II Brazilian Society of Rheumatology consensus for lupus nephritis diagnosis and treatment.

OBJECTIVE: To develop the second evidence-based Brazilian Society of Rheumatology consensus for diagnosis and treatment of lupus nephritis (LN). METHODS: Two methodologists and 20 rheumatologists from Lupus Comittee of Brazilian Society of Rheumatology participate in the development of this guideline. Fourteen PICO questions were defined and a systematic review was performed. Eligible randomized controlled trials were analyzed regarding complete renal remission, partial renal remission, serum creatinine, proteinuria, serum creatinine doubling, progression to end-stage renal disease, renal relapse, and severe adverse events (infections and mortality). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to develop these recommendations. Recommendations required ≥82% of agreement among the voting members and were classified as strongly in favor, weakly in favor, conditional, weakly against or strongly against a particular intervention. Other aspects of LN management (diagnosis, general principles of treatment, treatment of comorbidities and refractory cases) were evaluated through literature review and expert opinion. RESULTS: All SLE patients should undergo creatinine and urinalysis tests to assess renal involvement. Kidney biopsy is considered the gold standard for diagnosing LN but, if it is not available or there is a contraindication to the procedure, therapeutic decisions should be based on clinical and laboratory parameters. Fourteen recommendations were developed. Target Renal response (TRR) was defined as improvement or maintenance of renal function (±10% at baseline of treatment) combined with a decrease in 24-h proteinuria or 24-h UPCR of 25% at 3 months, a decrease of 50% at 6 months, and proteinuria < 0.8 g/24 h at 12 months. Hydroxychloroquine should be prescribed to all SLE patients, except in cases of contraindication. Glucocorticoids should be used at the lowest dose and for the minimal necessary period. In class III or IV (±V), mycophenolate (MMF), cyclophosphamide, MMF plus tacrolimus (TAC), MMF plus belimumab or TAC can be used as induction therapy. For maintenance therapy, MMF or azathioprine (AZA) are the first choice and TAC or cyclosporin or leflunomide can be used in patients who cannot use MMF or AZA. Rituximab can be prescribed in cases of refractory disease. In cases of failure in achieving TRR, it is important to assess adherence, immunosuppressant dosage, adjuvant therapy, comorbidities, and consider biopsy/rebiopsy. CONCLUSION: This consensus provides evidence-based data to guide LN diagnosis and treatment, supporting the development of public and supplementary health policies in Brazil.

Safety and efficacy of tofacitinib for the treatment of patients with juvenile idiopathic arthritis: preliminary results of an open-label, long-term extension study.

OBJECTIVES: We report the safety, tolerability and efficacy of tofacitinib in patients with juvenile idiopathic arthritis (JIA) in an ongoing long-term extension (LTE) study. METHODS: Patients (2-<18 years) with JIA who completed phase 1/3 index studies or discontinued for reasons excluding treatment-related serious adverse events (AEs) entered the LTE study and received tofacitinib 5 mg two times per day or equivalent weight-based doses. Safety outcomes included AEs, serious AEs and AEs of special interest. Efficacy outcomes included improvement since tofacitinib initiation per the JIA-American College of Rheumatology (ACR)70/90 criteria, JIA flare rate and disease activity measured by Juvenile Arthritis Disease Activity Score (JADAS)27, with inactive disease corresponding to JADAS ≤1.0. RESULTS: Of 225 patients with JIA (median (range) duration of treatment, 41.6 (1-103) months), 201 (89.3%) had AEs; 34 (15.1%) had serious AEs. 10 patients developed serious infections; three had herpes zoster. Two patients newly developed uveitis. Among patients with polyarticular course JIA, JIA-ACR70/90 response rates were 60.0% (78 of 130) and 33.6% (47 of 140), respectively, at month 1, and generally improved over time. JIA flare events generally occurred in <5% of patients through to month 48. Observed mean (SE) JADAS27 was 22.0 (0.6) at baseline, 6.2 (0.7) at month 1 and 2.8 (0.5) at month 48, with inactive disease in 28.8% (36 of 125) of patients at month 1 and 46.8% (29 of 82) at month 48. CONCLUSIONS: In this interim analysis of LTE study data in patients with JIA, safety findings were consistent with the known profile of tofacitinib, and efficacy was maintained up to month 48. TRIAL REGISTRATION NUMBER: NCT01500551.

Cell phenotypes as activity biomarkers in patients with Systemic Lupus Erythematosus

Abstract The pathogenesis of systemic lupus erythematosus (SLE) is complex. Few studies in Brazilian population have addressed cell phenotypes associated with immunological responses and their associations with SLE activity. The aim of this study is to investigate cell phenotypes associated to SLE diagnosis, treatment and activity. Twenty-eight SLE female patients (17 inactive, 11 active) and 10 healthy women were included in this study. Markers of natural killer (Nk), T and B cells in peripheral blood were evaluated by flow cytometry. Nkt cells were decreased only in SLE active patients. Activated CD4+, regulatory T FoxP3+ and B cells were decreased in both active and inactive SLE patients, compared to control group. The data corroborate the disruption of immune regulatory response in SLE patients and suggest phenotipic changes as possible biomarkers of SLE activity.

Cosmetic camouflage improves health-related quality of life in women with systemic lupus erythematosus and permanent skin damage: A controlled intervention study.

OBJECTIVE: To investigate the effect of cosmetic camouflage in health-related quality of life (HRQoL) in women with systemic lupus erythematosus (SLE) and permanent facial skin damage. METHODS: This is a randomized controlled clinical trial (Universal Trial Number: U1111-1210-2554e) with SLE women from outpatients using ACR/1997 and/or SLICC/2012 criteria, aged over 18 years old, with modified SLEDAI 2k < 4 and permanent facial skin damage, recruited in two tertiary centers to use cosmetic camouflage (n = 36) or no intervention (n = 20). Endpoints were score variations in SLE Quality of Life (SLEQoL) (total and each domain), Dermatology Life Quality Index (DLQI), Rosenberg self-esteem scale and Hospital Anxiety and Depression Scale (HADS), after daily use of cosmetic camouflage for 12 +/-2 weeks (Phase I), "as needed" use of cosmetic camouflage for another 12 +/-2 weeks (Phase II), and during total follow up (24 +/-2 weeks). Univariate and multivariate linear regressions were conducted by protocol analysis. RESULTS: Both groups were similar at baseline regarding age, disease duration, socio-demographic, clinical, laboratory and treatment characteristics. The comparison of score variations between intervention and control groups showed an independent HRQoL improvement in total SLEQoL score after using cosmetic camouflage in Phase I [ß -27.56 (CI 95% -47.86 to -7.27) p = 0.009] and total follow up [ß -28.04 (CI 95% -48.65 to -7.44) p = 0.09], specifically in mood, self-image and physical functioning domains. Also, there was an improvement in DLQI scores during Phase I [ß -7.65 (CI 95% -12.31 to -3.00) p = 0.002] and total follow up [ß -8.97(CI95% -12.99 to -4.94) p < 0.001). Scores for depression [ß -1.92 (CI 95% -3.67 to -0.16) p = 0.033], anxiety [ß -2.87 (CI 95% -5.67 to -0.07] p = 0.045] and self-esteem [ß 2.79 (CI 95% 0.13 to 5.46) p = 0.041] improved considering the total follow up. No significant changes occurred in the control group scores. CONCLUSION: The use of cosmetic camouflage improved the HRQoL in female SLE patients with permanent facial skin damage.

Correlation between active disease and hypercoagulability state in patients with systemic lupus erythematosus.

OBJECTIVE: This study has investigated whether high levels of Reticulocytes-C4d (R-C4d) and Platelets-C4d (P-C4d) reflecting recent activity in SLE patients are correlated with changes in natural anticoagulation components, coagulation activation and endothelial injury markers. METHODS: This study included three groups: 1) healthy women (control, n = 30); 2) women with low activity of the disease (SLEDAI 2 K ≤ 4, n = 30); 3) women with active disease (moderate or high activity) (SLEDAI 2 K > 4, n = 30). Median fluorescence intensity (MFI) of R-C4d and P-C4d were determined by flow cytometry using double labeling with specific monoclonal antibodies. Endothelial injury and hypercoagulability were evaluated by measuring Thrombomodulin and D-dimer levels. RESULTS: Higher MFI index of R-C4d were related to the recent activity of SLE, and higher expression of P-C4d indicated an elevated risk of thrombotic complications. Increased levels of soluble thrombomodulin and D-dimer were observed in patients with active SLE. CONCLUSION: R-C4d is helpful to monitor early disease activity and PC4-d may be an important tool to detect a prothrombotic phenotype in SLE. Elevated levels of D-dimer and thrombomodulin add value to P-C4d data and corroborate a hypercoagulable profile in women with SLE, contributing to an increased prothrombotic risk associated with inflammation.

Systemic lupus erythematosus: disease activity may influence the release of endothelial microparticles?

: To evaluate blood-borne endothelial microparticles (EMPs) in women with SLE and correlated these to disease activity as defined by the SLEDAI-2K score. The study takes cross-sectional design. A total of 90 age-matched women were recruited including: G1 (healthy volunteers, n = 30), G2 (women with SLE and low disease activity (SLEDAI-2K score ≤4; n = 30) and G3 (women with SLE and moderate/high disease activity (SLEDAI-2K score >4; n = 30). Blood was collected in 3.2% sodium citrate. Subsequently, the microparticles were purified by ultracentrifugation and labeled with anti-CD51/61 and anti-Annexin-V antibodies. Quantification and phenotyping were performed using flow cytometry. The number of EMPs was significantly higher in SLE patients compared with controls (P = 0.0178). When SLE patients were stratified according to disease activity, the number of EMPs was significantly increased in women with moderate-to-high disease activity compared with controls (P = 0.0074). We observed a correlation between the number of EMPs and age (r = -0.34; P = 0.0123) and between the number of EMPs and SLEDAI-2K score (r = 0.30; P = 0.04). Our results suggest that the SLE causes increased EMPs release, especially in patients with SLEDAI-2K score greater than 4. Although measurement of the EMPs could be useful in distinguishing patients with SLE from health controls, they have limited value in differentiating between SLE subtypes.

Síndrome de Felty e Calazar: um desafio para o reumatologista / Felty's syndrome and Kala-azar: a challenge for the rheumatologist

Os autores relatam o caso de uma paciente com artrite reumatoide que evoluiu com grave neutropenia e esplenomegalia, sendo firmado o diagnóstico de Síndrome de Felty, que posteriormente desenvolveu Calazar. Ambas têm apresentação clínica e laboratorial semelhantes, tornando o diagnóstico diferencial difícil. O relato deste caso objetiva chamar a atenção para o reconhecimento da infecção por leishmaniose visceral em pacientes portadores de doenças reumáticas, assim como a possibilidade de um paciente com Calazar mimetizar um quadro de doença reumática sistêmica.

Case report of a patient with rheumatoid arthritis who developed severe neutropenia, splenomegaly and was diagnosed with Felty's syndrome. The patient later developed Kala-azar. Both diseases have similar clinical and laboratory presentation, making the differential diagnosis difficult. The present case report aims at drawing attention to the identification of visceral Leishmaniasis infection in patients with rheumatic diseases, as well as possibility of a patient with Kala-azar mimicking a set of symptoms of systemic rheumatic disease.

Cicatrização do cólon após mucosectomia mecânica e sutura evertente em ratos / Healing of colon after mechanic mucosectomy and evertent suture in rats

A mucosectomia é utilizada durante a confecção de reservatórios ileais nas proctocolectomias por doença inflamatória intestinal. Entretanto, tem-se relatado aumento da incidência de obstruções intestinais em pacientes submetidos ao procedimento, sendo que o contato de uma grande área de submucosa poderia ser responsável pela ocorrência de estenoses, além de poder relacionar-se com aumento da pressão de ruptura desses segmentos. Com o objetivo de avaliar as alterações macroscópicas após a mucosectomia e a pressão de ruptura desses segmentos, foram estudados 16 ratos Holtzman distribuídos em dois grupos: A (n=8), anastomose colo-cólica em plano único extramucoso invertente com pontos separados de fio absorvível e B (n=8), mucosectomia e anastomose colocólica em plano único evertente com pontos separados de fio absorvível. No terceiro dia pós-operatório, foram estudadas as alterações macroscópicas e a pressão de ruptura dos segmentos colônicos contendo as anastomoses. Os resultados obtidos mostraram aumento na incidência e intensidade das aderências peritoneais nos animais do grupo B (p=0,01), incidência de 100% de estenoses das anastomoses, sem que ocorresse qualquer estenose no grupo A (p=0,01) e aumento não significativo na pressão de ruptura das anastomoses no grupo B (4,3 ± 2,4 mmHg vs. 10,5 ± 8,2 mmHg). Concluindo, a mucosectomia aumentou a reação inflamatória tecidual, sendo causa não só de aumento na pressão de ruptura como na incidência de estenoses de anastomoses colônicas de ratos.

The mucosectomy is used during the making of the ileal pouch in proctocolectomy due to inflammatory bowel disease. However, there are reports of increased incidence of intestinal obstructions in patients undergoing the procedure, when the contact of a large submucosal area could be responsible for the stenosis, and can relate to the increase of burst pressure of these segments. To evaluate the macroscopic alterations after the mucosectomy and the burst pressure of these segments, 16 Holtzman rats were studied divided into two groups: A (n = 8), colo-colic anastomosis in extra mucosal single invertent plan with separate absorbable sutures and B (n = 8), mucosectomy and colo-colic anastomosis in a single evertent plane with separate absorbable sutures. On the third post-operatory day the macroscopic alterations and burst pressure of the colony segments containing the anastomosis were studied. The found results showed increase in the incidence and intensity of peritoneal adherences in the animals of group B (p=0,01), incidence of 100% of the anastomosis steanosis, with no occurrence of stenosis in the group A (p=0,01), and no significant increase in the burst pressure in the group B (4,3 ± 2,4 mmHg vs. 10,5 ±8,2 mmHg). Conclusion : the mucosectomy increased the tissue inflammatory reaction, giving cause to the increase of the burst pressure as well as the incidence of colonic anastomosis steanaosis in rats.

Felty's syndrome and Kala-azar: a challenge for the rheumatologist.

Case report of a patient with rheumatoid arthritis who developed severe neutropenia, splenomegaly and was diagnosed with Felty's syndrome. The patient later developed Kala-azar. Both diseases have similar clinical and laboratory presentation, making the differential diagnosis difficult. The present case report aims at drawing attention to the identification of visceral Leishmaniasis infection in patients with rheumatic diseases, as well as possibility of a patient with Kala-azar mimicking a set of symptoms of systemic rheumatic disease.

A paracoccidioidomicose em pacientes atendidos no hospital das clínicas da UFMG (HC-UFMG) / Paracoccidioidomycosis in patients attended in a university hospital

A paracoccidioidomicose (PCM) é a infecção fúngica sistêmica de maior prevalência na América Latina. Sua real prevalência, entretanto, não é conhecida, pois não é de notificação compulsória. Foram analisados, retrospectivamente, 74 pacientes com PCM atendidos no HC, entre 1975 e 2001. AS informações foram analisadas através do aplicativo EPIINFO 6.04. Os pacientes apresentaram a seguinte distribuição: 1) 54 (73%) eram homens; 2) 43 (58,1%) residiam em áreas urbanas e 26(35,1%) em áreas rurais de MG; 3) 47 (63,5%) relataram contato com área rural; 4) 28 (37,8%) eram lavradores, 19 (25,7%) eram prestadores de serviços em áreas urbanas, 15 (20,3%) eram estudantes, 6 (8,1%) eram "do lar" e 4 (5,4%) eram domésticas; 5) 31 (41,9%) eram feodérmico, 21 (28,4%) eram leucodérmicos, e 19 (25,7%) melanodérmicos.

Paracoccidioidomycosis (PCM) is the most prevalent systemic fungal infection in Latin America. However, its real prevalence is not known because there is not compulsory notification. A sample of 74 patients with PCM attended in a university hospital, between 1975 and 2001, was evaluated. The data were analyzed through EPIINFO 6.04 program. The patients had the following distribuition: 1) 54 (73%) men. 2) 43 (58,1%) living in urban areas and 26 (35,1%)in rural areas of Minas Gerais State. 3) 47 (63,5%) reported contact with rural area. 4) 28 (37,8%) were rural workers, 19 (25,7%) worked in urban areas, 15 (20,3%) were students, 6 (8,1%) were housewives and 4 (5,4%) were domestic maids. 5) 31 (41;9%) were mulattos, 21 (28,4%) were white, and 19 (25,7%) were black.

Cromomicose causada por Foncecaea pedrosoi em paciente com lúpus eritematoso sistêmico / Chromomycosis caused by Fonsecaea pedrosoi in a patient with systemic lupus erythesatosus

Os autores descrevem um caso de lúpus eritematoso sistêmico (LES) em corticoterapia a longo prazo, que evoluiu com lesões cutâneas em membro superior esquerdo, sendo diagnosticada cromomicose causada por Fonsecaea pedrosoi. A prevalência da cromomicose é maior em pacientes imunocompetentes e sua associação com doenças imunossupressoras, incluindo as colagenoses, é rara.

Síndromes paraneoplásicas: atualização / Paranoplastic syndromes: review

Síndromes paraneoplásicas definem um grupo de sinais, sintomas e situações clínicas de disfunções metabólicas e envolvimento funcional de órgãos, resultado da ação do tumor contra o hospedeiro, mas sem relação direta com o tumor ou suas metástases. Podem indicar o primeiro sinal de malignidade ou indicar recidiva após o tratamento. A patogenia é complexa, envolvendo a produção tumoral de substâncias resultantes de alterações genéticas e imunológicas. Este artigo descreve as principais síndromes endócrinas, hematológicas, dermatologicas e neuromusculares, suas manifestações e sua patogenia.

Paraneoplastic syndromes define a group of signs, symptoms and clinical situations of metabolic dysfunction or organ-funtional involvement which are the result of the effects that the tumor exerts on the host. Their occurrence may be the first sign of malignancy or be a sign of disease relapse. The pathogenesis is complex and involves tumoral production of substances that result of genetic and imunological mechanisms. This article discribes the most important endocrinologic, hematologic, dermatologic and neuromuscular syndromes, including their pathogenesis and manifestations.