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All Rheumatology jobs for Fri Feb 3 2012

Rheumatology jobs in "Rheumatology - North Carolina (90 minutes to Winston-Salem, 2 hours to Charlotte and Asheville)" - NC

090526-697 Rheumatology - North Carolina (90 minutes to Winston-Salem, 2 hours to Charlotte and Asheville) NC Seeking BC/BE rheumatologist for multi-specialty group The practice currently has two

Rheumatology jobs in "Western Arizona's Colorado River resort - 2 hours to Phoenix, 1 hour to Bullhead City" - AZ

Lake Havasu City, "America's Home for the London Bridge", A Mecca of outdoor recreation, ideal climate, captivating scenery, beautiful yet rugged mountains, tranquil desert plus the

Rheumatology jobs in "Buffalo NY 100% Rheumatology Neurosciecne Group" - NY

Our practice, has a newly opened 21,000 sq. foot headquarters in upstate NY which is a lovely suburb of Buffalo. This main headquarters is The Brain and Spine Center. We also have six satellite

RHEUMATOLOGY jobs in "St. Petersburg, FL Rheumatologist" - FL

An excellent opportunity has become available for a Rheumatologist to join a large multispecialty Group in coastal Florida near Tampa Bay. This group currently has two rheumatologist on staff and call

RHEUMATOLOGY jobs in "Crystal River, FL Rheumatologist" - FL

Central western coastal Florida community in need of Rheumatologist to join solo female Rheumatologist due to patient demand in area covering 7 counties. Must be willing to practice mix ( close to 50%IM

RHEUMATOLOGY jobs in "Eastern Kentucky Rheumatologist" - KY

Eastern Kentucky in need of second full time Rheumatologist to join very busy solo Rheumatologist in private practice. Hospital is assisting with recruitment and financial package offering to include

RHEUMATOLOGY jobs in "Greenville, NC Rheumatologist" - NC

An excellent Rheumatology opportunity has just become available in eastern North Carolina. This employed position would be to join an established, premier multispecialty group of 80 physicians. You

RHEUMATOLOGY jobs in "Central Illinois Rheumatology" - IL

Rheumatology Opportunity - Central Illinois We are assisting a hospital employed multi specialty group in the recruitment of an additional Rheumatologist. Below are some points of interest: Teaching

RHEUMATOLOGY jobs in "Southwest Ohio Rheumatologist" - OH

Southwest Ohio Level I Trauma center in need of adding Rheumatologist due to growth and patient demand in draw area of almost 1,000,000 patient base. Busiest ER in state of Ohio with over 130,000 patient

Rheumatology jobs in "Rheumatologist - South Dakota" - SD

110119-1518 Rheumatologist - South Dakota SD Seeking BC/BE rheumatologist to join 2 others at 428 bed tertiary care facility Hospital employed opportunity J1/H1B sponsorship Competitive compensation

RHEUMATOLOGY jobs in "Central Texas Rheumatologist" - TX

Central Texas community in need of first full time 100% Rheumatology specialist due to patient demand in draw area of over 237,000. Currently all rheumatology consults are being handled by local Internists

RHEUMATOLOGY jobs in "Northeast Texas Rheumatology" - TX

Northeast Texas multi-specialty group in need of adding a full time Rheumatologist to their group due to patient demand serving over 250,000 draw area. Will have full support from local hospital as

Rheumatology jobs in "Rheumatologist - Mississippi" - MS

110127-1534 Rheumatologist - Mississippi MS Seeking BC/BE rheumatologist to join 3 others in multi-specialty group Slot available due to one member retiring Fabulous opportunity to be a part of

Rheumatology jobs in "Mid-Sized City in Central TX" - TX

Seeking Long-Term Fit in Wealthy Central TX Community! Join a solo physician's well-established practice and thriving patient base. The doctor will be retiring in a few years, and the

RHEUMATOLOGY jobs in "Spokane, WA Rheumatologist" - WA

Excellent Rheumatology opportunity has become available to take over established practice in Northeast Washington. Current Rheumatology clinic is housed in the multi-specialty clinic within walking

Rheumatology jobs in "Southwest KRC.0407.0401.09" - KS

KRC.0407.0401.09 Rheumatologist for multi-specialty group housing 25 physicians with 11 specialties. There is a large service area with many referrals from the region. This group also supports 2 satellite

RHEUMATOLOGY jobs in "Houston, TX Rheumatologist" - TX

We would like to make you aware of an excellent Rheumatology opportunity in Houston, TX. The incoming physician will be joining the one of the largest rheumatology practices in the area. The practice

Rheumatology jobs in "Rheumatology - Dayton, OH" - OH

111215-1829 Rheumatology - Dayton, OH OH Outstanding opportunity for a BC/BE Rheumatologist to join a well-established solo physician in private practice Partnership track opportunity State of

Rheumatology jobs in "Welcome" - MN

100104-881 Rheumatology/ - Minnesota MN Seeking BC/BE rheumatologist to join multi-specialty group practice J1 and H1Bs welcome Opportunity to practice 100% rheumatology or a combination of rheumatology

Rheumatology jobs in "Rheumatology - Minnesota" - MN

101109-1412 Rheumatology - Minnesota MN Seeking BC/BE rheumatologist to join multi-specialty group Full partnership offered after two years Two year guaranteed salary, signing bonus, production

Rheumatology jobs in "South Eastern Coastal" - FL

FL - SE Coastal Rheumatology opportunity. Our client has an opportunity for a BC/BE Rheumatologist to join an off-campus office. This is a new practice opportunity with a lot of growth potential. Candidates

Rheumatology jobs in "Greater Little Rock" - AR

We have an excellent opportunity for a BC/BE Rheumatologist in the Greater Little Rock area of Arkansas. Come join a well-established multi-specialty group or take the opportunity to establish a solo

Rheumatology jobs in "Inquire for details" - NC

BC/BE Rheumatologist is needed to join established and very busy single specialty practice (no internal medicine call responsibilities. Physicians do take ED rheumatology call, but hospital admits are

Rheumatology jobs in "Middle Tennessee" - TN

This is an excellent opportunity for a BE/BC Rheumatologist to establish a new solo practice in this very desirable middle Tennessee community. The practice is affiliated with a 200-bed medical

Rheumatology jobs in "SouthWest Region" - CT

RHEUMATOLOGY – Connecticut – Physician needed South / west CT- Rheumatologist needed. Hospital employed. Practice a mix of IM and Rheumatology. 160 Bed Yale affiliate hospital.

Rheumatology jobs in "Coastal Carolina" - NC

An additional rheumatologist doctor is needed to join a dynamic well run, physician owned Multi-Specialty Group in a major metro on the coast of South Carolina. Currently there is one rheumatologist

Rheumatology jobs in "Central Florida" - FL

Excellent Rheumatology Opportunity within two hours of the Gulf of Mexico, Atlantic Ocean, and Orlando. Growing Community with a strong need - Excellent opportunity in a great market without competition.

Rheumatology jobs in "South of Boston" - MA

RHEUMATOLOGY - South of Boston and easy access to Providence, Rhode Island - the largest physician group to span the southern coast of Massachusetts. currently have convenient office locations in Swansea,

Rheumatology jobs in "Iowa Locations" - IA

Excellent opportunity to join a large, well known healthcare system that has over 100 providers in 14 different Iowa locations, both metro and rural. This position is in a pop. of 75,000. Physician

Rheumatology jobs in "Charlotte area" - NC

Outstanding opportunity for B/E, B/C Rheumatologist to join established and very busy single specialty practice (no internal medicine call responsibilities) with Infusion Center located on site.

Rheumatology jobs in "Mission Hills" - CA

Rheumatology - Los Angeless San Fernando Valley, Live the Los Angeles life style with nearby beaches & mountains and world famous entertainment,

Rheumatology jobs in "Lake Placcid" - NY

RHEUMATOLOGY New York Lake Placcid region-- Physician needed -Northern New York Excellent earnings potential. Relocation/ sign on / loan repay negotiable. Take over for retiring Rheumatologist with

Rheumatology jobs in "Southeastern" - NY

RHEUMATOLOGY Physician needed- Southern New York - 20 year established practice looking to expand services. Located 2 hours north of New York City and 1 hour south of Albany. Multi specialty group practice

Rheumatology jobs in "College Town" - PA

Rheumatology- Central PA- Large Medical group located in central Pennsylvania. They have 50+ physicians and over 22 specialties and is owned and operated by physicians. They offer competitive guaranteed

Rheumatology jobs in "East Central" - AL

Our client, a progressive, not-for-profit, acute care facility serving the needs of east Central Alabama is currently recruiting for a hospital employed Rheumatologist to establish practice with a strong

Rheumatology jobs in "New Britain" - CT

Central Connecticut - Join well large Multispecialty group that that was established more than 50 years ago and has grown to include 75 providers covering 19 specialties and nine office locations.

Rheumatology jobs in "Springfield" - MA

Central MA on CT border. 100% Rheumatology. Multispecialty group seeking Rheumatologist to join one other as one physician is retiring. Financially stable group established 50 years ago. Full practice.

Rheumatology jobs in "New Britain" - CT

RHEUMATOLOGY Connecticut Physician needed - Central Connecticut - Join well large Multispecialty group that that was established more than 50 years ago and has grown to include 75 providers covering

Rheumatology jobs in "Baton Rouge" - LA

Join acclaimed healthcare system; 100% clinical practice VISTA Physician Search and Consulting is representing a clinic seeking a Rheumatologist. Highlights of this full-time position include:

Rheumatology jobs in "Baton Rouge" - LA

Lead Rheumatology department of acclaimed healthcare system VISTA Physician Search and Consulting is representing a clinic seeking a Chair of Rheumatology with a minimum of three years experience in

Rheumatology jobs in "Massillon" - OH

Hospital Employed or Private Practice. Trumbull Memorial Hospital seeks to recruit a BC/BE Rheumatologist for hospital succession planning. Current local physician is near retirement. Great opportunity

Rheumatology jobs in Illinois

All Rheumatology jobs in Illinois for Fri Feb 3 2012

Rheumatology jobs in "Manchester" - NH

Rheumatology, Southern NH, Dartmouth-Hitchcock is recruiting a Clinical Rheumatologist to join collegial group practice. Exceptional clinical and administrative support, a lifestyle

Rheumatology jobs in "Framingham" - MA

RHEUMATOLOGY Massachusetts Physician needed - Framingham area -Practice 100% Rheumatology. Well established medical group in desirable Boston suburb. Excellent public schools and affordable real

Rheumatology jobs in "Plattsburg" - NY

RHEUMATOLOGY New York Physician needed - Rheumatologist needed for beautiful Northern NY - Close proximity to Canadian border and Burlington VT. Great demand for Rheumatologist in the area. Currently

Rheumatology jobs in "Chesapeake" - WV

Join a large multi-specialty group in a world-class facility VISTA Physician Search and Consulting has a client seeking to add a Rheumatologist to a multi-specialty group in

Rheumatology jobs in "Middletown" - NY

RHEUMATOLOGY -New York -01915 Physician needed - Southern New York One hour to New York City! Top group in the state is once again adding to our dynamic staff. Partnership. Growth potential.

Rheumatology jobs in "Pittsfield" - MA

RHEUMATOLOGY Massachusetts 01201 Physician needed -Western MA Academic- 100% Rheumatology. Join one other Rheumatologist. This is a combined teaching and clinical position. 300 bed Teaching

Rheumatology jobs in "Portsmouth" - NH

RHEUMATOLOGY New Hampshire Physician needed -Southern New Hampshire/ coastal -Hospital employed Rheumatology practice. 2 other Rheumatologists. Practice 100% of your specialty. Light call. 209 bed

Rheumatology jobs in "Anchorage" - AK

Anchorage, Alaska -- Providence Alaska Medical Center is partnering with a private practice to bring a Rheumatologist to serve in breathtaking Anchorage. Position is set up for the right physician to

Rheumatology jobs in "NorthWest" - AL

Opportunity for Rheumatologist to join a primary care group or establish solo practice in northwest Alabama. Very strong need as no rheumatologists currently in the community, and consistently recommended

Rheumatology jobs in "Southwest" - MO

RECENTLY NAMED ‘BEST PLACES TO LIVE AND PLAY’ BY NATIONAL GEOGRAPHIC TRAVELER! PERFECT BALANCE OF OUTDOOR BEAUTY AND URBAN AMENITIES Consider this:

Rheumatology jobs in "Littleton" - NH

RHEUMATOLOGY New Hampshire Physician needed - Northern New Hampshire-100% Rheumatology. Excellent earnings potential! $25k sign on bonus and $100k loan repay !! 4 day work week.

Rheumatology jobs in "Littleton" - NH

RHEUMATOLOGY New Hampshire Physician needed - Northern New Hampshire-100% Rheumatology. Excellent earnings potential! $25k sign on bonus and $100k loan repay !! 4 day work week. 30

Rheumatology jobs in "Southboro" - MA

West of Boston. Practice 100% Rheumatology. For more than 35 years, our Medical Group has delivered exceptional care to the communities of Boston's dynamic Metrowest Region. Today, we are one of the

Rheumatology jobs in "Waterbury" - CT

RHEUMATOLOGY Connecticut Physician needed - Central Connecticut - Join well large Multispecialty group that that was established more than 50 years ago and has grown to include 75 providers covering

Rheumatology jobs in "Pocatello" - ID

Rheumatologist needed for Hospital Employed Position in Southeast Idaho Gateway to the Northwest - This city is located in southeast Idaho and nestled at 4,448 feet in

Rheumatology jobs in "Weymouth" - MA

South of Boston/ minutes to coast . Rheumatologist needed to join multi- specialty group located 20 minutes south of Boston. 6 office locations along the south shore and more than 55 providers. All

Rheumatology jobs in "Syracuse" - NY

Rheumatology--Physician Needed-Central New York-Competitive Salary with Full Benefit Package 13202-Syracuse region Seeking Rheumatologist for a 4-4.5 day schedule with 31-35 Patient

Rheumatology jobs in "Kingston" - NY

RHEUMATOLOGY New York Physician needed - Southern New York - 20 year established practice looking to expand services. We are located 2 hours north of New York City and 1 hour south of Albany. We are

Rheumatology jobs in "Northern" - NY

RHEUMATOLOGY New York---- Rheumatologist needed for beautiful Northern New York One hour to Montreal and easy drive to scenic Burlington Vermont. Great demand for Rheumatologist in the area. Currently

Rheumatology jobs in "Seacoast" - NH

RHEUMATOLOGY-Southern NH/minutes to coast- Rheumatologist needed to join 2 Rheumatologists. No call. Excellent salary and benefits package. The largest acute care hospital in Southern New Hampshire They

Rheumatology jobs in "Spokane" - WA

Rockwood Clinic seeks a Board Eligible or Board Certified Rheumatology Physician to join our group of two Rheumatologists and a Nurse Practitioner. This well established, consultative practice offers

Rheumatology jobs in "Central" - SC

RHEUMATOLOGY - PARTNERSHIP TRACK - PRIVATE GROUP - LAKE FRONT COMMUNITY - GREAT PLACE TO LIVE & PRACTICE - Join 1 Rheumatologist in a very busy growing community based practice. The practice resides

Rheumatology jobs in "Augusta" - GA

Rheumatology in Georgia An expanding multi-specialty group in Augusta , GA is seeking an additional Rheumatologist to join their thriving practice. They would welcome a physician

Rheumatology jobs in "Massena" - NY

Upstate New York Excellent salary, relocation up to $7,500; sign on bonus. Excellent referral base. The hospital will support the opportunity to develop candidates

Rheumatology jobs in "Norwich" - CT

RHEUMATOLOGY Connecticut Physician needed - E ast ern CT minutes to coast. Join 3 Rheumatologists in brand new state of the art office. Option for part time Rheumatology only or full time mix of

Rheumatology jobs in "Windham" - CT

RHEUMATOLOGY Connecticut Physician needed -Central Connecticut Excellent earnings potential. Sign on bonus and relocation allowance! Great opportunity to join hospital based practice. Located in desirable

Rheumatology jobs in "Lebanon" - NH

RHEUMATOLOGY - seeking experienced academic orientated Rheumatologist to join major academic center in tax free New Hampshire! Support activities in patient care, teaching and research. Position will

Rheumatology jobs in "Central" - NY

Rheumatology-Central N.Y. - group has served the Central area for over 50 years, the largest multispecialty group in the area. they have the option. IM is 4-4.5 day schedule with 31-35 Patient Contact

Rheumatology jobs in "Alabama" - AL

Excellent Rheumatology employment opportunity. Establish new practice with help of paid professional establishment practice services, $220K compensation, health benefits, retirement plan, malpractice

Rheumatology jobs in "Sherman" - TX

Rheumatologist needed for Practice near Dallas, Texas This is a city of 50,000 residents and home to several Fortune 100 industries as well as to Austin College, a vibrant arts community,

Rheumatology jobs in "Bangor" - ME

Rheumatology---Central Maine College town , excellent schools and minutes to the flagship campus of the University- 112-bed acute care, not-for-profit community hospital hospital service

Rheumatology jobs in "Boston" - MA

RHEUMATOLOGY – Massachusetts –Physician needed -South of Boston/ minutes to seacoast. Seeking Rheumatologist to join reputable group located 20 minutes south of Boston.

Rheumatology jobs in "Boston" - MA

Rheum---Boston---North of City- join 2 call 1:10---mix IM and Rheum

Rheumatology jobs in "Oleans" - NY

RHEUMATOLOGY New York Physician needed -Western New York Oleans region Practice Internal Medicine and Rheumatology to build to 100% Rheumatology very quickly. No IM call.

Rheumatology jobs in "Boston" - MA

Bostons Incredible Western Suburbs RHEUMATOLOGY Massachusetts Physician -Practice 100% Rheumatology. established medical group desirable Boston suburb. Excellent

Rheumatology jobs in "Bangor" - ME

RHEUMATOLOGIST -Maine Physician needed Central Maine - Bangor region with International Airport and one of the highest ranking towns in America. College Town Hospital employed position 400 bed medical

Rheumatology jobs in "Olean" - NY

Western New York Practice Internal Medicine and Rheumatology to build to 100% Rheumatology very quickly. No IM call. We are a physician owned group of 27 physicians and 13 mid-levels. Competitive

Rheumatology jobs in "Minot" - ND

Rheumatologist needed for North Dakota Hospital Employed Opportunity Minot serves as the central hub for north central and northwest North Dakota, as well as parts of Montana and the Canadian

Rheumatology jobs in "WA" - WA

This is a 200 provider, physician owned MSG in the Pacific Northwest. The opportunity is joining a young and energetic Rheumatologist with a service area of 250K. The practice will be a 100% specialty

An in vivo investigation of the initiation and progression of subchondral cysts in a rodent model of secondary osteoarthritis

IntroductionSubchondral bone cysts (SBC) have been identified in patients with knee Osteoarthritis (OA) as a cause of greater pain, loss of cartilage and increased chance of joint replacement surgery. Few studies monitor SBC longitudinally, and clinical research using three-dimensional imaging techniques, such as magnetic resonance imaging (MRI), is limited to retrospective analyses as SBC are identified within an OA patient cohort. The purpose of this study was to use dual-modality, preclinical imaging to monitor the initiation and progression of SBC occurring within an established rodent model of knee OA. Methods: Eight rodents underwent anterior cruciate ligament transection and partial medial meniscectomy (ACLX) of the right knee. In vivo 9.4 T MRI and micro-computed tomography (micro-CT) scans were performed consecutively prior to ACLX and 4, 8, and 12 weeks post-ACLX. Resultant images were co-registered using anatomical landmarks, which allowed for precise tracking of SBC size and composition throughout the study. The diameter of the SBC was measured, and the volumetric bone mineral density (vBMD) was calculated within the bone adjacent to SBC. At 12 weeks, the ACLX and contralateral knees were processed for histological analysis, immuno-histochemistry, and OARSI pathological scoring. Results: At 4 weeks post-ACLX, 75 % of the rodent knees had at least 1 cyst that formed in the medial tibial plateau; by 12 weeks all ACLX knees contained SBC. Imaging data revealed the SBC originate in the presence of a subchondral bone plate breach, with evolving composition over time. The diameter of the SBC increased significantly over time (p = 0.0033) and the vBMD significantly decreased at 8 weeks post-ACLX (p = 0.033). Histological analysis demonstrated positive staining for bone resorption and formation surrounding the SBC, which were consistently located beneath the joint surface with the greatest cartilage damage. Trabecular bone adjacent the SBC lacked viable osteocytes and - combined with bone marrow changes - indicated osteonecrosis. Conclusions: This study provides insight into the mechanisms leading to SBC formation in knee OA. The expansion of these lesions is due to stress-induced bone resorption from the incurred mechanical instability. Therefore we suggest these lesions can be more accurately described as a form of OA-induced osteonecrosis, rather than 'subchondral cysts'.

Specific post-translational histone modifications of neutrophil extracellular traps as immunogens and potential targets of lupus autoantibodies

IntroductionAutoreactivity to histones is a pervasive feature of several human autoimmune disorders including systemic lupus erythematosus (SLE). Specific post-translational modifications (PTMs) of histones within neutrophil extracellular traps (NETs) may potentially drive the process by which tolerance to these chromatin-associated proteins is broken. We hypothesized that NETs and their unique histone PTMs might be capable of inducing autoantibodies that target histones. Methods: We developed a novel and efficient method for the in vitro production, visualization, and broad profiling of histone-PTMs of human and murine NETs. We also immunized Balb/c mice with murine NETs and profiled their sera on autoantigen and histone peptide microarrays for evidence of autoantibody production to their immunogen. Results: We confirmed specificity toward acetyl-modified histone H2B as well as to other histone PTMs in sera from patients with SLE known to have autoreactivity against histones. We observed enrichment for distinctive histone marks of transcriptionally silent DNA during NETosis triggered by diverse stimuli. However, NETs derived from human and murine sources did not harbor many of the PTMs toward which autoreactivity was observed in patients with SLE or in MRL/lpr mice. Further, while murine NETs were weak autoantigens in vivo, there was only partial overlap in the IgG and IgM autoantibody profiles induced by vaccination of mice with NETs and those seen in patients with SLE. Conclusions: Isolated in vivo exposure to NETs is insufficient to break tolerance and may involve additional factors that have yet to be identified.

Therapy of lupus nephritis: lessons learned from clinical research and daily care to patients

Despite numerous randomized clinical trials over the last three decades for identifying the optimal treatment option for lupus nephritis, renal involvement still significantly impacts the survival and quality of life of patients with lupus and the search for the ideal immunosuppressive regimen is far from complete. The purpose of this review is to summarize the major recent achievements in the field. More specifically, the following topics will be discussed: intravenous cyclophosphamide versus mycophenolate mofetil (MMF) for induction; azathioprine versus MMF for maintenance; targeted therapies. The review will address clues for optimal global care, such as the need for complete initial evaluation, the importance of patient education, the unmasking of non-compliance to therapy, the reason for an early treatment switch in non-responding patients, the need for prolonged immunosuppression, optimal renal protection, and prevention of cardiovascular disease and other comorbidities.

A profile of immune response to herpesvirus is associated with radiographic damage in rheumatoid arthritis

IntroductionProgression of joint damage despite appropriate therapy remains a significant problem for patients with rheumatoid arthritis (RA). This study was undertaken to identify profiles of immune response that correlate with radiographic joint damage as a first step toward the discovery of new pathogenic mechanisms of joint destruction in RA. Methods: The study included 58 patients with RA and 15 healthy controls. The profiles of cytokine release from peripheral blood mononuclear cells (PBMC) in response to stimulation for 48 hours with one of six stimuli, or in media alone, were measured. Immune response profiles identified for each stimulus were correlated with radiographic joint damage as defined by the Sharp-van der Heijde score (SHS), before and after multivariable adjustment. For profiles correlated with the SHS, the distributions of individual cytokines were evaluated in patients according to the severity of joint damage and compared to healthy controls. Results: The immune response profile for cytomegalovirus (CMV) / Epstein-Barr virus (EBV) stimulation was correlated with both the SHS total and erosion scores (r = 0.31, p = 0.018 and r = 0.33, p = 0.011, respectively). After adjusting for age, sex, disease duration, autoantibody status, CMV/EBV serological status, current disease activity, disability, and treatments, the correlation of the CMV/EBV immune response and the SHS erosion score became stronger (r = 0.43, p < 0.003). The CMV/EBV immune response correlated with CMV IgG (r = 0.44, p < 0.001), but not with EBV IgG. The most important cytokines for the CMV/EBV immune response profile were IFN-gamma, IL-2, IL-4, IL-5, IL-13 and IL-17A, all of which are associated with T-cell immunity. Both the summary immune response score and the individual responses of IFN-gamma and IL-13 to CMV/EBV stimulation were associated with greater joint damage. Conclusions: A profile of immune response to purified CMV/EBV lysates is associated with radiographic joint damage. The correlation of this immune response to CMV serology implies possible involvement of latent CMV infection. Therefore, the findings suggest that the immune response to latent CMV infection could play a fundamental role in the progression of inflammation and structural joint damage in patients with RA.

Is there any scientific evidence for the use of glucosamine in the management of human osteoarthritis?

Glucosamine in its acetylated form is a natural constituent of some glycosaminoglycans (for example, hyaluronic acid and keratan sulfate) in the proteoglycans found in articular cartilage, intervertebral disc and synovial fluid. Glucosamine can be extracted and stabilized by chemical modification and used as a drug or a nutraceutical. It has been approved for the treatment of osteoarthritis (OA) in Europe to promote cartilage and joint health and is sold over the counter as a dietary supplement in the United States. Various formulations of glucosamine have been tested, including glucosamine sulfate and glucosamine hydrochloride. In vitro and in vivo studies have uncovered glucosamine's mechanisms of action on articular tissues (cartilage, synovial membrane and subchondral bone) and justified its efficacy by demonstrating structure-modifying and anti-inflammatory effects at high concentrations. However, results from clinical trials have raised many concerns. Pharmacokinetic studies have shown that glucosamine is easily absorbed, but the current treatment doses (for example, 1,500 mg/day) barely reach the required therapeutic concentration in plasma and tissue. The symptomatic effect size of glucosamine varies greatly depending on the formulation used and the quality of clinical trials. Importantly, the effect size reduces when evidence is accumulated chronologically and evidence for the structure-modifying effects of glucosamine are sparse. Hence, glucosamine was at first recommended by EULAR and OARSI for the management of knee pain and structure improvement in OA patients, but not in the most recent NICE guidelines. Consequently, the published recommendations for the management of OA require revision. Glucosamine is generally safe and although there are concerns about potential allergic and salt-related side effects of some formulations, no major adverse events have been reported so far. This paper examines all the in vitro and in vivo evidence for the mechanism of action of glucosamine as well as reviews the results of clinical trials. The pharmacokinetics, side effects and differences observed with different formulations of glucosamine and combination therapies are also considered. Finally, the importance of study design and criteria of evaluation are highlighted as new compounds represent new interesting options for the management of OA.

Extracellular nicotinamide phosphoribosyltransferase (NAMPT/visfatin) inhibits insulin-like growth factor-1 signaling and proteoglycan synthesis in human articular chondrocytes

IntroductionObesity is one of the major risk factors for the development of osteoarthritis (OA). Although the mechanical factors appear to be critical, recent studies have suggested a role for adipokines in cartilage degradation. Chondrocytes from osteoarthritic cartilage respond poorly to Insulin-like growth factor-1 (IGF-1) and the molecular mechanism(s) involved is not clearly understood. The purpose of this study was to determine the role of nicotinamide phosphoribosyltransferase (eNAMPT/visfatin), a newly described adipokine, in regulating IGF-1 function in chondrocytes. Methods: Human articular chondrocytes isolated from normal ankle cartilage were pretreated with (0.1-5.0 ug/ml) eNAMPT overnight followed by stimulation with IGF-1(50 ng/ml) for 24 hours and proteoglycan (PG) synthesis was measured by [35S] sulfate incorporation. Chondrocytes were pretreated with eNAMPT overnight followed by IGF-1 for 10 minutes, and the cell lysates were immunoblotted for various signaling proteins that are activated by IGF-1 by using phospho-specific antibodies. In addition, chondrocytes were pretreated with MEK inhibitor (U0126) prior to stimulation with eNAMPT and IGF-1. Results: Pre-treatment of chondrocytes with eNAMPT inhibited IGF-1-stimulated PG synthesis in a dose-dependent manner. Treatment of chondrocytes with eNAMPT inhibited IGF-1-induced phosphorylation of signaling molecules, including IRS-1 and AKT. Interestingly, pretreatment of chondrocytes with eNAMPT did not inhibit IGF-1-mediated phosphorylation of the IGF-1 receptor; however, it stimulated a sustained phosphorylation of the extracellular signal-regulated kinase (ERK)/ mitogen activated protein kinase (MAPK) signaling pathway. Inhibition of the ERK/MAPK signaling pathway restored IGF-1-mediated IRS-1 and AKT phosphorylation. Conclusions: Our study demonstrates that eNAMPT/visfatin inhibits IGF-1 function in articular chondrocytes by activating the ERK/MAPK pathway independent of the IGF-1 receptor. Since eNAMPT levels are elevated in the synovial fluid of OA patients, the signaling pathway activated by eNAMPT could contribute to IGF-1 resistance in OA.

Predictors of survival in a cohort of patients with polymyositis and dermatomyositis: effect of corticosteroids, methotrexate, and azathioprine

IntroductionThe idiopathic inflammatory myopathies are rare diseases for which data regarding the natural history, response to therapies, and factors affecting mortality are needed. We performed this study to examine the effects of treatment and clinical features on survival in polymyositis and dermatomyositis patients. Methods: 160 consecutive patients (77 polymyositis, 83 dermatomyositis) seen at the University of Michigan (1997-2003) were included. Medical records were abstracted for clinical, laboratory, and therapeutic data, including initial steroid regimen and immunosuppressive use. State vital records were utilized for mortality and cause of death data. Survival was modeled by left-truncated Kaplan-Meier estimation and Cox regression. Results: 5- and 10-year survival estimates were 77% (95% CI 66, 85), and 62% (95% CI 48, 73), respectively; rates were similar for polymyositis and dermatomyositis. Survival between sexes was similar through 5-years, and thereafter significantly lower for males (10-year survival: 18% male, 73% female; p=0.002 for 5-10 year interval). The sex disparity was restricted to the polymyositis group. Increasing age at diagnosis and non-white race were associated with lower survival. Intravenous versus oral corticosteroid use was associated with a higher risk of death among whites (hazard ratio 10.6, 95% CI 2.1, 52.8). Early survival was similar comparing patients treated with methotrexate versus azathioprine, but survival at 10 years was higher for the methotrexate-treated group (76% vs. 52%, p=0.046 for 5-10 year interval). Conclusions: Patients treated initially with intravenous corticosteroids had higher mortality, likely related to disease severity. Both methotrexate and azathioprine showed similar early survival benefit as first line immunosuppressives; survival was higher between 5-10 years in the methotrexate-treated group but could not be confirmed in multivariable modeling for the full follow-up period. Other important predictors of long-term survival included younger age, female sex, and the Caucasian race.

A randomised controlled trial of a self-management education program for osteoarthritis of the knee delivered by health professionals.

IntroductionOur aim was to determine whether a disease specific self-management program for primary care people with osteoarthritis (OA) of the knee (the OAK program), implemented by health professionals, would achieve and maintain clinically meaningful improvements in health related outcomes compared with a control group. Methods: Medical practitioners referred 146 primary care participants with OA of the knee. Volunteers with coexistent inflammatory joint disease or serious co-morbidities were excluded. Randomisation was to either control or OAK groups. The OAK group completed a 6 week self-management program. The control group had a 6 month waiting period before receiving the OAK program. Assessments occurred at baseline, 8 weeks and 6 months. Primary outcomes were Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain and function, SF-36. Secondary outcomes were visual analog scale (VAS) pain, timed up and go (TUG), knee range of motion, quadriceps and hamstring strength- isometric contraction. Response to treatment (responders) and minimal clinically important improvements (MCII) were determined. Results: In the OAK group VAS pain improved from baseline to week 8, mean (SE) 5.21 (0.30) to 3.65 (0.29) P=<0.001. During this time period improvements in the OAK group compared with the control group and responses to treatment were demonstrated in the following outcomes: WOMAC pain, physical function and total dimensions; SF-36, physical function, role physical, body pain, vitality and social functioning domains. Additionally from baseline to week 8, the proportion of MCII was greater among the OAK than the control group for all outcomes. For the period between baseline and month 6, WOMAC pain, physical function and total dimensions significantly improved in the OAK group compared to the control group, as did SF-36, physical function, role physical, body pain, vitality and social functioning domains, and hamstring strength in both legs. During this same period, TUG test, range of motion extension and left knee flexion improved when compared with the control group, although these improvements had little clinical relevance. Conclusions: Participants in the OAK program recorded statistically significant improvements in pain, quality of life and function as demonstrated by WOMAC and SF-36 at 8 weeks and 6 months compared with a control group.

Local administration of glucocorticoids decrease synovial citrullination in rheumatoid arthritis

IntroductionProtein citrullination is present in the rheumatoid synovium, presumably contributing to the perpetuation of chronic inflammation in the presence of specific autoimmunity. As a result, the present study examines the possibility that effective anti rheumatic treatment will decrease the level of synovial citrullination. Methods: Synovial biopsies were obtained from 11 rheumatoid arthritis (RA) patients before and after 8 weeks of treatment with 20 mg methotrexate weekly, 15 RA patients before and 2 weeks after an intra-articular glucocorticoid injection, 8 healthy individuals and 5 patients with osteoarthritis. Synovial inflammation was assessed by double blind semi quantitative analysis of lining thickness, cell infiltration and vascularity using a 4 points scale. Expression of citrullinated proteins (CP) with the monoclonal antibody F95 and peptidylarginine deiminase (PAD) 2 and 4 was assessed immunohistochemically by double blind semi-quantitative analysis. In vitro synovial fluid (SF), peripheral blood (PB) mononuclear cells (MC) and synovial explants obtained from RA patients were incubated with dexamethasone and analyzed by immunhistochemistry for expression of CP as well as PAD2 and PAD4 enzymes. Results: Presence of synovial CP was almost exclusive in RA compared to healthy synovium and correlated with the degree of local inflammation. Treatment with glucocorticoids but not methotrexate alters expression of synovial CP and PAD enzymes, in parallel with a decrease of synovial inflammation. Ex vivo and in vitro studies suggest also a direct effect of glucocorticoids on citrullination as demonstrated by the decrease in the level of citrullination and PAD expression following incubation of SFMC and synovial explants with dexamethasone. Conclusion: Synovial citrullination and PAD expression is depended on local inflammation and targeted by glucocorticoids.

Restrictive pulmonary function is more prevalent in patients with ankylosing spondylitis than in matched population controls and is associated with impaired spinal mobility: a comparative study

IntroductionPulmonary involvement is a known manifestation in patients with ankylosing spondylitis (AS). However, previous studies have been based on small samples and the reported prevalence and associations with typical clinical features vary. The purpose of this study was to compare pulmonary function (PF) in patients with AS and population controls, and to study associations between PF and disease related variables, cardio-respiratory fitness and demographic variables in patients with AS. Methods: In a cross-sectional controlled study, 147 AS patients and 121 controls underwent examinations including demographic variables, laboratory (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR)) and clinical measures (disease activity ankylosing spondylitis disease activity score, ASDAS), physical function (Bath ankylosing spondylitis functional index, BASFI), spinal mobility (Bath ankylosing spondylitis metrology index, BASMI), chest expansion, cardio-respiratory fitness (peak oxygen uptake, VO2peak ) and pulmonary function test (PFT) (spirometry)). Cumulative probability plots were used to visualize associations between the ASDAS and BASMI scores and the corresponding forced vital capacity (FVC%, percentage of predicted value controlled for the influence of confounding factors) score for each patient. Univariate ANCOVAs were performed to explore group differences in PF adjusting for relevant variables, and a multiple regression model was used to estimate the explanatory power of independent variables (demographic, disease related, VO2peak) on restrictive ventilatory impairment (FVC%). Results: AS patients showed significantly lower PF values compared with controls, and significantly more patients were categorized with restrictive pattern (18% vs. 0%, P<0.001). Cumulative probability plots showed significant associations between spinal mobility measures (BASMI) and FVC% for individual patients. BASMI, chest expansion and male gender contributed significantly and independently in a multiple regression model predicting the variation of FVC% in AS patients, whereas disease activity, physical function and VO2peak did not contribute significantly. The final model explained 45% of the variance in FVC% (P<0.001). Conclusions: This study showed significantly impaired pulmonary function in the AS patients compared to controls and reference data, and demonstrated a clear relationship between reduced spinal mobility and restrictive PF in AS patients. The results support the assumption of an association between musculoskeletal limitations and restrictive respiratory impairment in AS, emphasizing the importance of maintained spinal flexibility in the management of the disease. Further, patients with severely reduced spinal mobility should be referred to pulmonary function examination and relevant follow-up treatment.

Canes for knee osteoarthritis: is a randomised trial necessary?

In this issue of the Annals, Jones et al1 (pp 172) report the results of a randomised clinical trial (RCT) of canes for knee osteoarthritis. Current recommendations on the management of hip and knee osteoarthritis emphasise non-pharmacological interventions, with sticks or canes universally recommended in existing guidelines.2 According to the Osteoarthritis Research Society International (OARSI) recommendations for the management of hip and knee osteoarthritis one of 25 treatment propositions recommended is ‘Walking aids can reduce pain in patients with hip and knee OA. Patients should be given instruction in the optimal use of a cane or crutch in the contralateral hand. Frames or wheeled walkers are often preferable for those with bilateral disease.’3 In the National Institute for Health and Clinical Excellence (NICE) guideline for care and management of osteoarthritis in adults, assistive devices (such as walking sticks) are considered as...

The effect of biological agents on work participation in rheumatoid arthritis patients: a systematic review

This study reviewed the effect of biological agents on participation in paid work among patients with rheumatoid arthritis (RA). A systematic literature search was performed to identify published articles reporting the effect of biological agents on employment status, sick leave and/or presenteeism. The quality of included articles was assessed according to the guidelines as proposed by the Dutch Cochrane Centre. Narrative summaries were used to present the data separately for randomised controlled trials (RCTs) as well as controlled and uncontrolled cohort studies. 19 studies (six uncontrolled cohorts, seven controlled cohorts and six RCTs) were included, in which 11 259 patients were treated with biological agents. Employment status improved in four out of 13 studies, absence from work in all 10 studies and presenteeism in seven out of nine studies that reported this outcome. For absenteeism and presenteeism the statistical significance of change or difference was not always provided and results within studies were sometimes conflicting when using different time frames or alternative outcomes. The large heterogeneity in terms of population, design, analyses and most important in outcome measures limits interpretation of the data. RCTs as well as cohort studies showed positive results of biological agents on both absenteeism and presenteeism compared with other disease-modifying antirheumatic drugs (DMARD), continuing the failing DMARD, the general population or the situation before the start of biological agents. The effect on employment status was more conflicting, but 50% of studies that addressed patients with early methotrexate-naive RA showed a positive result on employment status.

Impact of cane use on pain, function, general health and energy expenditure during gait in patients with knee osteoarthritis: a randomised controlled trial

Objective To assess the impact of daily cane use during gait in relation to pain, function, general health and energy expenditure among patients with knee osteoarthritis. Method Sixty-four patients were randomly assigned to an experimental group (EG) or control group (CG). The EG used a cane every day for 2 months, whereas the CG did not use a cane in this period. The first outcome was pain and the second were function (Lequesne and WOMAC), general health (SF-36) and energy expenditure (gas analysis during the 6-minute walk test (6MWT) with and without a cane). Evaluations were performed at baseline, 30 and 60 days. Results The groups were homogeneous for all parameters at baseline. Compared with the CG, the EG significantly improved pain (ES 0.18), function - Lequesne (ES 0.13), some domains of SF-36 (role physical, ES 0.07 and bodily pain, ES 0.08) and distance on the 6MWT with the cane (ES 0.16). At the end of the 6MWT with the cane, the EG significantly improved energy expenditure (ES 0.21), carbon dioxide production (ES 0.12) and metabolic equivalents (ES 0.15) compared with the CG. Conclusion A cane can be used to diminish pain, improve function and some aspects of quality of life in patients with knee osteoarthritis. The prescription of a cane should take into account the substantial increase in energy expenditure in the first month of use, whereas energy expenditure is no longer a factor for concern by the end of the second month due to adaptation to cane use. The trial was registered in clinicaltrials.gov (NCT00698412).

Safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of the monoclonal antibody ASK8007 blocking osteopontin in patients with rheumatoid arthritis: a randomised, placebo controlled, proof-of-concept study

Objectives Osteopontin is an extracellular matrix protein with diverse immunomodulatory functions. The authors assessed the safety, tolerability, pharmacokinetics, pharmacodynamics and initial efficacy of the humanised monoclonal antibody ASK8007, which blocks osteopontin. Methods In this double-blind, multicentre, combined first-in-man, single-dose escalation (phase I, part A) and proof-of-concept, multiple-dose (phase IIA, part B) study, rheumatoid arthritis (RA) patients with active disease were randomly assigned to receive ASK8007 or placebo intravenously. Safety monitoring, pharmacokinetic and pharmacodynamic analyses and clinical assessments were performed throughout the study. The expression of phenotypic cell markers was evaluated in synovial tissue biopsy samples obtained at baseline and 43 days after initiation of treatment (part B) by immunohistochemistry and digital image analysis. Two co-primary efficacy endpoints were the change from baseline in the disease activity score evaluated in 28 joints (DAS28) and the change from baseline in the number of CD68 synovial sublining macrophages, both assessed on day 43 (part B). Results ASK8007 was overall safe and well tolerated up to the highest studied dose (20 mg/kg). Quantifiable concentrations of ASK8007 were detected in synovial fluid. No differences were observed for changes from baseline in DAS28 and CD68 sublining macrophages between ASK8007 and placebo-treated patients. Within the ASK8007 treatment group, there were also no apparent clinical responses or changes in sublining macrophages. In addition, ASK8007 treatment did not change other assessed biomarkers. Conclusions Osteopontin blockade is well tolerated and not related to safety concerns. These results consistently show that osteopontin blockade is unlikely to induce robust clinical improvement in RA patients.

In early rheumatoid arthritis, patients with a good initial response to methotrexate have excellent 2-year clinical outcomes, but radiological progression is not fully prevented: data from the methotrexate responders population in the SWEFOT trial

Objective To investigate the 2-year clinical and radiological outcomes of patients with early rheumatoid arthritis (RA; symptom duration <1 year) who had initially responded well to methotrexate monotherapy. Methods In the SWEFOT trial, all 487 patients started methotrexate (target dose 20 mg/week). After 3–4 months, 147 had low disease activity, 28-joint based disease activity score (DAS28) ≤3.2. These patients were not randomly selected but were followed in regular care for 2 years. Clinical outcomes and radiographic progression according to the van der Heijde modified Sharp (SvdH) score were analysed. Results The majority of the 147 patients continued on methotrexate monotherapy. After 1 and 2 years, DAS28 remission was achieved in 59.6% and 71.8% and mean observed DAS28 values were 2.53 and 2.25, respectively. Despite the favourable clinical course, a proportion of the patients progressed radiographically with a mean (SD) increase in the SvdH score after 2 years of 3.90 (6.84). There was no significant difference in progression between patients in DAS28 remission versus not in remission (p=0.73). At baseline, approximately half the patients had no radiographic damage, while after 2 years the proportion was approximately 20%. Conclusion Most early RA patients who achieve low disease activity after 3–4 months of methotrexate monotherapy continue to have low disease activity during 2 years follow-up, and additional treatment is needed infrequently. Some radiological progression occurs in most patients, and may be marked or severe in some, even despite sustained DAS28 remission. Close monitoring for radiological progression is thus warranted.

The prospective association between psychological distress and disease activity in rheumatoid arthritis: a multilevel regression analysis

Background Cross-sectional associations suggest a mutual impact of disease activity and psychological distress in rheumatoid arthritis (RA), but a prospective association has not been established. Objective To examine concurrent and prospective associations between psychological distress and disease activity. Methods Patients with RA (N=545, disease duration ≤1 year, age 18–83 years, 69% female, 64% rheumatoid factor (RF) positive) were monitored for 5 years. The Thompson joint score and erythrocyte sedimentation rate were assessed every 6 months. Depressed mood and anxiety were measured every 12 months. Multilevel regression analysis was used. RF positivity, age and female sex were included as covariates. Results Concurrent levels of psychological distress and disease activity were positively associated (p≤0.04). Prospectively, depressed mood was associated with disease activity levels 6 months later (p≤0.04). The Thompson joint score was associated with psychological distress levels 6 months later (p≤0.03) and also with an increase in depressed mood over the subsequent 6 months (p=0.02). No other significant prospective associations were found (p≥0.07). Conclusions Psychological distress and disease activity are positively associated when measured at the same time as well as when measured 6 months apart. While some support was found for the idea that a higher level of disease activity is a risk factor for an increase in psychological distress, the results do not support the notion that psychological distress is a risk factor for future exacerbation of disease activity.

Efficacy of tocilizumab in patients with moderate to severe active rheumatoid arthritis and a previous inadequate response to disease-modifying antirheumatic drugs: the ROSE study

Objective To evaluate efficacy of tocilizumab in US patients with moderate to severe active rheumatoid arthritis (RA) and inadequate clinical response to disease-modifying antirheumatic drugs (DMARD). Safety-related outcomes were also analysed. Methods The rapid onset and systemic efficacy study was a 24-week, randomised, double-blind trial. Patients were randomly assigned 2:1 to tocilizumab 8 mg/kg (n=412) or placebo (n=207) every 4 weeks while continuing background DMARD in both groups. Results The primary efficacy endpoint, percentage of patients achieving ACR50 response at week 24, was higher with tocilizumab versus placebo (30.1% vs 11.2%; p<0.0001). Percentages of ACR20 and ACR50 responders were significantly higher with tocilizumab versus placebo as early as week 4 and continued to week 24; more patients in the tocilizumab versus placebo group also achieved ACR70 responses beginning at week 8 (p<0.01). Significant improvements associated with tocilizumab versus placebo were seen in routine assessment of patient index data responses, EULAR good response, DAS28 and percentages of patients achieving low disease activity and clinical remission (based on DAS28). A substudy examining early response to therapy showed improved patient global assessment of disease activity (p=0.005) and pain (p=0.01) and DAS28 (p=0.007) with tocilizumab versus placebo at day 7. Safety findings were consistent with the known tocilizumab safety profile; rates of serious infections (per 100 patient-years) were 7.87 (95% CI 4.30 to 13.2) and 1.20 (95% CI 0.03 to 6.66) in the tocilizumab and placebo groups, respectively. Conclusions This study demonstrated the efficacy of tocilizumab in improving measures of disease activity in patients with RA who failed to respond adequately to DMARD therapy. Rapid improvement in clinical outcomes was demonstrated in a substudy as early as week 1 as shown by DAS28 scores, patient measures and C-reactive protein. Trial Registry no NCT00531817

Predicting low disease activity and remission using early treatment response to antitumour necrosis factor therapy in patients with rheumatoid arthritis: exploratory analyses from the TEMPO trial

Objective To derive and validate decision trees to categorise rheumatoid arthritis (RA) patients 12 weeks after starting etanercept with or without methotrexate into three groups: patients predicted to achieve low disease activity (LDA) at 1 year; patients predicted not to achieve LDA at 1 year and patients who needed additional time on therapy to be categorised. Methods Data from RA patients enrolled in the TEMPO trial were analysed. Classification and regression trees were used to develop and validate decision tree models with week 12 and earlier assessments that predicted long-term LDA. LDA, defined as disease activity score in 28 joints (DAS28) ≤3.2 or clinical disease activity index ≤10.0, was measured at 52 or 48 weeks. Demographics, laboratory data and clinical data at baseline and to week 12 were analysed as predictors of response. Results 39% (67/172) of patients receiving etanercept and 60% (115/193) of patients receiving etanercept plus methotrexate achieved LDA at week 52. For patients receiving etanercept, 53% were predicted to have LDA, 39% were predicted not to have LDA and 8% could not be categorised using DAS28 criteria at week 12. For patients receiving etanercept plus methotrexate, 63% were predicted to have LDA, 25% were predicted not to have LDA and 12% could not be categorised. Conclusion Most (80–90%) patients in TEMPO initiating etanercept with or without methotrexate could be predicted within 12 weeks of starting therapy as likely to have LDA or not at week 52. However, approximately 10–20% of patients needed additional time on therapy to decide whether to continue treatment.

Disability in rheumatoid arthritis in the era of biological treatments

Objective Rheumatoid arthritis (RA) is a disabling disease. The authors studied the impact of new, expensive and occasionally toxic biological treatments on disability outcomes in real-world populations of patients with RA. Methods The authors analysed Health Assessment Questionnaire Disability Index data on 4651 adult patients with RA collected prospectively from 1983 to 2006. They studied trends in disability using multilevel mixed-effects multivariable linear regression (mixed) models that adjusted for the effects of time trends in gender, ethnicity, age, smoking behaviour and disease duration. Results Overall, the patients were predominantly female (76%), were predominantly white (88%), had 13 years of education and have had RA for 13 years, on average. The time period from 1983 to 2006 saw major increases in the use of disease-modifying agents and biological agents, and a decrease in smoking. After adjustments, the disability rates declined at annual rates of 1.7% (1.5–1.8%) overall and 2.7% (2.4–3.1%) among men. The annual rate of disability declines in the biological era was greater than that in the preceding period, suggesting accelerated improvement. These declines were documented in all patient subgroups such as men, women, African–Americans, obese, older age groups and early disease (p<0.001), but not among the 1401 patients (where disability remained stable) who died on follow-up. Conclusion Aggressive use of traditional disease-modifying agents and introduction of biological agents were associated with substantial gains in disability outcomes. Our finding supports the prevailing notion that ‘tight inflammation control’ is a desirable therapeutic strategy.

The association between smoking and the development of psoriatic arthritis among psoriasis patients

Aim To investigate the association between smoking and psoriatic arthritis (PsA) among patients with psoriasis and its interaction with the HLA-C*06 allele. Methods In this exploratory case–control study, smoking status was determined at the time of the diagnosis of arthritis for PsA patients and at their first study visit for psoriasis patients, when they were confirmed not to have PsA. The proportions of patients exposed to smoking were compared in patients with PsA to those with psoriasis alone. A logistic regression model was constructed to test the independent association of smoking and PsA after adjusting for potential confounders. The statistical interaction between HLA-C*06 and smoking was tested through a regression model. Results The proportions of current and past smokers were higher in the psoriasis group compared with the PsA group (30.2% vs 23.4% and 26.7% vs 22.3%, p=0.001, respectively). On multivariate analysis being a current smoker versus a lifetime non-smoker remained inversely associated with PsA (OR 0.57, p=0.002), while past smoker versus lifetime non-smoker status was no longer significant. In a subgroup analysis, smoking remained inversely associated with PsA only among patients who were HLA-C*06 negative. Regression analysis revealed that the interaction between smoking status (ever smoked vs lifetime non-smoker) and HLA-C*06 was statistically significant (p=0.01). Conclusion Smoking may be inversely associated with PsA among psoriasis patients. This association is not present among HLA-C*06-positive individuals.

A mixed treatment comparison of the efficacy of anti-TNF agents in rheumatoid arthritis for methotrexate non-responders demonstrates differences between treatments: a Bayesian approach

Background A number of tumour necrosis factor α (TNFα) antagonists (anti-TNFα) are available to treat rheumatoid arthritis. All of these have demonstrated considerable efficacy in placebo controlled trials, but few head-to-head comparisons exist to date. This work's objective is to estimate the relative efficacy among licensed anti-TNFs in patients who have had an inadequate response to methotrexate (MTX). Different outcome measures are used to highlight the advantages of continuous measures in such analyses. Methods A systematic review identified randomised controlled trials comparing the efficacy of licensed anti-TNFα agents with placebo at 24 weeks in patients who have had an inadequate response to MTX. Relative efficacy was estimated using Bayesian mixed treatment comparison (MTC) models. Three different outcome measures were used: RR of achieving an American College of Rheumatology (ACR) 20 and ACR50 response and the percentage improvement in Health Assessment Questionnaire (HAQ) score. Results 16 published trials were included in the analysis. All anti-TNFs show considerably improved efficacy over placebo. The MTC results also provide evidence of some differences in efficacy of the TNFα antagonists. Etanercept appears superior to infliximab and golimumab, and certolizumab to infliximab and adalimumab. ACR results indicate improved efficacy of certolizumab over golimumab. On HAQ analysis, adalimumab, certolizumab, etanercept and golimumab appear superior to infliximab, and etanercept shows improved efficacy compared with adalimumab. Conclusions There are differences in efficacy among the TNFα antagonists. In a MTC, a continuous outcome measure has more strength to detect such differences than a binomial outcome measure because of its enhanced sensitivity to change.

Biphasic emergence of active tuberculosis in rheumatoid arthritis patients receiving TNF{alpha} inhibitors: the utility of IFN{gamma} assay

Objectives The risk of active tuberculosis increases in rheumatoid arthritis (RA) patients receiving antitumour necrosis factor alpha (TNFα) therapy. Longitudinal data concerning serial interferon (IFN) assays for detecting tuberculosis have been limited. This study investigated the time course of the development of active tuberculosis, and evaluated the utility of serial QuantiFERON-TB Gold (QFT-G) assays for detecting its emergence in RA patients undergoing long-term anti-TNFα therapy. Methods 242 RA patients who received anti-TNFα therapy and serial QFT-G assays were prospectively evaluated. QFT-G was performed by measuring IFN levels in whole blood treated with tuberculosis-specific antigens. Results Among 242 RA patients, 75 (31.0%) had a positive tuberculin skin test (TST) and 45 (18.6%) had positive QFT-G results, with another nine (3.7%) showing indeterminate QFT-G assay. Isoniazid prophylaxis was given to 37 patients with TST+/QFT-G+ results and 24 TST+/QFT-G– patients with TST induration diameter greater double equals10 mm. Four patients (three with baseline QFT-G+ results) developed tuberculosis within the first 3 months of anti-TNFα therapy, whereas five patients with baseline TST–/QFT-G– results developed active tuberculosis after 20–24 months' anti-TNFα therapy. Progressively rising levels of released IFN (2.17±0.98 vs 5.93±2.92 IU/ml in early secretory antigenic target-6-stimulated well; 1.12±0.84 vs 2.96±1.02 IU/ml in culture filtrate protein-10-stimulated well) were observed in those who developed tuberculosis early in anti-TNFα therapy. QFT-G conversion was found in baseline QFT-G-negative patients who developed tuberculosis late in treatment. Conclusion The emergence of active tuberculosis follows a biphasic pattern. Persistently high levels of released IFN or QFT-G conversion strongly indicate the development of active tuberculosis in patients undergoing long-term anti-TNFα therapy.

Undifferentiated arthritis characteristics and outcomes when applying the 2010 and 1987 criteria for rheumatoid arthritis

Objective Undifferentiated arthritis (UA) is a diagnosis ‘per exclusionem’. Therefore this patient population may change since the development of the ACR/EULAR 2010-criteria for RA. This study evaluated characteristics and outcomes of UA in its new shape. Second, it was evaluated whether the 2010-criteria and the Leiden prediction rule were congruent in categorizing UA-patients. Methods 2,472 early arthritis patients were studied. RA was classified according to either the 1987 or the 2010-criteria. UA was defined as not fulfilling existing classification criteria. UA-patients were compared for baseline characteristics and outcomes. In 1987-UA-patients both the 2010-criteria and the Leiden prediction rule were applied and categorization compared. Results 2010-UA-patients (n=776) had milder baseline characteristics than 1987-UA-patients (n=1,166). During follow-up, still 24% of the 2010-UA-patients fulfilled the 1987 RA-criteria compared to 32% of the 1987-UA-patients. The 2010-UA-patients started less frequent DMARD-therapy and reached more frequent sustained DMARD-free remission. 30% of 2010-criteria-positive patients were predicted to have a low risk on RA; these patients achieved more frequent DMARD-free sustained remission than other 2010-criteria-positive patients. Conclusion UA in the era of the 2010-criteria is less prevalent and milder at presentation and in outcome. This implies that UA-patients with unfavorable characteristics are now more often classified as RA.

Clinical manifestations of antiphospholipid syndrome (APS) with and without antiphospholipid antibodies (the so-called 'seronegative APS')

Objectives Although the medical literature currently provides a growing number of isolated case reports of patients with clinically well-defined antiphospholipid syndrome (APS) and persistently negative antiphospholipid antibodies (aPL), there are no studies including a series of patients addressing the clinical features of this condition. Methods The authors assessed clinical manifestations of APS in 154 patients: 87 patients with seropositive APS and 67 patients with thrombosis and/or pregnancy morbidity persistently negative for aPL and presenting with at least two additional non-criteria manifestations of APS (the so-called ‘seronegative APS’, SN-APS). Patients were interviewed at the time of recruitment, and a retrospective file review was carried out. Results There were no significant differences in the frequency of thrombotic events or obstetric morbidity in patients with SN-APS versus patients with seropositive APS: deep vein thrombosis (31.4% vs 31.0%), pulmonary embolism (23.8% vs 28.7%), stroke (14.9% vs 17.2%), transient ischaemic attack (11.9% vs 10.3%), early spontaneous abortions (67.1% vs 52.1%), stillbirths (62.5% vs 59.4%), prematurity (28.1% vs 21.7%) or pre-eclampsia (28.1% vs 23.1%). Conclusions Classic and SN-APS patients show similar clinical profiles. The results suggest that clinical management in patients with APS should not be based only on the presence of conventional aPL.

The association of treatment response and joint damage with ACPA-status in recent-onset RA: a subanalysis of the 8-year follow-up of the BeSt study

Objective Anticitrullinated protein antibodies (ACPAs) are suggested to identify different subsets of patients with rheumatoid arthritis (RA). The authors compared the clinical and radiological responses to Disease Activity Score (DAS)-steered treatment in patients with RA positive or RA negative for ACPA. Methods In the BehandelStrategieën (BeSt) study, 508 patients with recent-onset RA were randomised to four treatment strategies aimed at a DAS ≤2.4. Risks of damage progression and (drug-free) remission in 8 years were compared for ACPA-positive and ACPA-negative patients using logistic regression analysis. Functional ability and DAS components over time were compared using linear mixed models. Results DAS reduction was achieved similarly in ACPA-positive and ACPA-negative patients in all treatment strategy groups, with a similar need to adjust treatment because of inadequate response. Functional ability and remission rates were not different for ACPA-positive and ACPA-negative patients. ACPA-positive patients had more radiological damage progression, especially after initial monotherapy. They had a lower chance of achieving (persistent) drug-free remission. Conclusion Clinical response to treatment was similar in ACPA-positive and ACPA-negative patients. However, more ACPA-positive patients, especially those treated with initial monotherapy, had significant radiological damage progression, indicating that methotrexate monotherapy and DAS- (≤2.4) steered treatment might be insufficient to adequately suppress joint damage progression in these patients.

The pulmonary arterial hypertension quality enhancement research initiative: comparison of patients with idiopathic PAH to patients with systemic sclerosis-associated PAH

Objective The objective of this report is to compare baseline, management and survival characteristics in idiopathic pulmonary arterial hypertension (IPAH) with systemic sclerosis-associated pulmonary arterial hypertension (SSc-APAH) using data from the prospectively enrolled PAH Quality Enhancement Research Initiative. Methods Between August 2005 and July 2007, patients with IPAH and SSc-APAH were enrolled across 60 US sites and followed up for 3 years. Data on diagnostic tests, clinical variables, pulmonary arterial hypertension (PAH) medication and outcomes were recorded. Results With some exceptions, baseline clinical and laboratory characteristics were similar between the 279 patients with IPAH and the 228 with SSc-APAH. Patients with SSc-APAH were older at the time of PAH diagnosis, were more likely to be female and were antinuclear antibody positive. Patients with SSc-APAH had poorer spirometric results. During the 3-year follow-up, both groups were managed with prostacyclin and prostacyclin analogue treatment, endothelin receptor antagonists and phosphodiesterase type 5 inhibitors (PDE5i) singly or in combination. At 3 years, patients with SSc-APAH were more likely to be treated with PDE5i alone or with an endothelin receptor antagonist. Patients with SSc-APAH had a significantly lower survival rate compared to patients with IPAH (60% vs 77%, p<0.0001). Conclusions The cohort with SSc-APAH was older, was more severely ill, was more likely to be female, was managed with PDE5i and had reduced 3-year survival compared with the cohort with IPAH.

The anti-inflammatory effects of sympathectomy in murine antigen-induced arthritis are associated with a reduction of Th1 and Th17 responses

Background Both facilitatory and inhibitory effects of the sympathetic nervous system (SNS) on experimental arthritis have been reported. It is unknown whether such bidirectional effects are inherent to all experimental arthritis models and/or whether critical time windows exist for influences of the SNS on inflammation. Objectives To assess the effect of sympathectomy at different time points on the course and severity of murine antigen-induced arthritis (AIA). Methods AIA was induced in mice. Chemical sympathectomy with 6-hydroxydopamine was carried out either neonatally, in the immunisation phase, or immediately before AIA elicitation, or during the chronic phase. In sympathectomised and non-sympathectomised AIA mice the inflammatory process (joint swelling, histopathology of inflammation and joint destruction), pain-related behaviour and cellular and humoral immune responses were analysed. Results Sympathectomy during AIA induction or neonatal sympathectomy significantly reduced the severity of acute AIA. Neither sympathectomy in the immunisation phase nor in the chronic phase influenced AIA. Flare-up reactions were reduced by sympathectomy just before flare-up or during the initial acute AIA stage. Sympathectomised AIA mice showed less hyperalgesia. Sympathectomy significantly reduced interleukin (IL) 2, IL-17 and transforming growth factor β in supernatants from lymph nodes and/or spleen cells and antigen-specific Th1-associated IgG2a in serum; IgG1 titres were unaffected. The ß blocker, propranolol, and the norepinephrine reuptake inhibitor bupropion produced similar anti-inflammatory effects, whereas the ß-adrenergic agonist isoproterenol increased AIA severity in neonatally sympathectomised mice. Conclusions Sympathetic activity mainly increases the severity of acute episodes of immune-mediated arthritis. Therapeutic reduction of sympathetic activity at acute stages attenuates inflammation, hyperalgesia and proinflammatory immune parameters.

Comparison of rheumatoid articular adipose and synovial tissue reactivity to proinflammatory stimuli: contribution to adipocytokine network

Objectives (1) To compare spontaneous and stimuli-induced adipocytokine secretion by articular adipose tissue (AAT) and synovial membrane (SM) explants obtained from patients with rheumatoid arthritis (RA). (2) To investigate the biological activity of AAT and SM released factors. Methods Tissues were obtained from patients undergoing joint replacement surgery. Tissue explants were treated with proinflammatory cytokines relevant to RA pathogenesis (interleukin 1β (IL-1β), tumour necrosis factor (TNF), interferon , IL-15, IL-17, IL-23). Selected adipocytokine (TNF, IL-6, IL-8, IL-1β, IL-1Ra, adiponectin, leptin) concentrations were measured in culture supernatants using ELISA. The biological activity of tissue-conditioned media was evaluated by measuring production of selected factors (IL-6, IL-8, Dickkopf-1, osteoprotegerin) by fibroblast-like synoviocytes (FLS). Results Spontaneous cytokine release from AAT was ≤12% of that produced by SM, while leptin was secreted in similar amounts. AAT was highly reactive to proinflammatory cytokines (IL-1β>TNF). AAT treated with IL-1β released four times more leptin, similar amounts of IL-6 and IL-8 and about 20% of TNF, as compared with SM. Upon activation, the IL-1 receptor antagonist (IL-1Ra)/IL-1β ratio was higher in AAT than in SM cultures. Irrespective of activation status, SM produced twice as much adiponectin as AAT. Conditioned media from AAT and SM cultures similarly upregulated IL-6, IL-8, Dickkopf-1 and osteoprotegerin production by rheumatoid FLS. Conclusion Rheumatoid AAT is highly reactive tissue which upon stimulation secretes considerable amounts of proinflammatory (IL-6, IL-8, TNF) and anti-inflammatory (IL-1Ra) cytokines and classical adipokines. This tissue releases biologically active factors that intensify pathogenic activities of rheumatoid FLS. Thus, AAT should be considered an important contributor to the pathological processes taking place in the RA joint.

The ACPA recognition profile and subgrouping of ACPA-positive RA patients

Objective Anticitrullinated protein antibodies (ACPA) are the most predictive factor for the development of rheumatoid arthritis (RA). Epitope spreading towards more citrullinated epitopes occurs before the onset of RA. Here, the authors investigated whether specific epitope recognition allows the identification of specific RA subgroups and whether it is associated with clinical features of RA. Methods The reactivity of 661 patients with RA from the Leiden Early Arthritis Clinic against several citrullinated antigens was determined by ELISA. Cluster analyses were performed to identify subgroups of patients on the basis of their ACPA recognition profile. The association of the specific reactivities with clinical characteristics was studied. Results ACPA-positive patients displayed a heterogeneous ACPA recognition profile. After performing cluster analyses, no apparent clustering of patients was found, and on the basis of the reactivities analysed, 64 different subgroups could already be identified. The extent of epitope recognition was associated with anticyclic citrullinated peptide-2 levels. The recognition of specific citrullinated epitopes was not associated with baseline characteristics. Likewise, patients with an extended fine specificity repertoire did not display differences in baseline characteristics or joint damage after 7 years of follow-up using cyclic citrullinated peptide-2 levels as a proxy, compared to ACPA-positive patients recognising fewer peptides. Conclusion These data show that the ACPA response is highly diverse with respect to recognition of specific citrullinated epitopes. Furthermore, the authors' data indicate that clinical correlates in established ACPA-positive RA are independent from the specific (group of) citrullinated peptides recognised.

Transcriptome analysis reveals specific changes in osteoarthritis synovial fibroblasts

Objective Changes in rheumatoid arthritis synovial fibroblast (RASF) gene expression are usually defined by a comparison to osteoarthritis synovial fibroblasts (OASFs). This study was undertaken to analyse the transcriptome of OASFs as compared to RASFs and healthy synovial fibroblasts (HSFs). Methods The authors used microarray messenger RNA expression profiling of synovial fibroblasts cultured from osteoarthritis (OA), rheumatoid arthritis and normal synovial tissues. Quantitative real-time PCR of selected genes was performed to validate microarray data. Analysis of variance, Student t test and the Benjamini–Hochberg multiple testing correction method for multiple testing correction were used to determine the statistical significance of the changes between the three groups. Results Larger numbers of transcripts showed a differential expression in OASFs versus the other groups, rather than in RASFs versus HSFs. Cluster analysis confirmed that the differences between the three groups were mostly due to the differences between OA and the other groups. Functional classification identified a significant number of genes related to growth factor activities, cell adhesion, neurotransmission and Ras signalling that are differentially expressed in OASFs. Classical proinflammatory factors or proteases involved in cartilage degradation were not found to be overexpressed in OASFs. Conclusion Cultured OASFs display a more homogeneous transcriptomic profile than RASFs when compared to HSFs. This supports the participation of synovial fibroblasts in the pathogenesis of OA and may reflect global defects in the mesenchyma-derived lineages of the different tissues in OA joints. These data support individual heterogeneity among RASFs and advise against the use of OASFs as controls.

Articular inflammation is controlled by myeloid cell-derived interleukin 1 receptor antagonist during the acute phase of arthritis in mice

Objectives To define the cell type (myeloid vs other cells) specific effect of interleukin 1 (IL-1) receptor antagonist (IL-1Ra) deficiency on the acute inflammatory phase of arthritis. Methods Arthritis was induced by K/BxN serum transfer in wild-type (WT), IL-1Ra-deficient (IL-1Ra–/–) and conditional knockout mice. In the latter, IL-1Ra production was specifically targeted in myeloid cells (IL-1RaM) or in both hepatocytes and myeloid cells (IL-1RaH+M). Arthritis severity was clinically evaluated and ankle sections were scored for synovial inflammation and cartilage erosion. Quantitative RT-PCR, western blot and immunohistochemical analyses measured expression, localisation and cellular sources of the different IL-1Ra isoforms in arthritic joints. Results Total and myeloid cell-specific IL-1Ra deficiency was associated with increased arthritis severity, although disease incidence was similar to that of WT mice. Increased clinical scores were associated with exacerbated synovial inflammation. All IL-1Ra isoforms, except for intracellular (ic)IL-1Ra2, were expressed in arthritic joints of WT mice. In contrast, production of secreted (s)IL-1Ra and icIL-1Ra3 isoforms was markedly decreased in arthritic joints of both IL-1RaM and IL-1RaH+M mice. Immunohistochemical and western blot analyses suggested that the icIL-1Ra1 isoform is produced primarily by synovial fibroblasts. Conclusion Myeloid cell-derived IL-1Ra, including both sIL-1Ra and icIL-1Ra3 isoforms, controls articular inflammation during the acute phase of K/BxN serum transfer-induced arthritis.

Infrapatellar fat pad of patients with end-stage osteoarthritis inhibits catabolic mediators in cartilage

Objective Adipose tissue is known to release inflammatory cytokines and growth factors. In this exploratory study, the authors examined whether the infrapatellar fat pad (IPFP) closely located to cartilage in the knee joint can affect cartilage metabolism. In addition, the authors analysed whether the macrophage types present in IPFP could explain the effect on cartilage. Methods IPFP explants obtained during total knee replacement of 29 patients with osteoarthritis (OA) were used to make fat-conditioned medium (FCM). Explants of bovine cartilage were cultured with or without FCM. Nitric oxide (NO) and glycosaminoglycan release and gene expression of matrix-degrading enzymes in cartilage were analysed. To stimulate catabolic processes in the cartilage, the authors added interleukin 1β, and the effect of six FCMs was evaluated. The presence of different types of macrophages (CD68+, CD86+ and CD206+) in OA IPFPs was compared with subcutaneous adipose tissue samples and IPFP samples from patients with an anterior cruciate ligament rupture. Results FCM alone reduced NO and glycosaminoglycan release and matrix metalloproteinase (MMP)1 gene expression by the cartilage. Moreover, when catabolic conditions were enhanced with interleukin 1β, FCM inhibited NO production as well as MMP1 and MMP3 gene expression and increased collagen type II gene expression. Significantly more CD206+ cells were present in OA IPFP samples than in subcutaneous fat or anterior cruciate ligament IPFP samples. Conclusion In contrast to the authors' expectations, medium conditioned by end-stage OA IPFP inhibited catabolic processes in cartilage. CD206+ cells present in the IPFPs used for making the FCM might have contributed to the inhibition of catabolic processes in the cartilage.

Potential involvement of IL-22 and IL-22-producing cells in the inflamed salivary glands of patients with Sjogren's syndrome

Objectives In chronic inflammatory disorders, interleukin (IL)-22 may act either as a protective or as a pro-inflammatory cytokine. At mucosal sites, IL-22 is mainly produced by CD4+ T cells and by a subset of mucosal natural killer (NK) cells expressing the receptor NKp44 (NKp44+ NK cells). The aim of this study was to investigate the IL-22 expression in the salivary glands of patients with primary Sjögren's syndrome (pSS). Methods Minor salivary gland biopsies were obtained from 19 patients with pSS and 16 with non-specific chronic sialoadenitis. Quantitative gene expression analysis by TaqMan real-time PCR and immunohistochemistry for IL-17, IL-22, IL-23 and STAT3 (signal transducer and activator of transcription) was performed on salivary glands from patients and controls. The cellular sources of IL-22 among infiltrating inflammatory cells were also determined by fluorescence-activated cell sorting analysis and immunohistochemistry. Results IL-22, IL-23 and IL-17 were significantly increased at both protein and mRNA levels in the inflamed salivary glands of patients with pSS. STAT3 mRNA and the tyrosine phosphorylated corresponding protein were also significantly increased in pSS. Th17 and NKp44+ NK cells were the major cellular sources of IL-22 in patients with pSS. Conclusions Our results suggest that, together with IL-17 and IL-23, IL-22 may play a pro-inflammatory role in the pathogenesis of pSS.

Hypoxia: a critical regulator of early human tendinopathy

Objectives To seek evidence for the role of hypoxia in early human tendinopathy, and thereafter to explore mechanisms whereby tissue hypoxia may regulate apoptosis, inflammatory mediator expression and matrix regulation in human tenocytes. Methods Fifteen torn supraspinatus tendon (established pathology) and matched intact subscapularis tendon (representing ‘early pathology’) biopsies were collected from patients undergoing arthroscopic shoulder surgery. Control samples of the subscapularis tendon were collected from 10 patients undergoing arthroscopic stabilisation surgery. Markers of hypoxia were quantified by immunohistochemical methods. Human tendon-derived primary cells were derived from hamstring tendon tissue obtained during hamstring tendon anterior cruciate ligament reconstruction. The impact of hypoxia upon tenocyte biology ex vivo was measured using quantitative real-time PCR, multiplex cytokine assays, apoptotic proteomic profiling, immunohistochemistry and annexin V fluorescence-activated cell sorter staining. Results Increased expression of hypoxia-inducible factor 1α, Bcl-2 and clusterin was detected in subscapularis tendon samples compared with both matched torn samples and non-matched control samples (p<0.01). Hypoxic tenocytes exhibited increased production of proinflammatory cytokines (p<0.001), altered matrix regulation (p<0.01) with increased production of collagen type III operating through a mitogen-activated protein kinase-dependent pathway. Finally, hypoxia increased the expression of several mediators of apoptosis and thereby promoted tenocyte apoptosis. Conclusion Hypoxia promotes the expression of proinflammatory cytokines, key apoptotic mediators and drives matrix component synthesis towards a collagen type III profile by human tenocytes. The authors propose hypoxic cell injury as a critical pathophysiological mechanism in early tendinopathy offering novel therapeutic opportunities in the management of tendon disorders.

Cyclophosphamide is a highly effective and safe induction therapy in chronic periaortitis: a long-term follow-up of 35 patients with chronic periaortitis

Chronic periaortitis is a fibro-inflammatory disease of unknown aetiology with histopathological and laboratory findings suggesting an IgG4-related sclerosing disease in a subgroup of patients.1–3 Due to its inflammatory character and associated autoimmune phenomena, different immunosuppressive regimens have been suggested for treatment.4–9 In this study, we retrospectively examined the response to immunosuppressive treatment of 35 patients with chronic periaortitis applying the same study design as before.5 Imaging studies were performed and serum IgG4 levels were measured both at the time of diagnosis and during follow-up. Retroperitoneal tissue was examined histologically in four patients. Emphasis has been placed on the evaluation of cyclophosphamide in the induction therapy and the hitherto unknown value of serum IgG4 measurements in disease monitoring. The Wilcoxon signed-rank test was used for statistical analysis of the imaging...