Search

Guidelines and recommendations developed and/or endorsed by the American College of Rheumatology (ACR) are intended to provide general guidance for commonly encountered clinical scenarios. The recommendations do not dictate the care for an individual patient. The ACR considers adherence to the recommendations described in this guideline to be voluntary, with the ultimate determination regarding their application to be made by the clinicians in light of each patient’s individual circumstances. Guidelines and recommendations are intended to promote beneficial or desirable outcomes but cannot guarantee any specific outcome. Guidelines and recommendations developed and endorsed by the ACR are subject to periodic revision as warranted by the evolution of medical knowledge, technology, and practice. ACR recommendations are not intended to dictate payment or insurance decisions, or drug formularies or other third-party analyses. Third parties that cite ACR guidelines should state that these recommendations are not meant for this purpose. These recommendations cannot adequately convey all uncertainties and nuances of patient care. The American College of Rheumatology is an independent, professional, medical and scientific society that does not guarantee, warrant, or endorse any commercial product or service. OBJECTIVE. To develop updated guidelines for the pharmacologic management of rheumatoid arthritis. METHODS. We developed clinically relevant population, intervention, comparator, and outcomes (PICO) questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to rate the certainty of evidence. A voting panel comprising clinicians and patients achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS. The guideline addresses treatment with disease-modifying antirheumatic drugs (DMARDs), including conventional synthetic DMARDs, biologic DMARDs, and targeted synthetic DMARDs, use of glucocorticoids, and use of DMARDs in certain high-risk populations (i.e., those with liver disease, heart failure, lymphoproliferative disorders, previous serious infections, and nontuberculous mycobacterial lung disease). The guideline includes 44 recommendations (7 strong and 37 conditional). CONCLUSION. This clinical practice guideline is intended to serve as a tool to support clinician and patient decision-making. Recommendations are not prescriptive, and individual treatment decisions should be made through a shared decision-making process based on patients’ values, goals, preferences, and comorbidities.

BackgroundSystemic inflammation in rheumatoid arthritis (RA) is associated with metabolic changes. We used nuclear magnetic resonance (NMR) spectroscopy–based metabolomics to assess the relationship between an objective measure of systemic inflammation [C-reactive protein (CRP)] and both the serum and urinary metabolome in patients with newly presenting RA.MethodsSerum (n=126) and urine (n=83) samples were collected at initial presentation from disease modifying anti-rheumatic drug naïve RA patients for metabolomic profile assessment using 1-dimensional 1H-NMR spectroscopy. Metabolomics data were analysed using partial least square regression (PLS-R) and orthogonal projections to latent structure discriminant analysis (OPLS-DA) with cross validation.ResultsUsing PLS-R analysis, a relationship between the level of inflammation, as assessed by CRP, and the serum (p=0.001) and urinary (pConclusionsThis study consolidates our understanding of a previously identified relationship between serum metabolite profile and inflammation and provides novel evidence that there is a relationship between urinary metabolite profile and inflammation as measured by CRP. Identification of these metabolic perturbations provides insights into the pathogenesis of RA and may help in the identification of therapeutic targets.

To evaluate the perceptions of patients with rheumatoid arthritis (RA) about self-assessment of their disease activity after watching an educational video. Consecutive patients with RA consulting their rheumatologist in six Middle Eastern Countries were invited to watch an educational video developed to teach self-assessment using Disease Activity Score (DAS-28). Then, a rheumatology nurse conducted a semi-structured interview and collected the patients’ perception about the understanding of the video, feasibility, capability and confidence in performing self-assessment using Likert-type items. The degree of confidence with self-assessment was correlated to the patients’ socio-demographic characteristics. Sixty-two patients were included and had an overall positive reaction to the video. It was easy to understand in 96% and helped facilitate self-assessment in 92% of cases. Self-assessment was considered totally feasible in 74%, and 66% of patients were capable of always doing it, with a confidence of 60% (always) to 34% (sometimes). Confidence was associated with a higher educational level. Nevertheless, 77% of patients felt that the self-assessment would not fully replace the physician’s visit. Open-ended questions identified five themes: better understanding of the disease, easier communication with the rheumatologist, less consultation time, difficulty with the scoring part and importance of practice. Patients with RA felt that self-assessment was feasible and helpful in understanding RA, improving communication with the rheumatologist and shortening the visit time. Supplementary Information The online version contains supplementary material available at 10.1007/s00296-021-04799-2.

Background:Managing patients with chronic rheumatic diseases is increasingly relying on the collaboration of a multidisciplinary team, including the rheumatology nurse who can aid assessment of disease activity among other healthcare tasks.However, this practice, although common in Europe and North America, is still poorly implemented in the Middle eastern Arab countries (MEAC).Objectives:To evaluate the concordance between the physician’s and the nurse’s assessment of disease activity in patients with rheumatoid arthritis (RA) in the MEAC.Methods:During a routine patient visit to one of 9 rheumatology clinics located in 7 Middle Eastern Arab countries, the physician and the rheumatology nurse (who was already working in the clinic) performed the disease activity score 28 (DAS), Clinical Disease Activity Index (CDAI) and Simple Disease Activity Index (SDAI) in a blinded manner. The concordance regarding the 3 continuous scores was calculated using paired t-test. The agreement between physician- and nurse-DAS categories (remission, low, moderate and high disease activity) was calculated using weighted kappa for category comparison. Predictive factors of positive concordance between physician- and nurse-DAS were identified using binary logistic regression.Results:The study included 373 patients’ measurements over a period of two years (2018 to 2019). The mean age of the patients was 49.6 years (±28.2), 82.6% were females, and the mean disease duration was 11.3 years (±7.5).The mean physician-DAS was slightly higher (3.97 (±1.52)) than the nurse-DAS (3.90 (±1.54)) (p=0.002), with a mean difference of +0.08 [95%CI 0.03; 0.12] (Table 1). The difference in the DAS individual items, the CDAI and the SDAI were not statistically significant.Table 1.Comparison of the disease activity measures reported by the physician and by the nurse.PhysicianNursep-valueTotal Joint Count4.87 (2.26)5.02 (6.20)0.152Swollen Joint Count2.13 (3.88)2.15 (3.83)0.790Global Assessment3.30 (2.41)3.32 (2.43)0.702DAS-283.97 (1.52)3.90 (1.54)0.002CDAI14.26 (12.53)14.38 (12.59)0.515SDAI21.51 (23.57)21.61 (21.66)0.527When analyzing DAS as a categorical 4-items variable, the agreement between the physician and the nurse was present in 79.36% of the cases (weighted kappa was 0.77 [95%CI 0.73;0.83] which is considered as excellent, and was higher in patients with high disease activity (Figure 1).A positive concordance between the physician- and the nurse-DAS was associated with the country (higher in Egypt, pConclusion:The agreement between the DAS-28 performed by the physician and by the nurse was excellent and was associated with the country and a higher disease activity. The present study confirms that the support of a trained nurse for evaluating disease activity in RA is feasible in the Arab countries and may save some valuable time in the clinic, whilst maintaining the quality of care for patients with RA.Figure 1.Agreement between physician- and nurse-DAS categoriesAcknowledgements:The authors would like to acknowledge the patients for participating in the study and the assistants/ students/ nurses who assisted in the data collection: Dr. Fatima Abdul Majeed Al Hawaj, M. Atef Ahmed, M. Mohammad Alhusamiah, Ms Raquel De Guzman, Ms Lina Razzouk.Disclosure of Interests:None declared

Background:Involving the patients with rheumatoid arthritis (RA) in the assessment of their disease may increase their adherence to treatment, improve the disease outcomes and facilitate the application of telehealth. We previously reported an excellent concordance between the Disease Activity Score (DAS-28) performed by physicians and patients at the baseline visit of this prospective study (1).Objectives:To evaluate the persistence of the concordance between the physician’ and the patient’s assessment of disease activity in RA using DAS-28 after one year.Methods:At the baseline visit, patients with RA from 7 Middle Eastern Arab Countries (MEAC) were briefed about DAS-28 by their rheumatologist during a routine consultation and given smartphone access to a video in Arabic language explaining the performance of DAS-28. At 3, 6 and 12 months (± 3 months), the patients were asked to self-report DAS-28, blinded to the physician’s assessment. Concordance between the continuous DAS-28 at each visit was calculated using paired t-test numerically and the Bland-Altman method graphically. Agreement between physician- and patient-DAS categories (remission, low-, moderate- and high disease activity) was calculated at each visit using weighted kappa for category comparison. Weighted kappa of the different agreements were compared over time using their respective confidence intervals (CIs). Predictive factors of positive concordance between physician and patient-DAS were identified using binary logistic regression.Results:The study included 428 patients over a period of three years (2018 to 2020). The mean age of participants was 49.8 years, 82.5% were females, 44.3% had a university degree and the mean disease duration was 11.4 years.At baseline, the average patient-DAS was higher (4.06 (±1.52)) than the physician-DAS (3.97 (±1.52)). The mean difference was -0.09 [95%CI -0.14; -0.04] and most of the pairs were within the limit of agreement in the Bland-Altman graph, indicating a good concordance, particularly in cases of remission.During the study follow-up, 299 patients consulted for visit 2 (69.9% of the total population), 232 for visit 3 (54.2%) and 199 for visit 4 (46.5%). The weighted kappa was 0.80 [95%CI 0.76;0.85] at visit 1 and 0.79 [95%CI 0.72;0.88] at visit 4 (Figure 1 showing kappa for DAS-28, CDAI and SDAI as well). A minor numerical decrease in kappa was observed over time; however, the CIs were overlapping over the four visits and the agreement was considered stable, remaining in the excellent range. At visit 4, a positive concordance between the physician- and the patient-DAS was associated with the profession (lower in blue collar, p=0.001), the educational level (higher in high school and university, p=0.034) and the baseline physician’s DAS (higher in high disease activity, p=0.46).Conclusion:The agreement between the DAS-28 performed by the physician and by the patient was excellent at baseline and remained stable over one year. A positive concordance was associated with the profession, the educational level and the level of disease activity. The present study can help the rheumatologist make informed decisions about the patients who may be suitable for a remote evaluation of their disease activity, that can be of particular interest in the context of the COVID-19 pandemic.References:[1]Ziade N, Saad S, al Mashaleh M, et al. Perceptions of Patients with Rheumatoid Arthritis about Self-Assessment of Disease Activity after Watching an Educational Video: Qualitative Pilot Results from the Auto-DAS in Middle Eastern Arab Countries Study [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10).Acknowledgements:The authors would like to acknowledge the patients for participating in the study and the assistants/ students/ nurses who assisted in the data collection: Dr. Fatima Abdul Majeed Al Hawaj, M. Atef Ahmed, M. Mohammad Alhusamiah, Ms Raquel De Guzman, Ms Lina Razzouk.Disclosure of Interests:None declared

Recent metabolomics studies of Rheumatoid Arthritis (RA) reported few metabolites that were associated with the disease, either due to small cohort sizes or limited coverage of metabolic pathways. Our objective is to identify metabolites associated with RA and its cofounders using a new untargeted metabolomics platform. Moreover, to investigate the pathomechanism of RA by identifying correlations between RA-associated metabolites. 132 RA patients and 104 controls were analyzed for 927 metabolites. Metabolites were tested for association with RA using linear regression. OPLS-DA was used to discriminate RA patients from controls. Gaussian Graphical Models (GGMs) were used to identify correlated metabolites. 32 metabolites are identified as significantly (Bonferroni) associated with RA, including the previously reported metabolites as DHEAS, cortisol and androstenedione and extending that to a larger set of metabolites in the steroid pathway. RA classification using metabolic profiles shows a sensitivity of 91% and specificity of 88%. Steroid levels show variation among the RA patients according to the corticosteroid treatment; lowest in those taking the treatment at the time of the study, higher in those who never took the treatment, and highest in those who took it in the past. Finally, the GGM reflects metabolite relations from the steroidogenesis pathway.

Objective Genetic factors underlying susceptibility to rheumatoid arthritis (RA) in Arab populations are largely unknown. This genome-wide association study (GWAS) was undertaken to explore the generalizability of previously reported RA loci to Arab subjects and to discover new Arab-specific genetic loci. Methods The Genetics of Rheumatoid Arthritis in Some Arab States Study was designed to examine the genetics and clinical features of RA patients from Jordan, the Kingdom of Saudi Arabia, Lebanon, Qatar, and the United Arab Emirates. In total, >7 million single-nucleotide polymorphisms (SNPs) were tested for association with RA overall and with seropositive or seronegative RA in 511 RA cases and 352 healthy controls. In addition, replication of 15 signals was attempted in 283 RA cases and 221 healthy controls. A genetic risk score of 68 known RA SNPs was also examined in this study population. Results Three loci (HLA region, intergenic 5q13, and 17p13 at SMTNL2/GGT6) reached genome-wide significance in the analyses of association with RA and with seropositive RA, and for all 3 loci, evidence of independent replication was demonstrated. Consistent with the findings in European and East Asian populations, the association of RA with HLA–DRB1 amino acid position 11 conferred the strongest effect (P = 4.8 × 10−16), and a weighted genetic risk score of previously associated RA loci was found to be associated with RA (P = 3.41 × 10−5) and with seropositive RA (P = 1.48 × 10−6) in this population. In addition, 2 novel associations specific to Arab populations were found at the 5q13 and 17p13 loci. Conclusion This first RA GWAS in Arab populations confirms that established HLA-region and known RA risk alleles contribute strongly to the risk and severity of disease in some Arab groups, suggesting that the genetic architecture of RA is similar across ethnic groups. Moreover, this study identified 2 novel RA risk loci in Arabs, offering further population-specific insights into the pathophysiology of RA.

Background: Involving patients with rheumatoid arthritis (RA) in the assessment of their disease may increase adherence to treatment, improve disease outcomes and reduce consultation time. Objectives: To evaluate the concordance between physician and patient assessment of disease activity in RA using Disease Activity Score (DAS-28). Methods: During the routine consultation, patients were briefed about DAS-28 by their rheumatologist. Using a standard DAS-28 mannequin, physicians, patients and nurses reported the number of tender and swollen joint, inflammatory markers and global health on a 0-10 Likert scale. DAS-28, Clinical Disease Activity Index (CDAI) and Simple Disease Activity Index (SDAI) were calculated blindly by each participant. Agreement between physician- and patient-DAS categories was calculated using weighted kappa (WK) for category comparison. Concordance between physician- and patient-DAS was estimated using the Bland-Altman method. Predictive factors of positive concordance between physician and patient-DAS were identified using logistic regression. Results: Four hundred and twenty patients from 7 Middle-Eastern countries were included, with a mean age of 49 years (SD 12), 84% of females, disease duration of 11 years (SD 8). Mean physician-DAS-28 was 4.03 (SD 1.51). 65% had positive rheumatoid factor, 56% had positive ACPA, 30% had erosive disease and 34% were on biotherapy. Agreement between physician- and patient-DAS categories was 89%, WK was 0.84. WK were 0.80 for DAS physician-nurse, 0.79 for DAS patient-nurse, 0.83 for CDAI physician-patient and 0.88 for SDAI physician-patient agreements respectively. All activity measures were higher in patients compared to physicians, except for the swollen joints count. The mean difference between physician- and patient-DAS was -0.09 [95% CI -0.14; -0.04] and was smaller in patients in remission (Figure 1: Bland Altman plot). Concordance was statistically associated with CRP and patient SDAI. Conclusion: Concordance between patient and physician assessment of disease activity in RA was excellent and was higher using SDAI followed closely by DAS-28 and CDAI. Self-assessment of disease activity should be decided according to the physician’s clinical judgment. References: [1] Gossec L, et al. Arthritis Rheumatol 2016; 68 (suppl 10). [2] Smolen J, et al. Arthritis Research & Therapy (2016) 18:114. [3] Studenic Pet al. Arthritis Rheumatol. 2012;64(9):2814–23. The physician-patient DAS-mean is plotted on the X-axis. The physician-patient DAS-difference is plotted on the Y-Axis. The horizontal black line corresponds to the mean DAS difference (-0.09 [95% CI -0.14; -0.04]). The horizontal blue lines correspond to +/-1.96 SD. The vertical red line corresponds to the DAS-28 cut-off for remission (2.6). Disclosure of Interests: None declared

Clinical practice guidelines can assist rheumatologists in the proper prescription of newer treatment for rheumatoid arthritis (RA). The objective of this paper is to report on the recommendations for the management of patients with RA in the Eastern Mediterranean region. We adapted the 2015 American College of Rheumatology guidelines in two separate waves. We used the adolopment methodology, and followed the 18 steps of the “Guidelines 2.0” comprehensive checklist for guideline development. For each question, we updated the original guidelines’ evidence synthesis, and we developed an Evidence Profile (EP) and an Evidence to Decision (EtD) table. In the first wave, we adoloped eight out of the 15 original questions on early RA. The strength changed for five of these recommendations from strong to conditional, due to one or more of the following factors: cost, impact on health equities, the balance of benefits, and harms and acceptability. In the second wave, we adoloped eight out of the original 44 questions on established RA. The strength changed for two of these recommendations from strong to conditional, in both cases due to cost, impact on health equities, balance of benefits and harms, and acceptability. The panel also developed a good practice recommendation. We successfully adoloped 16 recommendations for the management of early and established RA in the Eastern Mediterranean region. The process proved feasible and sensitive to contextual factors.

This study aims at identifying metabolites that significantly associate with self-reported joint symptoms (diagnostic) and metabolites that can predict the change from a symptom-free status to the development of self-reported joint symptoms after a 7 years period (prognostic). More than 300 metabolites were analyzed for 2246 subjects from the longitudinal study of the KORA (Cooperative Health Research in the Region of Augsburg, Germany), specifically the fourth survey S4 and its 7-year follow-up study F4. Two types of self-reported symptoms, chronic joint inflammation and worn out joints, were used for the analyses. Diagnostic analysis identified dysregulated metabolites in cases with symptoms compared with controls. Prognostic analysis identified metabolites that differentiate subjects in S4 who remained symptom-free after 7 years (F4) from those who developed any combination of symptoms. 48 metabolites were identified as nominally significantly (p0.05) associated with the self-reported symptoms in the diagnostic analysis, among which steroids show Bonferroni significance. 45 metabolites were identified as nominally significantly associated with developing symptoms after 7 years, among which hippurate showed Bonferroni significance. We show that metabolic profiles of self-reported joint symptoms are in line with metabolites known to associate with various forms of arthritis and suggest that future studies may benefit from that by investigating the possible use of self-reporting/questionnaire along with metabolic markers for the early referral of patients for further diagnostic workup and treatment of arthritis.

Background Using a treatment target in rheumatoid arthritis (RA), such as DAS-28 and involving patients in their disease management can improve prognosis. Objectives To develop and implement an educational video that instructs patients with RA for self-assessment of disease activity using DAS-28. Methods Step 1:Initiation. Rheumatologists from some Middle Eastern Arab countries were invited to participate in this study. International experts and societies were contacted to access pre-existing educational material. Step 2: Development. Different material sources were synthetized and translated into Arabic and validated by the rheumatologists. The educational video was shot by a professional team with a real patient and a rheumatologist on set. Step 3. Validation. The final products (leaflets and video) were validated by the rheumatologists and tested with patients (figure 1). Obstacles were noted at the various study levels. Results 23 rheumatologists from 7 Middle Eastern Arab countries participated in the study. A one-page educational leaflet was developed in Arabic and English languages. An educational video presenting the treat-to-target concept and the basics of DAS performance was produced in Arabic language with English subtitles. Obstacles at the rheumatologist, patient, cultural and logistic levels were identified and the potential solutions were addressed by the study team. Conclusions Collaboration between several countries sharing the same language and similar cultural backgrounds was possible and able to produce an educational video aiming at the empowerment of RA patients for the self-assessment of their disease activity. The video will serve for future studies in the Arabic-speaking countries and will be available later for clinical use according to the rheumatologist’s clinical judgment. References [1] Smolenet al. Ann Rheum Dis2015;0:1–13. [2] Gossec, et al. Arthritis Rheumatol2016;68(suppl 10). [3] Studenic, et al. 2012;64(9):2814–23. www.nras.org.uk and www.das-score.nl Acknowledgements Professor Maxime Dougados, Paris. Disclosure of Interest None declared

There is limited information on the epidemiology and treatment patterns of rheumatoid arthritis (RA) across the Arab region. We aim in this study to describe the demographic characteristics, clinical profile, and treatment patterns of patients of Arab ancestry with RA.This is a cross sectional study of 895 patients with established rheumatoid arthritis enrolled from five sites (Jordan, Lebanon, Qatar, Kingdom of Saudi Arabia (KSA), and United Arab Emirates). Demographic characteristics, clinical profile, and treatment patterns are compared between the five countries.The majority of our patients are women, have an average disease duration of 10 years, are married and non-smokers, with completed secondary education. We report a high (80%) ever-use of methotrexate (MTX) and steroids among our RA population, while the ever-use of disease modifying anti-rheumatic drugs (DMARDs) and TNF-inhibitors average around 67% and 33%, respectively. There are variations in RA treatment use between the five country sites. Highest utilization of steroids is identified in Jordan and KSA (p-value0.001), while the highest ever-use of TNF-inhibitors is reported in KSA (p-value0.001).Disparities in usage of RA treatments among Arab patients are noted across the five countries. National gross domestic product (GDP), as well as some other unique features in each country likely affect these. Developing treatment guidelines specific to this region could contribute in delivering standardized therapies to RA patients.

A panel of experts commissioned by the American College of Rheumatology have recently reviewed the literature related to the treatment of patients with ankylosing spondylitis and nonradiographic axial spondyloarthritis. They published a set of recommendations for the management of common clinical questions for both active and stable disease, including the appropriate use of nonsteroidal anti-inflammatory drugs, tumor necrosis factor inhibitors, rehabilitation, education, and preventive care. This article summarizes these recommendations and provides key practical messages for physicians taking care of these patients.

A 48-year-old woman presented with isolated sixth cranial nerve palsy. She subsequently developed systemic lupus erythematosus (SLE) based on clinical and laboratory parameters. Three years later, she presented again with sixth cranial nerve palsy affecting the contralateral eye. Within 2 weeks of steroid initiation, complete recovery occurred. The unusual rare presentation of SLE in the current patient, as well as the pathogenesis and treatment of cranial neuropathy in SLE are discussed. Lupus (2010) 19, 201—205.

Polymyositis and dermatomyositis are autoimmune inflammatory myopathies characterized by muscle weakness and inflammation. Current recommended therapy includes corticosteroids as mainstay treatment in addition to immunosuppressant. We present herein a 25year-old female with dermatomyositis and cardiac involvement resistant to disease modifying anti-rheumatic drugs and anti-tumor necrosis factor-alpha. She was treated with anti-CD20 monoclonal antibody, rituximab. The patient demonstrated a remarkable clinical and laboratory response. B-cell depletion therapy with rituximab may be a viable option in patients with dermatomyositis and heart disease.

Longitudinal myelitis is an uncommon complication of systemic lupus erythematosus (SLE). We describe an unusual case of longitudinal myelitis and ischemic stroke in the presence of homozygous prothrombin G20210A, heterozygous MTHFR 677T mutations and the absence of antiphospholipid antibodies in a young woman with SLE. Lupus (2007) 16, 517—520.

Osteoarthritis is the most common degenerative joint disease and is particularly common in the elderly. Topical nonsteroidal anti-inflammatory drugs (NSAIDs) may represent a rational treatment in this situation because of their favorable side-effect profile. The majority of topical NSAIDs decrease pain and relieve functional disability caused by osteoarthritis over the short term, however, there are insufficient data for their long-term efficacy.

We report a 39-year-old primigravida, a case of systemic lupus erythematosus (SLE) and secondary anti-phospholipid syndrome (APS) with a smooth antenatal course who delivered by caesarean for non-reassuring foetal heart rate. On day 2 postoperatively, she developed a sudden severe colicky upper abdominal pain with tachypnoea, dyspnoea, and tachycardia, and blood pressure (BP) reaching 150/95 mmHg. Computed tomography of the abdomen revealed lesions consistent with liver infarction. She developed haemolytic anaemia, elevated liver enzymes, and low platelets (HELLP syndrome); heparin and methylprednisolone were started. On day 3, BP normalized, respiratory symptoms improved but abdominal symptoms persisted. Methylprednisolone was increased to 80 mg/day on day 8 when she had significant clinical response and was discharged on day 16. This case emphasizes that a morbid clinical course including liver infarction should be anticipated in patients with SLE and APS complicated with HELLP syndrome.

Behçet's disease is a chronic multisystem inflammatory disease characterized by the predominance of Th1 cytokines. The human leukocyte antigen-B 51 gene is associated with the disease in several ethnic groups, but it is not certain whether it is the susceptibility gene or if it is in linkage disequilibrium with other genes. Recent studies of polymorphisms of neighboring, as well as distant, genes to human leukocyte antigen-B 51 are helpful in elucidating the pathogenesis of the disease and could have therapeutic implications.

Background: Transient osteoporosis of the hip (TOH) is a rare clinical disorder of unknown etiology characterized by hip pain and functional disability that resolve spontaneously in 6-24 months. Objectives: To report 2 patients with TOH during pregnancy who had rapid resolution of their illness with the use of calcitonin. To review the literature on TOH with special emphasis on its treatment. Methods: A MEDLINE search of studies published from 1966 to 2002 was performed to review treatment options for TOH and their effect on the natural history of the disease. Results: Our 2 patients developed hip pain during pregnancy with classical changes of TOH on MRI. Both patients received calcitonin, 1 during pregnancy and 1 postpartum with resolution of their symptoms within 6 to 9 weeks. Previous reports in the literature of treatment of TOH showed that antiresorptive agents (bisphosphonates and calcitonin) had shortened the duration of the illness compared with the natural history of the disease. Conclusions: TOH is an under-recognized entity associated with pain and disability. The use of antiresorptive agents may be of help in reducing the duration of the disease. Relevance: To increase the recognition of TOH and to consider therapeutic interventions to shorten the duration of the disease. Semin Arthritis Rheum 32:388-397. © 2003 Elsevier Inc. All rights reserved.

Behçet disease is a chronic inflammatory systemic disorder, characterized by a relapsing and remitting course. It manifests with oral and genital ulcerations, skin lesions, uveitis, and vascular, central nervous system and gastrointestinal involvement. The main histopathological finding is a widespread vasculitis of the arteries and veins of any size. The cause of this disease is presumed to be multifactorial involving infectious triggers, genetic predisposition, and dysregulation of the immune system. As the clinical expression of Behçet disease is heterogeneous, pharmacological therapy is variable and depends largely on the severity of the disease and organ involvement. Treatment of Behçet disease continues to be based largely on anecdotal case reports, case series, and a few randomized clinical trials.

The biological, physical and functional status change was measured in 104 patients with recent (< 1 year) onset synovitis. Measurements were taken initially and at 1 year. The purpose was to determine which biological and physical measures correlated with poor performance. Patients completed questionnaires quantifying activity, (the Human Activity Profile [HAP] and Sickness Impact Profile [SIP]), pain (Wisconsin Brief Pain Inventory), fatigue (Multidimensional Assessment of Fatigue), sleep, and mood (POMS and CESD). They were evaluated for articular involvement (Ritchie Index) and biological markers of disease activity (platelets, sedimentation rate, C-reactive protein and rheumatoid factor) (RF). In all, 30 men and 74 women participated. A total of 45 patients met the American College of Rheumatology criteria for rheumatoid arthritis (RA); of these, 24 were rheumatoid factor (RF) positive, 18 had spondylitis, and 41 had unclassified arthritis. Low activity level at 1 year (HAP and SIP) correlated with high numbers of inflamed joints initially (p < 0.002); with more than 10 involved joints regardless of diagnostic group (p = 0.001); and joint symmetry (p < 0.009) A high platelet count was associated with low activity level at 1 year (p = 0.01); and high sedimentation rate was associated with more pain (p < 0.05). Low activity level (p < 0.04), fatigue (p = 0.03) and sleeplessness (p = 0.02) were correlated with RF+ RA.

Objective The recent identification of antigens or nucleic acids of infectious agents in the joints of patients with reactive arthritis has raised questions about whether chlamydial or other infectious agent nucleic acids are also present in normal joints. We had the opportunity to study synovium from 30 asymptomatic volunteer subjects by use of polymerase chain reaction (PCR) for attempted identification of Chlamydia and other infectious agents. Methods All subjects had blind needle synovial biopsies with the Parker-Pearson needle. DNA was extracted and PCR performed using primers for Chlamydia trachomatis, Chlamydia pneumoniae, Borrelia burgdorferi, and pan bacterial 16S ribosomal RNA (rRNA). Results Two subjects were identified with nucleic acid for the 16S rRNA gene of C trachomatis. All other PCR reactions were negative except for the pan bacterial 16S rRNA in the C trachomatis-positive subjects. Both subjects, although symptom free, had some evidence of synovial reaction. Conclusion C trachomatis appears to occasionally be disseminated to joints without producing overt disease.

Genetically determined differences in interleukin-10 (IL-10) and gamma interferon (IFN-γ) responses in mice correlate with clearance of Chlamydia pneumonitis infection. We measured the synovial expression of IL-10 and IFN-γ and additional cytokine genes in patients who had recent-onset Chlamydia -associated arthritis (Chl-AA). IL-10 and IFN-γ mRNA were relatively abundant in recent-onset Chl-AA.

Rheumatoid arthritis (RA) has been postulated to result from a synovial immune response to an unidentified antigen(s), which should be mirrored by the T cell response. Here we investigate the T cell receptor (TCR) repertoire in the synovial tissue of patients with arthritis of early to moderate duration. We developed a nested polymerase chain reaction (PCR) technique to examine the TCR repertoire of small biopsy specimens, and show that the method is highly sensitive. We apply this technique to synovial biopsies obtained from the knee joints of patients with early to moderate duration arthritis (average duration of arthritis 1 year, range 0.02–2.75 years). We examined biopsies from 5 normal individuals, 32 RA patients, 7 patients with seronegative spondyloarthropathy (Sp), and 12 patients with undifferentiated arthritis (UA). TCR message was detectable in 4/5 normals, 15/32 RA, 5/7 Sp, and 8/11 UA biopsies, with sampling error likely accounting for most negative biopsies. The average numbers of TCR Vβs detected per TCR-positive biopsy were 5.0 ± 3.7 for normals, 12.7 ± 8.4 for RA, 18.0 ± 7.4 for Sp patients, and 14.4 ± 10.2 for UA. Examination of TCR messages by single-stranded conformational polymorphism analysis showed similar proportions of dominant clones in the normals compared with the patients with inflammatory arthritis. Sequence analysis was performed on 33 dominant clones from 16 patients. Sequence alignment of the third hypervariable regions showed some evidence of disease-specific sequence clustering for Sp, while some RA sequences showed similarity to previously described motifs. These data indicate greater TCR heterogeneity in early Sp and UA compared with normal synovium. Disease-specific TCR sequences may occur in early RA and Sp.

Arayssi T, 2005, CLIN EXP RHEUMATOL, V23, P427; Fricker M, 2007, RHEUMATOL INT, V27, P493, DOI 10.1007-s00296-006-0252-y; Josselin L, 2008, ANN RHEUM DIS, V67, P1343, DOI 10.1136-ard.2007.083584; Levine TD, 2005, ARTHRITIS RHEUM, V52, P601, DOI 10.1002-art.20849; Sfikakis PP, 2007, RHEUMATOLOGY, V46, P736, DOI 10.1093-rheumatology-kem034; Touma Z, 2006, SCAND J RHEUMATOL, V35, P323, DOI 10.1080-03009740500484056; Touma Z, 2008, JOINT BONE SPINE, V75, P334, DOI 10.1016-j.jbspin.2007.05.011; UTHMAN I, 2005, CLIN RHEUMATOL, V25, P109; Uthman I, 2007, CLIN RHEUMATOL, V26, P2001, DOI 10.1007-s10067-007-0614-1; Uthman I, 2004, RHEUMATOLOGY, V43, P1198, DOI 10.1093-rheumatology-keh268; Uthman I, 2006, CLIN RHEUMATOL, V25, P540, DOI 10.1007-s10067-005-0029-9; Uthman I, 2004, CLIN RHEUMATOL, V23, P279, DOI 10.1007-s10067-004-0873-z; Uthman I, 2004, SEMIN ARTHRITIS RHEU, V33, P422, DOI 10.1016-j.semarthrit.2003.12.005; Uthman I, 2005, RHEUMATOLOGY, V44, P1200, DOI 10.1093-rheumatology-keh680; Uthman I, 2008, DERMATOLOGY, V216, P257, DOI 10.1159-000112938; Uthman IW, 2005, J AM ACAD DERMATOL, V53, P353, DOI 10.1016-j.jaad.2005.02.009; Wendling D, 2007, REV MED INTERNE, V28, P194, DOI 10.1016-j.revmed.2006.12.001; YAMOUT B, 2007, LUPUS, V100, P1

Sjogren's syndrome (SS) is an autoimmune disorder characterized by lymphocytic infiltration of lacrimal and salivary glands resulting in dry eyes and mouth. Other systemic manifestations include sy...

Disease activity in the rheumatic diseases can be defined as a reversible state, manifested by clinical, laboratory, or radiographical features. Disease activity occurs principally as a result of immunologic and inflammatory processes involving specific organs at a specific point in time. The multifaceted nature of clinical presentations in adults as well as in pediatric rheumatic diseases makes the assessment of disease activity challenging. Nevertheless, this assessment is fundamental in patient care and based on the use of valid, reliable, and interpretable instruments. The use of disease activity instruments enables clinicians, patients, and researchers to quantify and evaluate disease activity in a standardized way. The application of these instruments in a clinical care and research setting presents several challenges: namely, the administrative burden of the instrument, including the preparedness and skillfulness of the assessor, the mode of administration, the time required to complete the instrument, and the complexity of scoring. All of these factors need to be taken into consideration when choosing an instrument applicable in a particular setting. In the last decade, we have witnessed the emergence of a plethora of instruments developed to measure disease activity in the rheumatic diseases. This special issue contains five papers: four related to the assessment of activity in adult rheumatic diseases and one paper with a focus on pediatric rheumatic disease. Wong et al. “Measuring disease activity in psoriatic arthritis” provide a detailed review of the assessment of disease activity in psoriatic arthritis. Their paper highlights the currently available tools for the assessment of the various rheumatologic and dermatologic aspects of the disease and discusses the composite indices that have been developed, or are still under development. Dowsey and Choong “The utility of outcome measures in total knee replacement surgery” discuss the utility of outcome measures for total knee replacement surgery, most commonly performed to treat osteoarthritis. While the majority of patients have a substantial improvement in symptoms following this procedure, a proportion of patients report ongoing pain and poor function. The authors remind us that accurate and reproducible measurement of residual pain and functional impairment in patients undergoing arthroplasty forms an important basis for optimizing outcomes of this procedure. The paper by Dowsey et al. challenges our perception of disease “activity” in the rheumatic diseases and allows us to consider the overlap with the broader concept of “severity,” particularly in osteoarthritis, which does not traditionally follow a relapsing-remitting course. In an original research article, Ohrndorf et al. “Detailed joint region analysis of the 7-joint ultrasound score: evaluation of an arthritis patient cohort over one year” use ultrasound technique, specifically the 7-joint ultrasound (US7) score, to evaluate disease activity and the presence of erosions over one year in a cohort of patients with predominantly rheumatoid and psoriatic arthritis. They demonstrate a high synovitis score at baseline in the majority of patients, which diminishes over one year of treatment, corresponding with a decline in the DAS28 score. The responsiveness over time of ultrasound-based assessment of disease activity in inflammatory arthritis, compared with clinical-laboratory based assessment, and the prognostic significance of mild persistent synovitis detectable on ultrasound are yet to be conclusively demonstrated and quantified. However, the study by Ohrndorf et al. highlights the potential usefulness of imaging modalities in assessment of activity in the rheumatic diseases. Quimby et al. “Comparison of the systemic lupus erythematosus activity questionnaire and the systemic lupus erythematosus disease activity index in a black barbadian population” evaluate the use of the Systemic Lupus Activity Questionnaire (SLAQ), vis-a-vis the internationally accepted and validated Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and the physician global assessment (PGA). They conclude that SLAQ results in over-reporting of symptoms and is an inadequate disease monitoring tool. They underscore the use of laboratory measurements and highlight the need for a modified version that would be valid, feasible, and available to countries most burdened by SLE, yet least equipped to diagnose and manage the disease. Finally, Luca's and Feldman's “Disease activity measures in paediatric rheumatic diseases” provide a comprehensive review of assessment of disease activity in the pediatric population. Their paper explains the theoretical framework required for the development of disease activity measures citing the challenges encountered in this particular patient population. In addition, they summarize the most common disease activity measures used for Juvenile Idiopathic Arthritis (JIA), Juvenile Systemic Lupus Erythematosus (JSLE), and Juvenile Dermatomyositis (JDM) reminding us that more research is needed to determine the most appropriate measures to be used in clinical practice and the research environment. The assessment of disease activity in rheumatic diseases is very challenging but essential. Significant achievements have been made in improving the measurement properties of the instruments. Further research is needed to identify the measurement tools that are of the highest quality and can be conveniently used in clinics and in research studies.

Background and Aims Polymorphisms in the tumor necrosis factor (TNF) gene at the locations −308, −238, −863, −857 and −1031 have been studied in various ethnic groups for possible association with Behcet's disease. The aim of this meta-analysis is to examine the association between polymorphism in the TNF gene at the locations −308, −238, −863, −857 and −1031 and Behcet's disease. Methods A literature review was performed using MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials for original studies published in English up to October 31, 2009 and that examined the association of the TNF-α promoter polymorphisms with Behcet's disease. All pooled odds ratios (OR) were derived from random-effects model with its 95% confidence intervals (CI). We assessed statistical heterogeneity among studies using Cochrane Q test and by calculating I 2 . The Cochrane collaboration's software program, RevMan 5 was used to prepare and complete this review. Results The literature search resulted in 13 studies. Ten studies met the included criteria and thus were selected. Overall, −1031C (OR = 1.35, 95% CI=1.09–1.68), −238A (OR = 1.51, 95% CI=1.12–2.04) and −857T (OR = 0.76, 95% CI=0.58–0.98) had a significant association with Behcet's disease. The pooled estimates for the other polymorphisms were not statistically significantly associated with Behcet's disease; −308A and −863A. Conclusions Behcet's disease was associated with the −1031C, −238A and the −857T promoter polymorphisms in various ethnic groups.

A 57-year-old woman presented with 2 months history of right chest pain with direct tenderness and swelling over the right sternoclavicular joint. She had a 20-year history of skin rash over both soles and palms suggestive of pustulosis palmaris and plantaris without musculoskeletal symptoms. CT scan of the right sternoclavicular joint showed osteolysis of the joint and adjacent sclerosis. 99mTechnetium bone scan was abnormal with increased uptake over the joint and manubrium. She was diagnosed with SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, osteitis). This case report emphasizes the long duration that can lapse between onset of initial skin manifestations and musculoskeletal symptoms to define SAPHO syndrome.

Transient osteoporosis is a rare clinical syndrome of unknown etiology. It is believed that this syndrome is self-limiting; however, the data in the literature support the use of anti-resorptive agents that may reduce pain and decrease the duration of the illness. Herein, we describe two cases of transient osteoporosis of the hip and one case of transient osteoporosis of the knee where the use of oral bisphosphonates provided successful objective and subjective outcome.

Behçet’s disease (BD) is an idiopathic, chronic, relapsing, multi-systemic vasculitis characterized by recurrent oral and genital aphthous ulcers, ocular disease and skin lesions. Prevalence of BD is highest in countries along the ancient silk road from the Mediterranean basin to East Asia. By comparison, the prevalence in North American and Northern European countries is low. Gastrointestinal manifestations of Behçet’s disease are of particular importance as they are associated with significant morbidity and mortality. Although ileocecal involvement is most commonly described, BD may involve any segment of the intestinal tract as well as the various organs within the gastrointestinal system. Diagnosis is based on clinical criteria - there are no pathognomonic laboratory tests. Methods for monitoring disease activity on therapy are available but imperfect. Evidence-based treatment strategies are lacking. Different classes of medications have been successfully used for the treatment of intestinal BD which include 5-aminosalicylic acid, corticosteroids, immunomodulators, and anti-tumor necrosis factor alpha monoclonal antibody therapy. Like inflammatory bowel disease, surgery is reserved for those who are resistant to medical therapy. A subset of patients have a poor disease course. Accurate methods to detect these patients and the optimal strategy for their treatment are not known at this time.

Relapsing polychondritis is characterized by recurrent inflammation and destruction of the cartilage and connective tissue. Respiratory complications are frequently severe during the course of the disease and usually signal a poor prognosis. We report a case of a 47-year-old man with known relapsing polychondritis who presented with bilateral narrowing of the airways complicated by refractory cavitary Pseudomonas aeruginosa pneumonia. Despite an aggressive antibiotic regimen, the patient's pneumonia did not improve until bronchial stenting 4 months later.

The aim of this study is to describe the clinical features of Lebanese patients with Behcet's disease (BD) followed up at a tertiary care center in Lebanon. A retrospective review of medical records of 90 patients who fulfilled the International Study Group (ISG) criteria for diagnosis was performed. The clinical characteristics and severity score were compared with those reported from other populations of Arab and of Turkish origin using the same diagnostic criteria, and a comparison over two decades for the Lebanese population was made. The male-to-female ratio was 2.9:1, the mean age at onset, 25.4 years, and mean age at diagnosis, 29.2 years. One hundred percent of the patients had mouth ulceration; 72.2%, genital ulceration; 59.1%, arthritis; 55.7%, papulopustular skin lesion; 53.9%, ocular disease; 36.8%, vascular disease; 29.5%, erythema nodosum; and 23.0%, neurologic disease. The characteristics of our patient population are similar to that reported from other countries in the region. However, we found a higher prevalence of vascular and neurologic disease.

Objective: To describe the immunohistochemical characteristics of knee synovium from normal healthy subjects. Methods: 12 healthy subjects underwent needle biopsy of knee synovium. Using antibodies directed against CD3, CD4, CD8, L26, Kp-1,and HLA-DR, detailed quantitative immunohistochemical analysis of various cell subpopulations was undertaken. Results: The mean (SD) age of the subjects was 37 (9) years (five male, seven female). All had a negative history for arthritis, no knee pain, and a totally normal joint examination except for the presence of retropatellar crepitus in five. For technical reasons staining for all immunohistochemical markers could not be achieved in all subjects. CD3+ T lymphocytes were seen in nine of 10 subjects, either diffusely or, more commonly, in perivascular areas. CD4+ cells were seen in synovium in three of seven subjects and CD8+ cells in six of eight subjects, in almost equal numbers (CD4:CD8, 1.1:1). L26+ B lymphocytes were not seen in any biopsy. Kp1+ macrophages were found in 10 of 10 subjects, predominantly in surface lining cells, and in small numbers in diffuse and perivascular locations. HLA-DR+ cells were seen in 10 of 10 subjects, predominantly in surface lining cells and diffusely, but a few were seen perivascularly. Conclusions: Synovium from apparently normal subjects contained a wide range of different cell subpopulations but no B cells. The significance of these immune cells in normal synovium is unclear. A better understanding of their role in normal synovium may be important in analysing the transition to synovitis.

The objective of the study was to describe the practice patterns of the antiphospholipid syndrome (APS) as compared with consensus guidelines for diagnosis and to determine whether practice patterns correlate with patient demographics and physician specialty. A retrospective medical chart review was conducted at the American University Hospital, in Beirut, Lebanon. All adult and pediatric patients admitted to the hospital between 1 January and 31 December 1998 who underwent either anticardiolipinantibodies (aCL) or lupus anticoagulant(LA) testing were included in the study. Work-up of APS syndrome was compared with: (a) the consensus guidelines for clinical diagnosis; (b) physician specialty; and (c) patient demographics (age, gender, ethnicity, health insurance status). Eighty-seven patients fulfilled at least one clinical criterion for APS; 92% were for work-up of thrombosis and 8% for pregnancy morbidities. Fifty-one percent underwent both aCL and LA. Overall 38% (33) of patients had an abnormal test result, however only 18% (6) underwent retesting, of whom only two satisfied a minimum of 6 weeks between test and retest. The APS diagnostic work-up was requested by 11 different specialties. Rheumatologists were the most consistent in asking for both tests. APS is seen and diagnosed by a variety of medical specialties. Practice patterns as compared with the latest consensus are sub-optimal, and need to be improved. Interventions to help improve this have been discussed and are being implemented.

Background and Objectives: Leukotriene antagonists (LTAs), or antileukotrienes, are a new group of anti-inflammatory drugs used for the treatment of asthma. They might substitute for or allow tapering of corticosteroids in asthmatic patients. These drugs have been associated with the development of Churg-Strauss syndrome (CSS), a rare form of vasculitic angiitis. It is unclear whether the development of CSS is a direct drug effect or an unmasking of a preexisting condition on withdrawal of steroids for asthma. We present a case of CSS in a patient treated with montelukast and review the literature to analyze the association between LTAs and the development of CSS. Method: We reviewed the literature using MEDLINE from February 1966 to October 2000. To the cases identified, we present an additional case of a patient who underwent a diagnostic lung biopsy. Results: Twenty-two case reports of patients receiving LTAs who developed CSS were identified. The onset of CSS occurred 2 days to 10 months after starting treatment with LTAs. All patients had received inhaled or oral steroids for asthma. The interval between the last oral corticosteroid treatment and CSS onset ranged from 3 days to 8 months. Conclusions: To date, there is no compelling evidence that the development of CSS in asthmatic patients receiving LTAs results from a direct drug effect. Rather, it appears that tapering of corticosteroids in these patients unmasks the multiorgan manifestations of the disease. We believe that the use of LTAs should not be influenced by the apparent increase in the incidence of CSS and that these are still safe drugs for asthma. Semin Arthritis Rheum 31:218-227. Copyright 2002, Elsevier Science (USA). All rights reserved.

Background Variations exist in the prescription of non-biologic and biologic DMARDS for patients with Rheumatoid Arthritis (RA).Low and middle income countries use Methotrexate (MTX) and Biologics less frequently compared to high-income countries.These variations are attributed to provider and patient preferences, practice settings, and country's GDP1. Objectives To examine the prevalence of prescription of MTX & Anti-TNF drugs for RA treatment in some Arab States. Methods The Genetics of Rheumatoid Arthritis in some Arab States (GRAAS) is a multinational study designed to study the genetics & clinical characteristics of Arab RA patients from Jordan, Kingdom of Saudi Arabia (KSA),Lebanon, Qatar and the United Arab Emirates (UAE).Inclusion criteria are age≥18, Arab ancestry & diagnosis of RA based on ACR criteria.Data collected includes demographics,ancestry, disease duration, comorbidities,and the use of DMARDS.To assess prescribing patterns,we analyzed the prevalence of ever use of MTX and available anti-TNF (Infliximab,Etanercept and Adalimumab)in each of the countries.Because of difference in countries per Capita GDP,the countries were divided into two regions:Levant (Jordan and Lebanon) and Gulf (KSA and Qatar).Analysis using mean, standard deviation,t test,frequency and Chi square were used as appropriate.Adjusted analysis was done using logistic regression. Results 470 patients were included in the study.Mean age is 49±13.0 years.Female to male ratio is 5:1.Mean disease duration is 10.2±8.74 years. 52.3% of the patients were positive for both ACPA and RF. Patients from the Gulf were more likely to be seropositivethan patients from the Levant (57% vs 44% p=0.009) and significantly less likely to be seroengative (14%vs. 28% p

A 37-year-old woman, previously healthy, who in September 2001 noted sudden onset of erythema in both eyes, followed by vertigo, vomiting, tinnitus in both ears, and hearing loss in the left ear then in the right over 1-week period. Slit lamp examination revealed bilateral interstitial keratitis. Her physical examination was essentially unremarkable except for decreased hearing bilaterally, more so on the right. An audiogram conWrmed the presence of severe bilateral sensorineural hearing loss (SNHL), more so on the right. Brainstem auditory evoked response testing revealed delay of all waves on the left and no waves on the right. A gadolinium enhanced MRI of the brain conWrmed the presence of inXammation around the cochlea bilaterally. Her laboratory tests at that time showed a sedimentation rate of 26 mm/h, with a negative ANA, rheumatoid factor, anti-SSA and anti-SSB, anticardiolipins (IgG, IgM), c-ANCA and p-ANCA, and VDRL. A lumbar puncture was normal. Her chest X-ray, electrocardiogram and echocardiography were also normal. Accordingly, the diagnosis of Cogan’s syndrome was made. Therapy was initiated with topical steroid eye drops and oral prednisone at 1 mg/kg/day. The ocular symptoms improved within few days but after 3 weeks, the patient denied any clinical improvement in her hearing and audiogram conWrmed worsening of the SNHL on the left. After 3 weeks from the diagnosis of Cogan’s syndrome the Wrst dose of inXiximab was initiated at 3 mg/kg for three doses at 0, 2 and 6 weeks. After the Wrst dose of inXiximab, the patient reported decrease in the sensation of aural fullness and vertigo and subjective improvement in hearing, associated with improvement on the audiogram in the left ear. Methotrexate as 12.5 mg/week was added after the second dose of inXiximab. Because the hearing conditions remained stable oral prednisone was reduced gradually. Patient was lost of follow up after the third dose of inXiximab and returned after 2 years. She has stopped her medications since then and found to have subjective and objective deterioration for which she underwent left cochlear implant.

It has been recognized that primary Sjogren's syndrome predisposes to the development of lymphoproliferative disorders. However, it is so far uncertain whether these patients are at an increased risk for solid tumors. Herein we report two cases of primary Sjogren's syndrome complicated by breast and lung cancer and who have a strong family history for lymphoproliferative diseases.

Evaluation of: Mazieres B, Rouanet S, Guillon Y, Scarsi C, Reiner V: Topical ketoprofen patch in the treatment of tendinitis: a randomized, double-blind, placebo-controlled study. J. Rheumatol. 32(8), 1563–1570 (2005) [1]. This was a multicenter, double-blind, randomized, controlled trial to study the efficacy of the topical ketoprofen patch in the treatment of tendonitis. This trial suggests that using a ketoprofen once-daily 100 mg patch is helpful in the management of tendonitis. Topical nonsteroidal anti-inflammatory analgesics represent a promising alternative in the management of musculoskeletal pain for the aging population.

Stokes DG, 2003, SEMIN ARTHRITIS RHEU, V33, P1, DOI 10.1053-sarh.2003.50022; Uthman I, 1997, BRIT J RHEUMATOL, V36, P806

Hepatitis A virus is rarely associated with extrahepatic complications. A child presented with a history suggesting Raynaud's phenomenon and severe digital gangrene, as a complication of hepatitis A infection. Coagulation study results (protein C, protein S, antithrombin III, and activated protein C resistance) were all normal except for anticardiolipin antibodies, which were present on initial presentation and resolved later. Antinuclear antibodies, rheumatoid factor, lupus anticoagulant, antineutrophilic cytoplasmic antibodies, and Venereal Disease Research Laboratory test were all negative. Cryoglobulins were not detected. C3 and C4 levels were normal. Blood urea nitrogen and creatinine levels were normal as well. The patient was treated with aspirin and diclofenac, and improved slowly with complete resolution of gangrene and symptoms after 3 months. She remains asymptomatic 4 years later. Transient antiphospholipid syndrome or isolated Raynaud's phenomenon may be added to the list of extrahepatic complications of hepatitis A.