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1.
United European Gastroenterol J ; 12(6): 737-748, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38366868

RESUMO

BACKGROUND: The pathobiology of the non-destructive inflammatory bowel disease (IBD) lymphocytic colitis (LC) is poorly understood. We aimed to define an LC-specific mucosal transcriptome to gain insight into LC pathology, identify unique genomic signatures, and uncover potentially druggable disease pathways. METHODS: We performed bulk RNA-sequencing of LC and collagenous colitis (CC) colonic mucosa from patients with active disease, and healthy controls (n = 4-10 per cohort). Differential gene expression was analyzed by gene-set enrichment and deconvolution analyses to identify pathologically relevant pathways and cells, respectively, altered in LC. Key findings were validated using reverse transcription quantitative PCR and/or immunohistochemistry. Finally, we compared our data with a previous cohort of ulcerative colitis and Crohn's disease patients (n = 4 per group) to distinguish non-destructive from classic IBD. RESULTS: LC can be subdivided into channelopathic LC, which is governed by organic acid and ion transport dysregulation, and inflammatory LC, which is driven by microbial immune responses. Inflammatory LC displays an innate and adaptive immunity that is limited compared to CC and classic IBD. Conversely, we noted a distinct induction of regulatory non-coding RNA species in inflammatory LC samples. Moreover, compared with CC, water channel and cell adhesion molecule gene expression decreased in channelopathic LC, whereas it was accentuated in inflammatory LC and associated with reduced intestinal epithelial cell proliferation. CONCLUSIONS: We conclude that LC can be subdivided into channelopathic LC and inflammatory LC that could be pathomechanistically distinct subtypes despite their shared clinical presentation. Inflammatory LC exhibits a dampened immune response compared to CC and classic IBDs. Our results point to regulatory micro-RNAs as a potential disease-specific feature that may be amenable to therapeutic intervention.


Assuntos
Colite Linfocítica , Mucosa Intestinal , Humanos , Colite Linfocítica/genética , Colite Linfocítica/imunologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Mucosa Intestinal/metabolismo , Transcriptoma , Feminino , Colite Colagenosa/imunologia , Colite Colagenosa/genética , Colite Colagenosa/patologia , Colite Colagenosa/diagnóstico , Doença de Crohn/imunologia , Doença de Crohn/genética , Doença de Crohn/patologia , Doença de Crohn/diagnóstico , Masculino , Colo/imunologia , Colo/patologia , Pessoa de Meia-Idade , Estudos de Casos e Controles , Perfilação da Expressão Gênica , Colite Ulcerativa/imunologia , Colite Ulcerativa/genética , Colite Ulcerativa/patologia , Colite Ulcerativa/diagnóstico , Adulto
2.
J Crohns Colitis ; 16(1): 49-56, 2022 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-34232280

RESUMO

OBJECTIVE: Microscopic colitis [MC], encompassing collagenous colitis [CC] and lymphocytic colitis [LC], is an increasingly prevalent gastrointestinal disease with an unknown aetiology. Previous research has reported significant differences in the incidence of MC within Denmark, with the lowest incidence found in the most populated region [Capital Region of Denmark]. Our aim was to elucidate the causes of these regional differences. DESIGN: All incident MC patients [n = 14 302] with a recorded diagnosis of CC [n = 8437] or LC [n = 5865] entered in The Danish Pathology Register between 2001 and 2016 were matched to 10 reference individuals [n = 142 481]. Information regarding drug exposure, including proton pump inhibitors [PPIs], selective serotonin reuptake inhibitors [SSRIs], statins, and nonsteroidal anti-inflammatory drugs [NSAIDs], were retrieved from The Danish National Prescription Registry. Information regarding endoscopy rate, smoking-related diseases, and immune-mediated inflammatory diseases were acquired from The Danish National Patient Registry. RESULTS: Smoking, immune-mediated inflammatory diseases, exposure to PPIs, SSRIs, statins, and NSAIDs were significantly associated with MC in all Danish regions. The association between drug exposure and MC was weakest in the Capital Region of Denmark with an odds ratio of 1.8 (95% confidence interval [CI]: 1.61-2.01). The relative risk of undergoing a colonoscopy with biopsy was significantly increased in sex- and age-matched controls in all regions compared with controls from the Capital Region of Denmark, with the greatest risk found in the Region of Southern Denmark, 1.37 [95% CI: 1.26-1.50]. CONCLUSIONS: The cause of the regional differences in MC incidence in Denmark seems to be multifactorial, including variations in disease awareness and distribution of risk factors.


Assuntos
Colite Microscópica/diagnóstico , Colite Microscópica/epidemiologia , Colonoscopia/estatística & dados numéricos , Idoso , Estudos de Casos e Controles , Dinamarca/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Sistema de Registros , Fatores de Risco
3.
Front Med (Lausanne) ; 8: 727412, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722568

RESUMO

Introduction: Microscopic colitis (MC) is an inflammatory bowel condition with two subtypes, lymphocytic colitis (LC) and collagenous colitis (CC). Unlike patients with ulcerative colitis (UC) and non-inflamed individuals, MC patients have reduced risk of developing colorectal cancer, possibly due to increased immune surveillance in MC patients. Aim: To examine differences in levels of immunomodulatory molecules, including those involved in immune checkpoint mechanisms, in sera from patients with MC and in colonic biopsies from patients with MC and UC compared with controls. Methods: Using Luminex, 23 analytes (4-1BB, 4-1BBL, APRIL, BAFF, BTLA, CD27, CD28, CD80, CTLA-4, E-cadherin, Galectin-3, GITR, HVEM, IDO, IL-2Rα, LAG-3, MICA, MICB, PD-1, PD-L1, PD-L2, sCD40L and TIM-3) were studied in serum from patients with active MC (n = 35) and controls (n = 23), and in colonic biopsies from patients with active LC (n = 9), active CC (n = 16) and MC in histological remission (LC n = 6, CC n = 6), active UC (n = 15) and UC in remission (n = 12) and controls (n = 58). Results: In serum, IDO, PD-1, TIM-3, 4-1BB, CD27, and CD80 were decreased whereas 4-1BBL and IL-2Rα were increased in MC patients compared with controls. In contrast, in biopsies, levels of PD-L2 and 4-1BB were increased in MC and UC patients with active disease. Furthermore, in biopsies from CC and UC but not LC patients with active disease, CTLA-4, PD-1, APRIL, BAFF, and IL-2Rα were increased compared with controls. PD-L1 was increased in CC but not UC or LC patients. CD27 and TIM-3 were decreased in biopsies from MC patients in comparison to controls whereas levels of MICB were decreased in patients with active UC compared with controls. Conclusions: Compared with non-inflamed controls, levels of soluble and membrane-bound immunomodulatory molecules were systemically and locally altered in MC and UC patients, with most analytes being decreased in serum but enhanced in colonic biopsies. These findings contribute to knowledge about checkpoint molecules and their role as biomarkers in MC and may also contribute to knowledge about possible mechanisms behind the seemingly protective effects of MC against colorectal cancer.

4.
J Gastroenterol ; 56(10): 914-927, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34414506

RESUMO

BACKGROUND: Collagenous colitis (CC) is an inflammatory bowel disease where chronic diarrhoea is the main symptom. Diagnostic markers distinguishing between CC and other causes of chronic diarrhoea remain elusive. This study explores neutrophil gelatinase-associated lipocalin (NGAL) and its mRNA lipocalin2 (LCN2) as histological and faecal disease markers in CC. METHODS: NGAL/LCN2 were studied in colonic biopsies from CC patients before and during budesonide treatment using RNA sequencing (n = 9/group), in situ hybridization (ISH) (n = 13-22/group) and immunohistochemistry (IHC) (n = 14-25/group). Faecal samples from CC (n = 3-28/group), irritable bowel syndrome diarrhoea (IBS-D) (n = 14) and healthy controls (HC) (n = 15) were assayed for NGAL and calprotectin. RESULTS: NGAL/LCN2 protein and mRNA expression were upregulated in active CC vs HC, and vs paired samples of treated CC in clinical remission. IHC and ISH localized increased NGAL/LCN2 mainly to epithelium of active CC, compared to almost absence in HC and treated CC. In contrast, calprotectin was solely expressed in immune cells. Despite great individual differences, faecal NGAL was significantly increased in active CC compared to HC, IBS-D and treated CC and had high test sensitivity. Faecal calprotectin levels were variably increased in active CC, but the values remained below usual clinical cut-offs. CONCLUSION: NGAL/LCN2 is upregulated in the epithelium of active CC and reduced during budesonide-induced clinical remission to the level of HC and IBD-S. This was reflected in NGAL faecal concentrations. We propose NGAL as an IHC marker for disease activity in CC and a potential faecal biomarker discriminating CC from HC and IBS-D.


Assuntos
Biomarcadores/análise , Colite Colagenosa/diagnóstico , Lipocalina-2/análise , Adulto , China/epidemiologia , Colite Colagenosa/sangue , Colite Colagenosa/epidemiologia , Ensaio de Imunoadsorção Enzimática/métodos , Fezes/enzimologia , Fezes/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
5.
J Crohns Colitis ; 15(4): 594-602, 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33049029

RESUMO

BACKGROUND AND AIMS: The disease course of microscopic colitis [MC], encompassing collagenous colitis [CC] and lymphocytic colitis [LC], is not well known. In a Danish nationwide cohort, we evaluated the disease activity patterns as well as the risk of colorectal cancer [CRC] and mortality based on disease severity. METHODS: All incident MC patients [n = 14 302] with a recorded diagnosis of CC [n = 8437] or LC [n = 5865] in the Danish Pathology Register, entered between 2001 and 2016, were matched to 10 reference individuals [n = 142 481]. Incident cases of CRC after the index date were captured from the Danish Cancer Registry. Mortality data were ascertained from the Danish Registry of Causes of Death, and information about treatment was obtained from the Danish National Prescription Registry. The risk of CRC and mortality analyses were investigated by Cox regression and Kaplan-Meier estimates. RESULTS: We identified a self-limiting or transient disease course in 70.6% of LC patients and in 59.9% of CC patients, p <0.001. Less than 5% of MC patients experienced a budesonide-refractory disease course and were treated with immunomodulators or biologic treatment. A total of 2926 [20.5%] MC patients and 24 632 [17.3%] reference individuals died during the study period. MC patients with a severe disease had a relative risk [RR] of mortality of 1.41 (95% confidence interval [CI]: 1.32-1.50) compared with reference individuals. Only 90 MC patients were diagnosed with CRC during follow-up, corresponding to an RR of 0.48 [95% CI: 0.39-0.60]. CONCLUSIONS: A majority of MC patients experience an indolent disease course with a lower risk of developing CRC compared with the background population.


Assuntos
Colite Microscópica/epidemiologia , Neoplasias Colorretais/epidemiologia , Idoso , Estudos de Coortes , Colite Microscópica/mortalidade , Neoplasias Colorretais/mortalidade , Dinamarca/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Risco , Índice de Gravidade de Doença
6.
Int J Colorectal Dis ; 36(1): 151-159, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32920702

RESUMO

PURPOSE: The diagnosis microscopic colitis (MC) consisting of collagenous colitis (CC) and lymphocytic colitis (LC) relies on histological assessment of mucosal biopsies from the colon. The optimal biopsy strategy for reliable diagnosis of MC is controversial. The aim of this study was to evaluate the distribution of histopathological features of MC throughout the colon. METHODS: Mucosal biopsies from multiple colonic segments of patients with MC who participated in one of the three prospective European multicenter trials were analyzed. Histological slides were stained with hematoxylin-and-eosin, a connective tissue stain, and CD3 in selected cases. RESULTS: In total, 255 patients were included, 199 and 56 patients with CC and LC, respectively. Both groups exhibited a gradient with more pronounced inflammation in the lamina propria in the proximal colon compared with the distal colon. Similarly, the thickness of the subepithelial collagenous band in CC showed a gradient with higher values in the proximal colon. The mean number of intraepithelial lymphocytes was > 20 in all colonic segments in patients within both subgroups. Biopsies from 86 to 94% of individual segments were diagnostic, rectum excluded. Biopsies from non-diagnostic segments often showed features of another subgroup of MC. CONCLUSION: Conclusively, although the severity of the histological changes in MC differed in the colonic mucosa, the minimum criteria required for the diagnosis were present in the random biopsies from the majority of segments. Thus, our findings show MC to be a pancolitis, rectum excluded, questioning previously proclaimed patchiness throughout the colon.


Assuntos
Colite Colagenosa , Colite Microscópica , Colite , Biópsia , Colo , Humanos , Estudos Prospectivos
7.
Frontline Gastroenterol ; 11(3): 228-234, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32419914

RESUMO

Microscopic colitis (MC) is a treatable cause of chronic, non-bloody, watery diarrhoea, but physicians (particularly in primary care) are less familiar with MC than with other causes of chronic diarrhoea. The colon in patients with MC is usually macroscopically normal. MC can only be diagnosed by histological examination of colonic biopsies (subepithelial collagen band >10 µm (collagenous colitis) or >20 intraepithelial lymphocytes per 100 epithelial cells (lymphocytic colitis), both with lamina propria inflammation). The UK National Health Service exerts downward pressure to minimise colonoscopy referrals. Furthermore, biopsies are often not taken according to guidelines. These factors work against MC diagnosis. In this review, we note the high incidence of MC (comparable to ulcerative colitis and Crohn's disease) and its symptomatic overlap with irritable bowel syndrome. We also highlight problems with the recommendation by National Health Service/National Institute for Health and Care Excellence guidelines for inflammatory bowel diseases that colonoscopy referrals should be based on a faecal calprotectin level of ≥100 µg/g. Faecal calprotectin is <100 µg/g in over half of individuals with active MC, building into the system a propensity to misdiagnose MC as irritable bowel syndrome. This raises important questions-how many patients with MC have already been misdiagnosed, and how do we address this silent burden? Clarity is needed around pathways for MC management; MC is poorly acknowledged by the UK healthcare system and it is unlikely that best practices are being followed adequately. There is an opportunity to identify and treat patients with MC more effectively.

8.
J Crohns Colitis ; 14(7): 962-973, 2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-32016376

RESUMO

BACKGROUND AND AIMS: Diarrhoea is a common, debilitating symptom of gastrointestinal disorders. Pathomechanisms probably involve defects in trans-epithelial water transport, but the role of aquaporin [AQP] family water channels in diarrhoea-predominant diseases is unknown. We investigated the involvement of AQPs in the pathobiology of collagenous colitis [CC], which features chronic, watery diarrhoea despite overtly normal intestinal epithelial cells [IECs]. METHODS: We assessed the expression of all AQP family members in mucosal samples of CC patients before and during treatment with the corticosteroid drug budesonide, steroid-refractory CC patients and healthy controls. Samples were analysed by genome-wide mRNA sequencing [RNA-seq] and quantitative real-time PCR [qPCR]. In some patients, we performed tissue microdissection followed by RNA-seq to explore the IEC-specific CC transcriptome. We determined changes in the protein levels of the lead candidates in IEC by confocal microscopy. Finally, we investigated the regulation of AQP expression by corticosteroids in model cell lines. RESULTS: Using qPCR and RNA-seq, we identified loss of AQP8 expression as a hallmark of active CC, which was reverted by budesonide treatment in steroid-responsive but not refractory patients. Consistently, decreased AQP8 mRNA and protein levels were observed in IECs of patients with active CC, and steroid drugs increased AQP8 expression in model IECs. Moreover, low APQ8 expression was strongly associated with higher stool frequency in CC patients. CONCLUSION: Down-regulation of epithelial AQP8 may impair water resorption in active CC, resulting in watery diarrhoea. Our results suggest that AQP8 is a potential drug target for the treatment of diarrhoeal disorders.


Assuntos
Aquaporinas/genética , Aquaporinas/metabolismo , Colite Colagenosa/genética , Colite Colagenosa/metabolismo , Diarreia/genética , Diarreia/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Aquaporina 1/genética , Budesonida/farmacologia , Budesonida/uso terapêutico , Células CACO-2 , Colite Colagenosa/complicações , Colite Colagenosa/tratamento farmacológico , Dexametasona/farmacologia , Diarreia/etiologia , Regulação para Baixo/efeitos dos fármacos , Células Epiteliais/metabolismo , Feminino , Células HT29 , Homeostase , Humanos , Mucosa Intestinal/metabolismo , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/metabolismo , Água/metabolismo
9.
United European Gastroenterol J ; 7(9): 1234-1240, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31700636

RESUMO

Background: Microscopic colitis is an inflammatory bowel disease that causes chronic, watery diarrhoea. Microscopic colitis is usually effectively treated with budesonide, but some patients are refractory. Data on alternative treatments are sparse. Aims: The purpose of this study was to retrospectively evaluate outcome of microscopic colitis patients receiving anti-tumour necrosis factor therapy at our centre. Methods: Treatment results, including side effects, for all microscopic colitis patients receiving anti-tumour necrosis factor therapy were registered at week 12 and at end of follow-up. Clinical remission was defined as a mean of <3 stools and <1 watery stools/day/week and clinical response as a 50% reduction of mean stool frequency/day/week. Induction and maintenance treatment was either adalimumab or infliximab. Results: The study cohort comprised 18 patients; mean age at diagnosis was 47 years (range 19-77). Ten and eight patients, respectively, received adalimumab and infliximab as first-line anti-tumour necrosis factor; seven patients received second-line anti-tumour necrosis factor due to non-response, loss of response or side effects. At week 12, 9/18 patients had achieved remission, 6/18 were responders and 3/18 were non-responders. Of the nine remission patients, 3/18 (16%) had long-lasting clinical remission post-induction therapy alone. Five patients (28%) (one first-line, four second-line anti-tumour necrosis factor) were in remission and one patient (6%) responded to maintenance treatment; follow-up was mean 22 (range 4-60) months. Six patients (33%) had minor, reversible side effects. Conclusions: Over half of budesonide-refractory microscopic colitis patients can achieve clinical remission or response on anti-tumour necrosis factor agents. Prospective studies are mandatory to evaluate the efficacy and safety of anti-tumour necrosis factor treatments in budesonide-refractory microscopic colitis.


Assuntos
Adalimumab/uso terapêutico , Colite Microscópica/tratamento farmacológico , Infliximab/uso terapêutico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Budesonida/uso terapêutico , Feminino , Glucocorticoides/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Falha de Tratamento , Resultado do Tratamento , Adulto Jovem
10.
J Clin Med ; 8(11)2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31718057

RESUMO

Data on malignancy in patients with collagenous colitis (CC) is scarce. We aimed to determine the incidence of cancers in patients with CC. In a two-stages, observational study, data on cancers in patients diagnosed with CC during 2000-2015, were collected from two cohorts. The risk was calculated according to the age-standardized rate for the first cohort and according to the standardized incidence ratio for the second cohort. The first cohort comprised 738 patients (394 from Scotland and 344 from Sweden; mean age 71 ± 11 and 66 ± 13 years, respectively). The incidence rates for lung cancer (RR 3.9, p = 0.001), bladder cancer (RR 9.2, p = 0.019), and non-melanoma skin cancer (NMSC) (RR 15, p = 0.001) were increased. As the majority of NMSC cases (15/16) came from Sweden, a second Swedish cohort, comprising 1141 patients (863 women, mean age 65 years, range 20-95 years) was collected. There were 93 cancer cases (besides NMSC). The risk for colon cancer was decreased (SIR 0.23, p= 0.0087). The risk for cutaneous squamous cell carcinoma was instead markedly increased (SIR 3.27, p = 0.001).

11.
Lancet Gastroenterol Hepatol ; 4(4): 305-314, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30860066

RESUMO

Microscopic colitis is a chronic inflammatory disease of the colon that frequently causes chronic watery diarrhoea that might be accompanied by abdominal pain, nocturnal diarrhoea, urgency, and faecal incontinence. These symptoms lead to poor quality of life and increased health-care costs. Diagnosis relies on histological examination of multiple biopsy samples from the colonic mucosa, which often show no or only few abnormalities on endoscopy. Two major histological subtypes can be distinguished-collagenous colitis and lymphocytic colitis-but incomplete and variant forms with fewer characteristic features have been reported. Here we summarise the latest evidence on epidemiology, pathogenesis, and risk factors, and discuss established and novel therapeutic options for clinical remission. Finally, we propose an updated treatment algorithm. Further prospective studies are needed to clarify the natural history of microscopic colitis, supported by validated criteria for the assessment of disease activity.


Assuntos
Colite Microscópica/patologia , Colite Microscópica/fisiopatologia , Colo/patologia , Mucosa Intestinal/patologia , Dor Abdominal/etiologia , Idoso , Anti-Inflamatórios/uso terapêutico , Budesonida/uso terapêutico , Colite Microscópica/epidemiologia , Colite Microscópica/terapia , Diarreia/etiologia , Endoscopia/métodos , Incontinência Fecal/etiologia , Feminino , Custos de Cuidados de Saúde/estatística & dados numéricos , Humanos , Fatores Imunológicos/uso terapêutico , Incidência , Mucosa Intestinal/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Qualidade de Vida/psicologia , Indução de Remissão/métodos , Fatores de Risco
12.
J Crohns Colitis ; 13(3): 337-340, 2019 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-30329034

RESUMO

BACKGROUND: Evidence for second-line therapy in patients with microscopic colitis [MC] failing budesonide is scarce, although anti-tumour necrosis factors [anti-TNFs], methotrexate and azathioprine have been reported to be effective in small cohort studies. Vedolizumab, a monoclonal antibody targeting α4ß7-integrin, prevents homing of T-cells to the gut. We evaluated clinical remission with vedolizumab in budesonide-refractory MC patients. METHODS: We solicited gastroenterologists in Europe and Canada for cases of MC treated with vedolizumab. Vedolizumab 300 mg IV was administered at weeks 0, 2 and 6, and then every 8 weeks. Clinical remission and histological remission were defined as less than three stools per day and normalization of histology, respectively, after induction treatment. RESULTS: Eleven cases were retrieved (nine females, lymphocytic colitis [LC] n = 5, collagenous colitis [CC] n = 6). Median [interquartile range] disease duration at vedolizumab initiation was 51 [29-70] months. Nine of 11 patients had failed one immunosuppressant and ten of 11 at least one anti-TNF agent. After three infusions of vedolizumab, clinical remission was observed in 5/11 patients [two LC and three CC] of whom three remained well with maintenance therapy [median duration of 13 months]. Biopsies were obtained from 9/11 patients. Histological remission was observed in 3/4 patients with clinical remission [2/3 CC, 1/1 LC] and 0/5 patients without clinical improvement. CONCLUSION: In a series of highly refractory MC patients, vedolizumab induced clinical remission in 5/11 subjects, of whom 75% showed normalized histology. Larger randomized trials are needed to assess the efficacy of vedolizumab in patients with MC.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Colite Colagenosa/tratamento farmacológico , Colite Colagenosa/patologia , Colite Linfocítica/tratamento farmacológico , Colite Linfocítica/patologia , Fármacos Gastrointestinais/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Budesonida/uso terapêutico , Canadá , Europa (Continente) , Feminino , Humanos , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Retratamento , Estudos Retrospectivos
13.
Scand J Gastroenterol ; 53(4): 410-416, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29546806

RESUMO

OBJECTIVES: Onset of microscopic colitis (MC) in patients with ulcerative colitis (UC) or Crohn's disease (CD), or vice versa, has been reported occasionally but the subject is not well described. We therefore report a retrospective observational study of such patients and review the literature. METHODS: Forty-six Swedish gastroenterology clinics were contacted about patients with diagnoses of both inflammatory bowel disease (IBD) and MC. Publications were searched on PubMed. RESULTS: We identified 31 patients with onset of MC after a median (range) of 20 (2-52) years after diagnosis of IBD, or vice versa; 21 UC patients developed collagenous colitis (CC) (n = 16) or lymphocytic colitis (LC) (n = 5); nine CD patients developed CC (n = 5) or LC (n = 4); one CC patient developed CD. Of the 21 UC patients, 18 had extensive disease, whereas no consistent phenotype occurred in CD. Literature review revealed 27 comprehensive case reports of patients with diagnoses of both IBD and MC. Thirteen MC patients developed IBD, of which four required colectomy. Fourteen IBD patients later developed MC. There were incomplete clinical data in 115 additional reported patients. CONCLUSIONS: Altogether 173 patients with occurrence of both IBD and MC were found. The most common finding in our patients was onset of CC in a patient with UC. Although these are likely random associations of two different disorders, MC should be considered in the patient with UC or CD if there is onset of chronic watery diarrhoea without endoscopic relapse of IBD.


Assuntos
Colite Colagenosa/epidemiologia , Colite Linfocítica/epidemiologia , Colite Ulcerativa/complicações , Doença de Crohn/complicações , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Suécia , Adulto Jovem
14.
Scand J Gastroenterol ; 53(12): 1469-1475, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30600733

RESUMO

OBJECTIVE: Microscopic colitis (MC), encompassing collagenous colitis (CC) and lymphocytic colitis (LC), is a diagnosis which relies on histopathologic criteria. This report examines the validity of having a diagnosis of MC in Swedish pathology registers. METHODS: We reviewed patient charts from 215 randomly selected individuals from 15 pathology departments in five healthcare regions in Sweden with a relevant histopathology code for MC on colon biopsies. Information on clinical symptoms and laboratory data were obtained from medical chart review. We obtained sufficient data on 211 individuals for calculating positive predictive values (PPVs) for MC. RESULTS: In total, 200/211 patients with a histopathology diagnosis of MC were confirmed as also having a clinical diagnosis of MC after chart review, yielding a PPV of 95% (95%CI =91-97%). The PPV for CC was 95% (95%CI =87-98%) and 85% for LC (95%CI =78-90%). The median age at biopsy was 67 years (range 17-90 years), and 72% (n = 154) were women. The most common symptoms in patients with MC histopathology were diarrhea (96% of patients), weight loss (24%) and abdominal pain (13%). Four percent (4/111) of patients with available data on stool culture were positive for gastrointestinal pathogens (none had Clostridium difficile). In 81 patients with available celiac serology, five (6%) were positive. Twenty-six percent of all patients had at least one other autoimmune disease, the most frequent being hypothyroidism (8%) and celiac disease (6%). CONCLUSIONS: This study found a high validity for MC as recorded in Swedish pathology registers.


Assuntos
Colite Microscópica/diagnóstico , Colite Microscópica/patologia , Colo/patologia , Dor Abdominal/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Colite Microscópica/classificação , Colonoscopia , Diarreia/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Sistema de Registros , Suécia , Redução de Peso , Adulto Jovem
15.
Biochem Med (Zagreb) ; 27(1): 217-224, 2017 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-28392742

RESUMO

INTRODUCTION: The aim of this study was to assess pneumatic tube system (PTS) alteration on platelet function by the light transmission aggregometry (LTA) and whole blood aggregometry (WBA) method, and on the results of platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen. MATERIALS AND METHODS: Venous blood was collected into six 4.5 mL VACUETTE® 9NC coagulation sodium citrate 3.8% tubes (Greiner Bio-One International GmbH, Kremsmünster, Austria) from 49 intensive care unit (ICU) patients on dual anti-platelet therapy and immediately hand carried to the central laboratory. Blood samples were divided into 2 Groups: Group 1 samples (N = 49) underwent PTS (4 m/s) transport from the central laboratory to the distant laboratory and back to the central laboratory, whereas Group 2 samples (N = 49) were excluded from PTS forces. In both groups, LTA and WBA stimulated with collagen, adenosine-5'-diphosphate (ADP), arachidonic acid (AA) and thrombin-receptor-activated-peptide 6 (TRAP-6) as well as platelet count, PT, APTT, and fibrinogen were performed. RESULTS: No statistically significant differences were observed between blood samples with (Group 1) and without (Group 2) PTS transport (P values from 0.064 - 0.968). The AA-induced LTA (bias: 68.57%) exceeded the bias acceptance limit of ≤ 25%. CONCLUSIONS: Blood sample transportation with computer controlled PTS in our hospital had no statistically significant effects on platelet aggregation determined in patients with anti-platelet therapy. Although AA induced LTA showed a significant bias, the diagnostic accuracy was not influenced.


Assuntos
Coleta de Amostras Sanguíneas/instrumentação , Tempo de Tromboplastina Parcial , Inibidores da Agregação Plaquetária/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Testes de Função Plaquetária/métodos , Tempo de Protrombina , Meios de Transporte/métodos , Idoso , Idoso de 80 Anos ou mais , Coagulação Sanguínea/efeitos dos fármacos , Plaquetas/efeitos dos fármacos , Coleta de Amostras Sanguíneas/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ativação Plaquetária/efeitos dos fármacos , Contagem de Plaquetas , Meios de Transporte/instrumentação
16.
J Crohns Colitis ; 10(4): 449-54, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26721941

RESUMO

BACKGROUND: The relationship between clinical and histological parameters in collagenous colitis (CC) is poorly understood. Smoking is a risk factor for CC, whereas its impact on clinical activity and outcome is not well known. METHODS: In a post hoc analysis of pooled data from two randomized controlled trials we assessed the association between demographic data (gender, age, smoking habits, family history of inflammatory bowel disease), clinical variables (duration of symptoms, mean number of stools/watery stools per day, abdominal pain, clinical remission) and histological data (thickness of the collagen band, inflammation of the lamina propria, total numbers of intraepithelial lymphocytes, degeneration). Moreover, we analysed the predictive value of baseline parameters for clinical outcome in a logistic regression model. RESULTS: Pooled data were available from 202 patients with active CC, of whom 36% were current smokers, 29% former smokers and 35% non-smokers. Smoking status was associated with decreased ability to achieve clinical remission (current smokers vs non-smokers: odds ratio [OR] 0.31, 95% confidence interval [CI] 0.10-0.98, p = 0.045; former smokers vs non-smokers: OR 0.19, 95% CI 0.05-0.73, p = 0.016). Current smokers had an increased mean number of watery stools at baseline compared with non-smokers (p = 0.051) and increased mean number of watery stools per se was associated with decreased likelihood of obtaining clinical remission (OR 0.63, 95% CI 0.47-0.86, p = 0.003). Patient characteristics and histology at baseline had no association with clinical parameters and no predictive value for clinical outcome. CONCLUSION: Smoking worsens clinical symptoms in CC and is associated with an increased number of watery stools and decreased likelihood of achieving clinical remission. There is no significant association between histology and clinical data.


Assuntos
Colite Colagenosa/etiologia , Fumar/efeitos adversos , Idoso , Budesonida/uso terapêutico , Colite Colagenosa/diagnóstico , Colite Colagenosa/tratamento farmacológico , Colite Colagenosa/patologia , Colo/patologia , Feminino , Fármacos Gastrointestinais/uso terapêutico , Humanos , Masculino , Mesalamina/uso terapêutico , Pessoa de Meia-Idade , Prognóstico , Indução de Remissão , Resultado do Tratamento
17.
World J Gastroenterol ; 21(19): 6065-71, 2015 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-26019474

RESUMO

In this case report, we examined the levels of cytokines expressed before and during fecal stream diversion and after intestinal continuity was restored in a patient with collagenous colitis. We report the case of a 46-year-old woman with chronic, active collagenous colitis who either failed to achieve clinical remission or experienced adverse effects with the following drugs: loperamide, cholestyramine, budesonide, methotrexate and adalimumab. Due to the intractable nature of the disease and because the patient was having up to 15 watery bowel movements per day, she underwent a temporary ileostomy. Colonic biopsies were analyzed for mucosal cytokine protein levels before and during fecal stream diversion and after intestinal continuity was restored. Mucosal protein levels of interleukin (IL)-1ß, IL-2, IL-6, IL-12, IL-17 A, IL-23, TNF, IFN-γ, IL-4, IL-5, IL-10 and IL-13 were all higher during active disease and decreased to non-detectable or considerably lower levels during fecal stream diversion. One month after the restoration of bowel continuity, when the patient experienced a relapse of symptoms, IL-2, IL-23 and IL-21 levels were again increased. Our results indicate that fecal stream diversion in this patient suppressed the levels of all cytokines analyzed in colonic biopsies. With the recurrence of clinical symptoms and histological changes after bowel reconstruction, the levels of primarily proinflammatory cytokines increased. Our findings support the hypothesis that a luminal factor triggers the inflammation observed in collagenous colitis.


Assuntos
Colite Colagenosa/cirurgia , Colo/metabolismo , Citocinas/metabolismo , Ileostomia , Mediadores da Inflamação/metabolismo , Mucosa Intestinal/metabolismo , Biomarcadores/metabolismo , Biópsia , Colite Colagenosa/diagnóstico , Colite Colagenosa/imunologia , Colite Colagenosa/metabolismo , Colo/imunologia , Feminino , Humanos , Mucosa Intestinal/imunologia , Pessoa de Meia-Idade , Recidiva , Indução de Remissão , Fatores de Tempo , Resultado do Tratamento
18.
Dig Dis ; 33(2): 208-214, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25925924

RESUMO

Microscopic colitis (MC) is the common denominator for lymphocytic and collagenous colitis (CC). It is now recognized as a relatively frequent cause of diarrhea that equals the prevalence of inflammatory bowel disease. Patients are typically middle-aged women, but disease may occur at every age. Patients with MC report watery, non-bloody diarrhea in the absence of endoscopic and radiologic abnormalities. Lymphocytic colitis is characterized by an increased number of intraepithelial lymphocytes, and CC by a thickened subepithelial collagen band, whereas in both an increased mononuclear infiltration of the lamina propria is found. The pathogenesis of MC is largely unknown, but may relate to autoimmunity, adverse reactions to drugs or (bacterial) toxins, and abnormal collagen metabolism in the case of CC. Budesonide is so far the only drug that has proven efficacy in randomized controlled trials both for the induction and maintenance of remission. Patients who are nonresponsive, dependent or who experience side effects on budesonide may benefit from thiopurine or anti-TNF treatment, but these options are still experimental. The long-term prognosis of MC is good; it does not appear to predispose to malignancies and can in some cases be self-limiting. Further research and randomized clinical trials are required to expand our understanding of the natural course and the pathogenesis of MC.


Assuntos
Colite Microscópica/patologia , Colite Microscópica/diagnóstico , Colite Microscópica/epidemiologia , Colite Microscópica/etiologia , Diagnóstico Diferencial , Técnicas de Diagnóstico do Sistema Digestório , Predisposição Genética para Doença , Humanos , Fatores de Risco
19.
Clin Exp Gastroenterol ; 6: 149-52, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24039441

RESUMO

BACKGROUND: In most cases, collagenous colitis can be treated effectively with budesonide. However, some patients develop side effects or have chronic symptoms refractory to budesonide. This paper reports an open case series of patients intolerant or refractory to budesonide who were treated with methotrexate (MTX). METHODS AND PATIENTS: Nine patients (seven women) with a median (range) age of 62 (44-77) years were studied. Bowel movements were registered during 1 week prior to baseline and after 6 and 12 weeks' treatment, enabling calculation of the mean bowel movements/day. All patients underwent colonoscopy with biopsies before inclusion to confirm diagnosis. Open treatment with MTX was given 15 mg subcutaneously weekly for 6 weeks and was increased to 25 mg for a further 6 weeks if symptoms were unresponsive to the first 6 weeks' treatment. The endpoint was clinical remission, which was defined as a mean <3 stools/day and mean <1 watery stool/day/week at Week 12. The Short Health Scale was used at baseline and Week 12 to assess health-related quality of life. RESULTS: Five patients fulfilled the treatment according to the protocol and four patients discontinued the study after 3-6 weeks because of adverse events. No patient achieved clinical remission at Week 12. The mean stool frequency/day at baseline was 6.0 stools/day, thereof 5.4 watery stools/day and after 12 weeks treatment 6.4 stools/day, thereof 5.7 watery/day. No patient appreciated an improvement of health-related quality of life. CONCLUSION: Short-term treatment with MTX had no clinical effect in collagenous colitis patients intolerant or refractory to budesonide. Alternative therapies should be investigated in these patients.

20.
J Colloid Interface Sci ; 386(1): 240-51, 2012 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-22925119

RESUMO

The conductivity behavior of doped hydrocarbon systems is studied by applying impedance spectroscopy. In the case of 3,5-diisopropyl salicylato aluminum (III) the charge carriers are formed by dissociation of the compound and their concentration is proportional to the square root of the solute concentration. In hydrocarbon systems that consist of micelle forming compounds (sodium AOT/ lecithin) a linear dependence of charge carrier concentration on solute concentration is observed in the concentration regime where micelles are present. The conduction mechanisms are studied by numerical solution of a Poisson-Nernst-Planck system that describes the charge transport. We follow two different approaches to extract the degree of micelle dissociation from the impedance data. Firstly, by computing the response of a linear approximation of the Poisson-Nernst-Planck model, and secondly by computing the fully nonlinear response from direct numerical simulations using finite elements. For high and moderate frequencies both approaches agree very well with the experimental data. For small frequencies the response becomes nonlinear and the concept of impedance fails. Furthermore, the numerically computed values for the degree of dissociation are of the same order of magnitude as the values obtained with classical formulas, but still differ by a factor of about 1/3. The direct numerical simulation allows new insight into the conduction mechanisms for different frequency regimes.


Assuntos
Alcanos/química , Alumínio/química , Condutividade Elétrica , Lecitinas/química , Modelos Teóricos , Salicilatos/química , Micelas , Temperatura
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