Esophageal Symptoms and Diagnostic Workup

Section 1.1: Algorithm for dysphagia

Two questions from the history choose the first test for dysphagia. The first is where the bolus stops: oropharyngeal dysphagia is a problem of bolus initiation and transfer from mouth to upper esophagus, while esophageal dysphagia is a problem of bolus transit through the tubular esophagus to the stomach. The second is which foods cause trouble: mechanical narrowing produces a progressive solids-then-liquids pattern, while motility disorders affect solids and liquids equally from the start. Oropharyngeal dysphagia goes to videofluoroscopy with a speech therapist before EGD because EGD does not visualize the swallowing maneuver and a Zenker pouch can be perforated by blind intubation. Esophageal dysphagia goes to EGD with biopsies first, because EGD addresses both the structural differential and EoE simultaneously.

Oropharyngeal dysphagia is a failure of the initiation phase of swallowing, in which the tongue, soft palate, and pharyngeal constrictors must coordinate with relaxation of the upper esophageal sphincter to drive a bolus across the cricopharyngeus. Most cases are neuromuscular: stroke, Parkinson disease, ALS, myasthenia gravis, and head and neck radiation each disrupt one or more elements of that coordinated sequence. Zenker diverticulum is the structural exception in this category because it forms at the same anatomic transition. Patients describe coughing on swallow, nasal regurgitation when palatal closure fails, drooling when oral containment is impaired, and frank aspiration when the bolus reaches an unprotected airway. The diagnostic test of choice is the modified barium swallow, also called videofluoroscopic swallow study, performed with a speech-language pathologist who watches the bolus in real time across multiple consistencies and head positions. EGD has no role in primary oropharyngeal dysphagia evaluation because it does not visualize the swallowing event and provides no information about aspiration risk or compensatory maneuvers. A cricopharyngeal bar on barium reflects failure of the upper esophageal sphincter to relax and is treated with cricopharyngeal myotomy or, in selected patients, botulinum toxin to the cricopharyngeus.

Zenker diverticulum is the main reason barium swallow precedes EGD in oropharyngeal dysphagia. It is a false diverticulum (mucosa and submucosa only, no muscular layer) that herniates posteriorly through Killian triangle, the area of relative weakness between the oblique fibers of the inferior pharyngeal constrictor above and the transverse fibers of the cricopharyngeus below. The mechanism is functional outflow obstruction at the upper esophageal sphincter (incomplete cricopharyngeal relaxation, often called cricopharyngeal dysfunction) that drives intraluminal pressure into the wall during repeated swallowing over years. Most patients are in the seventh or eighth decade and roughly 90 percent present with dysphagia. The presentation that gives the diagnosis away is regurgitation of undigested food eaten hours or days earlier, halitosis from the trapped material, gurgling sounds during or after swallowing, chronic cough, and aspiration pneumonia from spillage of pouch contents into the airway. Diagnosis is made by barium swallow, which fills the pouch and shows a posterior outpouching at the cervical esophagus. EGD is avoided as the initial test because the scope tip can enter the pouch rather than the true lumen and perforate the diverticulum. Treatment is cricopharyngeal myotomy combined with diverticulotomy, performed open, by transoral stapled approach (which divides the wall between pouch and esophagus in a single firing), or by flexible endoscopic Z-POEM where the cricopharyngeus is divided through a submucosal tunnel.

Esophageal dysphagia begins with the symptom history, because the pattern usually tells you whether to expect a structural lesion or a motility disorder before any test is ordered. Mechanical narrowing produces dysphagia first to solids and only later to liquids as the lumen narrows further; the differential includes Schatzki ring, esophageal web, peptic stricture, eosinophilic esophagitis, and esophageal malignancy. Motility disorders produce dysphagia to solids and liquids together from the outset, because the propagated wave fails on every bolus regardless of consistency; the differential here is achalasia, distal esophageal spasm, jackhammer esophagus, and scleroderma esophagus.

EGD with esophageal biopsies is the first test in nearly every patient with esophageal dysphagia, because it covers the structural differential, identifies subtle eosinophilic esophagitis in mucosa that can look entirely normal at endoscopy, and rules out malignancy. Esophageal biopsies for EoE are obtained at two levels (proximal and distal, two to four samples each) even when the mucosa appears unremarkable, because EoE is a histologic diagnosis and the esophagus appears endoscopically normal in up to a third of cases (roughly 10 to 32 percent) (see Ch 5 for the EoE deep dive). Barium swallow is added when EGD is non-diagnostic or when motility is suspected, because the timed barium esophagram visualizes a tertiary contraction pattern, a bird-beak narrowing, or a corkscrew morphology that points to the manometric study that follows.

New dysphagia is itself an alarm symptom, and EGD with biopsies is the workup for esophageal dysphagia regardless of what other features the patient carries. The features people memorize as alarm features (age over 50, unintentional weight loss, iron deficiency anemia, overt or occult GI bleeding, progressive solid food dysphagia, persistent vomiting) do not trigger EGD because EGD is already happening. They raise the pretest probability of malignancy specifically, which changes urgency and changes what the endoscopist is looking for. Progressive solid food dysphagia in a 65-year-old smoker with weight loss is esophageal cancer until proven otherwise, and the workup goes from a routine EGD with biopsies to an EGD plus immediate staging if a mass is found.

What the boards test

Oropharyngeal dysphagia (coughing, nasal regurgitation, aspiration at swallow onset) goes to modified barium swallow with a speech pathologist, not EGD. Esophageal dysphagia goes to EGD with two-level biopsies even when the mucosa looks normal, because EoE is a histologic diagnosis. Solids-then-liquids means narrowing; solids and liquids from the start means motility. Alarm features do not change the test, only the cancer probability. When Zenker diverticulum is suspected, order barium before EGD, because blind intubation can perforate the pouch.

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Section 1.2: Globus, rumination, and functional esophageal pain

Globus, rumination, and functional chest pain are diagnosed after the structural and reflux workups come back normal. They arise from disordered gut-brain signaling (visceral hypersensitivity, learned somatic responses, or a behavioral re-swallow pattern), and all three are often mistaken for refractory GERD and treated with escalating PPI doses. When a patient who seems to have GERD does not respond to a PPI, consider these diagnoses; the treatment is a neuromodulator, a behavioral intervention, or, for rumination, diaphragmatic breathing, not more acid suppression.

Globus pharyngeus is the persistent or intermittent sensation of a lump, fullness, or tightness in the throat between meals, classically improved or unchanged by swallowing rather than worsened. The mechanism is multifactorial and includes hypertonic upper esophageal sphincter behavior, post-nasal drip, and reflux-related laryngeal sensitization in a subset, but in most patients no single physiologic abnormality is identified and the dominant driver is a heightened perception of normal pharyngeal sensation. The workup is targeted: rule out reflux and post-nasal drip with history and a focused exam, and look for a structural lesion only when alarm features (true dysphagia, weight loss, hoarseness, neck mass, smoking history) are present. Reassurance is the dominant management once the alarm screen is negative, because the natural history is benign and intervention beyond reassurance rarely improves outcome. PPI is not a default answer for globus.

Rumination syndrome is the effortless regurgitation of recently swallowed food into the mouth followed by re-swallowing or spitting, occurring without preceding nausea or retching, typically within ten to fifteen minutes of meal initiation. The mechanism is a learned, unintentional contraction of the abdominal wall and diaphragm that raises intra-abdominal pressure against a relaxed lower esophageal sphincter, producing retrograde flow of undigested gastric contents into the esophagus and pharynx. The Rome IV criteria require effortless regurgitation of recently swallowed food with re-swallowing or spitting, not preceded by retching, occurring on most days for at least three months with onset at least six months earlier. The diagnostic finding on high-resolution manometry with concurrent impedance is the abdominal-strain "R-wave" pressurization: a simultaneous rise in intra-gastric pressure and intra-esophageal pressure during the postprandial period without evidence of antecedent retching, often with the lower esophageal sphincter pressure dropping at the same instant.

The typical patient is young and has failed high-dose twice-daily PPI; the "regurgitation" occurs immediately after every meal, the material is recognizable as the food just eaten, and weight is often gained rather than lost. Treatment is diaphragmatic breathing taught by behavioral therapy (slow deep abdominal inspiration during the postprandial window, which is incompatible with the abdominal wall contraction that drives the rumination event) with cognitive behavioral therapy for refractory cases. Acid suppression has no role.

Functional chest pain is noncardiac chest pain after cardiac, GERD, EoE, and primary motility disorders have been excluded by appropriate testing. The mechanism is visceral hypersensitivity at the level of the esophageal afferent neurons and central pain processing pathways, in which non-painful esophageal events (low-volume reflux, normal contractions, mild distension) are perceived as pain because the gain on the pathway is set too high. Treatment is the neuromodulator: a low-dose tricyclic such as imipramine 25 to 50 mg or amitriptyline 25 to 50 mg at bedtime, an SSRI when TCAs are not tolerated, hypnotherapy, or cognitive behavioral therapy. The neuromodulator is the first-line drug class, not a higher PPI dose, because the lesion is in the pain processing pathway rather than the acid burden.

Functional heartburn and reflux hypersensitivity are the corresponding gut-brain disorders that present as heartburn and are detailed in the GERD chapter. Functional heartburn is heartburn with normal acid exposure time and negative symptom-reflux association, treated with a neuromodulator. Reflux hypersensitivity is heartburn with normal acid exposure time but positive symptom-reflux association, treated with combined neuromodulator and acid suppression because the patient genuinely associates symptoms with physiologic reflux events but the volume of acid exposure is below the threshold that defines GERD (see Ch 3 for the Lyon Consensus and pH-impedance interpretation).

What the boards test

When a patient who seems to have GERD fails a PPI, reconsider the diagnosis instead of raising the dose. Globus: lump between meals, unchanged or better with swallowing, managed with reassurance after an alarm screen. Rumination: effortless regurgitation of recognizable food within minutes of eating, R-wave on manometry-impedance, treated with diaphragmatic breathing. Functional chest pain: visceral hypersensitivity after cardiac, GERD, EoE, and motility causes are excluded, treated with a low-dose tricyclic.

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Section 1.3: Odynophagia workup

Odynophagia is mucosal injury until proven otherwise, and three history questions narrow the cause before any test: was a pill swallowed with too little water or while lying down, is the patient immunocompromised (HIV CD4 count, transplant status, chemotherapy, chronic inhaled or systemic steroids), and is there prior reflux or caustic injury (deep dive in the EoE and GI emergencies chapters, see Ch 5 for EoE and Ch 31 for caustic ingestion). The answers narrow the differential to one or two diagnoses before EGD, and the EGD is then directed toward biopsy of the appropriate site. Caustic injury is mentioned here only by name; the staging system, the airway management, and the long-term stricture surveillance are covered in the GI emergencies chapter.

Pill esophagitis is a direct mucosal injury where a tablet lodges and dissolves, most often at the aortic arch where the left mainstem bronchus indents the esophagus. The offenders are drugs that are acidic, hyperosmolar, or directly cytotoxic when dissolved: doxycycline and tetracycline, potassium chloride, bisphosphonates, NSAIDs, iron, and dabigatran among others. The history gives it away: sudden odynophagia hours to days after a specific pill taken with little water or at bedtime. When endoscopy is done it shows discrete shallow ulcers, often paired kissing ulcers, with normal intervening mucosa. Management is stopping the drug, sucralfate, and teaching upright dosing with a full glass of water (detailed in Ch 5, Section 5.6).

In infectious esophagitis, the patient's immune status narrows the differential before EGD. Candida is the most common and appears with inhaled or systemic steroids, PPI use, HIV with CD4 under 200, transplantation, antibiotics, and esophageal stasis; the endoscopy shows adherent white plaques and brushings show pseudohyphae, and fluconazole is first-line. HSV esophagitis produces shallow, volcano-edged ulcers, and the inclusions sit in squamous epithelial cells, so the biopsy targets the ulcer edge; treatment is acyclovir. CMV esophagitis produces large, deep, often solitary ulcers, and the owl-eye inclusions sit in stromal and endothelial cells, so the biopsy targets the ulcer base; treatment is IV ganciclovir followed by valganciclovir. The full recognition and treatment details for all three infections are in Ch 5.

A PPI user with concurrent inhaled corticosteroids and a fluconazole-responsive course points to Candida. A transplant recipient or a patient with HIV CD4 under 100 with deep solitary ulcers in the distal esophagus points to CMV. A volcano-edge shallow ulcer with multinucleated giant cells in epithelial cells at the edge points to HSV. The decision to skip empiric fluconazole and proceed directly to EGD is driven by severity of odynophagia, immunocompromised status, no response to a fluconazole trial, or clinical features suggesting a viral or pill etiology rather than Candida.

What the boards test

Take the exposure history before the scope: pill, immune status, prior reflux or caustic injury. Pill esophagitis is sudden odynophagia after a specific pill, with kissing ulcers at the aortic arch. Candida gives white plaques and is treated with fluconazole; skip the empiric trial and scope when odynophagia is severe, the host is immunocompromised, or fluconazole fails. HSV is sampled at the ulcer edge (epithelial inclusions) and CMV at the ulcer base (stromal and endothelial inclusions), because the inclusions live in different cells.

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Section 1.4: Post-surgical and systemic dysphagia

The causes in this section are missed by the standard EGD-then-manometry workup unless the history is taken: prior fundoplication or bariatric surgery, an autoimmune disease, chest or neck radiation, or neurologic findings. Each antireflux and bariatric operation has its own typical complications. Scleroderma esophagus, Sjogren, amyloid, and chemoradiation each compromise either peristalsis, salivary flow, muscular integrity, or mucosal architecture in ways that change how the swallow proceeds. The neuromuscular disorders (myasthenia gravis, ALS, polymyositis and dermatomyositis) attack the oropharyngeal phase and are recognized by the associated systemic findings and electromyography rather than the swallow study alone.

The Nissen fundoplication wraps 360 degrees of gastric fundus around the distal esophagus to create an antireflux barrier; partial fundoplications (Toupet at 270 degrees posterior, Dor at 180 degrees anterior) trade some reflux control for less postoperative dysphagia and less gas-bloat.

The slipped wrap occurs when the wrap migrates onto the proximal stomach rather than encircling the distal esophagus, producing the paradoxical combination of recurrent reflux (because the wrap no longer reinforces the lower esophageal sphincter) plus dysphagia (because the wrap now creates a relative obstruction at the gastric body). The tight wrap presents with early postoperative dysphagia, often immediately after surgery, because the wrap is too snug around the esophagus and the bolus cannot pass; treatment is pneumatic dilation in the early postoperative period or surgical revision if dilation fails. The gas-bloat syndrome is the inability to belch, leading to abdominal distension and sometimes bloating-related discomfort, because the wrap acts as a one-way valve that prevents transient lower esophageal sphincter relaxations from venting swallowed air. Telescoping occurs when the gastroesophageal junction slips upward through an intact wrap, distorting the anatomy in a way that reproduces both reflux and dysphagia.

Approximately 10 to 30 percent of patients resume antireflux medication within 5 years of fundoplication. Workup begins with barium swallow rather than EGD because barium shows the wrap geometry and the relationship of the gastroesophageal junction to the wrap; EGD follows for direct mucosal assessment. PPI is reintroduced for slipped wraps with reflux, dilation for the tight wrap, and surgical revision is reserved for refractory cases.

The cause of post-bariatric dysphagia depends on the operation. Sleeve gastrectomy creates a tubular stomach by stapling along the greater curvature, and the anatomic vulnerability is at the incisura angularis, where a kink, twist, or stricture at the staple line produces a fixed obstruction with progressive dysphagia and food intolerance. Sleeve gastrectomy also causes or exacerbates reflux rather than relieving it, because reduced gastric volume, loss of the angle of His, disrupted sling fibers at the gastroesophageal junction, and a higher intragastric pressure environment combine to drive reflux upward; this is why sleeve gastrectomy is generally avoided in morbidly obese patients with established GERD, and Roux-en-Y gastric bypass is the antireflux bariatric operation of choice in that population. Roux-en-Y gastric bypass produces dysphagia most often through anastomotic stricture at the gastrojejunal anastomosis, presenting weeks to months after surgery with progressive solid food intolerance; through-the-scope balloon dilation is the treatment, often requiring multiple sessions. Marginal ulcer at the gastrojejunal anastomosis presents with epigastric pain, dysphagia, and GI bleeding, and the predictable risk factors are smoking (the strongest modifiable factor), NSAID use, and Helicobacter pylori infection. Treatment is high-dose PPI plus reversal of the modifiable factors (tobacco cessation, NSAID discontinuation, H. pylori eradication if positive), with surgical revision reserved for refractory or perforating ulcers.

Scleroderma esophagus is the classic disorder of failed peristalsis with a hypotensive lower esophageal sphincter. Fibrosis of the smooth muscle segment abolishes the peristaltic wave while the same process drops LES pressure, so reflux pours back and is not cleared, producing erosive esophagitis, peptic stricture, and Barrett esophagus. Dysphagia in scleroderma therefore comes from two sources, weak transit and peptic stricture, and the management is aggressive acid suppression and dilation rather than fundoplication. The manometric criteria, serology, and management are covered in full in Ch 2, Section 2.4.

Sjogren syndrome produces dysphagia by removing the salivary contribution to swallowing rather than by damaging the esophagus directly. The mechanism is autoimmune lymphocytic infiltration of salivary and lacrimal glands, which produces xerostomia and reduces the lubrication and bolus formation that swallowing depends on. Patients describe difficulty initiating swallow with dry foods such as bread or crackers, often improved by water sips and worse at the end of the day. Treatment is salivary stimulation with pilocarpine 5 mg four times daily or cevimeline 30 mg three times daily (muscarinic agonists that increase salivary flow), saliva substitutes, careful oral hygiene to prevent the dental decay that follows xerostomia, and humidification of dry environments. The reduced salivary clearance is also a refractory-reflux clue when Sjogren and GERD coexist, because saliva normally contributes to esophageal acid clearance.

Amyloid causes dysphagia through infiltrative deposition of insoluble fibrils in the esophageal muscularis and submucosa. The two principal forms in adults are AL (light chain) amyloid in the setting of plasma cell dyscrasia, and ATTR (transthyretin) amyloid in either the hereditary or wild-type form. The hint at the bedside is macroglossia, which suggests AL amyloid in particular and warrants serum and urine immunofixation, free light chains, and a skeletal survey or marrow biopsy in the appropriate clinical setting. Dysphagia from amyloid reflects infiltration of the muscularis with replacement of contractile elements, and the manometric pattern is variable. Treatment is directed at the underlying amyloidogenic process (chemotherapy or autologous stem cell transplant for AL amyloid; tafamidis, patisiran, or inotersen for ATTR amyloid) rather than at the esophagus itself.

Chemoradiation injures the esophagus in an acute phase and a late phase. Acute radiation mucositis develops during or shortly after thoracic or head and neck radiation and presents with severe odynophagia, dysphagia, and dehydration; supportive care, topical anesthetics, opioid analgesia for severe cases, and nutritional support are the management. Late radiation stricture develops months to years after radiation and presents with progressive solid food dysphagia from fibrotic narrowing in the radiation field. Proactive swallow therapy during and after radiation reduces the rate of stricture and improves long-term swallowing function. Endoscopic dilation, often serial, is the treatment for established stricture; complete obstruction may require combined antegrade and retrograde rendezvous techniques.

The neuromuscular dysphagias attack the oropharyngeal phase and are recognized by the associated systemic findings rather than the swallow alone. Myasthenia gravis is autoimmune blockade of the postsynaptic acetylcholine receptor at the neuromuscular junction, and the clinical signature is fatigability that worsens with repeated effort and improves with rest, often with ptosis and diplopia. Anti-acetylcholine receptor antibodies are positive in the majority of generalized cases, with anti-MuSK antibodies covering a subset of seronegative patients. Treatment is pyridostigmine for symptomatic relief (an acetylcholinesterase inhibitor that prolongs acetylcholine action at the synapse), with immunosuppression and thymectomy for selected patients.

ALS produces oropharyngeal dysphagia through degeneration of bulbar motor neurons, with fasciculations, tongue atrophy, and progressive limb weakness as the supporting findings; electromyography shows the denervation pattern and confirms the diagnosis. Polymyositis and dermatomyositis are inflammatory myopathies presenting with symmetric proximal muscle weakness (difficulty rising from a chair or lifting the arms overhead), elevated creatine kinase, anti-Jo-1 antibodies in a subset, and oropharyngeal dysphagia in roughly half of patients with bulbar involvement. Dermatomyositis adds the cutaneous findings (heliotrope rash on the eyelids, Gottron papules over the knuckles, shawl sign on the upper chest and back) and carries an associated malignancy risk that warrants age-appropriate cancer screening, with gastric, lung, ovarian, breast, and lymphoma topping the list.

What the boards test

Ask about prior surgery, autoimmune disease, radiation, and neurologic symptoms. After fundoplication, barium comes first: tight wrap gives early dysphagia (dilate), slipped wrap gives reflux plus dysphagia, gas-bloat is the inability to belch. After sleeve gastrectomy, look for a stricture or kink at the incisura and expect worse reflux; after Roux-en-Y, look for anastomotic stricture or marginal ulcer (smoking, NSAIDs, H. pylori). Scleroderma is absent peristalsis plus a hypotensive LES, treated with twice-daily PPI and not fundoplication. Oropharyngeal dysphagia with systemic signs points to myasthenia, ALS, or inflammatory myopathy, with cancer screening in dermatomyositis.

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