The synovial and blood monocyte DNA methylomes mirror prognosis, evolution, and treatment in early arthritis.

Identifying predictive biomarkers at early stages of inflammatory arthritis is crucial for starting appropriate therapies to avoid poor outcomes. Monocytes (MOs) and macrophages, largely associated with arthritis, are contributors and sensors of inflammation through epigenetic modifications. In this study, we investigated associations between clinical features and DNA methylation in blood and synovial fluid (SF) MOs in a prospective cohort of patients with early inflammatory arthritis. DNA methylation profiles of undifferentiated arthritis (UA) blood MOs exhibited marked alterations in comparison with those from healthy donors. We identified additional differences both in blood and SF MOs after comparing patients with UA grouped by their future outcomes, i.e., good versus poor. Patient profiles in subsequent visits revealed a reversion toward a healthy level in both groups, those requiring disease-modifying antirheumatic drugs and those who remitted spontaneously. Changes in disease activity between visits also affected DNA methylation, which was partially concomitant in the SF of UA and in blood MOs of patients with rheumatoid arthritis. Epigenetic similarities between arthritis types allow a common prediction of disease activity. Our results constitute a resource of DNA methylation-based biomarkers of poor prognosis, disease activity, and treatment efficacy for the personalized clinical management of early inflammatory arthritis.

Palindromic Rheumatism: Just a Pre-rheumatoid Stage or Something Else?

Palindromic rheumatism (PR), a unique clinical entity, has a characteristic clinical presentation with a relapsing/remitting course. It is established that most patients with PR evolve to chronic disease, of which rheumatoid arthritis (RA) is by far the most common. The relationship between PR and RA is unclear, with similarities and differences between the two, and not all patients evolve to RA in the long-term. Therefore, PR is clearly a pre-RA stage for most, but not all, patients. Autoimmunity plays a substantial role in PR, with the same characteristic autoantibody profile observed in RA, although with some differences in the immune response repertoire. Autoinflammation may also be relevant in some cases of PR. Prognostic factors for RA progression are identified but their exact predictive value is not clear. There are several unmet needs in PR, such as the diagnostic criteria and clinical case definition, the pathogenic mechanisms involved in the unusual clinical course, and the evolution to RA, and our understanding of the therapeutic strategy that could best avoid progression to persistent and potentially destructive arthritis.

Anti-carbamylated protein antibody isotype pattern differs between palindromic rheumatism and rheumatoid arthritis.

BACKGROUND: A restricted response against citrullinated peptides/proteins, with less isotype usage, has been found in palindromic rheumatism (PR) in comparison with rheumatoid arthritis (RA). We hypothesized that this different antibody response may be observed for other post-translational modified proteins. We compared the prevalence and isotype usage of two specificities of anti-carbamylated peptide/protein antibodies (Anti-CarP) in patients with PR and RA. METHODS: Cross-sectional study including 54 patients with pure PR and 53 patients with RA, matched by sex, age, disease duration and ACPA. Anti-CarP specificities were determined by home-made enzyme-linked immunosorbent assay tests using a synthetic chimeric fibrin/filaggrin homocitrullinated peptide (CFFHP) and fetal calf serum (FCS) homocitrullinated protein as antigens. IgG, IgA and IgM isotypes were measured. RESULTS: Anti-CarP were positive (CFFHP or FCS) in 24% and 64% of patients with PR and RA, respectively (p < 0.005). All Anti-CarP isotype proportions were significantly lower in PR than in RA: Anti-CarP-IgG (24% versus 51%), Anti-CarP-IgA (7% versus 34%) and Anti-CarP-IgM (7% versus 36%). Mean titers of Anti-CarP isotypes were also lower in PR. In Anti-CarP positive patients, the isotype distribution differed between PR and RA: IgG Anti-CarP was used in all PR patients and in 79% of RA patients. By contrast, a significantly lower isotype usage of both IgA (31% versus 53%) and IgM (31% versus 56%) was observed in PR patients. No significant differences in clinical or demographic characteristics were observed according to Anti-CarP status in PR patients, except for a higher prevalence of ACPA and higher mean titers of ACPA and rheumatoid factor in Anti-CarP positive patients. CONCLUSION: Anti-CarP are found in patients with PR but in a lower proportion and with a different isotype usage from in RA, suggesting a distinct B cell response to homocitrullinated antigens in PR.

Genetic variation at the glycosaminoglycan metabolism pathway contributes to the risk of psoriatic arthritis but not psoriasis.

OBJECTIVE: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis affecting up to 30% of patients with psoriasis (Ps). To date, most of the known risk loci for PsA are shared with Ps, and identifying disease-specific variation has proven very challenging. The objective of the present study was to identify genetic variation specific for PsA. METHODS: We performed a genome-wide association study in a cohort of 835 patients with PsA and 1558 controls from Spain. Genetic association was tested at the single marker level and at the pathway level. Meta-analysis was performed with a case-control cohort of 2847 individuals from North America. To confirm the specificity of the genetic associations with PsA, we tested the associated variation using a purely cutaneous psoriasis cohort (PsC, n=614) and a rheumatoid arthritis cohort (RA, n=1191). Using network and drug-repurposing analyses, we further investigated the potential of the PsA-specific associations to guide the development of new drugs in PsA. RESULTS: We identified a new PsA risk single-nucleotide polymorphism at B3GNT2 locus (p=1.10e-08). At the pathway level, we found 14 genetic pathways significantly associated with PsA (pFDR<0.05). From these, the glycosaminoglycan (GAG) metabolism pathway was confirmed to be disease-specific after comparing the PsA cohort with the cohorts of patients with PsC and RA. Finally, we identified candidate drug targets in the GAG metabolism pathway as well as new PsA indications for approved drugs. CONCLUSION: These findings provide insights into the biological mechanisms that are specific for PsA and could contribute to develop more effective therapies.

Correction to: The beliefs of rheumatoid arthritis patients in their subcutaneous biological drug: strengths and areas of concern.

In the original publication, the family name of the last author was incorrect. The correct name should read as Jaime Calvo-Alén.

The beliefs of rheumatoid arthritis patients in their subcutaneous biological drug: strengths and areas of concern.

Patients' beliefs about their prescribed medication are an important factor influencing intentional non-adherence. This study describes rheumatoid arthritis (RA) patients' beliefs about their subcutaneous (SC) biological medication through the Beliefs about Medicines Questionnaire (BMQ), and potential associations. As part of the ARCO study (Study on Adherence of Rheumatoid arthritis patients to subCutaneous and Oral drugs), patients completed the BMQ specifically for their SC biological medication, encompassing a necessity and a concerns scale. The medication possession ratio (MPR) was calculated to assess adherence to the SC biological medication. The BMQ was completed by 321 patients. Between 71.0 and 89.7% of patients agreed/strongly agreed with necessity scale statements, and only 7.2% had low necessity scores. Between 20.0 and 49.8% of patients agreed/strongly agreed with four of five concern scale statements, and 72.3% agreed/strongly agreed with the concern statement regarding long-term medication effects. The percentage with high concerns was 58.9%, and was higher in patients not satisfied with, or with less fulfillment of, tolerability expectations. Non-adherence percentages were, respectively, 13.8 and 13.0% (p = 0.919) in those with high or low necessity, and 16.0 and 10.6% (p = 0.171) in those with high or low concerns. Most patients were categorized as 'ambivalent' (58.5%; high necessity/high concerns) or 'accepting' (36.1%; high necessity/low concerns) of their SC biological medication. The BMQ identified patients' concerns with their SC biological medication. Because patients' concerns could influence non-adherence to medication and future outcomes, physicians should address this issue in the clinic by informing patients and setting clear expectations.

Differing specificities and isotypes of anti-citrullinated peptide/protein antibodies in palindromic rheumatism and rheumatoid arthritis.

BACKGROUND: To analyze differences in the recognition of anti-citrullinated peptide/protein antibody (ACPA) citrullinated epitopes and isotypes in patients with palindromic rheumatism (PR) and rheumatoid arthritis (RA). METHODS: ACPA fine specificities (citrullinated peptides of enolase, fibrin, and vimentin) and isotypes (IgG, IgM, and IgA) were analyzed in 54 patients with longstanding PR and 54 patients with established RA. RESULTS: CCP2 tested positive in 66.7% of patients with PR and RA. The ACPA distribution of fine specificities and isotypes differed between PR and RA patients. PR patients had a lower frequency of fine ACPA specificities than RA patients, which was significant in the case of a peptide derived from vimentin (PR 24.1% vs. 59.3% RA; p < 0.001). The mean number of ACPA specificities was lower in PR than in RA patients, and only 25.9% of PR patients recognized ≥2 additional specificities compared with 46.3% of RA patients. Significantly less isotype usage, especially IgA, was observed in PR patients. CONCLUSION: The ACPA immune response differed in patients with PR and RA, with fewer fine specificities and isotype usage in patients with PR. Some patients with PR may have impaired maturation of the B-cell response against citrullinated peptides with no progression to RA.

Identification of patients at risk of non-adherence to oral antirheumatic drugs in rheumatoid arthritis using the Compliance Questionnaire in Rheumatology: an ARCO sub-study.

The ARCO study (Study on Adherence of Rheumatoid Arthritis patients to SubCutaneous and Oral Drugs), a multicenter, non-interventional retrospective study, was primarily designed to assess the percentage of patients [aged ≥18 years with an established rheumatoid arthritis (RA) diagnosis] with non-adherence to prescribed subcutaneous biologicals. This paper reports data for the secondary objective from a subset of patients, namely to evaluate non-adherence to prescribed oral antirheumatic drugs in RA patients in Spain using the validated Compliance Questionnaire Rheumatology (CQR). Patients also completed the Morisky-Green Medication Adherence Questionnaire, Beliefs about Medicines Questionnaire, and a questionnaire (developed and validated in Spain) on patient satisfaction with RA treatment and preferences. A total of 271 patients (76.7% females; mean age 55.6 years) were being treated with oral drugs for RA, of which 234 completed the CQR questionnaire. Non-adherence was reported in 49/234 (20.9%) patients. The proportion of non-adherence in younger patients (aged ≤48 years; 37.5%) was double that recorded in patients aged >48 years (p = 0.006). Patients with a perception of lower efficacy also had a higher risk of non-adherence (p = 0.012). Multivariable analysis showed that younger age and male gender were independently associated with risk of non-adherence. There was only slight agreement between the CQR and Morisky-Green assessment tools (kappa coefficient = 0.186), possibly reflecting the fact that both questionnaires measure slightly different aspects of medication adherence. In conclusion, one out of five RA patients was identified as at risk for non-adherence with the CQR, and this was more frequent in younger patients and in males.

Non-adherence to subcutaneous biological medication in patients with rheumatoid arthritis: a multicentre, non-interventional study.

OBJECTIVES: To evaluate non-adherence to prescribed subcutaneous biologicals in rheumatoid arthritis (RA) patients in Spain. METHODS: ARCO (Study on Adherence of Rheumatoid Arthritis patients to SubCutaneous and Oral Drugs) was a multicentre, non-interventional retrospective study involving 42 rheumatology clinics from representative hospitals throughout Spain. The primary objective was to assess the percentage of patients (aged ≥18 years with an established RA diagnosis) with non-adherence to prescribed subcutaneous biologicals using clinical records and hospital pharmacy dispensing logs as the primary information sources. Adherence was assessed using the Medication Possession Ratio (MPR). Additionally, patients completed the Morisky-Green Medication Adherence Questionnaire. RESULTS: A total of 364 patients (77.5% females, mean age 54.9 years, median RA duration since diagnosis 7.8 years) were enrolled in ARCO. Non-adherence (MPR ≤80%) was reported in 52/363 evaluable patients (14.3%), and was lower in patients receiving initial monthly drug administration (6.4%) than with weekly (17.4%; p=0.034) or every two weeks (14.4%; p=0.102) administration. By multivariate analysis, non-adherence was positively associated with RA duration above the median and with using induction doses. Monthly administration, compared to weekly administration, was inversely associated with non-adherence. Age, gender, order of administration, and changes in the interval of administration, showed no association with non-adherence. Compared with the MPR, the Morisky-Green questionnaire performed poorly in detecting non-adherence. CONCLUSIONS: Non-adherence to the prescribed subcutaneous biological drug occurred in 14.3% of patients with RA. Patients using the most convenient administration period (i.e. monthly) had better adherence than those using more frequent dosing schedules.

Retraso diagnóstico y terapéutico de la artritis reumatoide y su relación con dispositivos asistenciales en Catalunya. Estudio AUDIT / Diagnostic and therapeutic delay of rheumatoid arthritis and its relationship with health care devices in Catalonia. The AUDIT study

OBJETIVO: Analizar el retraso diagnóstico y terapéutico en pacientes con AR de reciente comienzo en 19 centros de Catalunya. MÉTODOS: Encuesta epidemiológica en 183 pacientes en que se cuantificaron los tiempos en relación con el retraso diagnostico midiendo: 1) aparición del primer síntoma hasta la primera visita a Reumatología; 2) desde la derivación hasta la primera visita de Reumatología; 3) entre aparición del primer síntoma hasta el diagnóstico, y 4) entre aparición del primer síntoma hasta el inicio del primer FAME. Se definió la existencia de 6 dispositivos asistenciales diferenciados. RESULTADOS: El tiempo medio desde el inicio de los síntomas hasta la instauración de un FAME en pacientes con AR en Catalunya es muy largo (11 meses). Pacientes atendidos en dispositivos como consultas de AR, consultas especializadas en atención primaria y sobre todo en consultas de artritis de inicio son tratados de manera más temprana con FAME. Conclusión. La existencia de determinados dispositivos asistenciales es fundamental para mejorar la atención precoz en la AR

OBJECTIVE: Diagnosis and therapy of patients with early onset rheumatoid arthritis (RA) is influenced by accessibility to specialized care devices. We attempted to analyze the impact of their availability. METHODS: We analyzed time related to diagnosis delay measuring: 1) Time from first clinical symptoms to the first visit with the Rheumatologist; 2) Time from referral to the first visit of Rheumatology; 3) Time between first symptom until final diagnosis; 4) time between first symptom until the initiation of the first disease-modifying antirheumatic drug (DMARD). The presence of these 6 rheumatology devices was defined: 1) early arthritis monographic clinics, 2) RA monographic clinics, 3) Mechanisms for fast programming, 4) Algorithms for referral from primary care (PC), 5) rheumatology consultation services in PC and 6) consulting services in PC. RESULTS: The mean time from onset of symptoms to diagnosis or the establishment of a DMARD in RA patients in Catalonia is very long (11 months). Patients seen in rheumatology devices such as RA monographic clinics, rheumatology consultation in PC and specially in early arthritis clinics are treated early with DMARDs. Conclusion. the existence of monographic clinics or consulting in primary care centers is essential to improve early care of RA patients

Diagnostic and therapeutic delay of rheumatoid arthritis and its relationship with health care devices in Catalonia. The AUDIT study. / Retraso diagnóstico y terapéutico de la artritis reumatoide y su relación con dispositivos asistenciales en Catalunya. Estudio AUDIT.

OBJECTIVE: Diagnosis and therapy of patients with early onset rheumatoid arthritis (RA) is influenced by accessibility to specialized care devices. We attempted to analyze the impact of their availability. METHODS: We analyzed time related to diagnosis delay measuring: 1) Time from first clinical symptoms to the first visit with the Rheumatologist; 2) Time from referral to the first visit of Rheumatology; 3) Time between first symptom until final diagnosis; 4) time between first symptom until the initiation of the first disease-modifying antirheumatic drug (DMARD). The presence of these 6 rheumatology devices was defined: 1) early arthritis monographic clinics, 2) RA monographic clinics, 3) Mechanisms for fast programming, 4) Algorithms for referral from primary care (PC), 5) rheumatology consultation services in PC and 6) consulting services in PC. RESULTS: The mean time from onset of symptoms to diagnosis or the establishment of a DMARD in RA patients in Catalonia is very long (11 months). Patients seen in rheumatology devices such as RA monographic clinics, rheumatology consultation in PC and specially in early arthritis clinics are treated early with DMARDs. CONCLUSION: the existence of monographic clinics or consulting in primary care centers is essential to improve early care of RA patients.

A deletion at ADAMTS9-MAGI1 locus is associated with psoriatic arthritis risk.

OBJECTIVE: Copy number variants (CNVs) have been associated with the risk to develop multiple autoimmune diseases. Our objective was to identify CNVs associated with the risk to develop psoriatic arthritis (PsA) using a genome-wide analysis approach. METHODS: A total of 835 patients with PsA and 1498 healthy controls were genotyped for CNVs using the Illumina HumanHap610 BeadChip genotyping platform. Genomic CNVs were characterised using CNstream analysis software and analysed for association using the χ(2) test. The most significant genomic CNV associations with PsA risk were independently tested in a validation sample of 1133 patients with PsA and 1831 healthy controls. In order to test for the specificity of the variants with PsA aetiology, we also analysed the association to a cohort of 822 patients with purely cutaneous psoriasis (PsC). RESULTS: A total of 165 common CNVs were identified in the genome-wide analysis. We found a highly significant association of an intergenic deletion between ADAMTS9 and MAGI1 genes on chromosome 3p14.1 (p=0.00014). Using the independent patient and control cohort, we validated the association between ADAMTS9-MAGI1 deletion and PsA risk (p=0.032). Using next-generation sequencing, we characterised the 26 kb associated deletion. Finally, analysing the PsC cohort we found a lower frequency of the deletion compared with the PsA cohort (p=0.0088) and a similar frequency to that of healthy controls (p>0.3). CONCLUSIONS: The present genome-wide scan for CNVs associated with PsA risk has identified a new deletion associated with disease risk and which is also differential from PsC risk.

PDE3A-SLCO1C1 locus is associated with response to anti-tumor necrosis factor therapy in psoriatic arthritis.

Aim: Variation at PDE3A-SLCO1C1 locus has been recently associated with the response to anti-TNF therapy in rheumatoid arthritis. We undertook the present study to determine whether PDE3A-SLCO1C1 is also associated with the response to anti-TNF therapy in psoriatic arthritis. Patients & methods: Genomic DNA was obtained from 81 psoriatic arthritis patients that had been treated with anti-TNF therapy. PDE3A-SLCO1C1 SNP rs3794271 was genotyped using Taqman realt-time PCR. The clinical response to anti-TNF therapy was measured as the change from baseline in the level of disease activity according to the DAS28 score. Results: A significant association between rs3794271 and anti-TNF response in psoriatic arthritis was found (beta = -0.71; p = 0.0036). Conclusion: PDE3A-SLCO1C1 locus is also associated with response to anti-TNF therapy in psoriatic arthritis. Original submitted 12 May 2014; Revision submitted 18 August 2014.

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.

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.

Diagnosis of tuberculosis infection by tuberculin skin test and a whole-blood interferon-γ release assay in patients considered for anti-tumor necrosis factor-α therapy.

To assess the performance of QuantiFERON®-TB Gold in-Tube (QFT-GIT; Cellestis, Carnegie, Australia) and tuberculin skin test (TST) in patients with immune-mediated inflammatory diseases (IMID), before anti-tumor necrosis factor-α (TNF-α) therapy, and to compare the results with those from the healthy population. Three hundred fourteen subjects (214 with IMID and 100 controls) underwent simultaneous QFT-GIT and TST. QFT-GIT was positive in 21% of IMID patients and in 16% of controls (P = 0.29). Among IMID patients, 21% tested positive by QFT-GIT and 24%, by TST (P = 0.30). Positive QFT-GIT results were not affected by immunosuppressive therapy (odds ratio, 0.78; 95% confidence interval [CI], 0.36-1.68; P = 0.52). Agreement between both tests in those patients who tested positive by one of the tests was 50% (95% CI, 37.2-62.8). QFT-GIT is useful for identifying IMID patients requiring treatment of latent tuberculosis before anti-TNF therapy. However, given the poor agreement between TST and QFT-GIT, we advocate a strategy of simultaneous testing to optimize diagnostic sensitivity.

Validity, reproducibility, and responsiveness of a twelve-joint simplified power doppler ultrasonographic assessment of joint inflammation in rheumatoid arthritis.

OBJECTIVE: To investigate the validity, reproducibility, and responsiveness of a simplified power Doppler ultrasound (PDUS) assessment of joint inflammation compared with a comprehensive 44-joint PDUS assessment in patients with rheumatoid arthritis (RA) who started therapy with a biologic agent. METHODS: A total of 160 patients with active RA who started a biologic agent were prospectively recruited in 18 Spanish centers. The patients underwent clinical and laboratory assessment and blinded PDUS examination at baseline and 6 months. A PDUS examination of 128 synovial sites in 44 joints was performed. US synovitis and PD signal were semiquantitatively graded from 1 to 3 in all synovial sites. US count and index for synovitis and PD signal were obtained. PDUS intraobserver and interobserver reliability were evaluated. A process of data reduction based on the frequency of involvement of synovial sites by both synovitis and PD signal was conducted. Construct and discriminant validity of a simplified PDUS assessment was investigated. RESULTS: A PDUS simplified assessment including 24 synovial sites from 12 joints detected 100% of patients with synovitis and 91% of patients with PD signal. There was a highly significant correlation between the 44-joint count and index for synovitis and PD signal and the 12-joint count and index for synovitis and PD signal at baseline and 6 months (r = 0.84-0.90, P < 0.0005). The smallest detectable difference was lower than the mean change in simplified PDUS variables. CONCLUSION: A 12-joint PDUS assessment of RA joint inflammation may be a valid, feasible method for multicenter monitoring of therapeutic response to biologic agents.

Palindromic rheumatism and other relapsing arthritis.

Patients with recurrent or relapsing arthritis are frequently seen in rheumatological practice. Besides crystal arthritis, the most frequent cause of recurrent arthritis, there are several diseases that may present clinically as intermittent mono- or polyarthritis. Palindromic rheumatism is the paradigm of this type of condition, but other diseases such as systemic autoinflammatory disorders (periodic fever syndromes), Whipple's disease, arthritis associated with hyperlipidemia, intermittent hydrarthrosis and other diseases should be taken into account in the differential diagnosis of patients with recurrent arthritis. In this chapter, we discuss recent developments in these diseases with special emphasis on palindromic rheumatism, a common condition whose close relationship with rheumatoid arthritis remains intriguing.

Diagnostic usefulness of synovial vascular morphology in chronic arthritis. A systematic survey of 100 cases.

OBJECTIVES: To assess the diagnostic usefulness of the systematic analysis of synovial vascular morphology in various inflammatory, early, and longstanding arthropathies, and to examine the validity of the vascular patterns in predicting the evolution of a group of patients with undifferentiated arthritis (UA). METHODS: One hundred patients who underwent rheumatologic arthroscopy of a symptomatic joint (85 knees, 11 wrists, 3 elbows, 1 metacarpophalangeal joint) were evaluated. The same observer, blinded to patient diagnosis, analyzed the video recordings of the arthroscopies. Vascular morphology was classified into 3 patterns: straight, tortuous, and mixed. RESULTS: Eighty-one patients had inflammatory arthritis: 35 rheumatoid arthritis (RA), 16 psoriatic arthritis (PsA), 13 spondyloarthropathies (SpA), and 17 UA. Forty-nine percent of patients with RA had a straight pattern, 28% a mixed, and 23% a tortuous one. The sensitivity rate of the straight pattern for RA was 77% and the specificity rate was 70%. Seventy-six percent of RA patients with a straight pattern were rheumatoid factor positive (RF+) against 25% of RA patients with a tortuous pattern. The odds ratio for RA associated to straight compared with tortuous pattern was 57.3 (95% confidence interval, 6.6 to 499.5; P <.001). Patients with PsA and SpA shared the same pattern and were analyzed as 1 group. Ninety-three percent of patients with PsA/SpA had a tortuous pattern, 4% a straight pattern, and 3% a mixed pattern. The sensitivity rate of the tortuous pattern for PsA/SpA was 61% and the specificity rate was 95%. During 2 years of follow-up, 6 of 17 patients with UA were definitely diagnosed: 4 RA (2 RF+ and straight pattern; 2 with a tortuous pattern, 1 with RF+ and HLA-B27+); 1 SpA and 1 PsA, both with a tortuous pattern. No differences in vascular patterns were observed according to disease duration. Our results indicate that vascular patterns are not modified by disease modifying antirheumatic drug (DMARD) treatment. The other 19 patients had osteoarthritis (n = 8) and calcium pyrophosphate dihydrate crystal deposition disease (n = 11) and their predominant vascular pattern was tortuous-like. CONCLUSIONS: Arthroscopic assessment of synovial vascular changes in chronic arthritis may be of diagnostic and pathogenetic interest, although differences between published studies suggest a need for consensus in evaluating vascular patterns. A straight pattern is strongly associated with RF + RA whereas a tortuous pattern is generally associated with PsA or SpA; these associations are independent of disease duration. The vascular pattern likely does not change qualitatively with DMARD therapy. The application of this technique to the diagnosis or prognosis of patients with UA may be a complementary tool for the treatment of these patients, but larger, prospective studies are necessary to confirm this hypothesis.