http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2013 , Hindawi Publishing Corporation . All rights reserved. Thu, 16 May 2013 08:18:00 +0000 http://www.hindawi.com/journals/ijr/2013/272595/ Some patients with autoimmune pancreatitis (AIP) form pancreatic stones suggestive of transformation into chronic pancreatitis (CP). The present study examined the underlying risk factors and mechanism of AIP progression to confirmed CP. We compared the clinical and laboratory parameters of subjects who progressed to confirmed CP with those of the subjucts who did not in a cohort of 73 type 1 AIP patients. A total of 16 (22%) AIP patients progressed to CP. Univariate analysis revealed that relapse was significantly more frequent in the progression group, and multivariate analysis indicated that pancreatic head swelling (OR 12.7, ) and nonnarrowing of the main pancreatic duct in the pancreatic body (OR 12.6, ) were significant independent risk factors for progression to CP. Kaplan-Meier testing showed that the progression rate to CP was approximately 10% at 3 years and 30% at 10 years in total AIP patients and 30% at 3 years and 60% at 10 years in subjects with both risk factors. AIP with pancreatic head swelling and a history of relapse may cause pancreatic juice stagnation and nonnarrowing of the main pancreatic duct in the pancreatic body, which can progress to advanced stage chronic pancreatitis. Masahiro Maruyama, Norikazu Arakura, Yayoi Ozaki, Takayuki Watanabe, Tetsuya Ito, Suguru Yoneda, Masafumi Maruyama, Takashi Muraki, Hideaki Hamano, Akihiro Matsumoto, and Shigeyuki Kawa Copyright © 2013 Masahiro Maruyama et al. All rights reserved. Sun, 07 Apr 2013 15:08:59 +0000 http://www.hindawi.com/journals/ijr/2013/912562/ Overview. The GiACTA trial is a multicenter, randomized, double-blind, and placebo-controlled study designed to test the ability of tocilizumab (TCZ), an interleukin (IL)-6 receptor antagonist, to maintain disease remission in patients with giant cell arteritis (GCA). Design. Approximately 100 centers will enroll 250 patients with active disease. The trial consists of a 52-week blinded treatment phase followed by 104 weeks of open-label extension. Patients will be randomized into one of four groups. Group A (TCZ 162 mg weekly plus a 6-month prednisone-taper); group B (TCZ 162 mg every other week plus a 6-month prednisone-taper); group C (placebo plus a 6-month prednisone-taper); and group D (placebo plus a 12-month prednisone taper). We hypothesize that patients assigned to TCZ in addition to a 6-month prednisone course are more likely to achieve the primary efficacy endpoint of sustained remission (SR) at 52 weeks compared with those assigned to a 6-month prednisone course alone, thus potentially minimizing the long-term adverse effects of corticosteroids. Conclusion. GiACTA will test the hypothesis that interference with IL-6 signaling exerts a beneficial effect on patients with GCA. The objective of this paper is to describe the design of the trial and address major issues related to its development. Sebastian H. Unizony, Bhaskar Dasgupta, Elena Fisheleva, Lucy Rowell, Georg Schett, Robert Spiera, Jochen Zwerina, Olivier Harari, and John H. Stone Copyright © 2013 Sebastian H. Unizony et al. All rights reserved. Wed, 03 Apr 2013 10:16:39 +0000 http://www.hindawi.com/journals/ijr/2013/347520/ This paper assessed the burden of adverse events (AEs) associated with azathioprine (AZA), cyclophosphamide (CYC), mycophenolate mofetil (MMF), methotrexate (MTX), and cyclosporine (CsA) in patients with systemic lupus erythematosus (SLE). Thirty-eight publications were included. Incidence of AEs ranged from 42.8% to 97.3%. Common AEs included infections (2.4–77%), gastrointestinal AEs (3.2–66.7%), and amenorrhea and/or ovarian complications (0–71%). More hematological cytopenias were associated with AZA (14 episodes) than MMF (2 episodes). CYC was associated with more infections than MMF (40–77% versus 12.5–32%, resp.) or AZA (17–77% versus 11–29%, resp.). Rates of hospitalized infections were similar between MMF and AZA patients, but higher for those taking CYC. There were more gynecological toxicities with CYC than MMF (32–36% versus 3.6–6%, resp.) or AZA (32–71% versus 8–18%, resp.). Discontinuation rates due to AEs were 0–44.4% across these medications. In summary, the incidence of AEs associated with SLE immunosuppressants was consistently high as reported in the literature; discontinuations due to these AEs were similar across treatments. Studies on the economic impact of these AEs were sparse and warrant further study. This paper highlights the need for more treatment options with better safety profiles. A. Oglesby, A. J. Shaul, T. Pokora, C. Paramore, L. Cragin, G. Dennis, S. Narayanan, and A. Weinstein Copyright © 2013 A. Oglesby et al. All rights reserved. Thu, 28 Feb 2013 18:11:43 +0000 http://www.hindawi.com/journals/ijr/2013/548502/ Objectives. To validate van der Helm-van Mil score (vHvM) and new ACR/EULAR criteria for the diagnosis of rheumatoid arthritis (RA) in patients with undifferentiated arthritis (UA). Patients and Methods. Adult patients with UA (swelling ≥2 joints of less than 6 months duration, without diagnosis, and never treated with disease modifying drugs). Results. Ninety-one patients were included. Mean age: 55.6 years (SD: 17.4), 74% females. Median symptoms duration was 2 months (IR: 1–4 months). Mean van der Helm-van Mil score was 6.9 (SD: 2). After a mean followup of 6.2 months (SD: 6), 40.7% patients fulfilled ACR 1987 RA classification criteria, 28.6% fulfilled other diagnostic criteria, and 31% remained as UA. Receiver operator characteristic curve's (ROC's) area under the curve (AUC) for the vHvM score for diagnosis of RA was 0.83. A cutoff value of 6.94 showed sensitivity of 81% and 79.7% specificity. For the new ACR/EULAR criteria, the ROC AUC was 0.93, and a value equal to or greater than 6 showed 86.5% sensitivity and 87% specificity. Conclusion. van der Helm-van Mil prediction score and the new ACR/EULAR criteria proved to be valuable for the diagnosis of RA in patients with early UA. Zaida Bedran, Cristian Quiroz, Javier Rosa, Luis J. Catoggio, and Enrique R. Soriano Copyright © 2013 Zaida Bedran et al. All rights reserved. Tue, 19 Feb 2013 12:55:51 +0000 http://www.hindawi.com/journals/ijr/2013/139608/ Objectives. To explore health care costs associated with ankylosing spondylitis (AS) in Turkey. Methods. Research-identified data from a system that processes claims for all Turkish health insurance funds were analyzed. Adult prevalent and incident AS patients with two AS visits at least 60 days apart, identified between June 1, 2010 and December 31, 2010, with at least 1 year of continuous health plan enrollment for the baseline and follow-up years were included in the study. Pharmacy, outpatient, and inpatient claims were compiled over the study period for the selected patients. Generalized linear models were used to estimate the expected annual costs, controlling for baseline demographic and clinical characteristics. Results. A total of 2.986 patients were identified, of which 603 were incident cases and 2.383 prevalent cases. The mean ages were 39 and 41 years, respectively, and 44% and 38% were women for incident and prevalent cases. Prevalent patients had higher comorbidity scores (5.01 versus 2.24, ) and were more likely to be prescribed nonsteroidal anti-inflammatory drugs (NSAIDs) (77% versus 72%, ) or biologics (35% versus 8%, ) relative to incident patients. Seventy-seven percent of prevalent patients were prescribed NSAIDs, followed by biologic and disease-modifying antirheumatic drugs (DMARDs). Total annual medical costs for incident AS patients were €2.253 and €4.233 for prevalent patients. Pharmacy costs accounted for a significant portion of total costs (88% for prevalent patient, 77% for incident patient), followed by physician office visit costs. Prior comorbidities and treatment type also significantly contributed to overall costs. Conclusion. Annual expenditures for AS patients in Turkey were comparable relative to European countries. Pharmaceutical expenditures cover a significant portion of the overall costs. Comparative effectiveness studies are necessary to further decrease health care costs of AS treatment. Onur Baser, Abdulkadir Burkan, Erdem Baser, Rasim Koselerli, Emre Ertugay, and Akif Altinbas Copyright © 2013 Onur Baser et al. All rights reserved. Wed, 16 Jan 2013 07:51:59 +0000 http://www.hindawi.com/journals/ijr/2013/532612/ John H. Stone, John K. C. Chan, Vikram Deshpande, Kazuichi Okazaki, Hisanori Umehara, and Yoh Zen Copyright © 2013 John H. Stone et al. All rights reserved. Thu, 27 Dec 2012 15:06:56 +0000 http://www.hindawi.com/journals/ijr/2012/348450/ Objective. To observe the effects of tripterygium glycosides tablet (TPT) on swelling degree, arthritis index (AI), pulmonary function, cytokines, the expression of regulatory T cells (Treg), and Foxp3 in rats of adjuvant arthritis. Methods. Rats were averagely divided into normal control (NC) group, model control (MC) group, methotrexate (MTX) group, and tripterygium glycosides tablet (TPT) group. Except for the rats of normal group, the others were intracutaneously injected with 0.1 mL of Freund’s complete adjuvant in the right hindlimb. NC group and MC group were treated with physiological saline. MTX group and TPT group were treated with MTX, TPT, respectively. Results. The levels of swelling degree, AI, the alveolar inflammation integral, TNF alpha (TNF-), and endothelium-1 (ET-1 ) in MC group were significantly increased (), and the levels of forced vital capacity (FVC), 25% vital capacity of the peak expiratory flow (FEF25), 50% vital capacity of the peak expiratory flow (FEF50), 75% vital capacity of the peak expiratory flow (FEF75), maximum midexpiratory flow (MMF), peak expiratory flow (PEF), interleukin-10 (IL-10), CD4+ CD25+ Treg, and Foxp3 were decreased (). The scores of alveolitis and ET-1 were decreased with treatment of TPT. The levels of FVC, FEF25, FEF50, FEF75, MMF, PEF, IL-10, and CD4+ CD25+ Treg in peripheral blood were increased. The expressions of Foxp3 protein and mRNA in lung tissue were also increased in TPT group. Conclusions. The paw swelling can be inhibited by TPT, and the inflammatory response in lung tissue was also decreased, which is a significant improvement in pulmonary function. The mechanism is probably associated with upregulating the expression of IL-10, Foxp3, and downregulating the level of TNF-. Wan Lei and Liu Jian Copyright © 2012 Wan Lei and Liu Jian. All rights reserved. Tue, 25 Dec 2012 08:50:50 +0000 http://www.hindawi.com/journals/ijr/2012/839425/ Over the past decade, the assessment of the disease activity in psoriatic arthritis (PsA) has rapidly evolved in view of the need for valid, feasible, and reliable outcome measures that can be ideally employed in longitudinal cohorts, clinical trials, and clinical practice as well as the growing paradigm of tight disease control and treating to target in the management of PsA. This paper reviews the currently available measures used in the assessment of the disease activity in PsA. The composite measures for PsA that are under development are also discussed. Priscilla C. H. Wong, Ying-Ying Leung, Edmund K. Li, and Lai-Shan Tam Copyright © 2012 Priscilla C. H. Wong et al. All rights reserved. Wed, 05 Dec 2012 16:33:17 +0000 http://www.hindawi.com/journals/ijr/2012/480784/ Objective. To investigate the association of lipoprotein(a) and atherosclerosis-related autoimmune diseases, to provide information on possible pathophysiologic mechanisms, and to give recommendations for Lp(a) determination and therapeutic options. Methods. We performed a systematic review of English language citations referring to the keywords “Lp(a)” AND “autoimmune disease” AND “atherosclerosis,” “Lp(a)” AND “immune system” OR “antiphospholipid (Hughes) syndrome (APS)” OR “rheumatoid arthritis” OR “Sjögren’s syndrome” OR “systemic lupus erythematosus” OR “systemic sclerosis” OR “systemic vasculitis” published between 1991 and 2011 using Medline database. Results. 22 out of 65 found articles were identified as relevant. Lp(a) association was highest in rheumatoid arthritis (RA), followed by systemic lupus erythematosus (SLE), moderate in APS and lowest in systemic sclerosis (SSc). There was no association found between Lp(a) and systemic vasculitis or Sjögren’s syndrome. Conclusion. Immune reactions are highly relevant in the pathophysiology of atherosclerosis, and patients with specific autoimmune diseases are at high risk for CVD. Elevated Lp(a) is an important risk factor for premature atherosclerosis and high Lp(a) levels are also associated with autoimmune diseases. Anti-Lp(a)-antibodies might be a possible explanation. Therapeutic approaches thus far include niacin, Lp(a)-apheresis, farnesoid x-receptor-agonists, and CETP-inhibitors being currently under investigation. I. Missala, U. Kassner, and E. Steinhagen-Thiessen Copyright © 2012 I. Missala et al. All rights reserved. Wed, 14 Nov 2012 11:51:43 +0000 http://www.hindawi.com/journals/ijr/2012/703138/ Hand osteoarthritis (HOA) is a prevalent condition for which treatments are based on analgesia and physical therapies. Our primary objective was to evaluate pain perception in participants with HOA by assessing the characteristics of nodal involvement, pain threshold in each hand joint, and radiological severity. We hypothesised that inflammation in hand osteoarthritis joints enhances sensitivity and firing of peripheral nociceptors, thereby causing chronic pain. Participants with proximal and distal interphalangeal (PIP and DIP) joint HOA and non-OA controls were recruited. Clinical parameters of joint involvement were measured including clinical nodes, VAS (visual analogue score) for pain (0–100 mm scale), HAQ (health assessment questionnaire), and Kellgren-Lawrence scores for radiological severity and pain threshold measurement were performed. The mean VAS in HOA participants was 59.3 mm ± 8.19 compared with 4.0 mm ± 1.89 in the control group (). Quantitative sensory testing (QST) demonstrated lower pain thresholds in DIP/PIP joints and other subgroups in the OA group including the thumb, metacarpophalangeal (MCPs), joints, and wrists () but not in controls (). Our data demonstrate that HOA subjects are sensitised to pain due to increased firing of peripheral nociceptors. Future work to evaluate mechanisms of peripheral sensitisation warrants further investigation. Julekha Wajed, Vivian Ejindu, Christine Heron, Monika Hermansson, Patrick Kiely, and Nidhi Sofat Copyright © 2012 Julekha Wajed et al. All rights reserved. Sun, 11 Nov 2012 13:38:53 +0000 http://www.hindawi.com/journals/ijr/2012/240689/ Introduction. Contemporary health policy promotes delivery of community-based health services to people with musculoskeletal conditions, including rheumatoid arthritis (RA). This emphasis requires a skilled workforce to deliver safe, effective care. We aimed to explore physiotherapy workforce readiness to co-manage consumers with RA by determining the RA-specific professional development (PD) needs in relation to work and educational characteristics of physiotherapists in Western Australia (WA). Methods. An e-survey was sent to physiotherapists regarding their confidence in co-managing people with RA and their PD needs. Data including years of clinical experience, current RA clinical caseload, professional qualifications, and primary clinical area of practice were collected. Results. 273 physiotherapists completed the survey. Overall confidence in managing people with RA was low (22.7–58.2%) and need for PD was high (45.1–95.2%). Physiotherapists with greater years of clinical experience, a caseload of consumers with RA, postgraduate qualifications in musculoskeletal physiotherapy, or who worked in the musculoskeletal area were more confident in managing people with RA and less likely to need PD. Online and face-to-face formats were preferred modes of PD delivery. Discussion. To enable community-based RA service delivery to be effectively established, subgroups within the current physiotherapy workforce require upskilling in the evidence-based management of consumers with RA. Robyn E. Fary, Helen Slater, Jason Chua, and Andrew M. Briggs Copyright © 2012 Robyn E. Fary et al. All rights reserved. Sun, 21 Oct 2012 10:09:21 +0000 http://www.hindawi.com/journals/ijr/2012/756291/ Whether tumor necrosis factor alpha (TNF-α) gene polymorphisms (SNPs) influence disease susceptibility and treatment of patients with juvenile idiopathic arthritis (JIA) is presently uncertain. TNF-α is one of the most important cytokine involved in JIA pathogenesis. Several single nucleotide polymorphisms (SNPs) have been identified within the region of the TNF-α gene but only a very small minority have proven functional consequences and have been associated with susceptibility to JIA. An association between some TNF-α SNPs and adult rheumatoid arthritis (RA) susceptibility, severity and clinical response to anti-TNF-α treatment has been reported. The most frenquetly studied TNF-α SNP is located at −308 position, where a substitution of the G allele with the rare A allele has been found. The presence of the allele −308A is associated to JIA and to a poor prognosis. Besides, the −308G genotype has been associated with a better response to anti-TNF-α therapy in JIA patients, confirming adult data. Psoriatic and oligoarticular arthritis are significantly associated to the −238 SNP only in some works. Studies considering other SNPs are conflicting and inconclusive. Large scale studies are required to define the contribution of TNF-α gene products to disease pathogenesis and anti-TNF-α therapeutic efficacy in JIA. A. Scardapane, L. Breda, M. Lucantoni, and F. Chiarelli Copyright © 2012 A. Scardapane et al. All rights reserved. Tue, 16 Oct 2012 09:29:59 +0000 http://www.hindawi.com/journals/ijr/2012/303506/ Objective. Immunoglobulin-G4-(IgG4-) related disease (IgG4 RD) is a fibrosing process characterized by a significant infiltration of IgG4-secreting plasma cells. IgG4 RD can affect almost all organs including salivary glands. Whether IgG4 RD plays a role in the development of sicca syndrome and particularly dry mouth syndrome remains to be investigated. Methods. We conducted a monocentric cohort study for two years to search for IgG4 RD features in patients with dry mouth syndrome using immunostainings of labial salivary gland specimens with anti-IgG4 antibody. Results. Among 60 patients presenting with dry mouth syndrome who underwent labial salivary gland biopsy, 18 showed positive immunostaining with the anti-IgG4 antibody including 4 patients with typical systemic IgG4 RD. Five also fulfilled criteria for Sjögren's syndrome. Conclusion. These findings suggest that clinical forms of IgG4 RD salivary involvement without salivary swelling may occur. This salivary involvement is probably overlooked in everyday practice and could represent a mild form of IgG4 RD. M. Hermet, M. André, J. L. Kémény, G. Le Guenno, P. Déchelotte, G. Guettrot-Imbert, A. Tridon, I. Delèvaux, M. Soubrier, and O. Aumaître Copyright © 2012 M. Hermet et al. All rights reserved. Mon, 03 Sep 2012 07:58:20 +0000 http://www.hindawi.com/journals/ijr/2012/121439/ Interstitial lung disease (ILD) is a major cause of morbidity and mortality in patients with systemic sclerosis (SSc). Although a large proportion of SSc patients have only limited interstitial involvement with an indolent course, in a significant minority ILD is progressive, requiring prompt treatment and careful monitoring. One of the main challenges for the clinician treating this highly variable disease is the early identification of patients at risk of progressive ILD, while avoiding potentially toxic treatments in those whose disease is inherently stable. Easily available and repeatable biomarkers that allow estimation of the risk of ILD progression and early response to treatment are highly desirable. In this paper, we review the evidence for circulating biomarkers with potential roles in diagnosis, monitoring of disease activity, or determining prognosis. Peripheral blood biomarkers offer the advantages of being readily obtained, non-invasive, and serially monitored. Several possible candidates have emerged from studies performed so far, including SP-D, KL-6, and CCL18. Presently however, there are few prospective studies evaluating the predictive ability of prospective biomarkers after adjustment for disease severity. Future carefully designed, prospective studies of well characterised patients with ILD, with optimal definition of disease severity and outcome measures are needed. Harpreet K. Lota and Elisabetta A. Renzoni Copyright © 2012 Harpreet K. Lota and Elisabetta A. Renzoni. All rights reserved. Sun, 26 Aug 2012 14:13:42 +0000 http://www.hindawi.com/journals/ijr/2012/602809/ Statement of Purpose. IgG4-related disease (IgG4-RD) is usually associated to an increase of serum IgG4 levels. However other conditions have also been associated to high serum IgG4 levels. Methods. All IgG subclasses analyses performed in our hospital over a one-year period were analyzed. When IgG4 level were over 1.35 g/L, the patient’s clinical observation was analyzed and both final diagnosis and reason leading to IgG subclasses analysis were recorded. Only polyclonal increases of IgG4 were considered. Summary of the Results. On 646 IgG subclass analysis performed, 59 patients had serum IgG4 over 1.35 g/L. The final diagnosis associated to serum IgG4 increase was very variable. Most patients (25%) presented with repeated infections, 13.5% with autoimmune diseases, and 10% with IgG4-RD. Other patients presented with cancer, primary immune deficiencies, idiopathic interstitial lung disease, cystic fibrosis, histiocytosis, or systemic vasculitis and 13.5% presented with various pathologies or no diagnosis. Mean IgG4 levels and IgG4/IgG ratio were higher in IgG4-RD than in other pathologies associated to elevated IgG4 levels. Conclusions. Our study confirms that elevation of serum IgG4 is not specific to IgG4-RD. Before retaining IgG4-RD diagnosis in cases of serum IgG4 above 1.35 g/L, several other pathological conditions should be excluded. Mikael Ebbo, Aurélie Grados, Emmanuelle Bernit, Frederic Vély, José Boucraut, Jean-Robert Harlé, Laurent Daniel, and Nicolas Schleinitz Copyright © 2012 Mikael Ebbo et al. All rights reserved. Wed, 15 Aug 2012 09:58:00 +0000 http://www.hindawi.com/journals/ijr/2012/285854/ Rheumatoid factor (RF) is currently used in the diagnosis of rheumatoid arthritis (RA). The discovery of anticitrullinated protein autoantibodies has led to the development of various new tests, such as anti-cyclic citrullinated peptide (anti-CCP) antibodies, and anti-mutated citrullinated vimentin (anti-MCV) antibodies, to diagnose RA. The aims of this study were to determine the sensitivity and specificity of anti-MCV antibodies in comparison with anti-CCP antibodies and RF in Omani Arab patients with RA and compare our findings with published values from different ethnic groups. The sensitivity of anti-MCV antibodies was 72% with 87% specificity. For anti-CCP antibodies the sensitivity was 52% and the specificity was 97%. The sensitivity of RF was 57% with 94% specificity. Anti-CCP antibodies have higher diagnostic specificity and positive predictive value than RF and anti-MCV antibodies. Anti-MCV antibodies have the highest sensitivity when compared to anti-CCP antibodies and RF. Anti-MCV antibodies do not appear to be very useful in the diagnosis of RA. However, long-term study is required to find out whether anti-MCV antibodies can be used as predictive test for incidence of RA. Ahmed Al-Shukaili, Saif Al-Ghafri, Safia Al-Marhoobi, and Juma Alkaabi Copyright © 2012 Ahmed Al-Shukaili et al. All rights reserved. Sun, 05 Aug 2012 10:24:53 +0000 http://www.hindawi.com/journals/ijr/2012/593039/ Objectives. To investigate the incidence of weight gain and hair loss as adverse effects of anti-TNF therapy in rheumatic diseases. Methods. Patients using anti-TNF therapy, who are followed in rheumatology clinic, were interviewed using a questionnaire to investigate the side effects of anti-TNF therapy. Patients who complained of hair loss and weight gain were asked additional questions concerning the relationship of these adverse effects to anti-TNF use, whether therapy was stopped because of these adverse effects and if the adverse effects reversed after stopping therapy. The files were reviewed to follow the weight change before, during, and after discontinuation of anti-TNF. Results. One hundred fifty consecutive patients (82 RA, 34 ankylosing spondylitis, 32 psoriatic arthritis, and 4 for other indications) were interviewed .Weight gain was observed in 20 patients (13.3%) with average gain of 5.5 Kg. Anti-TNF was stopped in five patients because of this adverse effect. Hair loss during anti-TNf therapy was reported in five females (3.3%) and anti-TNF therapy was stopped in all of them. Conclusion. Weight gain and hair loss appear to be associated with anti-TNF therapy and may be one reason for discontinuing the therapy. Abdo Lutf and Mohammed Hammoudeh Copyright © 2012 Abdo Lutf and Mohammed Hammoudeh. All rights reserved. Tue, 31 Jul 2012 13:43:46 +0000 http://www.hindawi.com/journals/ijr/2012/609795/ Although tubulointerstitial nephritis with IgG4+ plasma cell (PC) infiltration is a hallmark of IgG4-related kidney disease (IgG4-RKD), only a few studies are available about the minimum number of IgG4+ PC needed for diagnosis along with IgG4+/IgG+ PC ratio in the kidney. In addition, the significance of the deposition of IgG or complement as a reflection of humoral immunity involvement is still uncertain. In this study, we analyzed 20 Japanese patients with IgG4-RKD to evaluate the number of IgG4+ PCs along with IgG4+/IgG+ PC ratio and involvement of humoral immunity. The average number of IgG4+ PCs was 43.8/hpf and the average IgG4+/IgG+ or IgG4+/CD138+ ratio was 53%. IgG and C3 granular deposits on the tubular basement membrane (TBM) were detected by immunofluorescence microscopy in 13% and 47% of patients, respectively. Nine patients had a variety of glomerular lesions, and 7 of them had immunoglobulin or complement deposition in the glomerulus. In conclusion, we confirmed that infiltrating IgG4+ PCs > 10/hpf and/or IgG4/IgG (CD138)+ PCs > 40% was appropriate as an item of the diagnostic criteria for IgG4-RKD. A relatively high frequency of diverse glomerular lesions with immunoglobulin or complement deposits and deposits in TBM may be evidence of immune complex involvement in IgG4-related disease. Mitsuhiro Kawano, Ichiro Mizushima, Yutaka Yamaguchi, Naofumi Imai, Hitoshi Nakashima, Shinichi Nishi, Satoshi Hisano, Nobuaki Yamanaka, Motohisa Yamamoto, Hiroki Takahashi, Hisanori Umehara, Takao Saito, and Takako Saeki Copyright © 2012 Mitsuhiro Kawano et al. All rights reserved. Tue, 31 Jul 2012 12:45:51 +0000 http://www.hindawi.com/journals/ijr/2012/358371/ The number of patients with autoimmune pancreatitis who visited hospitals in Japan in 2007 was approximately 2709 (95% confidence interval; range 2540–3040). Because IgG4-related disease is a new clinical entity, there are no data with regard to its prevalence. To estimate the number of patients with IgG4-related disease in Japan, we randomly selected hospitals using stratification and asked them how many patients they had with IgG4-related disease in 2009. The number of patients with Mikulicz’s disease, IgG4-related retroperitoneal fibrosis, IgG4-related renal disease, IgG4-related pulmonary disease, and IgG4-related lymphadenopathy who visited hospitals in Japan in 2009 was approximately 4304 (95% confidence interval; range 3360–5048), 272 (95% confidence interval; range 264–306), 57 (95% confidence interval; range 47–66), 354 (95% confidence interval; range 283–424), and 203 (95% confidence interval; range 187–240), respectively. The total number of patients with IgG4-related disease without autoimmune pancreatitis in Japan was approximately 5190 (95% confidence interval; range 4141–6084). The male : female ratio was 1 : 0.77, and the average of age of disease onset was 58.8 years. The total number of patients with IgG4-related disease in Japan in 2009, including autoimmune pancreatitis, was approximately 8000. Kazushige Uchida, Atsushi Masamune, Tooru Shimosegawa, and Kazuichi Okazaki Copyright © 2012 Kazushige Uchida et al. All rights reserved. Tue, 17 Jul 2012 08:19:05 +0000 http://www.hindawi.com/journals/ijr/2012/584193/ Purpose. To investigate the association of cumulative lifetime knee joint force on the risk of self-reported medically-diagnosed knee osteoarthritis (OA). Methods. Exposure data on lifetime physical activity type (occupational, household, sport/recreation) and dose (frequency, intensity, duration) were collected from 4,269 Canadian men and women as part of the Physical Activity and Joint Heath cohort study. Subjects were ranked in terms of the “cumulative peak force index”, a measure of lifetime mechanical knee force. Multivariable logistic regression was conducted to obtain adjusted effects for mean lifetime knee force on the risk of knee OA. Results. High levels of total lifetime, occupational and household-related force were associated with an increased in risk of OA, with odds ratio’s ranging from approximately 1.3 to 2. Joint injury, high BMI and older age were related to risk of knee OA, consistent with previous studies. Conclusions. A newly developed measure of lifetime mechanical knee force from physical activity was employed to estimate the risk of self-reported, medically-diagnosed knee OA. While there are limitations, this paper suggests that high levels of total lifetime force (all domains combined), and occupational force in men and household force in women were risk factors for knee OA. Charles R. Ratzlaff, Mieke Koehoorn, Jolanda Cibere, and Jacek A. Kopec Copyright © 2012 Charles R. Ratzlaff et al. All rights reserved. Thu, 12 Jul 2012 08:18:01 +0000 http://www.hindawi.com/journals/ijr/2012/940831/ Autoimmune pancreatitis (AIP) was first used to describe cases of pancreatitis with narrowing of the pancreatic duct, enlargement of the pancreas, hyper-γ-globulinaemia, and antinuclear antibody (ANA) positivity serologically. The main differential diagnosis, is pancreatic cancer, which can be ruled out through radiological, serological, and histological investigations. The targets of ANA in patients with autoimmune pancreatitis do not appear to be similar to those found in other rheumatological diseases, as dsDNA, SS-A, and SS-B are not frequently recognized by AIP-related ANA. Other disease-specific autoantibodies, such as, antimitochondrial, antineutrophil cytoplasmic antibodies or diabetes-specific autoantibodies are virtually absent. Further studies have focused on the identification of pancreas-specific autoantigens and reported significant reactivity to lactoferrin, carbonic anhydrase, pancreas secretory trypsin inhibitor, amylase-alpha, heat-shock protein, and plasminogen-binding protein. This paper discusses the findings of these investigations and their relevance to the diagnosis, management, and pathogenesis of autoimmune pancreatitis. Daniel S. Smyk, Eirini I. Rigopoulou, Andreas L. Koutsoumpas, Stephen Kriese, Andrew K. Burroughs, and Dimitrios P. Bogdanos Copyright © 2012 Daniel S. Smyk et al. All rights reserved. Mon, 09 Jul 2012 10:07:04 +0000 http://www.hindawi.com/journals/ijr/2012/978396/ Methotrexate (MTX) is the most commonly used disease-modifying antirheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA). However, despite its efficacy and affordability, additional DMARDs or biologic agents are often required in order to achieve the recommended goals of low disease activity or remission. Although well tolerated by most, some patients develop important side effects such as cytopenias, gastrointestinal adverse events (stomatitis, nausea), or abnormal liver function tests, which may limit its use and may result in additional health care costs. Given the clinical implications of widespread use of MTX in RA, various studies have evaluated the role of potential biomarkers in predicting treatment effectiveness of MTX. These biomarkers include RBC MTX polyglutamate (PG) levels; genetic variation in genes from relevant biological and metabolic pathways; gene expression profiles; serum proteins. This paper provides an update on the current data regarding biomarkers of treatment response to MTX. Karina I. Halilova, Elizabeth E. Brown, Sarah L. Morgan, S. Louis Bridges Jr., Min-Ho Hwang, Donna K. Arnett, and Maria I. Danila Copyright © 2012 Karina I. Halilova et al. All rights reserved. Mon, 11 Jun 2012 10:40:58 +0000 http://www.hindawi.com/journals/ijr/2012/843970/ Objective. To determine the risk of intra- and periarticular cyst-like lesions of the knee joint in occupational kneeling. Methods. Magnetic resonance imaging of both knees (𝑛=282) was conducted in 92 male floor layers and 49 male graphic designers (referents), with a mean age of 55.6 years (range 42–70 years). The prevalence of cyst-like lesions was computed among floor layers and graphic designers, respectively, and associations with occupation summarized by odds ratio (OR) with 95% confidence intervals (CIs). Using logistic regression, models were adjusted for age, body mass index, knee injuries, and knee-straining sports. Results. Floor layers had a significantly higher prevalence of cyst-like lesions in the posterior part of the knee joint compared to graphic designers (OR 2.70, 95% CI 1.50–4.84). Floor layers also had a higher prevalence of fluid collections in the popliteus tendon recess (OR 2.17, 95% CI 0.99–4.77) and large cystic lesions of the popliteus muscle (OR 3.83, 95% CI 0.78–18.89). The prevalence of cystic lesions in the anterior part of the knee joint was low among floor layers (8.7%) and there was no significant difference between the two trade groups (𝑃=0.34). Conclusions. Occupational kneeling increases the risk of cyst-like lesions in the posterior part of the knee joint. Søren Rytter, Lilli Kirkeskov Jensen, Jens Peter Bonde, and Niels Egund Copyright © 2012 Søren Rytter et al. All rights reserved. Sun, 10 Jun 2012 14:17:43 +0000 http://www.hindawi.com/journals/ijr/2012/572539/ Lymphadenopathy is frequently observed in patients with immunoglobulin G4-related disease (IgG4-RD) and sometimes appears as the first manifestation of the disease. The diagnosis of IgG4-related lymphadenopathy is complicated owing to a great histological diversity, with at least 5 histological subtypes. Indeed, lymph node biopsy may be performed under the suspicion that the lymphadenopathy is a malignant lymphoma or other lymphoproliferative disorder. The diagnosis of IgG4-RD is characterized by both elevated serum IgG4 (>135 mg/dL) and histopathological features, including a dense lymphoplasmacytic infiltrate rich in IgG4+ plasma cells (IgG4+/IgG+ plasma cell ratio >40%). However, patients with hyper-interleukin (IL-) 6 syndromes such as multicentric Castleman’s disease, rheumatoid arthritis, and other immune-mediated conditions frequently show lymph node involvement and often fulfill the diagnostic criteria for IgG4-RD. Owing to these factors, IgG4-RD cannot be differentiated from hyper-IL-6 syndromes on the basis of histological findings alone. Laboratory analyses are crucial to differentiate between the 2 diseases. Hyper-IL-6 syndromes are characterized by elevated serum levels of IgG, IgA, IgM, and C-reactive protein (CRP); thrombocytosis; anemia; hypoalbuminemia; hypocholesterolemia. In contrast, IgG4-RD does not share any of these characteristics. Therefore, the diagnosis of IgG4-RD requires not only pathological findings but also clinical and laboratory analyses. Yasuharu Sato and Tadashi Yoshino Copyright © 2012 Yasuharu Sato and Tadashi Yoshino. All rights reserved. Mon, 04 Jun 2012 14:23:46 +0000 http://www.hindawi.com/journals/ijr/2012/718237/ Systemic lupus erythematosus (SLE) is a chronic, systemic, and autoimmune disease, whose etiology is still unknown. Although there has been progress in the treatment of SLE through the use of glucocorticoid and immunosuppressive drugs, these drugs have limited efficacy and pose significant risks of toxicity. Moreover, prognosis of patients with SLE has remained difficult to assess. TRIM21/Ro52/SS-A1, a 52-kDa protein, is an autoantigen recognized by antibodies in sera of patients with SLE and Sjögren's syndrome (SS), another systemic autoimmune disease, and anti-TRIM21 antibodies have been used as a diagnostic marker for decades. TRIM21 belongs to the tripartite motif-containing (TRIM) super family, which has been found to play important roles in innate and acquired immunity. Recently, TRIM21 has been shown to be involved in both physiological immune responses and pathological autoimmune processes. For example, TRIM21 ubiquitylates proteins of the interferon-regulatory factor (IRF) family and regulates type I interferon and proinflammatory cytokines. In this paper, we summarize molecular features of TRIM21 revealed so far and discuss its potential as an attractive therapeutic target for SLE. Ryusuke Yoshimi, Yoshiaki Ishigatsubo, and Keiko Ozato Copyright © 2012 Ryusuke Yoshimi et al. All rights reserved. Mon, 04 Jun 2012 10:14:07 +0000 http://www.hindawi.com/journals/ijr/2012/789164/ Patients with autoimmune pancreatitis have a striking polyclonal elevation of total IgG4 in serum. This observation has been confirmed and extended to other fibrotic conditions (that are therefore called IgG4-related disease) but as yet remains unexplained. The affected tissue contains many IgG4-producing plasma cells embedded in a fibrotic matrix originating from activated mesenchymal (stellate) cells. We propose that the process results from an unusual interaction between two regulatory systems: the regulatory arm of the immune system (including Bregs) and the tissue repair regulatory components orchestrated by the activated stellate cell. This interaction results in ongoing mutual activation, generating TGFbeta, IL10, and vitamin D. This environment suppresses most immune reactions but stimulates the development of IgG4-producing plasma cells. Laura C. Lighaam, Rob C. Aalberse, and Theo Rispens Copyright © 2012 Laura C. Lighaam et al. All rights reserved. Wed, 30 May 2012 18:47:35 +0000 http://www.hindawi.com/journals/ijr/2012/167096/ Behçet’s disease (BD) is an immune-mediated systemic vasculitis associated with HLAB51. Other gene associations are likely and may provide further insight into the pathogenesis of this disease. Fc-gamma receptors play an important role in regulating immune function. Copy number variation (CNV) of the Fc-gamma receptor 3B (FCGR3B) gene is associated with other inflammatory conditions and may also play a role in BD. The aim of this study was to determine whether CNV of the FCGR3B gene is associated with BD or its clinical features. FCGR3B copy number was determined for 187 Iranian patients and 178 ethnicity-matched controls using quantitative real-time PCR. The genotype frequencies were comparable in both BD patients and controls. The odds ratio for low copy number (<2CN) was 0.6 (𝑃=0.16) and the odds ratio for high copy number (>2CN) was 0.75 (𝑃=0.50). There was no association found between high or low CN of the FCGR3B gene and BD or its clinical features in this Iranian population. We are the first to report this finding which, when looked at in the context of other genetic studies, gives us further insight into the complex pathogenesis of BD. Rachel Black, Sue Lester, Emma Dunstan, Farhad Shahram, Abdolhadi Nadji, Noushin Bayat, Kayvan Saeedfar, Naghmeh Ziaei, Catherine Hill, Maureen Rischmueller, and Fereydoun Davatchi Copyright © 2012 Rachel Black et al. All rights reserved. Tue, 29 May 2012 16:07:36 +0000 http://www.hindawi.com/journals/ijr/2012/357071/ Recent studies suggest simultaneous or metachronous lesions in multiorgans characterized by elevated serum levels of IgG4 and abundant infiltration of IgG4-positive plasma cells with various degrees of fibrosis. Two Japanese research committees for IgG4-RD, one from fibrosclerosis (Okazaki team) and the other from lymph proliferation (Umehara team) supported by the “Research Program for Intractable Disease” of the Ministry of Health, Labor, and Welfare of Japan, have agreed with the unified nomenclature as “IgG4-RD” and proposed the comprehensive diagnostic criteria (CDC) for IgG4-RD. Validation of the CDC demonstrated satisfactory sensitivity for the practical use of general physicians and nonspecialists but low sensitivity in the organs to be difficult in taking biopsy specimens such as type1 autoimmune pancreatitis (IgG4-related AIP), compared with IgG4-related sialadenitis/dacryoadenitis (Mikulicz's disease) and IgG4-related kidney disease. Although the diagnostic criteria covering all IgG4-RD are hard to be established, combination with the CDC and organ-specific diagnostic criteria should improve sensitivity. Kazuichi Okazaki and Hisanori Umehara Copyright © 2012 Kazuichi Okazaki and Hisanori Umehara. All rights reserved. Sun, 27 May 2012 15:45:00 +0000 http://www.hindawi.com/journals/ijr/2012/232960/ IgG4-related disease (IgG4-RD) is a recently described systemic fibroinflammatory disease associated with elevated circulating levels of IgG4 and manifests a wide spectrum of clinical presentations. Although serum IgG4 level has been described to be the most sensitive and specific laboratory test for the diagnosis of IgG4-RD, it is recognized that an elevated serum IgG4 level can be encountered in other diseases. In this study, we sought to identify the frequency of IgG4-RD and other disease associations in patients with elevated serum IgG4 levels seen in clinical practice. Among 3,300 patients who underwent IgG subclass testing over a 2-year period from January 2009 to December 2010, 158 (4.8%) had an elevated serum IgG4 level (>140 mg/dL). IgG4 subclass testing was performed for evaluation of suspected IgG4-RD or immunodeficiency. Twenty-nine patients (18.4%) had definite or possible IgG4-RD. Among those patients without IgG4-RD, a broad spectrum of biliary tract, pancreatic, liver, and lung diseases, as well as systemic vasculitis, was diagnosed. We conclude that patients with elevated serum IgG4 levels encountered in clinical practice manifest a wide array of disorders, and only a small minority of them has IgG4-RD. Jay H. Ryu, Ryohei Horie, Hiroshi Sekiguchi, Tobias Peikert, and Eunhee S. Yi Copyright © 2012 Jay H. Ryu et al. All rights reserved. Mon, 21 May 2012 09:17:18 +0000 http://www.hindawi.com/journals/ijr/2012/310206/ Chronic nonbacterial osteomyelitis (CNO) with its most severe form chronic recurrent multifocal osteomyelitis (CRMO) is a non-bacterial osteitis of yet unknown origin. Secondary to the absence of both high-titer autoantibodies and autoreactive T lymphocytes, and the association with other autoimmune diseases, it was recently reclassified as an autoinflammatory disorder of the musculoskeletal system. Since its etiology is largely unknown, the diagnosis is based on clinical criteria, and treatment is empiric and not always successful. In this paper, we summarize recent advances in the understanding of possible etiopathogenetic mechanisms in CNO. Sigrun R. Hofmann, Angela Roesen-Wolff, Gabriele Hahn, and Christian M. Hedrich Copyright © 2012 Sigrun R. Hofmann et al. All rights reserved.