AssessmentsEsophageal disorders: Pathology review
USMLE® Step 1 style questions USMLE
A 65-year-old woman comes to the clinic due to difficulty swallowing and retrosternal pain. For the past 2 days, she has had pain with swallowing which has progressively worsened to the point of avoiding all food and drinks. She has not had similar symptoms in the past. Medical history is significant for coronary artery disease, hyperlipidemia, seasonal allergies, and osteoarthritis. The patient has smoked 1 pack of cigarettes per day for 30 years. Medications include aspirin, metoprolol, loratadine, lovastatin, and piroxicam as needed. Temperature is 37.0°C (98.6°F), pulse is 80/min, and blood pressure is 125/85 mmHg. The oral mucosa is clear without erythema or exudate. Cardiac auscultation reveals no murmurs, and ECG shows normal sinus rhythm without ischemic changes. The rest of the physical examination is normal. Endoscopy is obtained and shows multiple round ulcers in the proximal esophagus with relatively normal surrounding tissue. Which of the following is the most likely diagnosis?
Content Reviewers:Yifan Xiao, MD
Contributors:Elizabeth Nixon-Shapiro, MSMI, CMI, Tanner Marshall, MS, Sam Gillespie, BSc, Filip Vasiljević, MD
A 33-year-old named Ravi came to the clinic because he has difficulty swallowing food and water over the last 3 months. Physical examination shows significant weight loss, of 7-kg or 15-lb, since his last visit 4 months ago. Esophageal manometry shows incomplete lower esophageal sphincter relaxation in response to swallowing, while barium swallow reveals a dilated esophagus with an area of distal stenosis. At the same time, a 62-year-old man named Frank comes to the clinic because of bad breath, regurgitation of food overnight, and trouble swallowing food. He has had these symptoms for several months. He denies fever, chills, nausea, vomiting, or weight loss. Physical examination shows a mass on the side of the neck. v
Now, both Ravi and Frank have some form of the esophageal disorder. Esophageal disorders can be subdivided into: inflammatory esophageal disorders, or esophagitis, which are characterized by an inflammation of the esophageal lining along with dysphagia, and odynophagia; functional esophageal disorders, which affect the muscles and nerves that control the motility of the esophagus and cause intermittent dysphagia for solids and liquids; and mechanical esophageal disorders, which are characterized by the blockage of the passageway and they typically cause progressive dysphagia for solids.
First, there’s reflux esophagitis, which is associated with the reflux of gastric acid from the stomach back into the esophagus. Alternatively, pill-induced esophagitis, where a medication injures the esophagus thereby causing inflammation and possible upper GI bleeding. It is associated with medications such as nonsteroidal anti-inflammatory drugs or NSAIDs, bisphosphonates, tetracyclines, iron, and potassium chloride. In caustic esophagitis, caustic agents, such as strong acids like vinegar or strong bases like detergents, cause esophageal lesions.
The next one is infectious esophagitis, which is most commonly seen in immunocompromised individuals, such as HIV-positive individuals. The most common causes of HIV associated esophagitis include candida albicans, herpes simplex virus 1, and cytomegalovirus. A high yield fact to remember is that with candida esophagitis, the upper endoscopy will show patches of adherent, white or grey pseudomembranes on the underlying mucosa. The histopathology reveals yeast cells and pseudohyphae that invade mucosal cells of the esophagus. Any attempt to remove the pseudomembrane can cause bleeding in the underlying mucosa. With HSV esophagitis, a high yield fact to remember is that an upper endoscopy will show small vesicles and lesions that look like small punched-out ulcers; while the histopathology reveals eosinophilic intranuclear inclusions in multinuclear squamous cells at the margin of the ulcer. For your exam, you have to know that these inclusions are called Cowdry type A inclusions. CMV esophagitis features linear ulcers on the upper endoscopy, while histopathology reveals both intranuclear and cytoplasmic inclusions.
Finally, we have eosinophilic esophagitis, also called allergic esophagitis, which is characterized by eosinophils that infiltrated into the lining of the esophagus. This occurs as a reaction to food allergens and it can lead to dysphagia and food impaction. Eosinophilic esophagitis is most commonly seen in individuals who have other allergies and a high yield fact that’s often used as a clue is that their esophagitis will be unresponsive to GERD therapy. During an upper endoscopy, eosinophilic esophagitis is characterized by linear furrows and esophageal rings, which are thin mucosal bands that surround the esophagus.
Achalasia is when there’s impaired esophageal motility and the inability to relax the lower esophageal sphincter. The most common cause of primary achalasia is idiopathic degeneration or damage of postganglionic inhibitory neurons in the myenteric, or Auerbach, plexus of the esophagus. There’s also secondary achalasia which is caused by Trypanosoma Cruzi infection that cause Chagas disease, or extraesophageal malignancies. So normally, the neuron in the myenteric plexus release inhibitory neurotransmitters, such as nitric oxide and vasoactive intestinal peptide, which relax the lower esophageal sphincter. Eventually, the lack of inhibitory neurotransmitters leads to an increased resting lower esophageal sphincter tone, and this obstruction leads to dilatation of the esophagus. These individuals present with progressive dysphagia for both solids and liquids, regurgitation of undigested food, aspiration, chest pain, heartburn, and weight loss. In addition, they have an increased risk for esophageal squamous cell and adenocarcinoma.
For diagnosis, remember for your exam that barium swallow in achalasia reveals dilatation of the esophagus above the obstruction and tapering of the lower part of the esophagus near the lower esophageal sphincter. This is also known as the bird’s beak sign. The gold standard for diagnosis is esophageal manometry, which measures the strength and coordination of the esophageal contractions when a person swallows. This measurement is done at multiple levels, including the upper, middle, and lower esophagus, as well as the lower esophageal sphincter.
Now, you might be asked to analyze manometry findings on your exam so let’s go over this. Normally when a person swallows, involuntary contractions of the pharyngeal muscles propel the food into the esophagus. Propulsion of the food bolus is followed by the contraction of the cricopharyngeal muscle which initiates the peristaltic wave of the esophagus. This contraction is shown as an upward deflection on the upper esophageal manometry. Next, the middle esophageal manometry reflects normal peristalsis of the middle part of the esophagus. Finally, the lower esophageal manometry suggests the decrease in the lower esophageal sphincter that corresponds to its relaxation and the passing of the bolus into the stomach.
Now for your exam, you have to know that individuals with achalasia have normal findings in the upper part of the esophagus, decrease or absence of peristalsis in the middle part of the esophagus, and high pressure in the lower esophageal sphincter. For treatment, the obstruction can be corrected with balloon dilation or increased tone can managed with local injection of botulinum toxin.
In diffuse esophageal spasm, there’s periodic, non-peristaltic contractions that occur simultaneously with each other. In contrast to achalasia, diffuse esophageal spasm is associated with a normal lower esophageal sphincter tone since the spasms occur in the walls of the esophagus. For your exam, you have to know that these disorganized involuntary esophageal contractions can cause intermittent dysphagia for both solids and liquids, and occasional retrosternal chest pain. It’s important to note that the pain can mimic angina but it’s not associated with physical activity and is not relieved by rest; however this can still resemble unstable angina. Therefore, every person that is suspected of having diffuse esophageal spasm should undergo a complete cardiac work-up to rule out any cardiac pathology.
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