Gastrointestinal Pathology. Группа авторов

Infectious Esophagitis

      Definition, General Features, Predisposing Factors

      Infection is a common cause of esophagitis, particularly in immunocompromised patients but can also occur in apparently immunocompetent hosts with certain predisposing conditions. Fungi (Candida species) and viruses are responsible for most cases of infectious esophagitis, and dual infections may be encountered. Bacterial, mycobacterial, and parasitic esophagitis (e.g. Chagas disease due to Trypanosoma cruzi) are rarely encountered in esophageal biopsy material.

      Fungal Esophagitis

      Fungal infection due to Candida albicans is the most common cause of infectious esophagitis.

      Predisposing conditions are broad and include HIV infection/AIDS, other immunosuppressed conditions such as organ transplant, prolonged corticosteroid therapy as well as other conditions such as diabetes, malignancy, antibiotic therapy, acid‐suppressive therapy, and pregnancy. Infection due to Candida tropicalis and Candida (Torulopsis) glabrata has also been described, as well as infection due to other fungi such as Histoplasma capsulatum and Aspergillus species.

      Viral Esophagitis

Herpes simplex (HSV) is the most common etiology of viral esophagitis, and also occurs primarily in the setting of immunosuppression, such as solid organ and bone marrow transplantation, underlying malignancy, chemotherapy, and HIV infection (AIDS). These patients may also have disseminated infection at the time of diagnosis. It can also develop in healthy adults including pregnant women and children. Both HSV types 1 and 2 can infect the esophagus with type 1 being most common. Infection by varicella‐zoster virus (VZV) may also rarely occur in immunocompromised hosts.

Figure 2.1 Endoscopic appearance of distal esophagus with normal squamous mucosa.

Figure 2.2 Normal esophagus squamous mucosa with normal stratified non‐keratinizing epithelium.

Table 2.1 Normal esophageal mucosa.

Epithelium:

Non‐keratinizing squamous epithelium

Glycogen rich

10–20 cells thick (300–500 μm)

Basal proliferative zone up to 15%

Few scattered parabasal T lymphocytes and other specialized cells

Lamina propria:

Papillary length 1/3 to 1/2 of epithelial thickness

Muscularis mucosae

      Cytomegalovirus (CMV)‐induced esophagitis also typically occurs in the immunosuppressed population, particularly in the setting of HIV infection/AIDS, organ transplantation, chemotherapy, corticosteroid therapy, and other forms of long‐term immunosuppression. CMV may rarely cause esophagitis in immunocompetent patients, especially in the elderly.

      Bacterial Esophagitis

      Clinically significant bacterial esophagitis occurs almost exclusively in immunocompromised patients. Secondary bacterial colonization of areas of prior esophageal injury and ulceration is more common. Bacterial invasion of squamous mucosa or the deeper layers is required to establish a diagnosis of primary bacterial esophagitis. Gram‐positive bacteria are the most common causative organisms (including Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus viridans, and beta‐hemolytic streptococci).

      Mycobacterial Esophagitis

      The rare mycobacterial esophagitis typically occurs in the setting of advanced immunosuppression. Both Mycobacterium tuberculosis complex and Mycobacterium avium complex can be encountered.

      Parasitic Esophagitis

      Chagas disease involving the esophagus is an important cause of esophageal dysfunction (dysphagia) in endemic regions, such as Latin America. However, the organism and its pathologic effects are typically not identified on biopsy specimens.

      Clinical Features and Endoscopic Characteristics

Clinical and endoscopic features are specific to each condition. For candidal esophagitis, symptoms vary from none (especially in patients with mild disease from chronic inhaled steroids) to severe dysphagia and odynophagia in immunosuppressed patients. Candida appears as a white, cottage cheese‐like exudate, which is partially adherent to the epithelium (Figure 2.3). HSV and CMV both cause ulcerations. HSV ulcers are typically small, 1–3 mm, whereas CMV ulcers may be both deep and wide. Biopsy yield for the virus is highest from the edge of HSV ulcers and from the center of CMV ulcers. In practice, both are usually obtained. Other infections’ etiologies may have nonspecific findings. The inflammatory reaction of tuberculous esophagitis often imparts a radiologically detectable mass‐like lesion, whereas mucosal changes include linear ulcers and induration that preferentially affects the mid‐portion of the esophagus. Fistula formation and perforation may occur. Chagas disease presentation is similar to that of achalasia with manometric findings of a poorly relaxing lower esophageal sphincter and an aperistaltic esophagus body.

Figure 2.3 Endoscopic appearance of white exudate typical of Candida albicans in a patient on chronic inhaled corticosteroid.

      Microscopic Features

      Candida

      The biopsies typically show an active esophagitis with a mixed inflammatory infiltrate of neutrophils, lymphocytes, and eosinophils. Neutrophils are often present in small, superficial clusters associated with parakeratosis or squamous debris, which may be a diagnostic clue. Prominent intraepithelial neutrophils may be associated with abscesses, erosions, or ulcerations. The inflammatory response may be minimal in severely immunocompromised patients.

Yeast forms of C. albicans and pseudohyphae (with refractile cell walls) are usually present in superficial desquamated keratin debris (Figure 2.4). The yeast are 3–5 μm in diameter basophilic oval forms while the, nonseptate sausage‐like pseudohyphae are 3–5 μm in diameter and are arranged perpendicular to the epithelial surface. Occasional septate hyphae can be present. The presence of psuedohyphal and hyphal forms correlates with active infection. Most infections are superficial with isolated, intraepithelial fungal forms, and organisms in detached squamous cells. However, in immunocompromised hosts, deeper tissue invasion within ulcers and erosions may be seen. Candida are often conspicuous in routinely stained sections, although their appearance