Definition/General
Introduction:
Infectious esophagitis represents inflammation of esophageal mucosa caused by various infectious agents
Most commonly affects immunocompromised patients including HIV, transplant recipients, and diabetics
Candida albicans is the most common pathogen (60-70%)
Herpes simplex virus (HSV) and cytomegalovirus (CMV) are other important causes.
Origin:
Results from opportunistic infections in immunocompromised hosts
Normal esophageal mucosa has natural resistance to most pathogens
Impaired immunity allows pathogen colonization and invasion
Candida causes superficial infection
Viral pathogens (HSV, CMV) cause deeper mucosal damage.
Classification:
Fungal esophagitis: Candida (most common), Aspergillus, Histoplasma
Viral esophagitis: HSV-1/2, CMV, EBV, VZV
Bacterial esophagitis: rare, usually secondary
Parasitic esophagitis: very rare
Mixed infections possible in severely immunocompromised patients.
Epidemiology:
Predominantly affects immunocompromised patients
HIV patients with CD4+ <200 cells/μL
Solid organ transplant recipients
Hematologic malignancy patients on chemotherapy
Diabetic patients
Corticosteroid therapy patients
Increasing incidence with rise in immunocompromised population.
Clinical Features
Presentation:
Odynophagia (painful swallowing) most common symptom
Dysphagia (difficulty swallowing)
Retrosternal chest pain
Heartburn and acid reflux
Nausea and vomiting
Weight loss and decreased oral intake
Fever (especially viral causes)
Oral thrush often present with Candida.
Symptoms:
Severe odynophagia interfering with eating
Progressive dysphagia
Substernal burning pain
Constitutional symptoms (fever, malaise)
Oral candidiasis (white plaques)
Hoarseness (laryngeal involvement)
Aspiration symptoms (cough, pneumonia)
Dehydration from poor oral intake.
Risk Factors:
HIV infection (CD4+ <200)
Organ transplantation
Hematologic malignancies
Chemotherapy and radiation therapy
Prolonged corticosteroid use
Diabetes mellitus
Broad-spectrum antibiotics
Advanced age
Malnutrition.
Screening:
Upper endoscopy for diagnosis and pathogen identification
Biopsy and brushings for histology and culture
KOH preparation for fungal elements
Viral culture and PCR testing
Immunohistochemistry for viral antigens
Serology may be helpful in some cases.
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Gross Description
Appearance:
Candida esophagitis: white-yellow plaques and pseudomembranes
HSV esophagitis: small, shallow ulcers with raised borders
CMV esophagitis: large, deep, linear ulcerations
Diffuse erythema and friability
Mucosal edema and inflammation
Stricture formation in chronic cases.
Characteristics:
Candida: removable white plaques, "cottage cheese" appearance
HSV: vesicles progressing to shallow ulcers
CMV: large geographic ulcers with clean base
Friable mucosa with easy bleeding
Loss of normal mucosal folds
Narrowing of esophageal lumen in severe cases.
Size Location:
Candida: usually involves mid and distal esophagus
HSV: can affect any level of esophagus
CMV: typically distal esophagus
Patchy distribution common
Circumferential involvement in severe cases
Skip lesions may be present.
Multifocality:
Multifocal involvement typical
Patchy distribution along esophageal length
Coalescent lesions in severe cases
Proximal extension into hypopharynx possible
Associated gastric involvement in some cases
Concurrent oral involvement common with Candida.
Microscopic Description
Histological Features:
Candida: pseudohyphae and spores in superficial layers, acute inflammation
HSV: viral cytopathic effects, multinucleated giant cells, Cowdry A inclusions
CMV: enlarged cells with nuclear and cytoplasmic inclusions ("owl's eye")
Acute inflammation with neutrophils
Mucosal ulceration and necrosis.
Cellular Characteristics:
HSV: multinucleated giant cells with molding, margination of chromatin, Cowdry A inclusions
CMV: enlarged cells (cytomegaly) with large basophilic intranuclear inclusion, perinuclear halo
Candida: yeasts and pseudohyphae, often superficial
Inflammatory infiltrate predominantly neutrophilic.
Architectural Patterns:
Surface ulceration with fibrinopurulent exudate
Acute inflammation in lamina propria
Submucosal edema and vascular congestion
Reactive epithelial changes
Granulation tissue in healing phase
Fibrosis in chronic cases.
Grading Criteria:
Mild: superficial inflammation, minimal ulceration
Moderate: deeper inflammation, confluent ulcerations
Severe: transmural inflammation, extensive ulceration, potential perforation
Grading based on depth of involvement and extent of inflammation.
Immunohistochemistry
Positive Markers:
HSV: HSV-1/2 immunostain positive in infected cells
CMV: CMV immunostain positive in infected cells
Candida: GMS or PAS stain positive for fungal forms
CD68 highlights macrophages
CD3/CD20 for lymphocytes
Cytokeratin highlights reactive epithelium.
Negative Markers:
Viral markers negative in non-infected cells
Bacterial immunostains typically negative
Malignancy markers negative (rule out carcinoma)
Other viral markers negative (EBV, VZV unless coinfection)
Fungal stains negative for bacterial infections.
Diagnostic Utility:
Viral immunostains confirm specific viral etiology
HSV stain differentiates from CMV
CMV stain confirms cytomegalovirus
Fungal stains essential for Candida identification
Multiple stains may be needed for mixed infections
PCR testing more sensitive than immunostains.
Molecular Subtypes:
HSV-1 vs HSV-2 can be differentiated by typing
CMV strains may show drug resistance patterns
Candida species identification by culture and molecular methods
Antifungal resistance testing for refractory cases
Viral load quantification helpful for monitoring.
Molecular/Genetic
Genetic Mutations:
Host genetic factors affecting immune response
HLA associations with susceptibility
Cytokine gene polymorphisms
Pathogen mutations conferring drug resistance
HSV thymidine kinase mutations (acyclovir resistance)
CMV UL97 mutations (ganciclovir resistance).
Molecular Markers:
Viral DNA/RNA detection by PCR
Quantitative viral load testing
Antiviral resistance mutation analysis
Host immune markers (CD4+ count, immunoglobulin levels)
Inflammatory cytokines (IL-1β, TNF-α, IFN-γ).
Prognostic Significance:
Immune status most important prognostic factor
CD4+ count <50 indicates poor prognosis in HIV
Multidrug-resistant organisms indicate worse outcomes
Mixed infections more difficult to treat
Underlying malignancy affects response to treatment.
Therapeutic Targets:
Antifungal therapy: fluconazole, itraconazole, amphotericin B for Candida
Antiviral therapy: acyclovir, valacyclovir for HSV
ganciclovir, valganciclovir for CMV
Immune reconstitution in HIV patients
Prophylaxis in high-risk immunocompromised patients.
Differential Diagnosis
Similar Entities:
Reflux esophagitis
Pill esophagitis
Caustic injury
Eosinophilic esophagitis
Crohn disease of esophagus
Behçet disease
Aphthous ulcers
Malignancy (carcinoma, lymphoma).
Distinguishing Features:
Infectious: pathogen identification on stains/culture
Infectious: immunocompromised host
Reflux: distal location, basal cell hyperplasia
Pill: medication history, focal location
EoE: eosinophils >15/HPF
Crohn: granulomas, skip lesions
Malignancy: dysplasia or invasion.
Diagnostic Challenges:
Identifying specific pathogen requires appropriate stains
Mixed infections in severely immunocompromised
Negative cultures don't exclude infection
Reactive atypia mimicking dysplasia
Sampling issues in superficial infections.
Rare Variants:
Aspergillus esophagitis in neutropenic patients
Histoplasma esophagitis in endemic areas
EBV esophagitis in transplant patients
Varicella-zoster esophagitis
Bacterial esophagitis (Lactobacillus, Actinomyces)
Parasitic infections (very rare).
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
Esophageal biopsies with endoscopic findings of [ulceration/plaques/erythema]
Clinical History
Patient with [immunocompromised status] presenting with odynophagia and dysphagia
Microscopic Findings
Shows [acute/chronic] inflammation with [ulceration/surface changes]
Pathogen Identification
[Candida forms/Viral cytopathic effects/Other findings] identified
Special Stains
GMS/PAS: [positive/negative] for fungal forms
Immunostains: HSV [+/-], CMV [+/-] if performed
Diagnosis
[Candida/HSV/CMV/Other] esophagitis
Severity
[Mild/Moderate/Severe] based on extent of inflammation and ulceration
Recommendations
Appropriate [antifungal/antiviral] therapy. Clinical correlation and culture results recommended
Final Diagnosis
Infectious esophagitis, [specific pathogen], [severity grade]