The value of inquiring patients about local discomfort during blood pressure measurement for fibromyalgia detection. A cross-sectional study.

BACKGROUND: Fibromyalgia overlaps and/or mimics other rheumatic diseases and may be a confounding factor in the clinimetric assessment of these illnesses. Allodynia is a distinctive fibromyalgia feature that can be elicited during routine blood pressure measurement. For epidemiological purposes fibromyalgia can be diagnosed using the 2016 Wolfe et al. criteria questionnaire. No physical examination is required. OBJECTIVE: To evaluate the role of a straightforward question formulated during routine blood pressure measurement for fibromyalgia detection in a rheumatology outpatient clinic. PATIENTS AND METHODS: All adult patients attending our Rheumatology outpatient clinic were invited to participate. While awaiting their medical consultation, they filled-out the 2016 Wolfe et al. FM diagnostic criteria questionnaire. During the ensuing routine physical examination, the physician advanced the following guideline: "I am going to take your blood pressure; tell me if the cuff's pressure causes pain". Then, blood pressure cuff was inflated to 170 mm/Hg. Sphygmomanometry induced allodynia was defined as any local discomfort caused by blood pressure measurement. If a patient voiced any uneasiness, a follow-up dichotomic question was formulated "did it hurt much or little". Sphygmomanometry-induced allodynia was correlated with the presence of fibromyalgia according to the 2016 Wolfe diagnostic criteria. RESULTS: Four hundred and ninety-one patients were included in the study; most of them (84%) were female. The female cohort displayed the following features: Twenty five percent had fibromyalgia. Twenty seven percent had sphygmomanometry-induced allodynia. In women, sphygmomanometry-evoked allodynia had 63% sensitivity and 84% specificity for fibromyalgia diagnosis. The area under curve was 0.751. Moreover, having "much" local pain elicitation during blood pressure testing had 23% sensitivity and 96% specificity for fibromyalgia diagnosis. Men behaved differently; 15% fulfilled the fibromyalgia diagnostic criteria, but only 2% had sphygmomanometry induced allodynia. CONCLUSIONS: Inquiring female patients about local discomfort during routine blood pressure measurement is a simple and efficient procedure for fibromyalgia detection. This undemanding approach could be implemented in all clinical settings. There is marked sexual dimorphism in the link between sphygmomanometry-induced allodynia and fibromyalgia diagnosis. The presence of fibromyalgia is almost certain in those individuals having substantial pain elicitation during blood pressure measurement.

Senescent CD4+CD28null cells are increased in chronic hyperuricemia, show aberrant effector phenotypes, and are reversed after allopurinol therapy: a proof-of-concept pilot study.

To characterize CD4+CD28null cells in chronic hyperuricemia and investigate whether allopurinol could restore CD28 expression and the balance of T helper phenotypes. Asymptomatic individuals with chronic hyperuricemia and ultrasonographic findings evocative of urate deposition in the joints. Age- and gender-matched normouricemic individuals were also studied. Oral allopurinol at 150 mg/day for 4 weeks, followed by 300 mg/day through week 12. Color-flow cytometry on peripheral blood mononuclear cells (PBMC) with antibodies against CD4, CD28, T-bet (Th1), GATA-3 (Th2), and RORγt (Th17). Six patients (five men, median age of 53 years) and seven controls were studied. At baseline, hyperuricemic patients had more CD4+CD28null/CD4+ cells than normouricemic subjects (36.8% vs. 6.1%; p = 0.001), with a predominance of T-bet+ cells (98.5% vs. 6.6%; p = 0.001) and few RORγt+ cells (0.7% vs. 89.4%; p = 0.014). In hyperuricemic patients, the number of CD4+ cells/10,000 PBMC was similar before and after allopurinol (3378 vs. 3954; p = 0.843). Conversely, CD4+CD28null cells decreased from 36.8% (23.0-43.7) to 15.8% (4.7-28.1; p = 0.031). CD4+CD28nullT-bet+ cells decreased from 98.5% (95.0-99.4) to 88.3% (75.2-98.9; p = 0.062), CD4+CD28nullGATA-3+ cells increased from 0% (0-4.0) to 2.8% (0.1-15.6; p = 0.156), and CD4+CD28nullRORγt+ cells increased from 0.7% (0.4-7.0) to 4.5% (1.3-28.1; p = 0.031). The CD4+CD28null cell subset is abnormally expanded in chronic hyperuricemia, despite the absence of overt urate-related disease. Allopurinol may partially restore CD28 expression on CD4+ cells while enhancing the homeostatic balance of T helper phenotypes. ClinicalTrials.gov, number NCT04012294.

Anti-Ro52/TRIM21 antibodies are associated with aberrant inflammatory circuits in patients with systemic autoimmune rheumatic diseases.

INTRODUCTION: Anti-Ro52/TRIM21 antibodies are markers for several systemic autoimmune rheumatic diseases (SARD). OBJECTIVE: To assess whether anti-Ro52/TRIM21 antibodies are related to abnormalities in inflammatory circuits. METHODS: Cross-sectional study of consecutive outpatients with SARD. Anti-Ro52/TRIM21 antibodies and serum amyloid A protein were measured by ELISA; panels for 18 cytokines and nine chemokines were analyzed on a Luminex reading platform, while high-sensitivity C-reactive protein (hs-CRP) and complement were measured by nephelometry. RESULTS: Among 167 included patients, 143 had systemic lupus erythematosus (SLE), 16 had primary Sjögren's syndrome and eight had systemic sclerosis; 41 (24%) were positive for anti-Ro52/TRIM21 antibodies. Patients with anti-Ro52/TRIM21 antibodies had higher serum levels of IL-2, IL-4, IL-6, GM-CSF, IL-21, IL-22, hs-CRP and chemokines CCL4, CXCL8, CXCL10 and CXCL12, but lower levels of complement C4. Anti-Ro52/TRIM21 antibody titers were positively correlated with IL-2, IL-4, IL-6, IL-10, IL-21, IL-22, CXCL10, and hs-CRP, and negatively with complements C3 and C4. When only SLE patients were included, no association was identified between anti-Ro52/TRIM21 antibodies and disease activity or organ-specific involvement. CONCLUSIONS: Anti-Ro52/TRIM21 antibodies are associated with aberrant cytokine circuits and elevated levels of angiogenic molecules and neutrophil and monocyte chemoattractants, which suggests an active role for these antibodies in SARD.

INTRODUCCIÓN: Los anticuerpos anti-Ro52/TRIM21 son marcadores de varias enfermedades reumáticas autoinmunes sistémicas (ERAS). OBJETIVO: Evaluar si los anticuerpos anti-Ro52/TRIM21 están relacionados con anomalías en los circuitos inflamatorios. MÉTODOS: Estudio transversal de pacientes consecutivos y ambulatorios con ERAS. Los anticuerpos anti-Ro52/TRIM21 y la proteína amiloide sérica se midieron mediante ELISA; los paneles para 18 citocinas y nueve quimiocinas se analizaron en una plataforma de lectura Luminex; la proteína C reactiva (hs-CRP) y el complemento se midieron mediante nefelometría. RESULTADOS: Se incluyeron 167 pacientes, 143 con lupus eritematoso sistémico (LES), 16 con síndrome de Sjögren primario y ocho con esclerosis sistémica; 41 fueron positivos para anticuerpos anti-Ro52/TRIM21 (24 %). Los pacientes con anticuerpos anti-Ro52/TRIM21 tuvieron niveles séricos más altos de IL-2, IL-4, IL-6, GM-CSF, IL-21, IL-22, hs-CRP y quimiocinas CCL4, CXCL8, CXCL10 y CXCL12; y más bajos de complemento C4. Los títulos de anticuerpos anti-Ro52/TRIM21 correlacionaron positivamente con IL-2, IL-4, IL-6, IL-10, IL-21, IL-22, CXCL10 y hs-CRP; y negativamente con complemento C3 y C4. Al incluir solo LES, no se identificó asociación entre los anticuerpos anti-Ro52/TRIM21 y la actividad de la enfermedad o la afectación específica de órganos. CONCLUSIONES: Los anticuerpos anti-Ro52/TRIM21 se asocian a circuitos aberrantes de citocinas y niveles elevados de moléculas angiogénicas y quimioatrayentes de neutrófilos y monocitos, lo que sugiere un papel activo de esos anticuerpos en las ERAS.

Los anticuerpos anti-Ro52/TRIM21 están asociados a circuitos inflamatorios aberrantes en pacientes con enfermedades reumáticas autoinmunes sistémicas / Anti-Ro52/TRIM21 antibodies are associated with aberrant inflammatory circuits in patients with systemic autoimmune rheumatic diseases

Resumen Introducción: Los anticuerpos anti-Ro52/TRIM21 son marcadores de varias enfermedades reumáticas autoinmunes sistémicas (ERAS). Objetivo: Evaluar si los anticuerpos anti-Ro52/TRIM21 están relacionados con anomalías en los circuitos inflamatorios. Métodos: Estudio transversal de pacientes consecutivos y ambulatorios con ERAS. Los anticuerpos anti-Ro52/TRIM21 y la proteína amiloide sérica se midieron mediante ELISA; los paneles para 18 citocinas y nueve quimiocinas se analizaron en una plataforma de lectura Luminex; la proteína C reactiva (hs-CRP) y el complemento se midieron mediante nefelometría. Resultados: Se incluyeron 167 pacientes, 143 con lupus eritematoso sistémico (LES), 16 con síndrome de Sjögren primario y ocho con esclerosis sistémica; 41 fueron positivos para anticuerpos anti-Ro52/TRIM21 (24 %). Los pacientes con anticuerpos anti-Ro52/TRIM21 tuvieron niveles séricos más altos de IL-2, IL-4, IL-6, GM-CSF, IL-21, IL-22, hs-CRP y quimiocinas CCL4, CXCL8, CXCL10 y CXCL12; y más bajos de complemento C4. Los títulos de anticuerpos anti-Ro52/TRIM21 correlacionaron positivamente con IL-2, IL-4, IL-6, IL-10, IL-21, IL-22, CXCL10 y hs-CRP; y negativamente con complemento C3 y C4. Al incluir solo LES, no se identificó asociación entre los anticuerpos anti-Ro52/TRIM21 y la actividad de la enfermedad o la afectación específica de órganos. Conclusiones: Los anticuerpos anti-Ro52/TRIM21 se asocian a circuitos aberrantes de citocinas y niveles elevados de moléculas angiogénicas y quimioatrayentes de neutrófilos y monocitos, lo que sugiere un papel activo de esos anticuerpos en las ERAS.

Abstract Introduction: Anti-Ro52/TRIM21 antibodies are markers for several systemic autoimmune rheumatic diseases (SARD). Objective: To assess whether anti-Ro52/TRIM21 antibodies are related to abnormalities in inflammatory circuits. Methods: Cross-sectional study of consecutive outpatients with SARD. Anti-Ro52/TRIM21 antibodies and serum amyloid A protein were measured by ELISA; panels for 18 cytokines and nine chemokines were analyzed on a Luminex reading platform, while high-sensitivity C-reactive protein (hs-CRP) and complement were measured by nephelometry. Results: Among 167 included patients, 143 had systemic lupus erythematosus (SLE), 16 had primary Sjögren's syndrome and eight had systemic sclerosis; 41 (24%) were positive for anti-Ro52/TRIM21 antibodies. Patients with anti-Ro52/TRIM21 antibodies had higher serum levels of IL-2, IL-4, IL-6, GM-CSF, IL-21, IL-22, hs-CRP and chemokines CCL4, CXCL8, CXCL10 and CXCL12, but lower levels of complement C4. Anti-Ro52/TRIM21 antibody titers were positively correlated with IL-2, IL-4, IL-6, IL-10, IL-21, IL-22, CXCL10, and hs-CRP, and negatively with complement C3 and C4. When only SLE patients were included, no association was identified between anti-Ro52/TRIM21 antibodies and disease activity or organ-specific involvement. Conclusions: Anti-Ro52/TRIM21 antibodies are associated with aberrant cytokine circuits and elevated levels of angiogenic molecules and neutrophil and monocyte chemoattractants, which suggests an active role for these antibodies in SARD.

Cardiovascular risk in the postnatal life of children born to women with systemic lupus erythematous / Riesgo cardiovascular en la vida posnatal de hijos de mujeres con lupus eritematoso sistémico

Abstract Systemic lupus erythematous (SLE) is an autoimmune disease with clinical manifestations in multiple organs, primarily striking women of reproductive age. Women with SLE can became pregnant such as any other healthy woman and carrier their pregnancy to term due to the improvement of health systems, but their specific inflammatory conditions could affect the microenvironment in which the fetus grows, and influence the development of placenta and the fetal heart. Until now, there is very little evidence of any increased risk of postnatal cardiovascular disease (CVD) in the apparently healthy children from women with SLE, but it is this great variability in the effects of lupus on pregnant products is related to.

Resumen El lupus eritematoso sistémico (LES) es una enfermedad autoinmune que presenta diversas manifestaciones clínicas en múltiples órganos, y afecta principalmente a mujeres en edad reproductiva. Las mujeres con LES se pueden embarazar y llevar a término su embarazo, sin embargo, las condiciones inflamatorias específicas de la madre pueden modificar el microambiente en el que el embrión y el feto se desarrollan y afectar la formación y desarrollo de la placenta y el corazón fetal. Hasta ahora hay muy poca evidencia de que haya un mayor riesgo de enfermedad cardiovascular (ECV) en hijos aparentemente sanos de madres con LES, a pesar de que se sabe que hay un mayor riesgo de alteraciones cognitivas y neuronales, así como de desarrollar enfermedades autoinmunes en esos niños. El objetivo de esta revisión fue realizar una búsqueda bibliografía cruzando palabras clave acerca la enfermedad cardiovascular en hijos sanos de mujeres con LES. La evidencia mostró que la autoinmunidad materna puede favorecer la predisposición para el desarrollo de ECV en sus hijos, por medio de la modificación de señales que alteran el microambiente durante la gestación, lo que puede afectar la respuesta inmunitaria y cambios epigenéticos durante la vida posnatal.

Inflammasome Genes Polymorphisms and Susceptibility to Gout. Is There a Link?

ABSTRACT Background: The inflammatory response in gout disease is induced by the activation of NLR family pyrin domain-containing 3 (NLPR3) signaling pathway mediated by IL-1β release. Objective: The objective of the study was to determine the association between single nucleotide polymorphisms (SNPs) within NLRP3 inflammasome genes and gout susceptibility. Methods: Mexican patients with gout from the National Rehabilitation Institute and General Hospital of Mexico were enrolled. A healthy control group was also included. We analyzed the frequency and allelic distribution of eight SNPs from seven different genes within the NLRP3 inflammasome signaling pathway: TLR4 rs2149356, CD14 rs2569190, NLRP3 rs3806268, NLRP3 rs10754558, CARD8 rs2043211, IL-1β rs1143623, P2RX7 rs3751142, and PPARGC1B rs45520937 SNPs. Results: We found that the SNP rs45520937 of PPARGC1B was associated with the risk of developing gout when it was analyzed using the dominant model (Odds ratio [OR] = 2.30; 95% confidence interval [CI]: 1.09-4.86; p = 0.030), and it is proposed that the adaptor molecule CD14 rs2569190 polymorphism could be associated with a lower risk of gout under an additive model (OR= 0.41;95% CI: 0.16-1.05; p = 0.064). No significant associations were identified for the remaining SNPs. Conclusion: Our findings suggest that the PPARGC1B rs45520937 SNP is associated with gout susceptibility.

Inflammasome genes polymorphisms and susceptibility to gout. Is there a link?

Background: The inflammatory response in gout disease is induced by the activation of NLR family pyrin domain-containing 3 (NLPR3) signaling pathway mediated by IL-1ß release. Objective: The objective of the study was to determine the association between single nucleotide polymorphisms (SNPs) within NLRP3 inflammasome genes and gout susceptibility. Methods: Mexican patients with gout from the National Rehabilitation Institute and General Hospital of Mexico were enrolled. A healthy control group was also included. We analyzed the frequency and allelic distribution of eight SNPs from seven different genes within the NLRP3 inflammasome signaling pathway: TLR4 rs2149356, CD14 rs2569190, NLRP3 rs3806268, NLRP3 rs10754558, CARD8 rs2043211, IL-1ß rs1143623, P2RX7 rs3751142, and PPARGC1B rs45520937 SNPs. Results: We found that the SNP rs45520937 of PPARGC1B was associated with the risk of developing gout when it was analyzed using the dominant model (Odds ratio [OR] = 2.30; 95% confidence interval [CI]: 1.09-4.86; p = 0.030), and it is proposed that the adaptor molecule CD14 rs2569190 polymorphism could be associated with a lower risk of gout under an additive model (OR= 0.41;95% CI: 0.16-1.05; p = 0.064). No significant associations were identified for the remaining SNPs. Conclusion: Our findings suggest that the PPARGC1B rs45520937 SNP is associated with gout susceptibility.

Complex Regional Pain Syndrome Evolving to Full-Blown Fibromyalgia: A Proposal of Common Mechanisms.

BACKGROUND: Spread of complex regional pain syndrome (CRPS) outside the affected limb is a well-recognized phenomenon; nevertheless, the actual evolution from CRPS to fibromyalgia is poorly documented. Similar mechanisms have been recently put forward to explain the development of CRPS and fibromyalgia including dorsal root ganglia (DRG) hyperexcitability and small fiber neuropathy. OBJECTIVES: The aims of this study were to describe 3 cases with typical CRPS evolving to full-blown fibromyalgia and to discuss the potential pathogenetic mechanisms linking these debilitating illnesses. METHODS: This was a review of medical records and PubMed search on the relationship between CRPS-fibromyalgia with DRG and small nerve fiber neuropathy. RESULTS: Our 3 cases displayed over time orderly evolution from CRPS to fibromyalgia. Dorsal root ganglion hyperexcitability and small fiber neuropathy have been recently demonstrated in CRPS and in fibromyalgia. Dorsal root ganglia contain the small nerve fiber cell bodies surrounded by glial cells. After trauma, DRG perineuronal glial cells produce diverse proinflammatory mediators. Macrophages, lymphocytes, and satellite glial cells may drive the immune response to more rostrally and caudally located DRG and other spinal cord sites. Dorsal root ganglion metabolic changes may lead to small nerve fiber degeneration. This mechanism may explain the development of widespread pain and autonomic dysfunction. CONCLUSIONS: Clinicians should be aware that CRPS can evolve to full-blown fibromyalgia. Spreading of neuroinflammation through DRG glial cell activation could theoretically explain the transformation from regional to generalized complex pain syndrome.

Cardiovascular Manifestations of Systemic Vasculitides.

PURPOSE OF REVIEW: Vasculitis can cause heart disease and are associated with premature atherosclerosis, causing increased morbidity and mortality. Consequently, it is important to know how they can affect the cardiovascular system in order to detect and treat the abnormalities in earlier phases. RECENT FINDINGS: A clear increasing trend of inpatient burden of myocardial infarction and thromboembolic events in granulomatosis with polyangiitis has been observed lately. Behçet's disease has been linked to an increased risk of atrial fibrillation. Studies showing increased atherosclerosis and thromboembolic phenomena in vasculitis are continuously published. Improvement in imaging techniques has consistently showed that subclinical cardiovascular involvement is frequent. Vasculitis may affect seriously the cardiovascular system causing an important increase in morbidity and mortality. Subclinical involvement is frequent. Early treatment with immunosuppression and sometimes surgery, is of paramount importance to improve the prognosis.

FREQUENCY OF DEPRESSION AND ANXIETY SYMPTOMS IN MEXICAN PATIENTS WITH RHEUMATIC DISEASES DETERMINED BY SELF-ADMINISTERED QUESTIONNAIRES ADAPTED TO THE SPANISH LANGUAGE.

BACKGROUND: The frequency of depression and anxiety symptoms in Spanish-speaking patients suffering from rheumatic conditions is unknown when using self-administered detection tools. METHODS: A single-center, cross-sectional survey including 413 patients (341 women) with well-defined rheumatic diseases was conducted. The patient health questionnaire-9 (PHQ-9) and generalized anxiety disorder (GAD)-7 questionnaires were used to detect depression and anxiety symptoms, respectively. RESULTS: A total of 193 patients (46.7%) reported depression symptoms, and increased PHQ-9 scores were more frequently observed in women than in men (23% vs. 13%; p = 0.038), particularly in association with osteoarthritis, fibromyalgia, Sjögren's syndrome, and osteoporosis. From 88 patients (21.3%) with PHQ-9 scores ≥ 10 points (moderate-to-severe depression symptoms), 27 (30.6%) were previously diagnosed to have depression and only four were under antidepressant treatment. Anxiety symptoms were observed in 168 patients (40.6%) and classified as moderate-to-severe by elevated GAD-7 scores in 68 subjects (16.4%). Of them, 12 (17.6%) were previously diagnosed with GAD, but only 4 (5.8%) were under therapy. CONCLUSIONS: An unexpected and unusually high frequency of undiagnosed depression and anxiety symptoms was found in rheumatic patients. Self-administered screening tools adapted to the Spanish language are useful and may help clinicians to suspect these conditions.

Frequency of depression and anxiety symptoms in mexican patients with rheumatic diseases determined by self-administered questionnaires adapted to the spanish language

Abstract Background The frequency of depression and anxiety symptoms in Spanish-speaking patients suffering from rheumatic conditions is unknown when using self-administered detection tools. Methods A single-center, cross-sectional survey including 413 patients (341 women) with well-defined rheumatic diseases was conducted. The patient health questionnaire-9 (PHQ-9) and generalized anxiety disorder (GAD)-7 questionnaires were used to detect depression and anxiety symptoms, respectively. Results A total of 193 patients (46.7%) reported depression symptoms, and increased PHQ-9 scores were more frequently observed in women than in men (23% vs. 13%; p = 0.038), particularly in association with osteoarthritis, fibromyalgia, Sjögren’s syndrome, and osteoporosis. From 88 patients (21.3%) with PHQ-9 scores ≥ 10 points (moderate-to-severe depression symptoms), 27 (30.6%) were previously diagnosed to have depression and only four were under antidepressant treatment. Anxiety symptoms were observed in 168 patients (40.6%) and classified as moderate-to-severe by elevated GAD-7 scores in 68 subjects (16.4%). Of them, 12 (17.6%) were previously diagnosed with GAD, but only 4 (5.8%) were under therapy. Conclusions An unexpected and unusually high frequency of undiagnosed depression and anxiety symptoms was found in rheumatic patients. Self-administered screening tools adapted to the Spanish language are useful and may help clinicians to suspect these conditions.

Efecto de los antimaláricos sobre los diferentes dominios del índice de daño SLICC en pacientes de la cohorte GLADEL / Effect of antimalarials on the different domains of the SLICC damage index in patients of the GLADEL cohort

Objetivos: Estimar el efecto de los antimaláricos (AM) sobre los diferentes dominios del índice de daño SLICC (SDI). Métodos: Se estudiaron pacientes con diagnóstico clínico reciente (≤2 años) de lupus eritematoso sistémico (LES) de la cohorte GLADEL. Variable de estudio: aumento en los dominios del SDI desde el ingreso a la cohorte. Variables independientes: características sociodemográficas, clínicas, laboratorio y tratamientos. El efecto de los AM, como variable dependiente del tiempo, sobre los dominios más frecuentes del SDI (ajustado por factores de confusión) fue examinado con un modelo de regresión de Cox multivariado. Resultados: De 1466 pacientes estudiados, 1049 (72%) recibieron AM con un tiempo medio de exposición de 30 meses (Q1-Q3: 11-57) y 665 pacientes (45%) presentaron daño durante un seguimiento medio de 24 meses (Q1-Q3: 8-55); 301 eventos fueron cutáneos, 208 renales, 149 neuropsiquiátricos, 98 musculoesqueléticos, 88 cardiovasculares y 230 otros. Después de ajustar por factores de confusión, el uso de AM se asoció a un menor riesgo de daño renal (HR 0,652; IC 95%: 0,472-0,901) y en el límite de la significancia estadística (HR 0,701, IC 95%: 0,481-1,024) para el dominio neuropsiquiátrico. Conclusión: En GLADEL, el uso de AM se asoció independientemente a un menor riesgo de daño acumulado renal.

Objective: To assess the effects of antimalarials (AM) over the items of the SLICC Damage Index (SDI). Methods: Patients with recent (≤2 years) diagnosis of systemic lupus erythematosus (SLE) from the GLADEL cohort were studied. End-point: increase in items SDI since cohort entry. Independent variables (socio-demographic, clinical, laboratory and treatment) were included. The effect of AM as a time dependent variable on most frequent SDI items (adjusting for potential confounders) was examined with a multivariable Cox regression model. Results: Of the 1466 patients included in this analysis, 1049 (72%) received AM with a median exposure time of 30 months (Q1-Q3: 11-57). Damage occurred in 665 (45%) patients during a median follow-up time of 24 months (Q1-Q3: 8-55). There were 301 integument, 208 renal, 149 neuropsychiatric, 98 musculoskeletal, 88 cardiovascular and 230 others less frequently represented damages. After adjusting for potential confounders at any time during follow-up, a lower risk of renal damage (HR 0.652; 95% CI: 0.472-0.901) and borderline for neuropsychiatric damage (HR 0.701, 95% CI: 0.481-1.024) was found. Conclusion: In the GLADEL cohort, after adjustment for possible confounding factors, AM were independently associated with a reduced risk of renal damage accrual.

Levels of Cytokines and MicroRNAs in Individuals With Asymptomatic Hyperuricemia and Ultrasonographic Findings of Gout: A Bench-to-Bedside Approach.

OBJECTIVE: To assess potential associations among serum cytokines and microRNA (miR) levels with ultrasound (US) findings suggestive of urate deposits in chronic asymptomatic hyperuricemia and gout. METHODS: All participants underwent musculoskeletal US and measurements of serum interleukin-1ß (IL-1ß), IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, interferon-γ, tumor necrosis factor, monocyte chemoattractant protein 1, and epithelial neutrophil-activating peptide 78, as well as miR-146a, miR-155, and miR-223 levels. RESULTS: Thirty individuals with asymptomatic hyperuricemia, 31 normouricemic controls, and 30 patients with gout were included. The frequency of synovitis and double contour sign using US was similar between asymptomatic hyperuricemia (67% and 27%, respectively) and patients with gout (77% and 27%, respectively), and each had a higher frequency than controls (45% and 0%, respectively). Serum IL-6 and IL-8 levels were similar between patients with asymptomatic hyperuricemia (mean ± SD 69.7 ± 73.4 and 18.5 ± 25.6 pg/ml, respectively) and gout (mean ± SD 75.8 ± 47.6 and 24.4 ± 31.7 pg/ml, respectively), and higher than controls (mean ± SD 28.2 ± 17.6 and 7.4 ± 6.0 pg/ml, respectively). A similar distribution was observed for miR-155 levels in asymptomatic hyperuricemia, patients with gout, and controls (mean ± SD 0.22 ± 0.18, 0.20 ± 0.14, and 0.08 ± 0.04, respectively). Associations between morphostructural abnormalities suggestive of urate deposits (regardless of clinical diagnosis) and serum markers were assessed. Subjects with urate deposits had higher IL-6 (257.2 versus 47.0 pg/ml; P = 0.005), IL-8 (73.2 versus 12.0 pg/ml; P = 0.026), and miR-155 (0.21 versus 0.16; P = 0.015) levels than those without deposition findings. CONCLUSION: In individuals with chronic asymptomatic hyperuricemia, the presence of synovitis and double contour sign by US may represent a subclinical manifestation of monosodium urate crystal nucleation, capable of triggering inflammatory pathways (IL-6 and IL-8) and mechanisms of intercellular communication (miR-155), similar to what is observed in patients with gout.

Ambroxol for fibromyalgia: one group pretest-posttest open-label pilot study.

A consistent line of investigation proposes that fibromyalgia is a sympathetically maintained neuropathic pain syndrome. Dorsal root ganglia sodium channels may play a major role in fibromyalgia pain transmission. Ambroxol is a secretolytic agent used in the treatment of various airway disorders. Recently, it was discovered that this compound is also an efficient sodium channel blocker with potent anti-neuropathic pain properties. We evaluated the add-on effect of ambroxol to the treatment of fibromyalgia. We studied 25 patients with fibromyalgia. Ambroxol was prescribed at the usual clinical dose of 30 mg PO 3 times a day × 1 month. At the beginning and at the end of the study, all participants filled out the Revised Fibromyalgia Impact Questionnaire (FIQ-R) and the 2010 ACR diagnostic criteria including the widespread pain index (WPI). At the end of the study, FIQ-R decreased from a baseline value of 62 ± 15 to 51 ± 19 (p = 0.013). Pain visual analogue scale decreased from 77 ± 14 to 56 ± 30 (p = 0.018). WPI diminished from 14.6 ± 3.1 to 10.4 ± 5.3 (p = 0.001). Side effects were minor. In this pilot study, the use of ambroxol was associated to decreased fibromyalgia pain and improved fibromyalgia symptoms. The open nature of our study does not allow extracting the placebo effect from the positive results. The drug was well tolerated. Ambroxol newly recognized pharmacological properties could theoretically interfere with fibromyalgia pain pathways. Dose escalating-controlled studies seem warranted.

Antimalarial treatment may have a time-dependent effect on lupus survival: data from a multinational Latin American inception cohort.

OBJECTIVE: To evaluate the beneficial effect of antimalarial treatment on lupus survival in a large, multiethnic, international longitudinal inception cohort. METHODS: Socioeconomic and demographic characteristics, clinical manifestations, classification criteria, laboratory findings, and treatment variables were examined in patients with systemic lupus erythematosus (SLE) from the Grupo Latino Americano de Estudio del Lupus Eritematoso (GLADEL) cohort. The diagnosis of SLE, according to the American College of Rheumatology criteria, was assessed within 2 years of cohort entry. Cause of death was classified as active disease, infection, cardiovascular complications, thrombosis, malignancy, or other cause. Patients were subdivided by antimalarial use, grouped according to those who had received antimalarial drugs for at least 6 consecutive months (user) and those who had received antimalarial drugs for <6 consecutive months or who had never received antimalarial drugs (nonuser). RESULTS: Of the 1,480 patients included in the GLADEL cohort, 1,141 (77%) were considered antimalarial users, with a mean duration of drug exposure of 48.5 months (range 6-98 months). Death occurred in 89 patients (6.0%). A lower mortality rate was observed in antimalarial users compared with nonusers (4.4% versus 11.5%; P< 0.001). Seventy patients (6.1%) had received antimalarial drugs for 6-11 months, 146 (12.8%) for 1-2 years, and 925 (81.1%) for >2 years. Mortality rates among users by duration of antimalarial treatment (per 1,000 person-months of followup) were 3.85 (95% confidence interval [95% CI] 1.41-8.37), 2.7 (95% CI 1.41-4.76), and 0.54 (95% CI 0.37-0.77), respectively, while for nonusers, the mortality rate was 3.07 (95% CI 2.18-4.20) (P for trend < 0.001). After adjustment for potential confounders in a Cox regression model, antimalarial use was associated with a 38% reduction in the mortality rate (hazard ratio 0.62, 95% CI 0.39-0.99). CONCLUSION: Antimalarial drugs were shown to have a protective effect, possibly in a time-dependent manner, on SLE survival. These results suggest that the use of antimalarial treatment should be recommended for patients with lupus.

Circulating vascular endothelial growth factor concentrations in a case of pulmonary hypertrophic osteoarthropathy. Correlation with disease activity.

Vascular endothelial growth factor (VEGF) is a cytokine overexpressed in hypoxic and malignant pathologies. VEGF induces vascular hyperplasia, new bone formation, and edema. These histological abnormalities characterize hypertrophic osteoarthropathy. We describe a case of pulmonary hypertrophic osteoarthropathy with high circulating VEGF levels. Removal of the lung tumor led to a dramatic disappearance of the skeletal abnormalities and to reduction of circulating VEGF levels. Histochemical studies of the excised tumor confirmed abnormal VEGF production.

Prolactin, a neuroimmunomodulator implicated in the pathogenesis of rheumatic diseases

A prolactina (PRL) tem importantes propriedades imunorreguladoras e pode desempenhar algum papel na patogenia e expressao de certas doenças auto-imunes. A PRL é capaz de restaurar a imunocompetência em ratos e hipofisectomizados, é co-mitogênica em linfócitos murinos e humanos, induz a formaçao de receptores celulares de superfície para IL-2 e modula a expressao de vários genes relacionados a fatores de crescimento. A PRL também estimula a produçao de anticorpos. Por seu turno, mediadores imunes e inflamatórios estimulam a secreçao de hormônios pituitários. Os linfócitos podem produzir proteínas PRL-símiles biologicamente ativas e têm sido descritos receptores PRL-específicos nos linfócitos T e B. Além disso, hiperprolactinemia tem sido descrita em um subgrupo de pacientes com lúpus eritematoso sistêmico ativo. Na artrite reumatóide, foi demonstrada secreçao excessiva e supra-regulada de PRL. Altos níveis de PRL também foram encontrados em pacientes com síndrome de Sjögren primária e síndrome de Reiter. Esses dados sustentam uma interaçao entre PRL e sistema imune e o papel potencial deste hormônio imunorregulador na patogenia de certas doenças auto-imunes

Reactive arthritis: pathogenesis and clinical overview

As artrites reativas compreendem grande grupo de entidades, desencadeadas por vários agentes infecciosos, vista mais comumente em indivíduos de 30 anos ou menos e com forte ligaçao com fatores imunológicos. A infecçao precedente é geralmente intestinal ou geniturinária, apesar do agente envolvido poder permanecer desconhecido. Pele e vias aéreas superiores podem ser também a porta de entrada dessa infecçao antecedente. O quadro clínico é variável, sendo mais grave nos indivíduos com antígeno HLA-B27 positivo. As queixas iniciais podem ser as manifestaçoes extra-articulares. Sao altamente sugestivos de artrite reativa as deformidades em "salsicha" dos dedos de maos e pés, a lombalgia e a rigidez irradiada para membros inferiores e as entesites, particularmente do tendao de Aquiles. Pode haver incapacidade e aproximadamente um quarto dos pacientes desenvolve artrite crônica. Terapêutivca visando a prevençao de incapacidade é vital, pois a medicaçao tem pouco efeito sobre o comprometimento da coluna. Agentes antiiflamatórios e de segunda linha sao eficazes na grande maioria dos pacientes, especialmente para o envolvimento articular periférico. Terapia antibiótica pode ser eficaz em pacientes nos quais etiologias específicas estejam bem definidas