Herpes Oesophagitis

Infection of the oesophageal squamous epithelium by herpes simplex virus (mostly type 1), producing vesicles that rupture into shallow punched-out ulcers.

• Occurs in immunocompromised patients (HIV, transplantation, chemotherapy, corticosteroids, haematological malignancy) and also in otherwise healthy young adults (about 1 in 10 cases), in whom it is self-limiting in 1 to 2 weeks.
• Accounts for about 5 to 15% of infectious oesophagitis; reactivation of latent virus is more common than primary infection; in HIV it occurs at all CD4 counts.
• Mechanism: viral replication in epithelial cells, giant cell formation, cell lysis, and sloughing, with ulcers in the mid and distal oesophagus.

Acute odynophagia (prominent), retrosternal chest pain, dysphagia, fever, nausea, and weight loss; haematemesis in about 10%.

• Oral or labial herpetic lesions in about 20 to 30%; flu-like prodrome in healthy hosts.
• Differential diagnosis: Candida and cytomegalovirus oesophagitis, pill oesophagitis, reflux, eosinophilic oesophagitis, Crohn disease, Behcet disease, caustic injury, cancer.
• Complications: bleeding, perforation, fistula (tracheo-oesophageal or aortic, rare), stricture, superinfection with Candida, dehydration, and dissemination in immunosuppression.

Upper endoscopy: small vesicles early, then multiple shallow, well-circumscribed "punched-out" or volcano ulcers with raised edges in the mid and distal oesophagus, with normal intervening mucosa; in advanced disease, diffuse exudative ulceration.

• Biopsy of the ulcer edge (not the base): multinucleated giant cells with ground glass nuclei, intranuclear inclusion bodies, and positive immunohistochemistry or PCR; viral culture or PCR of brush specimens; biopsies also exclude Candida and cytomegalovirus.
• HIV test and CD4 count, full blood count, glucose, creatinine, liver tests.
• Barium swallow or CT for suspected perforation or fistula; chest X-ray for mediastinal air.

Immunocompetent patients with mild disease: supportive care only (analgesia, hydration, soft diet) is reasonable as it resolves in 1 to 2 weeks; antiviral therapy shortens the course: aciclovir 400 mg orally five times daily or valaciclovir 1 g three times daily for 7 to 14 days.

• Immunocompromised patients:
  • Oral therapy when swallowing is possible: aciclovir 400 mg five times daily, or valaciclovir 1 g three times daily, or famciclovir 500 mg three times daily, for 14 to 21 days.
  • Severe disease or inability to swallow: aciclovir 5 mg/kg IV every 8 hours (10 mg/kg every 8 hours in severe or neurological disease) until oral intake is possible, then oral therapy to complete 14 to 21 days; hydrate well and adjust for renal function.
  • Aciclovir-resistant virus (thymidine kinase deficiency, mostly in prolonged exposure): foscarnet 40 mg/kg IV every 8 hours (or 60 mg/kg every 8 hours) for 14 to 21 days with hydration and electrolyte monitoring; cidofovir 5 mg/kg weekly with probenecid and hydration as an alternative.
• Analgesia: paracetamol 1 g four times daily; viscous lidocaine 2% 15 mL before meals (maximum 8 doses a day); opioids for severe pain (morphine 2.5 to 5 mg orally every 4 hours as needed); omeprazole 20 to 40 mg daily for mucosal protection.
• Nutrition and fluids: soft or liquid diet, IV fluids, enteral tube feeding or parenteral nutrition if unable to swallow for more than 5 to 7 days.
• Reverse immunosuppression where possible: start antiretroviral therapy in HIV within 2 weeks, reduce corticosteroid dose, adjust chemotherapy timing.
• Suppression of frequent recurrences in immunosuppressed patients (3 or more a year): aciclovir 400 mg twice daily or valaciclovir 500 mg twice daily until immune recovery.
• Complications: bleeding (omeprazole 80 mg IV bolus then 8 mg/hour, endoscopic therapy), stricture (dilatation to 15 to 18 mm after healing), perforation or fistula (nil by mouth, antibiotics such as piperacillin-tazobactam 4.5 g IV every 6 hours, stenting or surgery).
• Special groups: children (aciclovir 10 mg/kg IV every 8 hours or 20 mg/kg orally four times daily for 14 to 21 days in immunocompromised patients; maximum 800 mg per dose); pregnancy (aciclovir 400 mg three times daily orally or 5 to 10 mg/kg IV every 8 hours is acceptable; avoid foscarnet unless needed); elderly (hydrate and adjust for renal function, watch for neurotoxicity); renal impairment (aciclovir 400 mg orally every 8 to 12 hours when creatinine clearance is 10 to 25 mL/min, and IV 5 mg/kg every 12 to 24 hours; valaciclovir 1 g every 12 to 24 hours); transplant recipients (reduce immunosuppression with the transplant team).
• Red flags: inability to swallow saliva, haematemesis, severe chest pain, fever with mediastinal air, no improvement in 5 to 7 days, aciclovir resistance, neurological signs.
• Follow-up: review at 3 to 7 days for response; repeat endoscopy at 2 to 4 weeks for non-response or severe disease; HIV viral load and CD4 count; renal function and hydration during IV therapy; a recurrence plan for immunosuppressed patients.