Infections of the Esophagus

 

Disease

 

Esophagitis an inflammation of the esophagus associated with dysphagia and odynophagia.

 

Etiology

Gastroesophageal Reflux Disease (GERD), infectious etiologies, or adverse effects of medications usually cause esophagitis.

Epidemiology

 

The chances of developing esophagitis increases with increased rates of immunosuppression. Symptomatic infection is high in individuals with AIDS, leukemia, and lymphoma but low (<5%) in the general medical population. Approximately 8-28% of patients with AIDS who are undergoing esophagogastroduodenoscopy (EGD) for dysphagia/odynophagia were found to have cultures positive for CMV.

 

Pathogenesis

Infective esophagitis is most commonly observed in immunosuppressed hosts. It can also occur in healthy individuals but to a lesser extent. A wide range of abnormalities in host defense may predispose an individual to these opportunistic infections, such as neutropenia, impaired chemotaxis and phagocytosis, alteration in humoral immunity, and impaired T-cell lymphocyte function. Steroids, cytotoxic agents, radiation, and immune modulators can 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 a persistently low CD4 counts, are more likely to get fungal esophagitis. Patients with systemic diseases (eg, diabetes mellitus, adrenal dysfunction, alcoholism) and the elderly are more likely to get infectious esophagitis. Illnesses that interfere with esophageal peristalsis, such as achalasia, progressive systemic sclerosis, and esophageal neoplasias, can also increase the likelihood of developing fungal esophagitis.

 

Manifestations

The patient usually has a history of immunosuppression, steroid therapy, recent antibiotic use, or systemic illness that supports the diagnosis.

Acute onset of difficult and painful swallowing (ie, dysphagia, odynophagia), heartburn retrosternal discomfort or pain, nausea, vomiting, fever, sepsis, abdominal pain, epigastric pain, occasionally hematemesis, anorexia, weight loss (depends on chronicity and severity of underlying illness), cough.

Oftentimes the patient will also have thrush in fungal esophagitis.

Diagnosis

 

Odynophagia is a symptom unique to esophagitis. If a patient with dysphagia also mentions pain then esophagogastroduodenoscopy (EGD) is the preferred procedure to confirm the diagnosis because it allows direct visualization and sampling of the mucosa.

 

Unique findings due to various causes of esophagitis:

 

Candida albicans- most (75%) also have thrush; plaques are usually creamy white or pale yellow, with underlying raw mucosa. Brushings should be obtained with a sheathed cytology brush, spread onto slides, and stained with periodic acid-Schiff, silver, or Gram stains. The presence of mycelial forms and masses of budding yeast is consistent with candidal infection.

 

HSV- Patient has abrupt onset of symptoms. Diagnosis is usually determined at endoscopy. The earliest esophageal lesions are rounded 1- to 3-mm vesicles in the middle to distal esophagus. Later on the centers slough to form discrete circumscribed ulcers with raised edges. The ulcers may look a lot like Candida plaques later in the infection. Biopsy of the edge of the ulcers can be used to look for multinucleated giant cells (Tzanck test), to culture for the virus, and to prepare histological sections for immunohistochemistry using monoclonal antibodies to HSV.

 

CMV- Unlike HSV esophagitis the onset of symptoms is more gradual. Esophagitis is the second most common GI manifestation of CMV after colitis. CMV esophagitis has been reported in transplant patients, patients undergoing long-term renal dialysis, patients with HIV/AIDS, and patients with other debilitating diseases. No cases of CMV have been reported in healthy hosts. Diagnosis is made by endoscopy with biopsies performed to culture for the virus. Usually large solitary shallow ulcers or multiple discrete lesions are present and are usually at the distal end of the esophagus.

 

HIV- Multiple, small, aphthoid (thrush-like) lesions are observed during the period of transient fever, chills, malaise, and rash of early HIV infection. Later, giant deep ulcers extending up several centimeters can be seen. Fistula formation, perforation, hemorrhage, or superinfection may complicate large ulcers.

 

VZV- Usually also have dermatologic lesions consistent with chickenpox or shingles. Endoscopy is also performed.

 

Treatment

Candida albicans- Clotrimazole

HSV or CMV- Ganciclovir

 

Some physicians also use steroids to lower the inflammatory response.

 

Prevention

 

Avoid situations that cause immunosuppression or destroy the normal flora composition (broad-spectrum antibiotic therapy).

 

Infections of the Stomach and Upper Duodenum

 

Disease

 

Chronic Gastritis- is the inflammation or irritation of the stomach lining. Chronic gastritis is usually caused by Helicobacter pylori.

 

Peptic ulcer disease (PUD)- is a term used to refer to a group of ulcerative disorders of the upper gastrointestinal tract involving principally the most proximal portion of the duodenum and the stomach. This term includes duodenal ulcers, gastric ulcers, ulcers associated with Zollinger-Ellison syndrome, and ulcers caused by gastrinomas. This term is also used when referring to gastric or duodenal ulcers due to drug ingestion and stress.

 

Duodenal ulcer disease- is a chronic and recurrent disease in which deep and sharply demarcated ulcers are produced. These are also called primary ulcers. Around 95% of these ulcers are found within the first portion of the duodenum. Around 90% occur within the 3 cm of the junction of the pyloric and duodenal mucosa. The ulcers are usually less than 1 cm in diameter and penetrate through the mucosa and submucosa and often into the muscularis propria. The ulcer floor has no intact epithelium and normally contains a zone of eosinophilic necrosis resting on a base of granulation tissue surrounded by variable amounts of fibrosis.

 

Gastric ulcer disease- Secondary ulcers are usually gastric in location and occur more commonly in infants and young children. Helicobacter pylori is also the cause of most of these ulcers (60-70%).

 

Etiology

 

Many things cause gastritis (a variety of medications, medical and surgical conditions, physical stresses, social habits, chemicals, and infections). The most common cause of infectious chronic gastritis (chronic active gastritis) is H. pylori.

 

Most ulcers (duodenal and gastric) are related to the inflammatory events associated with H. pylori infection and/or mucosal damage related to nonsteroidal anti-inflammatory drug (NSAID) use. It has been unequivocally demonstrated that treatment of H. pylori-related ulcer dramatically alters the natural history of this disease process.

 

Most cases of gastric cancer are also likely the consequence of lifelong H. pylori infection and the effect that this chronic infection has on mucosal carcinogenesis. But eradication of the infection is as yet, unproved as a method of preventing H. pylori-related cancers.

 

Epidemiology

 

Approximately two-thirds of the world's population is infected with H. pylori. In the United States, H. pylori is more prevalent among older adults (around 60-70% people over 60 years of age), African Americans, Hispanics, and lower socioeconomic groups. Each year there are 500,000 to 850,000 new cases of peptic ulcer disease and more than one million ulcer-related hospitalizations. Over 25 million Americans will suffer from an ulcer at some point during their lifetime. Most ulcers are caused by an infection, not spicy food, acid or stress. Primary peptic ulcers characteristically occur in children older than 10 years, most commonly occur in the duodenum, are associated with H. pylori gastritis, and may result in chronic or recurrent symptoms.

Peptic ulcer disease (PUD):                                               

 

Infectious gastritis (chronic active gastritis)- Male-to-female ratio of gastritis is approximately 1:1.

Studies have shown an association between long-term infection with H. pylori and the development of gastric cancer.

Person-to-person contact is the means of transmission of this bacterium. Humans are the only known reservoir.

Map showing percentages of population infected with H. pylori as determined by epidemiological studies. This image is from the Helicobacter Foundation website: www.helico.com

 

Pathogenesis

The mechanisms of mucosal injury in gastritis and PUD are thought to be an imbalance between acid production or pepsin, and defensive factors, such as mucus production, bicarbonate, and blood flow.

Infection with H. pylori, a short, spiral-shaped, microaerophilic gram-negative bacillus, is the leading cause of PUD and is associated with virtually all ulcers not induced by NSAIDs. H. pylori colonize the deep layers of the mucosal gel that coats the gastric mucosa and disrupts its protective properties. The bacterium is motile and it uses its corkscrew motility to migrate within the gastric and duodenal mucosa.

How the bacteria cause ulcers to form is not completely understood. However the ability of the bacteria to produce urease, a cytotoxic protein called vac A (vacuolating toxin) and to possess the cagA gene locus are important in pathogenesis of ulcer formation. The bacteria produce large amounts of urease allowing them to generate ammonium ions that buffer the gastric acid. The vac A protein causes vacuoles to form in certain cells and has also been demonstrated to cause pore formation in human cells.

Colonization of the stomach and duodenum is associated with an accumulation of inflammatory cells in the lamina propria. The inflammatory cells release cytokines that reduce somatostatin levels and cause an increase in gastrin levels. Damage to tissues results in gastritis. Eventually, an ulcer can form. H. pylori is thought to infect virtually all patients with chronic active gastritis. Chronic inflammation is thought to cause changes in the gastric mucosa that leads to gastric adenocarcinomas or lymphomas.

Manifestations

Primary peptic ulcer disease- The most common ulcer symptom is gnawing or burning pain in the epigastrium. This pain typically occurs when the stomach is empty (90 min to 3 hours after a meal), between meals and in the early morning hours, but it can also occur at other times. It may last from minutes to hours and may be relieved by eating or by taking antacids. Less common ulcer symptoms include nausea, vomiting, and loss of appetite. Bleeding can also occur; prolonged bleeding may cause anemia leading to weakness and fatigue. If bleeding is heavy, hematemesis, hematochezia, or melena may occur. These symptoms may last for weeks to months with remissions that may last months to years followed by recurrence of the symptoms. On physical exam epigastric tenderness is the most frequent finding (midline tenderness that is midway between the umbilicus and the xiphoid process.).

 

Diagnosis

 

Establish a H. pylori infection of the stomach and/or duodenum. This can include serological test, a C13 labeled urea breath test, endoscopy with biopsy. Endoscopy is quite useful in that it allows direct visualization of inflammation, ulcers and cancers. Biopsies can be performed and the material tested for the presence of urease and examined for inflammation and abnormal tissue growth.

 

Treatment

 

Triple therapy is suggested for peptic ulcer disease: A proton pump inhibitor (lansoprazole or omeprazole), amoxicillin, and clarithromycin. Penicillin allergic patients metronidazole can be substituted for the amoxicillin. Some also include bismuth (Pepto-Bismol) with the triple agent therapy.

 

Some suggest also treating gastritis as above to prevent development of cancer however; this is yet to be proven effective.

 

Prevention

 

No prevention methods or vaccines have been discovered thus far. Some suggest the treatment of chronic gastritis to prevent cancer formation. This is has not yet been shown to be effective.