Serum Levels of Infliximab and Anti-Infliximab Antibodies in Brazilian Patients with Crohn's Disease

OBJECTIVES: The aim of this study was to evaluate the quantitative serum level of infliximab (IFX) as well as the detection of anti-infliximab antibodies (ATIs) in patients with Crohn's disease (CD). METHOD: Forty patients with CD under treatment at a tertiary center in southeastern Brazil were evaluated. Their use of infliximab was continuous and regular. We analyzed and compared the differences in the IFX and ATI levels between the patients with active CD (CDA) and those with CD in remission (CDR). RESULTS: There was no difference in the IFX level between the CDA and CDR groups (p>0.05). Eighty percent of all patients had IFX levels above the therapeutic concentration (6-10 μg/mL). Two (9%) of the 22 patients with active disease and four (22.2%) of the 18 patients in remission had undetectable levels of IFX. Four (66.6%) of the six patients with undetectable levels of IFX had positive ATI levels; three of these patients were in remission, and one had active disease. In addition, the other two patients with undetectable levels of IFX presented ATI levels close to positivity (2.7 and 2.8 AU/ml). None of the patients with therapeutic or supratherapeutic IFX levels had positive ATI levels. CONCLUSIONS: The undetectable levels of IFX correlated with the detection of ATIs, which was independent of disease activity. Immunogenicity was not the main factor for the loss of response to IFX in our study, and the majority of patients in both groups (CDA and CDR) had supratherapeutic levels of IFX.

Deficiência de vitamina D entre pacientes com doença inflamatória intestinal na Argentina: um estudo transversal / Vitamin d deficiency among inflammatorybowel disease patients in argentina: a cross-sectional study

ABSTRACT BACKGROUND: An association has been established between low serum values of vitamin D and inflammatory bowel disease. There is a lack of evidence on whether this association is still observed in regions where sun exposure throughout the year is higher. OBJECTIVE: To compare the prevalence of vitamin D deficiency between inflammatory bowel disease patients and healthy controls. METHODS: Inflammatory bowel disease patients were consecutively enrolled as cases. Age and gender-matched healthy subjects who agreed to undertake a determination of serum vitamin D were enrolled as controls. Demographic features, medical treatment, need for hospital admission at diagnosis, steroid treatment, smoking, need for surgical treatment were evaluated as factors associated with vitamin D deficiency. RESULTS: Overall, 59 patients with a diagnosis of either Crohn's disease or ulcerative colitis were enrolled, as well as 56 controls. Median age was 41 years (19-79) and 56% were male. Vitamin D deficiency was observed in 66.1% of inflammatory bowel disease patients versus 21.42% of healthy controls (OR 7.15 (3.1-16.48), P=0.001). Among inflammatory bowel disease patients, male gender, disease duration, moderate-to-severe disease and hospital admission at the moment of diagnosis were found to be associated with vitamin D deficiency. On multivariate analysis, only longer disease duration [(OR 1.01 (1-1.06)] and hospital admission at diagnosis [(OR 5.63 (1.01-31.61)] were found to be significantly associated with the latter. CONCLUSION: Vitamin D deficiency was more frequent among inflammatory bowel disease patients. Longer disease duration and need for hospital admission at diagnosis were associated to vitamin D deficiency among these patients.

RESUMO CONTEXTO: Uma associação foi estabelecida entre os baixos valores séricos de vitamina D e doença inflamatória intestinal. Falta evidência se esta associação ainda é observada em regiões onde a exposição ao sol durante todo o ano é maior. OBJETIVO: Comparar a prevalência de deficiência de vitamina D entre pacientes com doença inflamatória intestinal e indivíduos controles saudáveis. MÉTODOS: Pacientes com doença inflamatória intestinal foram consecutivamente selecionados. Indivíduos saudáveis combinados da mesma idade e gênero que concordaram em fornecer uma determinação da vitamina D do soro foram considerados como controles. Características demográficas, tratamento médico, necessidade de admissão hospitalar no diagnóstico, tratamento de esteroides, tabagismo, necessidade de tratamento cirúrgico foram avaliados como fatores associados à deficiência de vitamina D. RESULTADOS: No geral, 59 pacientes com diagnóstico de doença de Crohn ou colite ulcerosa foram observados, bem como 56 controles. A idade mediana era de 41 anos (19-79) e 56% eram do sexo masculino. A deficiência de vitamina D foi observada em 66,1% dos pacientes com doença inflamatória intestinal versus 21,42% dos controles saudáveis (OR 7,15 (3.1-16.48), P=0,001). Entre os pacientes com doença inflamatória intestinal, sexo masculino, duração da doença, doença de moderada a severa e admissão hospitalar no momento do diagnóstico foram associados com a deficiência de vitamina D. Na análise multivariada, apenas a duração da doença [(OR 1; 1 (1-1,06)] e a admissão hospitalar no diagnóstico [(OR 5,63 (1,01-31,61)] foram encontradas significativamente associadas ao último. CONCLUSÃO: A deficiência de vitamina D foi mais frequente entre os pacientes com doença inflamatória intestinal. Maior duração da doença e necessidade de admissão hospitalar no diagnóstico foram associadas à deficiência de vitamina D entre esses pacientes.

Dosagem do nível sérico do infliximabe em pacientes com doença inflamatória intestinal em remissão: uma análise comparativa de dois diferentes métodos em uma coorte multicêntrica brasileira / Serum infliximab measurement in inflammatory bowel disease patients in remission: a comparative analysis of two different methods in a multicentric brazilian cohort

ABSTRACT BACKGROUND: Infliximab (IFX) therapeutic drug monitoring is an important tool to guide therapeutic decision in inflammatory bowel disease patients. Currently, there are two methods to measure trough levels of IFX, ELISA assays or rapid tests. Despite that the ELISA assay is the most used method in therapeutic drug monitoring, the results take long to be available for clinical use, and it needs to be performed by trained personnel. In contrary, the results of a rapid test take 20 to 30 minutes to be available and can be performed by non-trained lab personnel. OBJECTIVE: The aim of the study was to compare a rapid test (QB-IFX) for quantitative determination of IFX level to one ELISA assay in a cohort of inflammatory bowel disease patients. METHODS: Cross-sectional multicentric study with 49 inflammatory bowel disease patients on maintenance therapy with IFX. Blood samples for IFX serum levels were collected immediately before infusion. IFX serum levels were classified as undetectable, low (<3.0 μg/mL), adequate (3.1-7.0 μg/mL) or high (>7.1 μg/mL). A sensitivity and specificity of each test and a comparison between tests was based on ROC curves. RESULTS: Thirty-four Crohn's disease patients and 15 ulcerative colitis patients in clinical remission were evaluated. The majority of patients had low or adequate serum levels of IFX. In relation to the serum levels proportions with the two methods, there was no significant difference (P=0.84). The ROC analysis identified a concentration threshold >2.9 μg/mL with the QB-IFX test (area under the ROC, 0.82; P<0.0001, sensitivity, 100%; specificity, 61.9%), and >3.83 μg/mL using the ELISA assay (area under the ROC, 0.96; P<0.0001, sensitivity, 100%; specificity, 92.9%). CONCLUSION: QB-IFX and ELISA assays to measure IFX levels were comparable. Both methods had accurate sensitivity and specificity to detect undetectable, low and adequate levels, but had showed low specificity for supra therapeutic levels of IFX.

RESUMO CONTEXTO: A monitorização dos níveis séricos do infliximabe (IFX) é uma importante ferramenta para guiar a tomada de decisão nos pacientes com doença inflamatória intestinal. No presente momento existem dois tipos de métodos para quantificar nível sérico de IFX disponíveis no mercado: o ELISA e o teste rápido. O método ELISA é o mais usado em todo o mundo, todavia os resultados demoram de 1 a 2 dias para estar disponíveis para uso clínico. Além disso, o ELISA é um método que requer um técnico especializado para realizá-lo. Ao contrário, os resultados do teste rápido estão disponíveis em 20 a 30 minutos e esse pode ser realizado por um funcionário não especializado. OBJETIVO: O objetivo deste estudo foi comparar o teste rápido (QB-IFX) com o teste ELISA para determinação quantitativa do nível sérico de IFX em uma coorte de pacientes com doença inflamatória intestinal. MÉTODOS: Foi realizado um estudo transversal multicêntrico com inclusão de 49 pacientes em terapia de manutenção com IFX. Amostra sanguínea para dosagem sérica do IFX foi coletada imediatamente antes da infusão. A dosagem sérica do IFX foi classificada em indetectável, baixo (<3,0 μg/mL), adequado (3,1-7,0 μg/mL) ou alto (>7,1 μg/mL). A sensibilidade e a especificidade de cada teste e a comparação entre os testes foram avaliados através de curva ROC. RESULTADOS: Foram avaliados 34 pacientes com doença de Crohn e 15 pacientes com retocolite ulcerativa em remissão clínica da doença. A maioria dos pacientes apresentou níveis baixos ou adequados do IFX sérico de acordo com ambos os métodos de dosagem. Não houve diferença significativa entre os métodos quando avaliados categoricamente (P=0,84). A análise da curva ROC identificou limites de concentrações >2,9 μg/mL com o teste rápido QB-IFX (AUC ROC, 0,82; P<0,0001, sensibilidade: 100%; especificidade: 61.9%), e >3,83 μg/mL usando o método ELISA (AUC ROC, 0,96; P<0,0001, sensibilidade: 100%; especificidade: 92,9%). CONCLUSÃO: Os testes QB-IFX e ELISA foram comparáveis para dosagem do nível sérico de IFX. Ambos os métodos são acurados e apresentaram boa sensibilidade e especificidade para detecção de níveis indetectáveis, níveis baixos e níveis adequados, porém mostraram pouca especificidade para níveis supra terapêuticos da droga.

Importância da medida dos níveis de infliximabe em pacientes com doença inflamatória intestinal: uma coorte Brasileira / Importance of measuring levels of infliximab in patients treating inflammatory bowel disease in a brazilian cohort

ABSTRACT BACKGROUND: Crohn's disease and ulcerative colitis are chronic inflammatory bowel diseases. In such pathologies, there is an increased production of alpha tumor necrosis factor (TNF-α). Patients, in whom the conventional immunosuppressant treatment fails, require the use of immunobiological therapy, such as anti-TNF-α, a monoclonal antibody. Infliximab is an anti-TNF-α drug, a chimerical immunoglobulin, with a murine component, which is responsible for the generation of immunogenicity against the drug and formation of anti-TNF-α antibodies. The presence of anti-drug antibodies may be responsible for adverse events and reduction of the drug's effectiveness. Patients with inflammatory bowel diseases undergoing therapy with biological medication, such as infliximab, can relapse overtime and this may not be translated into clinical symptoms. Thus, there is a need for a method to evaluate the efficacy of the drug, through the measurement of serum infliximab levels, as well as antibodies research. OBJECTIVE: This study aimed to measure serum infliximab levels and anti-infliximab antibodies in patients with inflammatory bowel diseases post-induction phase and during maintenance therapy, and describe the therapeutic modifications that took place based on the serum levels results. METHODS: It was a retrospective study, that included forty-five patients, with a total of 63 samples of infliximab measurement. RESULTS: Twenty-one patients had an adequate infliximab serum level, 31 had subtherapeutic levels and 11 had supratherapeutic levels. Seven patients had their medication suspended due to therapeutic failure or high levels of antibodies to infliximab. CONCLUSION: In conclusion, only a third of the patients had adequate infliximab levels and 36% presented with subtherapeutic levels at the end of the induction phase. Therapy optimization occurred based in about 46% of the samples results, demonstrating the importance of having this tool to help the clinical handling of patients with inflammatory bowel diseases ongoing biologic therapy.

RESUMO CONTEÚDO: Doença de Crohn e retocolite ulcerativa são doenças inflamatórias intestinais crônicas. Nelas, ocorre aumento da produção de fator de necrose tumoral alfa (TNF-α). Pacientes que falham no tratamento convencional imunossupressor, requerem uso de terapia imunobio­lógica, que são anticorpos monoclonais, principalmente os anti-TNF-α. O infliximabe é uma droga anti-TNF-α, uma imunoglobulina quimérica, com componente murino. Este é responsável pela imunogenicidade da droga e a formação de anticorpos. Presença de anticorpos antidroga pode ser responsável pelos eventos adversos e redução da eficácia da droga. Pacientes com doenças inflamatórias intestinais, em terapia imunossupressora com medicação biológica como o infliximabe, podem ter recaída da doença e muitas vezes isso não se relaciona com a sintomatologia do paciente. Por isso há a necessidade de um método de avaliação do efeito da droga como a dosagem do nivel sérico do infliximabe, bem como da pesquisa de anticorpos. OBJETIVO: O estudo tem como objetivo conhecer os níveis séricos do infliximabe e dos anticorpos anti-infliximabe em pacientes com doença inflamatória intestinal em terapia de manutenção ou pós-indução e descrever as condutas terapêuticas que foram modificadas em função dos níveis séricos de infliximabe e anticorpos para infliximabe. MÉTODOS: Trata-se de estudo restrospectivo, com análise da dosagem dos níveis séricos de infliximabe e anticorpos para Infliximabe. Foram incluídos 45 pacientes, num total de 63 coletas de dosagem de infliximabe. RESULTADOS: Vinte e um paciente estavam com o nível sérico de infliximabe adequado, níveis subterapêuticos em 31 pacientes e níveis supraterapêuticos em 11 pacientes. Sete pacientes tiveram a medicação suspensa por falha terapêutica ou altos níveis de anticorpos para infliximabe. CONCLUSÃO: Apenas um terço dos pacientes apresentavam níveis adequados de infliximabe e 36% dos pacientes apresentavam níveis subterapêuticos ao término da indução. Em cerca de 46% das amostras a conduta adotada se baseou nos níveis de infliximabe e anticorpos para infliximabe demonstrando a importância de se ter esta ferramenta para auxílio no manejo clínico dos pacientes portadores de doenças inflamatórias intestinais em terapia biológica.

Alert for bone alterations and low serum concentrations of vitamin D in patients with intestinal inflammatory disease / Alerta para alterações ósseas e baixas concentrações séricas de vitamina D em pacientes com doença inflamatória intestinal

Summary Background: Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are characterized by chronic inflammation of the intestine that can reduce the absorption of nutrients such as vitamin D and calcium. Objective: To investigate bone alterations and serum levels of vitamin D in patients with IBD. Method: This was a cross-sectional study based on a review of medical records of patients from a private office in Curitiba, PR, Brazil. Serum levels of vitamin D and bone densitometry were measured at diagnosis of IBD. A total of 105 patients were included; 38 (58.4%) with CD; 27 (41.6%) with UC and 40 with irritable bowel syndrome (IBS) as comparison group. Results: When compared to patients with UC, CD patients showed a higher prevalence of bone alterations, being 15.8% with osteoporosis and 36.8% with osteopenia. In UC, bone alterations occurred in 29.6% of cases, 3.7% with osteoporosis and 25.9% with osteopenia. As for vitamin D levels, among CD patients, 10.5% had vitamin deficiency, 65.8% insufficiency and 23.7% were sufficient. In UC, 7.4% of cases had deficiency, 74.1% insufficiency and 18.5% had sufficient serum levels of vitamin D. In the group with IBS, deficiency was observed in 17.5% of cases, insufficiency in 55% and sufficiency in 27.5% of them. There was no significant difference between groups. Conclusion: IBD patients have a high prevalence of bone changes, especially those with CD. Serum levels of vitamin D are below the recommended in all the evaluated groups.

Resumo Introdução: A doença inflamatória intestinal (DII), como a doença de Crohn (DC) e a retocolite ulcerativa (RU), caracterizam-se pela inflamação crônica no intestino, que pode reduzir a absorção de vitamina D e cálcio. Objetivo: Investigar as alterações ósseas presentes em pacientes com DII e as dosagens séricas de vitamina D. Método: Estudo transversal analítico baseado na revisão de prontuários de pacientes com DII de um consultório privado de Curitiba, PR. Em todos os pacientes, foram dosadas as concentrações séricas de vitamina D e foi feita a densitometria óssea. Cento e cinco pacientes foram incluídos no estudo, dos quais 38 (58,4%) foram diagnosticados com DC, 27 (41.6%) com RU e 40 com síndrome do intestino irritável (SII) como grupo de comparação. Resultados: Quando comparados com pacientes com RU, os pacientes com DC apresentaram maior prevalência de alterações ósseas, sendo 15,8% com osteoporose e 36,8% com osteopenia. Na RU, as alterações ósseas ocorreram em 29,6% dos casos, 3,7% com osteoporose e 25,9% com osteopenia. Em relação às dosagens de vitamina D, dentre os pacientes com DC, 10,5% apresentavam deficiência, 65,8%, insuficiência e 23,7%, suficiência. Na RU, 7,4% dos casos tinham deficiência, 74,1%, insuficiência e 18,5%, suficiência. No grupo com SII, observaram-se deficiência em 17,5%, insuficiência em 55% e suficiência em 27,5%. Não foi observada diferença significativa entre os grupos. Conclusão: Pacientes com DII apresentaram alta prevalência de alterações ósseas, principalmente aqueles com DC. As concentrações séricas de vitamina D estão abaixo do recomendado em todos os grupos avaliados.

LOWER LEVELS OF VITAMIN D CORRELATE WITH CLINICAL DISEASE ACTIVITY AND QUALITY OF LIFE IN INFLAMMATORY BOWEL DISEASE

Background - Inflammatory bowel disease, comprising Crohn's disease and ulcerative colitis, is a group of debilitating conditions associated with deregulated mucosal immune response. Vitamin D has been implicated in immune response and gastrointestinal function. Objectives - To investigate the correlation between serum vitamin D levels and disease activity and quality of life in patients with inflammatory bowel disease. Methods - This cross-sectional study enrolled ambulatory patients with inflammatory bowel disease and assessed clinical disease activity and quality of life (Short Inflammatory Bowel Disease Questionnaire [SIBDQ]). Vitamin D levels were determined via serum 25-hydroxyvitamin D measurement; deficiency was defined as values <20 ng/mL. Statistical analysis was performed with SPSS vs 20.0. Results - A total of 76 patients were enrolled, 19 with ulcerative colitis (25%) and 57 with Crohn's disease (75%). Overall, mean serum 25-hydroxyvitamin D levels were low (26.0±10.0 ng/mL), while those in patients with Crohn's disease were significantly lower than ulcerative colitis (24.6±8.0 vs 30.0±12.5 ng/mL; P=0.032). Vitamin D deficiency was found in 30% of patients. Patients who were in clinical remission were found to have higher levels of vitamin D than those who were not in remission (28.0±10.3 vs 21.6±6.0 ng/mL, P=0.001). Inflammatory bowel disease patients with SIBDQ scores <50 were found to have significantly lower mean vitamin D levels compared with patients who had SIBDQ scores ≥50 (23.4±6.9 vs 27.9±10.8 ng/mL, P=0.041). Conclusions - A high proportion of patients with inflammatory bowel disease were vitamin D deficient, particularly patients with Crohn's disease. Both clinical disease activity and quality of life correlated significantly with lower levels of vitamin D, illustrating a clear need for supplementation in patients with inflammatory bowel disease.

Contexto - A doença inflamatória intestinal, que compreende a doença de Crohn e a colite ulcerosa, é um grupo de entidades incapacitantes associada a uma resposta imunitária desregulada. A vitamina D tem sido associada à resposta imune e funções gastrointestinais. Objetivo - Investigar a correlação entre os níveis séricos de vitamina D, a atividade clínica da doença e a qualidade de vida em doentes com doença inflamatória intestinal. Método - Estudo transversal que incluiu doentes em ambulatório com doença inflamatória intestinal avaliando a atividade clínica da doença e a qualidade de vida (Short Inflammatory Bowel Disease Questionnaire [SIBDQ]). Os níveis séricos de vitamina D foram determinados através dos níveis de 25-hidroxivitamina D; a deficiência de vitamina D foi definida para valores <20 ng/mL. Resultados - Foram incluídos 76 doentes, 19 com colite ulcerosa (25%) e 57 com doença de Crohn (75%). No global, os valores séricos médios de 25-hidroxivitamina D foram baixos (26,0±10,0 ng/mL), os doentes com doença de Crohn apresentaram níveis mais baixos do que os doentes com colite ulcerosa (24,6±8,0 vs 30,0±12,5 ng/mL; P=0,032). O défice de vitamina D foi identificado em 30% dos doentes. Os doentes em remissão clínica apresentaram níveis mais elevados de vitamina D (28,0±10,3 vs 21,6±6,0 ng/mL, P=0,001). Doentes com SIBDQ <50 apresentaram níveis significativamente inferiores de vitamina D em comparação com doentes com SIBDQ ≥50 (23,4±6,9 vs 27,9±10,8 ng/mL, P=0,041). Conclusão - Uma percentagem elevada de doentes apresentou deficiência de vitamina D, em particular doentes com doença de Crohn. A atividade clínica e a qualidade de vida dos doentes com doença inflamatória intestinal correlacionou-se com níveis mais baixos de vitamina D, ilustrando uma clara necessidade de suplementação desta vitamina em doentes com doença inflamatória intestinal.

Usefulness of C-Reactive Protein as a Disease Activity Marker in Crohn's Disease according to the Location of Disease

BACKGROUND/AIMS: C-reactive protein (CRP) is a serologic activity marker in Crohn's disease (CD), but it may be less useful in evaluating CD activity in ileal CD patients. We aimed to investigate the usefulness of CRP as a disease activity marker in CD according to disease location. METHODS: Korean CD patients in a single hospital were evaluated. Factors associated with elevated CRP concentration at the time of diagnosis of CD and the association between the physician's prediction regarding upcoming surgery and the sites of the lesions directly related to surgery were analyzed. RESULTS: Of 435 CD patients, 25.7%, 6.9%, and 67.4% had ileal, colonic, and ileocolonic CD, respectively. Multivariate analysis revealed that an elevated erythrocyte sedimentation rate, reduced serum albumin, CD activity index (CDAI) >220, and ileocolonic/colonic location were associated with an elevated CRP level and that the CRP level was significantly correlated with the CDAI in all CD patients (gamma=0.466, p<0.01). However, the correlation coefficient was dependent on the location, with values of 0.395, 0.456, and 0.527 in patients with an ileal, ileocolonic, and colonic disease location, respectively. Surgery for ileal lesions was less predictable than surgery for ileocolonic or colonic lesions during follow-up. CONCLUSIONS: CRP is less useful as a disease activity marker in patients with ileal CD than those with ileocolonic or colonic CD.

Nutritional Status and Growth in Korean Children with Crohn's Disease: A Single-Center Study

BACKGROUND/AIMS: Malnutrition and growth retardation are important issues in treating pediatric Crohn's disease (CD). Thus, we aimed to investigate the prevalence of various nutritional and growth parameters at the time of diagnosis in Korean children with CD. METHODS: Seventy-one children (<18 years) were enrolled. We analyzed the Z-scores of height-for-age (HAZ), weight-for-height (WHZ), body mass index for age (BMIZ), bone mineral density for age (BMDZ), and the biochemical markers measured at the time of diagnosis. RESULTS: At diagnosis, HAZ <-2 was observed in three patients (4%), WHZ <-2 in 20 patients (28%), BMIZ <-2 in 19 patients (27%), and BMDZ <-2 in 11 patients (18%). The HAZ was significantly lower in females and patients with extraintestinal manifestations, and the WHZ and BMIZ were significantly lower in patients with stricturing and penetrating disease. Subnormal serum levels were highly prevalent for hemoglobin, albumin, iron, ferritin, calcium, magnesium, folate, vitamin B12, and zinc. There was a significant correlation between nutritional status, growth retardation, and disease activity. CONCLUSIONS: Abnormal nutritional status was highly prevalent in Korean children with CD at the time of diagnosis and was associated with the extent, behavior, and activity of the disease.

25 (OH) vitamin D level in Crohn’s disease: association with sun exposure & disease activity.

Background & objectives: Western studies show that up to 65 per cent of patients with Crohn’s disease have low serum 25-hydroxy vitamin D concentrations, and 45 per cent of these patients have metabolic bone disease. No data are available from India or from any country with comparable climatic conditions or ethnicity. We carried out this study to measure the serum 25 (OH) vitamin D levels of Crohn’s disease patients and compare with matched controls and to assess the consequences of low 25 (OH) vitamin D levels on bone and mineral metabolism in these patients. Methods: Adult patients with Crohn’s disease were compared with age and sex matched patients diagnosed to have irritable bowel syndrome. Serum 25 (OH) vitamin D, the effect of disease characteristics, sunlight exposure and milk consumption on 25 (OH) vitamin D level, and the consequences of low 25 (OH) vitamin D level on bone and mineral metabolism were assessed. Results: Thirty four patients with Crohn’s disease (M:F, 24:10, age 39.2 ± 12.9 yr) and 34 controls (M:F, 24:10, age 38.9 ± 13.4 yr) were studied. 25 (OH) vitamin D levels were significantly lower in patients with Crohn’s disease as compared to controls (Crohn’s disease vs controls: 16.3 ± 10.8 vs 22.8 ± 11.9 ng/ml; P<0.05). The severity of disease activity as assessed by the Harvey Bradshaw score correlated negatively (Correlation coefficient -0.484, significance P<0.004), and the duration of sunlight exposure correlated positively (Correlation coefficient 0.327, significance P=0.007) with the serum 25 (OH) vitamin D level. Interpretation & conclusions: Serum 25 (OH) vitamin D levels were significantly lower among patients with Crohn’s disease as compared to age and sex matched controls. Further, 25 (OH) vitamin D levels in patients with Crohn’s disease were lower in those with severe disease activity and less sun exposure. Further studies need to be done to correlate low 25 (OH) vitamin D level with bone density and assess the effect of vitamin D supplementation in these patients.

Study the changes of the levels of some trace elements and minerals in patients with ulcerative colitis and Crohn's disease

Inflammatory bowel disease [IBD] is a chronic inflammatory process that involves the colon in Ulcerative colitis [UC] and may involve any part of the entire gastrointestinal tract in Crohn's disease [CD]. The aetiology and pathogenesis of IBD are still unclear. Nutrition plays an important role in pathogenesis and treatment. The aim of the present study was to study the level of some minerals and trace elements in inflammatory bowel disease and correlate their levels with the disease activity. The study was carried out on patients of previously diagnosed IBD [included 10 CD patients and 10 UC patients] as a patient group and ten healthy volunteers as a control group. The disease activity in all patients were assessed according to Crohn's disease activity index [CDAI], and Truelove and Witts criteria for ulcerative colitis. Sample collection of some minerals and trace elements were done on fasting serum samples including:- Calcium [Ca], Phosphorus [Ph], Magnesium, Chromium, Copper, Selenium, and Zinc. The results of plasma concentrations of some minerals and trace elements in ulcerative colitis, Crohn's disease patients and controls showed a significant reduction of serum calcium [P=0.000], serum phosphate [P=0.01], serum magnesium [P=0.000], serum copper [P=0.000], serum selenium [P=0.004],and serum zinc [P=0.000] in patients with UC and CD than controls. However, chromium was significantly elevated in UC and CD patients than controls [P=0.03, P=0.000 respectively]. Using inter-groups comparison; only serum calcium level showed a statistically significant difference in CD patients than UC patients. we found that the assessment of patient with IBD should include a focus on nutritional aspects even minerals and trace elements. Plasma or serum concentration of antioxidants including trace elements could be used as a biomarker of oxidative stress which has been established in IBD

Toxicidade da azatioprina na doença de Crohn: incidência, abordagem e evolução / Azathioprine toxicity in Crohn's disease: incidence, approach and course

OBJETIVO: A azatioprina (AZA) tem sido usada freqüentemente no tratamento da doença de Crohn (DC). O objetivo do presente estudo foi avaliar a freqüência, evolução e abordagem dos efeitos adversos da AZA no tratamento de pacientes com DC. MÉTODOS: Foram incluídos prospectivamente 106 pacientes portadores de DC em uso de AZA, de janeiro de 2002 a dezembro de 2006. Registraram-se dados clínicos e demográficos, com controle laboratorial mensal dos efeitos hematológicos e supervisão de reações adversas por meio de avaliação clínica. Realizou-se comparação entre os grupos com e sem efeitos adversos. RESULTADOS: Cinqüenta e seis (52,7 por cento) dos pacientes estudados apresentaram pelo menos um efeito adverso, requerendo redução transitória da dose da droga; 18 (17 por cento) necessitaram suspender definitivamente o uso de AZA, geralmente devido a reações de hipersensibilidade. Náuseas e vômitos, freqüentemente leves, ocorreram em 29 (27,4 por cento); a raça negra e aqueles com comorbidades apresentaram mais intolerância gástrica do que os brancos e aqueles sem outras doenças associadas (p=0,04). Leucopenia foi o efeito adverso mais freqüente, ocorrendo em 36 (34 por cento). O tempo de uso de AZA foi maior em pacientes com leucopenia do que nos não leucopênicos (p=0,001), enquanto a dose média de AZA foi menor naqueles com leucopenia comparados aos não leucopênicos (p=0,005). Não houve infecções graves, neoplasias ou óbitos durante o tratamento com AZA. CONCLUSÃO: A AZA mostrou ser uma droga relativamente segura no tratamento da DC, desde que seja mantida supervisão clínica e laboratorial periódica durante todo o tratamento.

OBJECTIVE: Azathioprine (AZA) is frequently used in Crohn's disease (CD) therapy. This paper aimed to evaluate the frequency, evolution and management of AZA side effects in CD patients. METHODS: One hundred and six CD patients under AZA therapy were evaluated prospectively from January 2002 to December 2006. Clinical and demographic data were recorded, together with a monthly laboratory control of hematological or other adverse reactions by means of clinical evaluation. Comparison was carried out between groups with and without side effects. RESULTS: At least one adverse reaction was found in 56 (52.7 percent) of the patients studied and required a transient drug reduction; 18 (17 percent) had to definitely stop use of AZA, often because of hypersensitivity reactions. Nausea, vomit, although slight, occurred in 29 (27.4 percent). The black race and those with co-morbidities had more gastric intolerance than Caucasians and those without other associated disease (p=0.04). Leucopoenia was the more frequent side effect observed, occurring in 36 (34 percent). The period of AZA use was longer for patients with leucopoenia than for those without (p=0.001), while the mean dose of AZA was lower for those with leucopoenia when compared to non-leucopoenics (p=0.005). No serious infections, malignancy or death was noticed as a consequence of AZA use. CONCLUSION: In this study use of AZA in therapy for Crohn's disease disclosed that the drug is satisfactorily safe as long as periodical clinical and laboratory supervision is carried out during treatment.

Níveis baixos de 25-hidroxivitamina D (25OHD) em pacientes com doença inflamatória intestinal e sua correlação com a densidade mineral óssea / Low levels of 25-hydroxyvitamin D (25OHD) in patients with inflammatory bowel disease and its correlation with bone mineral density

INTRODUÇÃO: Pacientes com doenças inflamatórias intestinais (DII) estão propensos a apresentar níveis baixos de vitamina D (25OHD) e densidade mineral óssea (DMO) diminuída. OBJETIVO: Verificar o nível de 25OHD em jovens com DII submetidos à avaliação clínica, dosagens bioquímicas rotineiras e medida da DMO de coluna lombar e fêmur, comparando-os com controles saudáveis. RESULTADOS: 39 pacientes com doença de Crohn (DC) (p = 0, 003) e 37 com retocolite ulcerativa inespecífica (RCUI) (p < 0,001) apresentaram níveis mais baixos de 25OHD comparados aos controles, 48,5 por cento dos pacientes com RCUI tinham deficiência de 25OHD. A DMO em coluna lombar foi mais baixa nos doentes (DC p = 0,001; RCUI p = 0,008). A 25OHD correlacionou-se significativamente com a DMO do fêmur total (r = 0,391; p = 0,027) e colo do fêmur (r = 0,384; p = 0,03) na DC. CONCLUSÃO: Foram encontrados níveis baixos de 25OHD e DMO em jovens com DII, sugerindo papel importante desta deficiência na patogênese da doença óssea desses pacientes.

Patients with inflammatory bowel disease (IBD) are at risk of having vitamin D deficiency (25-OHD) and low bone mineral density (BMD). OBJECTIVES: To measure 25OHD in a young group of IBD patients submitted to a clinical evaluation, routine biochemistry and BMD measurement (lumbar spine and proximal femur). RESULTS: 39 Crohn disease (CD) and 37 ulcerative colitis (UC) patients had lower serum levels of 25OHD compared to the control group (CD p = 0,003; UC p < 0,001), and 48.5 percent of the UC patients were 25OHD deficient. Lumbar spine BMD was lower in patients than controls (CD p = 0,001; UC p = 0,008). In CD patients, serum levels of 25OHD were significantly correlated with total femur (r = 0,391; p = 0,027) and femoral neck (r = 0,384; p = 0,03) BMD. CONCLUSION: It was found lower levels of 25OHD and BMD in young IBD patients compared to normal controls, suggesting an important role of 25OHD deficiency in the pathogenesis of the IBD bone disease.

Análise descritiva dos perfis social, clínico, laboratorial e antropométrico de pacientes com doenças inflamatórias intestinais, internados no Hospital Universitário Clementino Fraga Filho, Rio de Janeiro / Descriptive analysis of the social, clinical, laboratorial and anthropometric profiles of inflammatory bowel disease inwards patients from the Clementino Fraga Filho University Hospital, Rio de Janeiro, RJ, Brazil

RACIONAL: Estudos epidemiológicos sobre doenças inflamatórias intestinais no Brasil são limitados devido a dificuldades diagnósticas e reduzidas amostras populacionais estudadas. A maioria dos estudos de sua prevalência disponível é composta por amostras de pacientes sob acompanhamento em ambulatório, entretanto a análise do perfil de pacientes com doenças inflamatórias intestinais hospitalizados pode auxiliar na detecção de marcadores preditivos de sua gravidade, o que permitirá intervenções médicas precoces visando a redução da taxa de hospitalização e os gastos do sistema de saúde. OBJETIVOS: Descrever o perfil social, clínico, laboratorial e antropométrico dos pacientes adultos com doenças inflamatórias intestinais internados em hospital universitário terciário. MÉTODOS: Estudo prospectivo com 43 pacientes com doenças inflamatórias intestinais internados nas enfermarias clínicas e cirúrgicas e no setor de emergência do Hospital Universitário Clementino Fraga Filho da Universidade Federal do Rio de Janeiro, RJ. Foram caracterizados dados demográficos, presença de co-morbidades, localização e comportamento clínico, história cirúrgica, manifestações extra-intestinais utilizando-se definições padronizadas. Os resultados laboratoriais foram verificados nos prontuários e as medidas antropométricas foram realizadas durante a entrevista. RESULTADOS: A maioria dos pacientes apresentou doença de Crohn (72,1 por cento), com localização íleo-colônica (60 por cento) e com comportamento penetrante (77,4 por cento), enquanto no grupo retocolite ulcerativa idiopática predominou a pancolite (50 por cento). No grupo total de retocolite ulcerativa idiopática, a artralgia foi a manifestação extra-intestinal mais freqüente (44,2 por cento) e 97,7 por cento já havia apresentado algum tipo de complicação relacionada à doença de base. Apesar do uso de terapêutica específica para doenças inflamatórias intestinais prévio à hospitalização em 79,1 por cento...

BACKGROUND: The epidemiologic survey in Brazil is limited probably due to a diagnosis deficiency and a small number of population-based studies performed. The majority of the prevalence studies available have evaluated inflammatory bowel diseases outpatients, but the knowledge of the profile of inflammatory bowel diseases inpatients is important in order to detect predictive markers of disease severity that will allow earlier medical intervention decreasing the rate of hospitalization and reducing the Health System costs. AIM: To determine social, clinical, laboratorial and anthropometric profiles of hospitalized adults inflammatory bowel diseases patients of a tertiary university hospital. METHODS: Prospective study was performed with 43 inflammatory bowel diseases inpatients from clinical and surgical wards and emergency section of university hospital. We characterized demographic data, presence of comorbidities, disease location and behavior, surgical past-history, extra intestinal manifestations using standardized definitions. Laboratory results were abstracted from medical records and anthropometric measures were performed during our visit. RESULTS: The vast majority of the inflammatory bowel diseases patients had Crohn's disease (72.1 percent), with ileocolic involvement (60 percent), with a penetrating disease behavior (77.4 percent) while ulcerative colitis group presented mostly pancolitis (50 percent). Articular pain was the most common (44.2 percent) extra intestinal manifestation of inflammatory bowel diseases patients and 97.7 percent of them had at least one type of complication related to disease. Although, the previous use of specific medical therapies to inflammatory bowel diseases before the hospitalization (more frequently corticosteroids) was done (79 percent), the majority of the patients were hospitalized because of inflammatory bowel diseases activity. Disease activity was present in 80.7 percent of Crohn's disease...

Trombocitose e doença de Crohn / Thrombocytosis and Crohn disease

A correlaçäo entre trombocitose e atividade da doença de Crohn (DC) tem sido constatada por alguns autores. Entretanto, esta observaçäo näo tem sido extensamente utilizada pela existência de comprovaçöes limitadas. Assim, os autores analisaram, retrospectivamente, os dados dos últimos 30 pacientes atendidos na Disciplina de Gastroenterologia do Departamento de Clínica Médica do Hospital das Clínicas da Faculdade de Medicina da Universidade de Säo Paulo, e na clínica privada de um dos autores (A.B.). Levou-se em consideraçäo a contagem de plaquetas (método de Brecher-Cronkite; valores normais 200.000 a 400.000 plaquetas/mm3) e o índice clínico de atividade da DC segundo os critérios de Harvey e Bradshaw. Onze pacientes (37%) apresentaram trombocitose (x=500.818 + ou - 56.845) e o valor médio do índice clínico de atividade desse grupo foi 8,6 (intervalo de confiança: 6-13). Dezenove pacientes (63%) näo apresentaram trombocitose (267.789 + ou - 62.124) e o seu valor médio de atividade foi 5,7 (intervalo de confiança: 2-11). Diferença estatisticamente significante foi verificada entre os valores médios dos índices clínicos de atividade dos dois grupos (z=2,84, para alfa < ou = 0,05), bem como entre as médias do número de plaquetas/mm3 (z = 4,5, para alfa < ou = 0,05). Näo houve relaçäo estatisticamente significante entre trombocitose e formas íleo-cólica, jejuno-ileal e cólica da DC. Entretanto, dos nove pacientes da casuística com forma ileal, oito (88%) näo apresentaram trombocitose e tiveram índices de atividade < ou = 6. Os possíveis mecanismos fisiopatológicos da trombocitose na DC säo comentados e revisados. A relaçäo entre trombocitose e a atividade da DC, observada na presente casuística, näo constitui, certamente, elemento diagnóstico para a afecçäo, mas associadamente ao quadro clínico, pode representar importante parâmentro para indicar a atividade da doença