Corticosteroid and Biologic Use Not Associated With Adverse Outcomes for Inflammatory Bowel Disease Patients Hospitalized With COVID-19.

BACKGROUND: To date, studies investigating the inflammatory bowel disease (IBD) patient experience with coronavirus disease 2019 (COVID-19) have consistently reported that the observed rate of COVID-19 within this population is similar to the general population. Limited research has suggested that corticosteroid use in the IBD population may be associated with worse COVID-19 outcomes, but it is still yet to be determined if specific IBD-related clinical factors are associated with worse outcomes. Our goal was to describe clinical COVID-19 outcomes for IBD patients and to identify the clinical factors that may be associated with worse outcomes. METHODS: In this retrospective study, we utilized the inpatient database within the largest hospital network in the New York City Metropolitan area to identify all IBD patients with confirmed COVID-19. RESULTS: Of 83 IBD/COVID-19 patients presenting to a hospital network emergency room, 56 were hospitalized. Overall, 19.6% of hospitalized IBD patients died, compared with 22.2% of all hospital system COVID-19 patients during the time period. There was no association between pre-admission corticosteroid use or biologic treatment with a severe course of COVID-19. CONCLUSIONS: In contrast to some prior reports, we did not observe an association of pre-admission corticosteroid use and adverse outcomes. While the mortality rate was high for IBD/COVID-19 patients, it was not greater than that for hospitalized COVID-19 patients generally. Though our results are encouraging, we continue to support the recommendations of the leading gastrointestinal and IBD societies to regard our patients as "at risk", and to observe caution in their care.

The Changing Prognosis of Ulcerative Colitis and Crohn Disease by Decades.

We present a bird's eye view of the prognosis for both ulcerative colitis and Crohn disease as contained in the database of an Inflammatory Bowel Disease gastroenterologist covering the period from 1950 until the present utilizing the variables of medical therapy, surgical intervention, complications, and deaths by decades.

Increasing Pediatricians' Awareness of the Association between Anal Skin Tags and Earlier Diagnosis of Crohn's Disease.

OBJECTIVE: To seek the habits of pediatricians by which anorectal skin tags (AST) of Crohn's disease might be overlooked. METHODS: Questionnaires were sent to pediatricians affiliated with the Northwell Health System. RESULTS: Based on the responses, the majority of pediatricians did feel the abdomen of children presenting with abdominal pain or diarrhea but did not spread the buttocks to seek the presence of AST unless there was rectal pain, rectal bleeding, or, in some cases, loose stools. CONCLUSIONS: The diagnosis of Crohn's disease could be made earlier when asymptomatic AST are searched for in children with gastrointestinal symptoms.

Effects of Vedolizumab Therapy on Extraintestinal Manifestations in Inflammatory Bowel Disease.

BACKGROUND: Approximately 15-20% of ulcerative colitis patients and 20-40% of those with Crohn's disease experience extraintestinal manifestations (EIMs) of their inflammatory bowel disease (IBD). Clinicians who treat IBD must manage EIMs affecting multiple organs that variably correlate with intestinal disease activity. Vedolizumab is a monoclonal antibody for the treatment of IBD with a gut-selective mechanism of action. AIMS: This report evaluates whether vedolizumab is an effective treatment of EIMs, given its gut-specific mechanism of action. METHODS: We report 8 case studies of patients with various EIMs, including pyoderma gangrenosum, peripheral arthralgia/arthritis, axial arthropathies, erythema nodosum, and uveitis, who received vedolizumab therapy. RESULTS: Vedolizumab therapy was effective for pyoderma gangrenosum in ulcerative colitis, uveitis, erythema nodosum, polyarticular arthropathy, and ankylosing spondylitis/sacroiliitis but did not provide sustained benefit for the treatment of pyoderma gangrenosum in a patient with Crohn's disease. CONCLUSIONS: These cases demonstrate the potential of vedolizumab as a treatment of EIMs in patients with IBD.

Obesity/Bariatric Surgery and Crohn's Disease.

BACKGROUND: Crohn's disease (CD) following bariatric surgery has been previously described. It is not clear whether the clinical entity is due to rapid metabolism of fat, change in the bacterial milieu of the bowel, the loss of defense mechanisms of the stomach, or even a coincidence. OBJECTIVES: To present observations which might serve to sort out these various etiologies. DESIGN: We present 5 cases of colitis, ileocolitis or enteritis, some with fistula formation, with clinical onset following bariatric surgery and add these to the 7 cases previously identified as CD reported elsewhere. We provide the clinical features of these 12 cases to reconcile with causative mechanisms. LIMITATIONS: It remains possible that the onset of CD (or other inflammatory bowel disease) precedes the bariatric surgery which then accelerates the clinical manifestations described. Furthermore, without controls the association could remain a coincidence. CONCLUSIONS: We review the evidence for release of proinflammatory cells and cytokines contained in fat following the bariatric surgery, and also consider the roles that the surgical resection of stomach and shortening of the bowel may also bring about this syndrome. The earlier onset is more likely due to surgical loss of defenses of the stomach and the later onset to a metabolic alteration of the presurgical obesity, involving fat metabolism, and/or the microbiome. The role of characteristic creeping fat of CD is also addressed.

High Incidence of Recurrent Crohn's Disease Following Colectomy for Ulcerative Colitis Revealed with Long Follow-Up.

BACKGROUND AND AIMS: Ulcerative colitis (UC) patients with progression of their disease despite optimized medical therapy may warrant "curative" proctocolectomy with end ileostomy or ileo-anal pouch (IPAA) anastomosis. The aim of our study was to assess the incidence of later recurrent ileitis that lead to altering the initial diagnosis to Crohn's disease (CD). METHODS: A retrospective analysis was conducted on the inflammatory bowel disease database at Lenox Hill Hospital. The database consisted of patients that were diagnosed with UC or CD based on clinical assessment, endoscopic appearance, gross and histological examination, and imaging between 1960 and 2015. The post-colectomy follow-up period was at least 10 years. Recurrent disease was classified by evidence of transmural inflammation in the distal ileum, fistulizing disease, or stricturing disease. RESULTS: From our IBD database, we identified 128 patients who underwent elective or urgent colectomy with the preoperative diagnosis of UC. Thirty-two (25%) had either an IPAA or end ileostomy with documented recurrence of inflammation in the small bowel mucosa consistent with CD. There was no significant difference between the type of surgical approach and the chance of recurrent disease (p = .20). The average time to clinically significant recurrence was 5 years. CONCLUSION: The incidence of recurrent CD following colectomy for ulcerative colitis, when followed postoperatively for an average of 20 years, was 25%, considerably more than previously reported. Patients who come to colectomy for ulcerative colitis and are followed for at least 10 years show a high incidence of recurrent Crohn's disease in the ileostomy or ileo-anal pouch. Extended follow-up should be included in patients coming to colectomy for ulcerative colitis before they should be considered cured of their disease.

Sequential Crohn's Ileitis, Ileosigmoidal Fistula, Segmental Sigmoid Polyposis, and Sigmoid Stricture: The Natural History.

BACKGROUND: We have previously recognized segmental sigmoid polyps as an indicator of a fistula from Crohn's ileitis to the sigmoid or the proximal rectum. In the course of this study, we realized that many patients with this fistula had no sigmoid polyps, but the sigmoid was the site of marked inflammation and early or late stricture formation. Furthermore, in some patients with a stricture, the fistula was not recognized until the surgeon (or the pathologist) dissected an inflammatory peri-ileal and/or a perisigmoidal mass.In this study, we have sought to clarify the sequence of events by focusing on the segmental inflammation and the stricturing of the sigmoid so that its significance can be recognized as a local complication of the ileitis and the progression of its severity as opposed to arising sui generis. MATERIALS AND METHODS: From our database of >3000 patients with inflammatory bowel disease at Lenox Hill Hospital, we identified 45 patients with Crohn's ileitis and ileosigmoid fistula (ISF): 24 had segmental sigmoid polyps and 18 had segmental inflammatory sigmoid strictures. The fistula was first seen by imaging in 36 patients, but not until resection by the surgeon or dissection by the pathologist in 7 patients. RESULTS: The method of diagnosis for the initial recognition of the ISF and the sigmoid stricture is presented in Table 1. In 36 of the 45 cases, the ISF was recognized by radiologic imaging. In total, 31 of the 36 cases required surgical intervention, not because of the fistula, but because of small-bowel obstruction due to the ileitis. In 7 of the 31 (22%) cases, the fistula was recognized only by dissection of the inflammatory ileosigmoid mass by the surgeon or examination of the surgical specimen by the pathologist. The sequence of events from the originating ileitis to the ISF to the segmental sigmoid polyposis and stricture, with the resulting sigmoid obstruction, is shown in Figures 1A-E. CONCLUSIONS: We emphasize the natural history of the ISF so that its recognition will lead to earlier medical management of the originating ileitis. Furthermore, it adds evidence of the recognition that the causative agent of Crohn's disease is carried by the fecal stream.

Segmental sigmoid polyposis as a colonoscopic indicator of an ileosigmoid fistula in Crohn's ileitis.

BACKGROUND AND AIMS: Ileosigmoid fistulas (ISFs) are frequently undiagnosed prior to surgery. This study was designed to describe a polyp or cluster of polyps limited to the sigmoid colon as a marker of ISF in patients with ileitis. This novel finding will increase a gastroenterologist's opportunity to detect them preoperatively and their prognostic implication of worsening ileitis. METHODS: The medical records of patients with Crohn's disease and ISF were reviewed to determine whether colonoscopy had revealed polyposis limited to the sigmoid colon and its frequency. RESULTS: Thirty-seven patients with Crohn's ileitis complicated by ISF were identified from our database. Twenty had one or more sigmoid polyps without polyps elsewhere in the colon suggesting the site of fistula exit. Fifteen of the patients had ISF and five had ileorectal fistula (IRF). The fistula was detected by various means, including colonoscopy, sigmoidoscopy, small bowel X-ray series, barium enema, computed tomography, and magnetic resonance enterography. The ISF was generally diagnosed prior to the recognition and significance of the segmental polyps. These polyps were inflammatory or hyperplastic on pathologic review. CONCLUSION: Most ISFs and IRFs are now found preoperatively by imaging and some are incidental surgical findings. The segmental sigmoid polyps that we describe should help the gastroenterologist to be suspicious of ISF. The polyps are a surrogate marker for the progression of the fistula and the underlying ileitis as they tend to appear after the fistula has matured and lead to increased intensity of medical therapy well before surgical intervention is required.

Histological healing favors lower risk of colon carcinoma in extensive ulcerative colitis.

AIM: To search for the answer in extensive ulcerative colitis as to whether histological inflammation persisting despite endoscopic mucosal healing serves to increase the risk of colon cancer (CC) or high grade dysplasia (HGD). METHODS: This is a single center (Lenox Hill Hospital) retrospective cohort and descriptive study of extensive ulcerative colitis (UC) for 20 years or more with a minimum of 3 surveillance colonoscopies and biopsies performed after the first 10 years of UC diagnosis. Data analyzed included: duration of UC, date of diagnosis of (CC) or (HGD), number of surveillance colonoscopies, and biopsies showing histological inflammation and its severity in each of 6 segments when endoscopic appearance is normal. Two subgroups of patients were compared: group 1 patients who developed CC/HGD and group 2 patients who did not develop CC/HGD. RESULTS: Of 115 patients with longstanding UC reviewed, 68 patients met the inclusion criteria. Twenty patients were in group 1 and 48 in group 2. We identified the number of times for each patient when the endoscopic appearance was normal but biopsies nevertheless showed inflammation. Overall, histological disease activity in the absence of gross/endoscopic disease was found in 31.2% (95%CI: 28%-35%) of colonoscopies performed on the entire cohort of 68 patients. Histological disease activity when the colonoscopy showed an absence of gross disease activity was more common in group 1 than group 2 patients, 88% (95%CI: 72%-97%) vs 59% (95%CI: 53%-64%). Only 3/20 (15%) of patients in group 1 ever had a colonoscopy completely without demonstrated disease activity (i.e., no endoscopic or histological activity) as compared to 37/48 (77%) of patients in group 2, and only 3.3% (95%CI: 0.09%-8.3%) of colonoscopies in group 1 had no histological inflammation compared to 23% (95%CI: 20%-27%) in group 2. CONCLUSION: Progression to HGD or CC in extensive ulcerative colitis of long standing was more frequently encountered among those patients who demonstrate persistent histological inflammation in the absence of gross mucosal disease. Our findings support including the elimination of histological inflammation in the definition of mucosal healing, and support this endpoint as an appropriate goal of therapy because of its risk of increasing dysplasia and colon cancer.

6-Mercaptopurine/Azathioprine remains an important contributor in managing Crohn's disease.

Two large studies concluded that AZA started early after diagnosis of Crohn's disease have no late maintenance value. This is contrary to previous studies on 6MP for Crohn's disease and could lead to negating the value of two of the few drugs that have been proven successful. We here outline the many reasons why 6MP remains a valuable drug in the treatment of Crohn's disease.

Expert opinion: experience with 6-mercaptopurine in the treatment of inflammatory bowel disease.

Arbitrarily, modern day treatment of inflammatory bowel disease begins with the introduction of immunosuppressives for ulcerative colitis. Clinical improvement with sulfasalazine had been meaningful but modest. Treatment with adrenocorticotropic hormone and corticosteroids led to clinical responses never before realized but it took much too long to recognize that they were not capable of maintaining remission, that adverse reactions were subtle but potentially devastating and that some other agent would be necessary to capitalize on their transient advantage. This of course was true in the treatment of Crohn's disease as well. Not much was ever made of the role of sulfasalazine for Crohn's disease, but with the severing of the diazobond and the elimination of the sulphur component, the 5-aminosalacylic acid (5-ASA) products clearly led to clinical improvement, especially in cases of Crohn's colitis and those with ileitis where the 5-ASA product was released in the terminal ileum and more proximal in the small bowel as well as in ulcerative colitis. The induction of remission was first demonstrated by 6-mercaptopurine (6-MP) with case reports and uncontrolled trials in patients with ulcerative colitis, but its placebo controlled trial for Crohn's disease firmly established its role in inducing remission. No subsequent trial has confirmed its similar role for ulcerative colitis, but nevertheless clinicians know well that 6-MP works at least as well and probably more effectively for ulcerative colitis than for Crohn's disease. What changes have taken place utilizing 6-MP in the management of inflammatory bowel disease since its introduction in the 1960's and 1970's and its trial for Crohn's disease published in the New England Journal of Medicine in 1980?

Is treatment with 6-mercaptopurine for colitis associated with the development of colorectal cancer?

BACKGROUND: Patients with ulcerative colitis and Crohn's colitis have an increased risk of colon cancer influenced by the duration, extent, and severity of disease. Surveillance colonoscopy serves to detect cancer and precancerous dysplasia at the earliest possible time. Reduction of inflammation should theoretically reduce the development of cancer. Immunosuppressives should do so, but there is a fear that indeed the risk of cancer might be increased with their use. Our study was conducted to determine whether a relationship exists between receiving treatment with 6-MP for ulcerative and Crohn's colitis and increasing or decreasing the incidence of colorectal cancer (CRC). METHODS: We conducted a single-center, retrospective cohort study of patients with long standing colitis (ulcerative and Crohn's) using the database of the senior investigator (B.I.K.). Two groups were matched based on their propensity to receive treatment with 6-MP; one group received 6-MP treatment, the other did not. Both groups were compared on the incidence of colon cancer. RESULTS: No significant differences existed between the two cohorts with regard to type of disease, duration, extent, age, and sex. Six out of 27 patients not on 6-MP and seven out of 27 patients on 6-MP developed CRC (P= 1). CONCLUSIONS: We conclude that there is neither sufficient evidence currently to state that 6-MP is associated with an increased development of CRC, nor that it has a chemopreventive effect.

Prognosis of lymphoma in patients following treatment with 6-mercaptopurine/azathioprine for inflammatory bowel disease.

BACKGROUND: 6-Mercaptopurine (6-MP) and azathioprine (AZA) are effective for induction and maintenance therapy of Crohn's disease (CD) and ulcerative colitis (UC). There is an increased risk of lymphoma in patients with inflammatory bowel disease (IBD) treated with 6-MP/AZA. Little, however, is known about the prognosis of IBD patients treated with 6-MP/AZA who develop lymphoma. METHODS: We conducted a retrospective review of 8780 records from three tertiary IBD centers and the records of 600 lymphoma patients from an academic Hematology and Oncology Center. The primary endpoint variable was survival of IBD patients with a lymphoma diagnosis treated or not treated with 6-MP/AZA. A secondary endpoint was the relative survival rate (by gender, race, and ethnicity) extrapolated from the Surveillance Epidemiology and End Results (SEER) database, computed for each subject. RESULTS: Fourteen IBD patients were diagnosed with lymphoma. Twelve had CD and two had UC. Seven patients had treatment with 6-MP/AZA and seven had not. Two patients who received 6-MP/AZA died (both 1 year after diagnosis) and two patients who had not received 6-MP/AZA died (one after 2 years, another 3 years after diagnosis), all from lymphoma. Survival at last follow-up was similar to expected survival based on extrapolated SEER data for both 6-MP/AZA treated and untreated patients. CONCLUSIONS: We found no differences of survival with lymphoma between IBD patients and expected survival for the general population. Also, the prognosis for those IBD patients treated with 6-MP/AZA was not worse than lymphoma patients not treated with 6-MP/AZA. Statistical analysis, however, was limited by the small sample size and heterogeneity of the patients studied.

Evaluation of 22 genetic variants with Crohn's disease risk in the Ashkenazi Jewish population: a case-control study.

BACKGROUND: Crohn's disease (CD) has the highest prevalence among individuals of Ashkenazi Jewish (AJ) descent compared to non-Jewish Caucasian populations (NJ). We evaluated a set of well-established CD-susceptibility variants to determine if they can explain the increased CD risk in the AJ population. METHODS: We recruited 369 AJ CD patients and 503 AJ controls, genotyped 22 single nucleotide polymorphisms (SNPs) at or near 10 CD-associated genes, NOD2, IL23R, IRGM, ATG16L1, PTGER4, NKX2-3, IL12B, PTPN2, TNFSF15 and STAT3, and assessed their association with CD status. We generated genetic scores based on the risk allele count alone and the risk allele count weighed by the effect size, and evaluated their predictive value. RESULTS: Three NOD2 SNPs, two IL23R SNPs, and one SNP each at IRGM and PTGER4 were independently associated with CD risk. Carriage of 7 or more copies of these risk alleles or the weighted genetic risk score of 7 or greater correctly classified 92% (allelic count score) and 83% (weighted score) of the controls; however, only 29% and 47% of the cases were identified as having the disease, respectively. This cutoff was associated with a >4-fold increased disease risk (p < 10e-16). CONCLUSIONS: CD-associated genetic risks were similar to those reported in NJ population and are unlikely to explain the excess prevalence of the disease in AJ individuals. These results support the existence of novel, yet unidentified, genetic variants unique to this population. Understanding of ethnic and racial differences in disease susceptibility may help unravel the pathogenesis of CD leading to new personalized diagnostic and therapeutic approaches.