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This section of the handout will discuss infectious diseases of the esophagus (esophagitis), the stomach (gastritis and gastric ulcers), and the upper duodenum (duodenal ulcers). A general term used when referring to ulcers of the stomach and duodenum is peptic ulcer disease. Esophagitis usually occurs in immunocompromised persons.


Infectious esophagitis is an infection and inflammation of the esophagus that results in dysphagia and odynophagia.


Table ESU-1. Unique Manifestations of Esophagitis by Causative Agent

Causative Agent

Unique manifestation

Candida albicans

Patients usually also have acute pseudomembranous candidiasis

Herpes simplex virus (HSV)

Abrupt onset of symptoms
Earliest esophageal lesions are 1- to 3-mm round vesicles in the middle to distal esophagus
Multinuclear giant cells are present (identified by Tzanck test in biopsy material)

Cytomegalovirus (CMV)

Gradual onset of symptoms
No cases of CMV esophagitis have been reported in hosts with normal immune function
Large solitary, shallow ulcers or multiple discrete lesions at the distal end of the esophagus are often present

Human immuno-deficiency virus (HIV)

Early lesions are small and aphthoid (thrush-like) and occur during a period of transient fever, chills, malaise, and the rash seen in early HIV infection
Later, giant deep ulcers as large as several centimeters in diameter can be seen
Fistula formation, perforation, hemorrhage, or superinfection may complicate large ulcers

Varicella zoster virus

Patients usually have dermatologic lesions consistent with chickenpox or shingles
















Many different microorganisms can cause infectious esophagitis; however, the most common infectious cause of esophagitis is Candida albicans. Other causes include cytomegalovirus (CMV), herpes simplex virus (HSV), varicella zoster virus (VZV), and human immunodeficiency virus (HIV).

A patient with esophagitis has acute onset of dysphagia (difficulty swallowing), odynophagia (painful swallowing), heartburn, retrosternal discomfort or pain, nausea and vomiting, fever, abdominal pain, epigastric pain, anorexia, weight loss, and cough. See Table ESU-1 above for unique manifestations of infectious esophagitis listed by causative agent.



Infectious esophagitis usually occurs in immunosuppressed persons. A wide range of abnormalities in host defense may predispose an individual to this opportunistic infection, such as neutropenia, impaired chemotaxis, phagocytosis, alteration in humoral immunity, and impaired T-cell lymphocyte function. Corticosteroids, cytotoxic agents, radiation, and immune modulators may also contribute to impaired host immune function. Disruption of mucosal protective barriers and antibiotics that suppress the normal bacterial flora can also contribute to invasion of the esophagus by organisms in the normal flora.

Patients with HIV and persistently low CD4 counts are more likely to develop fungal esophagitis. Illnesses that interfere with esophageal peristalsis such as achalasia, progressive systemic sclerosis, and esophageal neoplasias can increase the likelihood of developing fungal esophagitis. Patients with systemic diseases, such as diabetes mellitus, adrenal dysfunction, and alcoholism, and the elderly are also more likely to develop infectious esophagitis.

Odynophagia, painful swallowing, is a symptom that is unique to infectious esophagitis. If a patient with dysphagia (difficulty in swallowing) also mentions odynophagia, esophagogastroduodenoscopy (EGD) is the preferred procedure to confirm the diagnosis because it allows direct visualization and sampling of the mucosal tissue.

Treatment and Prevention

Infectious esophagitis due to C albicans can be treated with antifungal medication. Patients with infectious esophagitis due to HSV or CMV can be treated with an antiviral. Corticosteroids can be given to reduce the inflammatory response. Patients should avoid situations that cause immunosuppression or destroy the composition of the normal flora (e.g., broad-spectrum antibiotic therapy).


Chronic active gastritis, gastric ulcer disease, and duodenal ulcer disease are inflammatory diseases that are usually caused by Helicobacter pylori. Chronic active gastritis is an inflammation or irritation of the stomach lining; gastric ulcer disease develops in the stomach; and duodenal ulcer disease is chronic and recurrent and results in deep and sharply demarcated ulcers within the first 3 cm of the duodenum. The more general term used is peptic ulcer disease (PUD), which includes both gastric and duodenal ulcer disease.


The most common cause of infectious chronic active gastritis and PUD is H pylori, a short, spiral-shaped, microaerophilic gram-negative bacillus. Most cases of gastric carcinoma are the consequence of lifelong H pylori infection and the effect that this chronic infection has on mucosal carcinogenesis.


Chronic active gastritis is usually asymptomatic; however, when symptoms do exist, they include pain or discomfort, with the pain usually located in the upper central portion of the abdomen (the “pit” of the stomach) (Table ESU-2). Symptoms can occur suddenly, which is particularly true in persons older than 65 years of age.

 Table ESU-2. Manifestations of Gastritis and Peptic Ulcer Disease (PUD)



Chronic active gastritis

Pain usually located in the upper central portion of the abdomen or the “pit” of the stomach, may feel like it is “going right straight through” as it travels from the belly to the back
Pain is aburning, aching, gnawing,orsore
Urge to belch, but belching either does not relieve the pain or relieves it only briefly. Nausea and vomiting (vomitus may be clear, green, or yellow and blood-streaked or completely bloody) 

Critically ill patient with chronic active gastritis

All the symptoms listed above for chronic active gastritis and in addition patients may:
Become pale and sweaty, and have tachycardia
Vomit blood, have bloody stools or dark sticky, foul-smelling stools

PUD (includes gastric and duodenal ulcers)

Gnawing or burning pain in the epigastrium
Bleeding that may result in anemia, weakness, and fatigue
Hematemesis, hematochezia, or melena

Unique characteristics of gastric and duodenal ulcerative disease

Gastric ulcer

Pain is made worse by eating

Duodenal ulcer

Pain is usually relieved by eating or by antacids

The most common symptom of PUD is gnawing or burning pain in the epigastrium, which typically occurs when the stomach is empty (90 minutes to 3 hours after a meal), between meals, and in the early morning hours (see Table ESU-2). The duration of pain may be minutes to hours. Symptoms of PUD may last for weeks to months with remissions that may last months to years followed by recurrence of the symptoms. 


Chronic active gastritis

Peptic ulcer disease


Infection with H pylori is associated with virtually all ulcers not induced by nonsteroidal antiinflammatory drugs (NSAIDs). H pylori cells colonize the deep layers of the mucosal gel that coats the gastric mucosa and disrupts its protective properties. The bacterium is motile and uses its “corkscrew”-like motility to migrate within the gastric and duodenal mucosa.

Researchers do not understand completely the pathogenesis of H pylori bacteria and the formation of ulcers. However, the ability of the bacteria to sense pH, produce flagella, urease, cytotoxic protein called vac A (vacuolating toxin), and the cagA gene product are important in the pathogenesis of ulcer formation. The bacteria produce large amounts of urease allowing them to generate ammonium ions, which buffer the gastric acid. The vac A protein causes vacuoles to form in certain cells and has been demonstrated to cause pore formation in human cells. The cagA gene product is injected in host cells by the bacteria, which causes several changes in host cell signaling.

Colonization of H pylori in the stomach and duodenum is associated with an accumulation of inflammatory cells in the lamina propria. The inflammatory cells release cytokines (e.g., tumor necrosis factor alpha, IL-1, and IL-8) that reduce somatostatin levels and cause an increase in gastrin levels. Damage to tissues results in gastritis and eventually causes an ulcer. The ulcers are usually less than 1 cm in diameter and penetrate through the mucosa and submucosa and into the muscularis propria. The ulcer floor has no intact epithelium; it normally contains a zone of eosinophilic necrosis resting on a base of granulation tissue surrounded by variable amounts of fibrosis. Researchers believe that H pylori infects virtually all patients who are diagnosed with chronic active gastritis.

Long-term inflammation of the stomach is believed to result in gastric carcinoma. In the stomach, chronic inflammation caused by persistent infection with H pylori is the most important risk factor for the development of adenocarcinoma. Some have shown that chronic increase in TNF-alpha production is an important instigator of cancer formation in the stomach. An extracellular protein produced by H pylori called TNF-alpha inducing protein (Tip-alpha) with other host cytokines initiates carcinogenesis over time. Tip-alpha is endocytosed by the gastric epithelial cells and through NF-kappaB produces increased amounts of TNF-alpha. Isolates of H pylori from patients with gastric carcinoma produce much more Tip-alpha that H pylori from patients without gastric cancer.

Another mechanism of carcinogenesis has also been proposed (Toller IMAltmeyer MKohler EHottiger MOMüller A. 2010. Inhibition of ADP ribosylation prevents and cures helicobacter-induced gastric preneoplasia. Cancer Res. Jul 15;70(14):5912-22). In a high-risk subset of infected individuals, H pylori causes multifocal corpus-predominant atrophic gastritis, which frequently progresses to intestinal metaplasia, occasionally to dysplasia, and rarely to adenocarcinoma. The early stages of this process develop as a result of gastric infiltration by TH1-polarized, MHC class II–restricted effector T cells. This T-cell subset is essential for the efficient control of H pylori infection and appears to either directly or indirectly induce gastric epithelial transformation.

Each of these processes (control of infection and carcinogenesis) depend on IFN-γ, which is secreted by TH1-polarized effector T cells both locally at the site of infection and in the gut-draining mesenteric lymph nodes (MLN). A recent study demonstrated that an inhibitor of ADP-ribosylating enzymes, PJ34, could stop the progression from gastritis to adenocarcinoma in a mouse model of stomach adenocarcinoma. They found that that PJ34 exerts its chemopreventive and therapeutic effects by suppressing IFN-γ production by mesenteric lymph node T cells. If IFN-γ is not produced then the effector T cells at the site of H pylori infection could not induce gastritis and carcinogenesis. This may also affect control of the bacterial infection. They propose that ADP-ribosylating enzymes in T cells may represent novel targets for the treatment of gastric premalignant lesions in patients that are refractory to Helicobacter eradication therapy.


Diagnosis of gastritis and PUD involves recognizing the common signs and symptoms and determining that H pylori infection is present; this can be determined with a serologic test, a C13 radiolabeled urea breath test, by endoscopy with tissue biopsy, or stool EIA antigen test. Endoscopy allows direct visualization of gastritis, ulcers, and carcinomas. Biopsy specimens can be tested for H pylori urease activity and examined for inflammation and abnormal tissue.

Treatment and Prevention

See pharmacology notes for current recommendations.

No prevention methods or vaccines have been discovered thus far for H pylori infection in humans. Treatment of patients with chronic gastritis and PUD lowered by 40% the number of patients who developed gastric carcinoma in a recent study in Japan. Unfortunately, the findings were not statistically significant for a number of reasons. Further studies are pending.



Send comments and email to Neal R. Chamberlain, Ph.D.,
Revised 3/4/21
©2016 Neal R. Chamberlain, Ph.D., All rights reserved

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