Transcriptomic characterization of classical monocytes highlights the involvement of immuno-inflammation in bone erosion in Rheumatoid Arthritis.

Introduction: Evidence-based data suggest that under inflammatory conditions, classical monocytes are the main source of osteoclasts and might be involved in bone erosion pathophysiology. Here, we analyze the transcriptomic profile of classical monocytes in erosive and non-erosive rheumatoid arthritis patients in order to better understand their contribution to bone erosion. Methods: Thirty-nine premenopausal RA patients were consecutively enrolled and divided into two groups based on the presence of bone erosions on hand joints. Classical monocytes were isolated from peripheral blood through negative selection, and RNA-seq was performed using a poly-A enrichment kit and Illumina® platform. Classical monocytes transcriptome from healthy age-matched women were also included to identify differentially expressed genes (DEGs). Therefore, gene sets analysis was performed to identify the enriched biological pathways. Results: RNA-seq analysis resulted in the identification of 1,140 DEGs of which 89 were up-regulated and 1,051 down-regulated in RA patients with bone erosion compared to those without bone erosions. Among up-regulated genes, there was a highlighted expression of IL18RAP and KLF14 related to the production of pro-inflammatory cytokines, innate and adaptive immune response. Genes related to collagen metabolism (LARP6) and bone formation process (PAPPA) were down-regulated in RA patients with erosions. Enriched pathways in patients with erosions were associated with greater activation of immune activation, and inflammation. Interestingly, pathways associated with osteoblast differentiation and regulation of Wnt signaling were less activated in RA patients with erosions. Conclusion: These findings suggest that alterations in expression of monocyte genes related to the inflammatory process and impairment of bone formation might have an important role in the pathophysiology of bone erosions in RA patients.

Lower hand grip in rheumatoid arthritis patients is associated with low finite element analysis using high resolution peripheral quantitative computed tomography scan of the 2nd metacarpophalangeal joint.

AIM: To evaluate hand function by hand grip test in rheumatoid arthritis (RA) patients, and its association with bone erosions and the estimated bone strength (finite element - FE analysis) through the analysis of the 2nd metacarpal head of the dominant hand using high resolution peripheral quantitative computed tomography (HR-pQCT). METHOD: Eighty-two female RA patients between 18-50 years old were selected. Demographic data, Health Questionnaire Assessment Disability Index (HAQ), Disease Activity Score of 28 joints (DAS)-28, simplified disease activity index (SDAI) and the hand grip test were set. The HR-pQCT scans of 2nd metacarpophalangeal joints of the dominant hand of all patients were performed according to SPECTRA group protocols. The images were used to assess bone erosions and FE analysis. The hand grip test was categorized in 2 groups and separately compared (< 18 vs ≥18 kgf). A logistic regression was performed using hand grip test <18 kgf as a dependent variable. RESULTS: A significant difference was found between the 2 groups regarding HAQ, inflammatory markers (erythrocyte sedimentation rate, C-reactive protein), DAS-28, SDAI, total volume of erosion and bone strength parameter (FE analysis - Failure Load [F.Load]). The logistic regression analysis showed that the risk factors associated with hand grip test <18 kgf were higher SDAI (odds ratio [OR] 0.912; 95% CI 0.837-0.993) and lower values of bone strength parameter (F.Load) (OR 1.007; 95% CI 1.002-1.012). CONCLUSION: Lower values of hand grip test were associated with higher disease activity score-SDAI and lower bone strength of 2nd metacarpal bone head of the dominant hand evaluated here through a FE analysis using HR-pQCT scan.

Evaluation of bone erosion in rheumatoid arthritis patients by high-resolution peripheral quantitative computed tomography scans: Comparison between two semi-automated programs in a three-dimensional setting.

AIM: The aim of this study was to compare OsiriX software with the previous published Medical Image Analysis Framework (MIAF) method to assess the volume of erosion in patients with rheumatoid arthritis (RA). METHODS: Forty RA patients underwent high-resolution peripheral quantitative computed tomography scans of the second and third metacarpophalangeal joints, and thirty-four patients with any bone erosion were enrolled. Two techniques were applied to erosion evaluation: (a) semi-automated MIAF software, and (b) semi-automated segmentation by free open-source Digital Imaging and Communications in Medicine viewer, OsiriX software. MIAF has been published before, but this is the first time that OsiriX has been used in this way in rheumatology. Bland & Altman plots described agreement between methods. RESULTS: Forty-eight erosions from 34 patients were analyzed. Mean age was 40.74 ± 5.32 years and mean disease duration was 10.68 ± 4.96 years. Both methods demonstrated a strong correlation regarding erosion volume (r = 0.96, P < 0.001). Median (interquartile range) of erosion volume was 12.14 (4.5-36.07) when MIAF was considered, and 11.80 (3.45-29.42) when the OsiriX tool was used (P = 0.139). MIAF and OsiriX showed good agreement when the Bland & Altman plot was performed. Evaluation by MIAF took 22.69 ± 6.71 minutes, whereas OsiriX took only 2.62 ± 1.09 minutes (P < 0.001). CONCLUSION: The three-dimensional segmentation of bone erosions can be done by both MIAF and OsiriX software with good agreement. However, because OsiriX is a widespread tool and faster, its method seems to be more feasible for evaluating peripheral bone damage, especially bone erosions.

Epidemiologic Features of Systemic Vasculitides in the Southeast Region of Brazil: Hospital-Based Survey.

BACKGROUND/OBJECTIVE: The epidemiology of vasculitis is variable in different geographic areas, and this issue has not been approached in Brazil yet. The objective of this study was to assess the frequency of vasculitis in specialized centers in Brazil. METHODS: This cross-sectional study was performed in 9 vasculitis outpatient clinics from 6 different states mainly from the Southeast and the Northeast regions of Brazil between 2015 and 2017. Diagnosis and/or classification criteria for Behçet disease (BD), Takayasu arteritis (TA), giant cell arteritis (GCA), polyarteritis nodosa (PAN), granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA), and cryoglobulinemic vasculitis (CryoVas) were used to include patients with at least 6 months of follow-up in this hospital-based survey. RESULTS: A total of 1233 patients with systemic vasculitis were included from the Southeast region. Behçet disease was the most frequent vasculitis (35.0%) followed by TA (26.4%), GPA (16.2%), PAN (5.8%), GCA (5.8%), EGPA (4.3%), MPA (3.4%), and CryoVas (3.0%). Up to 7.8% of vasculitis patients had a juvenile onset, and the frequency of vasculitides found in children and adolescents was as follows: TA (52.6%), BD (24.7%), GPA (12.4%), and PAN (10.3%). No cases of EGPA, MPA, and CryoVas were diagnosed before the age of 18 years. As a comparator, 103 vasculitis patients were included in the Northeast of Brazil where TA was found in 36.9% and BD in 31.1% of vasculitis cases. No GCA cases were found in the Northeast part of Brazil. CONCLUSIONS: Similar to the epidemiology of vasculitis in Asia, BD and TA are the most frequent vasculitis in Southeastern Brazilian referral centers.

Recommendations of the Brazilian Society of Rheumatology for the induction therapy of ANCA-associated vasculitis.

The purpose of these recommendations is to guide the appropriate induction treatment of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) patients with active disease. The recommendations proposed by the Vasculopathies Committee of the Brazilian Society Rheumatology for induction therapy of AAV, including granulomatosis with polyangiitis, microscopic polyangiitis and renal-limited vasculitis, were based on systematic literature review and expert opinion. Literature review was performed using Medline (PubMed), EMBASE and Cochrane database to retrieve articles until October 2016. PRISMA guidelines were used for the systematic review and articles were assessed according to the Oxford levels of evidence. Sixteen recommendations were made regarding different aspects of induction therapy for AAV. The purpose of these recommendations is to serve as a guide for therapeutic decisions by health care professionals in the management of AAV patients presenting active disease.

Recommendations of the Brazilian Society of Rheumatology for the induction therapy of ANCA-associated vasculitis / Recomendações da Sociedade Brasileira de Reumatologia para a terapia de indução para vasculite associada a ANCA

Abstract The purpose of these recommendations is to guide the appropriate induction treatment of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) patients with active disease. The recommendations proposed by the Vasculopathies Committee of the Brazilian Society Rheumatology for induction therapy of AAV, including granulomatosis with polyangiitis, microscopic polyangiitis and renal-limited vasculitis, were based on systematic literature review and expert opinion. Literature review was performed using Medline (PubMed), EMBASE and Cochrane database to retrieve articles until October 2016. PRISMA guidelines were used for the systematic review and articles were assessed according to the Oxford levels of evidence. Sixteen recommendations were made regarding different aspects of induction therapy for AAV. The purpose of these recommendations is to serve as a guide for therapeutic decisions by health care professionals in the management of AAV patients presenting active disease.

Resumo O objetivo destas recomendações é orientar o tratamento apropriado de indução em pacientes com vasculite associada a anticorpos anticitoplasma de neutrófilos (VAA) ativa. As recomendações propostas pelo Comitê de Vasculopatias da Sociedade Brasileira de Reumatologia para a terapia de indução para vasculites associadas aos anticorpos anticitoplasma de neutrófilos (VAA), inclusive granulomatose com poliangiite, poliangiite microscópica e vasculite limitada ao rim, foram baseadas em uma revisão sistemática da literatura e na opinião de especialistas. A revisão da literatura foi feita com as bases de dados Medline (PubMed), Embase e Cochrane para consultar artigos até outubro de 2016. As diretrizes Prisma (Preferred Reporting Items for Systematic Reviews and Meta-Analyses - Principais itens para reportar revisões sistemáticas e metanálises) foram usadas para a revisão sistemática e os artigos foram avaliados de acordo com os níveis de evidência Oxford. Dezesseis recomendações foram feitas em relação a diferentes aspectos da terapia de indução para VAA. O objetivo dessas recomendações é servir como um guia para decisões terapêuticas por profissionais da saúde no tratamento de pacientes com VAA que apresentem a doença ativa.

Endometriose e autoimunidade / Endometriosis and autoimmunity

A endometriose é caracterizada pela implantação de blocos de endométrio fora do útero, especialmente em ovários e peritônio. Dentre seus estigmas se destacam a dor pélvica, a dismenorreia e a infertilidade, que podem acompanhar as pacientes por longos anos, até que seja feito o diagnóstico. A endometriose agrega uma série de teorias, entre elas, a do fluxo menstrual retrógrado, a mais aceita atualmente. Embora seja a que mais impere, a teoria do refluxo menstrual é falha em explicar, individualmente, a doença, haja vista que este é um evento fisiológico na maior parte das mulheres, dando margem a outras hipóteses complementares, como a da autoimunidade. Em pacientes com endometriose, a autoimunidade pode ser evidenciada por uma série de mecanismos de natureza inflamatória autoimune, tais como: 1) presença de autoanticorpos; 2) disfunção de linfócitos T e B; 3) exacerbação de citocinas inflamatórias; e 4) polimorfismo do gene PTPN22, considerado um sinalizador da presença de doenças autoimunes e cogitado como futuro marcador de endometriose. Sendo assim, esta revisão bibliográfica tem como objetivo analisar os aspectos mais relevantes da relação endometriose e autoimunidade, contemplando três vertentes principais: imunidade humoral, imunidade celular e mutações do gene PTPN22...

Correlação de fadiga com dor e incapacidade na artrite reumatoide e na osteoartrite, respectivamente / Correlation of fatigue with pain and disability in rheumatoid arthritis and osteoarthritis, respectively

OBJETIVO: Investigar a correlação de fadiga com dor em pacientes com artrite reumatoide e de fadiga com incapacidade em pacientes com osteoartrite. MÉTODOS: Foram avaliados 20 pacientes com artrite reumatoide e 20 com osteoartrite. Fadiga foi avaliada com escala visual analógica e questionário de avaliação multidimensional de fadiga. Utilizou-se a escala visual analógica para avaliar dor e para a avaliação global da doença pelo paciente. Incapacidade foi avaliada pelo questionário de avaliação de saúde. Idade, gênero, duração da doença, escolaridade, renda mensal, uso de drogas antirreumáticas e comorbidades foram obtidos. A análise estatística incluiu teste exato de Fisher, Shapiro-Wilk, Kruskal-Wallis e Spearman. O nível de significância foi de 0,05. RESULTADOS: A fadiga mostrou-se significativamente aumentada na osteoartrite em comparação à artrite reumatoide quando se utilizou o questionário de avaliação multidimensional de fadiga (P < 0,05). Dor correlacionou-se com fadiga ao se utilizar a escala visual analógica ou o questionário de avaliação multidimensional de fadiga em artrite reumatoide (r = 0,46; P < 0,05). O questionário de avaliação de saúde foi associado à fadiga por escala visual analógica em osteoartrite (r = 0,54; P < 0,05). Avaliação global da doença pelo paciente correlacionou-se com fadiga pela escala visual analógica (r = 0,44; P < 0,003). Todas as pacientes eram mulheres, predominantemente idosas, com médias de idade semelhantes, longa duração de doença e baixa renda. CONCLUSÃO: Nossos resultados confirmam que em pacientes com artrite reumatoide a fadiga correlaciona-se com dor, enquanto em pacientes com osteoartrite ela associa-se à incapacidade. Portanto, fadiga tem diferentes correlatos em osteoartrite e artrite reumatoide. Sugerimos que incapacidade, e não dor, seja o correlato da fadiga em pacientes com osteoartrite.

OBJECTIVE: To investigate the correlation of fatigue with pain in rheumatoid arthritis patients and with disability in osteoarthritis patients. METHODS: Twenty patients with rheumatoid arthritis and 20 patients with osteoarthritis were evaluated. The degree of fatigue was evaluated with a visual analogue scale and the Multidimensional Assessment of Fatigue. Pain was evaluated with a visual analogue scale as well as Patient Global Assessment. For disability evaluation, the Health Assessment Questionnaire was performed. Age, gender, disease duration, education, income, antirheumatic drugs used and comorbidity were also obtained. Statistical analysis included Fisher exact, Shapiro-Wilk, Kruskal-Wallis and Spearman tests. The significance level was 0.05. RESULTS: Fatigue was more significantly increased in patients with osteoarthritis than in patients with rheumatoid arthritis when evaluated with Multidimensional Assessment of Fatigue (P < 0.05). Pain was found to correlate with fatigue evaluated with visual analogue scale or Multidimensional Assessment of Fatigue in patients with rheumatoid arthritis (r = 0.46; P < 0.05). Health Assessment Questionnaire was associated with fatigue visual analogue scale in patients with osteoarthritis (r = 0.54; P < 0.05). Patient Global Assessment correlates with fatigue visual analogue scale (r = 0.44; P < 0.003). Patients were similar in both groups: all females, similar mean age, with long disease duration and low income. CONCLUSION: Our results corroborate that fatigue in rheumatoid arthritis patients correlates with the degree of pain, while in osteoarthritis patients it is associated with disability. Therefore, we found that fatigue has different correlates in osteoarthritis and rheumatoid arthritis, and we suggest that disability, not pain, is a correlate of fatigue in osteoarthritis patients.

Correlation of fatigue with pain and disability in rheumatoid arthritis and osteoarthritis, respectively.

OBJECTIVE: To investigate the correlation of fatigue with pain in rheumatoid arthritis patients and with disability in osteoarthritis patients. METHODS: Twenty patients with rheumatoid arthritis and 20 patients with osteoarthritis were evaluated. The degree of fatigue was evaluated with a visual analogue scale and the Multidimensional Assessment of Fatigue. Pain was evaluated with a visual analogue scale as well as Patient Global Assessment. For disability evaluation, the Health Assessment Questionnaire was performed. Age, gender, disease duration, education, income, antirheumatic drugs used and comorbidity were also obtained. Statistical analysis included Fisher exact, Shapiro-Wilk, Kruskal-Wallis and Spearman tests. The significance level was 0.05. RESULTS: Fatigue was more significantly increased in patients with osteoarthritis than in patients with rheumatoid arthritis when evaluated with Multidimensional Assessment of Fatigue (P < 0.05). Pain was found to correlate with fatigue evaluated with visual analogue scale or Multidimensional Assessment of Fatigue in patients with rheumatoid arthritis (r = 0.46; P < 0.05). Health Assessment Questionnaire was associated with fatigue visual analogue scale in patients with osteoarthritis (r = 0.54; P < 0.05). Patient Global Assessment correlates with fatigue visual analogue scale (r = 0.44; P < 0.003). Patients were similar in both groups: all females, similar mean age, with long disease duration and low income. CONCLUSION: Our results corroborate that fatigue in rheumatoid arthritis patients correlates with the degree of pain, while in osteoarthritis patients it is associated with disability. Therefore, we found that fatigue has different correlates in osteoarthritis and rheumatoid arthritis, and we suggest that disability, not pain, is a correlate of fatigue in osteoarthritis patients.

Doença celíaca associada à tireoidite de Hashimoto e síndrome de Noonan / Celiac disease associated with Hashimoto's thyroiditis and Noonan syndrome

OBJETIVO: Relatar o caso clínico de uma criança portadora de doença celíaca, tireoidite de Hashimoto e síndrome de Noonan. DESCRIÇÃO DE CASO: Menina de dez anos e seis meses, branca, apresentando história de diarreia líquida há cinco meses e "aumento da barriga". Ao exame, mostrava peso de 20.580g (p<3), estatura de 114cm (p<3), hidratada, descorada 2+/4+ e consciente. Presença de fácies triangular, com hipertelorismo ocular aparente, posição antimongoloide das fendas palpebrais, orelhas em abano de baixa implantação, micrognatia, pescoço curto e pectus excavatum. O abdome mostrava-se globoso, flácido, indolor, com hérnia umbilical, fígado a 2cm do rebordo costal direito, linfedema em membro superior direito e edema de membros inferiores. Nos exames subsidiários, havia anemia microcítica e hipocrômica, déficit de proteínas totais, tireoidite de Hashimoto e atraso de cinco anos na idade óssea. Na ultrassonografia abdominal, as alças intestinais estavam levemente dilatadas. Devido ao linfedema e à diarreia crônica, a hipótese inicial foi de linfangiectasia intestinal, confirmada pela biópsia jejunal, que ainda mostrou padrão compatível de doença celíaca. O cariótipo foi 46XX com diagnóstico clínico de síndrome de Noonan. COMENTÁRIOS: As doenças autoimunes se associam; no caso apresentado, a doença celíaca se associou à tireoidite de Hashimoto, possivelmente pela presença de antígenos do sistema HLA. Já a associação de doença celíaca à síndrome de Noonan é muito rara, sendo este o terceiro relato na literatura.

OBJECTIVE: To describe the clinical case of a child with celiac disease, Hashimoto's thyroiditis and Noonan syndrome. CASE DESCRIPTION: A Caucasian girl aged ten years and six months had liquid diarrhea for five months, and a "distended belly". At the physical exam: weight of 20,580g (p<3), length of 114cm (p<3), hydrated, anemic 2+/4+ and conscious. The patient presented triangular facies, apparent ocular hypertelorism, antimongoloid position of the palpebral fissures, ears with low implantation, micrognathia, short neck and pectus excavatum. The abdomen was globular, flaccid and painless; the liver was 2cm below the right costal margin. Lymphedema in right upper limb and lower limb edema was also noted. Laboratory exams showed microcytic and hypochromic anemia, deficit of total proteins, Hashimoto's thyroiditis and a 5-year delay in bone age. Abdominal ultrasonography showed the bowel slightly dilated. Due to lymphedema and chronic diarrhea, the initial hypothesis was intestinal lymphangiectasis, which was confirmed by a jejunal biopsy, which also showed celiac disease. The genetic evaluation revealed a 46XX karyotype and a clinical diagnosis of Noonan syndrome. COMMENTS: Different autoimmune diseases can be associated. In this case, the celiac disease and the Hashimoto's thyroiditis are possibly related to the presence of HLA system antigens. However, the association of the celiac disease with the Noonan syndrome is very rare, and this is the third report in the literature.

Hemangiopericitoma da mama / Hemangiopericytoma of the breast

Hemangiopericitoma é uma incomum neoplasia mesenquimal, ricamente vascularizada, compostapor células indiferenciadas, descrita em várias localizações do corpo humano e raramente namama. Na maioria dos casos, possui comportamento biológico benigno. Relata-se um caso de hemangiopericitomade mama feminina, enfatizando aspectos clínicos e anatomopatológicos típicosdesta neoplasia.

Hemangiopericytoma is an uncommon richly vascular mesenchymal neoplasm, composed of undifferentiatedcells that has been described in various sites of the human body, but only rarely in the breast. Themajority of cases has a benign biological behavior. We report one case of hemangiopericytoma of femalebreast emphasizing typical clinical and anatomopathological features of this neoplasm.