Other viral pathogens

Varicella zoster virus (VZV) is a relatively uncommon agent of infectious esophagitis in immunologically normal subjects, but it causes a severe esophagitis in immunocompromised patients, usually accompanied by other signs of systemic dissemination (e.g. pneumonitis, hepatitis, encephalitis).37 The endoscopic appearance ranges from vesicles to necrotic ulcerations. Definite diagnosis requires biopsies both for routine histology (ballooning degeneration, multinucleated giant cells, intranuclear eosinophilic inclusion bodies) and for culture and immunohistochemical staining. The infection is treated with acyclovir or famciclovir; foscarnet is used for resistant viruses.

In a subject with clinical features consistent with infectious mononucleosis due to Epstein-Barr virus (EBV), the occurrence of nausea, dysphagia or hematemesis should raise the possibility of an infectious esophagitis. This however, develops only in a small minority of immunocompetent individuals, whereas in immunocompromised subjects, EBV-related infectious esophagitis has been reported.38 Oral acyclovir may be a reasonable therapy, even if benefits of antiviral therapy in EBV-related esophagi-tis are unproven.

The human papillovirus, like HSV usually infects squamous epithelial cells. The diagnosis requires histology39 (multinucleated giant cells, koilocytosis, cellular atypia) and immunohistochemical staining. Endoscopy reveals non-specific lesions such as yellow plaques, small nodules or patches with small villous projections. The condition is generally asymptomatic, and specific treatment may be unnecessary

In specific HIV-related esophagitis, HIV is a well-known risk factor for many other infections. However, it is agreed that HIV itself can lead to esophageal ulcerations,40 usually presenting as multiple, small and shallow lesions. This esophageal

Table 3.4 Drugs for viral esophagitis

Drug Duration

Acyclovir 7-10 days

Ganciclovir 14-28 days

Foscarnet 14-28 days

Famciclovir 7 days

Cidofovir 14 days

Dosage

20mg/kg per dose orally four times daily (80 mg/kg per day). Severe infections refractory to normal oral dosages or in which the patient is unable to swallow are treated with i.v. acyclovir, 15-30 mg/kg per day in 3 divided doses

5 mg/kg given intravenously twice per day

HSV infection: 40 mg/kg of body weight given either every 8 or every 12 h. This dose is injected slowly into a vein by an infusion pump over at least 1 h. CMV infection: 60 mg/kg, as above

In adults: 250 mg, three times daily orally

Remarks

A nucleoside analog available for both oral and intravenous administration. It is well tolerated; occasionally, rash, reversible renal failure or gastrointestinal symptoms occur. Dose adjustment should be made with renal impairment. Risk of renal insufficiency is reduced with adequate prehydration

Drugs of first choice for the treatment of serious systemic CMV infections. The need for maintenance therapy of gastrointestinal CMV infection remains unclear. Dosage reduction is recommended in patients with renal impairment. Main side-effects are: neutropenia, thrombocytopenia, central nervous system symptoms, abnormal liver function tests, fever and rash. Simultaneous administration of G-CSF or GM-CSF can prevent ganciclovir-associated neutropenia

Second-line parenteral antiviral, reserved for treatment of HSV or CMV infections resistant to conventional therapy. Main side-effects are: nephrotoxicity, anemia, gastrointestinal toxicity, hyper- and hypocalcemia, hypomagnesemia, hyper- and hypophosphatemia, hypokalemia, seizures. It is mainly used in the treatment of acyclovir-resistant HSV infections and ganciclovir-resistant CMV infections

Consider with acyclovir resistance, but limited experience in infectious esophagitis. Use with caution in subjects with renal insufficiency. Main side-effects similar to those for acyclovir

A novel monophosphate nucleotide analog effective against CMV, HVS-1, HVS-2 and EBV. Parenteral antiviral recently approved to treat CMV retinitis. No reports on the treatment of CMV esophagitis. Generally reserved for patients with serious CMV disease for whom ganciclovir and/or foscarnet therapy has failed. Main side-effects are: nephrotoxicity, proteinuria, glycosuria, neutropenia and metabolic acidosis

CMV, cytomegalovirus; G, granulocyte; CSF, colony-stimulating factor; GM, granulocyte/macrophage; HSV, herpes simplex virus; EBV, Epstein-Barr virus involvement may occur in the setting of a mononu-cleosis-like illness that develops around the time of the primary HIV infection. Biopsy specimens examined at electronic microscopy show enveloped viruslike particles with morphology compatible with that of retroviruses. In the later stages of HIV infection, when the CD4 lymphocyte count is below 100/mm3, large esophageal ulcerations can be observed. These ulcers are commonly defined as idiopathic esophageal ulcers (IEU) and appear as uniformly well-circumscribed lesions, without histological features of a viral cytopathic effect. It has been observed that HIV-associated IEU are diagnosed when biopsy, cytology and cultures are negative. Electron micrographs from the margins of some superficial ulcers have revealed viral particles morphologically similar to retroviruses. The poly-merase chain reaction (PCR) can identify the HIV genome in biopsy specimens, but it remains unclear whether HIV is pathogenic in esophageal ulcerations. Reports have revealed HIV histopathologically in esophageal biopsies from patients with Candida, HSV and CMV. It has been hypothesized that most esophageal disease in patients with advanced HIV infection is associated with specific pathogenic processes. However, HIV-induced ulcerations can occur and may require treatment with corticos-teroids.41 IEU present clinically in a fashion similar to CMV esophagitis; whereas bleeding is reported, strictures are rare. These ulcers usually respond well to oral corticosteroids or thalidomide. Despite the fact that these drugs may entail some risk for patients already immunosuppressed, this treatment is usually well tolerated.

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