Infectious Oesophagitis

Infection of the oesophageal mucosa by fungi, viruses, bacteria or mycobacteria, almost always in people with impaired local or systemic defences.

• Causes by frequency: Candida (50 to 70% of infectious cases), herpes simplex virus (5 to 15%), cytomegalovirus (10 to 20% in advanced HIV and transplant recipients), and rarely Mycobacterium tuberculosis, atypical mycobacteria, Histoplasma, bacteria, Cryptosporidium, and HIV-related idiopathic ulcer.
• Risk factors: HIV with CD4 count under 200 cells/microlitre (Candida) or under 100 (cytomegalovirus, idiopathic ulcers), inhaled or systemic corticosteroids, diabetes, haematological malignancy and chemotherapy, solid organ and stem cell transplantation, broad-spectrum antibiotics, proton pump inhibitors, achalasia and strictures with stasis, radiotherapy, and malnutrition.
• Burden: oesophageal candidiasis is an AIDS-defining illness; about 10 to 20% of patients with advanced untreated HIV develop it.
• Mechanism: loss of mucosal immunity allows colonisation and mucosal invasion with inflammation, ulceration and pseudomembrane formation.

Odynophagia (the characteristic symptom), dysphagia, retrosternal pain, nausea, fever (viral), weight loss, and reduced intake; haematemesis in cytomegalovirus and herpes ulcers.

• Oral thrush in 50 to 70% of Candida cases (its absence does not exclude it); oral or labial herpetic lesions in some herpes cases; features of HIV or immunosuppression.
• Differential diagnosis: pill oesophagitis, reflux oesophagitis, eosinophilic oesophagitis, caustic or radiation injury, oesophageal cancer, lymphoma, Kaposi sarcoma, coronary disease, achalasia.
• Complications: stricture, perforation and fistula (tracheo-oesophageal), bleeding, dehydration and malnutrition, candidaemia and disseminated infection, and recurrence.

HIV test and CD4 count, full blood count, glucose, creatinine, liver tests, cytomegalovirus PCR in blood for context (a negative result does not exclude disease).

• Empirical treatment is acceptable for suspected Candida in patients with HIV who have oral thrush and odynophagia; endoscopy if there is no response in 3 to 5 days, or in non-HIV patients.
• Upper endoscopy with biopsies and brushings:
  • Candida: white plaques that do not wash off, with underlying friable mucosa; brush cytology (pseudohyphae and yeast), culture with susceptibility testing.
  • Herpes simplex: small vesicles and shallow "punched-out" ulcers in the mid and distal oesophagus; biopsy from the ulcer edge (multinucleated giant cells with ground glass nuclei and intranuclear inclusions), immunohistochemistry or PCR.
  • Cytomegalovirus: large, deep, linear or serpiginous ulcers; biopsy from the ulcer base (enlarged cells with owl's-eye inclusions, immunohistochemistry or PCR).
  • HIV-related idiopathic ulcers: large ulcers with negative stains and cultures.
  • Other: acid-fast smear, Xpert MTB/RIF and mycobacterial culture, silver stains and fungal culture.
• Barium swallow or CT chest for suspected fistula, stricture or perforation.

• Candida (14 to 21 days): fluconazole 400 mg loading then 200 to 400 mg daily orally (or 400 mg IV daily).
• Refractory Candida: voriconazole 200 mg twice daily, posaconazole 300 mg daily after loading, or an echinocandin (caspofungin 70 mg IV then 50 mg daily, micafungin 150 mg daily, or anidulafungin 200 mg then 100 mg daily).
• Resistant Candida: amphotericin B deoxycholate 0.3 to 0.7 mg/kg/day.
• Herpes simplex virus: aciclovir 400 mg orally five times daily (or valaciclovir 1 g three times daily, or famciclovir 500 mg three times daily) for 14 to 21 days in immunocompromised patients and 7 to 14 days in healthy patients.
• Herpes simplex virus, IV treatment: aciclovir 5 mg/kg every 8 hours (10 mg/kg in severe disease) until swallowing improves; foscarnet 40 mg/kg IV every 8 hours for aciclovir resistance.
• Cytomegalovirus: ganciclovir 5 mg/kg IV every 12 hours for 3 to 6 weeks (renal dose adjustment), switching to valganciclovir 900 mg orally twice daily once swallowing is possible, until healing.
• Cytomegalovirus, resistance or neutropenia: foscarnet 90 mg/kg IV every 12 hours for ganciclovir resistance or neutropenia; cidofovir 5 mg/kg weekly for 2 weeks with probenecid and hydration for resistance (nephrotoxic). Give antiretroviral therapy within 2 weeks in HIV.
• HIV-related idiopathic ulcers: antiretroviral therapy and prednisolone 40 mg daily for 4 weeks then taper (after excluding infection), or thalidomide 100 to 200 mg daily at specialist centres (teratogenic).
• Mycobacterial or other infection: disease-specific antimicrobial treatment (for tuberculosis: isoniazid 5 mg/kg, rifampicin 10 mg/kg, pyrazinamide 25 mg/kg and ethambutol 15 mg/kg daily for 2 months, then isoniazid and rifampicin for 4 months).
• Supportive: analgesia with paracetamol 1 g four times daily, viscous lidocaine 2% 15 mL before meals (maximum 8 doses a day). IV fluids, nutritional support (enteral tube or parenteral nutrition for prolonged inability to swallow), omeprazole 20 to 40 mg daily for protection of damaged mucosa.
• Reverse the cause: start or optimise antiretroviral therapy, reduce corticosteroids or immunosuppression, control diabetes, and stop broad-spectrum antibiotics if possible; rinse the mouth after inhaled corticosteroids.
• Secondary prophylaxis for frequent recurrences (3 or more a year): fluconazole 100 to 200 mg daily or 3 times weekly; for cytomegalovirus, valganciclovir 900 mg daily only in selected immunosuppressed patients until immune recovery.
• Stricture: balloon or bougie dilatation to 15 to 18 mm after the infection is controlled.
• Special groups, children: fluconazole 6 mg/kg loading then 3 to 6 mg/kg daily, maximum 400 mg; aciclovir 10 mg/kg IV every 8 hours; ganciclovir 5 mg/kg every 12 hours.
• Special groups, pregnancy: use topical clotrimazole 10 mg troches five times daily or nystatin for mild Candida, amphotericin B for severe disease, and avoid high-dose fluconazole in the first trimester. Aciclovir is acceptable; ganciclovir only for life-threatening disease.
• Special groups, elderly: reduce renal-cleared drugs, screen for diabetes.
• Special groups, renal impairment: adjust fluconazole, aciclovir, ganciclovir, valganciclovir and foscarnet.
• Special groups, transplant recipients: reduce immunosuppression with specialists, and watch for drug interactions with azoles and tacrolimus.
• Red flags: inability to swallow, haematemesis, severe chest pain, fever with mediastinal air, no response in 5 to 7 days, neutropenia, CD4 count under 50 cells/microlitre.
• Follow-up: clinical review at 3 to 5 days (response to empirical therapy) and at 2 to 3 weeks. Repeat endoscopy for non-response or ulcers that persist. HIV viral load and CD4 count every 3 to 6 months; blood count and renal function weekly on ganciclovir or foscarnet.