How is esophageal thrush diagnosed?

Diagnosis of Esophageal Thrush (Candida Esophagitis)

Upper endoscopy with esophageal biopsies and brushings is the gold standard for diagnosing esophageal candidiasis, requiring histopathologic demonstration of characteristic yeast forms and pseudohyphae invading mucosal cells. 1

Clinical Assessment Prior to Endoscopy

Evaluate key risk factors and presenting symptoms:

• Immunosuppression status including HIV/AIDS, hematologic malignancies, solid organ transplantation, or prolonged granulocytopenia must be assessed 1
• Recent antibiotic exposure and corticosteroid use (both systemic and aerosolized) are significant predisposing factors 1
• Other risk conditions including diabetes mellitus, chronic kidney disease, chronic alcohol use, proton pump inhibitor use, malignancy, and esophageal motility disorders should be evaluated 1
• Characteristic symptoms include dysphagia, odynophagia (pain on swallowing), retrosternal burning pain, or altered taste 1, 2
• Oral thrush presence should be documented, though its absence does not exclude esophageal candidiasis—only 71% of patients with esophageal candidiasis have concurrent oral thrush 3

Definitive Diagnostic Procedures

Endoscopy with tissue sampling is mandatory:

• Esophagogastroduodenoscopy with biopsy should be performed in all patients with signs and symptoms of esophagitis, particularly if not responding to preemptive antifungal therapy 1
• Characteristic endoscopic findings include whitish nummular lesions, white mucosal plaque-like lesions, and exudates adherent to the mucosa that cannot be washed off with water irrigation 1, 2
• Both cytobrush specimens and esophageal biopsies should be obtained to identify fungal forms 1
• Histopathologic confirmation requires demonstration of characteristic Candida yeast forms and pseudohyphae invading mucosal cells using special fungal stains such as periodic acid-Schiff (PAS), Grocott's methenamine silver, or calcofluor white staining 1, 2

Critical Diagnostic Pitfall

Endoscopic appearance alone cannot accurately predict the diagnosis—specimen acquisition for laboratory study is mandatory, as visual findings can overlap with other conditions 4. Multiple biopsies from at least 2 levels should be obtained, as inflammatory conditions can be patchily distributed 4.

Alternative Diagnostic Approach in Resource-Limited Settings

Blind brushing of the esophagus via nasogastric tube (obtained between 20-35 cm from the incisors) has 96% sensitivity and 87% specificity for diagnosing Candida esophagitis in HIV-infected patients, offering a rapid and economical alternative when endoscopy is not immediately available 3. However, this approach is primarily validated in AIDS patients and should not replace endoscopy when available.

Essential Differential Diagnoses to Exclude

Additional biopsies must exclude other causes of white esophageal plaques:

• HSV esophagitis presents with shallow ulcers; separate biopsies should be sent for viral culture 1
• CMV esophagitis presents with deep ulcerations; immunohistochemistry should be performed 1
• Eosinophilic esophagitis requires ≥15 eosinophils per high-power field on biopsy from multiple levels (proximal and distal esophagus), with patients off PPI therapy for 2-4 weeks 4, 1
• Medication-induced ulceration typically shows 1-2 well-demarcated ulcers; medication history should be evaluated 1

When to Repeat Endoscopy

Repeat endoscopy is indicated in patients who fail to improve after appropriate antifungal therapy to evaluate for refractory infection, alternative or additional underlying causes of esophageal dysfunction, and development of azole resistance 1.