Epidemiology and Natural History of Perianal Crohn’s Disease: A Systematic Review and Meta-Analysis of Population-Based Cohorts

Background and Aims Perianal Crohn’s disease (pCD) is a potentially severe phenotype of CD. We conducted a systematic review with meta-analysis to estimate cumulative incidence, risk factors, and outcomes of pCD in population-based cohort studies. Methods Through a systematic literature review through March 1, 2021, we identified population-based inception cohort studies reporting cumulative incidence of perianal disease (primarily abscess and/or fistula) in patients with CD. We estimated the cumulative incidence of pCD at presentation and 1-, 5-, and 10-year follow-up, and risk factors for perianal disease and outcomes including risk of major (bowel resection, proctectomy, ostomy) and minor perianal (incision and drainage, seton placement, etc.) surgery. Results In 12 population-based studies, prevalence of pCD was 18.7% (95% confidence interval [CI], 12.5%-27.0%) with 1-, 5-, and 10-year risk of perianal disease being 14.3% (95% CI, 7.9%-24.6%), 17.6% (95% CI, 11.3%-26.5%), and 18.9% (95% CI, 15.0%-23.4%), respectively. Approximately 11.5% of patients (95% CI, 6.7%-19.0%) had perianal disease at or before CD diagnosis. Colonic disease location and rectal involvement were associated with higher risk of pCD. Overall, 63.3% of patients (95% CI, 53.3-72.3) required minor perianal surgery and 6.4% of patients (95% CI, 1.8%-20.6%) required major abdominal surgery for pCD. Use of biologic therapy for pCD is common and has steadily increased throughout the years. Conclusions Approximately 1 in 5 patients with CD develops perianal disease within 10 years of CD diagnosis, including 11.5% who have perianal disease at presentation. Approximately two-thirds of patients require perianal surgery, with a smaller fraction requiring major abdominal surgery.

Perianal disease onset age is associated with distinct disease features and need for intestinal resection in perianal Crohn’s disease: a ten-year hospital-based observational study in China

Background and aims The significance of different ages of perianal disease (PD) onset in patients with perianal Crohn’s disease (PCD) remains unknown. We aimed to investigate the impact of paediatric-onset PD (POP) and adult-onset PD (AOP) on the Crohn’s disease (CD) course in a Chinese cohort. Methods The medical records of diagnosed PCD patients from 2008 to 2018 were reviewed retrospectively. The cumulative incidence and predictors of intestinal resection were calculated using the Kaplan–Meier and logistic regression analysis. Results Complex perianal fistulas (71.7% vs 50.0%, p = 0.011) and infliximab (IFX) treatment (33.3% vs 22.0%, p = 0.044) were more common among the POP patients (age < 18 years old, n = 84). A younger PD onset age (15.1 ± 2.9 vs 30.2 ± 10.5 years, p < 0.001) and shorter PCD diagnostic delay (12 vs 24 months, p = 0.033) was found in the POP cohort. AOP patients (age ≥ 18 years old, n = 209) had a higher rate of current smoking (12.9% vs 4.8%, p = 0.040), stricturing behaviour (42.1% vs 27.4%, p = 0.024) and intestinal resection (21.1% vs 4.8%, p = 0.001). The cumulative probability of intestinal resection in AOP patients was higher than that in POP patients (p = 0.007). In multivariable analysis, AOP (OR: 4.939, 95% CI 1.538–15.855, p = 0.007), stricturing behaviour (OR: 1.810, 95% CI 1.008–3.251, p = 0.047) and rectal inflammation (OR: 3.166, 95% CI 1.119–8.959, p = 0.030) were predictive factors for CD-related intestinal resection in all PCD patients. AOP patients with complex perianal fistula (OR: 2.257, 95% CI 1.041–4.891, p = 0.039) and POP patients with rectal inflammation (OR: 3.166, 95% CI 1.119–8.959, p = 0.030) were more likely to suffer intestinal resection. The IFX administration significantly decreased the rate of intestinal resection in AOP patients (r = − 0.900, p = 0.037). Conclusions The AOP patients have more complicated luminal disease and higher rate of intestinal resection than COP patients. The perianal diseases onset-age can provide clinical treatment guidance for individual management of CD patients.

Running Behind “POPO”—Impact of Predictors of Poor Outcome for Treatment Stratification in Pediatric Crohn's Disease

Background and Aims: Intensifying therapy for Paediatric Crohn's Disease (CD) by early use of immunomodulators and biologics has been proposed for cases in which predictors of poor outcome (POPO) were present. We investigated therapy stratifying potential comparing POPO-positive and -negative CD patients from CEDATA-GPGE®, a German-Austrian Registry for Paediatric Inflammatory Bowel disease.Methods: CD patients (1–18 years) registered in CEDATA-GPGE® (2004–2018) within 3 months of diagnosis and at least two follow-up visits were included. Disease course and treatments over time were analysed regarding positivity of POPO criteria and test statistical properties.Results: 709/1084 patients included had at least one POPO criterion (65.4%): 177 patients (16.3%) had persistent disease (POPO2), 581 (53.6%) extensive disease (POPO3), 21 (1.9%) severe growth retardation POPO4, 47 (4.3%) stricturing/penetrating disease (POPO6) and 122 (11.3%) perianal disease (POPO7). Patients with persistent disease differed significantly in lack of sustained remission &gt;1 year (Odd Ratio (OR) 1.49 [1.07–2.07], p = 0.02), patients with initial growth failure in growth failure at end of observation (OR 51.16 [19.89–131.62], p &lt; 0.0001), patients with stricturing and penetrating disease as well as perianal disease in need for surgery (OR 17.76 [9.39–33.58], p &lt; 0.001; OR 2.56 [1.58–4.15], p &lt; 0.001, respectively). Positive Predictive Value for lack of sustained remission was &gt;60% for patients with initial growth failure, persistent or stricturing/penetrating disease.Conclusion: Predictors of poor outcome with complicated courses of disease were common in CEDATA-GPGE®. An early intensified approach for paediatric CD patients with POPO-positivity (POPO2-4, 6-7) should be considered, because they have an increased risk to fare poorly.

Biologics recommendations in the ECCO guidelines on therapeutics in Crohn's disease: medical treatment

In 2019, the European Crohn’s and Colitis Organisation released guidelines for the medical management of Crohn’s disease, concerning the induction of remission, the maintenance of remission and the treatment of fistulising perianal disease. This review summarises the key recommendations regarding the use of biologics in these settings.

Is Intestinal Diversion an Effective Treatment for Distal Crohn’s Disease?

Background Fecal diversion with an ileostomy is selectively used in cases of medically refractory Crohn’s proctocolitis or advanced perianal disease. The aim of this study was to evaluate clinical improvement after fecal diversion in Crohn’s disease (CD) and factors associated with clinical improvement. Methods A retrospective chart review of adult CD patients undergoing ileostomy formation for distal disease between 2000 and 2019 at 2 CD referral centers was conducted. The primary outcome was the rate of clinical improvement with diversion that allowed for successful restoration of intestinal continuity. Secondary outcomes included the rate of clinical and endoscopic improvement after fecal diversion, ileostomy morbidity, need for subsequent total proctocolectomy and end ileostomy, and factors associated with a clinical response to fecal diversion. Results A total of 132 patients with a median age of 36 years (interquartile range, 25–49) were included. Mean duration of disease was 16.2 years (10.4) years. Indication for surgery was medically refractory proctocolitis with perianal disease (n = 59; 45%), perianal disease alone (n = 24; 18%), colitis (n = 37; 28%), proctitis (n = 4; 3%), proctocolitis alone (n = 4; 3%), and ileitis with perianal disease (n = 4; 3%). Medications used before surgery included corticosteroids (n = 59; 45%), immunomodulators (n = 55; 42%) and biologics (n = 82; 62%). The clinical and endoscopic response to diversion was 43.2% (n = 57) and 23.9% (n = 16). At a median follow-up of 35.3 months (interquartile range, 10.6–74.5), 25 patients (19%) had improved and had ileostomy reversal, but 86 (65%) did not improve, with 50 (38%) undergoing total proctocolectomy for persistent symptoms. There were no significant predictors of clinical improvement. Conclusions The use of a “temporary” ileostomy is largely ineffective in achieving clinical response.

Perianal disease remains an understudied and difficult complication in leukemia patients.

e19016 Background: Perianal infection is a rare and poorly understood complication of patients with acute myeloid/lymphocytic leukemia (AML/ALL). With the advancements in oncology, patients are living longer in an immunocompromised state and thus bearing the inherent problems such as infections that arise with it. Perianal infection and its management impacts patients' quality of life as well as interrupts their ongoing oncologic treatment. The optimal treatment strategy for perianal infections in this highly immunocompromised group remains unclear, as does the selection and outcomes of patients for operative intervention. The aim of this study is to identify patient characteristics associated with perianal infection and to delineate outcomes in patients that undergo operative intervention. Methods: The National Inpatient Sample (NIS) database was used to identify hospitalized patients with diagnoses of perianal abscess and AML/ALL between 2007 and 2015. Patient data were weighted to obtain national estimates. Demographics and clinical characteristics were compared between patients with and without perianal disease using Rao-Scott Chi-square test for categorical variables, and weighted simple linear regression for continuous variables. Characteristics and outcomes were compared between patients who underwent operative or non-operative management. Results: There were 12,626 (0.7%) patients with perianal disease among 1,782,778 AML/ALL patient admissions. Patients with perianal disease were more likely to be younger (43.9 (42.5 – 45.3) years, p < 0.001), male (67.4% vs 32.6%, p < 0.001) and white (65.8% vs 54.8%, p < 0.001). Length of stay (18.4 days vs 9 days, p < 0.001) and hospital cost ($54K vs $25K, p < 0.001) were higher in those with perianal disease, but there was no difference in in-hospital mortality (5.5% in those with perianal diseases vs 6.2% in those without, p = 0.150). Greater proportion of patients without perianal disease were discharged to hospice (12.6% patients without perianal disease vs 5.1% patients with perianal disease, p < 0.001). Receiving a surgical intervention did not improve outcomes with respect to in-hospital mortality (5.9% operative vs 5.4 non-operative, p = 0.596), length of stay (20.2 days vs 18.2 days, p = 0.582) or hospital cost ($67K vs $53K, p = 0.525). Conclusions: Perianal disease is a rare but distressing complication in AML/ALL patients associated with longer hospital stays and higher hospital costs. Operative intervention for perianal disease did not reduce rates of in-hospital mortality, length of stay or hospital cost but it does impact the probability of discharge to hospice. Non-operative and operative intervention both remain equivocal in changing the outcomes these patients. Further studies are required to examine these associations and determine best practices for treatment of this condition in this complex patient population.

P202 De novo Inflamatory Bowel Disease after solid organ transplantation

Background The aim of this study was to determine the disease phenotype, evolution and therapeutic needs of de novo inflammatory bowel disease (IBD) in transplanted patients. Methods A retrospective single center study that included all patients who developed IBD after solid organ transplantation in a tertiary hospital. Data collected included transplant-related variables, IBD phenotype, course of the disease and its treatment. A control group of non-transplanted IBD patients was randomly selected. Results We included 17 post-transplanted IBD patients and 57 non-transplanted IBD patients. Post-trasplanted patients were older at diagnosis, had greater colonic involvement, with an inflammatory behaviour, absence of perianal involvement and extraintestinal manifestations compared to control group (Table 1). The most common immunosuppression regimen was tacrolimus+mycophenolate mofetil (MMF)+prednisone and the most frequent change after diagnosis was the switch of MMF for azathioprine. De novo IBD patients required less biological therapy than the control group (11.8 vs 42.1% p 0.02) and none required surgical intervention compared to 35.1% in the control group (p 0.002). Multivariate analysis carried out on the total population showed that active smoking, perianal disease and extraintestinal manifestations were associated with a greater need for biologics, while the only factor that influenced surgical risk was stricturing and penetrating behaviour of Crohn′s disease. Conclusion De novo IBD after solid organ transplantation has a favorable course, predominating the inflammatory behaviour and requiring less biological therapy and surgical interventions. The absence of extraintestinal manifestations and perianal disease stands out.

P339 Pregnant women with perianal Crohn’s Disease: suggestions for the improvement of the current guideline on delivery method

Background Pregnant women with active perianal Crohn’s disease (CD), have an indication for a caesarean section according to the current ECCO guidelines. This advice is based on the assumption that vaginal delivery leads to exacerbation of perianal disease and to worsening of faecal continence. However, there is no strong evidence to support this. This study aims to examine the effects of delivery method on perianal disease progression and faecal incontinence in women with perianal CD Methods In this retrospective cohort study, 209 women were selected from a large IBD database within a tertiary hospital in the Netherlands. All women are aged &gt;18 years, have perianal CD, and have at least one child. In addition, 102 women of this cohort completed a questionnaire. Faecal continence was scored using the Vaizey-score. Descriptive analysis using SPSS and linear regression analysis were performed. The outcome was corrected for the years after delivery (median 15, range 0-55). p-values &lt;0,05 were considered statistically significant. Results The caesarean section rate within this cohort was 27,8%, which is high when compared the general Dutch population (14%). Within the group of women who delivered at least one child vaginally (n=84), 25,5% reported an alteration of faecal continence, compared to 18,8% of the women who never had a vaginal delivery (n=18). No significant relation between mode of delivery and faecal continence was found (B 0,97 [-1,19-3,14] p 0,375). The average Vaizey-score within this cohort in women who delivered solely through caesarean section had a median Vaizey-score of 5 (range 0-12). Women who had at least one vaginal delivery had an median Vaizey-score of 7 (range 0-20). In a large study amongst the general Dutch population (n=1259) a median Vaizey-score of 11 (range 0-17) was reported. Conclusion Faecal incontinence after vaginal delivery in CD women with perianal fistula is not significantly increased. Therefore the current guideline to advice a caesarean section should be adjusted and other factors such as the location of the fistula should be taken into account. To draw solid conclusions, better registration of fistula location and objective documentation of fistula activity (using PDAI-score) and stool consistency is needed.

P542 Clinical presentation, disease behavior and management of inflammatory bowel disease at extremes of age

Background The natural history of patients with Montreal classification A2 group is well studied. Available studies on disease characteristics at extreme ages, which form 10%-25% of patients with IBD, focused on pediatric or elderly population, but not all age groups together.1 We aimed to compare the disease characteristics of pediatric- (≤16 years, P) and elderly- (≥60 years, E) onset IBD with 17-59Y middle aged group (M). Methods 266 consecutive patients with IBD were divided into 3 groups according to age of onset. Information about disease location, extent, behavior and need for immunosuppressants / biologics and surgery was entered in pro-forma. Results The table shows details of 258 (P 46, M 170, E 42) patients. 8 IBD-unclassified patients were not included in the analysis as numbers were too small to compare the differences. Among UC patients, pancolitis was more common in the pediatric population (p=0.018) and indolent behavior was more common in elderly population (p=0.005). Almost all UC patients requiring colectomy had extensive colitis(p=0.008). While among CD patients, elderly had more of ileal (p=0.04) and pediatric group had more colonic involvement (p=0.02). Perianal disease was least common in elderly CD group (p=0.03). There were no treatment differences in UC patient subgroups while elderly CD patients less frequently required steroids, biologics, immunosuppressants and surgery(p&lt;0.05) and younger CD patients needed biologics much more frequently (p=0.005). Conclusion Pediatric UC had more pancolitis(E3) while elderly UC had milder disease with EIM less frequently. Significant co-relation was noted between colectomy and extensive colitis. Pediatric CD patients had more colonic (L2) disease with more requirement of biologics, while elderly CD group had more common ileal (L1) disease, least common perianal disease and less requirement of all treatment modalities when compared to adults. This study highlights possible different Indian IBD disease spectrum in contrast to Western literature. 1. Nimmons D, Limdi JK. Elderly patients and inflammatory bowel disease. World J Gastrointest Pharmacol Ther. 2016;7:51–65.