You are in: eMedicine Specialties > Radiology > GASTROINTESTINAL Esophagitis, InfectiousArticle Last Updated: Sep 3, 2004AUTHOR AND EDITOR INFORMATIONSection 1 of 8
  Author: Arastoo Vossough, MD, PhD, Staff Physician, Department of Radiology, Hospital of the University of Pennsylvania Arastoo Vossough is a member of the following medical societies: American Roentgen Ray Society and Radiological Society of North America Coauthor(s): Marc S Levine, MD, Chief, Section of Gastrointestinal Radiology; Advisory Dean, School of M, Hospital of the University of Pennsylvania; Professor of Radiology, Department of Radiology, University of Pennsylvania School of Medicine Editors: Eric P Weinberg, MD, Associate Professor, Department of Radiology, University of Rochester Medical Center, Strong Memorial Hospital; Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand; Udo P Schmiedl, MD, PhD, Clinical Professor, Department of Radiology, University of Washington; Consulting Staff, Swedish Medical Center, University of Washington Medical Center, Seattle Radiologists; Robert M Krasny, MD, Consulting Staff, Department of Radiology, The Angeles Clinic and Research Institute; Eugene C Lin, MD, Consulting Staff, Department of Radiology, Virginia Mason Medical Center Author and Editor Disclosure Synonyms and related keywords: infectious esophagitis, esophageal infection, esophagitis, esophagus, Candida esophagitis, candidal esophagitis, viral esophagitis, bacterial esophagitis, HIV esophagitis, esophagitides, cytomegalovirus, cytomegaloviral esophagitis, CMV esophagitis, herpes esophagitis, esophageal candidiasis, tuberculous esophagitis, fungal overgrowth of the esophagus, Candida albicans, C albicans, Candida tropicalis, C tropicalis, Candida glabrata, C glabrata, Candida parapsilosis, C parapsilosis CANDIDA ESOPHAGITISSection 2 of 8
  Epidemiology Infection by Candida species is the most common cause of infectious esophagitis. Major predisposing factors include antibiotic use, radiation therapy or chemotherapy, hematologic malignancies, and AIDS. Other conditions associated with an increased incidence of Candida esophagitis include esophageal stasis, alcoholism, malnutrition, and advanced age. Occasionally, Candida esophagitis can occur in otherwise healthy individuals with no underlying esophageal or systemic disease. Pathophysiology Candida esophagitis results from fungal overgrowth of the esophagus, impaired cell-mediated immunity, or both. Fungal overgrowth typically occurs in the setting of esophageal stasis resulting from abnormal esophageal motility (eg, achalasia or scleroderma) or mechanical causes (eg, strictures). Impaired cell-mediated immunity can result from immunosuppressive therapy (with, eg, steroids or cytotoxic agents), malignancies, or AIDS. Chronic mucocutaneous candidiasis is a congenital immunodeficiency state that is also associated with Candida esophagitis. Candida albicans is the most common offending pathogen, but other Candida species, such as Candida tropicalis, Candida glabrata, and Candida parapsilosis, have also been implicated as rare causes of esophagitis. The pathologic appearance of Candida esophagitis ranges from a few superficial white plaques on the mucosal surface to a dense, thick pseudomembrane composed of desquamated squamous epithelial cells, fungus, and fibrin. Complications of esophageal candidiasis include ulceration and hemorrhage; esophageal obstruction secondary to stricture or mycetoma formation; and, rarely, fistula formation into the bronchial tree. Clinical findings The usual clinical presentation of Candida esophagitis is dysphagia and/or odynophagia in a patient with 1 or more predisposing factors for the condition. Symptoms are variable in severity, ranging from mild difficulty in swallowing to such intense odynophagia that the patient is unable to eat or swallow saliva. Other patients may present with chest pain or gastrointestinal tract bleeding, and occasionally, they may be asymptomatic. Oropharyngeal candidiasis is commonly associated with esophageal candidiasis; therefore, the presence of oral thrush may be helpful in suggesting the diagnosis of Candida esophagitis in the appropriate clinical setting. Nevertheless, only 50-75% of patients with Candida esophagitis have oropharyngeal disease, and some patients with oropharyngeal candidiasis and dysphagia are found to have other types of esophagitis; therefore, the correct diagnosis cannot always be suggested on the basis of clinical presentation. Depending on the severity of disease and the patient's immune status, treatment of Candida esophagitis includes topical nystatin, oral treatment with systemic antifungal agents, or even intravenous amphotericin B. For excellent patient education resources, visit eMedicine's Yeast and Fungal Infections Center. Also, see eMedicine's patient education article Candidiasis (Yeast Infection). Radiographic findings Because Candida esophagitis is primarily a mucosal disease, it often is difficult to recognize with single-contrast esophagography. In contrast, double-contrast esophagography has a sensitivity of 90% in detecting the condition. On double-contrast studies, Candida esophagitis initially is manifested by discrete plaquelike lesions in the esophagus. Usually, the plaques are oriented longitudinally, appearing en face as linear or irregular filling defects with normal intervening mucosa (see Image 1). The plaques may be localized or diffuse and usually are located in the upper or mid esophagus. Some patients may have multiple tiny plaques, which produce a finely granular or nodular appearance of the mucosa. In advanced Candida esophagitis, the esophagus may have a grossly irregular or shaggy appearance as a result of innumerable plaques and pseudomembranes, with trapping of barium between the lesions (see Image 2). This appearance is most commonly seen in patients with AIDS; therefore, the presence of a shaggy esophagus should suggest the possibility of AIDS in patients who are not yet known to be HIV positive. Some of the plaques and pseudomembranes may eventually be sloughed off, producing 1 or more areas of ulceration on a background of diffuse plaque formation. Occasionally, barium may also dissect beneath the pseudomembranes, resulting in an intramural dissection tract or double-barrel esophagus. Candida esophagitis is usually self-limiting, and most patients have a marked response to treatment with antifungal agents. However, necrotic mucosal debris and fungal mycelia in the esophagus occasionally form a mycetoma (eg, fungus ball) that causes obstruction. In other patients, severe Candida esophagitis may lead to development of strictures, which are typically long, smooth, tapered areas of narrowing. In patients with chronic stasis, such as those with advanced achalasia or scleroderma involving the esophagus, superimposed Candida esophagitis may manifest as tiny nodules, polypoid folds, or a lacy appearance in the esophagus. Other patients with scleroderma or achalasia may have a foamy esophagus with innumerable bubbles layering out in the barium column as a result of a yeast form of the infection (see Image 3). Other rare complications of esophageal candidiasis include perforation, tracheobronchial fistulas, and aortoesophageal fistulas. Differential diagnosis Glycogenic acanthosis, reflux esophagitis, herpes esophagitis, and superficial spreading carcinoma may produce findings similar to those seen in Candida esophagitis. However, patients with glycogenic acanthosis are almost always older individuals who have no esophageal symptoms, and the mucosal nodules of glycogenic acanthosis tend to have a more rounded appearance, whereas the plaques of candidiasis are more linear. Reflux esophagitis may also manifest as a nodular mucosa, but the nodules tend to be more poorly defined than those in candidiasis, and they are always contiguous with the gastroesophageal junction. Occasionally, herpes esophagitis manifests as multiple plaquelike lesions in the esophagus, but this infection is more commonly associated with small superficial ulcers (see the Herpes Esophagitis section below). Superficial spreading carcinoma may also manifest as a nodular mucosa, but the nodules tend to have poorly defined borders, producing a confluent area of disease. Undissolved effervescent particles and debris in the esophagus can be mistaken for the plaques of candidiasis. Thus, if infectious esophagitis is suggested clinically, a double-contrast study should initially be performed without the use of effervescent granules. HERPES ESOPHAGITISSection 3 of 8
Epidemiology After candidiasis, herpes simplex virus type I is the second most common cause of infectious esophagitis. Herpes esophagitis is most commonly seen in immunocompromised patients with AIDS, an underlying malignancy, or a debilitating illness or in patients who have been treated with radiation, steroids, or chemotherapy. However, herpes esophagitis occasionally occurs as an acute self-limiting disease in otherwise healthy patients who have no underlying immunologic problems. Although obtaining accurate figures regarding the prevalence of herpes esophagitis is difficult, this infection has been reported in approximately 1% of patients who are immunocompromised and in as many as 43% of patients at autopsy. Pathophysiology Initially, herpes esophagitis is manifested by the development of small vesicles that subsequently rupture to form discrete superficial ulcers on the mucosa. The epithelial cells at the edge of the ulcers are characterized by multinucleation, ground-glass nuclei, and characteristic eosinophilic Cowdry type A inclusion bodies. In immunocompetent patients, the host response promotes healing of the ulcers, but in patients who are severely immunocompromised, the condition may progress from discrete areas of ulceration to a diffuse hemorrhagic esophagitis. Necrotic herpetic ulcers may become superinfected by candidiasis. Clinical findings Patients with herpes esophagitis typically present with an acute onset of severe odynophagia. Other presenting findings include dysphagia, chest pain, and upper gastrointestinal tract bleeding. Although the presence of herpes labialis (cold sores) or herpetic lesions of the oropharynx should suggest the presence of herpetic esophagitis in the appropriate clinical setting, most patients have no concurrent oropharyngeal herpetic lesions. Moreover, some patients with odynophagia and oral herpes eventually are found to have Candida esophagitis. Therefore, the presence of other herpetic lesions is not accurately predictive of herpes esophagitis in patients with odynophagia. In immunocompetent patients, herpes esophagitis often spontaneously resolves within 1-2 weeks with conservative treatment involving analgesia and sedation. Rare complications of herpes esophagitis include perforation, tracheoesophageal fistulas, and dissemination to other organs. Radiographic findings On double-contrast esophagrams, herpes esophagitis usually manifests as multiple, small, superficial ulcers in the upper or mid esophagus on an otherwise normal background mucosa (see Image 4). The ulcers can have a punctate, linear, stellate, or volcano-like appearance, often with a thin halo of edema at the margins. The ulcers may be clustered together or widely separated with normal intervening mucosa. Severe herpes esophagitis may produce extensive ulceration and plaque formation, mimicking the appearance of Candida esophagitis. Differential diagnosis In the appropriate clinical setting, discrete superficial ulcers in the upper or mid esophagus without associated plaques should be highly suggestive of herpes esophagitis. In contrast, ulceration in Candida esophagitis almost invariably occurs on a background of extensive plaque formation. Candida and herpes esophagitis can often be diagnosed on double-contrast studies, obviating endoscopy. However, if radiographic findings are equivocal or if response to treatment is inadequate, endoscopy should be performed for a more definitive diagnosis. Other causes of small superficial ulcers in the upper or mid esophagus include drug-induced esophagitis and Crohn disease. However, these entities usually can be differentiated from infectious esophagitis on the basis of the clinical history. CYTOMEGALOVIRAL ESOPHAGITISSection 4 of 8
Epidemiology Cytomegalovirus (CMV) is a rather recently recognized cause of esophagitis. Asymptomatic CMV infection is common worldwide, and a large percentage of the world's population has been exposed to CMV. Before the AIDS epidemic, CMV infections of the esophagus were primarily found on postmortem examinations. The first clinical case of CMV esophagitis was not reported until 1985. Unlike herpes esophagitis, CMV esophagitis almost never occurs in immunocompetent patients, and the vast majority of affected individuals are found to have AIDS. Pathophysiology The most constant feature of CMV esophagitis is mucosal ulceration; the ulcers may be single or multiple. These lesions can be shallow or deep, and not infrequently, they are several centimeters or more in diameter. Infected epithelial cells in the esophagus become enlarged by a factor of 2-4 times (hence the term cytomegalic cells), and they contain eccentrically placed intranuclear inclusion bodies with surrounding halos. In contrast to herpes esophagitis, small granular cytoplasmic inclusions are seen in endothelial cells or fibroblasts near the base of the ulcers. A lymphomonocytic inflammatory response is also seen at the site of infection. Clinical findings CMV esophagitis is usually manifested by the development of severe odynophagia, dysphagia, or both, in patients with AIDS. In affected individuals, evidence of CMV infection may be present in other organs or tissues, such as the retina, liver, and colon. Occasionally, odynophagia may be so severe that the patients develop sitophobia (fear of eating), and parenteral alimentation is required. Radiographic findings On double-contrast esophagrams, CMV esophagitis is typically manifested by 1 or more giant and relatively flat ulcers, sometimes associated with small satellite ulcers (see Image 5). These ulcers may be ovoid, elongated, or diamond shaped, and they are frequently surrounded by a radiolucent rim of edematous mucosa. Less commonly, CMV esophagitis appears as small superficial ulcers that are indistinguishable from the ulcers of herpes esophagitis on barium studies. Differential diagnosis Because herpetic ulcers rarely become as large as those of infectious esophagitis, the presence of 1 or more giant ulcers suggests the possibility of CMV esophagitis in patients with AIDS. However, in patients who are HIV positive, giant esophageal ulcers can also be caused by HIV (see the HIV Esophagitis section below). Treatments for CMV esophagitis and HIV esophagitis are different. CMV esophagitis is usually treated with ganciclovir and foscarnet, which are potent antiviral agents that have significant bone marrow and renal toxicities, respectively. On the contrary, HIV esophagitis is treated with oral steroids. Because these entities cannot be reliably differentiated on the basis of the clinical and radiographic findings, endoscopy is required for a definitive diagnosis before patients are treated. When multiple esophageal biopsy specimens, brushings, and/or viral cultures are obtained, endoscopy has a sensitivity of greater than 95% in the diagnosis of CMV esophagitis. Other causes of giant esophageal ulcers include nasogastric intubation; endoscopic sclerotherapy; caustic injuries; and oral medications, such as nonsteroidal anti-inflammatory drugs, potassium chloride, and quinidine. However, the correct diagnosis can almost always be suggested on the basis of the clinical history. HIV ESOPHAGITISSection 5 of 8
Giant esophageal ulcers have been described in the esophagus in patients with AIDS in whom no other infectious etiology for the ulcers can be found. These ulcers have been termed idiopathic or HIV ulcers because they are believed to be caused by HIV. In fact, results of electron microscopy confirm the presence of HIV-like viral particles in these lesions. Although some patients with HIV ulcers may have undergone recent seroconversion, most are found to have chronic AIDS with CD4 counts of less than 100 cells per cubic millimeter. HIV ulcers are more common than generally recognized, accounting for as many as 40% of all esophageal ulcers in patients with AIDS. Clinical and radiographic findings Patients with HIV ulcers typically present with acute onset of severe odynophagia, dysphagia, or both. If the ulcers develop at the time of seroconversion, a characteristic maculopapular rash may be seen on the upper half of the body. The lesions usually appear on double-contrast esophagrams as 1 or more giant, flat ulcers (>1 cm in diameter) of the esophagus (see Image 6). This finding is sometimes associated with a cluster of small satellite ulcers. The ulcers are often surrounded by a radiolucent rim of edema. Because most HIV ulcers are indistinguishable from CMV ulcers on the basis of the clinical and radiographic criteria, CMV esophagitis must be excluded by means of endoscopy before a diagnosis of HIV esophagitis can be established. Biopsy specimens, brushings, and/or viral cultures from the esophagus may be needed. Differentiating these infections is essential because most cases of HIV esophagitis dramatically respond to treatment with oral steroids, whereas CMV esophagitis is treated with relatively toxic antiviral agents such as ganciclovir (see Cytomegalovirus Esophagitis). Endoscopy is required for a definitive diagnosis before patients are treated. MISCELLANEOUS INFECTIOUS ESOPHAGITIDESSection 6 of 8
Tuberculous esophagitis occurs primarily in patients with advanced pulmonary or mediastinal tuberculosis or in immunocompromised patients who have disseminated tuberculosis or other mycobacterial diseases. The esophagus is usually involved by erosion of the involved mediastinal lymph nodes abutting the esophagus. Barium studies or CT scans may reveal extrinsic compression or displacement of the esophagus due to enlarged collections of nodes in the adjacent mediastinum. In some patients, traction diverticula may develop in the upper or mid esophagus. Erosion of caseating nodes into the esophagus may result in the development of longitudinal or transverse sinus tracts or esophageal-airway fistulas. Similar tracts and fistulas may be seen in patients with radiation esophagitis, Crohn disease, trauma, or esophageal cancer. However, in these patients, the clinical history usually suggests the correct diagnosis. Intrinsic tuberculosis is extremely rare and characterized by mucosal plaques, ulcers, strictures, and fistulas. The development of dysphagia, coughing, or choking during swallowing suggests the possibility of esophageal involvement or fistula formation in a patient with tuberculosis. Other infections of the esophagus are rare and most often develop in patients with neutropenia, AIDS, burns, trauma, or generalized sepsis. Actinomycosis may produce severe esophagitis with deep ulcers and fistulous tracts to the mediastinum, pleural space, tracheobronchial tree, and skin. The diagnosis can be confirmed by the presence of characteristic sulfur granules on endoscopic biopsy specimens. Other infectious agents that may involve the esophagus include varicella-zoster virus; human papillomavirus; Epstein-Barr virus; and Staphylococcus, Streptococcus, Lactobacillus, Nocardia, Trypanosoma, Leishmania, Cryptosporidium, and Blastomyces species. MULTIMEDIASection 7 of 8
REFERENCESSection 8 of 8
Esophagitis, Infectious excerpt Article Last Updated: Sep 3, 2004 | ||||||||||||||||||||||||||||||||||||||||||
