Francisco Aires Corrêa Lima

Update on the brazilian consensus for the diagnosis and treatment of rheumatoid arthritis

Manoel Barros Bértolo(1), Claiton Viegas Brenol(2), Cláudia Goldenstein Schainberg(3), Fernando Neubarth(4), Francisco Aires Correa de Lima(5), Ieda Maria Laurindo(6), Inês Guimarães Silveira(7), Ivanio Alves Pereira(8), Marco Antonio Rocha Loures(9), Mario Newton de Azevedo(10), Max Victor Carioca de Freitas(11), Milton da Silveira Pedreira Neto(12), Ricardo Machado Xavier(13), Rina Dalva N. Giorgi(14), Sergio Candido Kowalski(15), Sonia Maria Alvarenga Anti(16)

The Wnt signaling pathway and rheumatoid arthritis.

The Wnt signaling pathways play a key role in cell renewal, and there are two such pathways. In patients with rheumatoid arthritis (RA), the synovial membrane expresses genes such as Wnt and Fz at higher levels than those observed in patients without RA. The Wnt proteins are glycoproteins that bind to receptors of the Fz family on the cell surface. The Wnt/Fz complex controls tissue formation during embryogenesis, as well as throughout the process of limb development and joint formation. Recent studies have suggested that this signaling pathway plays a role in the pathophysiology of RA. Greater knowledge of the role of the Wnt signaling pathway in RA could improve understanding of the differences in RA clinical presentation and prognosis. Further studies should also focus on Wnt family members as molecular targets in the treatment of RA.

Lack of association between the CC genotype of the rs7903146 polymorphism in the TCF7L2 gene and rheumatoid arthritis

INTRODUCTION TCF7L2 is a transcription factor involved in Wnt/beta-catenin signaling and which has a variant known to be consistently associated with type 2 diabetes risk and some studies have also indicated its association with risk of certain types of cancer. OBJECTIVE Since this pathway may be involved in the pathophysiology of other chronic inflammatory diseases such as rheumatoid arthritis, we aimed to investigate the effect of TCF7L2 polymorphism rs7903146 on rheumatoid arthritis severity in a Brazilian population. PATIENTS AND METHODS This polymorphism was genotyped in 208 patients with rheumatoid arthritis and in 104 healthy controls. We also analyzed the association of this polymorphism to smoking history, functional status classification and radiological indicators of disease severity. RESULTS The distribution of CC, CT and TT genotypes of SNP rs7903146 of the TCF7L2 gene was not different between patients and controls, and no association between the genotype and indicators of disease severity or smoking history was found. When data were evaluated using the dominant model, in which carriers of the CT and TT genotypes were grouped, an increase in the T allele was observed in patients positive for rheumatoid factor and erosions, although this was not significant. The frequency of T allele was also increased in patients with functional class II compared to class I (P = 0.032). CONCLUSION It is possible that the small number of patients included in this study may have restrained additional findings. Further studies are therefore needed to investigate the role of TCF7L2 gene variants in the risk of rheumatoid arthritis and its severity.

Cyclophosphamide administration routine in autoimmune rheumatic diseases: a review

Cyclophosphamide is an alkylating agent widely used for the treatment of malignant neoplasia and which can be used in the treatment of multiple rheumatic diseases. Medication administration errors may lead to its reduced efficacy or increased drug toxicity. Many errors occur in the administration of injectable drugs. The present study aimed at structuring a routine for cyclophosphamide use, as well as creating a document with pharmacotherapeutic guidelines for the patient. The routine is schematized in three phases: pre-chemotherapy, administration of cyclophosphamide, and post-chemotherapy, taking into account the drugs to be administered before and after cyclophosphamide in order to prevent adverse effects, including nausea and hemorrhagic cystitis. Adverse reactions can alter laboratory tests; thus, this routine included clinical management for changes in white blood cells, platelets, neutrophils, and sodium, including cyclophosphamide dose adjustment in the case of kidney disease. Cyclophosphamide is responsible for other rare - but serious - side effects, for instance, hepatotoxicity, severe hyponatremia and heart failure. Other adverse reactions include hair loss, amenorrhea and menopause. In this routine, we also entered guidelines to post-chemotherapy patients. The compatibility of injectable drugs with the vehicle used has been described, as well as stability and infusion times. The routine aimed at the rational use of cyclophosphamide, with prevention of adverse events and relapse episodes, factors that may burden the health care system.

Lúpus induzido por drogas: da imunologia básica à aplicada

Drug-induced lupus (DIL) has been described as the development of idiopathic systemic lupus erythematous-like symptoms, temporarily associated to the exposition to drugs, and as a rule, the condition is improved with the suspension of the triggering medication. The most classical association is with procainamide and hydralazine. Recently, with the introduction of new drugs in the clinical practice, an increase on the number of medications associated with the occurence of the disease has been reported, and the current list includes almost one hundred drugs associated to the occurrence of DIL. The basic DIL immunologic mechanism, although described for more than 60 years, is not yet fully understood. There are several hypotheses for the drug-induced autoimmunity process, and the phenomenon is generally interpreted as an inappropriate activation of the immune system. Among the several theories proposed, the most accepted ones are: the inhibition of the DNA methylation by some drugs, what would allow the activation of T-cells; the oxidation of some substances by monocytes, what would generate active metabolites that in turn would lead to the activation of antigen-presenting cells and/or the interference of the metabolites of some drugs with the immune system tolerance. Further studies should be conducted in order to elucidate the DIL immunopathogeny with the objective of developing specific treatments based on the better knowledge on the pathogenic mechanisms.

Rotina de administração de ciclofosfamida em doenças autoimunes reumáticas: uma revisão.

Cyclophosphamide (CPM) is an alkylating agent widely used for the treatment of malignant neoplasia and which can be used in the treatment of multiple rheumatic diseases. Medication administration errors may lead to its reduced efficacy or increased drug toxicity. Many errors occur in the administration of injectable drugs. The present study aimed at structuring a routine for cyclophosphamide use, as well as creating a document with pharmacotherapeutic guidelines for the patient. The routine is schematized in three phases: pre-chemotherapy (pre-ChT), administration of cyclophosphamide, and post-chemotherapy (post-ChT), taking into account the drugs to be administered before and after cyclophosphamide in order to prevent adverse effects, including nausea and hemorrhagic cystitis. Adverse reactions can alter laboratory tests; thus, this routine included clinical management for changes in white blood cells, platelets, neutrophils, and sodium, including cyclophosphamide dose adjustment in the case of kidney disease. Cyclophosphamide is responsible for other rare-but serious-side effects, for instance, hepatotoxicity, severe hyponatremia and heart failure. Other adverse reactions include hair loss, amenorrhea and menopause. In this routine, we also entered guidelines to post-chemotherapy patients. The compatibility of injectable drugs with the vehicle used has been described, as well as stability and infusion times. The routine aimed at the rational use of cyclophosphamide, with prevention of adverse events and relapse episodes, factors that may burden the health care system.

EGPA Associated to chCRR A Case Report Eosinophilic Granulomatosis with Polyangiitis Associated to Chromophobe Renal Cell Carcinoma: A Case Report

Sandra Maximiano de Oliveira1*, Cezar Kozak Simaan2, Leopoldo Luiz dos Santos Neto3, Cleandro Pires de Albuquerque1, Isadora Jochims4, Ana Paula Monteiro Gomides Reis2, Francisco Aires Côrrea Lima1, Daniel de Amorim Rondon1, Ana Carolina Emy Vicente Hidaka1, Ana Paula Faria Carvalho1, Talita Yokoy de Souza1 and Luciano Junqueira Guimarães1 1Rheumatology Department, Brasília University Hospital, Brazil 2Department of Rheumatology, Brasília University, Brazil 3Department of Internal Medicine, Brasília University, Brazil 4Brazilian Rheumatology Society, Brazil *Corresponding author: Sandra Maximiano de Oliveira, Rheumatology Department, Brasília University Hospital, Federal District, Brazil, Tel: +5561991776559; E-mail: sandramaximianoo@gmail.com