Vitamin D receptor gene polymorphisms influence on clinical profile and bone mineral density at different skeletal sites in postmenopausal osteoporotic women.

Bone remodeling is marked by bone synthesis and absorption balance, and any altered dynamic in this process leads to osteoporosis (OP). The interaction of hormonal, environmental and genetic factors regulate bone metabolism. Since vitamin D displays a classic role in bone metabolism regulation, acting through vitamin D receptor (VDR), the genetic variants within VDR were the first ones associated with bone density and remodelling. Therefore, we investigated whether three single nucleotide polymorphisms (SNPs) within VDR were associated with OP differential susceptibility and clinical profile from postmenopausal versus healthy women from Northeast Brazil. Genetic association study enrolling 146 postmenopausal osteoporotic women as the patient group and 95 healthy age-matched women as the control group. We assessed three SNPs within VDR (rs11168268, rs1540339 and rs3890733), considering the clinical profile of all patients. Our results showed an association of rs11168268 G/G genotype with higher bone mineral density (BMD) mean for the total hip (A/A = 0.828 ± 0.09; A/G = 0.081 ± 0.13; G/G = 0.876 ± 0.12, p = .039), and the rs3890733 T/T genotype was associated with increased OP risk in patients below 60 years old (odds ratio [OR] = 5.12, 95% confidence interval [CI ]= 1.13-23.27, p = .012). The rs1540339 T/T genotype was associated with protection for individuals with low melanin deposition when compared to the high melanin deposition group (OR = 0.24, 95%CI = 0.06-0.94, p = .029). Additionally, 61% of patients presented deficient vitamin D serum levels. The SNP rs11168268 G/G was associated with a significantly increased mean total hip BMD in patients OP, highlighting this SNP and its relationship with BMD.

Differential distribution of vitamin D receptor (VDR) gene variants and its expression in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disorder that displays an important genetic background. Vitamin D3 (VD3 ) through its receptor (VDR) plays an important immunomodulatory role in autoimmune misbalance, being capable of modulating immune responses. Genetic alterations in VDR gene may contribute to an altered risk in SLE development and clinical manifestations. We investigated VDR SNPs (single nucleotide polymorphisms) frequencies in 128 SLE patients and 138 healthy controls (HC) and mRNA differential expression in 29 patients and 17 HC regarding SLE susceptibility as well as clinical features. We observed that rs11168268 G allele (OR = 1.55, p = .01) and G/G genotype (OR = 2.69, p = .008) were associated with increased SLE susceptibility. The rs2248098 G allele and A/G and G/G genotypes were associated to lower SLE susceptibility (OR = 0.66, p = .01; OR = 0.46, p = .01; OR = 0.44, p = .02, respectively). Regarding clinical features, we observed lower risk for: rs11168268 A/G genotype and nephritis (OR = 0.31, p = .01); rs4760648 T/T genotype and photosensitivity (OR = 0.24, p = .02); rs1540339 T/T genotype and antibody anti-dsDNA (OR = 0.19, p = .015); rs3890733 T/T genotype and serositis (OR = 0.10, p = .01). We identified a significant downregulation in VDR expression levels when compared patients and controls overall (p = 1.04e-7 ), in Cdx-2 A/G and G/G (p = .008 and p = .014, respectively) and in patients with nephritis (p = .016) Our results suggested that VDR SNPs influence upon SLE susceptibility and in particular clinical features, acting on mRNA expression in SLE patients overall and the ones with nephritis.

Differential expression of the inflammasome complex genes in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder involving heterogeneous clinical manifestations and numerous susceptibility genes. Several findings evidence the critical role of inflammasomes in the predisposition to autoimmune diseases and in SLE. We investigated whether inflammasome polymorphins could affect susceptibility to develop and/or severity SLE. Moreover, differences in inflammasome activation in peripheral blood were also evaluated in SLE patients and controls. The distribution of 13 SNPs in eight inflammasome genes was evaluated. To assess inflammasome priming in peripheral blood monocytes of SLE and controls, differential expression of selected inflammasome genes and IL-1ß production was analyzed in resting condition as well as after LPS and ATP stimulation. Results showed that the gain-of-function variant rs10754558 (NLRP3) was significantly more frequent in SLE patients with nephritis, reinforcing the concept of a key role of NLRP3 inflammasome not only in SLE but also especially in kidney disease. SLE monocytes in resting condition showed a higher level of IL-1ß expression and produced higher levels of IL-1ß when stimulated with LPS+ATP comparing to controls. The stimulation induced a significant expression of NLRP1, AIM2, CASP1, and IL1B genes, suggesting that the NLRP1 inflammasome is responsible for the IL-1ß production observed in monocytes. These data emphasized once more the important contribution of inflammasome in SLE-associated inflammation.

Polymorphisms and expression of inflammasome genes are associated with the development and severity of rheumatoid arthritis in Brazilian patients.

OBJECTIVE: In the present study, we analyzed the possible association of inflammasome gene variants and expression to rheumatoid arthritis (RA)'s development and severity in the Brazilian population. MATERIALS AND METHODS: Thirteen single nucleotide polymorphisms within six inflammasome genes (NLRP1, NLRP3, NLRC4, AIM2, CARD8, CASP1) as well as IL1B and IL18 genes in two different Brazilian populations (from Northeast and Southeast Brazil) were analyzed. We also evaluated inflammasome gene expression profile in resting and LPS + ATP-treated monocytes from RA patients and healthy individuals. For genetic association study, 218 patients and 307 healthy controls were genotyped. For gene expression study, inflammasome genes mRNA levels of 12 patients and ten healthy individuals were assessed by qPCR. RESULTS: Our results showed that rs10754558 NLRP3 and rs2043211 CARD8 polymorphisms are associated with RA development (p value = 0.044, OR = 1.77, statistical power = 0.999) and severity measured by Health Assessment Questionnaire (HAQ) (p value = 0.03), respectively. Gene expression analyses showed that RA patients display activation of CASP1, IL1B and IL1R genes independently of LPS + ATP activation. In LPS + ATP-treated monocytes, NLRP3 and NLRC4 expressions were also significantly higher in patients compared with controls. CONCLUSIONS: The first reported results in Brazilian populations support the role of inflammasome in the development of RA.

Vitamin D receptor polymorphisms and expression profile in rheumatoid arthritis Brazilian patients.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and important joint commitment, being the most common systemic autoimmune disease worldwide. RA displays important genetic background with a variety of genes contributing to the immune balance breakdown. Recent studies have demonstrated that vitamin D, through its receptor (VDR), is able to regulate the immune balance and suppress the autoimmunity process, being a potential target in autoimmune diseases. In the present genetic association study, we assessed 5 Tag single nucleotide polymorphisms (SNPs) (rs11168268, rs2248098, rs1540339, rs4760648 and rs3890733), which cover most of the VDR gene, in three different Brazilian populations (from Northeast, Southeast and South Brazil). We also evaluated the VDR expression profile in whole blood and monocytes from RA patients. For genotyping study, 428 RA patients and 616 healthy controls were genotyped with fluorogenic allele specific probes on an ABI7500 platform. For gene expression study, VDR mRNA levels of 15 RA patients and 26 healthy individuals were assessed by RT-PCR. Our results showed that SNPs rs4760648 and rs3890733 are associated to RA susceptibility (p value = 0.0026, OR 1.31 and p value = 0.0091, OR 1.28 with statistical power = 0.999 and 0.993, respectively). Regarding RA clinical features, the studied SNPs did not show significant associations. The gene expression assays showed that VDR mRNA levels were down regulated in both whole blood (-3.3 fold) and monocytes (-3.2 fold) of RA patients when compared to healthy controls. Our results, the first reported for distinct Brazilian populations, support a role of the VDR gene in the susceptibility to RA.

T-cell specific upregulation of Sema4A as risk factor for autoimmunity in systemic lupus erythematosus and rheumatoid arthritis.

The aim of the present study was to evaluate the impact of SEMA4A genetic variants on expression of sema4A protein and its relation to autoimmunity development in Systemic Lupus Erythematosus and Rheumatoid Arthritis patients. A total of 541 SLE patients, 390 RA patients and 607 healthy individuals were genotyped. We also assessed SEMA4A mRNA expression from whole blood cells and the in vitro protein production from resting and activated T lymphocytes as well as mature dendritic cells from healthy individuals stratified according to their genotypes for SLE/RA associated SEMA4A variants. Our results showed that T/T genotype for rs3738581 SNP is associated with both RA and SLE development (p = .000053, OR = 2.35; p = .0019, OR = 2.07, respectively; statistical power = 100%) and also to an increased in vitro sema4A production in active T lymphocytes. Our findings are indicative of a T cell-specific upregulation of sema4A in the presence of T/T genotype, being a risk factor for SLE and RA.

25-Hydroxyivitamin D3 levels in patients with systemic lupus erythematosus and its association with clinical parameters and laboratory tests.

INTRODUCTION: The immunoregulatory role of vitamin D has been the object of a growing number of studies in patients with systemic lupus erythematosus (SLE). OBJECTIVES: To determine the serum levels of 25-hydroxyvitamin D3 [25(OH) D] in patients with SLE, and to assess the association of 25(OH)D insufficiency/deficiency with clinical parameters and laboratory tests. METHODS: Cross-sectional, prospective study performed at the SLE Clinic, Department of Rheumatology, Hospital das Clínicas, Universidade Federal de Pernambuco with convenience sampling, including 78 patients with SLE and 64 volunteers (comparison group), matched by gender and age. RESULTS: Insufficiency/deficiency of 25(OH)D was found in 45 (57.7%) patients with SLE and 25 (39%) individuals in the comparison group. The mean serum levels of 25(OH)D were 29.3 ng/mL (6.1-55.2 ng/mL) in patients with SLE and 33.12 ng/mL (15.9-63.8 ng/mL) in the comparison group, and this difference was statistically significant (P = 0.041). No statistically significant difference was observed between the mean ages of both groups. No statistically significant association was observed between 25(OH)D insufficiency/deficiency and the following: time to diagnosis; disease activity (SLEDAI > 6); fatigue; use of corticosteroids and antimalarials; and anti-DNA. CONCLUSIONS: High prevalence of 25(OH)D insufficiency/deficiency was found in patients with SLE (57.7%), with statistically significant difference as compared with the comparison group. No association of vitamin D insufficiency/deficiency was observed with the clinical variables and laboratory tests studied. The authors emphasize the importance of determining 25(OH)D serum levels in all patients with SLE, regardless of where they live and time to disease diagnosis.

Cytokine measurements in Brazilian postmenopausal osteoporosis patients reveal high levels of IL-8 / Dosagem de citocinas em pacientes brasileiras com osteoporose pós-menopausa revela altos níveis de IL-8

AIMS: Osteoporosis is a common disease that affects mostly women and has been associated with the immune system. The aims of this study were to evaluate the serum levels of inflammatory cytokines in women with postmenopausal osteoporosis and to investigate their relationship with clinical and laboratory parameters. METHODS: This study recruited patients with postmenopausal osteoporosis (osteoporosis group) and non-osteoporotic postmenopausal women (control group) matched for age. All patients and controls had their bone mineral density measured for the diagnosis of osteoporosis and answered a clinical questionnaire. Blood samples were collected for cytokine measurements. Cytokines IFN-γ, IL-1ß, IL-6, IL-8, IL-9, IL-10, IL-17A, IL-22, IL-27, IL-29, IL-35, and TNF-α were measured by an enzyme-linked immunosorbent assay. RESULTS: Twenty-nine out of the 52 (55.8%) postmenopausal osteoporosis patients showed high levels of IL-8, while no patients from the control group (n=21) showed IL-8 values above the detection limit (p<0.0001). Higher levels of IFN-γ and IL-35 were associated with the control group, with p values of 0.0053 and 0.0214, respectively. In the osteoporosis group, IFN-γ was correlated with longer duration of smoking (p=0.003), IFN-γ and IL-6 were correlated with higher age at menarche (p=0.0454 and p=0.0380), IL-22 was correlated with duration of menopause (p=0.0289) and IL-9 with calcium intake (p=0.019). The other cytokines showed no association or correlation with clinical parameters. CONCLUSIONS: IL-8 was elevated in the serum of patients with postmenopausal osteoporosis, perhaps because it may trigger osteoclast activation and bone wear in osteoporosis. Higher levels of IFN-γ, IL-6, IL-9, IL-22, IL-27, and IL-35 were also associated with the osteoporosis group patients and showed significant correlation with clinical parameters in postmenopausal osteoporosis.

OBJETIVOS: A osteoporose é uma doença comum, que afeta principalmente as mulheres e tem sido associada com o sistema imune. Este estudo objetivou avaliar níveis séricos de citocinas inflamatórias em mulheres pós-menopáusicas com osteoporose, assim como investigar as suas relações com parâmetros clínicos e laboratoriais. MÉTODOS: Este estudo recrutou pacientes com osteoporose pós-menopausa e voluntárias sem a doença, pareadas por idade. Todas as pacientes do grupo com osteoporose e as integrantes do grupo controle passaram pelo exame de mensuração de densidade óssea para diagnosticar a doença e todas responderam a um questionário clínico. Amostras de sangue foram coletadas para as dosagens séricas. As citocinas IFN-γ, IL-1ß, IL-6, IL-8, IL-9, IL-10, IL-17A, IL-22, IL-27, IL-29, IL-35 e TNF-α foram dosadas por ensaio imunoenzimático. RESULTADOS: Vinte e nove entre as 52 (55,8%) pacientes com osteoporose pós-menopausa mostraram altos níveis de IL-8, enquanto nenhuma integrante do grupo controle teve valores de IL-8 acima do nível de detecção do kit (p<0,0001). Altos níveis de IFN-γ and IL-35 foram associados ao grupo controle, com valores de p de 0,0053 and 0,0214 respectivamente. No grupo osteoporose, IFN-γ mostrou correlação com o tempo de duração do tabagismo (p=0,003). IFN-γ e IL-6 foram correlacionadas com a idade de ocorrência da menarca (p=0,0454 e p=0,0380). A citocina IL-22 correlacionou-se com a duração da menopausa (p=0,0289), e a IL-9 com a ingestão de mais cálcio na dieta (p=0,019). As outras citocinas dosadas não mostraram associações ou correlações com os parâmetros clínicos. CONCLUSÕES: A IL-8 mostrou-se elevada no soro das pacientes com osteoporose pós-menopausa, talvez por atuar como um gatilho para a ativação dos osteoclastos e desgaste ósseo que ocorre na osteoporose. Níveis mais altos de IFN-γ, IL-6, IL-9, IL-22, IL-27 e IL-35 também estiveram presentes no soro das pacientes do grupo osteoporose e mostraram associações significativas com os parâmetros clínicos na osteoporose pós-menopausa.

The importance of vitamin D levels in autoimmune diseases.

In addition to its role in calcium homeostasis, it is believed that the active form of vitamin D has immunomodulatory effects on cells of the immune system, particularly T lymphocytes, as well as on the production and action of several cytokines. The interaction of vitamin D with the immune system has been the target of a growing number of publications in recent years. Current studies have linked the deficiency of vitamin D with different autoimmune diseases, including insulin-dependent diabetes mellitus (IDDM), multiple sclerosis (MS), inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA). This article reviews the physiology and immunomodulatory role of vitamin D, emphasizing its involvement in rheumatic diseases such as SLE and RA.

Diarreia crônica como manifestação inicial do lúpus eritematoso sistêmico grave: relato de caso e revisão da literatura / Chronic diarrhea as the initial manifestation of severe systemic lupus erythematosus: case report and literature review

O lúpus eritematoso sistêmico é uma doença autoimune de etiologiadesconhecida que se caracteriza por períodos de remissão ede atividade envolvendo múltiplos órgãos. As manifestações gastrointestinaisdo lúpus eritematoso sistêmico ocorrem entre 25 e40% de todos os pacientes portadores da doença e podem estarassociadas à atividade da doença, ou serem consequência do seutratamento. Entre os sintomas gastrointestinais relacionados aolúpus eritematoso sistêmico, os mais frequentes são dor abdominal(secundária à serosite ou vasculite intestinal), vômitos ediarreia. Entretanto, diarreia crônica como manifestação inicialdo lúpus eritematoso sistêmico grave não tem sido descrito naliteratura, motivo pelo qual se decidiu relatar o presente casolúpus eritematoso sistêmico grave em apresentações iniciais atípicascomo a diarreia crônica. Paciente do gênero masculino, 18anos, com queixa de diarreia crônica, febre intermitente, asteniae emagrecimento há 4 meses. Durante a investigação foi evidenciadaproteinúria, artrite, anemia hemolítica e FAN positivofechando critérios para lúpus eritematoso sistêmico. Apesar deinstituída a terapêutica, evoluiu com acometimento grave deórgão-alvo (hemorragia pulmonar). Devido a sua abrangênciasalienta-se a importância de considerar as manifestações do tratogastrointestinal como primeiros sintomas da doença, proporcionandoum diagnóstico precoce, aumento da eficácia terapêutica,evitando assim possível desfecho grave ou fatal.

Systemic lupus erythematous is an autoimmune disease ofunknown etiology that is characterized by periods of remissionand activity involving multiple organs. Gastrointestinalmanifestations of systemic lupus erythematous occurbetween 25 and 40% of all patients with the disease andmay be associated with disease activity, or be a result of theirtreatment. Among gastrointestinal symptoms related to systemiclupus erythematous, the most common are abdominal pain(secondary to intestinal serositis or vasculitis), vomiting anddiarrhea. However, chronic diarrhea as the initial manifestationof severe systemic lupus erythematous has been describedin the literature, which is why it decided to report this case.Male patient, 18 years old, complaining of chronic diarrhea,intermittent fever, weakness and weight loss for four months.The diagnosis of systemic lupus erythematous was confirmed ofthe following criteria: proteinuria, arthritis, hemolytic anemiaand positive antinuclear antibody test. Although establishedtherapy, she developed severe involvement of the target organ(pulmonary hemorrhage). Due to the scope of systemic lupuserythematous, we emphasize the importance of considering themanifestations of gastrointestinal tract as first symptoms of thedisease, providing early diagnosis, increased therapeutic efficacy,thus avoiding possible severe or fatal outcome.

Níveis séricos de 25-hidroxivitamina D3 e sua associação com parâmetros clínicos e laboratoriais em pacientes com lúpus eritematoso sistêmico / 25-Hydroxyivitamin D3 levels in patients with systemic lupus erythematosus and its association with clinical parameters and laboratory tests

INTRODUÇÃO: O papel imunorregulatório da vitamina D tem sido alvo de um crescente número de estudos em pacientes com lúpus eritematoso sistêmico (LES). Objetivos: Determinar os níveis séricos de 25-hidroxivitamina D3 [25(OH)D] em pacientes com LES e verificar a associação da insuficiência/deficiência de 25(OH)D com parâmetros clínicos e laboratoriais. MÉTODOS:Estudo de corte transversal, prospectivo, realizado no ambulatório de LES do Serviço de Reumatologia do Hospital das Clínicas da Universidade Federal de Pernambuco. Foram incluídos 78 pacientes portadores de LES e 64 voluntários (grupo de comparação) pareados por gênero e idade. RESULTADOS: Constatou-se insuficiência/deficiência de 25(OH)D em 45 (57,7 por cento) pacientes com LES e em 25 (39 por cento) indivíduos do grupo de comparação. Os níveis séricos médios de 25(OH)D foram 29,3 ng/mL (6,1-55,2 ng/mL) nos pacientes com LES e 33,12 ng/mL (15,9-63,8 ng/mL) no grupo de comparação; essa diferença é considerada estatisticamente significante (P = 0,041). Não houve diferença estatisticamente significante entre as médias de idade dos dois grupos. Não houve associação estatisticamente significante entre insuficiência/deficiência de 25(OH)D e tempo de diagnóstico, atividade de doença (SLEDAI > 6), fadiga, uso de corticosteroides e de antimaláricos e anti-DNA. CONCLUSÕES:Foi constatada alta prevalência de insuficiência/deficiência de 25(OH)D nos pacientes com LES (57,7 por cento), com diferença estatisticamente significante em relação ao grupo de comparação. Não evidenciamos associação de insuficiência/deficiência de vitamina D com as variáveis clínicas e laboratoriais estudadas. Os autores enfatizam a importância da determinação dos níveis séricos de 25(OH)D em todos os pacientes com LES, independente de onde residam e do tempo de diagnóstico da doença.

INTRODUCTION: The immunoregulatory role of vitamin D has been the object of a growing number of studies in patients with systemic lupus erythematosus (SLE). OBJECTIVES: To determine the serum levels of 25-hydroxyvitamin D3 [25(OH) D] in patients with SLE, and to assess the association of 25(OH)D insufficiency/deficiency with clinical parameters and laboratory tests. METHODS: Cross-sectional, prospective study performed at the SLE Clinic, Department of Rheumatology, Hospital das Clínicas, Universidade Federal de Pernambuco with convenience sampling, including 78 patients with SLE and 64 volunteers (comparison group), matched by gender and age. RESULTS: Insufficiency/deficiency of 25(OH)D was found in 45 (57.7 percent) patients with SLE and 25 (39 percent) individuals in the comparison group. The mean serum levels of 25(OH)D were 29.3 ng/mL (6.1-55.2 ng/mL) in patients with SLE and 33.12 ng/mL (15.9-63.8 ng/mL) in the comparison group, and this difference was statistically significant (P = 0.041). No statistically significant difference was observed between the mean ages of both groups. No statistically significant association was observed between 25(OH)D insufficiency/deficiency and the following: time to diagnosis; disease activity (SLEDAI > 6); fatigue; use of corticosteroids and antimalarials; and anti-DNA. CONCLUSIONS: High prevalence of 25(OH)D insufficiency/deficiency was found in patients with SLE (57.7 percent), with statistically significant difference as compared with the comparison group. No association of vitamin D insufficiency/deficiency was observed with the clinical variables and laboratory tests studied. The authors emphasize the importance of determining 25(OH)D serum levels in all patients with SLE, regardless of where they live and time to disease diagnosis.

A importância dos níveis de vitamina D nas doenças autoimunes: [revisão] / The importance of vitamin D levels in autoimmune diseases: [review]

Além do seu papel na homeostase do cálcio, acredita-se que a forma ativa da vitamina D apresenta efeitos imunomoduladores sobre as células do sistema imunológico, sobretudo linfócitos T, bem como na produção e na ação de diversas citocinas. A interação da vitamina D com o sistema imunológico vem sendo alvo de um número crescente de publicações nos últimos anos. Estudos atuais têm relacionado a deficiência de vitamina D com várias doenças autoimunes, como diabetes mellitus insulino-dependente (DMID), esclerose múltipla (EM), doença inflamatória intestinal (DII), lúpus eritematoso sistêmico (LES) e artrite reumatoide (AR). O artigo faz uma revisão da fisiologia e do papel imunomodulador da vitamina D, enfatizando sua participação nas doenças reumatológicas, como o lúpus e a artrite reumatoide.

In addition to its role in calcium homeostasis, it is believed that the active form of vitamin D has immunomodulatory effects on cells of the immune system, particularly T lymphocytes, as well as on the production and action of several cytokines. The interaction of vitamin D with the immune system has been the target of a growing number of publications in recent years. Current studies have linked the deficiency of vitamin D with different autoimmune diseases, including insulin-dependent diabetes mellitus (IDDM), multiple sclerosis (MS), inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA). This article reviews the physiology and immunomodulatory role of vitamin D, emphasizing its involvement in rheumatic diseases such as SLE and RA.

Rituximabe na síndrome de Felty refratária / Rituximab in the refractory Felty's syndrome

Os autores relatam o caso de uma paciente de 29 anos com diagnóstico de artrite reumatoide soropositiva que com seis meses de evolução desenvolveu granulocitopenia severa e esplenomegalia, embora mantivesse em remissão o quadro articular. Não apresentou resposta à corticoterapia oral e em forma de pulsos, além do metotrexato e leflunomida, tendo apresentado reação adversa ao uso do infliximabe e falta de resposta ao adalimumabe. Diante das infecções de repetição, apesar dos vários esquemas de antibióticos e uso crônico do G-CSF, dos altos títulos de fator reumatoide, dos níveis elevados da VHS e da PCR, utilizou-se o rituximabe no esquema clássico de tratamento da artrite reumatoide. Houve resposta clínica completa com aumento crescente do número de neutrófilos e normalização dos mesmos além da queda dos títulos de fator reumatoide, da VHS e da PCR. Atualmente, a paciente encontra-se em remissão clínica e laboratorial, em uso de prednisona 5 mg/dia e metotrexato 10 mg/semana.

The authors report a case of a 29 year old woman who has seropositive rheumatoid arthritis for six months, and developed severe granulocytopenia and important splenomegaly, however she didnït show any joint inflammation. She did not respond either to pulse or oral steroids, or to oral methotrexate and leflunomide. She also developed an adverse reaction to the use of infliximab and did not respond well to adalimumab. Although she has had repeated infections, despite the various forms of antibiotics and long-term use of G-CSF, with high titers of rheumatoid factor, and high levels of ESR and CRP, the classic Rituximab method for treating rheumatoid arthritis was used. There was a good clinical response with an increase in the number of neutrophils following normalization of them, together with the reduction of rheumatoid factor titers, ESR and CRP. At the moment, the patient is in remission, according to both clinical and laboratory criteria and taking 5mg of prednisone per day and 10mg of methotrexate per week.

Sinusite fúngica crônica indolente / Chronic indolent fungal sinusitis

A sinusite fúngica crônica invasiva é uma doença granulomatosa crônica com invasão tecidual de parede de seios paranasais. Apesar de ser engêmica no Sudão, é incomum na maioria dos países, inclusive nos EUA. Os fungos do gênero Aspergillus são o principal agente etiológico. Ocorre em pacientes imunocompetentes, não-atópicos, com história de rinossinusite crônica. Habitualmente se manifesta quando há invação de estruturas adjacentes (órbita e tecido retroorbitário). Seu diagnóstico requer suspeição clínica. Os autores relatam um caso de sinusite fúngica crônica invasiva por Aspergillus spp. em paciente com história de sinusite prolongada, não diagnosticada por médicos pelo desconhecimento desta afecção, cuja queixa principal era exoftalmia.