Excerpt from Colitis

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Background

Colitis is an inflammation of the colon. It may be associated with enteritis (inflammation of the intestine) and/or proctitis (inflammation of the rectum). Inflammatory bowel disease (IBD) is a generic term used to describe 2 idiopathic disorders that are associated with gastrointestinal inflammation, Crohn disease (CD) and ulcerative colitis (UC). A study from Scotland reported a 3-fold rise in newly diagnosed CD from 1968-1983 and a 4.4-fold rise from 1968-1988. However, a consistent upward trend in cases of UC in the same period did not occur.

Pathophysiology

The pathophysiology of colitis differs because of various etiologies.

Necrotizing enterocolitis

Necrotizing enterocolitis (NEC) is common cause of colitis in newborns. Very small and ill preterm infants are particularly susceptible to NEC. Prematurity and the presence of bacteria in the GI tract are significant risk factors associated with NEC.

NEC appears to involve a final common pathway that includes the endogenous production of inflammatory mediators, such as endotoxin lipopolysaccharide, platelet-activating factor, tumor necrosis factor, and other cytokines, that are involved in intestinal injury. Hypoxic ischemia and aggressive enteral feedings are also associated in the pathogenesis of NEC. Varying degrees of mucosal and/or transmural necrosis of the intestine and colon exist. The distal ileum and proximal colon are involved most frequently, but, in severe cases, gangrene may involve the whole bowel from the rectum to the stomach. NEC presents with the gas accumulation in the submucosa of the bowel wall and progresses to necrosis leading to perforation of the bowel, peritonitis, and sepsis. Histological changes in NEC include mucosal edema, hemorrhage, coagulation necrosis, and mucosal ulceration.

Allergic colitis

In children aged 2 weeks to 1 year, the most common form of colitis is allergic colitis, which results from hypersensitivity commonly to cow's and soy milk. The so-called breast milk allergy is a status of food allergy induced in breastfed babies by heterologous proteins (typically cow's milk proteins) ingested by their mothers and appearing in their breast milk. The immunologic responses may vary from classic allergic mast cell activation to immune complex formation.

Pseudomembranous colitis

Pseudomembranous colitis is a form of inflammatory colitis characterized by the pathologic presence of pseudomembranes consisting of mucin, fibrin, necrotic cells, and polymorphonuclear leukocytes. This form of colitis is pathognomonic of infection by toxin-producing Clostridium difficile and develops as a result of altered normal microflora (usually by antibiotic therapy) that favors overgrowth and colonization of the intestine by Clostridium difficile and production of its toxins. Although every antibiotic has been reported to be associated with pseudomembranous colitis, clindamycin and amoxicillin are the antibiotics most frequently implicated in children.

Inflammatory bowel disease

IBD is an uncommon cause of chronic colitis in children but is becoming more frequent. The etiology is poorly understood. Genetic and environmental influences are involved in the pathogenesis of IBD. It can present in 2 different forms, UC and CD.

UC is characterized by inflammation and ulceration confined to colonic mucosa. CD is manifested by transmural inflammation and granulomas affecting any segment of the GI tract, including the colon. UC invariably involves the rectum and extends proximally without skipping segments. In contrast, CD has discontinuous patchy involvement of the GI tract, involving the small bowel, ileum, and colon. Growth failure results from malabsorption and loss of proteins from inflammation and damage to the mucosa; it is 3 times more likely to occur in children with CD than in children with UC.

The diarrhea also results from mucosal damage, bile acid malabsorption, bacterial overgrowth, and protein exudation from mucosa. Extraintestinal manifestations, which are slightly more common in CD than in UC, result from bacterial products and inflammatory mediators (eg, cytokines, prostaglandins, reactive oxygen metabolites) entering and subsequently being deposited in various tissues and organs, such as eye (uveitis), skin (erythema nodosum), liver (cholangitis, hepatitis), and joints (arthritis).

Bacterial colitis

Bacterial colitis is the most common cause of colitis, particularly beyond the first year of life. It can be caused by bacterial, viral, and parasitic agents. The most common bacterial agents are Escherichia coli (enterohemorrhagic E coli [EHEC] and enteroinvasive E coli [EIEC]) and species of Shigella, Salmonella, Campylobacter, and Yersinia.

Salmonella infections typically are spread by the fecal-oral route; the outbreaks commonly are associated with contaminated eggs, dairy products, and meats. Gastric acid is usually lethal to the organism, but susceptibility to infection is increased with decreased GI motility, rapid emptying of the stomach postgastrectomy, a large quantity of ingested bacteria, malnutrition, antibiotic use, and achlorhydria. Salmonellae can penetrate the epithelial layer to the level of the lamina propria and evoke a leukocyte response. Salmonellae cause diarrhea by producing several toxins and prostaglandins, stimulating the active secretion of fluids and electrolytes.

Shigella species attach to binding sites on the surface of the intestinal mucosal cells. The organism penetrates and proliferates in the cell, which leads to cell destruction, produces mucosal ulcerations, and causes bleeding. Shigellae also elaborate the exotoxins that produce diarrhea.

E coli may produce diarrhea because of several characteristics. Pathologic strains have been classified as enteropathogenic, enterotoxic, enteroinvasive, enteroaggregative, enteroadherent, and enterohemorrhagic. EHEC, including O157:H7 and O26:H11, cause hemorrhagic colitis and systemic complications (eg, hemolytic uremic syndrome [HUS]). The risk of developing HUS after infection with E coli O157 is estimated to be 10-15% in children. In typical infectious colitis, the lamina propria of the large intestine is infiltrated by polymorphonuclear leukocytes. On the other hand, EIEC share almost identical pathogenetic mechanisms with Shigella.

Parasitic colitis

Entamoeba histolytica is the most common cause of parasitic colitis in the world. Transmission is through ingestion of trophozoites, usually from water contamination, and person-to-person transmission because of poor sanitation. Balantidium coli is a large ciliated protozoan that manifests very similar to amebiasis.

Viral colitis caused by cytomegalovirus infection

Colitis caused by cytomegalovirus (CMV) infection is a rare form of colitis that typically is found in immunocompromised patients, such as organ recipients who are receiving immunosuppressive treatment. It results in deep round ulcerations that have a tendency to bleed easily and profusely.

Ischemic colitis

Ischemic colitis is a form of vasculitis that results from inflammation and ischemia of colonic mucosa, which causes rectal bleeding and abdominal pain. This form of colitis is common in Henoch-Schönlein purpura (HSP), which is considered one of the collagen vascular diseases.

Frequency

United States

The onset of IBD commonly occurs during adolescence and young adulthood. The risk of IBD in family members of an affected individual is 7-22%; a child's risk of acquiring the disease is more than 35% if both parents have the disease.

• The prevalence of UC in the United States is 100-200 per 100,000 population.
• The incidence of CD is approximately 3-4 per 100,000 population, and prevalence is 30-100 per 100,000 population.
• NEC affects 1-5% of patients admitting to neonatal intensive care units.
• NEC may occur in 2-5% of infants with birthweights less than 1500 g.
• In the United States, the prevalence of amebiasis in high-risk groups is reported to be 1-4%.

International

The incidence UC is highest in northern European countries and the United States (15/100,000); incidence is lowest in Japan and South Africa (1/100,000).

• A north-to-south gradient appears to be present, with higher incidence of both UC and CD in northern locations.
• The prevalence of amebic infections worldwide varies from 5-81%, with the highest frequency occurring in tropical climates.

Mortality/Morbidity

• Diarrheal diseases are some of the leading causes of morbidity and mortality in children worldwide, causing one billion episodes of illness and 3-5 million deaths annually.
• In the United States, 20-35 million episodes of diarrhea occur each year in the 16.5 million children who are younger than 5 years, resulting in 300-400 deaths.
• Medical treatment fails in 20% of patients who have NEC with pneumatosis intestinalis at diagnosis, resulting in a 9-25% mortality rate. The mortality rate of NEC is greater than 50% in infants with birthweights less than 1000 g.

Race

• The prevalence of IBD is increased among Jewish people of European Ashkenazi descent. A positive family history is the most consistent risk factor for children with IBD. HSP is common in white people.
• Food-allergic colitis is believed to be present in approximately 0.5% of all infants.

Sex

HSP is common in males.

Age

• NEC is a disease of newborns, with low and very low birth weight preterm infants being particularly susceptible.
• Allergic colitis is the most common form of colitis during the first year of life.
• IBD generally is diagnosed in children aged 5-16 years. IBD has a bimodal distribution with an early onset at ages 15-25 years and a second smaller peak at ages 50-80 years.
• HSP occurs in school-aged children and young adults.

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