed (1950-October 2009), Embase (1974-October 2009), and the Cochrane Library (up to October 2009) were searched using keywords and MeSH terms diuretics, adverse effects, and gout. For this review, the technique of “best evidence synthesis” was used. Studies reporting frequency, absolute or relative risks, odds ratio, or rate ratio of gouty arthritis in diuretic users compared with nonusers were selected and evaluated. Studies had to be published in English. Checklists from the Dutch Cochrane Centre were used to assess the quality of randomized controlled trials (RCTs), cohort, and case-control studies. Results: Two RCTs, 6 cohort studies, and 5 case-control studies met the inclusion criteria. The overall quality of the studies was moderate. In a RCT the rate ratio of gout for use of bendrofluazide vs placebo was 11.8 (95% CI 5.2-27.0). The other RCT found a rate ratio of 6.3 (95% CI 0.8-51) for use of hydrochlorothiazide plus triamterene vs placebo. Three cohort studies and 4 case-control studies found higher risks of gouty arthritis in users compared with nonusers of diuretics. Conclusions: There is a trend toward a higher risk for acute gouty arthritis attacks in patients on loop and thiazide diuretics, but the magnitude and independence is not consistent. Therefore, stopping these useful drugs in patients who develop gouty arthritis is not supported by the results of this review.

A Prospective Functional MRI Study for Executive Function in Patients with Systemic Lupus Erythematosus Without Neuropsychiatric Symptoms - Corrected Proof

Anselm Mak, Tao Ren, Erin Hui-yun Fu, Alicia Ai-cia Cheak, Roger Chun-man Ho — 2012-01-06

Objective: To study the functional brain activation signals before and after sufficient disease control in patients with systemic lupus erythematosus (SLE) without clinical neuropsychiatric symptoms. Methods: Blood-oxygen-level-dependent signals during event-related functional magnetic resonance imaging brain were recorded, while 14 new-onset SLE patients and 14 demographically and intelligence quotient matched healthy controls performed the computer-based Wisconsin card sorting test for assessing executive function, which probes strategic planning and goal-directed task performance during feedback evaluation (FE) and response selection (RS), respectively. Composite beta maps were constructed by a general linear model to identify regions of cortical activation. Blood-oxygen-level-dependent functional magnetic resonance imaging signals were compared between (1) new-onset SLE patients and healthy controls and (2) SLE patients before and after sufficient control of their disease activity. Results: During RS, SLE patients demonstrated significantly higher activation than healthy controls in both caudate bodies and Brodmann area (BA) 9 to enhance event anticipation, attention, and working memory, respectively, to compensate for the reduced activation during FE in BA6, 13, 24, and 32, which serve complex motor planning and decision-making, sensory integration, error detection, and conflict processing, respectively. Despite significant reduction of SLE activity, BA32 was activated during RS to compensate for reduced activation during FE in BA6, 9, 37, and 23/32, which serve motor planning, response inhibition and attention, color processing and word recognition, error detection, and conflict evaluation, respectively. Conclusions: Even without clinically overt neuropsychiatric symptoms, SLE patients recruited additional pathways to execute goal-directed tasks to compensate for their reduced strategic planning skill despite clinically sufficient disease control.

HFE C282Y Homozygosity Is Associated with an Increased Risk of Total Hip Replacement for Osteoarthritis - Corrected Proof

2011-12-30

Objective: The evidence for an association between mutations in the HFE (hemochromatosis) gene and the risk of hip or knee osteoarthritis is inconsistent. Total joint replacement is considered a surrogate measure for symptomatic end-stage osteoarthritis. We examined the relationship between HFE gene mutations and risk of total hip and knee replacement using a prospective cohort study. Methods: The Melbourne Collaborative Cohort Study recruited participants between 1990 and 1994. Participants born in Australia, New Zealand, the United Kingdom, or Ireland (n = 27,848) were genotyped for the HFE C282Y mutation. Total hip and knee replacements for osteoarthritis during 2001 to 2009 were ascertained from the Australian Orthopaedic Association National Joint Replacement Registry. Hazard ratios (HR)/odds ratios (OR) and confidence intervals (CI) were obtained from Cox regression or logistic regression. Results: Compared with those with no C282Y mutation, C282Y homozygotes had an increased risk of single total hip replacement (HR 1.94, 95% CI 1.04-3.62) and bilateral total hip replacement (OR 5.86, 95% CI 2.36-14.57) for osteoarthritis, adjusting for age, sex, body mass index, and educational level. Only 3 C282Y homozygotes had single total knee replacement; the HR was 0.51 (95% CI 0.16-1.57). C282Y/H63D compound heterozygosity was not related to the risk of total hip or knee replacement. Conclusions: HFE C282Y homozygosity was associated with an increased risk of both single and bilateral total hip replacement for osteoarthritis.

Autoimmune Manifestations of Kikuchi Disease - Corrected Proof

2011-12-22

Objectives: Kikuchi's disease (KD) has been associated with the presence of autoantibodies, systemic lupus erythematosus (SLE), and other autoimmune diseases. The aim of this study was to assess the frequency of autoimmune manifestations in a KD cohort with a long follow-up. Methods: Twenty patients with histologically confirmed KD since January 1990 until December 2010 were studied; 12 of them were periodically followed up as outpatients. Another 7 patients were contacted by telephone to offer them a specific consultation and a complete autoimmunity study. Results: Thirteen of 20 patients were women (65%) with a mean age of 29 years (range, 15-79). The age at diagnosis was higher in men (44 vs 27 years, P < 0.05). Lymphopenia was present in 75% of the patients (15/20) and was the more frequent hematological abnormality. The mean follow-up of the 17 patients included in the autoimmunity study was 119 months (range, 15-252). Autoimmune diseases were detected in 9 women (53%): SLE was diagnosed in 4 patients (2 SLE before, 1 simultaneous, and 1 after KD), 2 patients developed primary Sjögren's syndrome after KD, 1 thyroiditis before KD, 1 SLE-like, and 1 antiphospholipid antibodies after KD. Leukocytoclastic vasculitis was found in 2 patients; 1 of them eventually developed SLE. Female sex, painful adenopathies, and cytopenias were significantly associated with autoimmune diseases. Conclusions: Among patients with KD, only women developed autoimmune manifestations. Therefore, long-term follow-up and active surveillance of autoimmune diseases in patients with KD, especially women, are recommended.

Intrarenal Hemodynamic Parameters Correlate with Glomerular Filtration Rate and Digital Microvascular Damage in Patients with Systemic Sclerosis - Corrected Proof

2011-12-22

Objectives: To evaluate intrarenal arterial stiffness by Doppler ultrasound and examine the correlation between renal Doppler indices, glomerular filtration rate, and digital microvascular damage in systemic sclerosis patients. Methods: Thirty systemic sclerosis patients and 30 healthy controls were enrolled in this study. Doppler indices of intrarenal arterial stiffness, peak systolic flow velocity, end diastolic flow velocity, resistive index, pulsative index, and systolic/diastolic (S/D) ratio were measured on the interlobar artery of both kidneys. Glomerular filtration rate was measured using Tc99m diethylenetriamine pentaacetic acid (DTPA). Equation 7 from the Modification of Diet in Renal Disease was used to estimate glomerular filtration rate. Nailfold videocapillaroscopy findings were classified as early, active, and late patterns. Results: The intrarenal arterial stiffness, evaluated by Doppler indices, was higher in systemic sclerosis patients than healthy controls. In systemic sclerosis patients pulsative index (r = −0.69), resistive index (r = −0.75), and S/D ratio (r = −0.74) showed a negative correlation with measured glomerular filtration rate (P < 0001). High correlation (P = 0008) was observed between measured and estimated glomerular filtration rate (r = 0.55). Pulsative index, resistive index, and S/D ratio significantly increased with progression of capillaroscopic damage. Conversely, measured glomerular filtration rate significantly decreased with capillaroscopic damage progression. Conclusions: Doppler indices of intrarenal arterial stiffness are noninvasive diagnostic tests to evaluate renal damage in SSc patients. Intrarenal arterial stiffness and glomerular filtration rate correlate with capillaroscopic microvascular damage.

Arthritis in Systemic Sclerosis: Systematic Review of the Literature and Suggestions for the Performance of Future Clinical Trials in Systemic Sclerosis Arthritis - Corrected Proof

2011-12-19

Objectives: Musculoskeletal (MSK) pain is a frequent (between 40-80%) complaint of patients with systemic sclerosis (SSc). Unfortunately, there are virtually no systematic studies of the causes or the management of MSK involvement in SSc and with few exceptions there have been no controlled trials to determine what are and should be the best strategies for managing MSK pain and synovitis in patients with SSc. Methods: A literature search was conducted for published reports that have addressed the clinical assessment of “arthritis” and “musculoskeletal” involvement in SSc. The literature search was a prelude to developing recommendations/suggestions for performing clinical trials (preferably randomized) in the future in SSc-related arthritis. Results: The search netted a number of articles that reported clinical assessments of arthritis in SSc, but very few reported results of controlled clinical trials. Nevertheless, a prevalence of clinical arthritis and tools used to assess the involvement (clinical examination, functional assessments and assessments of quality of life, and radiographic imaging) was found. Conclusions: Most of the tools used to assess arthritis in SSc patients have not been validated and additional work is needed to develop a “core set” of variables for assessment of arthritis in SSc and its response to treatment. This report furnishes the background information that can help provide the building blocks for the development of a “core set” that can be used to chart the efficacy of new treatments for SSc-related arthritis in the future.

Patients with Retinal Vasculitis Rarely Suffer from Systemic Vasculitis - Corrected Proof

James T. Rosenbaum, Jennifer Ku, Amro Ali, Dongseok Choi, Eric B. Suhler — 2011-12-19

Objectives: Systemic vasculitis is often mistakenly assumed to be a common cause of retinal vasculitis. We sought to determine the relationship between retinal vasculitis and systemic vasculitis. Methods: A selected review was performed on 1390 charts of patients attending the uveitis clinic at the Oregon Health and Science University between 1985 and 2010. Included in the review were all patients with diagnoses commonly associated with retinal vasculitis and all patients who were diagnosed with a systemic vasculitis. Retinal vasculitis was identified by perivascular exudates, intraretinal hemorrhage, or cotton wool spots as seen on clinical examination or by vascular occlusion or leakage as identified by fluorescein angiogram. Results: Two hundred seven or 14.9% of patients with uveitis had retinal vasculitis as a component of the intraocular inflammation. Thirty-five patients had retinal vasculitis that was primary, ie, not associated with a systemic disease, and the dominant manifestation of the uveitis. Fourteen of the patients with retinal vasculitis had Behcet's disease. Only 11 of the 1390 patients with uveitis had a systemic vasculitis. Of these 11, four had retinal vasculitis including 1 secondary to a cytomegalovirus retinitis. Thus, systemic vasculitis was directly responsible for 1.4% or 3 of 207 cases of retinal vasculitis. Nonvasculitic systemic diseases such as sarcoidosis (n = 13), syndromes confined to the eye such as pars planitis (n = 36), and intraocular infections (n = 29) were far more common causes of retinal vasculitis. Conclusions: Retinal vasculitis is a relatively common feature of uveitis. Patients with retinal vasculitis, however, rarely suffer from 1 of the classical systemic vasculitides.

Measurement of Autoantibodies in Pediatric-Onset Systemic Lupus Erythematosus and Their Relationship with Disease-Associated Manifestations - Corrected Proof

2011-12-19

Objective: To evaluate an autoantibody profile in pediatric-onset systemic lupus erythematosus (SLE) patients to determine clinical and statistical associations with disease-associated manifestations. Methods: Sera from 53 SLE patients and 22 healthy individuals were collected. Antibodies to C1q, histone, chromatin, ribosomal P, dsDNA, and high-avidity dsDNA were measured by enzyme-linked immunosorbent assays. Patient records were evaluated for clinical and laboratory associations. Results: The most prevalent autoantibodies found in the SLE cohort were anti-C1q antibodies (n = 32, 60%), which correlated significantly with proteinuria and decreased complement levels (P < 0.05). Anti-C1q and antihistone antibodies were significantly elevated in patients with class III/IV nephritis compared with class I/II/V nephritis (P = 0.041). SLE patients with active nephritis at the time of sample collection demonstrated significantly elevated levels of anti-C1q antibodies compared with those without active nephritis, also exhibiting 100% sensitivity for active nephritis, proteinuria, and urinary casts. Antibodies to C1q, dsDNA, histone, and chromatin were significantly elevated in patients with active disease (P < 0.01). Chart-documented anti-dsDNA antibodies were positive in 28 SLE patients, INOVA anti-dsDNA antibodies in 25 patients, and high-avidity anti-dsDNA antibodies in 8 patients. Antihistone correlated significantly with leukopenia and hemolytic anemia (P < 0.05). Conclusions: This study indicates the importance of measuring anti-C1q antibodies in pediatric-onset SLE patients because elevated anti-C1q antibodies may be more indicative of renal disease activity, showing significant correlation with proteinuria, urinary casts, and active nephritis. Antibodies to C1q, histone, chromatin, and dsDNA exhibited the strongest association with clinical features, indicating the importance of measuring all of these antibodies in pediatric-onset SLE patients.

Registry of the Spanish Network for Systemic Sclerosis: Clinical Pattern According to Cutaneous Subsets and Immunological Status - Corrected Proof

2011-12-14

Objective: To investigate the incidence of clinical and immunological characteristics of a large cohort of Spanish patients with scleroderma (SSc) and identifying factors associated with particular organ manifestations assessed by a nationwide cross-sectional analysis. Methods: We classified SSc patients in 4 subsets using a modification of LeRoy and Medsger classification that included: “prescleroderma” (pre-SSc), limited cutaneous SSc (lcSSc), diffuse cutaneous SSc (dcSSc), and SSc sine scleroderma (ssSSc). Fourteen Spanish centers participated in patient recruitment. On January 2008, the database included 916 consecutive Spanish SSc patients, 801 women (87.4%) and 115 men (12.6%), all of whom fulfilled the classification criteria proposed by LeRoy and Medsger. Epidemiological, clinical, and laboratory data were collected according to a standard protocol. Mean age at diagnosis was 51.2 ± 15.1 years and mean age at disease onset was 44.9.0 ± 15.8 years. lcSSc was the most frequent subset (61.8%) followed by dcSSc (26.5%), ssSSc (7.5%), and preSSc (4%) subsets. Gender ratios were as follows: dcSSc subset, 200 women and 43 men (4.7:1); lcSSc subset, 503 women and 63 men (ratio 7.9:1), and ssSSc subset, 62 women and 7 men (ratio 8.9:1). Digital ulcers, interstitial lung disease (ILD), musculoeskeletal and esophageal involvement, and scleroderma renal crisis were more frequent in dcSSc than lcSSc and ssSSc subsets. The incidence of pulmonary arterial hypertension assessed by echocardiography was similar in all subsets but mean estimated systolic pulmonary arterial pressure was higher in ssSSc than in lcSSc subset (47.3 ± 23.9 mm Hg vs 39.6 ± 19.2 mm Hg; P < 0.03). Cardiac involvement was identified more frequently in ssSSc than in dcSSc and lcSSc subsets (49.3% vs 32.5% and 31.1%, respectively; P = 0.015 and P = 0.004 for both comparisons). Acro-osteolysis (8.2% vs 2.4%, P = 0.049), calcinosis (19.8% vs 7.2%, P < 0.05), and sicca syndrome (37.5% vs 14.5%, P < 0.0001) were more frequent in lcSSc than in ssSSc subsets. The frequency of clinical manifestations related to the presence of anticentromere antibodies or antitopoisomerase I antibodies was very similar to that identified in patients categorized to lcSSc and dcSSc, respectively. However, in multivariate studies, the ranking of the variables according to their overall explanatory effect on the model showed that the contributory effect of the antibody status was not greater than that of the clinical categorization into lcSSc and dcSSc for the majority of disease manifestations, but, in important manifestations, as ILD, absence of anticentromere antibodies was an independent predictor factor. Conclusions: The classification of SSc into dcSSc, lcSSc, and ssSSc subsets is the one that most closely reflects the natural history of the disease, as they presented clear clinical differences. The immunological profile helps to define important visceral alteration as ILD. Finally, to improve early diagnosis of SSc, patients with preSSc should be considered both to trace the true evolution of the disease and to define which patients could benefit from therapeutic measures able to prevent the appearance of visceral involvements.

Korean Observational Study Network for Arthritis (KORONA): Establishment of a Prospective Multicenter Cohort for Rheumatoid Arthritis in South Korea - Corrected Proof

2011-12-12

Objectives: The object of this study was to introduce the KORean Observational study Network for Arthritis (KORONA) registry with an emphasis on the design of the Korean rheumatoid arthritis (RA) national database, as well as to provide an overview of the RA patients who are currently registered in KORONA. Methods: The KORONA was established in July 2009 by the Clinical Research Center for Rheumatoid Arthritis (CRCRA) in South Korea. KORONA is based on a prospective protocol and standard, defined data collection instruments. Demographic and clinical features, laboratory and radiologic data, health-related outcomes, treatment side effects, resource utilization, and health behaviors of the RA cohort patients are recorded in a database. Results: A total of 23 institutions, which are about 38% of the rheumatologic departments at tertiary academic hospitals across South Korea, are part of KORONA. The quality control of data collection and management has been performed through annual monitoring and auditing, staff training, and providing standard operation protocol by the executive committee of CRCRA. As of 31 December 2010, 4721 patients with established RA were included in KORONA, because an annual survey had started to be performed in July 2010. Conclusions: KORONA is the first nationwide Korean RA-specific cohort and it will provide valuable “real-world” information for Korean RA patients.

Utility of Erythrocyte Sedimentation Rate and C-Reactive Protein for the Diagnosis of Giant Cell Arteritis - Corrected Proof

2011-11-28

Objectives: To evaluate the utility of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) for the diagnosis of giant cell arteritis (GCA) and to determine the frequency of normal ESR and CRP at diagnosis of GCA.Methods: All patients undergoing temporal artery biopsy (TAB) between 2000 and 2008 were identified. Only subjects with both ESR and CRP at the time of TAB were included. The medical records of all patients were reviewed.Results: We included 764 patients (65% women), mean age 72.7 (±9.27) years, who underwent TAB. Biopsy was consistent with GCA in 177 patients (23%). Elevated CRP and elevated ESR provided a sensitivity of 86.9% and 84.1%, respectively, for a positive TAB. The odds ratio of a concordantly elevated ESR and CRP for positive TAB was 3.06 (95% CI 2.03, 4.62), whereas the odds ratio for concordantly normal ESR and CRP was 0.49 (95% CI 0.29, 0.83). Seven patients (4%) with a positive TAB for GCA had a normal ESR and CRP at diagnosis. Compared with GCA patients with elevated markers of inflammation, a greater proportion of these patients had polymyalgia rheumatica symptoms (P = 0.008), whereas constitutional symptoms, anemia and thrombocytosis, were observed less often (P < 0.05).Conclusions: CRP is a more sensitive marker than ESR for a positive TAB that is diagnostic of GCA. There may be clinical utility in obtaining both tests in the evaluation of patients with suspected GCA. A small proportion of patients with GCA may have normal inflammatory markers at diagnosis.

Short-Term and Long-Term Outcome of Anti-Jo1-Positive Patients with Anti-Ro52 Antibody - Corrected Proof

2011-11-11

Objectives: The aims of the present study were to (1) assess clinical features and long-term outcome in anti-Jo1-positive patients with anti-Ro52 antibody; (2) compare characteristics of anti-Jo1-positive patients with and without anti-Ro52 antibody; and (3) compare features of anti-Ro52-positive patients with and without anti-Jo1 antibody.Methods: The medical records of 89 consecutive anti-Jo1-positive patients with antisynthetase syndrome (ASS) were reviewed; 36 of these patients had coexistent anti-Ro52 antibody. Furthermore, the medical records of 13 consecutive anti-Ro52-positive patients without anti-Jo1 antibody were also reviewed.Results: Nine anti-Jo1-positive patients (25%) with anti-Ro-52 antibody achieved remission of ASS, whereas 19 other patients (52.8%) improved and 8 patients (22.2%) worsened their clinical status. Anti-Jo1-positive patients with anti-Ro52 antibody experienced ASS-related complications: interstitial lung disease (n = 28), esophageal dysfunction (n = 9), and joint manifestations (n = 25), including periarticular hydroxyapatite calcifications and erosions of metacarpophalangeal and interphalangeal joints and wrists (n = 3); 7 anti-Ro52-positive patients (19.4%) had cancer. Anti-Jo1-positive patients with anti-Ro52 antibody, compared with those without, more commonly experienced deterioration of myositis and joint involvement, symptomatic form of ILD, and cancer; they also had decreased survival rate (P = 0.05). We further found that anti-Ro52-positive patients with anti-Jo1 antibody, compared with those without, were younger and more frequently exhibited ILD with poorer prognosis.Conclusions: Our series underlines that the presence of anti-Ro52 antibody is associated with a particular phenotype of ASS, leading to more severe myositis and joint impairment. Moreover, the coexistence of anti-Ro52 antibody seems to be associated with an increased risk of cancer. We therefore suggest that anti-Jo1-positive patients should routinely undergo the search for anti-Ro52 antibody, as this autoantibody appears to impact patients' prognosis.

Ultrasound-Defined Remission and Active Disease in Rheumatoid Arthritis: Association with Clinical and Serologic Parameters - Corrected Proof

2011-11-07

Objective: To assess the association of clinical and/or serological parameters with ultrasound-defined disease activity in rheumatoid arthritis (RA).Methods: Retrospective analysis of 149 consecutive RA patients routinely assessed by sonography of the wrists, metacarpo-phalangeal, and proximal interphalangeal joints. Semiquantitative scoring of synovial hypertrophy/effusion and power Doppler (PD) signals was performed. Sonographic remission was defined by the absence of PD signals. Number of tender and swollen joints, global assessment of disease activity by the physician (VAS-phys) and patient (VAS-pt), C-reactive protein (CRP), erythrocyte sedimentation rate, duration of morning stiffness (MS), simplified disease activity index, disease activity score for 28 joints, clinical disease activity index, and health assessment questionnaires were recorded.Results: PD signals as a sign of active disease were observed in 117 (78.5%) RA patients. CRP, erythrocyte sedimentation rate, and MS were higher in patients with PD signals than in patients in remission. CRP >5.0 mg/L (normal values 0-5.0 mg/L), MS >15 minutes, or the combination of both revealed odds ratios of 5.0, 3.0, or 18.9, respectively, to indicate sonography-defined active disease. The other parameters showed no association with the presence or absence of PD-signals.Conclusions: Sonography-defined disease activity is associated with CRP and MS, whereas current composite scores and its clinical components did not match this definition.

Hand Tendon Involvement in Rheumatoid Arthritis: An Ultrasound Study - Corrected Proof

2011-11-07

Objective: To assess the prevalence and the distribution of tendon involvement in the hands and wrists of patients with rheumatoid arthritis (RA) describing in detail the ultrasound (US) morphostructural and vascular tendon abnormalities.Methods: Ninety consecutive RA patients were included in the study. The following tendons were scanned bilaterally: flexor pollicis longus tendon, flexor digitorum superficialis, and profundus tendons of the II to the V fingers (at both finger and carpal tunnel levels), flexor carpi radialis tendon, and extensor tendons of the 6 compartments on the dorsal aspect of the wrist. The presence of US findings indicative of tenosynovitis and tendon damage was investigated.Results: Tenosynovitis was found in at least 1 anatomic site of 44 (48.8%) of 90 patients. Tendon damage was found in at least 1 anatomic site of 39 (43.3%) of 90 patients. The focal tendon echotexture derangement was found in 294 of 5400 (5.4%) tendons, the partial and complete tears in 14 (0.3%), and in 3 (0.06%) tendons, respectively. The most frequently involved tendons were the flexor tendons of the II, III, and IV fingers and the extensor carpi ulnaris tendon.Conclusions: The present study provides evidence in favor of the ability of US to reveal a relatively high frequency of tendon involvement at the hand and wrist level in RA patients. These data can both facilitate US examinations in daily clinical practice and direct further investigations in the US assessment of tendon involvement in RA.