Background: Enthesitis is a remarkable feature of ankylosing spondylitis (AS) not specifically approached by the available measuring tools for the disease. Ultrasonography (US) has proved to be an excellent technique for the assessment of tendon pathology. Objective: To test a Sonographic Entheseal Index (SEI) of the lower limbs in a cohort of patients with AS, as a potential measuring tool. Methods: 44 patients with AS and 10 healthy controls were enrolled. Bath Ankylosing Spondylitis Functional Index and Bath Ankylosing Spondylitis Disease Activity Index, pain at entheseal points, severity of symptoms, acute-phase reactants, Schober's test and stage of sacroiliitis were recorded. Patients underwent US examination of five entheseal regions from both lower limbs by two experts. Hypoechogenicity, increased tendon thickness, peritendinous oedema and bursitis were considered signs of active inflammation. Insertional bone erosions, intratendinous calcifications, decreased thickness and tears were considered signs of chronic injury. Each alteration independently scored one point. Data were analysed with Spearman's correlation method. Results: A significant interobserver correlation in SEI scores (p,0.001) and a fine discriminative power between controls and patients were observed. Acute entheseal lesions predominated (63% vs 37%), the most frequent alteration being tendon hypoechogenicity (43%). 72% of all lesions were located at the foot. The SEI correlated with reduction of Schober's test (p,0.02), but not with other activity or severity parameters. Conclusions: A scoring method such as the SEI may be of help in characterising entheseal injury in AS, and for decision making in these patients.

IntroductionA number of genetic-association studies have identified genes contributing to ankylosing spondylitis (AS) susceptibility but such approaches provide little information as to the gene activity changes occurring during the disease process. Transcriptional profiling generates a 'snapshot' of the sampled cells' activity and thus can provide insights into the molecular processes driving the disease process. We undertook a whole-genome microarray approach to identify candidate genes associated with AS and validated these gene-expression changes in a larger sample cohort.MethodsA total of 18 active AS patients, classified according to the New York criteria, and 18 gender- and age-matched controls were profiled using Illumina HT-12 whole-genome expression BeadChips which carry cDNAs for 48,000 genes and transcripts. Class comparison analysis identified a number of differentially expressed candidate genes. These candidate genes were then validated in a larger cohort using qPCR-based TaqMan low density arrays (TLDAs).ResultsA total of 239 probes corresponding to 221 genes were identified as being significantly different between patients and controls with a P-value <0.0005 (80% confidence level of false discovery rate). Forty-seven genes were then selected for validation studies, using the TLDAs. Thirteen of these genes were validated in the second patient cohort with 12 downregulated 1.3- to 2-fold and only 1 upregulated (1.6-fold). Among a number of identified genes with well-documented inflammatory roles we also validated genes that might be of great interest to the understanding of AS progression such as SPOCK2 (osteonectin) and EP300, which modulate cartilage and bone metabolism.ConclusionsWe have validated a gene expression signature for AS from whole blood and identified strong candidate genes that may play roles in both the inflammatory and joint destruction aspects of the disease.

W e present a case of recurrent auricular chondritis, which developed after two injections of a luteinising hormone-releasing hormone (LH-RH) analogue buserelin combined with oral treatment of a pure antiandrogen bicalutamide (Casodex). The patient was treated successfully with a continuous moderate dose of corticosteroids together with azathioprine and methotrexate. Complete repair of the deformed ear followed 7 months after starting the treatment.Relapsing polychondritis (RP) is a chronic autoimmune cartilaginous inflammation. Auricular chondritis is a presenting sign in over 85% of patients, in which patients' ears become red, swollen, and tender. We observed a painless form of recurrent auricular chondritis complicated by severe cartilage damage. CASE REPORTA 69 year old man had a history of old myocardial infarction and prostatic adenocarcinoma (Gleason score VI, stage T2B NO MO). He underwent two injections of an LH-RH analogue buserelin (Suprefact Depot, Aventis Pharma), combined with a pure antiandrogen bicalutamide (Casodex; AstraZeneca).Five months after starting treatment he presented with a painless redness and swelling of his right ear, which spared the lobe. This inflammation, showing inflammatory mononuclear infiltrate, progressed to include dropping and deformity of the upper part of the ear, and resolved spontaneously after 3 months (figs 1A and 2). The patient was then referred to the rheumatologist.Besides the dropped pinna, no systemic manifestations were found on physical examination and the patient's neurological status was unremarkable, including normal pain perception. Retinal screening showed no vasculitic changes. Routine laboratory investigation was normal except for raised inflammatory markers: erythrocyte sedimentation rate and C reactive protein. Serum immunoelectrophoresis, antinuclear antibodies, antineutrophil cytoplasmic antibodies, rheumatoid factor, prostate-specific antigen were normal. Viral serology, tuberculin test, and Venereal Disease research Laboratory test were negative. Ultrasound of large vessels and echocardiography were normal. A chest x ray examination and computed tomography (CT), abdominal CT, and bone scan were unremarkable.Owing to serious coronary disease, the lack of active auricular inflammation and systemic disease, and because buserelin treatment had been stopped, it was decided to observe the patient without treatment. However, painless auricular chondritis of the opposite side occurred 3 months later, supporting an initial suspicion of relapsing polychondritis. Prednisone 40 mg/day and azathioprine 100 mg/day were given. Corticosteroids were tapered to 20 mg/day for 1 month after reduction of inflammation in the opposite ear. Azathioprine treatment was stopped when the liver enzyme level was significantly raised after 2 months of treatment. A daily dose of prednisone 20 mg/day was continued, and oral methotrexate 7.5 mg/week was started after the liver function returned to normal. Partial repair of the auricular cartilage was noted 2 months later and f...

The objective of this study was to assess whether clinical measures of rheumatoid arthritis activity and severity were influenced by tumor necrosis factor-alpha (TNF-α) promoter genotype/haplotype markers. Each patient's disease activity was assessed by the disease activity score using 28 joint counts (DAS28) and functional capacity by the Health Assessment Questionnaire (HAQ) score. Systemic manifestations, radiological damage evaluated by the Sharp/van der Heijde (SvdH) score, disease-modifying anti-rheumatic drug use, joint surgeries, and work disability were also assessed. The promoter region of the TNF-α gene, between nucleotides -1,318 and +49, was sequenced using an automated platform. Five hundred fifty-four patients were evaluated and genotyped for 10 single-nucleotide polymorphism (SNP) markers, but 5 of these markers were excluded due to failure to fall within HardyWeinberg equilibrium or to monomorphism. Patients with more than 10 years of disease duration (DD) presented significant associations between the -857 SNP and systemic manifestations, as well as joint surgeries. Associations were also found between the -308 SNP and work disability in patients with ACR = American College of Rheumatology; DAS28 = disease activity score using 28 joint counts; DD = disease duration; DMARD = disease-modifying anti-rheumatic drug; EM = expectation-maximization; ESR = erythrocyte sedimentation rate; HAQ = Health Assessment Questionnaire; NF-κB = nuclear factor-kappa-B; PCR = polymerase chain reaction; RA = rheumatoid arthritis; RF = rheumatoid factor; SNP = single-nucleotide polymorphism; SvdH = Sharp/van der Heijde; TNF-α = tumor necrosis factor-alpha. Arthritis Research & TherapyVol 9 No 2 Fonseca et al. Page 2 of 10(page number not for citation purposes) more than 2 years of DD and radiological damage in patients with less than 10 years of DD. A borderline effect was found between the -238 SNP and HAQ score and radiological damage in patients with 2 to 10 years of DD. An association was also found between haplotypes and the SvdH score for those with more than 10 years of DD. An association was found between some TNF-α promoter SNPs and systemic manifestations, radiological progression, HAQ score, work disability, and joint surgeries, particularly in some classes of DD and between haplotypes and radiological progression for those with more than 10 years of DD.

DAS28, CDAI and SDAI cut-offs do not translate into the same clinical information in Reuma.pt. Although this might be expected for the original DAS28 cut-offs, when compared with CDAI and SDAI significant disagreement was also found for the DAS28 modified cut-offs. For visits where patients are in CDAI or SDAI remission, we also find disagreement between these two indices, which may contradict previous conclusions that acute phase reactants add little to composite disease activity indices for RA.

Human leukocyte antigen (HLA)-B27 is the mostly known major histocompatibility complex (MHC) gene associated with ankylosing spondylitis (AS). Nonetheless, there is substantial evidence that other MHC genes appear to be associated with the disease, although it has not yet been established whether these associations are driven by direct associations or by linkage disequilibrium (LD) mechanisms. We aimed to investigate the contributions of HLA class I and II alleles and B27-haplotypes for AS in a case-control study. A total of 188 HLA-B27 AS cases and 189 HLA-B27 healthy controls were selected and typed for HLA class I and II by the Luminex polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSOP) method. Allelic and haplotypic distributions were estimated by maximum likelihood method using Arlequin v3.11 and statistical analysis were performed by Stata10.1. No associations were found between non-HLA-B27 loci and AS susceptibility, but several associations were observed for phenotypic features of the disease. DRB1*08 was identified as a risk factor for uveitis and DQB1*04 seems to provide protection for AS severity (functional, metrological and radiological indexes). A*02/B27/C*02/DRB1*01/DQB1*05 [P<0.0001; odds ratio (OR) = 39.06; 95% confidence interval (CI) (2.34-651)] is the only haplotype that seems to confer susceptibility to AS. Moreover, the haplotype A*02/B27/C*01/DRB1*08/DQB1*04 seems to provide protection for disease functional and radiological repercussions. Our findings are compatible with the hypothesis that other genes within the HLA region besides HLA-B27 might play some role in AS susceptibility and severity.

The availability of population-specific normative data regarding disease severity measures is essential for patient assessment. The goals of the current study were to characterize the pattern of ankylosing spondylitis (AS) in Portuguese patients and to develop reference centile charts for BASDAI, BASFI, BASMI and mSASSS, the most widely used assessment tools in AS. AS cases were recruited from hospital outpatient clinics, with AS defined according to the modified New York criteria. Demographic and clinical data were recorded. All radiographs were evaluated by two independent experienced readers. Centile charts for BASDAI, BASFI, BASMI and mSASSS were constructed for both genders, using generalized linear models and regression models with duration of disease as independent variable. A total of 369 patients (62.3% male, mean±(SD) age 45.4±13.2 years, mean±(SD) disease duration 11.4 ± 10.5 years, 70.7% B27-positive) were included. Family history of AS in a first-degree relative was reported in 17.6% of the cases. Regarding clinical disease pattern, at the time of assessment 42.3% had axial disease, 2.4% peripheral disease, 40.9% mixed disease and 7.1% isolated enthesopatic disease. Anterior uveitis Matthew A Brown and Jaime C Branco equally contributed to this study.

Our objective was to (i) compare FIDIS Rheuma, a new multiplexed immunoassay designed for simultaneous detection of IgM class rheumatoid factors (RF) directed against Fc determinants of IgG from humans and animals, with agglutination and ELISA (conventional methods) and (ii) evaluate the clinical sensitivity and specificity of biological markers for rheumatoid arthritis (RA). To do this, FIDIS technology was employed using the Luminex system. It consists of distinct color-coded microsphere sets, a flow cytometer, and digital signal processing hardware and software. Agglutination and ELISA tests were performed with commercial kits. The study included 134 samples from RA patients and 105 from healthy blood donors. For human specificity, we compared FIDIS with latex agglutination and ELISA. Relative sensitivities were 98.9% and 88.5% and specificities were 90.2% and 94.6%, respectively. For animal specificity, we compared FIDIS with Waaler-Rose and ELISA. The results were 84.9% and 71.9% for the sensitivities and 97.5% and 98.4% for the specificities, respectively. Detection of IgG anti-CCP by ELISA and IgG antikeratin by immunofluorescence was also determined in order to compare their clinical sensitivity and specificity with IgM-RF, according to the method used. The results were: IgG anti-CCP 72.3%, 97.2%; IgG antikeratin 36.6%, 100%; latex agglutination 66.4%, 97.2%; Waaler-Rose 55.9%, 96.3%; FIDIS human 73.9%, 92.1%; FIDIS animal 49.2%, 97.2%; ELISA human 93.2%, 95.5%; and ELISA animal 74.6%, 91.3%. The results showed the efficiency of FIDIS with analytical performance equivalent to the conventional methods, but having the advantage of giving quantitative results (IU/mL).