Inflammatory Bowel Disease Flashcards
What are the common types of inflammatory bowel disease (IBD) in children?
Classic IBD consists of Crohn’s disease (CD) and ulcerative colitis (UC).
Unclassified IBD (IBD-U) is of increasing importance, and must be diagnosed accurately to reduce the risk of inappropriate surgical interventions for the incorrect type of IBD.
Approximately 10–15% of pediatric patients will be diagnosed with IBD-U, as they cannot be definitively categorized with CD or UC.
A diagnosis of indeterminate colitis (IC) may only be used in the situation in which a colectomy has been performed, and the distinction between CD and UC still remains uncertain.
What are the predisposing risk factors for Crohn’s disease?
Crohn’s disease is most likely the result of an interplay between genetic susceptibility, exposure to environmental factors, and intestinal microflora.
The result is an abnormal mucosal immune response, leading to compromised epithelial barrier function and adaptive immune dysregulation.
A family history of CD is seen in up to 12% of patients at diagnosis, though this rate may change during the patient’s life.
Ashkenazi Jews exhibit a 3–4 times increased risk of developing the disease.
There is an increasing number of alleles that have been associated with pediatric CD.
Commonly detected variants in the risk loci for both CD and UC are able to explain only a small fraction of the expected heritability.
Causative genes include NOD2, IL23R, CARD9 and RNF186.
What are the predisposing risk factors for ulcerative colitis?
Similar to CD, UC is most likely the result of an interplay between genetic susceptibility, exposure to environmental factors, and intestinal microflora [1].
The estimated prevalence of IBD among family members with UC is 8–12%.
The advent of Genome Wide Association Study (GWAS) has led to greater understanding of the links between HLA loci and UC.
Strong associations have been shown with HLA DRB1, HLA DQA1 and HLA-DRB*01:03 [2].
When does inflammatory bowel disease most commonly affect children?
Approximately 25% of IBD patients will present before the age of 20 years.
The peak onset in children is during adolescence, with a pediatric incidence of 10 per 100,000 children in USA and Canada [1].
Pediatric UC has a tendency to have more extensive disease than adult-onset UC at the time of diagnosis.
However, the gene expression in adult and pediatric patients is shared.
What are the extra-intestinal symptoms of inflammatory bowel disease?
Dermatological: Erythema nodosum, pyoderma gangrenous
Musculoskeletal: Arthritis, growth failure, osteopenia, osteoporosis, ankylosing spondylitis
Hepatic: Primary sclerosing cholangitis, autoimmune hepatitis
Ocular: Episcleritis, uveitis, iritis
Renal: Nephrolithiasis
Pancreatic: Pancreatitis
Hematological: Anemia, venous thromboembolism
What is very early onset inflammatory bowel disease (VEO-IBD)?
The age at onset of IBD is intimately linked with the clinical presentations and progression of the disease.
Pediatric-onset IBD (<17years), early-onset IBD (<10years), VEO-IBD (<6years), infantile-onset IBD (<2years), and neonatal-onset IBD (<28 days) may all present in different ways with regards to disease location and severity.
Children with onset during the neonatal or infantile periods suffer from a more severe disease course, are known to have higher rates of affected first-degree relatives, and are more resistant to immunosuppressive therapies.
In addition, it has been demonstrated that patients with VEO-IBD have an increased gene-variant burden, compared with patients that are older at diagnosis.
It is important to consider a potential immunodeficiency syndrome in children with VEO-IBD, due to the high prevalence of gastrointestinal symptoms in children with an immunodeficiency.
Describe the common laboratory findings in patients with inflammatory bowel disease.
According to the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), initial blood tests should include a complete blood count, at least two inflammatory markers, albumin, transaminases and ƴGT. It has been established that fecal calprotectin is superior for the detection of intestinal inflammation to any blood investigation.
The sensitivity for fecal calprotectin in the diag- nosis of IBD has been shown to be as high as 0.97.
How has the radiological investigation of patients with inflammatory bowel disease changed in the last decade?
The radiological investigation of pediatric IBD has been significantly altered in the last decade by the increasing utilization of magnetic resonance imaging (MRI).
The main advantage of MRI, particularly in the pediatric population, is the avoid- ance of ionizing radiation.
Pelvic MRI is particularly useful in the assessment of perianal disease, which is a common presenting feature in pediatric CD.
Whilst upper gastrointestinal contrast studies (small bowel follow-through) were previously the mainstay of small bowel imaging, magnetic resonance enterography (MRE) is now considered the modality of choice for evaluation of the small bowel.
This is particularly useful when assessing children prior to colectomy, as the presence and extent of small bowel disease is critical to operative planning.
How do the endoscopic findings differ between Crohn’s disease and ulcerative colitis?
CROHN'S Fistulae often present Usually spared Skip lesions Cobble-stone appearance Involvement common (>25%) Ulceration
ULCERATIVE COLITIS Rare to have anal lesions Present in rectum in the majority Contiguous Circumferential (Colon) Backwash ileitis (10%) Spared Esophagus
What are the standardized scoring systems for pediatric inflammatory bowel disease?
The pediatric Crohn’s disease activity index (PCDAI) was developed in 1991 by Hyams and colleagues to provide a reproducible stratification system for disease severity [3].
The components of the PCDAI include:
(1) subjective recall of symptoms (abdominal pain, stool frequency and character, general well-being);
(2) objective measures (gender, age, hematocrit, ESR, albumin); and;
(3) examination findings (weight, height, abdomen, perianal disease, extra-intestinal manifestations).
The combined score may then be used to determine the severity of disease (<10=remission, 11–30=mild disease, >30=moderate/severe).
The PCDAI has been shown to closely correlate with the global assessment performed by physicians, and may be used to assess the effect of treatments.
The pediatric ulcerative colitis activity index (PUCAI) was developed in 2007 by Turner and colleagues. [4]
The authors sought to create a non-invasive activity index of UC that was reproducible, and accurately assessed response to treatment.
The components of the PUCAI include:
(1) abdominal pain;
(2) rectal bleeding;
(3) stool consistency;
(4) stool frequency;
(5) nocturnal stools; and;
(6) activity level.
The combined score may then be used to determine the severity of disease (<10 = remission, 11–34 = mild disease, 35–64 = moderate; 65–85 = severe). In addition, a change in the PUCAI score ≥20 was defined as significant.
Describe the medical management of a pediatric patient with inflammatory bowel disease.
The introduction of biologic therapies, with a greater focus upon targeting of the immune system, has radically altered the management of pediatric IBD.
These therapies, including anti-TNF agents and monoclonal antibodies to lymphocytes and interleukins, now augment the more traditional treatments in pediatric patients.
The predominant goals of medical therapy are control of symptoms, induction and maintenance of remission, and avoidance of complications (stricture, fistula, abscess, malignancy).
The mainstays of therapy include:
(1) corticosteroids (largely used for induction therapy);
(2) 5-aminosalicylates (exert a topical immunomodulatory and anti-inflammatory effect);
(3) thiopurines (immunosuppressive agents effective in maintaining remission);
(4) methotrexate (immunomodulator effective at inducing and maintaining remission);
(5) exclusive enteral nutrition (useful in induction, but rarely tolerated for prolonged periods); and;
(6) biologics (used in both induction and maintenance).
Is the use of Infliximab associated with an increased risk of long-term malignancy?
Biologic agents have transformed the management of pediatric IBD, with particular efficacy in children with perianal and fistulizing disease [4].
However, there have been concerns regarding the potential increased risk of malignancy associated with prolonged administration.
Hyams and colleagues demonstrated, in a large prospective study of 5766 pediatric IBD patients, that there was no increased risk of malignancy, nor development of hemophagocytic lymphohistiocytosis, with infliximab [5].
What are the nutritional implications for children with inflammatory bowel disease?
A detailed and purposeful approach to nutrition in children with IBD is essential to reduce the long-term risks of the disease, and should be an integral part of the follow-up of pediatric IBD patients.
Children with IBD exhibit greater risks for malnutrition and impaired linear growth, as well as self-imposed food elimina- tion diets.
In addition, steroid therapies are well known to exert a direct effect on patient growth.
During periods of active disease, it may be required to further supplement macronutrients, including proteins, carbohydrates and fats.
Which children with Crohn’s disease require operative intervention?
The requirement for operative intervention in pediatric CD has decreased significantly due to the marked improvements in medical management of the disease.
However, one-third of children with CD will still require an operation within 5 years of diagnosis for variable indications, including fistula formation, stricturing and/or bowel obstruction [6].
Unlike UC, operative interventions in CD are palliative, and preservation of bowel length is critical.
Children with CD may require elective or emergency operative interventions.
Elective indications include stricture formation, enteric fistula formation, failure to comply with medical therapy, complications related to medical therapy, growth retardation, and delayed puberty.
Emergency indications include perforation, complete small bowel obstruction, hemorrhage, abscess formation and/or generalized peritonitis.
Proximal diversion, with the formation of a temporary ileostomy within unaffected ileum, may be useful to reduce the inflammatory load in children with significant colonic disease.
Which children with ulcerative colitis require operative intervention?
Unlike CD, UC is a mucosal disease confined to the colon and rectum and is, therefore, able to be cured with resection.
In addition, UC carries a greater risk of developing cancer related to colitis, with 5% of patients affected.
Children with UC may require elective or emergency operative intervention, with up to 45% of all patients requiring surgery at some stage.
Elective indications include children with active or steroid-dependent UC, failure of maximal medical therapy, and/or colonic dysplasia.
These patients require a procto-colectomy, J-pouch formation and ileal pouch-anal anastomosis, with sparing of the dentate line.
The majority of surgeons will employ a two-stage procedure, with covering ileostomy formation, dependent upon the age of the patient and the duration of disease.
Emergency indications include colonic perforation, severe rectal bleeding, and/ or toxic megacolon.
In these settings, an abdominal colectomy with ileostomy formation and retention of a Hartmann pouch, will reduce the long-term risks for the patient.
What are the psychological impacts of pediatric inflammatory bowel disease?
The psychological impact of IBD in children and adolescents should not be underestimated.
Potential risk factors for increased psychological morbidity include an older age at diagnosis, a lower socioeconomic status, female gender in adolescent patients, increased severity of disease, and use of corticosteroids. Increased psychological morbidity may lead to poorer medication compliance, increased episodes of abdominal pain, and increased utilization of antidepressant medications.
A 17-year-old female presents with a 5-day history of vague lower abdominal pain and increased urinary urgency and fre-quency. She has also noticed bubbles of air in her urine, which is mal-odorous. She thinks she has lost about 5 pounds (2 kg) over the past 2 months because she is simply not hungry. Further, every time she eats she develops abdominal pain. The patient denies any trauma, use of medications, or any past serious illness. To further evaluate this patient, what is the study of choice?
Choices:
1. Blood cultures
2. Colonoscopy
3. CT abdomen
4. Dye injection in the rectum
Answer: 3 - CT abdomen
Explanations:
• This patient may have Crohn disease and has developed an enter-ovesical fistula.
•Sometimes the inflamed bowel will fistulize with the bladder and present with air in the urine, pneumaturia.
•One can do cystoscopy, fistulography, or colonoscopy to look for a fistula within the bladder.
• However, CT can help assess for Crohn disease and possible fistulas.
CT scan is very sensitive for peri-fistular inflammation.
StatPearls
Which of the following is true regarding Crohn’s disease?
A Between 10% and 20% of children have inflammation in the colon only.
B 70% of children with the disease have inflammation of the lower part of the ileum.
C In about 15%–20% of people, the disease runs in the family.
D Mutations in one gene, called CARD15, are present in about 40% of people with Crohn’s disease.
E All of the above.
E
In about 15%–20% of people, the disease runs in the family. This is especially true of people who develop the disease at a younger age.
Several genes have been linked to the disease, but there is no clear pattern to how these genes interact to cause the disease.
mutations in one gene, called CARD15, are present in about 40% of people with Crohn’s disease. However, this gene is also frequently present in healthy people who never develop this disease.
As many as 70% of children with the disease have inflammation of the lower part of the ileum. more than half of these children also have inflammation in variable segments of the colon.
About 10%–20% of children have inflammation in the colon only.
Another 10%–15% have inflammation scattered around the small bowel, mainly in the middle section (jejunum and upper ileum).
A very small number have inflammation only in the stomach and the duodenum.
SPSE 1
Which of the following is not a routine investigation to detect Crohn’s disease?
A upper GI endoscopy
B ileo colonoscopy
C inflammatory markers
D barium enema
E all of the above
D
Because of advances in diagnostic modalities, barium enema is not routinely performed in Crohn’s disease.
When endoscopic intubation of the intestine is not possible, radiological studies are necessary to determine disease extent and location.
Small-bowel enema for small-bowel disease and double contrast barium enema for large-bowel disease are recommended.
Complementary imaging procedures may be performed, including ultrasonography, CT, and/or MRI.
Differentiation between inflammatory and fibrostenotic bowel stenosis would be very helpful, but current techniques do not permit an accurate distinction.
SPSE 1
Which of the following investigations is least helpful in the diagnosis of Crohn’s disease?
A ileo colonoscopy
B ultrasound for pelvic collection
C wireless capsule endoscopy (WCE) to diagnose strictures
D CT scan of the abdomen
E Lower GI contrast study
C
WCE represents an advance for small-bowel imaging, but large prospective studies are needed to confirm the diagnostic relevance in Crohn’s disease.
WCE may be considered in symptomatic patients with suspected small-bowel Crohn’s disease in whom a stricture/stenosis has been excluded, endoscopy of terminal ileum is normal or not possible, and in whom fluoroscopic or cross-sectional imaging has not showed lesions.
SPSE 1
