Infectious Diseases of the Gastrointestinal Tract

Viral Infections

A wide variety of viruses affect the GI tract. Manifestations of disease vary with the type of virus, specific site of infection, and immune status of the patient.

Cytomegalovirus

Cytomegalovirus (CMV) infection occurs in both immunocompromised and immunocompetent persons and may be found throughout the GI tract. The pathogenesis in truly healthy patients is poorly understood. An underlying immunocompromised state should be considered when CMV infection is diagnosed because it is an opportunistic pathogen in patients with many conditions that compromise immunity, including those with acquired immunodeficiency syndrome (AIDS) or solid organ or bone marrow transplant recipients, as well those who receive prolonged immunomodulator or steroid therapy for immune-mediated or autoimmune disorders.

Clinical Features

Symptoms vary with the immune status of the patient and the specific site of infection. In immunocompromised individuals, CMV esophagitis causes odynophagia, whereas gastroenteritis is marked by abdominal pain, diarrhea (either bloody or watery), fever, and weight loss. Hypertrophic gastropathy with protein-losing enteropathy resembling Menetrier’s disease has rarely been reported in association with CMV gastritis. Primary infections in healthy, immunocompetent persons are often self-limited. CMV superinfection is known to exacerbate other chronic GI diseases, such as ulcerative colitis and Crohn’s disease; in such cases, it is associated with toxic megacolon, refractoriness to medical therapy, and high mortality.

Pathologic Features

Gross Findings

Cytomegalovirus causes a wide variety of gross lesions with ulcers being the most common finding ( Fig. 9.1 ); they may be single or multiple and either superficial or deep. The ulcers often have a well-demarcated, “punched-out” appearance. Other gross findings include hemorrhagic colitis, pseudomembranous colitis, and obstructive mass lesions.

Segmental colonic involvement with linear ulcers mimicking Crohn’s disease have been well documented in colonic CMV infection. Rarely, severe ulcerative CMV infection may lead to bowel perforation.

Microscopic Findings

The histologic spectrum of CMV infection also varies widely, often depending on the patient’s immune status. Typical histologic features include mixed inflammation with numerous neutrophils and mucosal ulceration with prominent granulation tissue. Epithelial cell apoptosis may be prominent ( Fig. 9.2A ). Virtually no associated inflammatory reaction may be seen in severely immunocompromised patients. Inclusions are preferentially found in endothelial cells and stromal cells and only rarely in epithelial cells; thus, they are usually seen deep in ulcer bases.

The characteristic “owl’s eye” intranuclear inclusions are visible on routine (hematoxylin and eosin) preparations, as are brightly eosinophilic, granular intracytoplasmic inclusions ( Fig. 9.2B ). Occasionally, CMV infection of endothelial cells of mucosal and submucosal vessels of the bowel initiates inflammatory mediators, leading to vascular thrombosis and subsequent bowel ischemia. Segmental bowel ischemia caused by infection with CMV shows histologic features that are similar to other causes of ischemia (hemorrhagic necrosis and crypt withering). In addition to CMV inclusions, the vessels may show marked inflammation and necrosis.

Cytomegalovirus—Pathologic Features

Gross Findings

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  Most commonly ulcers, single or multiple, shallow or deep

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  May also manifest as colitis (hemorrhagic or pseudomembranous) or obstructive mass

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  Segmental or linear ulceration may mimic Crohn’s disease grossly

Microscopic Findings

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  Characteristic inclusions: “owl’s eye” inclusions in the nuclei of endothelial and stromal cells

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  Granular eosinophilic inclusions in the cytoplasm of endothelial and stromal cells

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  Mixed inflammation with prominent neutrophils and apoptosis

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  No associated inflammatory reaction may be seen, particularly in severely immunocompromised patients

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  Endothelial infection may cause ischemia

Differential Diagnosis

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  Other viral infections, particularly adenovirus

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  Crohn’s disease

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  Graft-versus-host disease

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  Ischemic colitis

Differential Diagnosis

The differential diagnoses are primarily other viral infections, particularly adenovirus. CMV inclusions and are present within both the nucleus and cytoplasm. Adenovirus inclusions, by comparison, are crescent shaped or have irregular outlines, are generally within surface epithelium, and are only intranuclear. The distinction between CMV infection and graft-versus-host disease (GVHD) in bone marrow transplant patients may be particularly difficult because both clinical and histologic features are similar. Immunohistochemistry (IHC) may be used to rule out CMV infection in this setting. As mentioned previously, CMV infection may produce architectural distortion, deep “fissuring” ulcers, and skip lesions that simulate Crohn disease but does not produce neural hyperplasia, transmural lymphoid aggregates, muscularis mucosae hypertrophy, or pyloric metaplasia. Of course, a careful search for inclusions should confirm the diagnosis of CMV infection in cases with features of both disorders (although the two may coincide; Fig. 9.3 ).

Herpesvirus

Herpetic infection is most commonly seen in the esophagus and anorectum. The symptoms and pathologic features of herpes simplex virus type 1 (HSV-1) versus HSV-2 are indistinguishable. Herpetic proctitis is the most common cause of nongonococcal proctitis in homosexual men. In immunocompetent patients, herpes outbreaks are often self-limiting; immunocompromised persons may be at risk for dissemination and life-threatening illness.

Pathologic Features

Gross Findings

Ulcers are the most common findings in the esophagus, but one may also see intact vesicles. Severe cases may be characterized by diffuse erosive esophagitis. In herpetic proctitis, perianal vesicles are common, and they may extend into the anal canal and rectum. In herpetic colitis, the most typical finding is multiple and confluent ulcers. The surrounding mucosa is often hemorrhagic and friable, and “cobblestoning” of the mucosa may be seen.

Microscopic Findings

Ulcers are associated with increased neutrophils in the lamina propria, and perivascular lymphocytic cuffing. The inflammatory exudate often contains sloughed epithelial cells. Two types of characteristic nuclear inclusions may be found: (1) the more common smudged, ground-glass nuclear inclusion with peripheral darker, marginated chromatin ( Fig. 9.4 ), and (2) the acidophilic inclusions with a surrounding clear halo and peripheral chromatin margination (Cowdry type A inclusion). They are usually present in squamous epithelial cells at the edges of ulcers and are often multiple.

Adenovirus

Adenovirus infection is second only to rotavirus as a cause of self-limiting childhood diarrhea. However, it has recently gained much attention as a cause of diarrhea in immunocompromised patients, especially those with AIDS and patients who have undergone transplantation (particularly bone marrow transplantation). Adenovirus infection of the GI tract is strongly associated with concomitant acute GVHD.

Clinical Features

Virtually all patients present with diarrhea, sometimes accompanied by fever, weight loss, lower GI bleeding, and abdominal pain.

Pathologic Features

Gross Findings

Endoscopic findings typically include erythematous, friable, and granular mucosa.

Microscopic Findings

Histologic features of adenovirus infection include epithelial changes such as superficial cellular degeneration, apoptosis of epithelial cells, and focal acute inflammation. Severe cases may show ulceration and exudate. Characteristic homogeneous, smudgy, eosinophilic inclusions may be seen lining the nucleus. Adenovirus inclusions are, except in rare circumstances, limited to epithelial cells; inclusions are most common within surface epithelium but may also be seen in the crypt epithelium. Inclusions are particularly common in surface goblet cells, in which they are often crescent shaped ( Fig. 9.5 ).

Adenovirus—Pathologic Features

Gross Findings

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  Erythematous, friable, and granular mucosa

Microscopic Findings

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  Superficial cellular degeneration, apoptosis of epithelial cells, and focal acute inflammation; severe cases may show ulceration and exudate

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  Inclusions

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    Homogeneous, smudgy, eosinophilic inclusions fill the nucleus.

  • ■

    Inclusions can be crescent shaped or targetoid

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    Most common within surface epithelium, particularly goblet cells, but can be seen in crypt epithelial cells; almost never in endothelial and mesenchymal cells

Differential Diagnosis

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  Other viral infections, particularly cytomegalovirus

Human Immunodeficiency Virus–Associated Ulcerative Esophagitis

Human immunodeficiency virus (HIV) has been implicated in the pathogenesis of chronic esophageal ulcers in infected patients, due, in part, to detection of viral proteins in ulcerated mucosa. The diagnosis is one of exclusion; thus, one should thoroughly evaluate other possibilities, including other viral infections and medication-induced injuries. Ulcers may contain atypical-appearing fibroblasts, and the associated squamous mucosa may be atrophic.

Aids Enterocolopathy

AIDS enterocolopathy is a term that describes morphologic changes seen in the gut of patients with HIV/AIDS and chronic diarrhea, for which no other infectious cause has been identified. Some argue that these changes represent either primary infection of gut epithelial cells with HIV or a secondary autoimmune reaction to viral infection. Others believe that this is a poorly understood term that does not clearly represent a specific disease entity and thus should not be used at all. The controversy arises because asymptomatic patients may have similar morphologic findings on biopsy, and conversely, severely symptomatic patients may have normal biopsy findings. In addition, there is always the added concern that a causative pathogen simply has been missed.

Patients with AIDS enterocolopathy often have chronic diarrhea, but some are asymptomatic. Colonoscopy is usually normal. The small bowel is more commonly affected than the colon. Histologic features include increased apoptotic activity ( Fig. 9.6 ) and decreased numbers of mitotic figures relative to extent of mucosal injury; the changes resemble those seen in mild GVHD and chemotherapy-related mucosal injuries. The differential diagnosis includes conditions that are associated with prominent apoptosis, such as GVHD, chemotherapy- and drug-related injury, and other viral infections Other infectious agents should be rigorously excluded.

Bacterial Infections

A seemingly endless array of bacterial species are pathogenic in the GI tract. Many produce nonspecific changes, but others may be identified in tissue sections or produce inflammatory patterns that are suggestive of specific infections. This section covers major bacterial pathogens, emphasizing features that guide pathologists and clinicians in reaching a correct diagnosis.

Sarcina Ventriculi and Related Organisms

Sarcina spp. are gram-positive cocci that may be found associated with ulcerated gastric mucosa. Severe complications for S. ventriculi infection are rare, and the organism is found in stool of healthy individuals; thus, its pathogenicity remains controversial.

Pathologic Features

Gross Findings

Endoscopic findings include retained food and bile, masses, gastritis, and ulcers.

Microscopic Findings

Sarcina organisms do not invade the gastric mucosa and do not typically evoke an inflammatory response. This supports the notion that the organisms are not pathogenic; however, they may colonize preexisting ulcers, which increases the risk of perforation or emphysematous gastritis ( Fig. 9.7A ). They are spherical to cuboidal organisms that span 1.8 to 3 μm and have refractile cell walls, resembling vegetable matter ( Fig. 9.7B ). They occur in a “tetrad packet” arrangement of four organisms or multiples of four, reflecting cell division in multiple planes.

Sarcina ventriculi —Pathologic Features

Gross Findings

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  Ulcers

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  Gastritis

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  Retained food

Microscopic Findings

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  Tetrads of non-invasive spherical to cuboidal organisms

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  Associated mucosal ulceration

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  Differential Diagnosis

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  Micrococcus

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  Staphylococcus

Tropheryma Whipplei (Whipple Disease)

Whipple disease is a rare, multisystemic infectious disorder caused by the bacillus, Tropheryma whipplei (formerly T. whippelii ). The disease predominantly occurs in middle-aged white men; however, recent studies show increased incidence in women. It has historically shown a predilection for farmers and carpenters. Some point to detection of T. whipplei in asymptomatic individuals and familial cases as evidence of a possible genetic susceptibility to a commensal organism.

Clinical Features

Whipple disease may affect virtually any organ system, but the classic presentation includes diarrhea, weight loss, fever, abdominal lymphadenopathy, and arthralgia. A substantial proportion of patients experience cardiovascular and pulmonary symptoms. The most severe form of disease includes neuropsychiatric manifestations, such as ophthalmoplegia, myoclonus, and dementia.

Pathologic Features

Gross Findings

The duodenal mucosa may show thickened small intestinal folds that are coated with yellow-white plaques. The adjacent mucosa may appear erythematous or friable.

Microscopic Findings

Whipple disease is most commonly diagnosed in duodenal biopsy specimens. Involvement of the liver, esophagus, stomach, colon, and mesenteric lymph nodes has also been documented. In small bowel biopsies, the villi are blunted by expansion of the lamina propria with foamy macrophages ( Fig. 9.8A ). In addition, there may be neutrophilic activity, fat vacuoles (small collections of extracellular lipid droplets), and lymphangiectasia. Foamy macrophages contain periodic acid–Schiff (PAS)–positive bacillary organisms ( Fig. 9.8B ).

Tropheryma whipplei —Pathologic Features

Gross Findings

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  Enlarged mucosal folds

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  Yellow-white plaques

Microscopic Findings

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  Villous blunting

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  Foamy macrophages expand the lamina propria and submucosa

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  Periodic acid–Schiff–positive bacillary organisms within foamy macrophages

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  Neutrophilic infiltrates

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  Fat droplets and lymphangiectasia in the mucosa

Differential Diagnosis

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  Histoplasma capsulatum

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  Mycobacterium avium-intracellulare complex

Bacterial Enterocolitis

Diarrhea resulting from bacterial infection is a significant worldwide health problem. Escherichia coli and Salmonella, Shigella , and Campylobacter spp. are the most commonly identified pathogens. Many bacterial infections of the gut are related to ingestion of contaminated water or food or travel to countries where these organisms are endemic. Although bacteria are often recovered by culture or identified by molecular means, surgical pathologists may play a valuable role in diagnosis. A general classification of colonic bacterial infections by histologic pattern is given in Table 9.1 .

Despite the large number of infectious agents that may affect the colon, the histologic features that they produce may be generally categorized as follows:

• 1.

  Organisms producing very mild or no histologic changes (e.g., enteroadherent E. coli [EAEC])

• 2.

  Organisms producing the histologic features of acute infectious/self-limited colitis or focal active colitis, such as Campylobacter spp.

• 3.

  Organisms producing suggestive or diagnostic histologic features, such as pseudomembranes, granulomas, or ischemic changes

The pattern of acute self-limited colitis or focal active colitis is one of the most common seen in infectious colitis. Typical histologic features include cryptitis, with or without increased neutrophils in the lamina propria and crypt abscesses; preservation of crypt architecture; and lack of basal plasmacytosis. The acute inflammatory component may be most prominent in the mid to upper crypts. The lack of crypt distortion and basal lymphoplasmacytosis helps distinguish acute self-limited colitis from early IBD.

Escherichia Coli

Diarrheagenic E. coli organisms are classified into five groups: enterotoxigenic, enteropathogenic, enteroadherent, enteroinvasive, and enterohemorrhagic. If pathogenic E. coli is suspected, the clinical laboratory should be notified to search for it specifically because cultures may be a valuable diagnostic aid.

Enterotoxigenic E. coli is a major cause of traveler’s diarrhea, but patients are seldom examined via biopsy, and the pathology has not been well characterized in humans. Enteropathogenic E. coli (EPEC) predominantly affects infants and neonates. Biopsy is not generally performed and is not diagnostically useful, although occasionally gram-negative rods may be seen at the surface of the mucosa ( Fig. 9.9 ). EAEC is similar to the enteropathogenic group and is also an important cause of traveler’s diarrhea and pediatric diarrhea worldwide. Both EPEC and EAEC have been increasingly recognized as causes of chronic diarrhea and wasting in AIDS patients. Endoscopic findings are usually unremarkable, but histologic examination shows a coating of adherent bacteria at the surface epithelium, which may stain gram negative. Degenerated surface epithelial cells with associated intraepithelial inflammatory cells may also be present. Enteroinvasive E. coli (EIEC) is similar to Shigella both genetically and in its clinical presentation and pathogenesis. Given its capacity for invasion, EIEC produces a severe dysentery-like diarrheal illness that can be a particular problem in patients with AIDS. The gross and microscopic pathology of EIEC has not been well described.

Enterohemorrhagic Escherichia Coli

The most common strain of EHEC is 0157:H7. This infectious disease is probably markedly underdiagnosed. This organism adheres to intestinal epithelial cells and produces a cytotoxin similar to that produced by Shigella dysenteriae ; however, there is no invasion. Although contaminated meat is the most frequent mode of transmission, infection may also occur through contaminated water, milk, produce, and person-to-person contact.

Clinical Features

Symptoms usually consist of bloody diarrhea with severe abdominal cramps and mild or no fever. Nonbloody, watery diarrhea may occur, however. Only one-third of patients have fecal leukocytes. Rarely, this infection leads to frank lower GI bleeding. Affected persons may develop hemolytic-uremic syndrome or thrombotic thrombocytopenic purpura, and children and older adults are at particular risk for serious, systemic illness.

Pathologic Features

Gross Findings

Endoscopically, patients have colonic edema, erosions, ulcers, and hemorrhage, and the right colon is usually more severely affected. The edema may be so marked as to cause obstruction.

Microscopic Findings

The histopathologic features are those of ischemic colitis because the toxin is believed to induce an ischemic insult. These features include lamina propria and submucosal hemorrhage ( Fig. 9.10 ), with associated mucosal acute inflammation, crypt withering, and necrosis. Intimal thickening and luminal thrombi may be seen in small vessels, and pseudomembranes are occasionally present ( Fig. 9.11 ). Necrosis and hemorrhage of the superficial colonic crypts with sparing of the deeper compartment is characteristic of enterohemorrhagic E. coli but may also be seen in other types of ischemia. A combination of ischemic changes and features of acute colitis should raise suspicion for infection.

Enterohemorrhagic Escherichia coli —Pathologic Features

Gross Findings

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  Colonic edema, erosions, ulcers, and hemorrhage

Microscopic Findings

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  Mimics ischemic colitis of other causes

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  Microthrombi may be seen within small vessels

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  Pseudomembranes may be present

Differential Diagnosis

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  Ischemic colitis of other causes

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  Clostridioides difficile –related pseudomembranous colitis

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  Rarely, idiopathic inflammatory bowel disease

Salmonellosis

Salmonella , which are gram-negative bacilli, are transmitted through food and water and are particularly prevalent where sanitation is poor. They are an important cause of both food poisoning and traveler’s diarrhea. The discussion of Salmonella spp. may be generally divided into typhoid and nontyphoid species. Enteric (typhoid) fever is usually caused by S. typhi ; the most common nontyphoid species include Salmonella enteritidis, Salmonella typhimurium, Salmonella muenchen, Salmonella anatum, Salmonella paratyphi , and Salmonella give . Although historically enteric fever was considered much more severe than nontyphoid salmonellosis, more recent literature suggests a greater degree of overlap (both clinically and pathologically). The infective dose is relatively low (∼10 ³ organisms may cause human disease). Patients with low gastric acidity and patients with AIDS have a greater risk for Salmonella infection and associated complications.

Clinical Features

There are numerous manifestations of Salmonella infection, including an asymptomatic carrier state (often the organism is harbored in the gallbladder), a self-limited gastroenteritis, typhoid fever, and septicemia. Patients with typhoid (enteric) fever typically present with fever (which generally rises over several days), abdominal pain, headache, and occasionally initial constipation. Abdominal rash (“rose spots”), delirium, hepatosplenomegaly, and leukopenia are fairly common. The diarrhea, which begins in the second or third week of infection, is first watery but may progress to severe GI bleeding and perforation. Nontyphoid Salmonella spp. generally cause a milder, self-limited gastroenteritis with vomiting, nausea, fever, and watery diarrhea. Occasionally, these species cause bloody diarrhea or toxic megacolon.

Pathologic Features

Gross Findings

In enteric fever, any anatomic segment of the alimentary tract may be involved, but the characteristic pathology is most prominent in the ileum, appendix, and right colon and is associated with Peyer’s patches. Grossly, the bowel wall is thickened, and raised nodules may be seen corresponding to hyperplastic Peyer’s patches. Aphthoid ulcers overlying Peyer’s patches, linear ulcers, discoid ulcers, or full-thickness ulceration and necrosis are common as disease progresses. Perforation and toxic megacolon may also be seen, as may suppurative mesenteric lymphadenitis. Occasionally, the mucosa is grossly normal or only mildly inflamed and edematous. Endoscopic findings in nontyphoid salmonellosis include mucosal redness, ulceration, and exudates, but the characteristic nodularity and marked edema are not generally seen.

Microscopic Findings

Macrophages predominate in enteric fever ( Fig. 9.12A ). Peyer’s patches become hyperplastic, and then acute inflammation of the overlying epithelium is seen ( Fig. 9.12B ). Eventually, the lymphoid follicles are infiltrated and obliterated by macrophages. Necrosis begins in the Peyer’s patch and spreads to surrounding mucosa, which eventually ulcerates. The ulcers are typically deep, with the base at the muscularis propria. Typhoid fever may also show features more consistent with acute self-limited colitis, including prominent neutrophils, cryptitis, crypt abscesses, and overlying fibrinous exudate. Granulomas are occasionally seen. In nontyphoid salmonellosis, the pathologic features are those of acute self-limited colitis of any infectious cause. Occasionally, significant crypt distortion may be seen.

Salmonellosis —Pathologic Features

Gross Findings

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  Typhoid

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  Characteristic pathology most prominent in ileum, appendix, and right colon

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  Markedly thickened bowel, raised nodules correspond to hyperplastic Peyer’s patches

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  Aphthoid ulcers overlying Peyer’s patches, linear ulcers, discoid ulcers, or full-thickness ulceration and necrosis are common

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  Perforation and toxic megacolon rarely seen

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  Suppurative mesenteric lymphadenitis may be present

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  Nontyphoid

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  Generally milder findings, including mucosal redness, ulceration, and exudates

Microscopic Findings

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  Typhoid

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  Macrophage is the predominant inflammatory cell

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  Hyperplastic Peyer’s patches with overlying acute inflammation; eventually, frank ulceration begins in Peyer’s patch and spreads to surrounding mucosa

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  Lymphoid follicles are infiltrated and obliterated by macrophages

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  Neutrophils are usually limited to erosions overlying hyperplastic Peyer’s patches

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  Ulcers are typically very deep, with the base at the muscularis propria.

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  Rare granulomas

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  Nontyphoid

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  Features of acute self-limited colitis

Differential Diagnosis

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  Other bacterial infections ( Yersinia spp., Shigella spp.)

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  Crohn’s disease

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  Ulcerative colitis

Shigellosis

Shigella spp. are virulent, invasive, gram-negative bacilli that cause severe bloody diarrhea. They are a major cause of infectious diarrhea worldwide. Shigella dysenteriae is the most common species isolated, although Shigella sonnei and Shigella flexneri are increasingly reported in the United States. The infective dose is low (as few as 10–100 in S. dysenteriae type 1). Shigella spp. are generally ingested from water contaminated with feces, but person-to-person transmission is also possible through the fecal–oral route. Infants; young children; and malnourished, immunocompromised, and debilitated patients are most commonly affected in developed countries. Like salmonellosis, rare cases of chronic shigellosis may simulate IBD grossly and microscopically.

Clinical Features

Symptoms include abdominal pain, fever, and watery diarrhea followed by bloody diarrhea. Chronic disease is rare. Perforation and hemolytic-uremic syndrome associated with Shigella infection have been rarely described. Most studies of mortality in shigellosis were performed in underdeveloped nations, and figures range from 2% to 10%. The mortality rate is significantly higher (>20%) if patients become septic.

Campylobacter SPP .

Campylobacter spp., particularly Campylobacter jejuni , are major causes of diarrhea worldwide. Campylobacter is the most common stool isolate identified in the United States. It is transmitted by the fecal–oral route; is found in contaminated meat, water, and milk; and is a common animal pathogen. C. jejuni is most commonly associated with gastroenteritis; Campylobacter fetus and the other less common species are more often seen in immunosuppressed patients and homosexual men. The importance of C. fetus may be underrecognized as a result of the difficulty of culturing it under conditions used for other Campylobacter strains. The infective dose is low (ingestion of as few as 500 organisms may cause disease), and invasion may occur.

Clinical Features

Patients typically have fever, malaise, abdominal pain (often severe), and watery diarrhea, often bloody and with fecal leukocytes. Symptoms generally present within 1 to 5 days of exposure and last for 4 to 10 days. Relapse is common, although it is usually less severe than the original attack. Immunosuppressed patients have a higher incidence of symptomatic infection, and symptoms are more severe. Most infections are self-limited, especially in healthy patients. Of note, Guillain-Barré syndrome and reactive arthropathy are associated with Campylobacter infection.

Pathologic Features

Gross Findings

Endoscopic findings include friable colonic mucosa with associated erythema and hemorrhage.

Microscopic Findings

Histologic examination most frequently shows features of acute infectious or self-limited colitis, including cryptitis, crypt abscesses, surface epithelial damage, and a lymphoplasmacytic infiltrate in the lamina propria ( Fig. 9.13 ). Marked edema and superficial mucosal erosion with associated hemorrhage may be seen. Findings may be patchy. Although the mucosal architecture is usually well-preserved in Campylobacter infection, mild crypt distortion may occasionally be seen.

Campylobacter spp.—Pathologic Features

Gross Findings

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  Friable colonic mucosa

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  Erythema and hemorrhage

Microscopic Findings

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  Acute self-limited colitis pattern

Differential Diagnosis

• ■

  Other infections that cause the acute self-limited colitis pattern

Yersiniosis

Yersinia enterocolitica and Yersinia pseudotuberculosis are the two Yersinia species pertinent to human GI disease. Yersinia is one of the most common causes of bacterial enteritis in Western and Northern Europe, and numerous cases have been documented in North America and Australia. Yersinia spp. may be found in many food products, including meats (particularly undercooked pork), dairy products, and water.

Clinical Features

These gram-negative coccobacilli are causative agents in appendicitis, ileitis, colitis, and mesenteric lymphadenitis. In addition, they are responsible for many cases of isolated granulomatous appendicitis. Infection with either species may cause symptoms and signs of an acute abdomen, chronic abdominal pain, and diarrhea. Although yersiniosis is usually a self-limited process, chronic infections (including chronic colitis) and persistent abdominal pain have been well documented. Immunocompromised and debilitated patients, as well as patients on deferoxamine or with iron overload resulting from other causes, are at significant risk for serious disease.

Pathologic Features

Gross Findings

Grossly, involved bowel has a thickened, edematous wall with nodular inflammatory masses centered around Peyer’s patches. Aphthoid and linear ulcers may be seen. Involved appendices are enlarged and mimic suppurative granulomatous appendicitis; perforation is often seen. Involved lymph nodes may show gross foci of necrosis.

Microscopic Findings

Both suppurative and granulomatous patterns of inflammation may be seen, and a mixture of the two is common. GI infection with Y. pseudotuberculosis has characteristically been described as a granulomatous process with central microabscesses, almost always accompanied by mesenteric adenopathy. Infection with Y. enterocolitica has not typically been associated with discrete granulomas but has been characterized by hyperplastic Peyer’s patches with overlying ulceration and accompanying acute inflammation, hemorrhagic necrosis, and palisading histiocytes. Recent studies have shown that there is significant overlap between the histologic features of Y. enterocolitica and Y. pseudotuberculosis infection and that either species may show epithelioid granulomas ( Fig. 9.14A ), lymphoid hyperplasia (see Fig. 9.13B ), epithelioid granulomas with prominent lymphoid cuffing (see Fig. 9.13C ), transmural lymphoid aggregates, giant cells, mucosal ulceration, cryptitis, and concomitant lymph node involvement. Some cases show only nonspecific features of acute self-limited colitis.

Yersinia spp.—Pathologic Features

Gross Findings

• ■

  Thickened, edematous wall with nodular inflammatory masses centered around Peyer’s patches

• ■

  Aphthoid and linear ulcers may be seen

• ■

  Involved appendices are enlarged and mimic typical suppurative appendicitis; perforation is frequent

• ■

  Mesenteric lymph node involvement is common

Microscopic Findings

• ■

  Often mix of both suppurative and granulomatous patterns of inflammation

• ■

  Lymphoid hyperplasia, epithelioid granulomas with prominent lymphoid cuffing and sometimes central abscesses, transmural lymphoid aggregates, giant cells, mucosal ulceration, and cryptitis

• ■

  There is significant overlap between the histologic features of Yersinia enterocolitica and Yersinia pseudotuberculosis infection

• ■

  Rare cases show only acute self-limited colitis

Differential Diagnosis

• ■

  Primarily Crohn’s disease

• ■

  Other infections such as Mycobacterium tuberculosis , Salmonella spp.

Vibrio Cholerae and Related Organisms

Vibrio cholerae and other members of the genus, Vibrio ( Vibrio parahaemolyticus , Vibrio vulnificus , Vibrio alginolyticus ), are gram-negative bacilli found in saltwater environments. Consequently, infection is usually acquired from consumption of contaminated raw or undercooked seafood. The illness known as cholera is caused by toxigenic serogroups of V. cholerae O1 and O139. Toxigenic V. cholerae has been responsible for several global pandemics of life-threatening gastroenteritis. The O75 and O141 serogroups produce less severe disease. In the United States, the Florida Gulf coast and Atlantic coast are the most common sources of infection.

Clinical Features

Cholera is characterized by voluminous watery diarrhea, sometimes exceeding 1 L/hr, in the absence of pain or fever. The intestinal mucosal lining may also be shed, appearing as white flecks of tissue in so-called “rice water stool”. Vomiting is also common. The copious release of fluids can lead to severe dehydration and electrolyte imbalance.