Situação vacinal de pacientes com doença inflamatória intestinal / Immunization status of patients with inflammatory bowel disease

ABSTRACT BACKGROUND: Treatment for inflammatory bowel disease (IBD) includes a variety of immunosuppressants and biological agents, which increase the risk of infections due to altered cellular and humoral immunity. Prevention of these infections can be done through vaccination, however, patients with IBD are usually under-immunized. OBJECTIVE: Analyze the immunization status of patients with IBD and confront it with the current recommendations to verify if the immunization guidelines are being followed correctly. METHODS: Analytical cross-sectional study including 239 IBD patients being regularly followed in the Gastroenterology Service from Hospital de Clínicas da Universidade Federal do Paraná, which were subjected to a survey about their relevant demographic data and immunization status. RESULTS: The amount of patients that declared being unaware of their immunization status is high - between 34.3% (Tdap) and 52% (meningococcal) - excepting IIV, hepatitis B and HPV. The vaccines with the largest rates of patients declaring to have taken it are inactivated influenza vaccine (72.4%), BCG (55.3%), hepatitis B (48.3%), measles, mumps and rubella vaccine (43.8%) and DTaP (43%). The vaccines with the lowest rates of patients declaring to have taken it are Haemophilus influenza type b (0.8%), herpes zoster (2.1%) and HPV (3.4%). Patients that are being treated or have been treated with biological therapy have the largest immunization coverage for inactivated influenza vaccine (81%) and PPSV23 (25.9%), also they have the largest awareness rates for those vaccines. CONCLUSION: Although being a specialized service linked to a university hospital, vaccination coverage and patients' awareness rates proved to be below the desirable level. Vaccination and recovery of the immunization history is recommended immediately after the diagnosis of IBD, regardless of the use of biological agents. Those findings support the need of implementing hospital guidelines and constantly verifying its application by the multidisciplinary team in specialized services in IBD.

RESUMO CONTEXTO: No tratamento de doenças inflamatórias intestinais (DII) são usados imunossupressores e agentes biológicos, o que aumenta o risco de infecções pela alteração da imunidade celular e humoral. A prevenção de algumas dessas infecções pode ser feita pela vacinação, entretanto pacientes com DII apresentam baixas taxas de cobertura vacinal. OBJETIVO: Analisar a situação vacinal de pacientes com DII e comparar com a recomendação vigente na literatura para verificar se os esquemas de imunização estão sendo corretamente aplicados nessa população. MÉTODOS: Estudo transversal analítico com 239 pacientes com DII em acompanhamento no Serviço de Gastroenterologia do Hospital de Clínicas da Universidade Federal do Paraná, os quais foram submetidos a um questionário sobre dados demográficos relevantes e sobre a situação vacinal. RESULTADOS: A taxa de pacientes que declarou não ter conhecimento de sua situação vacinal é alta - entre 34,3% (dTpa) e 52% (meningocócica) - com exceção das vacinas influenza, hepatite B e HPV. As vacinas com maior taxa de pacientes que declararam ter recebido a vacina são influenza (72,4%), BCG (55,3%), hepatite B (48,3%), tríplice viral (43,8%) e DTPa (43%). As vacinas com menor taxa de pacientes que declararam ter recebido a vacina são Haemophilus influenza b (0,8%), herpes zoster (2,1%) e HPV (3,4%). Pacientes que fazem ou já fizeram tratamento com agentes biológicos têm melhor cobertura vacinal das vacinas para influenza (81%) e PP23V (25,9%), além de maior conhecimento sobre o estado vacinal para essas vacinas. CONCLUSÃO: Apesar de se tratar de um serviço especializado ligado a um hospital universitário, a cobertura vacinal e o conhecimento dos pacientes sobre as vacinas estão abaixo do desejado. A recuperação do histórico vacinal e a recomendação das vacinas necessárias devem ser realizadas logo após o diagnóstico de DII, independentemente do uso de agentes biológicos. Esses achados indicam a necessidade da criação e monitoramento constante da aplicação de um protocolo pela equipe multidisciplinar de serviços especializados em DII.

Tuberculin skin testing in inflammatory bowel disease patients from an endemic area of Brazil

Objective: Inflammatory bowel disease (IBD) is a chronic disorder involving the gastrointestinal tract. Immunosuppressive drugs are usually prescribed to treat IBD patients, and this treatment can lead to tuberculosis reactivation. This paper aimed to analyze tuberculin skin test (TST) results in IBD patients at a reference center in Brazil. Methods: We evaluated TST results in IBD patients using a cross-sectional study. We also analyzed the medical records of patients treated at a reference IBD outpatient unit where TST is routinely performed. Results: We reviewed 119 medical records of 57 (47.9%) Crohn's disease (CD), 57 (47.9%) ulcerative colitis (UC) and 5 (4.2%) indeterminate colitis (IC) patients. The mean (SD) age was 43.5 (13.7) years old. TST was positive in 24 (20.2%) of the patients. TST was positive in 16/57 (28.1%) UC and 6/57 (10.5%) CD patients (prevalence ratio [PR] 2.7). Forty-one patients (34.5%) were taking immunosuppressive drugs (azathioprine or prednisone) at the time of the TST, and six of these patients (14.6%) had positive test results. Two patients using infliximab had negative TST results. Thirty-five of the 41 patients (85.4%) on immunosuppressive treatment were anergic compared with 73.1% (57/78) of the untreated patients (PR 1.2). Conclusions: Patients with IBD have TST results similar to the general Brazilian population. Within the IBD population, CD patients have a lower frequency of TST positivity than UC patients. .

Associação de polimorfismos nas sequências regulatórias dos genes HLA-G, IL-10 e TNF e a sua respectiva expressão gênica em lesões de mucosa em pacientes portadores de doença inflamatória intestinal / Association of HLA-G, IL-10 and TNF regulatory sequence polymorphisms and respective gene expression in biopsies of Brazilian patients with Inflammatory Bowel Disease

Fatores genéticos e imunológicos foram associados à patogenese da doença inflamatória intestinal (DII), ela inclui Retocolite Ulcerativa Idiopática (RCUI) e doença de Crohn (CD). A hiperresponsividade de celulas B e a autoreatividade de células T contribuem para a polarização da resposta imune Th1 em CD e Th2 em RCUI. Sítios polimórficos na região 3'não traduzida do gene HLA-G (completa) e região promotora dos genes IL-10 ( - 1082A/G e - 819C/T) e TNF (completa) foram associados a susceptibilidade a diversas doenças. Estudamos 217 portadores de DII e 249 doadores saudáveis, pareados por sexo e idade. A ascendência africana foi maior em RCUI e caucasiana em DC (p =0,005). Comparados aos controles, o genótipo HLA - G 14bpINS - INS (associado com baixa expressão de HLA - G) (p =0,006) e IL - 10 - 1082G - G (associado com alta expressão de IL - 10) (p =0,030) foram menos frequentes em pacientes com DC, possivelmente contribuindo para a polarização Th1, mas não foram encontradas diferenças nas frequências de TNF. Em RCUI, as frequências do alelo HLA-G +3003C (p =0,015) e genótipo +3003C-T (p =0,003) estavam aumentadas. Apesar da alta frequência do alelo T em africanos, após estratifica rmos por ascendência, o genótipo +3003C - T ainda estava mais frequente em pacientes com ascendência africana (p =0,012)...

Genetic and immunological factors have been associated with inflammatory bowel disease (IBD) pathogenesis, encompassing ulcerative colitis (UC) and Crohn's disease (CD).B cell hyperresponsiveness and T cell auto-reactivity have contributedto a Th1 polarization immune response in CD and a Th2 polarization in UC. Sincepolymorphic sites at the 3’untranslated region (3’UTR)...

Factors Associated with Vaccination among Inflammatory Bowel Disease Patients in Korea / 대한소화기학회지

BACKGROUND/AIMS: Vaccinations are generally recommended in patients with inflammatory bowel disease (IBD). However, several studies showed low rates of vaccinations in IBD patients. Furthermore, vaccination rate among IBD patients in Korea has never been investigated. We investigated the vaccination rate among IBD patients in Korea and evaluated some factors that might affect the vaccination rate. METHODS: From November 2011 to February 2012, a total of 192 patients with IBD who visited Samsung Medical Center (Seoul, Korea) answered the IRB-approved questionnaire. The questionnaire included their sex, age, residence, past medical history, type of IBD, duration of illness, medications, history of vaccination about measles-mumps-rubella (MMR), varicella, tetanus-diphtheria (Td), influenza, hepatitis A and B, pneumococcus and human papilloma virus (HPV). RESULTS: One hundred twenty one (63.0%) male and 71 (37.0%) female answered the questionnaire. The mean age of the enrolled patients was 39.7 (18-76) years. Eighty four patients (43.8%) had ulcerative colitis and 108 patients (56.3%) had Crohn's disease (CD). The percentage of the patients who had got vaccination was 42.2% for MMR, 34.9% for varicella, 15.6% for Td, 37.5% for influenza, 15.6% for hepatitis A, 52.6% for hepatitis B, 6.3% for pneumococcus and 11.3% for HPV respectively. Not knowing the necessity or the existence were the common reasons for non-vaccination. Age less than 40 years, CD patients and duration of illness less than 10 years were associated with a higher vaccination rate (p=0.002, 0.015 and 0.020, respectively). CONCLUSIONS: Immunization rates for recommended vaccinations were very low in patients with IBD. Efforts to improve vaccination rate are needed.

¿Son útiles los marcadores serológicos ASCA y p-ANCA en la enfermedad inflamatoria intestinal? / Are useful the ASCA and p-ANCA serologic markers in inflammatory bowel disease?

Background: Several studies have suggested that Anti-Saccharomyces cerevisiae antibodies (ASCA) and perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) are useful serological markers associated with inflammatory bowel disease (IBD). However, neither the indication nor its use in clinical practice have been clearly established. Aim: to assess whether the presence of these markers have a possible diagnostic role and clinical significance. Patients and Methods: Retrospective chart review of 93 patients, average age 42 years, 48 female. ASCA and p-ANCA were determinated by ELISA and IFI. The sensitivity (S), specificity (E), positive and negative predictive values (PPV and NPV), and X2 were determinated. Results: Sixty eight patients with IBD (35 Crohn´s disease (CD), 31 ulcerative colitis (UC), one IBD unclassified and one indeterminate colitis patients) and 25 patients with other gastrointestinal diseases. In the total group of patients the S and E of ASCA and p-ANCA for diagnosis of CD and UC was 48.6 percent, 74.1 percent and 77.4 percent, 82.3 percent respectively. In patients with IBD, the presence of ASCA(+)/p-ANCA(-) had a S, E, PPV, and NPV for diagnosis of CD 37.1 percent, 93.5 percent, 86.7 percent and 56.9 percent respectively. On the other hand, the presence of ASCA(-)/p-ANCA(+) had a S, E, PPV, and NPV for diagnosis of UC 64.5 percent, 85.7 percent, 80 percent and 73.1 percent respectively. The evolution of IBD patients was not associated with the presence of these markers. Conclusions: Our study showed that both p-ANCA and ASCA did not have an important role in the differential diagnosis of CD and UC and in their prognosis. New strategies to differentiate CD and UC and to determinate their prognosis are needed.

Existen estudios que han sugerido que los anticuerpos Anti-Saccharomyces cerevisiae (ASCA) y los anticuerpos anticitoplasma de los neutrófilos perinuclear (p-ANCA), son marcadores serológicos asociados a las enfermedades inflamatorias intestinales (EII). Sin embargo, su indicación y uso en la práctica clínica no han sido aún clarificados. Objetivos: Evaluar si la presencia de estos marcadores posee algún papel en el diagnóstico y pronóstico. Pacientes y Métodos: Noventa y tres pacientes, edad promedio 42 años, 48 mujeres. Los anticuerpos ASCA fueron determinados por técnica de ELISA y los p-ANCA por IFI. Se calculó la sensibilidad (S), especificidad (E), valor predictivo positivo (VPP) y negativo (VPN) y X2. Resultados: Se incluyen sesenta y siete pacientes con EII (35 enfermedad de Crohn (EC), 31 colitis ulcerosa (CU), uno con EII no clasificable y un paciente con Colitis Indeterminada) y 25 pacientes con otras enfermedades gastrointestinales. En el grupo total de pacientes, la S y E de ASCA y p-ANCA para el diagnóstico de EC y CU fue de 48,6 y 74,1 por ciento y 77,4 y 82,3 por ciento respectivamente. En pacientes con diagnóstico establecido de EII, la presencia de ASCA(+)/p-ANCA(-) tuvo una S, E, VPP y VPN para el diagnóstico de EC 37,1, 93,5, 86,7 y 56,9 por ciento, respectivamente. Por otro lado, la presencia de ASCA(-)/p-ANCA(+) tuvo una S, E, VPP y VPN para el diagnóstico de CU 64,5, 85,7, 80 y 73,1 por ciento, respectivamente. La evolución favorable o desfavorable de los pacientes con EII (EC o CU) no se correlacionó con la presencia (positividad) de uno o ambos marcadores (p ≥ 1). Conclusiones: Nuestro estudio demostró que los marcadores serológicos ASCA y ANCA utilizados en conjunto no poseen actualmente un papel importante en la diferenciación de la EC de la CU, como tampoco para establecer un pronóstico de su evolución. Por lo tanto, es necesario encontrar nuevas estrategias para poder diferenciar estos dos cuadros y poder determinar...

[Three case of IBD or exacerbation of IBD after ovulation induction]

Ulcerative colitis [UC] and Crohn's disease [CD], collectively referred to as inflammatory bowel disease [IBD], present with different histology and cytokine profiles. While the precise mechanisms underlying the development of IBD are not known, sufficient data have been collected to suggest that it results from a complex interplay of genetic, environmental, and immunologic factors. An inappropriate mucosal immune response to normal intestinal constituents is a key feature, leading to an imbalance in local pro- and anti-inflammatory cytokines. Neutrophil and monocyte influx occurs with subsequent secretion of oxygen radicals and enzymes, leading to tissue damage. Here we report three patients with sever symptom of IBD after ovarian stimulation. Cytokine profile after ovarian stimulation may contribute to the altered intestinal permeability due to increase in systemic inflammatory cytokines and neutrophil or macrophage activation. In our hypothesis ovulation induction can induce inflammation in intestinal mucosa or exacerbate previous IBD by different cytokines

Small intestinal inflammation following oral infection with Toxoplasma gondii does not occur exclusively in C57BL/6 mice: review of 70 reports from the literature

Small intestinal immunopathology following oral infection with tissue cysts of Toxoplasma gondii has been described in C57BL/6 mice. Seven days after infection, mice develop severe small intestinal necrosis and succumb to infection. The immunopathology is mediated by local overproduction of Th1-type cytokines, a so-called "cytokine storm". The immunopathogenesis of this pathology resembles that of inflammatory bowel disease in humans, i.e., Crohn's disease. In this review, we show that the development of intestinal pathology following oral ingestion of T. gondii is not limited to C57BL/6 mice, but frequently occurs in nature. Using a Pubmed search, we identified 70 publications that report the development of gastrointestinal inflammation following infection with T. gondii in 63 animal species. Of these publications, 53 reports are on accidental ingestion of T. gondii in 49 different animal species and 17 reports are on experimental infections in 19 different animal species. Thus, oral infection with T. gondii appears to cause immunopathology in a large number of animal species in addition to mice. This manuscript reviews the common features of small intestinal immunopathology in the animal kingdom and speculates on consequences of this immunopathology for humankind.

Enfermedad inflamatoria intestinal: Una mirada inmunológica: [revisión] / Inflammatory bowel diseases: An immunological approach: [review]

Inflammatory bowel diseases (IBD) are inflammatory diseases with a multifactorial component that involve the intestinal tract. The two relevant IBD syndromes are Crohn's disease (CD) and ulcerative colitis (UC). One factor involved in IBD development is a genetic predisposition, associated to NOD2/CARD15 and Toll-like receptor 4 (TLR4) polymorphisms that might favor infectious enterocolitis that is possibly associated to the development of IBD. The identification of specific immunologic alterations in IBD and their relationship to the etiology of the disease is a relevant research topic. The role of intra and extracellular molecules, such as transcription factors and cytokines that are involved in the inflammatory response, needs to be understood. The relevance of immunologic molecules that might drive the immune response to a T helper (Th) 1, Th 2 or the recently described Th 17 phenotype, has been demonstrated in animal models and clinical studies with IBD patients. CD and UC predominantly behave with a Th 1 and Th 2 immune phenotype, respectively. Recently, an association between CD and Th 17 has been reported. The knowledge acquired from immunologic and molecular research will help to develop accurate diagnostic methods and efficient therapies.

Good bug, bad bug: in the case of enteric inflammatory disease does the epithelium decide?

Many studies demonstrate that intestinal inflammation is either initiated or exaggerated by a component of the normal microbiota, most likely commensal bacteria or products derived from these organisms. We review the nature of human inflammatory bowel disease, the evidence for the involvement of the normal bacterial flora in these disorders and the relevance of maintaining the integrity of the epithelial barrier. Moreover, we, and others, have shown abnormal mitochondria structure in tissue resections from patients with inflammatory bowel disease and tissues from rodents that demonstrated psychological stress-induced increases in epithelial permeability. Thus, we also consider the possibility that a defect in epithelial mitochondrial function would predispose an individual to respond to their commensal bacteria flora - no longer considering them as a beneficial passive inhabitant, but rather perceiving them as a threatening and pro-inflammatory stimulus. In support of this postulate, we discuss our recent findings from an in vitro model showing that the human colon-derived T84 cell line exposed to the metabolic stressor, dinitrophenol, and the non-pathogenic, non-invasive, Escherichia coli (strain HB101) display a loss of barrier function, increased signal transduction and increased production of the chemokine, interleukin 8.

Alteraciones inmunológicas humorales en las enfermedades inflamatorias del colon / Inmunological alterations in inflamatory bowel diseases

Se presentan los hallazgos inmunológicos humorales en 18 casos de colitis ulcerosa (CU) y dos con Enfermedad de Crohn (EC). La duración de la enfermedad en el grupo estudiado fue de 3 meses a cinco años. Quince eran hispanos y cinco de origen europeo. Diez pertenecían a cada sexo y tuvieron edad media de 38 años. Todos poseían activa la enfermedad, demostrada con colonoscopia y biopsias múltiples, en el momento de incluirlos en el protocolo de investigación. Alteración de laguna de las inmunoglobulinas estudiadas (IgA, IgG e IgM) se observó en 13 pacientes y valores normales en los otros siete. IgA elevada en 11 (cifra promedio de 332,45 mg por ciento ), normal en 7 disminuida en dos. IgG estuvo aumentada en dos, decrecida en uno y normal en 17 casos. La IgM se vio incrementada en 5 y normal en el resto. En 12 casos donde se determinó la IgA secretoria en saliva, se encontró presente. Anticuerpos antinucleares se estudiaron en 8 y fueron todos negativos. Antimúsculo liso se investigó en 15, con tres positivos, Antimitocondria se encontró positivo en uno y negativo en trece. CH50 estuvo disminuido en 2 de 11 estudiados, C3 con valores inferiores a lo normal en 3 de 4 investigados y C4 en 2 de 4 analizados. No hubo correlación entre las alteraciones de las inmunoglobulinas y la edad, sexo, tipo o extensión de la enfermedad, duración y tratamiento recibido. Tampoco se consiguió correlación entre los valores bajos de complemento en algunos casos, la positividad de autoanticuerpos y los parámetros clínicos antes mencionados. Concluimos afirmando que la mayor parte de nuestros enfermos con EII, tienen alteración cuantitativa del compartimiento humoral. Por lo tanto, consideramos necesario el estudio inmunológico en las personas portadoras de dichas enfermedades y hacer un seguimiento futuro, para poder evaluar el verdadero significado de los hallazgos mencionados