Flávia Patrícia Sena Teixeira Santos

Basal Activation of Type I Interferons (Alpha2 and Beta) and 2'5'OAS Genes: Insights into Differential Expression Profiles of Interferon System Components in Systemic Sclerosis.

Objective. Systemic sclerosis (SSc) is a complex autoimmune disease in which interferons (IFNs) may play an essential role. We hypothesized that type I and III IFNs may be found in increased levels in patients and be responsible for SSc autoimmune status. Methods. Type I and III IFN and ISG basal expression profiles were measured by qPCR using RNA from PBMCs of patients and controls . Results. Type I IFNs are increased in SSc patients, while no induction of type III IFNs was detected. This induction cannot be related to IRF7, since no upregulation of this gene was seen on patients. Of the ISGs tested, 2′5′OAS levels were increased in patients, while 6–16 and MxA levels were not. Conclusions. While there is no indication of type III IFN induction, increased levels of type I IFNs may lead to abnormal regulation of ISGs that can be responsible for immune system alterations described for SSc.

Differential upregulation of human 2′5′OAS genes on systemic sclerosis: Detection of increased basal levels of OASL and OAS2 genes through a qPCR based assay

Abstract 2′5′OAS are template-independent RNA polymerases with antiviral activity and important to homeostasis maintenance. Here we have developed quantitative PCR (qPCR) reactions for the detection of each individual 2′5′OAS human gene and used them to evaluate these gene levels in systemic sclerosis patients cells. The method was efficient for quantification of 2′5′OAS genes on human cells after interferon (IFN) treatment, and revealed that primary cells from patients with systemic sclerosis have increased basal levels of OASL and OAS2 genes. When treated, patients cells are able to induce all four 2′5′OAS genes. Our hypothesis is that abnormally circulating type I IFNs on the disease could be establishing a desensitized state on patients cells, making them refractory to subsequent IFN doses, and that OASL and OAS2 genes upregulation may be due to an IFN-independent stimulus. Further characterizing the biological activities of these genes, their induction pathways and their regulatory functions can lead to better understanding of systemic sclerosis molecular mechanisms and of their biological activities.

Lúpus eritematoso sistêmico e pancreatite aguda: relato de dois casos

A pancreatite aguda e uma manifestacao incomum do lupus eritematoso sistemico (LES) e a frequencia desta associacao nao e conhecida. Contudo, a pancreatite aguda e um diagnostico diferencial importante na avaliacao da dor abdominal em pacientes com LES. Os pacientes, normalmente, apresentam dor de intensidade variavel, algumas vezes simulando abdome agudo. Varios fatores tem sido implicados na patogenese desta condicao, tais como fenomenos autoimunes, vasculite, anticorpos antifosfolipides e drogas. O papel dos corticosteroides como um fator etiologico e ainda controverso. Alem disso, em alguns relatos a manutencao do corticosteroide foi fundamental na recuperacao dos pacientes. Relatamos duas pacientes com lupus eritematoso sistemico que apresentaram pancreatite aguda. Em nenhum dos casos havia evidencias de quaisquer fatores predisponentes conhecidos para a pancreatite aguda, portanto esta condicao foi considerada uma manifestacao de atividade lupica. Uma das pacientes faleceu por sindrome da resposta inflamatoria sistemica secundaria a pancreatite. No outro caso, utilizouse corticoide em doses de estresse durante o tratamento, com boa evolucao.

Guidelines for the management and treatment of periodic fever syndromes familial Mediterranean fever

OBJECTIVE To establish guidelines based on scientific evidence for the management of familial Mediterranean fever. DESCRIPTION OF THE EVIDENCE COLLECTION METHOD The Guideline was prepared from 5 clinical questions that were structured through PICO (Patient, Intervention or indicator, Comparison and Outcome), to search key primary scientific information databases. After defining the potential studies to support the recommendations, these were graduated considering their strength of evidence and grade of recommendation. RESULTS 10,341 articles were retrieved and evaluated by title and abstract; from these, 46 articles were selected to support the recommendations. RECOMMENDATIONS 1. The diagnosis of FMF is based on clinical manifestations, characterized by recurrent febrile episodes associated with abdominal pain, chest or arthritis of large joints. 2. FMF is a genetic disease presenting an autosomal recessive trait, caused by mutation in the MEFV gene. 3. Laboratory tests are not specific, demonstrating high serum levels of inflammatory proteins in the acute phase of the disease, but also often showing high levels even between attacks. SAA serum levels may be especially useful in monitoring the effectiveness of treatment. 4. The therapy of choice is colchicine; this drug has proven its effectiveness in preventing acute inflammatory episodes and progression toward amyloidosis in adults. 5. Based on the available information, the use of biological drugs appears to be an alternative for patients with FMF who do not respond or are intolerant to therapy with colchicine.

Pioderma gangrenoso: um desafio para o reumatologista

O pioderma gangrenoso (PG) faz parte do espectro das dermatoses neutrofilicas, processos que tem em comum um padrao histologico similar, formado por infiltrado de leucocitos polimorfonucleares, de carater nao infeccioso e nao neoplasico e sem vasculite primaria. Caracteriza-se por ulceras dolorosas, com bordas imprecisas, de variados tamanhos e profundidade, localizadas principalmente nos membros inferiores, mas outras partes da pele, mucosas e outros orgaos podem estar envolvidos. A doenca tem grande morbidade e seu curso pode ser cronico ou recidivante. A patogenese nao e bem conhecida. Em 50 a 70% dos pacientes, esta associado a uma doenca de base, como doenca inflamatoria intestinal, doencas reumaticas, hematologicas ou malignidades; pode apresentar-se de forma isolada. Sao analisados dois pacientes com o diagnostico de pioderma gangrenoso e artrite associada, para ressaltar a importância do conhecimento dessa dermatose pelo reumatologista, ja que o acometimento articular ocorre em cerca de 37% dos pacientes que apresentam essa sindrome neutrofilica.O pioderma gangrenoso (PG) faz parte do espectro das dermatoses neutrofilicas, processos que tem em comum um padrao histologico similar, formado por infiltrado de leucocitos polimorfonucleares, de carater nao infeccioso e nao neoplasico e sem vasculite primaria. Caracteriza-se por ulceras dolorosas, com bordas imprecisas, de variados tamanhos e profundidade, localizadas principalmente nos membros inferiores, mas outras partes da pele, mucosas e outros orgaos podem estar envolvidos. A doenca tem grande morbidade e seu curso pode ser cronico ou recidivante. A patogenese nao e bem conhecida. Em 50 a 70% dos pacientes, esta associado a uma doenca de base, como doenca inflamatoria intestinal, doencas reumaticas, hematologicas ou malignidades; pode apresentar-se de forma isolada. Sao analisados dois pacientes com o diagnostico de pioderma gangrenoso e artrite associada, para ressaltar a importância do conhecimento dessa dermatose pelo reumatologista, ja que o acometimento articular ocorre em cerca de 37% dos pacientes que apresentam essa sindrome neutrofilica.

Guidelines for the management and treatment of periodic fever syndromes: periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome

OBJECTIVE To establish guidelines based on scientific evidence for the management of periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome. DESCRIPTION OF THE EVIDENCE COLLECTION METHOD The Guideline was prepared from 5 clinical questions that were structured through PICO (Patient, Intervention or indicator, Comparison and Outcome), to search in key primary scientific information databases. After defining the potential studies to support the recommendations, these were graduated considering their strength of evidence and grade of recommendation. RESULTS 806 articles were retrieved and evaluated by title and abstract; from these, 32 articles were selected to support the recommendations. RECOMMENDATIONS 1. PFAPA is a diagnosis of exclusion established on clinical grounds, and one must suspect of this problem in children with recurrent and periodic febrile episodes of unknown origin, or with recurrent tonsillitis interspersed with asymptomatic periods, especially in children in good general condition and with preservation of weight and height development. 2. Laboratory findings are nonspecific. Additional tests do not reveal pathognomonic changes. 3. The evidence supporting an indication for surgical treatment (tonsillectomy with or without adenoidectomy), is based on two non-blinded randomized clinical trials with small numbers of patients. 4. The use of prednisone at the onset of fever in patients with PFAPA proved to be an effective strategy. There is still need for more qualified evidence to support its use in patients with PFAPA. 5. Despite promising results obtained in studies with IL-1β inhibitors, such studies are limited to a few case reports.

Guidelines for the management and treatment of periodic fever syndromes: Cryopyrin-associated periodic syndromes (cryopyrinopathies - CAPS).

OBJECTIVE To establish guidelines based on cientific evidences for the management of cryopyrin associated periodic syndromes. DESCRIPTION OF THE EVIDENCE COLLECTION METHOD The Guideline was prepared from 4 clinical questions that were structured through PICO (Patient, Intervention or indicator, Comparison and Outcome), to search in key primary scientific information databases. After defining the potential studies to support the recommendations, these were graduated considering their strength of evidence and grade of recommendation. RESULTS 1215 articles were retrieved and evaluated by title and abstract; from these, 42 articles were selected to support the recommendations. RECOMMENDATIONS 1. The diagnosis of CAPS is based on clinical history and clinical manifestations, and later confirmed by genetic study. CAPS may manifest itself in three phenotypes: FCAS (mild form), MWS (intermediate form) and CINCA (severe form). Neurological, ophthalmic, otorhinolaryngological and radiological assessments may be highly valuable in distinguishing between syndromes; 2. The genetic diagnosis with NLRP3 gene analysis must be conducted in suspected cases of CAPS, i.e., individuals presenting before 20 years of age, recurrent episodes of inflammation expressed by a mild fever and urticaria; 3. Laboratory abnormalities include leukocytosis and elevated serum levels of inflammatory proteins; and 4. Targeted therapies directed against interleukin-1 lead to rapid remission of symptoms in most patients. However, there are important limitations on the long-term safety. None of the three anti-IL-1β inhibitors prevents progression of bone lesions.