Eugenio de Miguel

Female gout. Clinical spectrum and uric acid metabolism.

We reviewed the clinical features and uric acid metabolism in 37 female patients with gout. In 32 female patients (86%), gout was diagnosed after menopause. Among the five premenopausal patients, four had renal insufficiency and one had superactivity of phosphoribosylpyrophosphate synthetase. More than 50% of the female patients had osteoarthritis, hypertension, or renal insufficiency or were treated with diuretics. Comparison with 220 male patients with gout showed that female patients developed gout significantly later, more frequently had associated diseases, and more often were receiving diuretics, whereas significantly more male than female patients had alcoholism. The articular features of gout were similar in both groups. However, the prevalence of tophi was higher and its localization different in female than in male patients. Female patients with gout had a higher mean serum urate concentration and a lower mean urinary uric acid excretion than did male patients with gout. These differences were significant and independent of the effects of age, renal insufficiency, alcoholism, or previous diuretic intake. Renal underexcretion of uric acid appears to be more severe in female than in male patients with gout.

After treat-to-target: can a targeted ultrasound initiative improve RA outcomes?

For patients with rheumatoid arthritis (RA), remission can be achieved with tight control of inflammation and early use of disease modifying agents. The importance of remission as an outcome has been recently highlighted by European League Against Rheumatism recommendations. However, remission when defined by clinical remission criteria (disease activity score, simplified disease activity index, etc) does not always equate to the complete absence of inflammation as measured by new sensitive imaging techniques such as ultrasound (US) . There is evidence that imaging synovitis is frequently found in these patients and associated with adverse clinical and functional outcomes. This article reviews the data regarding remission, ultrasound imaging and outcomes in patients with RA to provide the background to a consensus statement from an international collaboration of ultrasonographers and rheumatologists who have recently formed a research network - the Targeted Ultrasound Initiative (TUI) group. The statement proposes that targeting therapy to PD activity provides superior outcomes compared with treating to clinical targets alone and introduces the rationale for a new randomised trial using targeted ultrasound in RA.

High prevalence of ultrasonographic synovitis and enthesopathy in patients with psoriasis without psoriatic arthritis: a prospective case–control study

OBJECTIVE To investigate the presence of synovitis, tenosynovitis and enthesitis with power Doppler (PD) ultrasonography (US) in patients with psoriasis without musculoskeletal diseases as compared with controls with other skin diseases without musculoskeletal disorders. METHODS A total of 162 patients with plaque psoriasis and 60 age-matched controls with other skin diseases, all without musculoskeletal diseases, were prospectively recruited at 14 centres. They underwent dermatological and rheumatological assessment and a blinded PDUS evaluation. Clinical assessment included demographics, comorbidities, severity of psoriasis, work and sport activities and musculoskeletal clinical examination. PDUS evaluation consisted of the detection of grey scale (GS) synovitis and synovial PD signal in 36 joints, GS tenosynovitis and tenosynovial PD signal at 22 sites, and GS enthesopathy and entheseal PD signal in 18 entheses. RESULTS US synovitis and enthesopathy were significantly more frequent in psoriatic patients than in controls (P = 0.024 and 0.005, respectively). The percentage of joints with US synovitis was 3.2% in the psoriasis group and 1.3% in the control group (P < 0.0005). US enthesopathy was present in 11.6% of entheses in the psoriasis group and 5.3% of entheses in the control group (P < 0.0005). Entheseal PD signal was found in 10 (7.4%) psoriatic patients, whereas no controls showed this finding (P = 0.05). Among demographic and clinical data, having psoriasis was the only significant predictive variable of the presence of US synovitis [odds ratio (OR) 2.1; P = 0.007] and enthesopathy (OR 2.6; P = 0.027). CONCLUSION Psoriatic patients showed a significant prevalence of asymptomatic US synovitis and enthesopathy, which may indicate a subclinical musculoskeletal involvement.

Gout. Imaging of gout: findings and utility

Imaging is a helpful tool for clinicians to evaluate diseases that induce chronic joint inflammation. Chronic gout is associated with changes in joint structures that may be evaluated with diverse imaging techniques. Plain radiographs show typical changes only in advanced chronic gout. Computed tomography may best evaluate bone changes, whereas magnetic resonance imaging is suitable to evaluate soft tissues, synovial membrane thickness, and inflammatory changes. Ultrasonography is a tool that may be used in the clinical setting, allowing evaluation of cartilage, soft tissues, urate crystal deposition, and synovial membrane inflammation. Also ultrasound-guided puncture may be useful for obtaining samples for crystal observation. Any of these techniques deserve some consideration for feasibility and implementation both in clinical practice and as outcome measures for clinical trials. In clinical practice they may be considered mainly for evaluating the presence and extent of crystal deposition, and structural changes that may impair function or functional outcomes, and also to monitor the response to urate-lowering therapy.

Differential effects of gastrin-releasing peptide, neuropeptide Y, somatostatin and vasoactive intestinal peptide on interleukin-1β, interleukin-6 and tumor necrosis factor-α production by whole blood cells from healthy young and old subjects

In the present study, we have investigated the effect in vitro of gastrin-releasing peptide (GRP, 10(-10) M), neuropeptide Y (NPY, 10(-10) M), somatostatin (10(-10) M) and vasoactive intestinal peptide (VIP, 10(-9) M) on the production of IL-1 beta, IL-6 and TNF alpha by peripheral whole blood cells from healthy young and old people. We have found that GRP, NPY, somatostatin and VIP stimulated the production of IL-1 beta in old subjects, and NPY, somatostatin and VIP in young ones. In addition, the production of IL-6 was enhanced by GRP, NPY and VIP in young and old people. The TNF alpha production was stimulated by NPY and somatostatin in young subjects, and by NPY, somatostatin and VIP in old ones, whereas GRP produced a decrease of TNF alpha in young persons. GRP in old subjects and VIP in young and old subjects stimulated in a great degree the LPS-induced IL-6 production by whole blood cells. On the contrary, GRP and VIP inhibited highly the LPS-induced TNF alpha production in young controls. Our results show that these neuropeptides, when added to whole blood cells at physiological concentrations, are able to stimulate the production of IL-1 beta, IL-6 and TNF alpha in a differential way according to the subject age.

Diagnostic accuracy of enthesis ultrasound in the diagnosis of early spondyloarthritis

Objective To determine the sensitivity and specificity of enthesis ultrasound for the diagnostic classification of early spondyloarthritis. Methods A cross-sectional, blinded and controlled study. Standardised bilateral ultrasound of six entheses (Madrid sonography enthesitis index (MASEI)) was performed. Accepted diagnostic classification criteria were used as the gold standard. Validity was analysed by receiver operating characteristic (ROC) curves. Values of p<0.05 were considered significant. Results 113 early spondyloarthritis patients were included (58 women/55 men), 57 non-inflammatory control individuals (29 women/28 men) and 24 inflammatory control individuals (11 women/13 men). The evolution time of spondyloarthritis was 10.9±7.1 months. At least some grade of sacroiliitis on x-ray was present in 59 patients, but only five fulfilled the radiographic sacroiliitis New York criteria. Human leucocyte antigen B27 (HLA-B27) was positive in 42% of patients. No statistical differences were found for the enthesis score among diagnostic spondyloarthritis subtypes form of presentation (axial, peripheral or mixed) or HLA-B27 positivity. The MASEI score achieved statistical significance for gender. The ultrasound score was 23.36±11.40 (mean±SD) in spondyloarthritis patients and 12.26±6.85 and 16.04±9.94 in the non-inflammatory and inflammatory control groups (p<0.001), respectively. The ROC area under the curve was 0.82, and a cut-off point of ≥20 points achieved a likelihood ratio of 5.30 and a specificity of 89.47%. Conclusions Entheses are affected early in spondyloarthritis, and the incidence of involvement is higher in men and independent of the spondyloarthritis diagnostic subtype, HLA-B27 status or presentation pattern. The enthesis ultrasound score seems to have diagnostic accuracy and may be useful for improving the diagnostic accuracy of early spondyloarthritis.

INCREASED PLASMA LEVELS OF HOMOCYSTEINE AND OTHER THIOL COMPOUNDS IN RHEUMATOID ARTHRITIS WOMEN

OBJECTIVES Since moderate hyperhomocysteinemia is an independent risk factor for vascular disease and physiological thiol compounds mediate Cu2+- and Fe3+-dependent low-density lipoprotein (LDL) oxidation, we have studied the total plasma concentrations of thiol compounds including methionine as precursor of homocysteine in rheumatoid arthritis patients, in which the high mortality found is associated with cardiovascular disease. DESIGN AND METHODS Thirty-eight women with rheumatoid arthritis and 25 age-matched control women were studied. Plasma was used to measure thiol compounds and amino acids by HPLC. RESULTS Rheumatoid arthritis patients showed significantly higher levels than healthy controls of total plasma homocysteine (17.3 +/- 7.8 vs. 7.6 +/- 1.9; p <0.001), cysteine (293 +/- 61 vs. 201 +/- 45; p < 0.001), cysteinglycine (32.7 +/- 8.3 vs. 22.3 +/- 4.7; p < 0.001) and methionine (25 +/- 9 vs. 18 +/- 3; p < 0.01), whereas total glutathione levels were not increased (4.7 +/- 2.0 vs. 4.1 +/- 1.6). CONCLUSIONS The increased levels of thiol compounds found in rheumatoid. arthritis patients may be implicated in the increased incidence of cardiovascular disease found in these patients by means of the toxic effect of homocysteine on endothelium and the increased susceptibility of LDL to oxidation by increased plasma amounts of thiol compounds such as cysteine.

Effect of calcitonin gene-related peptide, neuropeptide Y, substance P, and vasoactive intestinal peptide on interleukin-1β, interleukin-6 and tumor necrosis factor-alpha production by peripheral whole blood cells from rheumatoid arthritis and osteoarthritis patients

In the present study, we have investigated the in vitro effect of calcitonin-related peptide (CGRP), neuropeptide Y (NPY), substance P (SP) and vasoactive intestinal peptide (VIP) at concentrations of 10(-8), 10(-9) and 10(-10) M on the production of different proinflammatory cytokines or chemokines such as IL-1beta, IL-6 and TNFalpha by peripheral whole blood cells from patients with rheumatoid arthritis, as well as from osteoarthritis patients studied as a control group without immunoinflammatory background. We have found that CGRP, NPY, SP and VIP stimulated significantly the production of those cytokines and chemokines in rheumatoid arthritis patients. In general, the stimulation was higher at the 10(-9) M concentration, with SP and VIP, and in rheumatoid arthritis patients compared to osteoarthritis ones. Neuropeptides did not significantly modify the LPS-induced cytokine production by whole blood cells. The results indicate that physiological concentrations of the neuropeptides studied can modulate the inflammatory and immunological response, stimulating significantly the production of inflammatory cytokines by human whole blood cells in rheumatoid arthritis patients, as well as, in a minor way, in osteoarthritis patients.

An audit of the variability of diagnosis and management of gout in the rheumatology setting: the gout evaluation and management study.

Objective:The objectives of the study were to evaluate the rate of variability in diagnosis and treatment of the patients with gout in the rheumatology setting and to estimate the rate of adjustment to the European League Against Rheumatism recommendations as a key step to improve the quality of care in gout. Methods:The GEMA (Gout Evaluation and MAnagement) study is a cross-sectional audit in which 803 files of patients with an International Classification of Diseases code of gout were randomly chosen from 41 rheumatology units. The data collected regarded the clinical management of gout. Indicators based on the European League Against Rheumatism recommendations were created, and information on the fulfillment of the recommendations was retrieved. The mean adjustment and 95% confidence interval (CI) were estimated for each recommendation. Results:Patients from whose files information was retrieved were very representative of gout (94% were men, with a mean age of 60 years, 43% obese, 62% hypertensive, more than 25% with tophaceous gout, 61% hyperlipidemic). A diagnosis based on the observation of monosodium urate crystals on the microscope had been made in only 26%; thus, the adjustment to diagnostic recommendations was low, 26.0% (95% CI, 18.9%-33.1%). The adjustment to the recommendations on evaluating comorbidity was 50.6% (95% CI, 46.6%-54.5%). Mean adjustment to recommendations on management, in general, was better, especially those regarding acute flares (100%), and lifestyle changes, with 71.4% (95% CI, 63.7%-79.1%) with treatment using urate-lowering drugs could be improved (mean adjustment, 52.1% [95% CI, 43.1-61.1]). Conclusions:Overall, implementation of clinical care in gout should be put on further attention to diagnosis, time-consuming evaluation of comorbidities, and long-term control of serum urate levels.

Enthesis inflammation in recurrent acute anterior uveitis without spondylarthritis

OBJECTIVE To investigate whether patients with idiopathic recurrent acute anterior uveitis (AAU) have enthesis alterations comparable with those in patients with spondylarthritis (SpA). METHODS A blinded, controlled study of enthesis evident on ultrasound (US) examination was performed in 100 patients and controls classified into 5 groups, as follows: patients with confirmed SpA (group 1), patients with recurrent AAU who were positive for HLA-B27 and did not have SpA (group 2), patients with recurrent AAU who were negative for HLA-B27 and did not have SpA (group 3), patients with forms of uveitis other than those related to SpA (group 4), and healthy controls (group 5). In total, 12 enthesis locations were explored in each patient and control subject by 2 ultrasonographers who were blinded with regard to the diagnosis. A newly developed US method, the Madrid Sonography Enthesitis Index (MASEI), in which the diagnosis of SpA is determined as a cutoff score of 18 points, was used. RESULTS A total of 1,200 entheses were explored by US in 100 patients and controls. The MASEI cutoff limit was met or exceeded by 81%, 55.6%, 40%, 10%, and 19% of the subjects in the 5 groups, respectively. The MASEI score was significantly higher in groups 1 and 2 than in groups 4 and 5. The differences between groups 1 and 3 were also found to be significant. CONCLUSION Our findings indicate that a high percentage of HLA-B27-positive patients with idiopathic recurrent AAU without features of SpA have enthesis lesions comparable with those seen in patients with SpA. These data suggest that patients with recurrent AAU, especially those who are HLA-B27 positive, have an abortive or incomplete form of SpA.