Early Rheumatoid Arthritis in Latin America: Low Socioeconomic Status Related to High Disease Activity at Baseline

Objective. To determine the influence of socioeconomic factors on disease activity in a Latin American (LA) early rheumatoid arthritis (RA) multinational inception cohort at baseline. Methods. Clinical evaluation, ethnicity, socioeconomic status (SES), 4-variable Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR), Health Assessment Questionnaire (HAQ) disability index (DI), and erosions were recorded in 1,093 patients with early RA (<1 year from onset). Multivariate analyses evaluated influences of sex, age, marital status, education, medical coverage, SES, and ethnicity on HAQ DI, DAS28-ESR, and presence of erosions. Results. Ethnicities included 43% Mestizo, 31% Caucasian, 19% African LA, 4% Amerindian, and 3% other. Fifty-eight percent were of low/low-middle SES, 42% had <8 years of education, 21% had no medical coverage, median disease duration was 6 months (25th, 75th percentiles 4, 9 months), median HAQ DI score was 1.25 (25th, 75th percentiles 0.63, 2.00), median DAS28-ESR score was 6.2 (25th, 75th percentiles 4.9, 7.2), and 25% had erosions. Women and Mestizos, African LA, and Amerindians had earlier onset than men or Caucasians (P < 0.01). When adjusted by country, the analysis of covariance model showed that low/low-middle SES, female sex, partial coverage, and older age were associated with worse HAQ DI scores; only low/low-middle SES was associated with higher DAS28 scores. Statistically significant differences were found in HAQ DI and DAS28 scores between countries. When excluding country, low/low-middle SES, female sex, and no coverage were associated with worse HAQ DI and DAS28 scores, whereas separated/divorced/widowed status was associated with worse HAQ DI scores and age was associated with worse DAS28 scores. Logistic regression showed that older age, no coverage, and the Amerindian and other ethnic groups were associated with erosions. Conclusion. We compared early RA patients from the main LA ethnic groups. Our findings suggest that low/low-middle SES is important in determining disease activity. A more genetic-related background for erosions is possible.

The presence of anti-citrullinated protein antibodies (ACPA) and rheumatoid factor on patients with rheumatoid arthritis (RA) does not interfere with the chance of clinical remission in a follow-up of 3 years

Autoantibodies in early rheumatoid arthritis (RA) have important diagnostic value. The association between the presence of autoantibodies against cyclic citrullinated peptide and the response to treatment is controversial. To prospectively evaluate a cohort of patients with early rheumatoid arthritis (< 12 months of symptoms) in order to determine the association between serological markers (rheumatoid factor (RF), anti-citrullinated protein antibodies) such as anti-cyclic citrullinated peptide antibodies (anti-CCP) and citrullinated anti-vimentin (anti-Sa) with the occurrence of clinical remission, forty patients diagnosed with early RA at the time of diagnosis were evaluated and followed for 3 years, in use of standardized therapeutic treatment. Demographic and clinical data were recorded, disease activity score 28 (DAS 28), as well as serology tests (ELISA) for RF (IgM, IgG, and IgA), anti-CCP (CCP2, CCP3, and CCP3.1) and anti-Sa in the initial evaluation and at 3, 6, 12, 18, 24, and 36 months of follow-up. The outcome evaluated was the percentage of patients with clinical remission, which was defined by DAS 28 lower than 2.6. Comparisons were made through the Student t test, mixed-effects regression analysis, and analysis of variance (significance level of 5%). The mean age was 45 years, and a female predominance was observed (90%). At the time of diagnosis, RF was observed in 50% of cases (RF IgA-42%, RF IgG-30%, and RF IgM-50%), anti-CCP in 50% (no difference between CCP2, CCP3, and CCP3.1) and anti-Sa in 10%. After 3 years, no change in the RF prevalence and anti-CCP was observed, but the anti-Sa increased to 17.5% (P = 0.001). The percentage of patients in remission, low, moderate, and intense disease activity, according to the DAS 28, was of 0, 0, 7.5, and 92.5% (initial evaluation) and 22.5, 7.5, 32.5, and 37.5% (after 3 years). There were no associations of the presence of autoantibodies in baseline evaluation and in serial analysis with the percentage of clinical remission during follow-up of 3 years The presence of autoantibodies in early RA has no predictive value for clinical remission in early RA.

Adalimumab induced-inflammatory myopathy in rheumatoid arthritis

The application of immunobiologics for the rheumatoid arthritis treatment may present as a rare complication the development of inflammatory myopathy. Until this moment, there have been described in literature only seven cases of inhibitors of tumor necrosis factor induced-myositis. In this paper, we report the case of the patient with 39 years-old with eight years of arthritis rheumatoid and that due to refractory to various immunosuppressive drugs, the adalimumab was introduced, and evolved to dermatomyositis status.

Videolaryngostroboscopy and voice evaluation in patients with rheumatoid arthritis

Arthritis may affect the larynx and produce symptoms such as hoarseness and vocal fatigue. Objective: This paper aimed to evaluate the laryngeal manifestations of rheumatoid arthritis. Methods: This is prospective study assessed 27 patients with rheumatoid arthritis with the aid of videolaryngostroboscopy, auditory-perceptual analysis of the speech using the GIRBAS scale, acoustic analysis and the Voice Handicap Index questionnaire. Results: Nineteen patients had laryngeal complaints, the main ones being intermittent dysphonia and sensation of a foreign body in the throat. The most frequent laryngoscopical finding was overlapping arytenoids. Three patients had low pitch, nine patients had mild dysphonia and roughness. Median acoustic measures were: F0, 198.39 Hz; Jitter, 0.815; Shimmer, 4.915; and NHR, 0.144. Regarding the Voice Handicap Index, the median score was zero in all domains. There was a statistically significant correlation between voice complaints and the domains of this index. Functional classes were significantly correlated to: overlapping arytenoids (p = 0.001), PPQ (p = 0.0257), Shimmer (p = 0.0295), APQ (p = 0.0195), and the VHI physical (p = 0.0227) and total domains (p = 0.0425). Conclusion: Laryngeal complaints were reported by 70.4% of the patients and laryngoscopical alterations were observed in 48% of the subjects. Voice acoustic evaluation and self-perception were altered.

TOMOGRAPHIC ANALYSIS FOR C2 SCREW PLACEMENT IN RHEUMATOID ARTHRITIS PATIENTS

Objective: A morphological analysis of the bone structure of 02 in patients with rheumatoid arthritis in order to enhance the security of the stabilization procedures for this vertebra. Methods: We retrospectively analyzed 20 CT scans of the cervical spine performed in patients with rheumatoid arthritis; the following parameters were measured: spinolaminar angle, thickness and length of C2 lamina. Results: The mean values are: 5.92mm and 5.87mm for thickness of right and left laminae retrospectively, 27.75mm for right lamina length and 27.94mm for left lamina length, and 44.7 degrees for spinolaminar angle. Conclusion: The values obtained are consistent with studies in normal subjects published by other groups, with no apparent need for change in the screw placement technique. Level of Evidence IV, Case Series.

Pierre-Auguste Renoir (1841-1919) and rheumatoid arthritis

Pierre-Auguste Renoir (1841-1919), one of the world's most celebrated impressionist painters, suffered from rheumatoid arthritis for most of his life. His symptoms developed when he was in his 50s and they became aggressive at about the age of 60 years that led to almost complete disability when he was 70 years old. Although the deformities he suffered because of the rheumatoid arthritis were disabling, Renoir never stopped painting nor decreased the quality of his work. The transition between styles adopted by the painter (Impressionist, Dry and Pearly periods) bear no relationship to the stages of flare-ups or the establishment of joint deformities due to rheumatoid arthritis. His work shows aspects of the body's ability to overcome pain and physical limitation.

Differential Gene Expression Profiles May Differentiate Responder and Nonresponder Patients with Rheumatoid Arthritis for Methotrexate (MTX) Monotherapy and MTX plus Tumor Necrosis Factor Inhibitor Combined Therapy

Objective. We aimed to evaluate whether the differential gene expression profiles of patients with rheumatoid arthritis (RA) could distinguish responders from nonresponders to methotrexate (MTX) and, in the case of MTX nonresponders, responsiveness to MTX plus anti-tumor necrosis factor-alpha (anti-TNF) combined therapy. Methods. We evaluated 25 patients with RA taking MTX 15-20 mg/week as a monotherapy (8 responders and 17 nonresponders). All MTX nonresponders received intliximab and were reassessed after 20 weeks to evaluate their anti-TNF responsiveness using the European League Against Rheumatism response criteria. A differential gene expression analysis from peripheral blood mononuclear cells was performed in terms of hierarchical gene clustering, and an evaluation of differentially expressed genes was performed using the significance analysis of microarrays program. Results. Hierarchical gene expression clustering discriminated MTX responders from nonresponders, and MTX plus anti-TNF responders from nonresponders. The evaluation of only highly modulated genes (fold change > 1.3 or < 0.7) yielded 5 induced (4 antiapoptotic and CCL4) and 4 repressed (4 proapoptotic) genes in MTX nonresponders compared to responders. In MTX plus anti-TNF nonresponders, the CCL4, CD83, and BCL2A1 genes were induced in relation to responders. Conclusion. Study of the gene expression profiles of RA peripheral blood cells permitted differentiation of responders from nonresponders to MTX and anti-TNF. Several candidate genes in MTX non-responders (CCL4, HTRA2, PRKCD, BCL2A1, CAV1, TNIP1 CASP8AP2, MXD1, and BTG2) and 3 genes in MTX plus anti-TNF nonresponders (CCL4, CD83, and BCL2A1) were identified for further study. (First Release July 1 2012; J Rheumatol 2012;39:1524-32; doi:10.3899/jrheum.120092)

Determinants of discordance in patients' and physicians' rating of rheumatoid arthritis disease activity

Objective To assess the determinants of patients' (PTGL) and physicians' (MDGL) global assessment of rheumatoid arthritis (RA) activity and factors associated with discordance among them. Methods. A total of 7,028 patients in the Quantitative Standard Monitoring of Patients with RA study had PTGL and MDGL assessed at the same clinic visit on a 0-10-cm visual analog scale (VAS). Three patient groups were defined: concordant rating group (PTGL and MDGL within >= 2 cm), higher patient rating group (PTGL exceeding MDGL by > 2 cm), and lower patient rating group (PTGL less than MDGL by > 2 cm). Multivariable regression analysis was used to identify determinants of PTGL and MDGL and their discordance. Results. The mean +/- SD VAS scores for PTGL and MDGL were 4.01 +/- 2.70 and 2.91 +/- 2.37, respectively. Pain was overwhelmingly the single most important determinant of PTGL, followed by fatigue. In contrast, MDGL was most influenced by swollen joint count (SJC), followed by erythrocyte sedimentation rate (ESR) and tender joint count (TJC). A total of 4,454 (63.4%), 2,106 (30%), and 468 (6.6%) patients were in the concordant, higher, and lower patient rating groups, respectively. Odds of higher patient rating increased with higher pain, fatigue, psychological distress, age, and morning stiffness, and decreased with higher SJC, TJC, and ESR. Lower patient rating odds increased with higher SJC, TJC, and ESR, and decreased with lower fatigue levels. Conclusion. Nearly 36% of patients had discordance in RA activity assessment from their physicians. Sensitivity to the "disease experience" of patients, particularly pain and fatigue, is warranted for effective care of RA.

Persistent Periodontal Disease Hampers Anti-Tumor Necrosis Factor Treatment Response in Rheumatoid Arthritis

Objective: This study aimed to evaluate prospectively the influence and the evolution of periodontal disease (PD) in rheumatoid arthritis (RA) patients submitted to anti-tumor necrosis factor (TNF) therapy. Methods: Eighteen patients with RA (according to the American College of Rheumatology criteria) were assessed for PD before (BL) and after 6 months (6M) of anti-TNF treatment: 15 infliximab, 2 adalimumab, and 1 etanercept. Periodontal assessment included plaque and gingival bleeding indices, probing pocket depth, cementoenamel junction, and clinical attachment level. Rheumatologic evaluation was performed blinded to the dentist's assessment: demographic data, clinical manifestations, and disease activity (Disease Activity Score using 28 joints [DAS28], erythrocyte sedimentation rate [ESR], and C-reactive protein [CRP]). Results: The median age and disease duration of patients with RA were 50 years (25-71 y) and 94% were female. Periodontal disease was diagnosed in 8 patients (44.4%). Comparing BL to 6M, periodontal parameters in the entire group remained stable (P > 0.05) throughout the study (plaque and gingival bleeding indices, probing pocket depth, cementoenamel junction, and clinical attachment level), whereas an improvement in most analyzed RA parameters was observed in the same period: DAS28 (5.5 vs. 3.9, P = 0.02), ESR (21 vs. 12.5 mm/first hour, P = 0.07), and CRP (7.8 vs. 2.8 mg/dL, P = 0.25). Further analysis revealed that this improvement was restricted to the group of patients without PD (DAS28 [5.5 vs. 3.6, P = 0.04], ESR [23.0 vs. 11.5 mm/first hour, P = 0.008], and CRP [7.4 vs. 2.1, P = 0.01]). In contrast, patients with PD had lack of response, with no significant differences in disease activity parameters between BL and 6M: DAS28 (5.2 vs. 4.4, P = 0.11), ESR (17.0 vs. 21.0, P = 0.56), and CRP (9.0 vs. 8.8, P = 0.55). Conclusions: This study supports the notion that PD may affect TNF blocker efficacy in patients with RA. The possibility that a sustained gingival inflammatory state may hamper treatment response in this disease has high clinical interest because this is a treatable condition.

Bilateral asymptomatic fibrous-ankylosis of the temporomandibular joint associated with rheumatoid arthritis: a case report

The American Academy of Orofacial Pain (AAOP) defines ankylosis of the temporomandibular joint (TMJ) as a restriction of movements due to intracapsular fibrous adhesions, fibrous changes in capsular ligaments (fibrous-ankylosis) and osseous mass formation resulting in the fusion of the articular components (osseous-ankylosis). The clinical features of the fibrous-ankylosis are severely limited mouth-opening capacity (limited range of motion during the opening), usually no pain and no joint sounds, marked deflection to the affected side and marked limitation of movement to the contralateral side. A variety of factors may cause TMJ ankylosis, such as trauma, local and systemic inflammatory conditions, neoplasms and TMJ infection. Rheumatoid arthritis (RA) is one of the systemic inflammatory conditions that affect the TMJ and can cause ankylosis. The aim of this study is to present a case of a female patient diagnosed with bilateral asymptomatic fibrous-ankylosis of the TMJ associated with asymptomatic rheumatoid arthritis. This case illustrates the importance of a comprehensive clinical examination and correct diagnosis of an unusual condition causing severe mouth opening limitation.

High frequency of osteoporosis and fractures in women with dermatomyositis/polymyositis

Bone mass was only previously studied in juvenile dermatomyositis/polymyositis (DM/PM) patients. Therefore, the objective this study was to evaluate the prevalence of osteoporosis and fractures in adult DM/PM. Forty female DM/PM and 78 age-, gender-, and BMI-matched healthy controls were studied. Medical charts and clinical interviews of all patients were evaluated for demographic and clinical data, including disease activity, cumulative doses of glucocorticoid, menarche and menopause age, and fractures. Bone mineral density (BMD) using dual X-ray absorptiometry (DXA) were measured at lumbar spine (L1-L4) and hip. A decreased BMD in lumbar spine [0.902 (0.136) vs. 0.965 (0.141) g/cm(2), P = 0.022] and femoral neck [0.729 (0.12) vs. 0.784 (0.127) g/cm(2), P = 0.027] was observed in patients compared to controls. In addition, osteoporosis was more frequent in patients than in controls in both lumbar spine (20 vs. 3.8%, P = 0.007) and the femoral neck (27.5 vs. 10.3%, P = 0.016). Moreover, a high prevalence of fractures was found in patients in comparison to healthy subjects (17.9 vs. 5.1%, P = 0.040; OR = 3.92; CI 95%: 1.07-14.33). Comparing DM/PM patients with (n = 17) and without (n = 23) osteoporosis/fractures, significant differences were observed regarding age [56.8 (11.9) vs. 48.3 (13.2) years, P = 0.042], weight [62.05 (13.56) vs. 71.51 (11.46) kg, P = 0.022] and frequency of post menopausal women (94.1 vs. 65.2%, P = 0.0002). No differences were observed concerning height, lean mass, total fat mass, disease activity, mean value of creatine kinase, cumulative glucocorticoid dose, or bisphosphonate use. Logistic regression analysis revealed a negative association between the presence of osteoporosis/fractures and weight (OR: 0.92, 95% CI: 0.85-0.98; P = 0.016). This is the first study that analyzed bone mass in adult DM/PM patients and it demonstrated that about one quarter of these patients have osteoporosis/fracture.

Diagnóstico por imagem da artrite reumatoide inicial

O diagnóstico precoce da artrite reumatoide é essencial para o manejo adequado da condição. Atualmente, considera-se que a fase inicial da doença constitui uma janela de oportunidade terapêutica para a artrite reumatoide. Embora o diagnóstico seja primordialmente clínico, o desenvolvimento e o aprimoramento de métodos laboratoriais e de imagem têm contribuído para o diagnóstico mais precoce e a determinação da conduta na artrite reumatoide inicial. Neste artigo os autores revisam o papel dos principais métodos de imagem utilizados para a avaliação da artrite reumatoide inicial, notadamente a radiologia convencional, a ultrassonografia e a ressonância magnética.

Incapacitação e qualidade de vida não são influenciadas pela prevalência de autoanticorpos em pacientes com artrite reumatoide inicial - resultados da Coorte Brasília

INTRODUÇÃO: Embora muitos estudos sugiram que a presença de autoanticorpos, tais como fator reumatoide (FR) e/ou antipeptídeos citrulinados cíclicos (anti-CCP), sejam preditores de danos articulares na artrite reumatoide (AR), a associação entre os questionários de incapacidade e de qualidade de vida ainda são desconhecidos. OBJETIVOS: Avaliar a correlação entre os questionários Health Assessment Questionnaire (HAQ) e Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) com marcadores como FR, anti-CCP e antivimentina citrulinada (anti-Sa). PACIENTES E MÉTODOS: Foram avaliados no momento do diagnóstico 65 pacientes da Coorte Brasília com AR inicial. Foram realizadas sorologias (ELISA) para FR (IgM, IgG e IgA), anti-CCP (CCP2, CCP3 e CCP3.1) e anti-Sa, com a aplicação do HAQ e SF-36 na avaliação inicial. RESULTADOS: A idade média foi de 45 anos, predominando o gênero feminino (86%). Na avaliação inicial, o FR foi positivo em 32 indivíduos (49,23%); anti-CCP em 34 indivíduos (52,3%); e anti-Sa em nove indivíduos (13,8%). O escore inicial do HAQ foi de 1,8. Os escores dos domínios do SF-36 foram: emocional, 19,3; social, 43,1; dor, 25,43; estado geral, 57,6; saúde mental, 48,1; vitalidade, 49,5; físico, 4,6; e limitação por aspecto físico, 24,7. HAQ e escores do SF-36 não variaram com os níveis de autoanticorpos. CONCLUSÃO: Muitos pacientes com AR inicial apresentam comprometimento na qualidade de vida relacionada aos domínios da capacidade física e mental. Embora FR e anti-CCP tenham sido relacionados com dano articular e pior prognóstico clínico, não há correlação entre os questionários e as avaliações da qualidade de vida e incapacidade.

TNF blockers show distinct patterns of immune response to the pandemic influenza A H1N1 vaccine in inflammatory arthritis patients

Methods. One hundred and twenty patients (RA, n = 41; AS, n = 57; PsA, n = 22) on anti-TNF agents (monoclonal, n = 94; soluble receptor, n = 26) were compared with 116 inflammatory arthritis patients under DMARDs and 117 healthy controls. Seroprotection, seroconversion (SC), geometric mean titre, factor increase in geometric mean titre and adverse events were evaluated 21 days after vaccination. Results. After immunization, SC rates (58.2% vs 74.3%, P = 0.017) were significantly lower in SpA patients receiving anti-TNF therapy, whereas no difference was observed in RA patients receiving this therapy compared with healthy controls (P = 0.067). SpA patients receiving mAbs (infliximab/adalimumab) had a significantly lower SC rate compared with healthy controls (51.6% vs 74.3%, P = 0.002) or those on DMARDs (51.6% vs 74.7%, P = 0.005), whereas no difference was observed for patients on etanercept (86.7% vs 74.3%, P = 0.091). Further analysis of non-seroconverting and seroconverting SpA patients revealed that the former group had a higher mean age (P = 0.003), a higher frequency of anti-TNF (P = 0.031) and mAbs (P = 0.001) and a lower frequency of MTX (P = 0.028). In multivariate logistic regression, only older age (P = 0.015) and mAb treatment (P = 0.023) remained significant factors for non-SC in SpA patients. Conclusion. This study revealed a distinct disease pattern of immune response to the pandemic influenza vaccine in inflammatory arthritis patients receiving anti-TNF agents, illustrated by a reduced immunogenicity solely in SpA patients using mAbs. Trial Registration: ClinicalTrials.gov, ext-link-type="uri" xlink:href="www.clinicaltrials.gov" xmlns:xlink="http://www.w3.org/1999/xlink">www.clinicaltrials.gov, NCT01151644.

Experimental arthritis exacerbates Aggregatibacter actinomycetemcomitans-induced periodontitis in mice

Aim This study aimed to investigate whether chronic antigen-induced arthritis (AIA) influences infection-induced periodontitis (PD) in mice and whether PD modifies the clinical course of AIA. The contribution of anti-TNF-a therapy was also evaluated. Materials and methods The PD was induced in C57BL/6 mice by oral infection with Aggregatibacter actinomycetemcomitans. AIA was induced after infection. Anti-TNF-a and chlorhexidine therapies were used to investigate the role of TNF-a and oral infection on PD and AIA interaction. Maxillae, knee joints, lymph nodes and serum samples were used for histomorphometric, immunoenzymatic and/or real time-PCR analyses. Results Antigen-induced arthritis exacerbated alveolar bone loss triggered by PD infection. In contrast, PD did not influence AIA in the evaluated time-points. PD exacerbation was associated with enhanced production of IFN-? in maxillae and expression of the Th1 transcription factor tBET in submandibular lymph nodes. Increased serum levels of IL-6 and C-reactive protein were also detected. Anti-TNF-a and antiseptic therapies prevented the development and exacerbation of infectious-PD. Anti-TNF-a therapy also resulted in reduced expression of IFN-?, TNF-a and IL-17 in maxillae. Conclusions Altogether, the current results indicate that the exacerbation of infection-induced PD by arthritis is associated with an alteration in lymphocyte polarization pattern and increased systemic immunoreactivity. This process was ameliorated by anti-TNF-a and antiseptic therapies.