What is the differential diagnosis and treatment for esophagitis in a patient undergoing chemotherapy?

Esophagitis on Chemotherapy: Differential Diagnosis and Treatment

In patients undergoing chemotherapy who develop esophagitis, the primary differential includes infectious esophagitis (particularly Candida), chemotherapy-induced mucositis, radiation recall esophagitis (if prior radiation), and GERD-related inflammation, with treatment centered on proton pump inhibitors at 40 mg daily, antifungal therapy when candidosis is suspected, and aggressive symptomatic management with topical anesthetics and systemic analgesics. 1, 2

Differential Diagnosis

Infectious Esophagitis

• Candida esophagitis occurs in up to 16% of patients with chemotherapy-induced esophagitis and should be strongly suspected in any patient with grade ≥2 symptoms 3, 1
• Physical examination of the mouth and oropharynx for white patches/thrush is essential, as 61% of patients with esophagitis have oropharyngeal candidiasis 4
• Esophageal candidiasis was cultured in 50% of patients with chemotherapy-induced esophageal lesions in one series 4
• Persistent or worsening esophagitis despite treatment warrants empiric antifungal therapy or endoscopic evaluation 1, 2

Chemotherapy-Induced Mucositis

• Direct mucosal toxicity from chemotherapeutic agents causes superficial ulceration and inflammation 4
• Typically correlates with leukopenia and concurrent oropharyngeal soreness 4
• Evolution and persistence of esophagitis correlates with patient survival—those with persistent monilial esophagitis had 100% mortality within 24 days from systemic candidiasis 4

Radiation Recall Esophagitis

• Occurs with low radiation doses (<2,000 rad) when combined with adriamycin or actinomycin D 5
• Characterized by recurrent episodes of esophagitis with each subsequent chemotherapy course ("recall phenomenon") 5
• Can progress to irreversible stricture formation 5

GERD and Reflux Esophagitis

• Baseline GERD may be exacerbated by chemotherapy-induced nausea, vomiting, and altered motility 3
• Proton pump inhibitor use increases significantly during and after treatment 6

Treatment Algorithm

Initial Pharmacological Management

Step 1: Acid Suppression

• Initiate proton pump inhibitor at 40 mg daily from the start of chemotherapy and continue for 3 months after completion 3, 1
• Lansoprazole 30 mg daily or omeprazole 40 mg daily are appropriate choices 7, 8

Step 2: Evaluate for Candidiasis

• Examine oropharynx for white patches or thrush 1, 2
• If grade ≥2 esophagitis or delayed recovery beyond expected timeframe, initiate empiric antifungal therapy 1, 2
• Consider endoscopy if symptoms persist despite antifungal treatment 4

Step 3: Symptomatic Pain Management

• Topical anesthetics: viscous lidocaine for direct mucosal pain relief 3, 1, 2
• Systemic analgesics following WHO pain ladder, using soluble or liquid formulations 2
• Opioids as needed for severe pain 3

Step 4: Avoid Ineffective Therapies

• Do not use NSAIDs (indomethacin, naproxen)—they show no benefit and may worsen symptoms 3, 1, 2
• Sucralfate has not demonstrated significant benefit in randomized trials 3, 1, 9, 2

Nutritional Support

Immediate Assessment

• All patients should receive nutritional risk assessment and counseling by trained professionals before, during, and after chemotherapy 3
• Target intake: ≥30 kcal and 1.0-1.5 g protein per kg body weight daily 3

Intervention Thresholds

• If oral intake results in >5% body weight loss despite support, initiate enteral or parenteral feeding promptly 3, 1
• Nasogastric tube feeding is preferred over PEG for temporary support 1
• Liquid nutritional supplements if patient can swallow liquids 1

Dietary Modifications

• Avoid irritants: alcohol, bulky foods, spicy foods, very hot or cold foods, citrus products 1, 9
• Small, frequent meals of soft or pureed consistency 1

Expected Clinical Course and Monitoring

Timeline for Chemotherapy-Induced Esophagitis

• Symptoms typically develop during active chemotherapy, especially with concurrent leukopenia 4
• Resolution should occur within 8 weeks after chemotherapy completion in uncomplicated cases 1, 9
• Persistent symptoms beyond 8 weeks warrant evaluation for complications (strictures, persistent candidiasis, systemic fungal infection) 1, 4

Prognostic Indicators

• Persistent monilial esophagitis despite treatment is associated with progression to systemic candidiasis and poor survival 4
• Resolution of esophagitis correlates with improved survival—patients with complete resolution survived average of 1.5 years versus 24 days in those with persistent infection 4

Special Considerations

Concurrent Chemoradiotherapy

• Grade 3-4 esophagitis occurs in 20-30% of patients receiving concurrent chemoradiation versus <5% with chemotherapy alone 3, 2
• Acute radiation esophagitis typically begins during week 3 of treatment, peaks 2 weeks after completion, and resolves by 8 weeks 3, 1, 2
• More intensive supportive care required for combined modality treatment 2

Endoscopic Evaluation

• Endoscopy is more accurate than radiography for detecting chemotherapy-induced esophagitis 4
• Consider endoscopy for: grade ≥2 symptoms, persistent symptoms despite treatment, or concern for stricture formation 1, 4
• Endoscopy reveals superficial ulceration and white mucosal patches in nearly all cases 4

Long-term Sequelae

• Dysphagia persists in 27% and odynophagia in 11% of patients at 10-14 months after combined chemotherapy and mediastinal radiation 6
• Stricture formation may occur as late complication requiring endoscopic dilation 1, 5

Common Pitfalls to Avoid

• Do not dismiss persistent esophageal symptoms as "expected" chemotherapy side effects—they may indicate life-threatening systemic candidiasis 4
• Do not rely on radiographic studies alone—endoscopy detects esophagitis in 100% of cases versus only 33% by radiography 4
• Do not delay antifungal therapy in patients with grade ≥2 esophagitis and oropharyngeal candidiasis—progression to systemic infection is associated with high mortality 4
• Do not use sucralfate or NSAIDs expecting therapeutic benefit—evidence shows no efficacy 3, 1, 2