Inflammatory bowel disease (IBD) is a chronic disease affecting mainly young people in their reproductive years. IBD therefore has a major impact on patients’ family planning decisions. Management of ...IBD in pregnancy requires a challenging balance between optimal disease control and drug safety considerations.
This article aims to provide a framework for clinical decision making in IBD based on review of the literature on pregnancy-related topics.
Medline searches with search terms ‘IBD’, ‘Crohn's disease’ or ‘ulcerative colitis’ in combination with keywords for the topics fertility, pregnancy, congenital abnormalities and drugs names of drugs used for treatment of IBD.
IBD patients have normal fertility, except for women after ileal pouch-anal anastomosis (IPAA) and men under sulfasalazine treatment. Achieving and maintaining disease remission is a key factor for successful pregnancy outcomes in this population, as active disease at conception carries an increased risk of preterm delivery and low birth weight.
Clinicians should discuss the need for drug therapy to maintain remission with their patients in order to ensure therapy compliance. Most IBD drugs are compatible with pregnancy, except for methotrexate and thalidomide. If possible, anti-TNF therapy should be stopped by the end of the second trimester and the choice of delivery route should be discussed with the patient.
Disease control prior to conception and throughout pregnancy is the cornerstone of successful pregnancy management in IBD patients.
BACKGROUND: Idiopathic Thrombocytopenic Purpura (ITP) is an acquired haematological disorder with an incidence of 1 to 6 per 100,000/year. ITP and inflammatory bowel disease (IBD) comorbidity has ...been reported in the literature, but insights regarding the course, outcome and optimal management are limited by its rarity. The current study aimed to evaluate the clinical presentation and outcome of ITP in patients with IBD.
METHODS: This multicentre retrospective case series was performed as part of the ECCO Collaborative Network of Exceptionally Rare case reports (CONFER) project. Cases of patients with ITP and IBD were collected by participating investigators. Clinical data were recorded in a standardised collection form.
RESULTS: This report includes 32 patients with concurrent ITP and IBD:10 were females, median age was 32.0 interquartile range (IQR) 20.5-39.5. 14 patients had a diagnosis of Crohn's disease (CD) and the other 18 had of ulcerative colitis (UC). The diagnosis of IBD preceded the ITP in 26 patients (median time between diagnoses was 7.0 years IQR, 1.5-9.5). Among those patients, 17 patients were in clinical remission at ITP diagnosis. 13 patients were treated with mesalamine, 4 with oral corticosteroids, 1 with rectal corticosteroids, 2 with azathioprine, and 5 with anti-TNF agents. The median platelet count was 35,000/mmc (IQR, 10,000-70,000). 8 patients had rectal bleeding, 13 had skin purpura, 3 had epistaxis, 6 had mucosal petechiae, and 13 were asymptomatic. Regarding ITP treatment, 19 were treated with corticosteroids, 1 with Anti-RhD immunoglobulin, 12 with intravenous immunoglobulins (IVIG), 4 with thrombopoietin, 3 with rituximab and 6 patients eventually required splenectomy. 10 patients needed no treatment directed to the ITP.Three patients required colectomy during term long follow-up, due to IBD or cancer and not to massive bleeding as a complication of ITP. One patient of eight patients who presented with rectal bleeding required splenectomy, and none required urgent colectomy. Two patients died during the follow-up, one of them due to bleeding complication located in the upper gastrointestinal tract.Median follow-up time was 6.5 years IQR, 3-10. With long-term follow-up, all patients had platelet count above 50,000/mmc, and 24 were in IBD clinical remission.
CONCLUSION: Most ITP cases in this case series occurred after the IBD diagnosis and responded well to regular ITP treatment. The course of the ITP in the IBD patients follows an expected course, including response to medical therapy and low rates of splenectomy.
Earlier studies have provided varying risk estimates for lymphoma in patients with inflammatory bowel disease (IBD), but often have been limited by detection biases (especially during the first year ...of follow-up evaluation), misclassification, and small sample size; and rarely reflect modern-day management of IBD.
We performed a binational register-based cohort study (Sweden and Denmark) from 1969 to 2019. We compared 164,716 patients with IBD with 1,639,027 matched general population reference individuals. Cox regression estimated hazard ratios (HRs) for incident lymphoma by lymphoma subtype, excluding the first year of follow-up evaluation.
From 1969 to 2019, 258 patients with Crohn’s disease (CD), 479 patients with ulcerative colitis (UC), and 6675 matched reference individuals developed lymphoma. This corresponded to incidence rates of 35 (CD) and 34 (UC) per 100,000 person-years in IBD patients, compared with 28 and 33 per 100,000 person-years in their matched reference individuals. Although both CD (HR, 1.32; 95% CI, 1.16–1.50) and UC (HR, 1.09; 95% CI, 1.00–1.20) were associated with an increase in lymphoma, the 10-year cumulative incidence difference was low even in CD patients (0.08%; 95% CI, 0.02–0.13). HRs have increased in the past 2 decades, corresponding to increasing use of immunomodulators and biologics during the same time period. HRs were increased for aggressive B-cell non-Hodgkin lymphoma in CD and UC patients, and for T-cell non-Hodgkin lymphoma in CD patients. Although the highest HRs were observed in patients exposed to combination therapy (immunomodulators and biologics) or second-line biologics, we also found increased HRs in patients naïve to such drugs.
During the past 20 years, the risk of lymphomas have increased in CD, but not in UC, and were driven mainly by T-cell lymphomas and aggressive B-cell lymphomas.
Etrolizumab (rhuMAb β7, anti-β7, PRO145223) is a humanised monoclonal antibody targeting the β7 subunit of the heterodimeric integrins α4β7 and αEβ7, which are implicated in leucocyte migration and ...retention in ulcerative colitis (UC). This randomised phase I study evaluated the safety and pharmacology of etrolizumab in patients with moderate to severe UC.
In the single ascending dose (SAD) stage, etrolizumab (0.3, 1.0, 3.0, 10 mg/kg intravenous, 3.0 mg/kg subcutaneous (SC) or placebo) was administered 4:1 (n=25) in each cohort. In the multiple dose (MD) stage, new patients received monthly etrolizumab (0.5 mg/kg SC (n=4), 1.5 mg/kg SC (n=5), 3.0 mg/kg SC (n=4), 4.0 mg/kg intravenous (n=5)) or placebo (n=5). The pharmacokinetics was studied and Mayo Clinic Score evaluated at baseline, day 29 (SAD), and days 43 and 71 (MD).
In the SAD stage, there were no dose limiting toxicities, infusion or injection site reactions. Two impaired wound healing serious adverse events occurred in two patients receiving etrolizumab. In the MD stage, there were no dose limiting toxicities, and no infusion or injection site reactions. Headache was the most common adverse event, occurring more often in etrolizumab patients. Antietrolizumab antibodies were detected in two subjects. The duration of β7 receptor full occupancy was dose related. A clinical response was observed in 12/18 patients, and clinical remission in 3/18 patients treated with etrolizumab in the MD stage, compared with 4/5 and 1/5 placebo patients, respectively.
Etrolizumab is well tolerated in moderate to severe UC. Further investigation is warranted.
Inflammatory bowel diseases (IBDs) are complex, multifactorial disorders characterized by chronic relapsing intestinal inflammation. Although etiology remains largely unknown, recent research has ...suggested that genetic factors, environment, microbiota, and immune response are involved in the pathogenesis. Epidemiological evidence for a genetic contribution is defined: 15% of patients with Crohn's Disease (CD) have an affected family member with IBD, and twin studies for CD have shown 50% concordance in monozygotic twins compared to <10% in dizygotics. The most recent and largest genetic association studies, which employed genome-wide association data for over 75,000 patients and controls, identified 163 susceptibility loci for IBD. More recently, a trans-ethnic analysis, including over 20,000 individuals, identified an additional 38 new IBD loci. Although most cases are correlated with polygenic contribution toward genetic susceptibility, there is a spectrum of rare genetic disorders that can contribute to early-onset IBD (before 5 years) or very early onset IBD (before 2 years). Genetic variants that cause these disorders have a wide effect on gene function. These variants are so rare in allele frequency that the genetic signals are not detected in genome-wide association studies of patients with IBD. With recent advances in sequencing techniques, ~50 genetic disorders have been identified and associated with IBD-like immunopathology. Monogenic defects have been found to alter intestinal immune homeostasis through many mechanisms. Candidate gene resequencing should be carried out in early-onset patients in clinical practice. The evidence that genetic factors contribute in small part to disease pathogenesis confirms the important role of microbial and environmental factors. Epigenetic factors can mediate interactions between environment and genome. Epigenetic mechanisms could affect development and progression of IBD. Epigenomics is an emerging field, and future studies could provide new insight into the pathogenesis of IBD.
Commensal gut microbiota play an important role in regulating metabolic and inflammatory conditions. Reshaping intestinal microbiota through pharmacologic means may be a viable treatment option. We ...sought to delineate the functional characteristics of glucocorticoid-mediated alterations on gut microbiota and their subsequent repercussions on host mucin regulation and colonic inflammation.
Adult male C57Bl/6 mice, germ-free, Muc2-heterozygote (±), or Muc2-knockout (-/-) were injected with dexamethasone, a synthetic glucocorticoid, for 4 weeks. Fecal samples were collected for gut microbiota analysis through 16S rRNA terminal restriction fragment length polymorphism and amplicon sequencing. Intestinal mucosa was collected for mucin gene expression studies. Germ-free mice were conventionalized with gut microbes from treated and nontreated groups to determine their functional capacities in recipient hosts.
Exposure to dexamethasone in wild-type mice led to substantial shifts in gut microbiota over a 4-week period. Furthermore, a significant downregulation of colonic Muc2 gene expression was observed after treatment. Muc2-knockout mice harbored a proinflammatory environment of gut microbes, characterized by the increase or decrease in prevalence of specific microbiota populations such as Clostridiales and Lactobacillaceae, respectively. This colitogenic phenotype was transmissible to IL10-knockout mice, a genetically susceptible model of colonic inflammatory disorders. Microbiota from donors pretreated with dexamethasone, however, ameliorated symptoms of inflammation.
Commensal gut bacteria may be a key mediator of the anti-inflammatory effects observed in the large intestine after glucocorticoid exposure. These findings underscore the notion that intestinal microbes comprise a "microbial organ" essential for host physiology that can be targeted by therapeutic approaches to restore intestinal homeostasis.
Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract, which includes Crohn's disease (CD) and ulcerative colitis (UC). These diseases have become important ...health problems. Medical therapy for IBD has advanced dramatically in the last decade with the introduction of targeted biologic therapies, the optimization of older therapies, including rugs such as immunomodulators and 5-aminosalicylic acid (5-ASA), and a better understanding of the mucosal immune system and the genetics involved in the pathogenesis of IBD. The goal of IBD therapy is to induce and maintain remission. The current treatment paradigm involves a step-up approach, moving to aggressive, powerful therapies only when milder therapies with fewer potential side effects fail or when patients declare themselves to have an aggressive disease. This review focuses on the current treatments for inflammatory bowel disease.
In this study, a series of novel anti-inflammatory compounds with high activity and low toxicity were designed and synthesized based on the natural product pterostilbene skeleton. According to the ...strategy of pharmacophore combination, we introduced thiazole moiety into pterostilbene skeleton to design and synthesize a novel series of pterostilbene derivatives (a total of 41 compounds), and lipopolysaccharide (LPS)-treated RAW 264.7 cells were screened for anti-inflammatory activity and cytotoxicity. Among them, compound 8 was found to be the most active (against NO: IC50 = 0.6 μM) compared with pterostilbene and indomethacin. Anti-inflammatory mechanism studies revealed that compound 8 inhibited pro-inflammatory cytokines by blocking the NF-κB/MAPK signaling pathway in LPS-treated RAW 264.7 cells. In vivo experiments showed that compound 8 had a good relieving effect on DSS-induced acute colitis in mice, and also demonstrated a good safety in acute toxicity experiments. In conclusion, compound 8 may be a promising anti-inflammatory lead compound in the treatment of acute colitis.
Variability in endoscopic assessment necessitates rigorous investigation of descriptors for scoring severity of ulcerative colitis (UC).
To evaluate variation in the overall endoscopic assessment of ...severity, the intra- and interindividual variation of descriptive terms and to create an Ulcerative Colitis Endoscopic Index of Severity which could be validated.
A two-phase study used a library of 670 video sigmoidoscopies from patients with Mayo Clinic scores 0-11, supplemented by 10 videos from five people without UC and five hospitalised patients with acute severe UC. In phase 1, each of 10 investigators viewed 16/24 videos to assess agreement on the Baron score with a central reader and agreed definitions of 10 endoscopic descriptors. In phase 2, each of 30 different investigators rated 25/60 different videos for the descriptors and assessed overall severity on a 0-100 visual analogue scale. κ Statistics tested inter- and intraobserver variability for each descriptor. A general linear mixed regression model based on logit link and β distribution of variance was used to predict overall endoscopic severity from descriptors.
There was 76% agreement for 'severe', but 27% agreement for 'normal' appearances between phase I investigators and the central reader. In phase 2, weighted κ values ranged from 0.34 to 0.65 and 0.30 to 0.45 within and between observers for the 10 descriptors. The final model incorporated vascular pattern, (normal/patchy/complete obliteration) bleeding (none/mucosal/luminal mild/luminal moderate or severe), erosions and ulcers (none/erosions/superficial/deep), each with precise definitions, which explained 90% of the variance (pR(2), Akaike Information Criterion) in the overall assessment of endoscopic severity, predictions varying from 4 to 93 on a 100-point scale (from normal to worst endoscopic severity).
The Ulcerative Colitis Endoscopic Index of Severity accurately predicts overall assessment of endoscopic severity of UC. Validity and responsiveness need further testing before it can be applied as an outcome measure in clinical trials or clinical practice.
Summary
Background
The Disease Severity Index (DSI) is a novel tool to predict disease severity in inflammatory bowel disease (IBD). However, its ability to predict disease complications and the ...presence of psychosocial comorbidity is unclear. Aims: To assess prospectively associations between the DSI and psychological symptoms, quality‐of‐life (QoL) and disease outcomes in an IBD cohort.
Methods
Patients with IBD undergoing ileocolonoscopy were followed prospectively for 12 months. DSI, psychological symptoms (perceived stress (PSS‐10), depression (PHQ‐9), anxiety (GAD‐7)) and QoL (IBDQ‐32) scores were assessed at baseline. Logistic regression identified variables predicting a complicated IBD course at 12 months (composite outcome of need for escalation of biological/immunomodulator for disease relapse, recurrent corticosteroid use, IBD‐related hospitalisation and surgery). Receiver operating characteristics (ROC) analysis identified optimal DSI thresholds predicting a complicated disease course and multivariable logistic regression assessed the risk of reaching this outcome.
Results
One hundred and seventy‐two patients were recruited (100 Crohn's disease, 91 female). Median DSI was 21 (IQR 11–32) and 97 patients had endoscopically active disease at baseline. The DSI was significantly higher in patients with symptoms of moderate–severe stress (PSS‐10 > 14, p < 0.01), depression (PHQ‐9 ≥ 10, p < 0.01), anxiety (GAD‐7 ≥ 10, p < 0.05) and impaired quality‐of‐life (IBDQ‐32 < 168, p < 0.01). Only the baseline DSI (OR 1.05, p < 0.01) and endoscopically active disease (OR 6.12, p < 0.01) were associated with a complicated IBD course. A DSI > 23 was strongly predictive of a complicated IBD course (OR 8.31, p < 0.001).
Conclusions
The DSI is associated with psychological distress, impaired QoL and predicts a more complicated disease course in patients with IBD.
The Disease Severity Index (DSI) for inflammatory bowel disease (IBD) is associated with psychological symptoms, quality‐of‐life (QoL) and predicts a more complicated disease course.
PDF
