Candida Oesophagitis

Fungal infection of the oesophagus, mostly by Candida albicans (about 90%), sometimes by C. glabrata, C. krusei, C. tropicalis and C. parapsilosis, forming white plaques on inflamed mucosa.

• It is the commonest cause of infectious oesophagitis and an AIDS-defining illness (found in about 10 to 20% of patients with untreated HIV and CD4 counts under 200 cells/microlitre).
• Other risk factors: inhaled or oral corticosteroids, diabetes mellitus, haematological malignancy, chemotherapy, transplantation, broad-spectrum antibiotics, proton pump inhibitors, achalasia and strictures, radiotherapy, chronic kidney disease, malnutrition, old age; healthy adults can rarely be affected.
• Mechanism: colonisation then invasion of the squamous epithelium by hyphae, with a pseudomembrane of fungus, fibrin and inflammatory cells.

Odynophagia, dysphagia, retrosternal burning pain, nausea; fever is uncommon; weight loss in prolonged disease; some patients have no symptoms.

• Oral thrush in 50 to 70% (white plaques on tongue, palate and cheeks); angular cheilitis; signs of HIV or immunosuppression.
• Differential diagnosis: herpes oesophagitis, cytomegalovirus oesophagitis, pill oesophagitis, reflux oesophagitis, eosinophilic oesophagitis, glycogenic acanthosis, oesophageal cancer, lymphoma.
• Complications: stricture (about 5%), bleeding, perforation (rare), tracheo-oesophageal fistula, dehydration and malnutrition, candidaemia and disseminated candidiasis (especially in neutropenia), and recurrence in about 30 to 50% without immune recovery.

In HIV patients with oral thrush and odynophagia, empirical antifungal treatment is acceptable; investigate if there is no response in 3 to 5 days.

• Upper endoscopy: white or yellow plaques of varying size, from small to confluent, that adhere to the mucosa and leave friable mucosa when removed; grading by plaque size and confluence guides severity, and ulcers or strictures in severe disease.
• Brush cytology and biopsy: yeast and pseudohyphae on periodic acid-Schiff or Gomori stain; culture with species identification and susceptibility testing (especially after fluconazole exposure).
• HIV test and CD4 count, full blood count, glucose and HbA1c, creatinine, liver tests, blood cultures when febrile or neutropenic.
• CT or barium swallow for fistula, stricture or perforation; exclude coexisting herpes or cytomegalovirus by biopsy.

First-line oral therapy for 14 to 21 days: fluconazole 400 mg on day 1 then 200 to 400 mg once daily (3 to 6 mg/kg/day in children, maximum 400 mg); improvement is expected in 3 to 5 days.

• Unable to swallow or severe disease: fluconazole 400 mg IV daily, or an echinocandin: caspofungin 70 mg IV on day 1 then 50 mg daily, micafungin 150 mg IV daily, or anidulafungin 200 mg on day 1 then 100 mg daily, for 14 to 21 days.
• Fluconazole-refractory or non-albicans species (C. glabrata, C. krusei): caspofungin 70 mg IV on day 1 then 50 mg daily, micafungin 150 mg IV daily, or anidulafungin 200 mg on day 1 then 100 mg daily, or voriconazole 6 mg/kg IV twice daily for 2 doses then 4 mg/kg twice daily (200 mg orally twice daily), or posaconazole 300 mg twice daily on day 1 then 300 mg daily, or amphotericin B deoxycholate 0.3 to 0.7 mg/kg/day; check drug interactions and liver tests.
• Mild disease with oral thrush only: nystatin suspension 100,000 units/mL, 4 to 6 mL four times daily swish and swallow, or clotrimazole troche 10 mg five times daily for 7 to 14 days, but systemic therapy is needed for oesophageal disease.
• Analgesia: paracetamol 1 g four times daily; viscous lidocaine 2% 15 mL before meals (maximum 8 doses a day); soft or liquid diet; omeprazole 20 mg daily may be used for mucosal protection (acid suppression itself raises the risk of candidiasis, so stop when healed).
• Remove the cause: start or optimise antiretroviral therapy within 2 weeks in HIV; control diabetes; reduce corticosteroids; rinse the mouth and use a spacer after inhaled corticosteroids; stop unneeded antibiotics and acid suppression.
• Secondary prophylaxis for frequent recurrence (3 or more episodes a year): fluconazole 100 to 200 mg once daily or 200 mg three times weekly until immune recovery (CD4 count above 200 cells/microlitre).
• Stricture: balloon or bougie dilatation to 15 to 18 mm after infection control; perforation or fistula: nil by mouth, IV antifungal and antibiotics, and surgical or stent management.
• Candidaemia or disseminated disease: echinocandin (micafungin 100 mg IV daily or caspofungin 70 mg then 50 mg daily) for at least 14 days after the first negative blood culture, with eye examination and removal of central lines.
• Special groups: children (fluconazole 6 mg/kg on day 1 then 3 to 6 mg/kg daily, maximum 400 mg; caspofungin 70 mg/m2 on day 1 then 50 mg/m2 daily; look for immunodeficiency or HIV); pregnancy (avoid fluconazole at 400 mg or more in the first trimester; use topical clotrimazole or nystatin for mild disease, and liposomal amphotericin B 3 mg/kg/day for severe disease; echinocandins have limited data); elderly (screen for diabetes and swallowing disorders, check interactions); renal impairment (halve the fluconazole dose when creatinine clearance is under 50 mL/min; avoid amphotericin B if possible); hepatic impairment (monitor azole levels and liver tests); transplant recipients (azoles raise tacrolimus, ciclosporin and sirolimus levels, so reduce doses and monitor).
• Red flags: inability to swallow, fever and neutropenia, haematemesis, severe chest pain, no response by 5 to 7 days, CD4 count under 50 cells/microlitre, relapse during prophylaxis.
• Follow-up: review at 3 to 5 days for response and at completion; repeat endoscopy for non-response, to confirm the species and exclude other causes; liver tests during azole therapy; CD4 count and viral load every 3 to 6 months.