A 32-year-old man with newly diagnosed HIV (CD4 count 35 cells/μL) presents with fever, severe odynophagia, and dysphagia for 1 week. Endoscopy reveals multiple large, deep, confluent ulcers in the esophagus with white exudate. Biopsy shows intranuclear inclusions and multinucleated giant cells. Blood cultures are negative. What is the most likely causative organism and the recommended first-line antiviral therapy?

Explanation

## Clinical Diagnosis **Key Point:** CMV esophagitis is the classic presentation in patients with CD4 < 50 cells/μL. The combination of large, deep, confluent ulcers with white exudate and histologic findings of intranuclear inclusions and multinucleated giant cells is diagnostic of CMV. ## Histopathologic Features | Virus | Ulcer Depth | Exudate | Intranuclear Inclusions | Multinucleated Giant Cells | |-------|-------------|---------|-------------------------|----------------------------| | CMV | Large, deep | White | "Owl's eye" (prominent) | Present | | HSV | Small, shallow | Fibrinous | Marginal, less prominent | Present | | VZV | Variable | Fibrinous | Marginal | Present | | Candida | Superficial | White/yellow | Absent | Absent | **High-Yield:** CMV esophagitis occurs almost exclusively at CD4 < 50 cells/μL. HSV esophagitis occurs at CD4 50–200 and presents with smaller, more superficial ulcers. ## Pathophysiology 1. Severe immunosuppression allows reactivation of latent CMV 2. Lytic infection of esophageal epithelium 3. Characteristic "owl's eye" intranuclear inclusions (large, prominent, with halo) 4. Extensive ulceration with deep necrosis ## Management **Clinical Pearl:** Ganciclovir is the first-line agent for CMV esophagitis: - **Dosing:** 5 mg/kg IV twice daily for 14–21 days - **Mechanism:** Inhibits CMV DNA polymerase (requires viral kinase phosphorylation) - **Monitoring:** Weekly CBC for myelosuppression (neutropenia, thrombocytopenia) - **Alternative:** Foscarnet 90 mg/kg IV twice daily if ganciclovir-resistant or intolerant **Key Point:** Immune reconstitution with antiretroviral therapy (ART) is critical. CMV esophagitis typically resolves with CD4 recovery to > 50 cells/μL on ART, even without prolonged antiviral therapy. **Mnemonic:** CD4 < 50 = CMV disease (retinitis, esophagitis, colitis, encephalitis) [cite:Harrison 21e Ch 197; CDC Guidelines on Opportunistic Infections in HIV]