Eosinophilic and Infectious Esophagitis: Infectious and Direct-Injury Esophagitis

0:00Welcome to Board Pearls. This is episode two of two of the Eosinophilic and Infectious Esophagitis chapter, in the Esophageal Disorders module. This episode is the infections and the direct chemical injuries of the esophagus, and one principle links all of them: the lining got hurt by something that touched it. That something is an organism the patient's defenses couldn't keep down, a tablet that lodged where the esophagus narrows, or a swallowed corrosive. How deep the injury goes reflects how long the agent stayed in contact, where it sits reflects local anatomy, the patient's immune status tells you which organism is likely, and where you biopsy has to match where the organism lives in the wall. Keep those in mind and the differential sorts out.

0:43Start with Candida, the most common esophageal infection and the first thing to think of when a patient with any immune-compromise risk factor has painful swallowing. It's an overgrowth of yeast that already lives on the lining, normally held down by saliva, stomach acid, the esophagus's own propulsion, and cell-mediated immunity, so when any of those defenses drops, the yeast proliferates and invades. The immune status is what points you there. HIV with a CD4 count under two hundred is the classic setting, and esophageal Candida can be the AIDS-defining illness in someone not known to have HIV, which is why an unexpectedly severe case with no obvious explanation earns an HIV test. Transplant recipients, patients on systemic or even inhaled steroids, and poorly controlled diabetics are all at risk, and the classic primary-care version is the asthmatic on an inhaled steroid and a proton pump inhibitor, because the inhaled steroid drops local immunity while the acid blocker removes the acid barrier. Long-term broad-spectrum antibiotics and anything that causes food to stagnate, like achalasia or a stricture, add to it.

1:52The complaint is painful swallowing, sometimes with reduced intake and weight loss. Oral thrush is present in many but not all, and its absence doesn't exclude esophageal disease, especially in inhaled-steroid users who rinse. The scope shows white or yellow-white plaques stuck to the lining, usually in the mid and lower esophagus, and the discriminating feature is that they don't wash off with irrigation, which separates them from food residue. Brushings show the yeast and its filaments, the pseudohyphae that mark invasion. Treatment is fluconazole, two hundred to four hundred milligrams a day for fourteen to twenty-one days, higher than for oral thrush because the invaded lining needs higher tissue levels, given intravenously if the patient can't swallow. An echinocandin is reserved for disease that fails fluconazole, for the critically ill, or for resistant species, and the one to name in the transplant patient who's already failed an azole is Candida glabrata. And the durable prevention in HIV isn't chronic antifungal, which just selects resistance, it's rebuilding the immune system with antiretroviral therapy.

2:54A few other things make a white esophagus and should sit next to Candida in your mind at the scope: keratin plaques from chronic injury and tobacco, sloughing sheets of epithelium associated with certain drugs and conditions, and severe CMV that can look like heavy Candida. The move in any white-esophagus case is to biopsy or brush, so you rule out a viral or pill process before you commit to an empiric antifungal. An empiric fluconazole trial without scoping is reasonable only in a low-risk patient with classic plaques and oral thrush; severe pain, immunocompromise, or atypical findings go straight to endoscopy with biopsy.

3:32Now the viral infections, and the distinction between them is one of the cleanest mechanistic ideas in the whole subject: herpes infects the surface epithelium, while CMV infects the deeper tissue, the endothelial and stromal cells beneath. That one fact drives everything. It drives the ulcer depth, because a surface infection makes shallow ulcers and a deep infection makes deep ones. It drives where you biopsy, because the live infected cells for herpes are at the ulcer edge and for CMV are at the ulcer base. And it drives what the pathologist sees, because the inclusions show up in different cell types. It also sets up the most common trap on this material: biopsying the base of a CMV ulcer instead of the edge is right, but biopsying the base of a herpes ulcer gives you nondiagnostic granulation tissue.

4:21Herpes shows multiple shallow, sharply defined ulcers with raised, rolled edges, the volcano-edge look, scattered through the mid and lower esophagus, each starting as a little blister that ruptures. The infected cells, at the edge, are multinucleated giant cells with the chromatin pushed to the rim and the nuclei molding against each other, carrying the Cowdry inclusions. So you biopsy the heaped-up edge; biopsy the base and you miss it. Herpes has a broad host range: transplant and chemotherapy patients, but also healthy young adults, often with recent oral herpes, where it's self-limited. Treatment in the immunocompromised patient is acyclovir, four hundred milligrams by mouth five times a day for fourteen to twenty-one days, intravenous for severe disease or when they can't swallow, with foscarnet for resistant virus; the healthy patient often needs little more than support through the pain.

5:14CMV shows the opposite: one or a few large, deep ulcers low in the esophagus, often snaking or geographic, deeper and more extensive than herpes. The infected cell is a big endothelial or stromal cell in the granulation tissue at the ulcer base, carrying the owl-eye nuclear inclusion, which is exactly why you biopsy the base. A blood PCR supports systemic CMV but doesn't prove esophageal involvement, and a negative one doesn't exclude it, so the diagnosis lives in the biopsy. The host is deeper immunosuppression: HIV with a CD4 under a hundred, transplant especially in the first several months, and neutropenia. Treatment is intravenous ganciclovir, five milligrams per kilogram every twelve hours for induction, transitioning to oral valganciclovir at nine hundred milligrams daily, with foscarnet when ganciclovir fails or causes too much marrow suppression. And any invasive CMV should get an eye exam, because CMV retinitis often travels with it and threatens sight.

6:13So the way to hold the viral pair: herpes makes shallow volcano-edge ulcers, you biopsy the edge, you see epithelial giant cells with Cowdry inclusions, and you give acyclovir; CMV makes deep geographic ulcers low down, you biopsy the base, you see owl-eye inclusions in the deeper stromal cells, and you give ganciclovir then valganciclovir. A heavily immunosuppressed patient can have both, in which case you treat both, and severe disease with negative biopsies but high suspicion can be treated empirically while the pathology is pending.

6:47Now the direct chemical injuries, tied together by the same idea that organized the infections: contact time sets the depth. A slowly dissolving tablet is the chemical in pill injury and a swallowed corrosive is the chemical in caustic injury, and in both the wound depends on how long it sat and what chemistry it brought.

7:07Pill esophagitis is direct injury where a tablet lodged against the wall and dissolved in place, and the mechanism varies by drug: low pH for doxycycline, tetracycline, vitamin C, and iron; high concentration for extended-release potassium; direct toxicity for NSAIDs, aspirin, bisphosphonates, dabigatran, quinidine, and clindamycin. The classic offenders to recognize are doxycycline and tetracycline, potassium chloride, the bisphosphonates, NSAIDs and aspirin, iron, and dabigatran. The risk factors all come down to contact time: a pill taken with too little water, taken lying down or right before bed, or held up by a motility problem or a stricture, and older adults are overrepresented from polypharmacy and reduced saliva. The story is sudden pain behind the breastbone hours to days after a specific pill, classically taken at bedtime with a small sip of water, and the history is the diagnostic key. On the scope, discrete shallow ulcers with normal lining in between, most often at the level of the aortic arch where the airway indents the esophagus, and paired kissing ulcers on opposite walls are the classic look. Treatment is stopping the drug, a sucralfate slurry to coat it, and a short course of acid suppression if reflux is contributing, with the crucial part being prevention: take pills upright with a full glass of water and stay up for thirty minutes. Recurrent pill injury in the same patient should prompt a look for an underlying motility problem or stricture.

8:42Caustic injury is a swallowed corrosive, and the chemistry sets the depth in a way worth understanding. Strong alkali, the lye in drain and oven cleaners, causes liquefactive necrosis, dissolving membranes and proteins and penetrating rapidly and deeply through the wall toward the mediastinum until tissue fluid buffers it, and it preferentially damages the esophagus because it passes the mouth quickly and pools in the esophageal lumen, with stomach acid partially neutralizing it once it arrives below. Strong acid, in toilet-bowl and pool cleaners, causes coagulative necrosis, denaturing proteins into a surface eschar that limits further penetration, and it moves through the esophagus faster and pools in the stomach, so it biases the injury there. The generalization to keep is alkali damages the esophagus, acid damages the stomach, and that carries most cases even though severe ingestion of either can injure anywhere. Two things sit outside it: household bleach is too dilute to usually cause severe injury, and a swallowed disc battery in a child is a separate emergency, generating alkali at its negative pole within hours and needing urgent endoscopic removal.

9:46The initial management of a caustic ingestion starts with the airway, which is the immediate priority, because throat and glottic swelling can progress fast, so you intubate early for stridor, drooling, voice change, or extensive oropharyngeal burns. The patient is kept nil by mouth with IV fluids and analgesia. Three things are explicitly not done, and the reasoning saves you memorizing: no emetics, because vomiting re-exposes the esophagus and can perforate weakened tissue; no neutralizing agents, because that reaction gives off heat and adds a thermal burn to the chemical one; and no blind nasogastric tube early, because it can trigger retching and perforate injured mucosa, though it can be placed under endoscopic guidance during staging if feeding access is needed. Charcoal doesn't work and antibiotics aren't routine unless there's perforation or aspiration.

10:38You scope within a day or two to grade the injury, using the Zargar scale: grade zero normal, grade one edema and redness, grade two-A superficial ulceration with exudate, grade two-B deep focal or circumferential ulceration, grade three focal or extensive necrosis, and grade four perforation. The grade decides disposition: the low grades go home on a liquid diet with observation, while deep ulceration and necrosis go to the ICU, kept nil by mouth with feeding access placed to bypass the injured esophagus and surgery consulted, and extensive necrosis carries high mortality and may need esophagectomy. And you don't scope the unstable patient, the one with signs of perforation, or one with severe airway necrosis; there you image with CT and consult surgery directly. On drugs, acid suppression helps healing, but systemic steroids aren't routinely useful for stricture prevention and are avoided in the deepest injuries because they impair healing, and antibiotics are reserved for perforation or aspiration.

11:40The long-term consequences are what make this more than an acute event. Strictures develop as the deep injuries heal with fibrosis, over the following weeks, managed with graduated dilation and sometimes stenting. And squamous cell carcinoma develops with a very long latency, decades later, at a dramatically elevated risk, which is why surveillance endoscopy starting roughly fifteen to twenty years after a significant injury is recommended. So the load-bearing point is that a caustic ingestion isn't just an emergency, it's a lifelong premalignant condition that needs counseling and surveillance.

12:15So the whole episode on the principle it began with: the injured lining tells you the agent if you read three things together. The immune status narrows the infection before you scope, Candida in the steroid-and-acid-blocker patient and the HIV patient under a CD4 of two hundred, and the viruses in deeper immunosuppression, CMV especially under a hundred. The ulcer shape tells you the organism: shallow volcano-edge ulcers are herpes, deep low geographic ulcers are CMV, discrete shallow ulcers at the aortic arch with normal lining between them are a pill, and plaques that don't wash off are Candida. The biopsy has to match where the organism lives: the edge for herpes, the base for CMV, the plaque for Candida. And in the chemical injuries, contact time and chemistry set the depth, alkali going deep into the esophagus and acid biasing toward the stomach, with the Zargar grade deciding whether the patient goes home, to a ward, to the ICU, or to the operating room.

13:17The next chapter turns to peptic ulcer disease and Helicobacter pylori, where the question is no longer which agent injured the lining but how to clear an organism that's gotten harder to kill. Bismuth quadruple therapy and acid-blocker-based regimens have replaced the old clarithromycin triple therapy as first-line in most patients, salvage regimens are built around avoiding drugs the patient has already had, and NSAID and H. pylori risks multiply rather than add, so you prevent ulcers by combining acid suppression with eradication when both are present.

13:47For the full chapter, the practice vignettes, and the topic-tagged question bank, head to board pearls dot com. You'll find the rest of the series on Apple Podcasts, Spotify, or wherever you listen to podcasts. That brings us to the end of episode two of two of chapter five, and I'll see you in the next one.