Current treatment strategies for inflammatory bowel disease patients at the risk of developing cancer: a comprehensive review

Inflammatory bowel disease (IBD) is a chronic condition that affects the digestive tract and can lead to inflammation and damage to the intestinal lining. IBD patients with cancer encounter difficulties since cancer treatment weakens their immune systems. A multidisciplinary strategy that strikes a balance between the requirement to manage IBD symptoms and the potential effects of treatment on cancer is necessary for effective care of IBD in cancer patients. To reduce inflammation and avoid problems, IBD in cancer patients is often managed by closely monitoring IBD symptoms in conjunction with the necessary medication and surgical intervention. Anti-inflammatory medications, immunomodulators, and biologic therapies may be used for medical care, and surgical options may include resection of the diseased intestine or removal of the entire colon. The current study provides a paradigm for shared decision-making involving the patient, gastroenterologist, and oncologist while considering recent findings on the safety of IBD medicines, cancer, and recurrent cancer risk in individuals with IBD. We hope to summarize the pertinent research in this review and offer useful advice. (AU)

Biological therapy in psoriatic arthritis patients with and without previous biologic experience / Terapia biológica em pacientes com artrite psoriásica com e sem experiência prévia no uso de medicamentos biológicos

Objective: this study evaluated the biological therapy effects on disease activity, functionality, quality of life, drug survival, and safety of patients with psoriatic arthritis naïve and experienced in biological therapy. Methods: a one-year prospective observational study was performed. The outcomes assessed were drug survival, disease activity, functionality, quality of life, and safety. Multiple linear regression was used to assess predictive factors for clinical re-sponse. Results: a total of 205 patients were included, 155 of whom were biologic naïve and 50 biologic experienced. Drug survival rate was greater for naïve patients than experienced patients at 6 months, but not at 12 months. Drug survival rates were 71.5% for naïve patients and 70.0% for experienced patients at 12 months. All clinical parameters improved for both biologic naïve and experienced patients. At 12 months, 63% of naïve patients and 52% of expe-rienced patients had an improvement in their quality of life. Besides, 48% of naïve patients and 42% of experienced patients had an improvement in functionality. The axial disease improved in 67% of naïve individuals and 56% of experienced patients. Good control of peripheral disease was achieved by 49% of naïve patients and 44% of experi-enced patients. Female sex, use of etanercept or infliximab, and lower functionality or quality of life at baseline were the main predictors of poor clinical response. Conclusion: Patients' health improved after starting biological therapy. In general, biologic experienced patients had more adverse reactions and lesser effectiveness (AU)

Objetivo: avaliar os efeitos da terapia biológica sobre a atividade da doença, funcionalidade, qualidade de vida, per-sistência no tratamento e segurança em pacientes com artrite psoriásica sem experiência e com experiência prévia em terapia biológica. Métodos: um estudo observacional prospectivo de um ano foi realizado. Os desfechos avaliados foram a persistência no tratamento, atividade da doença, funcionalidade, qualidade de vida e segurança. Um modelo de regressão linear múltipla foi utilizado para avaliar os fatores preditores de resposta clínica. Resultados: foram incluídos 205 pacientes, dos quais 155 não tinham e 50 tinham experiência prévia com medicamentos biológicos. As taxas de persistência no tratamento foram maiores para pacientes sem experiência prévia em comparação aos experientes em seis meses de acompanhamento, mas não em 12 meses. As taxas de persistência no tratamento foram 71,5% em pa-cientes sem experiência prévia e 70% em pacientes com experiência prévia em 12 meses. Todos os desfechos clínicos avaliados melhoraram em ambos os grupos de pacientes. Aos 12 meses, 63% dos pacientes sem experiência prévia e 52% dos pacientes com experiência prévia apresentaram melhora na qualidade de vida. Além disso, 48% dos pacientes sem experiência prévia e 42% dos pacientes com experiência prévia apresentaram melhora na funcionalidade. A do-ença axial melhorou em 67% dos pacientes sem experiência prévia e em 56% dos pacientes com experiência prévia. Um bom controle da doença articular periférica foi observado em 49% dos pacientes sem experiência prévia e em 44% dos pacientes com experiência prévia. Os principais fatores preditores de pior resposta clínica foram sexo feminino, uso de etanercepte ou infliximabe, bem como pior funcionalidade e qualidade de vida no início do estudo. Conclusão:a saúde dos pacientes melhorou após o início do tratamento com os medicamentos biológicos. Em geral, pacientes com experiência prévia com medicamentos biológicos apresentaram mais reações adversas e menor efetividade (AU)

Effects of systemic inflammation due to hepatic ischemia-reperfusion injury upon lean or obese visceral adipose tissue

Purpose: To evaluate how the induction of liver damage by ischemia and reperfusion affects the adipose tissue of lean and obese mice. Methods: Lean and diet-induced obese mice were subjected to liver ischemia (30 min) followed by 6 h of reperfusion. The vascular stromal fraction of visceral adipose tissue was analyzed by cytometry, and gene expression was evaluated by an Array assay and by RT-qPCR. Intestinal permeability was assessed by oral administration of fluorescein isothiocyanate (FITC)-dextran and endotoxemia by serum endotoxin measurements using a limulus amebocyte lysate assay. Results: It was found that, after liver ischemia and reperfusion, there is an infiltration of neutrophils, monocytes, and lymphocytes, as well as an increase in the gene expression that encode cytokines, chemokines and their receptors in the visceral adipose tissue of lean mice. This inflammatory response was associated with the presence of endotoxemia in lean mice. However, these changes were not observed in the visceral adipose tissue of obese mice. Conclusions: Liver ischemia and reperfusion induce an acute inflammatory response in adipose tissue of lean mice characterized by an intense chemokine induction and leukocyte infiltration; however, inflammatory alterations are already present at baseline in the obese adipose tissue and liver ischemia and reperfusion do not injure further.

Terapias biológicas y tuberculosis en pediatría / Biological therapies and tuberculosis in pediatrics

En los últimos años, ha habido un aumento sostenido del uso de terapias inmunomoduladoras como las terapias biológicas y en un período más reciente, de las terapias con moléculas pequeñas. Estos tratamientos constituyen un factor de riesgo más para enfermar de tuberculosis en adultos y aunque en menor grado, también en niños, especialmente con el uso de anti TNF-α, por lo que antes de iniciar una terapia biológica, hay que descartar la tuberculosis activa y la latente. En el tratamiento de una tuberculosis activa producida por un biológico se debe prolongar la etapa de continuación a 9 meses. Es importante el seguimiento clínico prolongado en años de quienes usan o han completado el uso de estas terapias. Hay que posponer la vacunación BCG en los hijos de madres que usaron terapias biológicas durante la gestación hasta la edad 6 a 12 meses de los niños. El foco de esta revisión está centrado en la tuberculosis por progresión de una forma latente a una activa o por un contacto estrecho con una persona con tuberculosis pulmonar en pacientes que reciben terapias biológicas anti TNF alfa de uso inmunoreumatológico.

In recent years, there has been a sustained increase in the use of immunomodulatory therapies such as biologic therapies and, more recently, small molecule therapies. Those therapies have become another risk factor for tuberculosis in adults and, although to lesser degree, also in children, especially some of them, such as anti-TNF α. Before starting biological therapy, active tuberculosis and latent tuberculosis must be ruled out. In the treatment of active tuberculosis caused by a biologic, the continuation stage should be extended to 9 months. Long-term clinical follow-up in years of those who use them or have completed their use, is important. BCG vaccine should be postponed in children of mother who used biologic therapies during pregnancy until the children ́s age 6 to 12 months. The focus of this review is centered on tuberculosis due to progression from a latent to an active form or due to close contact with a person with pulmonary tuberculosis in patients receiving anti-TNF alpha biological therapies for immunorheumatology use.

Neuroprotective effects of voluntary exercise and Yisaipu after traumatic brain injury in mice / 生理学报

The mechanisms underlying exercise-induced neuroprotective effects after traumatic brain injury (TBI) remained elusive, and there is a lack of effective treatments for TBI. In this study, we investigated the effects of an integrative approach of exercise and Yisaipu (TNFR-IgG fusion protein, TNF inhibitor) in a mouse TBI model. Male C57BL/6J mice were randomly assigned to a sedentary group or a group that followed a voluntary exercise regimen. The effects of 6-week prophylactic preconditioning exercise (PE) alone or in combination with post-TBI Yisaipu treatment on moderate TBI associated deficits were examined. The results showed that combined treatments of PE and post-TBI Yisaipu were superior to single treatments on reducing sensorimotor and gait dysfunctions in mice. These functional improvements were accompanied by reduced systemic inflammation largely via decreased serum TNF-α, boosted autophagic flux, and mitigated lesion volume after TBI. Given these neuroprotective effects, composite approaches such as a combination of exercise and TNF inhibitor may be a promising strategy for facilitating functional recovery from TBI and are worth further investigation.

Evaluation of factors affecting the frequency and clinical course of COVID-19 in patients using anti-TNF-alpha agents

SUMMARY OBJECTIVES: Patients being treated with anti-tumor necrosis factor-alpha (anti-TNF-alpha) agents were reported to have better prognosis related to COVID-19. We evaluated the factors affecting the frequency, clinical course, and outcome of COVID-19 in patients treated with anti-TNF-alpha agents. METHODS: Patients with rheumatoid diseases and chronic inflammatory bowel diseases treated with anti-TNF-alpha agents were evaluated retrospectively. The laboratory data in routine visits, frequency of COVID-19, pneumonia, hospitalization and/or intensive care unit (ICU) follow-up and, mortality were recorded. The factors related to COVID-19 frequency and clinical outcome were evaluated. RESULTS: A total of 324 patients (177 males [54.6%] and 147 females [45.4%], mean age: 45.3±12.16 years) was included in the study. In all, 44 (13.6%) patients had COVID-19; of these, 11 (25%) developed pneumonia, 7 (15.9%) were hospitalized, and 1 (2.3%) was followed up in ICU. There was no mortality. The patients with COVID-19 pneumonia were older (mean age: 52±11 years versus 41±12 years, p=0.01), had hypertension and coronary artery disease more frequently (5 cases [55.6%] versus 4 cases [44.4], p=0.02 and 2 cases [100%] versus 0 cases [0%], p=0.014, respectively), and lower eosinophil % (1.35±1.79% versus 2.3±1.45%, p=0.016). The diabetes mellitus was more frequent (66.7 versus 33.3%, p=0.013), and mean eosinophil % was lower among inpatients compared with outpatients (1.29±2.22% versus 2.19±1.37%, p=0.02). CONCLUSIONS: We concluded that the patients treated with anti-TNF-alpha agents having COVID-19 might have mild clinical course and better prognosis.

Herpetic whitlow in a child with AIDS: the importance of Tzanck test in the diagnosis

Abstract Herpetic whitlow is a viral infection of the fingers caused by the herpes simplex virus. The disease has a bimodal age distribution, affecting children under 10 years of age and young adults between 20 and 30 years old. It can be easily mistaken for panaritium or bacterial cellulitis. In patients with AIDS, atypical, chronic and recurrent ulcerated lesions occur. The Tzanck test allows a quick and low-cost diagnosis of herpes simplex virus infection. The authors report the case of a child with AIDS with painful finger ulcers in which the diagnosis was confirmed by the Tzanck test.

Interstitial lung disease due to anti-TNF use in the treatment of psoriasis

Abstract Psoriasis is a chronic inflammatory disease that affects the skin variably, according to genetic and environmental factors. Some patients may benefit from systemic treatment with immunobiological agents, drugs that can be accompanied by several adverse effects. A case of a 58-year-old patient undergoing treatment for psoriasis with adalimumab for five years is reported. Alterations compatible with interstitial pneumonia were detected with important regression after adalimumab discontinuation. This case is relevant due to the scarcity of reports on late pulmonary adverse effect of anti-TNF treatment of psoriasis.

Análise do perfil clínico e epidemiológico de pacientes com artrite psoriásica em ambulatório de reumatologia na Região Amazônica / Clinical and epidemiological profile analysis of patients with psoriatic arthritis in a rheumatology clinic in the Amazon Region

Objetivo: Conhecer o perfil clínico e epidemiológico de pacien- tes portadores de artrite psoriásica de uma região brasileira. Método: Pesquisa observacional, transversal, epidemiológica e documental, baseada na coleta de dados obtidos a partir da análise de 53 prontuários de pacientes cadastrados do Ambu- latório de Reumatologia da Universidade do Estado do Pará, na Região Amazônica. Resultados: Houve predominância do padrão do tipo poliartrite simétrica, sem distinção entre os sexos, com a presença de manifestações extra-articulares, pso- ríase em placas, em uso de metotrexato em doses médias. Con- clusão: Apesar da etiopatogenia da doença ser dependente de fatores genéticos, ambientais e imunológicos e da população amazônica ser muito particular, de uma miscigenação entre eu- ropeus, ameríndios e negros, o perfil clínico e epidemiológicos dos pacientes do Ambulatório de Reumatologia da Universidade do Estado do Pará é semelhante ao das literaturas nacional e internacional.

Objective: To know the clinical and epidemiologic profile of pso- riatic arthritis patients of a Brazilian region. Method: This is an observational, cross-sectional, epidemiological, and documental study, based on the data obtained from the analysis of the medi- cal records of 53 patients registered on the Rheumatology Cli- nic of the Universidade do Estado do Pará, in the Amazon area. Results: There was a predominance of the symmetrical polyar- ticular pattern, with no sexual distinction, extra articular invol- vement, plaque psoriasis, and treatment withn methotrexate, in medium doses. Conclusion: Despite the etiopathogenesis being dependent on genetic, environmental, and immunological fac- tors, and the population of the Amazon being a mix of Europeans, Amerindians, and black people, the clinical and epidemiological profile of the patients of the Rheumatology clinic of the Univer- sidade do Estado do Pará is similar to the ones described on the national and international literature.

Informe diário de evidências COVID-19: busca realizada em 18 de junho de 2020 / COVID-19 daily evidence report: search conducted on June 18, 2020

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referente ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 12 artigos e 9 protocolos.

Informe diário de evidências COVID-19: busca realizada em 21 de maio de 2020 / COVID-19 daily evidence report: search conducted on May 21, 2020

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referente ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 21 artigos.

Analysis of cardiovascular risk and carotid intima-media thickness in patients with psoriasis

Abstract Background: Psoriasis is associated with atherosclerosis and increased cardiovascular risk. Currently, an automated ultrasound, called quantitative intima media thickness, has proven to be a useful method to evaluate subclinical atherosclerosis. Objectives: To compare increased cardiovascular risk in psoriasis patients receiving two types of treatments: Methotrexate and tumor necrosis factor inhibitor and to evaluate the correlation between the Framingham score and quantitative intima media thickness. Methods: Fifty patients with plaque psoriasis were selected from June 2017 to July 2018, divided into two groups, receiving methotrexate and tumor necrosis factor inhibitor. Measurement of abdominal circumference, blood pressure, body mass index and presence of metabolic syndrome were performed. Afterwards, the patients were evaluated for increased cardiovascular risk with the Framingham score and for the quantitative intima media thickness of the carotid arteries. Results: The mean age was 54.8 (±12.5) with a slight male predominance (58%). Overall, 84% of the patients had elevated waist circumference, 82% had a body mass index above ideal, and 50% had a metabolic syndrome. For the correlation between quantitative intima media thickness and Framingham Score, Pearson's linear correlation coefficient was 0.617 (p < 0.001), indicating a moderate to strong positive association. Study limitations: The protective effect of the therapies cited in relation to the increased cardiovascular risk was not evaluated. Conclusions: A moderate to strong positive association was found correlating the Framingham Score values with the quantitative intima media thickness measurement and it is not possible to state which drug has the highest increased cardiovascular risk.

Incidencia de tuberculosis en pacientes que reciben fármacos anti-TNF( / Incidence of tuberculosis in patients receiving tumor necrosis factor-( blockers / Incidência de tuberculose em pacientes que recebem fármacos anti-TNF(

Resumen: Introducción: la tuberculosis (TB) es una complicación frecuente del uso de fármacos anti-TNF(. Ocurre por reactivación de una infección latente o por progresión de una infección reciente. Objetivos: conocer la incidencia de TB en la población que recibió fármacos anti- TNF(, analizar las formas de presentación y la realización de pesquisa de infección latente previo al inicio del tratamiento. Método: estudio de cohorte retrospectiva. Se incluyeron los pacientes que recibieron fármacos anti- TNF( entre 2010 y 2016. Los datos se obtuvieron de los sistemas informáticos del Fondo Nacional de Recursos y del Programa Nacional de Tuberculosis. Se calculó la incidencia de TB y se describieron los casos que desarrollaron TB. Resultados: se incluyeron 991 tratamientos para un total de 980 pacientes. Se reportaron nueve casos de TB. La incidencia global fue de 419,9 (IC 95% 191,9-591,2) por 100.000 personas/año. Solo hubo casos de TB en pacientes tratados con adalimumab. El cribado de infección tuberculosa latente (ITBL) previo al inicio del fármaco fue heterogéneo y predominaron las formas de TB diseminadas (6/9) sobre la afectación pulmonar aislada (3/9). En todos los casos se suspendió el anti- TNF( al diagnóstico de TB y en ningún caso se retomó. Conclusiones: la incidencia de TB en la población de pacientes bajo tratamiento con anti- TNF( fue 16,5 veces mayor que en la población general. Predominaron las formas de TB diseminadas y se dieron casos en sujetos que habían recibido tratamiento de ITBL previo al inicio del fármaco, sugiriendo que el riesgo persiste mientras exista exposición a éste.

Summary: Introduction: tuberculosis (TB) is a frequent complication in patients receiving tumor necrosis factor-alpha (TNF-() blockers. It occurs upon the reactivation of a latent infection or the progression of a recent infection. Objective: to learn about the incidence of TB in a population receiving tumor necrosis factor-alpha (TNF-() blockers, to analyze the presentation of this condition and to conduct a latent infection research prior to the initiation of therapy. Method: retrospective cohort study. Patients receiving tumor necrosis factor-alpha (TNF-() blockers between 2010 and 2016 were included in the study. Data were obtained from the IT systems of the National Resources Fund and the National Tuberculosis Program. The incidence of TB was calculated and the cases developing TB were described. Results: 991 treatments were included for 980 patients in total. 9 cases of TB were reported. Global incidence was 419.9 (IC 95% 191.9-591.2) out of 100,000 people per year. Cases of TB were only seen in patients treated with adalimumab. Screening for LTBI upon initiation of the drug was heterogeneous and the disseminated forms of TB prevailed (6/9) over isolated pulmonary affectation (3/9). In all cases anti- TNF( was suspended when TB was diagnosed, and it was not reinitiated. Conclusions: the incidence of TB in patients receiving tumor necrosis factor-alpha (TNF-() blockers was 16.5 times greater than in the general population. Disseminated forms of TB prevailed, and some cases occurred in individuals who had received LTBI therapy prior to the initiation of the drug, suggesting the risk persists as long as there is exposure to the drug.

Resumo: Introdução: a tuberculose (TB) é uma complicação frequente do uso de fármacos anti- TNF(. É causada pela reativação de uma infecção latente ou pela evolução de uma infecção recente. Objetivos: conhecer a incidência de TB na população que recebeu fármacos anti- TNF(, analisar as formas de apresentação e a realização de pesquisa de infecção latente prévia ao início do tratamento. Método: estudo de coorte retrospectivo. Foram incluídos todos os pacientes que receberam fármacos anti- TNF( no período 2010-2016. Os dados foram obtidos dos registros informatizados do Fondo Nacional de Recursos e do Programa Nacional de Tuberculosis. A incidência de TB foi calculada e foram descritos os casos que desenvolveram esta patologia. Resultados: foram incluídos 991 tratamentos para um total de 980 pacientes. Nove casos de TB foram registrados. A incidência global foi de 419,9 (IC 95% 191,9-591,2) por 100.000 pessoas/ano. Somente foram registrados casos de TB em pacientes tratados com adalimumab. A triagem de infecção tuberculosa latente (ITBL) prévia ao início do fármaco foi heterogênea e predominaram as formas de TB disseminadas (6/9) sobre a pulmonar isolada (3/9). Em todos os casos o uso de anti- TNF( foi suspenso definitivamente quando o diagnóstico de TB foi realizado. Conclusões: a incidência de TB na população de pacientes em tratamento com anti- TNF( foi 16,5 vezes maior que na população em geral. Predominaram as formas disseminadas de TB e foram registrados casos em pacientes que haviam recebido tratamento para ITBL prévio ao início do fármaco, sugerindo que o risco persiste enquanto houver exposição a este.

Predictive factors for loss of response to anti-tnf in crohns disease / Fatores preditivos da perda de resposta aos anti-tnf na doença de crohn

ABSTRACT Background: Anti-TNF drugs are a fundamental part of the treatment of Crohn's disease (CD), so identifying factors related to loss of response is of great importance in clinical practice. Aim: Identify potential factors related to loss of response to anti-TNF agents in Crohn's disease patients. Methods: This is a prospective study of CD patients attending a specialized outpatient clinic using a specific form, including patients with more than one year of follow-up on anti-TNF (Infliximab, Adalimumab or Certolizumab pegol). The information obtained was tabulated and analyzed to identify possible reasons for the loss of response to anti-TNF agents; results were submitted to statistical analysis by chi-square teste considering significant p<0.05. Results: Sixty-four patients were included, most of them females (56.3%), predominant age group between 26 and 55 years, of whom 25 required optimization, 23 remained in remission with the usual dose and interval, and 16 required switch; most of those who needed switch had hematological problems such as anemia and/or had already undergone surgical treatment for CD. Conclusions: Anemia and prior CD surgery have been linked to loss of anti-TNF response.

RESUMO Racional: Os anti-TNF são parte fundamental no tratamento da doença de Crohn (DC), portanto, identificar os fatores relacionados à perda de resposta tem grande importância na prática clínica. Objetivo: Identificar potenciais fatores relacionados a perda de resposta aos agentes anti-TNF em pacientes com DC. Métodos: Trata-se de um estudo prospectivo de pacientes com DC frequentadores de ambulatório especializado por meio de formulário específico, incluindo-se pacientes com mais de um ano de acompanhamento em uso de anti-TNF (Infliximabe, Adalimumabe ou Certolizumabe pegol). As informações obtidas foram tabuladas e analizadas para identificação de eventuais motivos para a perda de resposta aos agentes; os resultados foram submetidos a tratamento estatístico por meio do teste qui-quadrado considerando-se significante p<0,05. Resultados: Foram incluídos 64 pacientes, sendo a maioria do sexo feminino (56,3%), faixa etária predominante entre 26 e 55 anos, dos quais 25 necessitaram otimização, 23 se mantiveram em remissão com a dose e intervalo habituais, e 16 necessitaram troca de medicamento; a maioria dos que necessitaram troca tinham alterações hematológicas como anemia e/ou já haviam sido submetidos a tratamento cirúrgico pela doença. Conclusões: Anemia e operação prévia por DC foram relacionados a perda de resposta aos anti-TNF.

Ankylosing spondylitis and psoriatic arthritis: revisiting screening of latent tuberculosis infection and its follow-up during anti-tumor necrosis factor therapy in an endemic area

OBJECTIVES: To retrospectively evaluate the performance and distinctive pattern of latent tuberculosis (TB) infection (LTBI) screening and treatment in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) under anti-tumor necrosis factor (TNF) therapy and determine the relevance of re-exposure and other risk factors for TB development. METHODS: A total of 135 and 83 patients with AS and PsA, respectively, were evaluated for LTBI treatment before receiving anti-TNF drugs via the tuberculin skin test (TST), chest radiography, and TB exposure history assessment. All subjects were evaluated for TB infection at 3-month intervals. RESULTS: The patients with AS were more often treated for LTBI than were those with PsA (42% versus 30%, p=0.043). The former also presented a higher frequency of TST positivity (93% versus 64%, p=0.002), although they had a lower frequency of exposure history (18% versus 52%, p=0.027) and previous TB (0.7% versus 6%, p=0.03). During follow-up [median, 5.8 years; interquartile range (1QR), 2.2-9.0 years], 11/218 (5%) patients developed active TB (AS, n=7; PsA, n=4). TB re-exposure was the main cause in seven patients (64%) after 12 months of therapy (median, 21.9 months; IQR, 14.2-42.8 months) and five LTBI-negative patients. TB was identified within the first year in four patients (36.3%) (median, 5.3 months; IQR, 1.2-8.8 months), two of whom were LTBI-positive. There was no difference in the TB-free survival according to the anti-TNF drug type/class; neither synthetic drug nor prednisone use was related to TB occurrence (p>0.05). CONCLUSION: Known re-exposure is the most critical factor for incident TB cases in spondyloarthritis. There are also some distinct features in AS and PsA LTBI screening, considering the higher frequency of LTBI and TST positivities in patients with AS. Annual risk reassessment taking into consideration these peculiar features and including the TST should be recommended for patients in endemic countries.

Incidence of tuberculosis infection in spondyloarthritis patients treated with biological and conventional disease-modifying anti-rheumatic drugs in an endemic area

Introduction: Registries of spondyloarthritis (SpA) patients' follow-up provided evidence that tumor necrosis factor inhibitors (TNFi) increase the incidence of active tuberculosis infection (TB). However, most of these registries are from low burden TB areas. Few studies evaluated the safety of biologic agents in TB endemic areas. This study compares the TB incidence rate (TB IR) in anti-TNF-naïve and anti-TNF-experienced subjects with SpA in a high TB incidence setting.Methods: In this retrospective cohort study, medical records from patients attending a SpA clinic during 13 years (2004 to 2016) in a university hospital were reviewed. The TB IR was calculated and expressed as number of events per 105 patients/year; the incidence rate ratio (IRR) associated with the use of TNFi was calculated.Results: A total of 277 patients, 173 anti-TNF-naïve and 104 anti-TNF-experienced subjects, were evaluated; 35.7% (N = 35) of patients who were prescribed an anti-TNF drug were diagnosed with latent tuberculosis infection (LTBI). Total follow-up time (person-years) was 1667.8 for anti-TNF-naïve and 394.9 for anti-TNF-experienced patients. TB IR (95% CI) was 299.8 (37.4-562.2) for anti-TNF naïve and 1012.9 (25.3-2000.5) for anti-TNF experienced subjects. The IRR associated with the use of TNFi was 10.4 (2.3- 47.9).Conclusions: In this high TB incidence setting, SpA patients exposed to anti-TNF therapy had a higher incidence of TB compared to anti-TNF-naïve subjects, although the TB incidence in the control group was significant.(AU)

Anti TNF como inductor de lupus cutáneo: caso clínico / Anti TNF as inducer of cutaneous lupus: clinical case

El mayor acceso a las terapias biológicas para el tratamiento de múltiples enfer-medades autoinmune trae consigo el mayor riesgo de padecer eventos adversos relacionados al uso de estos2,4. Presentamos un caso clínico de una paciente con diagnóstico de artritis reumatoide en tratamiento con ANTI TNF

The greater access to biological therapies for the treatment of multiple autoim-mune diseases brings with it the greatest risk of suffering adverse events related to the use of these (2,4). We present a clinical case of a patient diagnosed with rheumatoid arthritis in treatment with ANTI TNF

Análise da frequência de uveítes em pacientes com espondiloartrites, suas complicações e associação com parâmetros clínicos da doença / Analysis of the frequency of uveitis in spondyloarthritis patients and associations with clinical parameters of the disease

Resumo Objetivo: A uveíte anterior aguda é a principal manifestação extra-articular na espondiloartrite. O objetivo deste estudo foi analisar se a presença da uveíte se associa com diferentes manifestações clínicas, laboratoriais, radiológicas e a terapêutica nos pacientes com espondiloartrite. Métodos: Estudo observacional retrospectivo realizado com 153 pacientes portadores de espondiloartrite atendidos no período de 1997 a 2017 na Grande Florianópolis, Brasil. Foram analisados dados demográficos, laboratoriais, clínicos e do tratamento de pacientes com espondiloartrite em relação a presença ou não de uveíte. Resultados: A uveíte foi encontrada em 26,8% dos pacientes. A presença de complicações foi rara, ocorrendo catarata em somente quatro pacientes e glaucoma em dois deles. Foi observada uma tendência a maior frequência de uveíte anterior aguda no sexo masculino (p=0,06), nos pacientes com história familiar (p=0,19) e HLA-B27 positivos (p=0,14). Pacientes com espondiloartrite e uveíte mais frequentemente usavam anti-TNF (p=0,04) e apresentavam sacroiliite em exames de imagem (p=0,02). Não observou-se associação entre a uveíte e o acometimento cardiovascular (p=0,44), cutâneo (p=0,13) ou gastrointestinal (p=0,10). Conclusão: A uveíte que ocorre em pacientes com espondiloartrite é comum, tem predomínio no sexo masculino e é mais frequente em pacientes com HLA-B27 positivo. O uso de imunobiológicos como o anti-TNF é frequente nos pacientes com uveíte.

Abstract Objective: Acute anterior uveitis (AAU) is the most common extra-articular manifestation of spondyloarthritis. The aim of this study is to analyze if the presence of uveitis is associated with a diferent clinical manifestation, laboratorial, radiological and therapetiuc among spondyloarthritis patients. Methods: This was a observational retrospective study with 153 patients with spondyloarthritis attended in the period from 1997 to 2017 in Florianopolis, Brazil. It was analyzed demografical, laboratorial, clinical and therapeutic data in spondyloarthritis patients with or without uveitis. Results: 26,8% of the patients with spondyloarthritis presented uveitis. The presence of complications was rare, with cataract occurring in only four patients and glaucoma in two of them. A higher frequency of acute anterior uveitis in males (p = 0.06) was observed in patients with a family history (p = 0.19) and HLA-B27 positive (p = 0.14). Patients with spondyloarthritis and uveitis more frequently used anti-TNF (p = 0.04) and presented sacroiliitis on imaging tests (p = 0.02). There was no association between uveitis and cardiovascular (p = 0.44), cutaneous (p = 0.13) or gastrointestinal involvement (p = 0.10). Conclusion: Uveitis in patients with spondylarthritis is common, predominantly in males, and more frequently in HLA-B27 positive patients. The use of immunobiological agents such as anti-TNF is common in patients with uveitis.

A fatal case of tuberculous meningitis in a child with juvenile idiopathic arthritis: a diagnostic challenge

Abstract The prognosis of tuberculous meningitis, a rare form of extrapulmonary tuberculosis, depends on the stage of treatment initiation. We report a fatal case of tuberculous meningitis. The patient had received successive tumor necrosis factor (TNF) antagonists and abatacept to treat juvenile idiopathic arthritis, with negative results for polymerase chain reaction and acid-fast bacilli on smear, had normal cerebrospinal fluid (CSF) adenosine deaminase and glucose levels. Six weeks post-admission, the CSF culture demonstrated Mycobacterium tuberculosis. The altered immunological responses caused by anti-TNF treatment made the diagnosis challenging. Clinicians should bear this in mind and, if suspected, treatment should be initiated immediately.