Cytomegalovirus Oesophagitis

Cytomegalovirus infection of the oesophageal mucosa causing large, deep ulcers, mainly in severely immunocompromised patients.

• Occurs in advanced HIV (CD4 count under 100 cells/microlitre, especially under 50), solid organ and stem cell transplant recipients, patients on high-dose corticosteroids or biologic and other immunosuppressants (for example for inflammatory bowel disease), haematological malignancy, and critical illness; it makes up about 10 to 20% of infectious oesophagitis in these groups.
• Usually from reactivation of latent infection; viraemia may or may not be present.
• Mechanism: viral replication in endothelial cells and fibroblasts in the submucosa causes vasculitis, ischaemia and deep ulceration of the mucosa.

Odynophagia, dysphagia, retrosternal pain, nausea, fever, weight loss; haematemesis or melaena in about 10 to 20%; diarrhoea or abdominal pain if there is other gastrointestinal disease.

• Evidence of CMV elsewhere: retinitis (floaters, visual loss), colitis, pneumonitis, hepatitis.
• Differential diagnosis: Candida and herpes oesophagitis, HIV-related idiopathic oesophageal ulcer, pill oesophagitis, reflux, lymphoma, Kaposi sarcoma, mycobacterial infection, cancer.
• Complications: bleeding (can be massive), perforation, tracheo-oesophageal fistula, stricture, dehydration and malnutrition, and dissemination.

HIV test, CD4 count and viral load, full blood count (leucopenia), creatinine, liver tests; blood cytomegalovirus PCR (a positive result supports but does not confirm oesophageal disease, and a negative result does not exclude it); fundoscopy for retinitis.

• Upper endoscopy: one or several large (more than 1 cm), deep, linear or serpiginous ulcers with well-demarcated edges in the distal oesophagus, surrounded by normal mucosa; sometimes small ulcers or diffuse erosions.
• Biopsies from the ulcer base (the site of infected endothelial and stromal cells; take at least 6 to 10): enlarged cells with intranuclear "owl's-eye" inclusions and cytoplasmic inclusions, with immunohistochemistry confirmation and PCR; biopsies also for Candida, herpes and mycobacteria.
• CT chest or barium swallow for perforation or fistula.

Antiviral therapy for 3 to 6 weeks (until symptoms resolve and ulcers heal):

• Ganciclovir 5 mg/kg IV every 12 hours (renal dose adjustment: creatinine clearance 50 to 69 mL/min 2.5 mg/kg every 12 hours; 25 to 49 mL/min 2.5 mg/kg daily; 10 to 24 mL/min 1.25 mg/kg daily), then valganciclovir 900 mg orally twice daily once swallowing and absorption are adequate (adjust for renal function), to complete the course.
• Foscarnet 90 mg/kg IV every 12 hours (or 60 mg/kg every 8 hours) for ganciclovir resistance, intolerance or neutropenia (full blood count under 0.5 x 10^9/L neutrophils), with saline hydration (1 to 2 L before each dose), electrolytes (calcium, magnesium, potassium, phosphate) and creatinine monitoring.
• Cidofovir 5 mg/kg IV weekly for 2 weeks then every 2 weeks, with probenecid 2 g 3 hours before and 1 g at 2 and 8 hours after, and saline hydration, for resistant disease (nephrotoxic).

```{=html} <!-- --> ``` - Monitor blood counts twice weekly on ganciclovir; filgrastim 300 micrograms SC daily if neutrophils are under 0.5 x 10^9/L; reduce the dose or switch to foscarnet if neutropenia persists.

• Reverse immunosuppression: start or optimise antiretroviral therapy in HIV within 2 weeks of antiviral start; reduce immunosuppressive drugs in transplant and other patients, with specialist input.
• Supportive care: analgesia with paracetamol 1 g four times daily and viscous lidocaine 2% 15 mL before meals (maximum 8 doses a day); opioid for severe pain; omeprazole 20 to 40 mg daily for mucosal protection; soft or liquid diet; IV fluids; nutritional support by tube or parenteral route if oral intake fails for more than 5 to 7 days.
• Bleeding: omeprazole 80 mg IV bolus then 8 mg/hour for 72 hours, endoscopic therapy, transfusion at 70 g/L (80 g/L in cardiovascular disease), angiographic embolisation; perforation: nil by mouth, antibiotics (piperacillin-tazobactam 4.5 g IV every 6 hours), and surgical or stent management.
• Stricture: balloon dilatation to 15 to 18 mm after healing.
• Secondary prophylaxis is not routinely needed when immune recovery occurs; in persistent profound immunosuppression consider valganciclovir 900 mg once daily for 3 to 6 months.
• Special groups: children (ganciclovir 5 mg/kg IV every 12 hours for 2 to 3 weeks, then valganciclovir 16 mg/kg twice daily, maximum 900 mg, with blood count monitoring); pregnancy (ganciclovir and valganciclovir are teratogenic and are used only for life-threatening disease; foscarnet is an alternative with limited data; specialist care); elderly (renal dose adjustment, blood count and cognitive monitoring); renal impairment (adjust ganciclovir and valganciclovir doses to creatinine clearance, and avoid foscarnet and cidofovir unless essential); transplant recipients (reduce immunosuppression with the transplant team, check CMV PCR in blood).
• Red flags: haematemesis, inability to swallow saliva, severe chest pain, fever with mediastinal air, visual symptoms (retinitis), neutropenia, no response in 14 days, CD4 count under 50 cells/microlitre.
• Follow-up: clinical review at 1 week and 2 to 3 weeks; blood count twice weekly and creatinine and electrolytes weekly during therapy; repeat endoscopy for non-response after 2 to 3 weeks (consider resistance testing); CD4 count and viral load every 3 months; ophthalmology review in HIV with CD4 count under 100 cells/microlitre.