Management Of Crohn Research Articles

Crohn’s Disease: Pathophysiology, and Management

Background: The incidence of crohn’s disease reaches up to 20 per 100,000 people per year, with a median age of 30 years, and is higher in the developed world. Although the exact cause and pathophysiology is unknown, several environmental and genetic factors have been linked with higher risk or severity of the disease. Methodology: We conducted this review using a comprehensive search of MEDLINE, PubMed, and EMBASE, January 1985, through February 2017. The following search terms were used: crohn’s disease, inflammatory bowel disease, genetics of crohn’s disease, diagnosis of IBD, management crohn’s disease Aim of the study: In this review, we aim to study the pathophysiology, diagnosis and management of crohn’s disease. We will pay special attention to the newer biological drugs used in management. Conclusion: Crohn’s disease is usually managed with medical treatment, although many patients will need to undergo surgery at least once. Treatment usually aims at the induction and maintenance of a remission without the excessive use and dependence of steroids. Achieving higher quality of life is the main goal of any modality of treatment.

Comparison of time until elective intestinal resection regarding previous anti-tumor necrosis factor exposure: a Brazilian study on patients with Crohn's disease.

Background/AimsThe use of anti-tumor necrosis factor (anti-TNF) agents seems to reduce surgical rates and delay surgical procedures in prospective trials and population-based studies in the management of Crohn's disease (CD). This study aimed to identify whether preoperative anti-TNF agents influence the time from diagnosis to surgery.MethodsAn observational retrospective cohort study was conducted on patients with CD submitted to intestinal resections due to complications or medical therapy failure in a period of 7 years. The patients were allocated into 2 groups according to their previous exposure to anti-TNF agents in the preoperative period. Epidemiological aspects regarding age at diagnosis, smoking, perianal disease, and preoperative conventional therapy were considered. A Kaplan-Meier survival analysis was used to outline possible differences between the groups regarding the time to surgery.ResultsA total of 123 patients were included (71 and 52 with and without previous exposure to biologics, respectively). The overall time to surgery was 108±6.9 months (maximum, 276 months). The survival estimation revealed no difference in the mean time to intestinal resection between the groups (99.78±10.62 months in the patients without and 114.01±9.07 months in those with previous anti-TNF use) (log-rank P=0.35). There was no significant difference in the time to surgery regarding perianal CD (P=0.49), smoking (P=0.63), preoperative azathioprine (P=0.073) and steroid use (P=0.58).ConclusionsThe time from diagnosis to surgery was not influenced by the preoperative use of anti-TNF therapy in this cohort of patients.

Is top-down therapy a more effective alternative to conventional step-up therapy for Crohn's disease?

The management of Crohn’s disease involves immunosuppressive protocols in a step-up approach that progresses through a therapeutic pyramid with several tiers of medication. Medications at the top are considered more potent but present greater risk. A new top-down approach to therapy inverts this procedure, using top-tier drugs for initial treatment. A critical appraisal of the current literature relating to top-down therapy was performed to evaluate its merit. A literature search was conducted on PubMed, Ovid, and PubMed Central to identify studies of the efficacy of top-down therapy. Papers were appraised critically using the Scottish Intercollegiate Guidelines Network score to evaluate current evidence for the use of top-down therapy. Nineteen studies were identified, including six randomized controlled trials, thirteen cohort studies, and two cost-benefit studies. Early combined therapy involving both biologics and immunomodulators was found to be effective at improving patient outcomes; however, early biologics alone were not shown to have a clear benefit over step-up therapy. Likewise, the early use of immunomodulators alone showed inconsistent results with respect to efficacy in terms of both remission and surgical outcomes. Evidence for application in pediatric populations was also inconclusive. The cost-benefit analyses found that top-down therapy merits investigation, as it proved to be economical given current data. Top-down therapy has the potential of being a viable alternative to step-up therapy, but further studies are needed to determine the most appropriate patients to receive this treatment.

Updates in the Medical Management of Crohn’s Disease

Updates in the Medical Management of Crohn’s Disease

A Unique Case of Rituximab-Induced Crohnʼs Disease: A Case Report and Review of Literature

Rituximab is a humanized monoclonal antibody against CD20 which is a mainstay of therapy for a wide variety of B cell malignancies. There are only two reported cases of Crohn's disease following treatment with Rituximab in the literature. We present a very unique case of a 58 year old female who was treated with Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisolone (R-CHOP) regimen for initial diagnosis of follicular cell lymphoma of the tonsils. She was treated with prolonged maintenance Rituximab treatment for a recurrence of the lymphoma two years later and the treatment was continued for two and a half years. Three years later she was noted to have increased activity in the terminal ilium and mesenteric lymph nodes on a routine positron emission tomography (PET) scan. At that time, she was asymptomatic and refused any further workup or treatment. Another PET scan done two years later showed enlarged mesenteric lymph nodes with increased activity in the terminal ileum and the spleen. A colonoscopy performed at that time revealed inflammation with extensive ulceration in the terminal ileum. Biopsy demonstrated severely active chronic nonspecific ileitis with ulceration and a small granulomatous lesion. She was then re-treated again with 4 cycles of rituximab for a presumed recurrence. Two months after the treatment, she developed severe abdominal pain leading to an emergency room visit. A computerized tomography (CT) scan showed thickening in the distal descending colon as well as the entire sigmoid colon with surrounding fat stranding. She was treated with oral ciprofloxacin and metronidazole for 10 days with improvement in the symptoms. In a follow-up PET scan done a month later, the mesenteric adenopathy resolved but the activity in the terminal ileum was unchanged and there was new activity in the sigmoid colon. The patient refused further endoscopic examination, however the PET scan findings of worsening of the bowel inflammation and resolution of the adenopathy strongly suggests Rituximab induced Crohn's disease. This case portrays the importance of being alert to the possibility of Crohn's disease occurring as complication of Rituximab treatment. This case is unique as the Crohn's disease occurred almost three years after the initial Rituximab treatment. Management of Crohn's disease in patients with a history of lymphoma can be challenging due to the risk of lymphoma from Anti-TNF and immunomodulatory treatments.Figure: PET Scan showing increased uptake in the mesenteric lymph nodes and terminal ileum.Figure: Colonoscopy image of the terminal ileum.

Anti-TNF Alpha-Induced Psoriasis: A Rare Paradoxical Side Effect

Introduction: TNF-α inhibitors are widely used in the management of Crohn's disease (CD) and psoriasis. These agents can paradoxically cause psoriasis. We present a case report of Crohn's disease patient on infliximab therapy who developed psoriasis. Case report: A 45 year old man with a history of Crohn's colitis, well controlled on infliximab, came to clinic for evaluation of pruritic rash for 2-3 weeks that started on his legs initially and spread to involve his arms, chest, and back. He denied systemic symptoms, use of new medications or skin products, sick contact and recent travel. His CD was in remission for more than 1 year, and the last dose of infliximab was given 4 weeks ago. Skin exam revealed well-demarcated, erythematous plaques with overlying adherent scales involving chest, abdomen, back, legs and extensor surfaces of both arms. The patient was referred to dermatology for further evaluation. Punch skin biopsy revealed psoriasis. It was attributed to the use of infliximab. He was treated with topical steroids and UVB phototherapy with minimal improvement. Infliximab was held and planned to switch to other biologic agents for maintenance of CD. Discussion: CD is characterized by transmural inflammation of the gastrointestinal tract due to inflammatory cytokines such as interleukin (IL)-12 and TNF-α, resulting in symptoms of CD. TNF-α inhibitors, e.g., infliximab are effective in inducing and maintaining remission in moderate to severe CD patients. Plaque-type psoriasis, guttate psoriasis, palmoplantar pustulosis, psoriasis of the nail and scalp have been described in the literature with the use of these agents. Estimated prevalence is 0.6% to 5.3%. Previously reported cases have a wide diversity as far as agent types, gender and age of patients, treatment duration, type of eruption, and presence or absence of personal or family history of psoriasis are concerned. Pustular eruption resembling palmoplantar pustulosis is the most characteristic pattern, and it has been reported in about one-third of all reported cases. Pathogenesis of TNF-α inhibitors induced psoriasis involves a disruption in cytokine balance allowing unopposed interferon-α production by dendritic cells. In most cases, topical steroid therapy is enough. UVB phototherapy or discontinuation of TNF-α inhibitor or switching to an alternative anti-TNF agent is required in severe cases.Figure: Rash on back.Figure: Rash on elbow.

Utility of CT enterography in the evaluation of small bowel pathologies

Background: Radiology has been the primary investigation tool for small intestine because of technical challenges in endoscopy. Barium studies and computed tomography (CT) have been the most useful modalities over the years; however, neither is a complete investigation by itself. CT enterography offers the possibility of a single comprehensive radiological evaluation. The present study was undertaken to study the accuracy of CT enterography in characterising various small bowel pathologies.Methods: A total of 84 patients clinically suspected or known to have small intestinal disease underwent CT enterography on a 64 slice MDCT. The radiologic findings were correlated with clinical, endoscopy, histopathology and operative findings.Results: A wide variety of pathologies can be diagnosed accurately on CT enterography. In our study, majority of the patients had non-neoplastic pathologies (79%). Neoplastic lesions were detected in 21% of the patients of which 14% were malignant. There was good correlation between CT enterography and endoscopy, histopathology and operative findings. The ability of CT enterography to differentiate acute inflammation from chronic changes is valuable in management of Crohn’s disease.Conclusions: CT enterography should be considered as the investigation of choice for radiological evaluation of small bowel pathologies as it provides a comprehensive evaluation of the disease process.

Recommendations of the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU) on the monitoring, prevention and treatment of post-operative recurrence in Crohn's disease

Despite the availability of new, powerful drugs for Crohn's disease, a significant proportion of patients will undergo an intestinal resection to control the disease as it develops. In the absence of an effective preventative treatment, the appearance of new intestinal lesions after surgery for Crohn's disease is the norm; this is known as post-operative recurrence and may appear very early on, even a few weeks after the surgical resection. Furthermore, the drugs that are currently available for the prevention of post-operative recurrence have a limited effect; up to 50% of cases present recurrent Crohn's disease activity despite the preventative treatment, which may require further surgery with the consequent loss of intestinal function, leading some patients to suffer from short bowel syndrome as an irreversible complication. The management of Crohn's disease patients who undergo an intestinal resection should thus be geared towards prevention, early detection and, in the worst case scenario, the treatment of post-operative recurrence. This article reviews the natural history, diagnostic measures, monitoring, prevention and treatment of post-operative recurrence, and proposes recommendations based on existing knowledge.

The impact of panenteric capsule endoscopy on the management of Crohn's disease.

Crohn's disease (CD) is a chronic inflammatory disease, in most patients involving the small and large bowel. In recent years, with the use of small bowel video capsule endoscopy (SBCE), it has become clear that in 50% or more of adults with established CD there is not only distal but also proximal small bowel involvement that suggests poor prognosis. A great deal of effort has been put into early diagnosis and stratification of patients into low versus high risk, thus directing treatment from step-up, or accelerated step-up, to top-down therapies. SBCE has been used for assessment of small bowel pathologies for over 15 years, mainly for occult gastrointestinal bleeding and suspected CD. In recent years, a colonic capsule, with cameras on both sides and a wider angle of view, has been developed and is used by some to survey both small and large bowel. Recently the same capsule, with adjustments, has been released in Europe, concentrating (with specialized software) on inflammatory bowel disease. In this review I summarize the new data regarding the use of SBCE as well as the small bowel colon (SBC) versions of capsule endoscopy in established CD and the ways these could alter the management of such patients.

Recomendaciones del Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU) sobre la monitorización, prevención y tratamiento de la recurrencia posquirúrgica en la enfermedad de Crohn

Despite the availability of new, powerful drugs for Crohn's disease, a significant proportion of patients will undergo an intestinal resection to control the disease as it develops. In the absence of an effective preventative treatment, the appearance of new intestinal lesions after surgery for Crohn's disease is the norm; this is known as post-operative recurrence and may appear very early on, even a few weeks after the surgical resection. Furthermore, the drugs that are currently available for the prevention of post-operative recurrence have a limited effect; up to 50% of cases present recurrent Crohn's disease activity despite the preventative treatment, which may require further surgery with the consequent loss of intestinal function, leading some patients to suffer from short bowel syndrome as an irreversible complication. The management of Crohn's disease patients who undergo an intestinal resection should thus be geared towards prevention, early detection and, in the worst case scenario, the treatment of post-operative recurrence. This article reviews the natural history, diagnostic measures, monitoring, prevention and treatment of post-operative recurrence, and proposes recommendations based on existing knowledge.

When “pouchitis” isn׳t pouchitis: Crohn׳s disease and surgical complications

Restorative proctocolectomy with ileal pouch-anal anastomosis is the definitive operation of choice for the surgical treatment of patients with ulcerative colitis that is refractory to medical therapy or with dysplasia. However, pouch dysfunction due to inflammatory and non-inflammatory diseases frequently affect patients after surgery and have a significant impact on quality of life. Accurate diagnosis is important to guide further therapy and it is essential to differentiate pouchitis from Crohn׳s disease or surgical complications. This article reviews diagnosis and management of Crohn׳s disease and surgical complications affecting the ileal pouch.

Factors Associated with Fecal Incontinence in Women of Childbearing Age with Crohn's Disease.

Fecal incontinence is common in women with Crohn's disease, but little is known about the impact of childbirth, perianal Crohn's disease, and past surgical history on fecal incontinence. Self-administered questionnaires were mailed to consecutive women referred to a tertiary gastroenterology centre with a focus on fecal incontinence and childbirth. These data were cross-referenced with a prospective database of the same patients' own Crohn's disease histories. Fecal incontinence was defined as a Cleveland Clinic Incontinence Score ≥5. Factors associated with fecal incontinence were analyzed. A total of 173 patients were assessed, including 113 parous women. The prevalence of fecal incontinence was 37.5% (95% CI, 30.7-45.0). The disease duration, a history of anal surgery for fistula, the number of childbirths per woman and Crohn's activity were all independently associated with fecal incontinence in a multivariate analysis model. Specifically, among the group of parous women, fecal incontinence was associated with prior abdominal surgery, prior anal surgery, and Crohn's activity. The mode of delivery was not statistically associated with fecal incontinence. Fecal incontinence is a significant complaint in at least one-third of women of childbearing age with Crohn's disease. Patients'disease and treatment histories seem to have a comparable effect to their childbirth history concerning the presence of fecal incontinence. Both physicians and surgeons who are involved in the management of Crohn's disease need to keep this in mind.

Systematic review with meta-analysis: comparative efficacy of biologics for induction and maintenance of mucosal healing in Crohn's disease and ulcerative colitis controlled trials.

Mucosal healing is an important therapeutic endpoint in the management of Crohn's disease (CD) and ulcerative colitis (UC). Limited data exist regarding the comparative efficacy of various therapies in achieving this outcome. To perform a systematic review and meta-analysis of biologics for induction and maintenance of mucosal healing in Crohn's disease and ulcerative colitis. We performed a systematic review and meta-analysis of randomised controlled trials (RCT) examining mucosal healing as an endpoint of immunosuppressives, anti-tumour necrosis factor α (anti-TNF) or anti-integrin monoclonal antibody therapy for moderate-to-severe CD or UC. Pooled effect sizes for induction and maintenance of mucosal healing were calculated and pairwise treatment comparisons evaluated using a Bayesian network meta-analysis. A total of 12 RCTs were included in the meta-analysis (CD - 2 induction, 4 maintenance; UC - 8 induction, 5 maintenance). Duration of follow-up was 6-12weeks for induction and 32-54weeks for maintenance trials. In CD, anti-TNFs were more effective than placebo for maintaining mucosal healing [28% vs. 1%, Odds ratio (OR) 19.71, 95% confidence interval (CI) 3.51-110.84]. In UC, anti-TNFs and anti-integrins were more effective than placebo for inducing (45% vs. 30%) and maintaining mucosal healing (33% vs. 18%). In network analysis, adalimumab therapy was inferior to infliximab [OR 0.45, 95% credible interval (CrI) 0.25-0.82] and combination infliximab-azathioprine (OR 0.32, 95% CrI 0.12-0.84) for inducing mucosal healing in UC. There was no statistically significant pairwise difference between vedolizumab and anti-TNF agents in UC. Anti-TNF and anti-integrin biological agents are effective in inducing mucosal healing in UC, with adalimumab being inferior to infliximab or combination therapy. Infliximab and adalimumab were similar in CD.

Crohn's disease for the general physician: management.

Crohn's disease presents to general physicians in a variety of ways. The previous article outlined clinical features and initial investigations, and this article covers management of Crohn's disease, including monitoring and drug toxicity.

P165 Impact of double balloon endoscopy on management of small bowel Crohn's disease

Background: Since Double Balloon Endoscopy (DBE) enables us to examine deep small bowel either oral or anal it could be of great utility in the management of Crohn's disease (CD) patients. Aim: To evaluate the diagnostic yield and therapeutic impact of DBE on small bowel CD. Methods: The medical records of 180 CD patients, from October 2009 to April 2015, were retrospectively analyzed. Patients were included if they had known CD based on clinical, colonoscopic and histological findings and had been subjected to DBE. If one patient underwent more than one DBE examination only the first evaluation was considered. The primary end point of our study was to evaluate small bowel involvement that is beyond the reach of conventional colonoscopy. The secondary endpoints were to determine the impact of DBE findings on management strategy of CD. The diagnostic yield of DBE in small bowel CD was determined. In addition, the changes in medical treatment, endoscopic intervention and surgical procedures, within three months after DBE, were analyzed. Results: Among 180 patients with CD, 90 patients underwent 168 DBE examinations and included. The mean age of included patients was 40±13.6 years. They were 63 males and 27 females. Eighty-two (91%) patients with established CD underwent DBE for evaluation of small bowel involvement and 8 (9%) patients underwent DBE because of suspicion of CD and had been newly diagnosed. The overall diagnostic yield of DBE was 69%. Within 3 months after DBE examination the management strategy of CD changed in 47 (52.2%) patients, based on DBE findings. The medical treatment escalated in 20 (32%) patients, and decreased in 7 (11%). 14 (24%) patients underwent DBE assisted balloon dilatation, and 6 (9.6%) patients underwent CD-related surgery. Conclusions: DBE is able to uncover small bowel involvement in a significant proportion of CD patients. The DBE findings modified the management strategy in at least one half of CD patients.

P255 Predictors of negative C-reactive protein in active Crohn's disease

Background: Due to its wide accessibility, fast availability and proven correlation with disease activity, C-reactive protein (CRP) remains an essential tool in the management of Crohn's disease (CD), namely when it comes to decide the appropriate treatment in a given situation. However, the correlation of CRP with CD activity is not perfect. It is therefore of great importance to identify the group of patients with active disease and negative CRP. Methods: We performed a retrospective case-control study, with inclusion of CD patients with proven active disease as demonstrated by endoscopic and/or radiologic examinations. The CRP's cut-off value used to separate patients in two groups (cases and controls) was 1 mg/dL. Demographic, phenotypic and clinical characteristics were collected. Statistical analysis was performed with SPSS 20.0. Results: We included 88 patients (42 men, 46 women) with a mean age of 34±10.8 years and median of disease duration of 1.23 years (interquartile range 0.07–6.16). Twelve (13.6%) of these patients had negative CRP. There weren't statistically significant differences in CD activity between cases and controls, as evaluated by Harvey-Bradshaw index. Upon exploratory analysis, there were statistically significant differences regarding gender as 21.4% of men vs 6.5% of women had a negative CRP (p=0.04). Even though location was not a significant predictor, all patients with a negative CRP had ileal involvement. On multivariate analysis, gender remained a significant predictor, with an Odds ratios (OR) of 5.64 [Confidence Interval (CI) 95% 1.30–24.39; p=0.02). There was also a tendency to a higher probability of negative CRP in isolated ileal disease (OR 3.87; CI95% 0.97–15.34; p=0.055). There were no differences in age, behaviour, disease duration, previous abdominal surgery or smoking status. Conclusions: Despite being a useful tool CRP has some limitations and it can be negative in cases of active disease. In patients with the identified characteristics (ie men with ileal disease) other methods should be used to exclude with confidence the presence of inflammatory activity.

Management of Crohn's disease in Taiwan: consensus guideline of the Taiwan Society of Inflammatory Bowel Disease.

Crohn's disease (CD) is a chronic relapsing and remitting inflammatory disease of the gastrointestinal tract. CD is rare in Taiwan and other Asian countries, but its prevalence and incidence have been steadily increasing. A steering committee was established by the Taiwan Society of Inflammatory Bowel Disease to formulate statements on the diagnosis and management of CD taking into account currently available evidence and the expert opinion of the committee. Thorough clinical, endoscopic, and histological assessments are required for accurate diagnosis of CD. Computed tomography and magnetic resonance imaging are complementary to endoscopic evaluation for disease staging and detecting complications. The goals of CD management are to induce and maintain remission, reduce the risk of complications, and improve quality of life. Corticosteroids are the mainstay for inducing re-mission. Immunomodulating and biologic therapies should be used to maintain remission. Patients should be evaluated for hepatitis B virus and tuberculosis infection prior to treatment and receive regular surveillance for cancer. These consensus statements are based on current local evidence with consideration of factors, and could be serve as concise and practical guidelines for supporting clinicians in the management of patients with CD in Taiwan.

Preoperative use of anti-tumor necrosis factor therapy in Crohn's disease: promises and pitfalls.

Recent advances in medical and surgical therapy were achieved during the last two decades in the management of Crohn's disease (CD). Anti-tumor necrosis factor (anti-TNF) agents are widely used worldwide. However, a significant proportion of patients still need surgical resections. The impact of previous exposure to these agents on the perioperative and postoperative outcomes is still controversial. In this critical review, we aimed to position the strategy of intentional preoperative use of anti-TNF agents in the management of CD. The indications and contraindications for this strategy are detailed, and despite scarce evidence, the possible advantages and disadvantages of the intentional use of anti-TNF agents before abdominal surgery in CD are discussed.

CEUS in Crohn’s Disease

Ultrasonography has advanced the diagnostic potential of ultrasound in the assessment of Crohn’s disease. Ultrasonography is not only a method used by radiologists, but also a clinical tool that can be applied to evaluate the patient bedside. The GI wall is most often visualized as a layered structure normally consisting of 3-9 layers, depending on the frequency applied, but usually 5 layers are observed. When examining the intestines, it is preferable to use frequencies above 7.5 MHz to enable optimal visualisation of wall layers, thickened bowel walls and target lesions. Disease activity in Crohn’s disease using bowel wall thickness and Doppler measurements as a marker of inflammation can also be obtained by ultrasound. By adding CEUS, enhancement in different wall layers can be evaluated and quantified in Crohn’s disease and this correlates to clinical activity index (CDAI) with good sensitivity and specificity. Quantitative measurements of bowel enhancement obtained by CEUS also correlate with severity grade determined at endoscopy. In patients with a stricture of the bowel and resultant bowel obstruction, it is important to determine if there is active inflammation at the site of stricture or if the obstructed segment is fibrotic. Preliminary studies indicate that CEUS appears to be useful in the recognition of a cicatricial stenosis in patients with Crohn's disease. Using CEUS, the active inflammatory components will enhance whereas the fibrotic stricture will enhance less. Distinguishing abscesses from inflammatory infiltrates is an important clinical task in the management of Crohn’s disease. If the tissue close to an affected bowel loop is completely devoid of microbubble signals, most likely this lesion represents avascular abscesses rather than inflammatory infiltrates. In the upcoming update of EFSUMB guidelines on CEUS, new indications are monitoring of treatment response and follow-up of transplanted patients. In conclusion, CEUS is a useful clinical tool in the management of patients with Crohn’s disease, particularly to estimate disease activity and to diagnose complications.

Postoperative Management of Crohn’s Disease: What Can We Do to Prevent Recurrence?

<p>Crohn’s disease (CD) is a chronic inflammatory bowel disease with a relapsing, remitting course. Approximately one in four CD patients requires surgery within five years of diagnosis. Unfortunately, surgery is rarely curative and up to 70% of CD patients experience endoscopic recurrence and 40% have clinical disease recurrence within 18 months after surgery.</p><p> </p><p>This review is aimed at providing internists and gastroenterologists a foundation for the management of patients who underwent ileocecal resection for CD. We provide an overview of the current definitions of postoperative recurrence and prognostic factors for postoperative CD recurrence. As recent studies raised concerns about the value of these factors, we examine the evidence behind the current risk stratification algorithm and pharmacologic treatment recommendations. Lastly, we discuss future directions for research.</p>