Spectrum of lymphomas across different drug treatment groups in rheumatoid arthritis: a European registries collaborative project.

BACKGROUND: Lymphomas comprise a heterogeneous group of malignant diseases with highly variable prognosis. Rheumatoid arthritis (RA) is associated with a twofold increased risk of both Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL). It is unknown whether treatment with biologic disease-modifying antirheumatic drugs (bDMARDs) affect the risk of specific lymphoma subtypes. METHODS: Patients never exposed to (bionaïve) or ever treated with bDMARDs from 12 European biologic registers were followed prospectively for the occurrence of first ever histologically confirmed lymphoma. Patients were considered exposed to a bDMARD after having received the first dose. Lymphomas were attributed to the most recently received bDMARD. RESULTS: Among 124 997 patients (mean age 59 years; 73.7% female), 533 lymphomas were reported. Of these, 9.5% were HL, 83.8% B-cell NHL and 6.8% T-cell NHL. No cases of hepatosplenic T-cell lymphoma were observed. Diffuse large B-cell lymphoma (DLBCL) was the most frequent B-cell NHL subtype (55.8% of all B-cell NHLs). The subtype distributions were similar between bionaïve patients and those treated with tumour necrosis factor inhibitors (TNFi). For other bDMARDs, the numbers of cases were too small to draw any conclusions. Patients with RA developed more DLBCLs and less chronic lymphocytic leukaemia compared with the general population. CONCLUSION: This large collaborative analysis of European registries has successfully collated subtype information on 533 lymphomas. While the subtype distribution differs between RA and the general population, there was no evidence of any modification of the distribution of lymphoma subtypes in patients with RA treated with TNFi compared with bionaïve patients.

Differing local and systemic inflammatory burden in polyarticular psoriatic arthritis and rheumatoid arthritis patients on anti-TNF treatment in clinical remission.

OBJECTIVES: To analyse clinical, serological and sonographic differences between rheumatoid arthritis (RA) and polyarticular psoriatic arthritis (PsA) patients on anti-TNF therapy in clinical remission. METHODS: Angiogenic and proinflammatory cytokine serum levels were determined by multiplex ELISA in patients with RA and PsA in clinical remission (DAS28-ESR<2.6), clinically-active RA patients (DAS28>3.2) and healthy controls. Ultrasound (US) scans were made of both wrists and hands. RESULTS: 30 RA and 47 PsA patients in remission, 22 active RA patients and 20 healthy controls were included. PsA patients had significantly lower disease activity according to DAS28-ESR (p=0.006) but not according to DAS28-CRP (p=0.319), and lower serum levels of proinflammatory and angiogenic cytokines than RA patients in remission. PsA patients had cytokine levels similar to healthy controls, while RA patients in remission had similar levels to those of active RA patients. Globally, 31 (40.25%) patients in remission had a PD signal and 12 had SH>2 plus PD [1 PsA vs. 11 RA (p=0.0001)], meeting the criteria for ultrasound-defined active synovitis (UdAS). Patients with UdAS had significantly higher levels of IL-6, IL-20, PIGF and SDF1. More PsA patients were on tapered doses of anti-TNF (63.8%), and more frequently as monotherapy (72.3%), compared with RA patients (26.6% and 20%, respectively). CONCLUSIONS: Polyarticular PsA patients in remission had lower levels of local (US synovitis) and systemic inflammation than RA patients in remission, even though a significantly higher percentage of PsA patients were on tapered doses of anti-TNF, mainly in monotherapy.

Effectiveness of tocilizumab with and without synthetic disease-modifying antirheumatic drugs in rheumatoid arthritis: results from a European collaborative study.

OBJECTIVES: To examine the effectiveness of tocilizumab (TCZ) with and without synthetic disease-modifying antirheumatic drugs (sDMARDs) in a large observational study. METHODS: Patients with rheumatoid arthritis treated with TCZ who had a baseline visit and information on concomitant sDMARDs were included. According to baseline data, patients were considered as taking TCZ as monotherapy or combination with sDMARDs. Main study outcomes were the change of Clinical Disease Activity Index (CDAI) and TCZ retention. The prescription of TCZ as monotherapy was analysed using logistic regression. CDAI change was analysed with a mixed-effects model for longitudinal data. TCZ retention was analysed with a stratified extended Cox model. RESULTS: Multiple-adjusted analysis suggests that prescription of TCZ as monotherapy varied according to age, corticosteroid use, country of the registry and year of treatment initiation. The change of disease activity assessed by CDAI as well as the likelihood to be in remission were not significantly different whether TCZ was used as monotherapy or in combination with sDMARDs in a covariate-adjusted analysis. Estimates for unadjusted median TCZ retention were 2.3 years (95% CI 1.8 to 2.7) for monotherapy and 3.7 years (lower 95% CI limit 3.1, upper limit not estimable) for combination therapies. In a covariate-adjusted analysis, TCZ retention was also reduced when used as monotherapy, with an increasing difference between mono and combination therapy over time after 1.5 years (p=0.002). CONCLUSIONS: TCZ with or without concomitant sDMARDs resulted in comparable clinical response as assessed by CDAI change, but TCZ retention was shorter under monotherapy of TCZ.

Morphea associated with the use of adalimumab: a case report and review of the literature.

Therapy with TNF blockers may induce cutaneous adverse events, but the development of morphea, a localized scleroderma lesion, is extremely infrequent. We describe a 37-year-old man with ankylosing spondylitis treated with adalimumab who developed morphea lesions in the lower limbs after 12 months of treatment. Adalimumab was discontinued, which resulted in progressive improvement in the skin lesions, with only mild hyperpigmentation remaining. We also review reports of morphea and other adverse cutaneous events related to anti-TNF treatment.

[Descriptive study of intrapartum antibiotic prophylaxis of neonatal infection by group B Streptococcus in Txagorritxu]. / Infección neonatal: estudio descriptivo de profilaxis antibiótica.

INTRODUCTION: GBS is one of the most important causes of neonatal sepsis of vertical transmission (1-2% of the carriers). The infection may involve newborn's death or severe complications. The culture of vaginal and rectal GBS is a screening test and it is performed to all pregnant women between 35-37 weeks of gestation. If it is positive, intrapartum penicillin is prescribed. If it is negative or unknown, the antibiotic per protocol is given according to risk factors: rupture of membranes more than 18 hours, intrapartum temperature, or prematurity. The aim of this study is to quantify women who receive intrapartum antibiotic in relation to the positive culture and achievement with the SEGO's recommendation. MATERIAL AND METHODS: It describes a sample of 261 women of the Txagorritxu Hospital who have given birth during the work shift of researchers, excluding cesarean sections. VARIABLES: results of culture, antibiotic administration. Data were collected by reviewing and analyzed medical records using SPSS 17.0. RESULTS: From 261 women, 69 (26.4%) received antibiotic administration. From 69, 46 (66.67%) had a positive culture. 26 (37.68%) received antibiotics according to risk factors, although their cultures were negative or unknown. DISCUSSION: The results suggest there is a correct application of the SEGO's recommendation. Carrier women with no risk factors would not have received antibiotic therapy without screening.

On mobility trends analysis of COVID-19 dissemination in Mexico City.

This work presents a tool for forecasting the spread of the new coronavirus in Mexico City, which is based on a mathematical model with a metapopulation structure that uses Bayesian statistics and is inspired by a data-driven approach. The daily mobility of people in Mexico City is mathematically represented by an origin-destination matrix using the open mobility data from Google and the Transportation Mexican Survey. This matrix is incorporated in a compartmental model. We calibrate the model against borough-level incidence data collected between 27 February 2020 and 27 October 2020, while using Bayesian inference to estimate critical epidemiological characteristics associated with the coronavirus spread. Given that working with metapopulation models leads to rather high computational time consumption, and parameter estimation of these models may lead to high memory RAM consumption, we do a clustering analysis that is based on mobility trends to work on these clusters of borough separately instead of taken all of the boroughs together at once. This clustering analysis can be implemented in smaller or larger scales in different parts of the world. In addition, this clustering analysis is divided into the phases that the government of Mexico City has set up to restrict individual movement in the city. We also calculate the reproductive number in Mexico City using the next generation operator method and the inferred model parameters obtaining that this threshold is in the interval (1.2713, 1.3054). Our analysis of mobility trends can be helpful when making public health decisions.

Ilium osteitis as the main manifestation of the SAPHO syndrome: response to infliximab therapy and review of the literature.

OBJECTIVE: To analyze the clinical efficacy of anti-tumor necrosis factor (TNF)-alpha therapy in the SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome. We describe 2 new cases with ilium osteitis as the main SAPHO syndrome feature and review reported cases treated with anti-TNF-alpha. METHODS: A literature search of SAPHO syndrome cases treated with TNF-alpha blocking therapy with special emphasis on osteoarticular and skin responses was performed. RESULTS: Eighteen cases were identified: 17 SAPHO syndrome and 1 chronic recurrent multifocal osteomyelitis, a juvenile variant of SAPHO syndrome. Sixteen were reported cases and 2 were nonreported cases seen in our arthritis unit. Sixteen patients received infliximab and 2 received etanercept, with an early, sustained clinical improvement in most cases. CONCLUSIONS: Anti-TNF-alpha therapies are effective treatment for patients with refractory SAPHO syndrome, not only for cutaneous lesions but also for persistent bone lesions such as osteitis.

Recommendations for the Management of Comorbidity in Patients With Axial Spondyloarthritis in Clinical Practice. / Recomendaciones para el manejo de la comorbilidad en la práctica clínica en pacientes con espondiloartritis axial.

OBJECTIVES: To identify priorities among comorbidities in axial spondyloarthritis (AxSpA) and recommend how to follow them from an eminently practical perspective. METHODS: A multidisciplinary group was selected (10 rheumatologists-six of them experts in AxSpA-, 2 general practitioners, an internist, a cardiologist, a gastroenterologist and a psychologist). In a first discussion meeting, the scope and users were established and a list of comorbidities was voted based on frequency and impact. The panelists had to defend the inclusion of each comorbidity/item in the document with consistent arguments. Four panelists and two methodologists developed systematic reviews on controversial topics. In a second meeting, the results of the reviews and the arguments concerning the items to be included were presented. After the meeting, the final document was drafted. RESULTS: The final document includes two checklists, one for health professionals and another for patients; they incorporate cardiovascular risk, renal comorbidities, gastrointestinal risk, lifestyle, risk of infections and vaccinations, pulmonary involvement, concomitant medication, psycho-affective disorders, osteoporosis, and risk of fracture. In addition, the document reflects the arguments favoring the inclusion of each item and how to record the items for subsequent collection. The panel considered it also appropriate to likewise establish «practices to avoid¼ applicable to comorbidity in AxSpA. CONCLUSIONS: Two checklists and a list of situations to avoid were generated to facilitate the management of comorbidities in AxSpA. In a future step, their utility and acceptance will be tested by a broad group of users that includes doctors, patients and nurses.

Rituximab Retreatment in Rheumatoid Arthritis in a Real-life Cohort: Data from the CERERRA Collaboration.

OBJECTIVE: Several aspects of rituximab (RTX) retreatment in rheumatoid arthritis (RA) need to be further elucidated. The aim of this study was to describe the effect of repeated courses of RTX on disease activity and to compare 2 retreatment strategies, fixed-interval versus on-flare retreatment, in a large international, observational, collaborative study. METHODS: In the first analysis, patients with RA who received at least 4 cycles with RTX were included. In the second analysis, patients who received at least 1 RTX retreatment and for whom information about the strategy for retreatment was available were identified. Two retreatment strategies (fixed-interval vs on-flare) were compared by fitting-adjusted, mixed-effects models of 28-joint Disease Activity Score (DAS28) over time for first and second retreatment. RESULTS: A total of 1530 patients met the eligibility criteria for the first analysis. Significant reductions of mean DAS28 between the starts of subsequent treatment cycles were observed (at start of first treatment cycle: 5.5; second: 4.3; third: 3.8; and fourth: 3.5), suggesting improved response after each additional cycle (p < 0.0001 for all pairwise comparisons). A total of 800 patients qualified for the second analysis: 616 were retreated on flare and 184 at fixed interval. For the first retreatment, the fixed-interval retreatment group yielded significantly better results than the on-flare group (estimated marginal mean DAS28 = 3.8, 95% CI 3.6-4.1 vs 4.6, 95% CI 4.5-4.7, p < 0.0001). Similar results were found for the second retreatment. CONCLUSION: Repeated treatment with RTX leads to further clinical improvement after the first course of RTX. A fixed-interval retreatment strategy seems to be more effective than on-flare retreatment.

A New Method for Individualized Digoxin Dosing in Elderly Patients.

BACKGROUND: Digoxin is a frequently prescribed drug in the elderly population. Estimated glomerular filtration rate is widely used to adjust dosages. The HUGE value is a tool for differentiating the presence or absence of chronic kidney disease in elderly patients. We aimed to investigate the usefulness of the HUGE value to predict the initial dose of digoxin in patients aged older than 70 years. METHODS: We reviewed retrospectively the medical records of patients aged older than 70 years with serum digoxin concentrations (SDCs) monitored over a 6-month period (63 patients). A linear regression relating the patient's SDC, maintenance dose of digoxin and the HUGE value was estimated to generate a dosage equation. This equation was validated retrospectively (33 patients) and prospectively (35 patients) in comparison with two existing methods based on creatinine clearance. RESULTS: An equation (HUGE_DIG) was generated to calculate the initial digoxin dose to reach a specific target SDC. Thus, to achieve a SDC of 0.8 ng/mL: Digoxin (mg/day) = 0.091 - 0.006 x HUGE. After retrospective validation, the calculated digoxin doses with this equation were administered in the prospective phase and we did not observe statistical differences between measured and desired SDCs. Moreover, the predictive performance of our equation was better than that obtained with the compared methods. CONCLUSIONS: We offer a new validated digoxin dosing equation for elderly patients. Our results support the need to perform digoxin dosing in elderly people, bearing in mind the changes in renal physiology secondary to ageing and not merely the estimated glomerular filtration rate.

Laryngeal assessment by videolaryngostroboscopy in patients with rheumatoid arthritis.

AIM: To evaluate the larynx involvement in patients with rheumatoid arthritis (RA) in a clinical setting and correlate with the different clinical features related to more aggressive disease. METHODS: Cross-sectional study including 36 consecutive patients with RA. Reflux symptoms were evaluated by the Reflux Symptom Index (RSI) and vocal cord impairment by the Voice Handicap Index-10 (VHI-10). Laryngeal involvement was done by videolaryngostroboscopy (VLS). RESULTS: The mean age was 56,3 ± 14 years with a mean disease duration of 2,6 ± 3,1 years (range 0-16 years). Voice use was considered as professional users in 33%. Twenty-four (67%) out of 36 patients had abnormal findings of VLS. One patient had larynx nodules (bamboo nodules). Eleven patients (31%) were diagnosed with muscle tension dysphonia, and there were symptoms and signs of pharyngeal-laryngeal reflux in 23 (64%) patients. No signs of cricoarytenoid joint impairment was found. CONCLUSIONS: Organic larynx involvement was uncommon in patients with RA. However symptoms and signs of pharyngeal-laryngeal reflux were seen in around 60% of patients. There was no correlation between the clinical phenotype, severity of disease, immunological profile or treatment with VLS findings.

Reduction of biological agent dose in rheumatic diseases: descriptive analysis of 153 patients in clinical practice conditions.

OBJECTIVE: To analyze the frequency and characteristics of dose reduction of biological agents in a cohort of patients with chronic arthritis, in clinical practice conditions in a tertiary level hospital. MATERIAL AND METHODS: Descriptive, cross-sectional study, which included all patients, followed consecutively during 6 months (June 2011-November 2011), by one investigator, with patients who at least have received one dose of biological agents in 2011. RESULTS: We included 153 patients: Rheumatoid arthritis (RA) (n=82), ankylosing spondylitis (n=29), psoriatic arthritis (n=20), and miscellaneous group (n=22). Mean disease duration was 14.9±7.7 years. At the time of analysis, 70 patients (45.7%) were receiving low doses of biological therapy (50% in miscellaneous group group, 50% in psoriatic arthritis, 48.2% in ankylosing spondylitis, and 42.6% in RA). Mean time of dosage reduction was 17.4±17.5 months. The most common biological agents used in low dose were: etanercept, adalimumab and tocilizumab; 57.6%, 54.9% and 40% respectively, in patients with a reduced dose of biological therapy. The patients at low dose of biological therapy compared with standard dose, had similar mean disease duration, but received significantly less DMARDs, glucocorticoids and NSAIDs, and similar biological agent duration. RA patients with reduced biological treatment, at the time of analysis, had higher remission rates versus patients receiving a standard dose (82.9% vs 34%, p<0.0001). The medical decision at the time of analysis was to maintain low-dosage biological treatment in almost all patients. CONCLUSION: In our clinical practice, 45.7% of our chronic arthritis patients receive low dose of biological therapy, after achieving remission or low activity at standard doses, maintaining a good control of the disease.

Is there subclinical synovitis in patients with palindromic rheumatism in the intercritical period? a clinical and ultrasonographic study according to anticitrullinated protein antibody status.

OBJECTIVE: To investigate the presence of subclinical synovitis by ultrasound (US) and the clinical phenotype in patients with palindromic rheumatism (PR) according to anticitrullinated protein antibody (ACPA) status. METHODS: Fifty-four patients with PR were studied. Clinical, demographic, serological, and therapeutic characteristics were compared in ACPA-positive and ACPA-negative patients. US searching for synovial hypertrophy (SH) and power Doppler signal (PDUS) in 22 joints of the hands was performed in the intercritical period. The results were compared according to ACPA status and with a healthy control group (n = 30). In 10 patients, US was performed during the joint attack. RESULTS: Most patients were female (63%) with a mean disease duration of 11.6 ± 10.7 years. Thirty-six patients (66.7%) were ACPA-positive. ACPA-positive patients had a shorter duration of attacks, a younger age, and less knee involvement at disease onset. US examination showed SH grade ≥ 1 in 79.6% of patients with PR and 50% of controls. Significant US results (SH ≥ 2 or PDUS) were observed in 2.7% and 1.4% of joints assessed and in 33% and 25.9% of patients with PR, respectively. Only 4 patients (7.4%) had US active synovitis (SH ≥ 2 plus PDUS) in at least 1 joint. US assessment showed no significant differences between ACPA-positive and ACPA-negative patients. PDUS was observed in 7 out of 10 patients during attacks. CONCLUSION: Some differences emerged in the clinical phenotype of PR according to ACPA status. Most patients with PR do not have US subclinical synovitis in the intercritical period, even those who are ACPA-positive.

Efficacy of tocilizumab in conventional treatment-refractory adult-onset Still's disease: multicenter retrospective open-label study of thirty-four patients.

OBJECTIVE: Adult-onset Still's disease (AOSD) is frequently refractory to standard therapy. Tocilizumab (TCZ) has demonstrated efficacy in single cases and in small series of patients with AOSD. The aim of this multicenter study was to assess the efficacy of TCZ in patients with AOSD refractory to conventional treatment. METHODS: This was a retrospective open-label study of TCZ treatment in 34 patients with AOSD who had experienced an inadequate response to corticosteroids and at least 1 standard synthetic immunosuppressive drug and also, in many cases, biologic agents. RESULTS: The mean ± SD age of the patients (8 men and 26 women) was 38.7 ± 16.1 years. The median duration of AOSD before TCZ was initiated was 4.2 years (interquartile range [IQR] 1-9 years). The initial dosages of intravenous TCZ were 8 mg/kg every 4 weeks in 22 patients, 4 mg/kg every 4 weeks in 2 patients, and 8 mg/kg every 2 weeks in 10 patients. TCZ treatment resulted in rapid and maintained improvement in both clinical and laboratory parameters. After 1 year of TCZ therapy, the incidence of joint manifestations had decreased from 97.1% at baseline to 32.4%, the incidence of both cutaneous manifestations and fever had decreased from 58.8% to 5.9%, and the incidence of lymphadenopathy had decreased from 29.4% to 0%. A dramatic reduction in laboratory markers of inflammation, including the C-reactive protein level, the erythrocyte sedimentation rate, and the ferritin level, was achieved. The median dosage of prednisone was also reduced, from 13.8 mg/day (IQR 5-45) at the initiation of TCZ to 2.5 mg/day (IQR 0-30) at 12 months. After a median followup of 19 months (IQR 12-31 months), only 2 patients required permanent discontinuation of TCZ therapy because of severe infections. CONCLUSION: TCZ treatment was associated with rapid and maintained clinical and laboratory improvement in patients with AOSD refractory to standard treatment. However, joint manifestations seem to be more refractory to treatment compared with systemic manifestations.

Cutaneous adverse events during treatment of chronic inflammatory rheumatic conditions with tumor necrosis factor antagonists: study using the Spanish registry of adverse events of biological therapies in rheumatic diseases.

OBJECTIVE: To analyze the incidence rate (IR) and risk factors of cutaneous adverse events (CAE) in patients with chronic inflammatory rheumatic diseases treated with tumor necrosis factor (TNF) antagonists. METHODS: We analyzed all patients from the BIOBADASER (Base de Datos de Productos Biológicos de la Sociedad Española de Reumatología) registry treated with a TNF antagonist (infliximab, etanercept, or adalimumab). Data collected included age, sex, diagnosis and duration of rheumatic disease, type of TNF antagonist, and concomitant treatment. Type of CAE was classified as local or systemic cutaneous manifestation related to treatment administration (infusion reaction), infection, malignancy, or autoimmune skin disease. Time of onset of CAE and outcome were also recorded. The IRs of CAE per 1,000 patient-years of exposure with 95% confidence intervals (95% CIs) were estimated. Multivariable analysis was performed to identify potential risk factors for CAE. RESULTS: A total of 5,437 patients were included, representing 17,330 patient-years of exposure. A total of 920 CAE were reported; the IRs per 1,000 patient-years were 53 (95% CI 50-57) for CAE, 28 (95% CI 25-30) for infection, 15 (95% CI 13-17) for infusion reactions, 5 (95% CI 4-6) for autoimmune skin diseases, and 3 (95% CI 2-4) for skin malignancy. The mean time between starting TNF antagonist treatment and CAE was 1.78 years. In 32% of patients, CAE required TNF antagonist withdrawal. The main risk factors for CAE were female sex and treatment with infliximab, leflunomide, and glucocorticoids. CONCLUSION: The IR of CAE in patients treated with TNF antagonists is significant and should be addressed carefully, and withdrawal of therapy is required in some cases.

Differences in synovial fluid cytokine levels but not in synovial tissue cell infiltrate between anti-citrullinated peptide/protein antibody-positive and -negative rheumatoid arthritis patients.

INTRODUCTION: Comparative data on synovial cell infiltrate and cytokine levels in anti citrullinated peptide/protein antibody (ACPA)-positive and ACPA negative rheumatoid arthritis (RA) patients are scarce. Our aim was to analyze synovial cell infiltrate and synovial fluid (SF) levels of cytokines in patients with RA according to the presence or absence of ACPA in serum. METHODS: A cross-sectional study in a single center including consecutive RA patients was performed. Patients were defined as 'ACPA negative' if serum was negative to two different ACPAs [second generation commercial anti-cyclic citrullinated peptide antibodies (CCP2) and chimeric fibrin/filaggrin citrullinated antibodies]. Parallel synovial tissue (ST) biopsies and SF were obtained by knee arthroscopy. Synovial cell infiltrate and endothelial cells were analyzed by immunohistochemistry and SF levels of Th1, Th2, Th17 and pro-inflammatory cytokines by Quantibody(R) Human Array. RESULTS: A total of 83 patients underwent arthroscopy, with a mean age of 55.9 ± 12 years, and mean disease duration of 45 months (interquartile range, IQR 10.8 to 122). 62% were female and 77% were ACPA positive. No significant differences were found in clinical variables, acute phase reactants, synovial cell infiltrate or lymphoid neogenesis (LN) between ACPA positive and negative patients. However ACPA positive patients had significantly higher levels of IL-1ß, IL-10, IL-17 F and CC chemokine ligand 20 (CCL-20) than ACPA negative patients. CONCLUSIONS: In our cohort of patients with RA no significant differences were found in synovial cell infiltrate or synovial LN according to ACPA status. However, ACPA positive patients had higher levels of T-cell derived and pro-inflammatory cytokines than ACPA negative patients. As systemic and local inflammation was similar in the two groups, these findings support a distinct synovial physiopathology.

Palindromic rheumatism with positive anticitrullinated peptide/protein antibodies is not synonymous with rheumatoid arthritis. A longterm followup study.

OBJECTIVE: To analyze longterm progression to rheumatoid arthritis (RA) and the predictive value of anticitrullinated peptide/protein antibodies (ACPA) in palindromic rheumatism (PR). METHODS: We selected all patients in our clinic with PR who had at least 1 ACPA measurement. We included only patients with pure PR, defined as no evidence of associated rheumatic disease at the first serum ACPA measurement. Clinical characteristics, serum ACPA levels, duration of PR until serum ACPA measurement, and total followup time were recorded. The outcome variable was the definitive diagnosis of RA. The prognostic value of ACPA status in pure PR for a definite diagnosis of RA was analyzed by different statistical methods. RESULTS: Seventy-one patients (54 women/17 men) with a PR diagnosis were included. Serum ACPA were positive in 52.1%. After a mean followup of 7.6 ± 4.7 years since the first ACPA measurement, 24 patients (33.8%) progressed to chronic disease: 22% RA, 5.6% systemic lupus erythematosus, and 5.6% other diseases. The positive likelihood ratio of ACPA status for RA was 1.45, and the area under the receiver-operating characteristic curve of ACPA titers was 0.60 (95% CI 0.45-0.75). Progression to RA was more frequently seen in ACPA-positive than in ACPA-negative patients (29.7% vs 14.7%), but the difference was not significant (hazard ratio 2.46, 95% CI 0.77-7.86). Mean ACPA levels of patients with pure PR did not differ significantly from those of patients who progressed to RA. CONCLUSION: ACPA are frequently found in the sera of patients with PR, and a significant proportion of these patients do not progress to RA in the long term.

Lung sarcoidosis induced by TNF antagonists in rheumatoid arthritis: a case presentation and a literature review.

We report on a 72 year-old woman with long-standing rheumatoid arthritis diagnosed as granulomatosis due to pulmonary sarcoidosis after 49 months of treatment with etanercept. A clinical and radiological improvement was seen after tumor necrosis factor (TNF) antagonist withdrawal plus a course of steroids. Currently, 27 cases of histological proven sarcoidosis with pulmonary involvement have been reported in relation to anti-TNF therapy, with etanercept being more frequent in comparison with the anti-TNF monoclonal antibodies infliximab and adalimumab. Potential pathogenic mechanisms of the paradoxical effect of anti-TNF treatment is discussed. It is important for clinicians to be aware of this potential and uncommon complication of biological therapy with TNF antagonists.

Health-related quality of life in patients with osteoarthritis after total knee replacement: factors influencing outcomes at 36 months of follow-up.

OBJECTIVES: (1) To evaluate health-related quality of life (HRQL) in patients with severe osteoarthritis (OA) undergoing total knee replacement (TKR) and (2) to identify the influence of sociodemographic, clinical, intra-operative and postoperative variables on HRQL at 36 months after TKR. DESIGN: Prospective study with a 36-month follow-up. Preoperative interviews were carried out with 90 in-patients. The disease-specific Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire was used to measure the health status. Sociodemographic, clinical, intra-operative degree of difficulty, in-patient and postoperative data were collected. Associations were analyzed using linear regression models. RESULTS: Of the 90 potentially eligible patients, 67 (54 females, mean age 74.83, standard deviation [SD] 5.57) completed follow-up assessment. There were significant differences between preoperative and postoperative WOMAC pain, stiffness and function scores (P<0.001, P=0.005 and P<0.001, respectively). Variables retained in each of the models explained between 15% and 23% (R(2) adjusted) of the variability of each WOMAC dimension. Higher preoperative WOMAC scores were associated with greater postoperative improvement (P<0.001). Chronic musculoskeletal pain unrelated to knee OA was associated with higher WOMAC pain, stiffness and function dimension scores (P=0.004, P=0.029 and P=0.005, respectively). Severe (Class III) obesity (body mass index [BMI] 35-39.9) was associated with more pain (P=0.049). CONCLUSIONS: In patients with severe OA, HRQL significantly improved at 36 months after TKR, especially in the pain dimension. Lower preoperative WOMAC scores, chronic pain unrelated to knee OA, and severe obesity negatively influenced postoperative WOMAC scores. This disease-specific questionnaire may help to identify patients at increased risk of negative outcomes after surgery.