Objective.To identify empirical evidence of diagnostic delay in spondyloarthritis (SpA), determine whether sex-related differences persist, and conduct an analysis from that perspective of the possible causes, including the influence of quality research, in this group of inflammatory rheumatic diseases.Methods.A systematic review was done of delay in diagnosis of SpA in MEDLINE and EMBASE and other sources. Study quality was determined in line with the Strengthening The Reporting of OBservational studies in Epidemiology (STROBE) statement. A metaanalysis of 13 papers reporting sex-disaggregated data was performed to evaluate sex-related differences in diagnostic delay. The global effect of diagnostic delay by sex was calculated using means difference (D) through a fixed effects model.Results.The review included 23,883 patients (32.3% women) from 42 papers. No significant differences between the sexes were detected for symptoms at disease onset or during evolution. However, the mean for delay in diagnosis of SpA showed sex-related differences, being 8.8 years (7.4–10.1) for women and 6.5 (5.6–7.4) for men (p = 0.01). Only 40% of papers had high quality. A metaanalysis included 12,073 participants (31.2% women). The mean global effect was D = 0.6 years (0.31–0.89), indicating that men were diagnosed 0.6 year (7 months) before women.Conclusion.Delay in diagnosis of SpA persists, and is longer in women than in men. There are no significant sex-related differences in symptoms that could explain sex-related differences in diagnostic delay. Methodological and possible publication bias could result in sex-biased medical practice.

Competing interests MA declares speaking fees and research grants from Grunenthal, Menarini and Horizon. Patient and public involvementPatients and/or the public were not involved in the design, conduct, reporting or dissemination plans of this research. Patient consent for publication Not required.Provenance and peer review Not commissioned; internally peer reviewed. This article is made freely available for use in accordance with BMJ's website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.

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Anti-TNF-α therapy is effective and relatively safe in refractory BD uveitis.

Objective. To compare the efficacy of infliximab (IFX) versus adalimumab (ADA) as a first-line biologic drug over 1 year of treatment in a large series of patients with refractory uveitis due to Behçet's disease (BD).Methods.We conducted an open-label multicenter study of IFX versus ADA for BD-related uveitis refractory to conventional nonbiologic treatment. IFX or ADA was chosen as the first-line biologic agent based on physician and patient agreement. Patients received 3-5 mg/kg intravenous IFX at 0, 2, and 6 weeks and every 4-8 weeks thereafter, or 40 mg subcutaneous ADA every other week without a loading dose. Ocular parameters were compared between the 2 groups.Results. The study included 177 patients (316 affected eyes), of whom 103 received IFX and 74 received ADA. There were no significant baseline differences between treatment groups in main demographic features, previous therapy, or ocular sign severity. After 1 year of therapy, we observed an improvement in all ocular parameters in both groups. However, patients receiving ADA had significantly better outcomes in some parameters, including improvement in anterior chamber inflammation (92.31% versus 78.18% for IFX; P = 0.06), improvement in vitritis (93.33% versus 78.95% for IFX; P = 0.04), and best-corrected visual acuity (mean ± SD 0.81 ± 0.26 versus 0.67 ± 0.34 for IFX; P = 0.001). A nonsignificant difference was seen for macular thickness (mean ± SD 250.62 ± 36.85 for ADA versus 264.89 ± 59.74 for IFX; P = 0.15), and improvement in retinal vasculitis was similar between the 2 groups (95% for ADA versus 97% for IFX; P = 0.28). The drug retention rate was higher in the ADA group (95.24% versus 84.95% for IFX; P = 0.042).Conclusion. Although both IFX and ADA are efficacious in refractory BD-related uveitis, ADA appears to be associated with better outcomes than IFX after 1 year of follow-up. 9 Manuel Díaz-Llopis, MD, PhD, ATIENZA-MATEOETAL | PATIENTS AND METHODS Study design, enrollment criteria, and definitions.We conducted an observational, open-label multicenter study including 177 patients with refractory uveitis due to BD who were treated with IFX or ADA as first-line biologic therapy. The dosing schedule was as follows: for IFX, 3-5 mg/kg intravenously (IV) at

Graves’ orbitopathy (GO) is the most common extrathyroidal manifestation of Graves’ disease (GD). Our aim was to assess the efficacy and safety of Tocilizumab (TCZ) in GO refractory to conventional therapy. This was an open-label multicenter study of glucocorticoid-resistant GO treated with TCZ. The main outcomes were the best-corrected visual acuity (BVCA), Clinical Activity Score (CAS) and intraocular pressure (IOP). These outcome variables were assessed at baseline, 1st, 3rd, 6th and 12th month after TCZ therapy onset. The severity of GO was assessed according to the European Group on Graves’ Orbitopathy (EUGOGO). We studied 48 (38 women and 10 men) patients (95 eyes); mean age ± standard deviation 51 ± 11.8 years. Before TCZ and besides oral glucocorticoids, they had received IV methylprednisolone (n = 43), or selenium (n = 11). GO disease was moderate (n =29) or severe (n = 19) and dysthyroid optic neuropathy (DON) (n = 7). TCZ was used in monotherapy (n = 45) or combined (n = 3) at a dose of 8 mg/kg IV every four weeks (n = 43) or 162 mg/s.c. every week (n = 5). TCZ yielded a significant improvement in all of the main outcomes at the 1st month that was maintained at one year. Comparing the baseline with data at 1 year all of the variables improved; BCVA (0.78 ± 0.25 vs. 0.9 ± 0.16; p = 0.0001), CAS (4.64 ± 1.5 vs. 1.05 ± 1.27; p = 0.0001) and intraocular pressure (IOP) (19.05 ± 4.1 vs. 16.73 ± 3.4 mmHg; p = 0.007). After a mean follow-up of 16.1 ± 2.1 months, low disease activity (CAS ≤ 3), was achieved in 88 eyes (92.6%) and TCZ was withdrawn in 29 cases due to low disease activity (n = 25) or inefficacy (n = 4). No serious adverse events were observed. In conclusion, TCZ is a useful and safe therapeutic option in refractory GO treatment.

The objective of this study was to determine whether monosodium urate (MSU) crystals are phagocytosed in the synovial fluid (SF) of the asymptomatic joints of patients with gout. SF samples were obtained from 20 asymptomatic knees of 19 different patients. Cell and differential counts were done. Intracellular MSU crystals were identified by ordinary and polarizing light microscopy. We found that in 19 out of the 20 SF samples intracellular MSU crystals have been found. A mean of 22.55% [confidence interval (CI) 13.92, 31.18; range 0-62] of all the cells contained intracellular MSU crystals. The majority of the cells which contained intracellular crystals were mononuclear cells (MC), and polymorphonuclear (PMN) leucocytes containing intracellular crystals accounted only for 0.5% (CI 0, 1.05; range 0-5) of the total. The total cell count was 527 cells/mm3 (CI 226, 828, range;: 30-2670). Poor correlation was found between the percentage of cells with intracellular crystals and both the total cell count (r = -0.22) and the percentage of PMN leucocytes (r = -0.26). We conclude that cells containing phagocytosed MSU crystals--generally mononuclear cells--are a regular finding in the SF of asymptomatic joints of patients with gout. This finding indicates that other factors besides intra-articular interaction between crystals and cells are necessary to produce arthritis in gouty patients.

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