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Background: Psoriatic arthritis (PsA) has been inconsistently associated with common NOD2 gene variants, although some of these studies did not include patient stratification by clinical phenotype., Objectives: To analyse the association between the three common NOD2 variants (R702W, G908R and L1007fs) and clinical phenotypes of PsA, particularly with surrogate markers of severe joint destruction., Patients and Methods: A total of 183 unrelated PsA patients and 187 controls were included. Demographic, clinical, biological and immunological characteristics were collected. Genotypes for the three common NOD2 gene variants were obtained by PCR and direct sequencing., Results: NOD2 variants in PsA patients (7.6%) are just as prevalent as in healthy controls (7.5%). 18.5% of PsA patients carrying at least one NOD2 variant underwent joint surgery compared with 4.5% of those without these variants (p=0.019). Multivariate analysis confirmed this finding (OR 8.82, CI 1.7-46.3). There was no requirement for early surgery in patients carrying the NOD2 variants but there was an increased possibility of requiring surgery at similar times of disease duration. No other association with clinical features and NOD2 status carrier was found., Conclusions: Common NOD2 gene variants are not associated with PsA, but might increase the risk of undergoing joint replacement surgery, suggesting that this autoinflammatory-associated gene could act as a phenotypic modifier gene in PsA patients by increasing the risk of joint destruction. Given the small number of PsA patients with joint surgery included, we consider our findings a new hypothesis that will need further testing.

Enthesis is a structure frequently involved in spondyloarthritides. According to a recent hypothesis, it may play a key role in the pathogenesis of these entities. The present review discusses the most important aspects of current knowledge of enthesis, such as its anatomy and the extracellular matrix components present within it. Clinical evaluation and the new imaging techniques (magnetic resonance imaging and ultrasound) that complement its evaluation will be briefly described. Immunohistological studies as well as animal models developed with enthesis molecules underline the importance of enthesis in the pathogenesis of spondyloarthritides. Finally, the latest research assessing the T cell response to enthesis components in patients with ankylosing spondylitis will be reviewed., (Copyright © 2006 Elsevier España S.L. Barcelona. Published by Elsevier Espana. All rights reserved.)

Objective: To assess the prevalence of HLA-B27 and its subtypes in both the normal population and in patients with Ankylosing Spondylitis (AS) in Galicia, Northwest Spain., Methods: The prevalence of HLA-B27 in the normal population was determined by checking the number of HLA-B27 positive samples in 308 subjects from different areas of Galicia who had donated organs over a period of 4 years. A total of 106 patients with the diagnosis of AS, according to the modified New York clinical criteria for definitive ankylosing spondylitis, were collected from three very representative areas of Galicia. HLA-B27 was determined by PCR using the primers E91s and E136as, while 11 subtypes of HLA-B27 were analyzed using a commercial kit., Results: The prevalence of HLA-B27 in organ donors was 9.34%. HLA-B27 was present in 94.3% of patients with AS. Subtypes B*2701, B*2709 and B*2710 were not found. The subtypes found in the normal population were; B*2705 (79.5%), B*2702 (18%) and B*2708 (2.5%). The subtypes associated with AS were B*2705 (88%) and B*2702 (12%)., Conclusion: The prevalence of HLA-B27 in Galicia was 9.34%, which is higher than previously published in Spain. The frequency of the subtypes associated with AS was similar to that reported for other Spanish regions.

Objectives: The intra-articular injection of hyaluronan (HA) was originally used in the treatment of osteoarthritis (OA) to increase the viscosity of synovial fluid. However, some findings suggest that the activity of HA cannot be solely explained by its biomechanical properties. The aim of this study was to analyze the in vitro biological effects of HA on human OA chondrocytes and the impact of its molecular weight (MW) on those effects., Methods: Cells were isolated from cartilage obtained during joint replacement surgery in OA patients. The chondrocytes were cultured for 24 hours to detect prostaglandin E2 (PGE2) and for 48 hours to measure nitric oxide (NO), after which they were pre-incubated with HA and stimulated with interleukin-1 (IL-1) at 5 ng/ml. Two commercial HA preparations with different MWs were used: Hyalgan (500-730 kDa, HA, Bioibérica S.A.) and Synvisc (hylan of 6,000 kDa, Biomatrix Inc). NO was detected by the Greiss reaction and PGE2 was quantified by a commercial EIA in the supernatant. Apoptosis was induced by an NO donor (sodium nitroprusside, SNP) and the effect of HA on apoptosis was quantified by flow cytometry., Results: Neither HA preparation studied had any effect on the basal production of NO or PGE2. However, the 500-730 kDa HA at 200 microg/ml reduced the synthesis of both IL-1-induced NO and PGE2 by 70% and 45% respectively. Furthermore both HA preparations at 200 microg/ml decreased the apoptosis induced by SNP, 500-730 kDa to 40% and 6,000 kDa to 36%., Conclusion: HA may induce biological effects in addition to acting as a viscoelastic substance. This study suggests that HA preparations are different due to differences in biological activity resulting from MW.

Objective: To identify in polymyalgia rheumatica the best set of predictors for a positive temporal artery biopsy and to define predictive models with either a high or low probability of giant cell arteritis (GCA)., Patients and Methods: Retrospective study of 227 patients, 137 with polymyalgia rheumatica unassociated with arteritis (group A) and 90 with polymyalgia associated with biopsy-proven giant cell arteritis (group B or training set). Data on demographic features, clinical and laboratory abnormalities were collected. Risk factors for arteritis were estimated by nonlinear logistic regressions. Simple predictive models were constructed with those predictors more related to arteritis by multivariable analysis. These models were then tested in group B and in 89 cases of arteritis without polymyalgia rheumatica (group C or test set)., Results: The best predictors of arteritis were a new headache odds ratio (OR) 13.6 (95% confidence interval [CI] 4.7 to 39.3); age at onset < 70 years OR 0.11 (CI 0.04 to 0.35); abnormal temporal arteries OR 4.2 (CI 1.3 to 13.7); raised liver enzymes OR 2.9 (CI 1.1 to 7.8), and jaw claudication OR 4.8 (CI 1.0 to 22.7). Amaurosis was only observed in patients with arteritis. Three subsets had a very high risk of arteritis: (1) Patients with recent headache, abnormal arteries, and > or = 70 years at disease onset: sensitivity 44%, positive predictive value (PPV) 93%, likelihood ratio (LR) 20.3; (2) patients with a new headache, jaw claudication, and abnormal arteries: sensitivity 34.4%, PPV 96.9%, LR 47.2; and (3) those, that in addition to the last 3 features, were > or = 70 years of age at disease onset: sensitivity 26.7%, PPV 100%. We could also identify a subset with a very low risk of arteritis constituted by patients < 70 years, without headache, and with clinically normal temporal arteries: sensitivity 1.1%, PPV 1.7%, LR 0.03. In group C or the test set, these four predictive models correctly identified 57.3%, 29.2%, 23.6, and 3.4% of patients, respectively., Conclusions: In polymyalgia rheumatica it is feasible to identify subsets with a very high likelihood of GCA. Although in some of these subsets the diagnosis of arteritis is almost certain, we suggest that even then it should be confirmed by temporal artery biopsy. By contrast, in those patients with polymyalgia < 70 years and without cranial features of giant cell arteritis, the risk of vasculitis is so low that the biopsy could be initially avoided and the patient treated with low-dose corticosteroids.

Background: An erythrocyte sedimentation rate (ESR) of at least 40 mm/h is considered an important requisite for the diagnosis of polymyalgia rheumatica (PMR). However, the relative frequency and clinical features of PMR in patients without a significantly increased ESR are unclear., Methods: We performed a retrospective study of patients diagnosed as having PMR at the rheumatology divisions of 3 teaching hospitals. The diagnosis of PMR was established, regardless of the ESR, in 201 consecutive patients fulfilling the following criteria: (1) age 50 years or older, (2) severe proximal pain for more than 1 month in at least 2 of 3 areas: neck, shoulder, and/or pelvic girdles, and (3) rapid resolution of the syndrome while taking low-dose prednisone. Patients with giant cell arteritis were previously excluded from the study. The frequency and clinical features of patients with PMR and an ESR lower than 40 mm/h were analyzed. A comparative study between these patients and those with high ESRs was performed., Results: An ESR lower than 40 mm/h was found in 41 patients (20.4%). These patients were younger (P = .02), were more frequently men (P = .006), and experienced a lower frequency of fever (P = .003) and weight loss (P = .07). Furthermore, these patients were characterized by an absence of anemia (P = .002) and a lower frequency of abnormal protein electrophoresis results (P < .001). Otherwise, their clinical syndrome, response to therapy, and frequency of relapses were similar to those of patients with classic PMR. In the entire population of 201 patients, the ESR was related to the length of treatment, number of areas involved, presence of fever, weight loss, and laboratory test result abnormalities, but it was unrelated to the duration of the illness prior to diagnosis., Conclusions: It is not uncommon to find a patient with PMR with an ESR lower than 40 mm/h. This syndrome is more frequent in men and it is clinically less severe than the classic form of PMR. Its recognition will allow these patients to benefit from an effective treatment with low-dose corticosteroids.

Objective: To assess the frequency and clinical features of an acute febrile toxic reaction (AFTR) in patients with refractory rheumatoid arthritis (RA) receiving combined therapy with methotrexate (MTX) and azathioprine (AZA)., Methods: A cohort of 43 RA patients being treated with MTX/AZA combination therapy were studied. In all of them, RA had been refractory to single-therapy disease-modifying antirheumatic drugs. We analyzed the frequency and clinical features of AFTR, which consisted mainly of the development of fever, leukocytosis, and cutaneous leukocytoclastic vasculitis when AZA was added to the MTX regimen., Results: Four of the 43 patients (9.3%) who had been receiving long-term, well-tolerated treatment with MTX (mean +/- SD 375.5 +/- 159.5 days, range 227-561 days) developed AFTR shortly (mean +/- SD 25.7 +/- 13.6 days, range 17-46 days) after the addition of AZA to the regimen. The AFTR resolved rapidly (3 +/- 1.4 days) after discontinuation of AZA and MTX. In 2 cases, rechallenge with AZA and MTX was linked to a new flare of AFTR., Conclusion: The knowledge of this side effect is particularly important because it mimics a severe infectious complication related to immunosuppressive therapy, and because rechallenge can produce severe toxicity. Most of the new combined therapies for RA do not seem to be more toxic than single-drug treatment. Nevertheless, clinicians should be aware of a possible increase in side effects due to drug interactions or some other unidentified mechanism.

Background: The aim of the present was to study the clinical features of a wide series of patients with giant cell arteritis (GCA) diagnosed with accurate criteria and to evaluate the sensitivity of the criteria proposed by the ACR for classification of GCA., Methods: A retrospective analysis of 191 patients with GCA, 184 of whom were diagnosed by biopsy and 7 due to their clinical manifestations was carried out., Results: The age was 73 +/- 7 years with the most frequent symptoms being headache (87%), abnormalities in the temporal arteries (75%), general malaise (60%), rheumatic polymyalgia (49%) and mandibular claudication (40%). The frequency of GCA was equal in both genders although the most complex syndrome was observed in women with a greater frequency of polymyalgia (p < 0.005), jaw claudication (p < 0.01) and anemia (p < 0.01). The patients with polymyalgia were characterized by a predominance of the polymyalgic syndrome in the initial phases and a higher frequency of amaurosis. Out of 47 patients with amaurosis, 23 remained with permanent unit or bilateral blindness. Unilateral biopsy of the temporal artery was diagnosed in 91% of the cases (CI 95%; 86 to 95%) increasing to 96.3% (CI 95%; 92 to 98%) on biopsy of both arteries. Ninety-eight percent of the patients (CI 95%; 95 to 99%) had 3 or more GCA criteria for classification as GCA., Conclusions: The clinical manifestations of giant cell arteritis in Spain, with the exception of an equal frequency in both sexes, are similar to that described in other series of patients selected with strict criteria. The present data confirm the sensitivity of the criteria proposed by the ACR for the classification of giant cell arteritis although its application does not avoid the need for temporal artery biopsy for diagnosis. Unilateral biopsy is usually suffice in most of the cases.

The association of systemic lupus erythematosus (SLE) and autoimmune thyroiditis has been previously described. We report a woman with negative antinuclear antibodies (ANA) and criteria for the diagnosis of SLE. The patient was also diagnosed with autoimmune thyroiditis. We review the clinical characteristics and the association of both entities. We also remark in this case the association of autoimmune thyroiditis with seronegative SLE.

A patient who consulted because of diarrhea was diagnosed of thyroid medullar carcinoma (TMC) associated to pheochromocytoma. All members of his family were studied for a possible family variety of TMC with a genetic origin. In the 21 family members studied basal and calcium-pentagastrin stimulated calcitonin levels were determined and parathyroid and adrenal gland function were explored to rule out pheochromocytoma. Elevated levels of calcitonin agreed with pathological findings of TMC. Pheochromocytoma carriers had altered catecholamines and an abnormal abdominal CT scan. The clinical, analytical and radiologic findings in the four affected family members are described. The histopathological study revealed a pheochromocytoma in one case and bilateral TMC in two cases. The cytology of aspiration biopsy samples was positive for TMC in three cases. The importance of calcitonin determinations is emphasized as well as the obligatory determination of catecholamines and adrenal CT scan in order to rule out the coexistance of pheochromocytoma. The reasons for not utilizing gammagraphy with meta-iodine benzyl guanidine in these four cases are also explained.