Crohn’s disease in childhood: modern approaches to treatment (a literature review)

The aim of the work. To provide world experience and features of Crohn’s disease (CD) treatment in children by reviewing and analyzing modern scientific literary sources, given the need to develop a unified therapeutic strategy for CD in childhood. The relevance of CD treatment in children stems from its debut in childhood in a large number of patients, in connection with this, a more severe and aggressive course; the presence of various surgical complications, a high risk of malignancy, and the absence of generally accepted approaches to conservative and surgical treatment. The analysis of the results of modern scientific and clinical studies on the treatment of CD in children with the characteristics of drug groups and their individual representatives, methods of treatment for patients with surgical complications of CD in childhood, lifestyle correction, psychosocial adaptation, enteral nutrition, rehabilitation, and dispensary observation is presented. The principle of a cascade approach to the treatment of CD is illustrated by an example of the WGO recommendations. Conclusions. The treatment of CD should be individual and comprehensive, with the simultaneous correction of local manifestations of the disease, surgical complications and changes in the general condition of a patient, as well as with dieting and lifestyle correction. The expected therapeutic effect of the use in children with CD of a large number of the proposed groups of medications is debatable or clinically unproven, which necessitates the implementation of further scientific and clinical research. The information presented will help doctors determine the optimal range of individual medical, rehabilitation measures and recommendations for everyone with CD in childhood and effectively provide active follow-up for patients.

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Crohn’s disease: a population-based study of surgery in the age of biological therapy

International Journal of Colorectal Disease ◽

10.1007/s00384-021-03930-w ◽

2021 ◽

Author(s):

Christian Stöss ◽

Maximilian Berlet ◽

Stefan Reischl ◽

Ulrich Nitsche ◽

Marie-Christin Weber ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Minimally Invasive ◽

Biological Therapy ◽

Hospital Admissions ◽

Diagnosis Related Groups ◽

Age Distribution ◽

Considerable Proportion ◽

Discharge Data ◽

Number Of Patients

Abstract Purpose Despite primary conservative therapy for Crohn’s disease, a considerable proportion of patients ultimately needs to undergo surgery. Presumably, due to the increased use of biologics, the number of surgeries might have decreased. This study aimed to delineate current case numbers and trends in surgery in the era of biological therapy for Crohn’s disease. Methods Nationwide standardized hospital discharge data (diagnosis-related groups statistics) from 2010 to 2017 were used. All patients who were admitted as inpatient Crohn’s disease cases in Germany were included. Time-related development of admission numbers, rate of surgery, morbidity, and mortality of inpatient Crohn’s disease cases were analyzed. Results A total number of 201,165 Crohn’s disease cases were included. Within the analyzed time period, the total number of hospital admissions increased by 10.6% (n = 23,301 vs. 26,069). While gender and age distribution remained comparable, patients with comorbidities such as stenosis formation (2010: 10.1%, 2017: 13.4%) or malnutrition (2010: 0.8%, 2017: 3.2%) were increasingly admitted. The total number of all analyzed operations for Crohn’s disease increased by 7.5% (2010: n = 1567; 2017: n = 1694). On average, 6.8 ± 0.2% of all inpatient patients received ileocolonic resections. Procedures have increasingly been performed minimally invasive (2010: n = 353; 2017: n = 687). The number of postoperative complications remained low. Conclusion Despite the development of novel immunotherapeutics, the number of patients requiring surgery for Crohn’s disease remains stable. Interestingly, patients have been increasingly hospitalized with stenosis and malnutrition. The trend towards more minimally invasive operations has not relevantly changed the rate of overall complications.

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Improved Biochemical Parameters in Patients Who Undergo Early Resection in Isolated Ileocaecal Crohn’s Disease

Surgery Research and Practice ◽

10.1155/2017/4396573 ◽

2017 ◽

Vol 2017 ◽

pp. 1-5

Author(s):

Mirzafaraz Saeed ◽

Hari Hullur ◽

Amro Salem ◽

Abbas Ali ◽

Yousif Sahib ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Surgical Resection ◽

Complete Blood Count ◽

Long Term Results ◽

Number Of Patients ◽

Long Term Follow Up ◽

One Year

Introduction. The aim of this study is to evaluate the outcome of introduction of early surgery in the course of isolated ileocecal Crohn’s disease, where there is no absolute indication of surgery. Methods. Observational study involving patients with isolated ileocecal Crohn’s disease who underwent early surgical resection (within one year of the presentation of the hospital). A complete blood count, ESR, and CRP were done and compared between the preoperative value, 1st postoperative visit (3-4 weeks), and last follow-up visit. Statistical analysis was done using Analysis of Variance (ANOVA) to compare the different figures. Results. There was a statistically significant increase in the hemoglobin levels between preoperative, postoperative, and long-term follow-up and a significant decrease in leukocyte count between the pre- and postoperative values (F=19.8, p<0.001 and F=8.9, p=0.002, resp.). Similarly, the ESR and CRP values were decreased significantly at long-term follow-up (F=8.5, p=0.019 and F=8.3, p=0.013, resp.). Conclusion. Early surgical resection in isolated ileocaecal Crohn’s disease achieved significant biochemical improvements. These successful results in this small number of patients indicate that early surgical intervention may provide better outcomes. These initial results encourage larger and comparative studies of long-term results versus long-term use of biological agents.

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CROHN’S DISEASE IN CHILDREN: THE CURRENT STATE OF THE PROBLEM

PEDIATRIA Journal named after G N SPERANSKY ◽

10.24110/0031-403x-2021-100-6-78-85 ◽

2021 ◽

Vol 100 (6) ◽

pp. 78-85

Author(s):

A.S. Bekin ◽

◽

E.Yu. Dyakonova ◽

A.N. Surkov ◽

A.P. Fisenko ◽

...

Keyword(s):

Crohn’S Disease ◽

Surgical Treatment ◽

Crohn's Disease ◽

Granulomatous Inflammation ◽

Unknown Etiology ◽

Systemic Complications ◽

Current State ◽

Conservative And Surgical Treatment ◽

Scientific Ideas ◽

Local And Systemic Complications

Crohn's disease (CD) is chronic recurrent bowel disease of unknown etiology, characterized by segmental transmural granulomatous inflammation, mainly with the development of local and systemic complications. Despite the active development of conservative therapy methods, the number of drug-resistant forms of CD and complications of the disease requiring surgical treatment continues to increase. The article reflects modern scientific ideas about the methods of diagnosis, conservative and surgical treatment of CD in children.

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Prevalence of Fistulizing Crohn’s Disease in the United States: Estimate From a Systematic Literature Review Attempt and Population-Based Database Analysis

Inflammatory Bowel Diseases ◽

10.1093/ibd/izz056 ◽

2019 ◽

Vol 25 (11) ◽

pp. 1773-1779 ◽

Cited By ~ 8

Author(s):

David A Schwartz ◽

Ignacio Tagarro ◽

Mary Carmen Díez ◽

William J Sandborn

Keyword(s):

United States ◽

Health Care ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Literature Review ◽

Systematic Literature Review ◽

The United States ◽

Population Based ◽

Number Of Patients ◽

Reported Data

Abstract Background Fistulas may arise as a relevant complication of Crohn’s disease (CD). Despite their clinical significance and the substantial burden imposed on patients, limited data are available on the epidemiology of fistulizing CD in the United States. Methods A systematic literature review was conducted to identify data published between 1970 and 2017 on the epidemiology of fistulas in patients with CD, with the aim to estimate the number of prevalent cases in the United States. Retrieved titles and abstracts were screened by 2 independent researchers for inclusion criteria (US population-based studies reporting data on the epidemiology of fistulizing CD). To validate the literature-based estimate, data from a US claims database (Truven Health MarketScan database) were analyzed. This database has broad geographic coverage, with health care data for >60 million patients during the period of the analysis. Results The literature search retrieved 7 articles for full-text review, and only 1 met the criteria for inclusion. This study described the cumulative incidence of fistulas in a CD population from Minnesota over 20 years. From the reported data, the estimated number of prevalent cases with fistulizing CD in the United States was ~76,600 in 2017 (~52,900 anal, ~7400 rectovaginal, ~2300 enterocutaneous, and ~14,100 internal). Analysis from the US health care database resulted in an estimated number of ~75,700 patients, confirming the robustness of the original estimate from the literature. Conclusions Based on 2 separate analyses, the estimated number of patients with fistulizing CD in the United States is ~77,000 patients.

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P096 Which patients with known Crohn’s disease after an ileo-colonoscopy will benefit most from small bowel capsule endoscopy?

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab076.225 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S193-S194

Author(s):

N Viazis ◽

A Mountaki ◽

K Koustenis ◽

C Veretanos ◽

K Arvanitis ◽

...

Keyword(s):

Crohn’S Disease ◽

Small Bowel ◽

Crohn's Disease ◽

Capsule Endoscopy ◽

Terminal Ileum ◽

Imaging Techniques ◽

Clinical Manifestations ◽

Endoscopic Techniques ◽

Proximal Small Bowel ◽

Number Of Patients

Abstract Background Ileo-colonoscopy with biopsies is considered the gold standard for the diagnosis and management of Crohn’s disease (CD). In contrast, the role of small bowel capsule endoscopy (SBCE) is limited currently in cases where ileo-colonoscopy and imaging techniques raise doubts on the diagnosis or cannot explain certain clinical manifestations of Crohn’s disease. The aim of our study was to determine whether there are patients with endoscopically confirmed established CD who could get additional benefit by SBCE. Methods Retrospective analysis of prospectively collected data from 6301 patients subjected to SBCE in our department from 1st March 2003 to 18th February 2021. Patients with CD diagnosed by ileo-colonoscopy or total colonoscopy only (because the ileo-caecal valve could not be intubated) prior to SBCE were included in the study and biopsies. SBCE had been performed only in patients who lacked any clinical and/or imaging (CT/MRE) evidence of bowel obstruction. The presence and extent of mucosal lesions, namely local and/or diffuse erythema, erosions and ulcers (aphthous, superficial and/or deep) throughout the small intestine, which may be difficult to identify by traditional imaging, could either explain clinical manifestations unrelated to the findings of colonoscopy or led onto reassessment of applied treatments were sought by SBCE. Results The study sample consisted of 1002 patients (males/females: 511/491, mean age ± SD: 52.6±27.3). Among these, CD had been diagnosed with colonoscopy (and not ileo-colonoscopy) in 293 (29.2%) subjects and small bowel involvement was seen in 104 (35.5%) patients. The vast majority of these patients had lesions only in the terminal ileum (n=81, 77.8%), while the remaining patients (n=23, 22.2%) had additional lesions in more proximal parts of the small bowel. Among the 709 (70.8%) patients in whom CD had been diagnosed by ileo-colonoscopy, lesions in the terminal ileum were found in 407 (57.4 %) patients; SBCE revealed more proximal lesions in 104 patients (25.5%). In the remaining 307 patients (43.3%) in whom ileo-colonoscopy did not reveal terminal ileum involvement, more proximal small bowel lesions were seen in 35 (11.4%) patients. These lesions were mainly apthoid ulcers or larger ulcers, findings that led to a change in therapeutic management in 17 patients (48.6%). Conclusion SBCE identifies more proximal small bowel lesions in a substantial number of patients with CD established by traditional endoscopic techniques. When these lesions are more severe and extensive they may lead onto re-evaluation of the personalized therapeutic strategies.

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Current Overview on the Use of Mesenchymal Stem Cells for Perianal Fistula Treatment in Patients with Crohn’s Disease

Life ◽

10.3390/life11111133 ◽

2021 ◽

Vol 11 (11) ◽

pp. 1133

Author(s):

Marcin Włodarczyk ◽

Katarzyna Czerwińska ◽

Jakub Włodarczyk ◽

Jakub Fichna ◽

Adam Dziki ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Treatment Options ◽

Perianal Fistula ◽

Current Treatment ◽

Culture Conditions ◽

Optimal Dosage ◽

Number Of Patients

Perianal fistula in patients with Crohn’s disease is an extremely challenging condition. The disease tends to reoccur, and with current treatment options, a large number of patients are left with active ailment and experience major morbidity. In recent years, hopeful results regarding local use of mesenchymal stem cells (MSCs) in perianal Crohn’s disease have been published. Although to this day there are no clear guidelines determining optimal dosage, injections frequency and culture conditions, their efficiency has proven to be much higher than conventionally used methods. According to studies, they can effectively induce as well as maintain fistula closure. This approach also avoids common side effects related to conventional surgical treatment.

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P345 Lack of anti-TNF drugs levels in fistula tissue: A reason for non-response in Crohn’s perianal fistula?

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.474 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S330-S331

Author(s):

S Adegbola ◽

M Sarafian ◽

K Sahnan ◽

A Pechlivanis ◽

R Phillips ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Limit Of Detection ◽

Significant Proportion ◽

Perianal Fistula ◽

Serum Levels ◽

Positive Control ◽

Response To Therapy ◽

Perianal Fistulas ◽

Number Of Patients

Abstract Background Anti-TNF therapy is recommended as a treatment for patients with Crohn ́s perianal fistulas. However, a significant proportion of patients have a sub-optimal response to anti-TNF therapy. Higher serum levels of anti-TNF agents have been associated with improved outcomes in perianal Crohn’s disease. Currently, it is unknown whether anti-TNF agent levels can be detected in tissue from fistula tracts themselves and whether this is associated with response. Methods We undertook a pilot study to develop a method to measure fistula tissue levels of anti-TNF medication (infliximab and adalimumab) using a targeted proteomic technique that employs ‘signature peptide detection’ following trypsin digestion called ultraperformance liquid chromatography–mass spectrometry (UPLC-MS), to quantify a protein. The targeted UPLC- MS/MS detection and quantification method implemented were previously validated. Biopsies were obtained from patients with Crohn’s disease who underwent an examination under anaesthesia for worsening fistula symptoms despite maintenance anti-TNF therapy. Idiopathic (cryptoglandular) tissues from purposively sampled matched (age/gender) patients were analysed as negative controls and these samples were spiked with anti-TNF drugs as positive controls. Results Tissue was sampled from the fistula tracts of seven patients with Crohn’s perianal disease (5 patients were on adalimumab and 2 patients were on infliximab). The limit of detection (LOD) and linearity range of the method was assessed for each drug in the spiked idiopathic fistula samples. Infliximab and adalimumab had a LOD of 0.004 and 2 μg/ml respectively with linearity demonstrated for both drugs. The anti-TNF drugs, infliximab and adalimumab, were not detected in fistula samples from any of the Crohn’s patients despite detection in ‘spiked’ positive control samples. In addition, to validate the result, samples were concentrated (x10) and still there was no detection of the drugs in the test samples. Conclusion The anti-TNF drugs adalimumab and infliximab were not detected in fistula biopsy samples from patients with Crohn ́s perianal fistulas with refractory symptoms despite maintenance therapy. This raises the question on the role of tissue penetrance of anti-TNF drugs in response to therapy. Further work is required in a larger number of patients to validate the findings observed and investigate whether any correlation exists between tissue and serum levels of anti-TNF and clinical outcome.

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P370 Endoscopic balloon dilatation in paediatric stricturing Crohn’s disease: A retrospective collaborative study of the paediatric IBD Porto group of ESPGHAN

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.499 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S349-S349

Author(s):

O Ledder ◽

J Viala ◽

D Urlep ◽

D Serban ◽

L De Ridder ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Balloon Dilatation ◽

Surgical Intervention ◽

Collaborative Study ◽

Ileocecal Valve ◽

Duodenal Perforation ◽

Endoscopic Balloon Dilatation ◽

Number Of Patients ◽

Endoscopic Balloon

Abstract Background Endoscopic balloon dilatation (EBD) is an effective management strategy in stricturing Crohn’s disease (CD). While adult studies showed a high success rate of improved symptoms and avoiding surgical intervention, very little has been published in children. We thus present a multi-centre retrospective cohort study of EBD in paediatric CD from 9 centres affiliated with the Paediatric IBD Porto group of ESPGHAN. Methods Demographics, imaging, serological data, clinical indices (including the newly-developed modified CD obstructive score (mCDOS)), post-EBD complications and need for surgical intervention were recorded on electronic case report forms. Results Thirty-nine balloon dilatations were performed on 34 children (20 (59%) male, mean age 14.3 ± 3.4 years, median disease duration 3.5 years (IQR 1.1–5.8)). Successful avoidance of surgical intervention was recorded in 26 (76%) children, during a median follow-up period of 24 weeks (IQR 8–24). There was an increase in number of patients in clinical remission (wPCDAI < 12.5) following EBD from 20% pre-dilation to 36% (ns), 53% (p = 0.017) and 57% (p = 0.015) at weeks 2, 8 and 24, respectively. There was a trend to reduced mCDOS, from 5 (IQR 0–15) at baseline to 5 (0–6.25) (ns), 5 (0–5) (p = 0.04), and 0 (0–7.5) (ns), respectively. The stricture was primary in 31 (79%) children (17 in the ileocecal valve (ICV) region, 3 in the terminal ileum, 9 in the colon and 1 in the duodenum), 7 of whom had multiple strictures. Eight (21%) children had an anastomotic stricture. Median stricture length was 3 cm (IQR 2–4.7), bowel wall thickness 7 mm (IQR 5–8) and median pre-stenotic dilatation of 4.5 cm (IQR 4–5). Median maximal dilatation diameter was 15 mm (IQR 12–18) with the successful passage of the colonoscope in 26/39 (67%). There were 3 (8%) post-dilatation complications including one bleed following rectal dilatation (with spontaneous resolution) and 2 perforations (1 duodenal perforation managed conservatively and 1 ICV perforation requiring surgical resection). Conclusion EBD is an effective and safe technique in paediatric stricturing CD with over 75% avoiding surgery by one year and 8% complications. Further data are required to better identify optimal stricture features and dilatation diameter in children.

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P115 Real-world experience of peri-operative treatments on surgical complications after Ileo-caecal resection in Crohn’s disease

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.244 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S193-S194

Author(s):

S Di Stefano ◽

C Liefferinckx ◽

A Cremer ◽

L Amininejad ◽

A Van Gossum ◽

...

Keyword(s):

Risk Factors ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Anastomotic Leakage ◽

Surgical Complications ◽

Protective Role ◽

Infectious Complications ◽

Surgical Recurrence ◽

The Impact

Abstract Background The current recommendations remain vague as to whether biologics are safe or deleterious when surgery is contemplated in patients with Crohn’s disease (CD). Conflicting data do not enable to adopt a definitive position on the time to surgery. The aims of this study were to evaluate the impact of perioperative treatments on the rate of surgical complications and to report surgical recurrence rate of CD after ileo-caecal (IC) resection. Methods This was a retrospective monocentric cohort study of consecutive CD patients who underwent IC resection between 1996 and 2018. An ethical committee has been approved (P2019/376). The overall rate of surgical complications was evaluated within 30 days after surgery. The effect of pre- and postoperative treatments was assessed on overall morbidity, general and infectious complications, anastomotic leakage and risk factors. Statistical analyses were performed using SPSS. Results Demographic data of the 165 CD patients who underwent a primary IC resection are presented in Table 1. The median age at time of the first IC resection was 35 years (IQR 24–44) while the median follow-up was 6.1 years (IQR 1–11). The overall rate of complications was 18% including 8.7% and 3.3% patients with infectious complications and anastomotic leakage, respectively. No risk factors have been found to be associated with surgical complications. In particular, immunosuppressants and biologics did not increase the risk of surgical complications. Twenty-four per cent of patients (n = 39/160) needed a second IC resection due to stenosis at the anastomosis site in 69.2% of cases (n = 27/39). Surgical recurrence was found to increase linearly over time with a second surgery after a median follow-up of 8 years (IQR 2–12). Anti-TNF used as post-operative treatment had a protective role on surgical recurrence in multivariable regression with odd ration (OR) of 0.15, p = 0.001 (Table 2). Conclusion Prevalence of complications after an IC resection in CD patients was of 18% in this retrospective monocentric cohort. No risk factors were found to be associated with surgical complications. Anti-TNF seems to have a protective role on surgical recurrence.

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45 Years with Dalziel's (Crohn's) Disease

Scottish Medical Journal ◽

10.1177/003693308102600211 ◽

1981 ◽

Vol 26 (2) ◽

pp. 145-147 ◽

Cited By ~ 1

Author(s):

E. M. Quigley ◽

P. R. Mills ◽

G. Watkinson

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Case History ◽

Surgical Complications ◽

Surgical Intervention ◽

Regional Enteritis

A patient with chronic regional enteritis, diagnosed in Glasgow in 1935 who has now survived for 45 years despite nine operations and the development of multiple nutritional and post-surgical complications is described. Her case history, one of the longest in the literature provides a unique record of the course of this disease and of the consequences of surgical intervention.

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