Basics
Description
Ulcerative colitis (UC) is a chronic, relapsing, inflammatory disease of the colon, which extends continuously from the rectum proximally to a varying extent. UC is categorized as an inflammatory bowel disease (IBD), along with Crohn disease (CD). Unlike CD, UC does not affect the small bowel.
Epidemiology
- The incidence of pediatric-onset UC is between 1 and 4/100,000 children/year in most North American and European regions.
- Roughly 15 " 20% of patients with UC develop the disease before the age of 18 years.
- Incidence peaks between 15 and 30 years of age.
Etiology
The precise cause of UC, as with IBD in general, is unknown, but is thought to involve both genetic predisposition and environmental triggers.
Risk Factors
Genetics
- Family history of IBD in ¢ ¼15 " 20% of patients with UC
- There is an increased incidence of family history in patients diagnosed prior to 20 years of age.
- Higher concordance in monozygotic than in dizygotic twins
- Genome-wide association studies (GWAS) have identified multiple loci associated with UC. Mutations in genes involving intestinal barrier functions are seen in UC more often than healthy controls.
- Recent studies identified five new IBD susceptibility loci that are associated with early-onset disease.
Diagnosis
Patients with UC typically present with bloody diarrhea, tenesmus, and lower quadrant abdominal pain. When symptoms become severe, weight loss, fatigue, and vomiting can be seen. Colonoscopy with histopathologic review of biopsies is the gold standard in diagnosis of UC.
History
A detailed history is important in making the diagnosis:
- Rectal bleeding (90%)
- Abdominal pain (90%)
- Diarrhea (50%)
- Weight loss (10%)
- Growth failure
- Recent travel (enteric infections)
- Antibiotic use (Clostridium difficile)
- Family history of IBD
Physical Exam
- Fever, tachycardia
- Evidence of weight loss or poor growth
- Signs of anemia
- Uveitis
- Mouth sores
- Arthritis
- Abdominal tenderness typically in lower quadrants or abdominal distention
- Perianal/rectal examination (UC is not typically associated with perianal disease, but hemorrhoids or erythema can be seen.)
Diagnostic Tests & Interpretation
Lab
- CBC
- Iron deficiency anemia and anemia of chronic disease can be seen.
- Thrombocytosis is another frequent finding.
- Iron studies (iron deficiency)
- ESR, CRP; disease activity
- Electrolytes (hydration), CMP. Serum albumin may be low, hypoalbuminemia may be present in fulminant colitis.
- Liver panel (hepatobiliary disease)
- Perinuclear antineutrophil cytoplasmic antibody (pANCA; positive in 80% of UC patients, 20% of CD patients)
- Stool for blood, white cells (colitis)
- Fecal calprotectin and fecal lactoferrin: may be elevated during times of active inflammation
- Stool cultures:
- C. difficile, Salmonella, Shigella, Campylobacter, Yersinia, Escherichia coli (enterohemorrhagic), Aeromonas, amebiasis, cytomegalovirus
Imaging
- Plain abdominal radiograph
- Important in diagnosing perforation, ileus, obstruction, and toxic megacolon
- In toxic megacolon, the colon is dilated, and there are multiple air " fluid levels indicative of ileus. Serial x-rays are mandatory.
- An upper GI with small bowel follow-through (UGI/SBFT) may help to exclude small intestinal inflammation indicative of CD.
- New imaging modalities, such as MR enterography (MRE), CT enterography, are currently being performed in place of UGI/SBFT. MRE has the advantage of avoiding radiation exposure.
- MRI may have a role in differentiating transmural and mucosal inflammation and is useful for demonstrating perianal fistulas more consistent with CD than UC.
- Right upper quadrant ultrasound may be useful for evaluating associated hepatobiliary disease if it is suspected.
- Endoscopic retrograde cholangiopancreatography (ERCP) or MRCP are also useful in diagnosing primary sclerosing cholangitis (3% of UC patients).
Diagnostic Procedures/Other
- Colonoscopy (with biopsies) is the gold standard and is necessary to confirm the diagnosis of UC. It is critical to visualize and biopsy the entire colon, including terminal ileum, to differentiate CD from UC.
- Upper endoscopy may increase chances of detecting CD and may detect chronic gastritis sometimes seen with UC.
- Video capsule endoscopy (VCE) is more sensitive than UGI/SBFT for diagnosing small bowel disease indicative of CD rather than UC.
- Pitfalls:
- Infectious colitis (especially C. difficile) can mimic the findings of UC so this should first be ruled out with stool culture. Recurrent C. difficile occurs frequently in UC.
- Differentiating Crohn colitis from UC: Small intestinal inflammation and perianal disease (fistula, abscess) are more indicative of CD.
- Serum inflammatory markers and CBC may be normal in children with active colitis especially with mild disease.
- The combination of positive pANCA and negative anti " Saccharomyces cerevisiae antibody (ASCA) has a reported sensitivity of 60 " 70% and a specificity of 95 " 97% for UC in adults. The sensitivity and specificity are lower for pediatric patients.
- Toxic megacolon is a surgical emergency. It is characterized by a dilated colon at risk for breakdown of its barrier to toxins entering the systemic circulation. Signs and symptoms include peritonitis, mental status changes, and fluid and electrolyte imbalance. Plain abdominal radiograph shows a segment or total colonic dilatation. Risk factors include new diagnosis of UC, pancolitis, concurrent use of opiates and/or anticholinergics, and recent colonoscopy.
Pathologic Findings
- Chronic or chronic active colitis, with continuous inflammation limited to the mucosa
- Crypt architectural distortion, cryptitis (aggregation of inflammatory cells in the crypt epithelium), crypt abscesses
- Site of colon affected:
- Rectum (virtually 100%)
- Left side (50 " 60%)
- Pancolitis (10%)
- Small intestine is technically not involved, but occasionally the terminal ileum of patients with UC can be found to have mild inflammation on radiologic or histologic examination. This is thought to be from refluxed colonic contents (backwash ileitis).
- Skip lesions are not seen in UC.
- Chronic gastritis may be present in patients with UC.
Differential Diagnosis
- Infectious colitis: C. difficile, Salmonella, Shigella, Campylobacter, Yersinia, E. coli (enterohemorrhagic), Aeromonas, cytomegalovirus
- Crohn disease
- Congenital Hirschsprung enterocolitis
- Bleeding juvenile polyps
- Milk protein allergy especially in infants
- Immunodeficiency states (rare) onset of colitis within the first 2 years of life, often with perianal involvement; skin folliculitis, or eczema; other fungal or bacterial infections
- Eosinophilic colitis
- Autoimmune enteropathy
- Hemolytic-uremic syndrome
- Henoch-Sch ¶nlein purpura
- Trauma due to anal sex or sexual abuse
Treatment
Medication
- Mild disease can be treated with oral mesalamine, topical corticosteroid enema or foam, or mesalamine enema/suppositories.
- For mild to moderate disease, Budesonide MMX is a once-daily, extended-release budesonide, which has been shown to induce remission in adults with mild to moderate UC and has fewer side effects than systemic corticosteroids.
- For moderate disease, mesalamine, a short course of oral corticosteroid and the addition of an immunomodulators such as azathioprine or 6-mercaptopurine may help to maintain disease remission and minimize the need for recurrent steroid use.
- Antibodies against tumor necrosis factor (TNF)-α include infliximab and adalimumab; both are used in the treatment of moderate to severe UC or steroid-resistant UC.
- Vedolizumab is an anti-integrin, which is a steroid-sparing agent used for induction and maintenance of moderate to severe UC in adults.α4 ²7 integrins are expressed on B and T lymphocytes and facilitate binding to intestinal vasculature. Vedolizumab is a gut-selective antibody that blocks gut lymphocyte recruitment by blocking its interaction with mucosal addressin cell adhesion molecule-1.
- Fulminant disease: hospitalization, if concern for toxic megacolon " complete bowel rest with total parenteral nutrition, broad-spectrum antibiotics, discontinuation of anticholinergics and narcotics, avoidance of endoscopy, IV corticosteroids, serial abdominal radiographs, frequent examinations, stool monitoring (frequency, amount of blood, and volume of stool output); early surgical consult
- If treatment of acute symptoms with IV steroids fails (after 3 " 5 days), therapy with tacrolimus, cyclosporine, or infliximab can be started.
- Pediatric Ulcerative Colitis Activity Index (PUCAI): obtained on day 3 " 5; may identify patients with severe UC who will require escalation of therapy. Prevents unnecessary prolonged exposure to corticosteroids
- Short-term medications for severe colitis should be used as a bridge to surgery or to transition to another steroid-sparing agent, such as an immunomodulator or biologic.
- Tacrolimus (PO) 0.1 mg/kg/dose every 12 hours with goal trough levels of 10 " 15 ng/mL after 2 days.
- Cyclosporine (IV): 4 mg/kg/24 h for 2 weeks (therapeutic levels vary depending on the technique used in the laboratory)
- Cyclosporine (PO): 6 " 8 mg/kg/24 h for 6 " 8 months
- Tacrolimus and cyclosporine are both nephrotoxic. Should only be used by experienced clinicians
- Trimethoprim/sulfamethoxazole should be given for Pneumocystis carinii prophylaxis.
- 5-amionosalycilates:
- Mesalamine (PO): 40 " 60 mg/kg/24 h (maximum 4.8 g/day)
- Mesalamine (enema): 4 g at bedtime (for proctitis or isolated left-sided disease)
- Mesalamine (suppository): 500 mg b.i.d.
- Corticosteroids:
- Methylprednisolone (IV): 1 " 2 mg/kg/24 h (equivalent to prednisone 60 mg maximum)
- Prednisone (PO): 1 " 2 mg/kg/24 h oral (up to maximum 60 mg/day)
- For proctitis and isolated left-sided disease
- Hydrocortisone enema: 100 mg once to twice daily
- Hydrocortisone foam: 80 mg once to twice daily
- Budesonide multimatrix system 9 mg/24 h orally
- Immunomodulators:
- Mercaptopurine (6-MP) (PO): 1 " 1.5 mg/kg/24 h or azathioprine (PO): 2 mg/kg/24 h
- Check thiopurine methyltransferase genetics or activity prior to initiation to avoid pancytopenia in those who lack this enzyme. Also monitor CBC and lipase every 2 weeks on initiation and with dosing changes to look for cytopenias or pancreatitis.
- Biologics:
- Infliximab (IV): 5 mg/kg weeks 0, 2, 6, then every 8 weeks, dose and frequency can be increased to capture symptoms
- Adalimumab (IM): for patients weighing 40 kg and greater, 160 mg on week 0, 80 mg on week 2, followed by 20 or 40 mg every 2 weeks starting on week 4. Reduce dosage by 50% for patients <40 kg.
- Anti-integrin
- Vedolizumab (adult dosage) 300 mg IV weeks 0, 2, 6 weeks then every 8 weeks and can be increased to every 4 weeks to capture symptoms.
Surgery/Other Procedures
- Patients with fulminant disease who fail medical therapy should be referred for colectomy.
- Patients with chronically active disease unresponsive to medication, growth failure, or with corticosteroid dependence should also consider colectomy.
- Because UC is limited to the colon, colectomy is considered a curative procedure. It also eliminates the elevated colon cancer risk.
- Sometimes surgery is urgently required for perforation, significant and persistent bleeding, toxic megacolon, and failure of medical treatment.
- Can be electively performed for chronic incapacitating disease, growth failure, corticosteroid dependence, dysplastic changes in the colon, or long-standing disease (usually after 10 years).
- Ileoanal anastomosis and pouch construction is surgery of choice for most pediatric patients and usually is performed in 3 stages over 6 months. 10% of cases are subsequently found to have Crohn disease after colectomy.
Ongoing Care
Follow-up Recommendations
- Outpatient follow-up with a pediatric gastroenterologist should be arranged.
- Important parameters to follow routinely include abdominal symptoms, rectal bleeding, stool frequency/consistency, height/weight, hemoglobin, WBC count (for patients on immunosuppressives), ESR, albumin, bilirubin, and liver enzymes.
- There is ongoing debate about monitoring for mucosal healing in UC. Adult studies have shown better outcomes, reduction in disease progression, and fewer complications in individuals who achieve mucosal healing.
- Colon cancer screening with colonoscopy should be performed within 10 years of diagnosis.
Complications
- Bleeding
- Anemia
- Toxic megacolon
- Extraintestinal manifestations include hepatobiliary disease (3 " 5%), uveitis (up to 4%), arthritis affecting large joints (10%), spondylitis (6%), erythema nodosum (>5%), pyoderma gangrenosum (>1%), renal calculi (5%).
- Malignancy risk is 8% 10 " 25 years after colitis is diagnosed and it increases ¢ ¼10% for every subsequent decade.
- Colonic stricture
- Thrombosis: Patients with IBD have a 3-fold higher risk of thrombosis compared to individuals without IBD. This risk rises further to 15-fold with disease flares. Presentation with calf pain or shortness of breath should prompt evaluation for deep vein thrombosis or pulmonary embolism.
Additional Reading
- Bousvaros A, Antonioli DA, Colletti RB, et al. Differentiating ulcerative colitis from Crohn disease in children and young adults: a report of a working group of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the Crohn 's and Colitis Foundation of America. J Ped Gastroenterol Nutr. 2007;44(5):653 " 674. [View Abstract]
- Bousvaros A, Kirschner BS, Werlin SL, et al. Oral tacrolimus treatment of severe colitis in children. J Pediatr. 2000;137(6):794 " 799. [View Abstract]
- Feagan BG, Rutgeerts P, Sands BE, et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2013;369(8):699 " 710. [View Abstract]
- Hyams JS, Lerer T, Griffiths A, et al. Outcome following infliximab therapy in children with ulcerative colitis. Am J Gastroenterol. 2010;105(6):1430 " 1436. [View Abstract]
- Lees CW, Barrett JC, Parkes M, et al. New IBD genetics: common pathways with other diseases. Gut. 2011;60(12):1739 " 1753. [View Abstract]
- Loftus EV Jr. Epidemiology and risk factors for colorectal dysplasia and cancer in ulcerative colitis. Gastroenterol Clin North Am. 2006;35(3):517 " 531. [View Abstract]
- Shikhare G, Kugathasan S. Inflammatory bowel disease in children: current trends. J Gastroenterol. 2010;45(7):673 " 682. [View Abstract]
- Turner D, Levine A, Escher JA, et al. Management of pediatric ulcerative colitis: joint ECCO and ESPGHAN evidence-based consensus guidelines. J Pediatr Gastroenterol Nutr. 2012;55(3):340 " 361. [View Abstract]
- Zitomersky NL, Verhave M, Trenor CC III. Thrombosis and inflammatory bowel disease: a call for improved awareness and prevention. Inflamm Bowel Dis. 2011;17(1):458 " 470. [View Abstract]
Codes
ICD10
- K51.90 Ulcerative colitis, unspecified, without complications
- K51.911 Ulcerative colitis, unspecified with rectal bleeding
- K51.912 Ulcerative colitis, unspecified with intestinal obstruction
FAQ
- Q: Will my child have this disease forever?
- A: Some people will have only the initial attack and then be symptom-free, but usually and more often in pediatrics, individuals will have episodes of recurrences and remissions. Surgical removal of the colon represents a curative procedure, although some patients may develop inflammation in the pouch created out of the remaining bowel (pouchitis).
- Q: What is the cause of UC?
- A: Both genetic and environmental factors are important in the development of UC.
- Q: Where can I learn more about UC?
- A: The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition provides a Web site for children with IBD and their families (www.gastrokids.org). The Crohn 's and Colitis Foundation of America (www.CCFA.org) is a nonprofit organization dedicated to the care and education of people with CD and UC.