Position statement of the Brazilian society of Rheumatology on mesna use as a preventive therapy for bladder disease in patients with systemic autoimmune diseases and systemic vasculitis under cyclophosphamide treatment.

OBJECTIVE: To review current literature to support the use of mesna as a preventive therapy for hemorrhagic cystitis and bladder cancer in patients with systemic autoimmune diseases and systemic vasculitis treated with cyclophosphamide. MATERIALS AND METHODS: The search for articles was conducted systematically through MEDLINE, LILACS, Cochrane Library, and Embase databases. Only articles in English were selected. For available records, titles and abstracts were selected independently by two investigators. RESULTS: Eighteen studies were selected for analysis. The known adverse effects of cyclophosphamide were hematological toxicity, infections, gonadal toxicity, teratogenicity, increased risk for malignancy and hemorrhagic cystitis. Long-term toxicity was highly dependent on cyclophosphamide cumulative dose. The risk of bladder cancer is especially higher in long-term exposure and with cumulative doses above 36 g. The risk remains high for years after drug discontinuation. Hemorrhagic cystitis is highly correlated with cumulative dose and its incidence ranges between 12 and 41%, but it seems to be lower with new regimens with reduced cyclophosphamide dose. No randomized controlled trials were found to analyze the use of mesna in systemic autoimmune rheumatic diseases and systemic vasculitis. Retrospective studies yielded conflicting results. Uncontrolled prospective studies with positive results were considered at high risk of bias. No evidence was found to support the use of mesna during the treatment with cyclophosphamide for autoimmune diseases or systemic vasculitis to prevent hemorrhagic cystitis and bladder cancer. In the scenarios of high cumulative cyclophosphamide dose (i.e., > 30 g), patients with restricted fluid intake, neurogenic bladder, therapy with oral anticoagulants, and chronic kidney disease, mesna could be considered. CONCLUSION: The current evidence was found to be insufficient to support the routine use of mesna for the prophylaxis of hemorrhagic cystitis and bladder cancer in patients being treated for systemic autoimmune diseases and systemic vasculitis with cyclophosphamide. The use may be considered for selected cases.

Magnetic resonance imaging findings in patients with polymyalgia rheumatica.

Objective: To describe the prevalence of magnetic resonance imaging (MRI) findings in patients with the clinical diagnosis of polymyalgia rheumatica (PMR). Materials and Methods: Sixteen consecutive patients with untreated PMR, meeting the American College of Rheumatology criteria, underwent MRI examinations of the shoulder(s), hip(s), or both, depending on clinical complaints. Six patients also underwent MRI of the spine. Results: We evaluated 24 shoulders, among which we identified subacromial-subdeltoid bursitis in 21 (87.5%), glenohumeral joint effusion in 17 (70.8%), and fluid distention of the long head of the biceps tendon sheath in 15 (62.5%). Peritendinitis and capsular edema were observed in 21 (87.5%) and 17 (70.8%) shoulders, respectively. We also evaluated 17 hips, identifying hip joint effusion in 12 (70.6%), trochanteric bursitis in 11 (64.7%), peritendinitis in 17 (100%), and capsular edema in 14 (82.4%). All six of the patients who underwent MRI of the spine were found to have interspinous bursitis. Conclusion: Subacromial-subdeltoid bursitis, glenohumeral joint effusion, and hip joint effusion are common findings in patients with PMR. In addition, such patients appear to be highly susceptible to peritendinitis and capsular edema. There is a need for case-control studies to validate our data and to determine the real impact that these findings have on the diagnosis of PMR by MRI.

Objetivo: Descrever os achados de ressonância magnética (RM) mais prevalentes em pacientes com diagnóstico clínico de polimialgia reumática (PMR). Materiais e Métodos: Dezesseis pacientes com PMR não tratada, classificados pelos critérios do American College of Rheumatology, foram submetidos a RM do ombro e/ou quadril, segundo suas queixas clínicas. Seis pacientes também foram submetidos a RM da coluna. Resultados: Foram avaliados 24 ombros, identificando-se bursite subacromial-subdeltoide em 21 (87,5%), sinovite glenoumeral em 17 (70,8%) e distensão líquida da bainha do tendão da cabeça longa do bíceps em 15 (62,5%). Peritendinite e edema capsular foram observados em 21 (87,5%) e 17 (70,8%) ombros, respectivamente. Dezessete quadris foram analisados, identificando-se sinovite em 12 (70,6%), bursite trocantérica em 11 (64,7%), peritendinite em 17 (100%) e edema capsular em 14 (82,4%). Os seis pacientes que realizaram RM da coluna apresentavam bursite interespinhosa. Conclusão: Bursite subacromial-subdeltoide, sinovite glenoumeral e do quadril são achados de imagem prevalentes em pacientes com PMR. Além disso, achados como peritendinite e edema capsular tiveram alta prevalência nesses pacientes. Estudos de casocontrole devem ser realizados para validar esses dados e estabelecer o real impacto desses achados no diagnóstico de PMR.

Magnetic resonance imaging findings in patients with polymyalgia rheumatica / Achados de ressonância magnética em pacientes com polimialgia reumática

Abstract Objective: To describe the prevalence of magnetic resonance imaging (MRI) findings in patients with the clinical diagnosis of polymyalgia rheumatica (PMR). Materials and Methods: Sixteen consecutive patients with untreated PMR, meeting the American College of Rheumatology criteria, underwent MRI examinations of the shoulder(s), hip(s), or both, depending on clinical complaints. Six patients also underwent MRI of the spine. Results: We evaluated 24 shoulders, among which we identified subacromial-subdeltoid bursitis in 21 (87.5%), glenohumeral joint effusion in 17 (70.8%), and fluid distention of the long head of the biceps tendon sheath in 15 (62.5%). Peritendinitis and capsular edema were observed in 21 (87.5%) and 17 (70.8%) shoulders, respectively. We also evaluated 17 hips, identifying hip joint effusion in 12 (70.6%), trochanteric bursitis in 11 (64.7%), peritendinitis in 17 (100%), and capsular edema in 14 (82.4%). All six of the patients who underwent MRI of the spine were found to have interspinous bursitis. Conclusion: Subacromial-subdeltoid bursitis, glenohumeral joint effusion, and hip joint effusion are common findings in patients with PMR. In addition, such patients appear to be highly susceptible to peritendinitis and capsular edema. There is a need for case-control studies to validate our data and to determine the real impact that these findings have on the diagnosis of PMR by MRI.

Resumo Objetivo: Descrever os achados de ressonância magnética (RM) mais prevalentes em pacientes com diagnóstico clínico de polimialgia reumática (PMR). Materiais e Métodos: Dezesseis pacientes com PMR não tratada, classificados pelos critérios do American College of Rheumatology, foram submetidos a RM do ombro e/ou quadril, segundo suas queixas clínicas. Seis pacientes também foram submetidos a RM da coluna. Resultados: Foram avaliados 24 ombros, identificando-se bursite subacromial-subdeltoide em 21 (87,5%), sinovite glenoumeral em 17 (70,8%) e distensão líquida da bainha do tendão da cabeça longa do bíceps em 15 (62,5%). Peritendinite e edema capsular foram observados em 21 (87,5%) e 17 (70,8%) ombros, respectivamente. Dezessete quadris foram analisados, identificando-se sinovite em 12 (70,6%), bursite trocantérica em 11 (64,7%), peritendinite em 17 (100%) e edema capsular em 14 (82,4%). Os seis pacientes que realizaram RM da coluna apresentavam bursite interespinhosa. Conclusão: Bursite subacromial-subdeltoide, sinovite glenoumeral e do quadril são achados de imagem prevalentes em pacientes com PMR. Além disso, achados como peritendinite e edema capsular tiveram alta prevalência nesses pacientes. Estudos de caso- controle devem ser realizados para validar esses dados e estabelecer o real impacto desses achados no diagnóstico de PMR.

Drug-related demyelinating syndromes: understanding risk factors, pathophysiological mechanisms and magnetic resonance imaging findings.

Some drugs and medications can precipitate immune system deregulations, which might be confused with recurrent demyelinating diseases, such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMO), exacerbations of an existing disease, neoplastic lesions or other conditions. In this narrative review we describe some of the most relevant drugs and medications associated with iatrogenic demyelination. The anthelminthic agent levamisole is a frequent cocaine adulterant and can precipitate an exacerbated immune response attacking the central nervous system (CNS). High-efficacy multiple sclerosis (MS) drugs might induce a selective CNS immunosuppression, making it susceptible for opportunistic infections that course with demyelination, such as progressive multifocal leukoencephalopathy. Sometimes, the interruption of a high-efficacy drug to treat MS can induce a rapid CNS reentry of lymphocytes, exacerbating demyelinating processes and triggering rebound syndromes. Furthermore, selective cytokines inhibition, such as anti-TNFα agents, might induce an imbalance between cell death and proliferation inducing a paradoxical increase of CNS tumor necrosis factor (TNF), affecting the activity of lymphocytes, microglia and macrophages, triggering aberrant inflammation and demyelination. Immune checkpoint inhibitors are a new class of antineoplastic drugs that enhance the immune response against tumor cells by an upregulation of T-cell activity. However, this hyperactivation of the immune system might be associated with induction of unwanted autoimmune responses. In this paper we review the risk factors, the possible pathological mechanisms and the magnetic resonance imaging (MRI) findings of these drug-related demyelinating syndromes.

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.

Rituximab for induction and maintenance therapy of granulomatosis with polyangiitis: a single-centre cohort study on 114 patients.

OBJECTIVES: To assess efficacy and safety of rituximab (RTX) induction and maintenance therapy for granulomatosis with polyangiitis (GPA) in a single-centre cohort study. METHODS: All patients with active GPA, not enrolled in trials, who received ⩾1 RTX infusion(s) for induction were included. At remission, protocolized maintenance RTX infusions were given every 6 months for 18 months. Kaplan-Meier curves were used to estimate survival rates. Univariable analyses identified factors associated with remission failure and relapse, and Cox models retained independent predictors of relapse. RESULTS: One hundred and fourteen adults with relapsing (65%), refractory/grumbling (22%) or new-onset (13%) GPA received RTX for induction; 100 were given ⩾1 RTX maintenance infusion(s) and 90 received 500 mg every 6 months. Median daily prednisone induction dose was 30 mg; 76% of patients were still receiving a median daily prednisone dose of 5 mg at 2 years. Median follow-up was 3.6 years. Respective 2-year relapse-free survival and RTX retention rates were 85 and 78%. Serious infection and serious adverse event rates were 4.9 and 8.1 per 100 patient-years, respectively. Refractory/grumbling vs new-onset and/or relapsing GPA (P < 0.01 for each individually; P < 0.001 vs the latter two taken together), pachymeningitis (P < 0.05), pure granulomatous disease (P < 0.05) or estimated glomerular filtration rate ⩾60 ml/min (P < 0.01) were associated with remission failure. Multivariate analyses retained refractory/grumbling GPA (P = 0.05), subglottic stenosis (P < 0.005), ENT involvement (P = 0.01) and skin involvement (P < 0.0005) as independent predictors of relapse. CONCLUSION: RTX induction and low-dose preemptive maintenance can effectively and safely induce sustained remission in GPA in a real-life setting.

Serum uric acid levels are associated with lupus nephritis in patients with normal renal function.

Uric acid has been recognised as a potential marker of endothelial dysfunction and kidney disease but there are scarce data about its importance in systemic lupus erythematosus (SLE) nephritis. This study aimed to evaluate serum uric acid (UA) levels in lupus nephritis (LN), by comparing SLE patients with normal renal function, with and without nephritis. Forty-six female SLE patients were consecutively selected and divided in two groups according to renal activity at the evaluation: presence of a recently diagnosed lupus nephritis (LN+, n = 18) and absence of lupus nephritis (LN-, n = 28). Age-matched healthy women were selected (CONTROL, n = 28). Patients with gout, creatinine clearance lower than 80 ml/min and use of drugs that interfere in UA were excluded. Laboratory and clinical data were analysed by appropriate tests. A multivariate analysis was performed, and a receiver operating characteristic (ROC) curve was plotted, and the area under the curve was calculated to assess the diagnostic strength of UA in LN. The mean age was similar among LN+, LN- and CONTROL groups (32.44 ± 6.09 vs. 30.68 ± 5.36 vs. 30.86 ± 5.00 years, p = 0.52). UA was significantly higher in LN+ compared to LN- (5.54 ± 1.67 vs. 3.65 ± 1.090 mg/dL, p < 0.001) and CONTROL (5.54 ± 1.67 vs. 3.92 ± 0.95 mg/dL p < 0.001). Multivariate analysis confirmed that high UA was an independent variable related to LN (p < 0.001). The cut-off value for UA using the ROC curve was 4.47 mg/dL (AUC 0.86, p = 0.00004, CI 95% 0.75-0.96). Lupus nephritis was associated with higher UA. Hyperuricemia as a predictor of renal damage in SLE needs to be evaluated in further studies.

Radiotherapy for a breast cancer patient with Schnitzler syndrome: Report of acute toxicity and early follow-up.

This article provides description about acute toxicity and early follow-up of one patient treated for breast cancer and Schnitzler syndrome. There are no previously reported cases exploring this interaction on medical literature. The expected radiodermitis to occur in the region treated with radiotherapy along with urticarial-like lesions might be challenging in view of the interaction between symptoms and therapeutic measures.

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.

Whole-body (99m)Tc-octreotide scintigraphy with SPECT/CT to detect occult tumor inducing paraneoplastic osteomalacia.

A 32-year-old woman presented with progressive myalgia, bone pain, fatigue, insufficiency hip fractures, high urine phosphate, and low serum phosphate and vitamin D levels. These findings were suggestive of oncogenic osteomalacia. A whole-body Tc-octreotide scintigraphy with SPECT/CT showed uptake on a sclerotic intramedullary lesion in the left medial tibia plateau. MRI depicted a solid lesion. The lesion was surgically removed; the patient became asymptomatic, and follow-up laboratory results normalized. Histopathologic examination revealed a vascular hemangiopericytoma-like tumor, positive for somatostatin receptor (SSR-2). Whole-body Tc-octreotide scintigraphy with SPECT/CT may detect occult oncogenic osteomalacia tumors.

Rituximab for induction and maintenance therapy in granulomatosis with polyangiitis (Wegener's). Results of a single-center cohort study on 66 patients.

The aim of this study was to evaluate the efficacy and safety of rituximab (RTX) associated with glucocorticoid treatment based on disease severity, as a remission induction treatment for granulomatosis with polyangiitis (GPA) (Wegener's) and to analyze the results of long-term maintenance therapy with low doses of RTX in a routine time-based protocol. This single-center retrospective study used standardized data collection from all GPA patients receiving RTX between 2002 and 2013. The remission induction regimen consisted of RTX and glucocorticoids, adapted according to disease severity. Once remission was achieved, patients received RTX maintenance treatment (500 mg every 6 months) for 18 months. Sixty-six GPA patients received RTX for remission induction. After six months, a response had been achieved in 78.8% of these patients, with a moderate oral prednisone regimen (mean dose at baseline, 32.8 ± 23.4 mg/day). Subglottic stenosis increased the risk of treatment failure (OR = 31.2, P = 0.0104). RTX maintenance treatment was continued for 18 months in 92% of the GPA patients, who were followed for 34.2 ± 26.2 months (mean total cumulative RTX dose of 4.6 ± 1.7 g). The relapse rate was 11.2/100 patient-years. The relapses occur a mean of 13.5 ± 14.7 months after the last RTX infusion. Twenty-one severe adverse events were recorded; 13.6% patients had severe infections. We conclude that in this single-center cohort, RTX associated with glucocorticoid treatment adapted for disease severity appeared to induce remission effectively in GPA patients. Maintenance treatment with low doses of RTX in a routine time-based protocol was safe and associated with low rates of relapse on treatment.

Creatine supplementation in fibromyalgia: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To investigate the efficacy and safety of creatine supplementation in fibromyalgia patients. METHODS: A 16-week, randomized, double-blind, placebo-controlled, parallel-group trial was conducted. Fibromyalgia patients were randomly assigned to receive either creatine monohydrate or placebo in a double-blind manner. The patients were evaluated at baseline and after 16 weeks. Muscle function, aerobic conditioning, cognitive function, quality of sleep, quality of life, kidney function, and adverse events were assessed. Muscle phosphorylcreatine content was measured through (31) P magnetic resonance spectroscopy. RESULTS: After the intervention, the creatine group presented higher muscle phosphorylcreatine content when compared with the placebo group (+80.3% versus -2.7%; P = 0.04). Furthermore, the creatine group presented greater muscle strength than the placebo group in the leg press and chest press exercises (+9.8% and +1.2% for creatine versus -0.5% and -7.2% for placebo, respectively; P = 0.02 and P = 0.002, respectively). Isometric strength was greater in the creatine group than in the placebo group (+6.4% versus -3.2%; P = 0.007). However, no general changes were observed in aerobic conditioning, pain, cognitive function, quality of sleep, and quality of life. Food intake remained unaltered and no side effects were reported. CONCLUSION: Creatine supplementation increased intramuscular phosphorylcreatine content and improved lower- and upper-body muscle function, with minor changes in other fibromyalgia features. These findings introduce creatine supplementation as a useful dietary intervention to improve muscle function in fibromyalgia patients.

Anticorpo antiproteína P ribossomal em pacientes com hepatite autoimune / Anti-ribosomal P protein antibody in autoimmune hepatitis patients

Introdução: Os anticorpos antiproteína P ribossomal (anti-P) são considerados marcadores sorológicos específicos do Lúpus Eritematoso Sistêmico (LES) e estão associados a acometimento hepático nesta doença. As semelhanças entre a hepatite autoimune (HAI) e a hepatite associada ao LES levou ao questionamento se o anticorpo anti-P também estaria presente na HAI. Objetivo: Avaliar a frequência e significância clínica do anticorpo anti-P em uma grande coorte de pacientes com HAI. Métodos: Foram analisados os soros de 96 pacientes com HAI, coletados no diagnóstico e comparados com 82 soros de indivíduos saudáveis. Todos os soros foram testados para a presença do anticorpo anti-P pelo método de ELISA, do anticorpo anti-DNA de dupla fita pelo método de imunofluorescência indireta usando Crithidia luciliae e do anticorpo anti-Sm pelo método de ELISA. Os critérios de exclusão adotados foram a presença de outros anticorpos específicos de LES como o anti-DNA de dupla fita (n=1) e o anti-Sm (n=2) ou se o paciente apresentasse o diagnóstico de LES definido pelo Colégio Americano de Reumatologia (n=0). Os prontuários médicos foram revisados para dados demográficos, clínicos e resultados de exames laboratoriais relacionados a hepatopatia e anticorpos específicos de HAI. Resultado: Títulos moderados ou alto (> 40 U) de anti-P foram encontrados em 9,7% (9/93) dos pacientes com HAI e em nenhum dos controles (p = 0,003). No diagnóstico, os pacientes com anti-P positivo ou negativo apresentavam características demográficas/clínicas semelhantes, como a frequência de cirrose (44,4% vs 28,5%, p = 0,44) e exames laboratoriais relacionados a hepatite (p > 0,05). Entretanto, ao final do seguimento destes pacientes (média de 10,2 ± 4,9 anos), os pacientes positivos para anticorpos anti-P apresentaram uma maior frequência de cirrose quando comparados a pacientes negativos para anti-P (100% vs 60%, p = 0,04). Conclusão: a demonstração da presença do anticorpo anti-P em pacientes com HAI...

Background: Autoantibodies to ribosomal P proteins (anti-rib P) are specific serological markers for systemic lupus erythematosus (SLE) and are associated with liver involvement in this disease. The similarity in autoimmune background between autoimmune hepatitis (AIH) and SLE- associated hepatitis raises the possibility that anti-rib P antibodies might also have relevance in AIH. Aims: To evaluate the frequency and clinical significance of anti-rib P antibodies in a large AIH cohort. Methods: Sera obtained at diagnosis of 96 AIH patients and of 82 healthy controls were tested for IgG anti-ribosomal P protein by ELISA. All of the sera were also screened for other lupus-specific autoantibodies, three patients with the presence of anti-dsDNA (n=1) and anti-Sm (n = 2) were excluded. Results: Moderate to high titers (> 40 U) of anti-rib P antibody were found in 9.7% (9/93) of the AIH patients and none of the controls (P = 0.003). At presentation, AIH patients with and without anti-rib P antibodies had similar demographic/clinical features, including the frequency of cirrhosis (44.4% vs. 28.5%, P = 0.44), hepatic laboratorial findings (p > 0.05). Importantly, at the final observation (follow-up period 10.2 ± 4.9 years), the AIH patients with anti-rib P had a significantly higher frequency of cirrhosis compared to the negative group (100% vs. 60%, P = 0.04). Conclusion: The novel demonstration of anti-rib P in AIH patients without clinical or laboratory evidence of SLE suggests a common underlying mechanism targeting the liver in these two diseases. In addition, this antibody appears to predict the patients with worse AIH prognoses...

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.

Cardiac autonomic impairment and chronotropic incompetence in fibromyalgia.

INTRODUCTION: We aimed to gather knowledge on the cardiac autonomic modulation in patients with fibromyalgia (FM) in response to exercise and to investigate whether this population suffers from chronotropic incompetence (CI). METHODS: Fourteen women with FM (age: 46 ± 3 years; body mass index (BMI): 26.6 ± 1.4 kg/m2) and 14 gender-, BMI- (25.4 ± 1.3 kg/m2), and age-matched (age: 41 ± 4 years) healthy individuals (CTRL) took part in this cross-sectional study. A treadmill cardiorespiratory test was performed and heart-rate (HR) response during exercise was evaluated by the chronotropic reserve. HR recovery (deltaHRR) was defined as the difference between HR at peak exercise and at both first (deltaHRR1) and second (deltaHRR2) minutes after the exercise test. RESULTS: FM patients presented lower maximal oxygen consumption (VO2 max) when compared with healthy subjects (22 ± 1 versus CTRL: 32 ± 2 mL/kg/minute, respectively; P < 0.001). Additionally, FM patients presented lower chronotropic reserve (72.5 ± 5 versus CTRL: 106.1 ± 6, P < 0.001), deltaHRR1 (24.5 ± 3 versus CTRL: 32.6 ± 2, P = 0.059) and deltaHRR2 (34.3 ± 4 versus CTRL: 50.8 ± 3, P = 0.002) than their healthy peers. The prevalence of CI was 57.1% among patients with FM. CONCLUSIONS: Patients with FM who undertook a graded exercise test may present CI and delayed HR recovery, both being indicative of cardiac autonomic impairment and higher risk of cardiovascular events and mortality.

Reduced seroprotection after pandemic H1N1 influenza adjuvant-free vaccination in patients with rheumatoid arthritis: implications for clinical practice.

BACKGROUND: Reduced response to pandemic (2009) H1N1 (pH1N1) vaccine in patients with rheumatoid arthritis (RA) was recently reported. OBJECTIVES: To evaluate the contribution of age, disease activity, medication and previous antibody levels to this reduced response. METHODS: 340 adult RA patients and 234 healthy controls were assessed before and 21 days after adjuvant-free influenza A/California/7/2009 (pH1N1) vaccine. Disease activity (DAS28), current treatment and pH1N1 antibody titres were collected. Seroprotection, seroconversion and factor increase in geometric mean titre (GMT) were calculated and adverse events registered. RESULTS: RA and controls showed similar (p>0.05) prevaccination GMT (8.0 vs 9.3) and seroprotection (10.8% vs 11.5%). After vaccination a significant reduction (p<0.001) was observed in all endpoints: GMT and factor increase in GMT, seroprotection and seroconversion rates. Disease activity did not preclude seroconversion or seroprotection and remained unchanged in 97.4% of patients. Methotrexate was the only disease-modifying antirheumatic drug associated with reduced responses (p=0.001). Vaccination was well tolerated. CONCLUSIONS: The data confirmed both short-term anti-pH1N1 vaccine safety and, different from most studies with seasonal influenza, reduced seroprotection in RA patients, unrelated to disease activity and to most medications (except methotrexate). Extrapolation of immune responses from one vaccine to another may therefore not be possible and specific immunisation strategies (possibly booster) may be needed. Clinicaltrials.gov no NCT01151644.

Immunogenicity and safety of the 2009 non-adjuvanted influenza A/H1N1 vaccine in a large cohort of autoimmune rheumatic diseases.

BACKGROUND: Despite the WHO recommendation that the 2010-2011 trivalent seasonal flu vaccine must contain A/California/7/2009/H1N1-like virus there is no consistent data regarding its immunogenicity and safety in a large autoimmune rheumatic disease (ARD) population. METHODS: 1668 ARD patients (systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ankylosing spondylitis (AS), systemic sclerosis, psoriatic arthritis (PsA), Behçet's disease (BD), mixed connective tissue disease, primary antiphospholipid syndrome (PAPS), dermatomyositis (DM), primary Sjögren's syndrome, Takayasu's arteritis, polymyositis and Granulomatosis with polyangiitis (Wegener's) (GPA)) and 234 healthy controls were vaccinated with a non-adjuvanted influenza A/California/7/2009(H1N1) virus-like strain flu. Subjects were evaluated before vaccination and 21 days post-vaccination. The percentage of seroprotection, seroconversion and the factor increase in geometric mean titre (GMT) were calculated. RESULTS: /st> After immunisation, seroprotection rates (68.5% vs 82.9% p<0.0001), seroconversion rates (63.4% vs 76.9%, p<0.001) and the factor increase in GMT (8.9 vs 13.2 p<0.0001) were significantly lower in ARD than controls. Analysis of specific diseases revealed that seroprotection significantly reduced in SLE (p<0.0001), RA (p<0.0001), PsA (p=0.0006), AS (p=0.04), BD (p=0.04) and DM (p=0.04) patients than controls. The seroconversion rates in SLE (p<0.0001), RA (p<0.0001) and PsA (p=0.0006) patients and the increase in GMTs in SLE (p<0.0001), RA (p<0.0001) and PsA (p<0.0001) patients were also reduced compared with controls. Moderate and severe side effects were not reported. CONCLUSIONS: The novel recognition of a diverse vaccine immunogenicity profile in distinct ARDs supports the notion that a booster dose may be recommended for diseases with suboptimal immune responses. This large study also settles the issue of vaccine safety. (ClinicalTrials.gov #NCT01151644).