Case Based Pediatrics For Medical Students and Residents
Department of Pediatrics, University of Hawaii John A. Burns School of Medicine
Chapter IX.11. Inflammatory Bowel Disease
Alan K. Ikeda, MD
August 2003

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This is a 16 year old female who presents with fever and diarrhea. Further questioning finds that she has had similar episodes in the past few years, but none as severe as the current episode. She does not weigh herself regularly so weight loss could not be confirmed. However, she does admit that her clothes feel somewhat looser than last year. Her menstrual periods are regular. Her last menstrual period began two weeks ago.

Exam: VS T 37.0, P 85, RR 18, BP 100/65, oxygen saturation 100% in room air. Height is at the 50th percentile. Weight is at the 5th percentile. She is a thin appearing female in no acute distress. HEENT exam is significant for slightly tacky oral mucous membranes. Her eyes are not sunken. Neck is supple without lymphadenopathy. Her heart has a regular rhythm, but slight tachycardia with no murmurs. Her lungs are clear with good aeration. Her abdomen appears scaphoid. There are mildly hyperactive bowel sounds with diffuse vague abdominal pain without any point tenderness. No masses or organomegaly are noted. Her extremities are cool to at the distal limbs, but warm and dry otherwise. Her pulses are good with brisk capillary refill. No rashes are noted. Her breasts and genitalia are Tanner stage 3-4. Rectal exam demonstrates non-specific discomfort without masses or severe tenderness. Her anus is normal externally. Her stool is guaiac positive.

A CBC shows mild microcytic, hypochromic anemia and thrombocytopenia. Wright's stain of the stool for fecal leukocytes is positive for WBCs, but no eosinophils. Stool, blood and urine cultures are obtained.


Inflammatory bowel disease (IBD) is a term that is used to describe chronic inflammatory diseases of the gut. It usually refers to Crohn's disease and ulcerative colitis.

Crohn's disease (CD) is also known as regional enteritis. The disease is described as discontinuous (regional) areas of transmural inflammation that affect any part of the GI tract (mouth to anus). Ulcerative colitis (UC) is described as a process that results in diffuse superficial colonic ulceration.

Although there are some discrepancies over previous misdiagnoses of IBD as infectious gastroenteritis, most experts agree that the incidence of UC has increased over the first half of the 1900s. Since then, the prevalence of UC has plateaued, while Crohn's disease has increased during the 1950s-1980s. The incidence of UC, as compared to CD is similar worldwide. Both have an increased prevalence in the Northern regions of the world. The two diseases are prevalent in North America, northwestern Europe, and in the United Kingdom. This is in comparison to the decreased rates in Southern Europe, South Africa, and Australia. IBD is rare in Asia, Africa, and South America.

UC and CD are both diseases of late adolescence and early adulthood. However, there have been documented cases of IBD diagnosed in infancy and childhood. The incidence of UC is equal in the male and female gender. Crohn's disease is more common in females than males by 20-30%, but in the younger pediatric age groups, males have a greater incidence. Caucasians, especially Ashkenazi Jewish, have a greater risk than other ethnicities.

Although the precise mechanism of IBD is still unknown, there is a general consensus that it is multifactorial. There is currently no known infectious agent that has been identified/isolated, which reproducibly causes IBD. Still, infection may be a "triggering event" for an acute episode of IBD. Viruses and Mycobacterium paratuberculosis are some of the organisms that have been studied.

Genetics is a likely contributor in the pathogenesis of IBD. In CD, monozygotic twins have a concordance rate of 44%, while just 4% in dizygotic twins. UC has less of a genetic preponderance as monozygotic twins have a concordance rate of 6% to 25%. There are multiple studies attempting to isolate the gene(s) involved in this disease that are beyond the scope of this chapter.

Dietary components have also been studied. No toxin or antigen has been isolated. In a retrospective study, CD has been associated with "westernization" of the diet or an increased of intake of animal proteins, total fat and animal fat.

Some interesting modulating factors are the protective effects of breastfeeding against CD and appendectomy against UC. Cigarette smoking increases the risk for CD while it decreases the risk for UC.

The big picture is that multiple events have an additive effect that results in an abnormal mucosal immune response, which leads to intestinal inflammation. If this inflammatory response is not well regulated, then chronic IBD develops.

Common Comparative Aspects of CD and UC:
DescriptionAge
Crohn's Disease
Ulcerative Colitis
Location
Mouth to anus
50% ileocolic
30% small intestine
10% colonic
Colon only
Abdominal mass
common
rare
Perianal disease
common
rare
Strictures
common
unusual
Fistula
common
unusual
Risk of cancer
increased slightly
increased greatly
Histology
Transmural inflammation
Skip areas
Aphthoid lesions,
Fissuring ulceration,
Granuloma,
Fibrosis
Mucosal inflammation,
Diffuse involvement,
Crypt abscesses,
Crypt distortion
Microscopic
Edema, increase in mononuclear cells in the lamina propria. Again, the hallmark is transmural extension into the bowel wall and adventitia.
Active UC: Neutrophils in the mucosa, goblet cell mucus depletion, and clumps of neutrophils in crypt lumens.
Clinical presentation
Abdominal pain,
Anemia,
Weight loss,
Falling off growth curve,
Delayed puberty,
Perianal lesions,
Finger clubbing
Bloody, mucusy diarrhea,
Lower abdominal cramps (less common),
Abdominal tenderness,
Vomiting,
Fever,
Weight loss

Crohn's Disease commonly presents with crampy abdominal pain, recurrent fever, weight loss, and diarrhea. Abdominal pain is diffuse and more severe than in UC and often worse in the lower right quadrant. Rectal bleeding is seen in about a third of the cases. Weight loss, poor weight gain, anorexia, and delayed growth occur in 40% of cases. This growth abnormality may present as short stature and/or delay in sexual maturation. Perianal disease may be the presenting complaint. Further examination may show a fistula, skin tags, or recurrent abscesses.

Ulcerative colitis presents with bloody stools, abdominal pain, and tenesmus. 100% of cases present with bloody mucinous stool. Mild disease is defined as less than 6 stools per day, no fever, no anemia, and no hypoalbuminemia. Moderate disease is described as more than 6 stools per day, fever, anemia, and hypoalbuminemia. 90% of cases present with mild to moderate disease. Severe disease exhibits high fever, abdominal tenderness, distention, tachycardia, leukocytosis, hemorrhage, severe anemia, and more than eight stools per day. Rare complications that may arise include toxic megacolon and intestinal perforation.

Extraintestinal complications of IBD may involve the joints (arthralgias are more common than arthritis), integument (erythema nodosum and pyoderma gangrenosum), eyes (episcleritis, uveitis, and rarely, orbital myositis), hepatobiliary system (sclerosing cholangitis, chronic active hepatitis), pancreas (pancreatitis), renal system (nephrolithiasis, hydronephrosis), coagulation system (hypercoagulability), and bone (decreased bone density).

The diagnosis is based on clinical presentation, radiologic findings, endoscopy with mucosal biopsy, and exclusion of other causes. Since corticosteroids will likely be used for treatment, stool cultures are done to rule out infectious causes. The stool may need to be evaluated for tuberculosis and schistosomiasis. Double-contrast barium enema may show diminished colonic haustrations in UC. In CD, it may identify nodularity, skip areas, a string sign, and fistula formation. Colonoscopy is superior to evaluate the large bowel because of its increased sensitivity and biopsy capability for histologic assessment.

Hematologic findings may exhibit anemia and thrombocytopenia. Further studies may show specific nutritional deficiencies including iron deficiency, hypoalbuminemia, and elevated transaminases. There have been recent advances in serologic testing, which in addition to screening for IBD, can differentiate between CD and UC. Anti-neutrophil cytoplasmic antibodies (ANCA) and anti-Saccharomyces cerevisiae antibody (ASCA) are laboratory tests that are used to serve this purpose. ANCAs are immunoglobulin IgG antibodies that are directed against neutrophil cytoplasmic components. Initially ANCAs had been studied in Wegener's granulomatosis and necrotizing vasculitis. By utilizing immunofluorescence studies, UC can be identified as it demonstrates perinuclear staining (pANCA). The test is specific in separating IBD from infectious colitis and other GI disorders. Unfortunately, the sensitivity is only 50-65%. ASCAs are IgG and IgA antibodies that bind to mannose sequences in the cell wall of S. cerevisiae strain Sul. The specificity and sensitivity of this test is also suboptimal. It is positive in 55-60% of people with CD and 5-10% of those with other GI disorders. Its low sensitivity and specificity have kept these studies from replacing definitive radiologic and endoscopic studies. The tests are also limited in the cases where they are most needed. In CD limited to the colon, the pANCA may also be positive. ASCA is also less likely to be positive in CD limited to the colon. Thus, the dilemma remains in which the clinician attempts to distinguish UC from CD involving the colon only.

Sulfasalazine is the usual treatment for mild to moderate UC and Crohn's disease of the colon. Sulfasalazine is not effective in small bowel CD. In moderate to severe UC and Crohn's disease of the small bowel, corticosteroids are used. Care must be taken to rule out bacterial causes of diarrhea prior to starting systemic corticosteroid therapy. Severe UC is treated with hyperalimentation, high dose corticosteroids, sulfasalazine, and cyclosporine. Corticosteroids may result in growth retardation. Metronidazole is used to treat perirectal fistulae in patients with CD. Metronidazole is used for both active disease, as well as prevention of recurrence. Azathioprine and 6-mercaptopurine are immunomodulating drugs which are used to reduce inflammation of the intestines, so that the corticosteroid doses can be reduced. Cyclosporine and tacrolimus inhibit cell-mediated immunity. Anti-TNF-alpha is a newer intervention that may be beneficial.

Surgical resection is indicated when there are intractable symptoms despite medical therapy, intestinal complications, intra-abdominal abscesses, bowel-bladder fistula, perforation, and/or hemorrhage. Surgical resection does not necessarily result in a cure. In some patients, elective colectomy is performed to reduce or eliminate the risk of colon cancer.

Crohn's disease may be subdivided into 3 categories: 1) The fistulizing type may form fistulas that are entero-enteric (between bowel segments), bowel-bladder, enterocutaneous (bowel to skin), perianal fistulas, and/or intra-abdominal abscess. 2) Patients with fibrostenosing disease have persistent abdominal pain and radiologic findings consistent with stenoses of the small or large intestine. 3) The inflammatory category includes patients who do not fit either of the two diseases or had been in one category and now fit in another. As listed above, growth impairment may occur either secondary to the illness or to therapy.

Death in CD is rare in children. Adults with Crohn's colitis may have the same risk for cancer as do patients with UC. The overall risk for colorectal cancer is 8% after twenty years of disease. This risk is increased in those affected by perianal disease. Most patients undergo resection of the affected segment within 20 years, which decreases the overall incidence of carcinoma.

Ulcerative colitis is also divided into 3 categories, which include mild, moderate and severe disease. One large study noted 70% of children entering remission by three months despite their initial severity level. The greater the severity of the disease, the greater was the likelihood of undergoing a colectomy. Nine percent and 25% those with moderate to severe disease underwent colectomy by 1 and 5 years, respectively.

After 10 years of disease, the risk for colorectal cancer increases. About 12% of those with disease for 10 to 25 years will have colorectal cancer. Since there is such a high risk, regular colonoscopic surveillance is recommended, which identifies colorectal cancer at a potentially curable stage 65% of the time. However, these biannual examinations that start at 7-10 years of disease were not found to be cost effective. A more sensitive, specific and reliable screening test is currently being sought.


Questions

1. What portion(s) of the GI tract are affected by CD versus UC?

2. Which IBD has a greater association with cancer?

3. What are the common histologic findings in CD and UC?

4. Name three extraintestinal findings in IBD?

5. Describe the three types of CD and UC.


References

Chapter 8: Gastroenterology. Marino B, Snead K, McMillan JA (eds). Blueprints in Pediatrics. 1997, Malden, MA: Blackwell Science, pp. 86-88.

Griffiths AM, Buller HB. Chapter 41: Inflammatory Bowel Disease. In: Walker WA, Durie PR, Hamilton JR, Walker-Smith JA, Watkins JB (eds). Pediatric Gastrointestinal Disease, 2000, pp. 613-652.

Hyams JS. Inflammatory Bowel Disease. Pediatr Rev 2000;21(9):291295.

Hyams JS, Treem WR. Chapter 11: Gastrointestinal Diseases. In: Dworkin PH (ed). Pediatrics, 3rd edition, 1996. Media, PA: Williams & Wilkins, pp. 332-335.

Siberry GK, Iannone R. The Harriet Lane Handbook: A Manual for Pediatric House Officers. 15th edition. 2000, St. Louis: Mosby, Inc., pp. 251-257.

Thompson NP, et al. Genetics versus the environment in inflammatory bowel disease: results of a British twin study. Brit Med J 1996;312:95-96.

Tysk C, et al. Ulcerative Colitis and Crohn's Disease in an unselected population of monozygotic and dizygotic twins. A study of heritability and the influence of smoking. Gut 1988;29:990-996.


Answers to questions

1. CD affects the gut anywhere between the mouth to the anus, while UC affects the colon.

2. UC has a greater risk for cancer. CD only slightly increases the risk for cancer.

3. CD: Transmural inflammation, skip areas, aphthoid lesions, fissuring ulceration, granuloma, fibrosis. UC: Mucosal inflammation, diffuse involvement, crypt abscesses, crypt distortion.

4. Joints: arthralgias are more common than arthritis. Integument: erythema nodosum and pyoderma gangrenosum. Eyes: episcleritis, uveitis, and rarely, orbital myositis. Hepatobiliary system: sclerosing cholangitis, chronic active hepatitis. Pancreas: pancreatitis. Renal system: nephrolithiasis, hydronephrosis. Coagulation system: hypercoagulability. Bone: decreased bone density.

5. Crohn's disease may be subdivided into 3 categories: 1) The fistulizing type, 2) Patients with fibrostenosing disease, and 3) The inflammatory category. Ulcerative colitis is divided into three categories: mild, moderate, severe.


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