Inflammatory Enterocolitis

Acknowledgments

The author acknowledges substantial use of the work of David A. Blanco and Harpreet Pall from the previous edition of this chapter.

Inflammatory enterocolitis is a pathologic diagnosis characterized by ileal, colonic, and/or rectal inflammation that can range from superficial patches of leukocyte infiltration to extensive exudative ulcerations of the entire intestinal wall. Inflammatory enterocolitis should be considered in the differential diagnosis of a child who comes to medical attention with diarrhea that is accompanied by fever, abdominal pain, hematochezia, dysentery, or tenesmus. There are a multitude of infectious and noninfectious causes of inflammatory enterocolitis ( Table 57.1 ). Infection is the major cause, with bacteria predominating. The focus of this chapter is the clinical approach to infectious causes. Pathogen-specific chapters contain more in-depth information on each agent. Neonatal necrotizing enterocolitis is discussed in Chapter 94 .

TABLE 57.1

Causes of Inflammatory Enterocolitis

Infectious Etiologies ^a			Noninfectious or No Specific Enteropathogen Associated ^b
Bacterial	Parasitic	Viral	Noninfectious or No Specific Enteropathogen Associated ^b
Aeromonas hydrophila Campylobacter jejuni or coli Clostridiodes difficile Shiga toxin-producing E. coli Enteroinvasive E. coli Mycobacterium avium complex ^c Mycobacterium tuberculosis Salmonella spp . Shigella spp. Vibrio parahaemolyticus Yersinia spp.	Cryptosporidium parvum Entamoeba histolytica Schistosoma spp. Strongyloides stercoralis	SARS-CoV-2 CMV ^c HIV enteropathy	Intussusception Necrotizing enterocolitis Inflammatory bowel disease Hirschsprung enterocolitis Staphylococcal toxic shock syndrome Congenital secretory diarrhea Hyperthyroidism Food intolerance Neoplasia Cystic fibrosis Celiac disease Disaccharidase deficiency Allergic colitis Typhlitis ^c

CMV, Cytomegalovirus; HIV, human immunodeficiency virus.

a Enteric pathogens that cause diarrhea by mechanisms that produce little or no inflammation are not included (e.g., rotavirus and other common viral etiologies, bacterial secretory diarrhea such as enterotoxigenic Escherichia coli and cholera, and agents that disrupt the cellular architecture, such as enteropathogenic E. coli or have unknown mechanisms, such as Giardia spp., microsporidium).

b Conditions that can cause blood in stool without inflammation, such as, anal fissures, intussusception, juvenile polyps, and Meckel diverticulum are not included.

c Primarily occurs in immunocompromised patients.

Etiologic Agents

Classical Bacterial Enteropathogens: Shigella, Salmonella, Campylobacter , and Yersinia

Most enterocolitis in children is caused by the four classical gram-negative bacterial pathogens: Shigella , nontyphoidal Salmonella (NTS)¸ Campylobacter , and Yersinia . These agents share clinical presentations and many epidemiologic and pathogenic features.

Shigella Species

Shigella is the leading cause of bacillary dysentery worldwide. Most infections result from endemic disease among young children living in low- and middle-income countries (LMIC), where morbidity and mortality remain high. In high resource settings, Shigella causes endemic diarrhea in young children and outbreaks where there is suboptimal hygiene such as childcare settings, prisons, and travel to LMIC (including military), and in men who have sex with men (MSM). Four species cause disease: S. sonnei (predominates in industrialized and transitional countries), S. flexneri (predominates in LMIC), and less often S. boydii and S. dysenteriae (in LMIC). ^, ^,

Salmonella enterica subspecies enterica

S. enterica are motile, gram-negative facultative anaerobic bacilli. The most clinically important strains can be classified into the human-restricted Salmonella that cause typhoid fever ( S. enterica serovars Typhi and Paratyphi A and B) and NTS, comprising all other serovars, which are the leading cause of bacterial enterocolitis in the US among all ages. ^, S. enterica serovar Enteritidis is the most common serovar of NTS, while the previously dominant S. Typhimurium is decreasing, possibly due to widespread vaccination of chickens against it. S. Infantis infections are increasing and a new, highly antibiotic resistant strain found in chickens has emerged. Certain serovars are prone to causing invasive disease such as, S. Choleraesuis, Dublin, and Heidelberg, as are antibiotic-resistant strains. S. Enteritidis and S. Typhimurium are the main causes of NTS in LMIC. An invasive strain of S . Typhimurium with high mortality, sequence type (ST)313, is circulating in sub-Saharan Africa.

Campylobacter Species

Disease in humans is caused mainly by C. jejuni (90%–95% of intestinal infections), C. coli , and C. fetus . C. fetus has unique growth characteristics and a propensity to cause systemic disease.

Yersinia Species

Two species of Yersinia are the most recognized human diarrheal pathogens, Yersinia enterocolitica (the major cause) and Y. pseudotuberculosis.

Clostridioides (formerly Clostridium ) difficile Infection

Clostridioides difficile is a spore-forming, anaerobic, gram-positive bacillus that is widely distributed in nature, with a reservoir in infected people and contaminated environments, particularly in nursing homes, healthcare and childcare facilities. Strains that produce protein exotoxins A and B are pathogenic for humans. ^, In the 2000s, hypervirulent strains of C. difficile emerged globally, such as the fluoroquinolone-resistant North American Pulse Field Type 1, ribotype 027 (NAP1/BI/027) strain. This strain has been identified in 10%–20% of pediatric C. difficile infection (CDI) in a US study, but it remains uncertain whether it causes more severe disease.

Diarrheagenic Escherichia coli

Five pathotypes of E. coli cause diarrhea: (1) Shiga toxin–producing (STEC), a cause of bloody diarrhea and hemolytic uremic syndrome (HUS) most often due to serotype O157-H7; (2) enteroinvasive (EIEC), which is genetically, biochemically and clinically nearly identical to Shigella , and a rare cause of foodborne outbreaks; (3) enteropathogenic (EPEC), a cause of watery diarrhea in infants in LMIC; (4) enterotoxigenic (ETEC), a common etiology of secretory diarrhea in infants from LMIC and travelers to LMIC; and (5) enteroaggregative (EAEC), associated with acute or persistent watery diarrhea in some studies. Each pathotype except ETEC can cause some degree of intestinal inflammation. Only STEC, the most clinically and epidemiologically important E. coli causing enterocolitis, will be discussed in this chapter.

Aeromonas and Vibrio Species

Aeromon as spp. are motile, gram-negative facultative anaerobic bacilli found in soil and aquatic environments. A. hydrophila in particular has been associated with pediatric enterocolitis, especially in Asia. Vibrio spp. other than Vibrio cholerae, such as V. parahaemolyticus , can cause inflammatory enteritis with watery diarrhea.

SARS-CoV-2 Infection

Enteritis is a common presenting manifestation of both primary SARS-CoV-2 infection in children and MIS-C. ^, It can be the sole manifestation, and severe disease can occur.

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