The most likely diagnosis is pill-induced esophagitis. This patient has retrosternal chest pain after taking doxycycline for Lyme disease. Pill-induced esophagitis has been observed with alendronate, quinidine, tetracycline, doxycycline, potassium chloride, ferrous sulfate, and mexiletine. Pills typically cause local injury at sites of anatomic narrowing of the esophagus, such as the aortic arch, gastroesophageal junction, or the esophageal indentation caused by an enlarged left atrium. Clinical symptoms include chest pain, dysphagia, and odynophagia. Symptoms may begin hours to days after starting therapy, and stopping the medication will often lead to symptom relief. Preventive strategies to decrease pill-induced esophagitis are to drink plenty of water with the medication and avoid lying down for 30 minutes after ingestion.

Barrett esophagus (BE) is present when columnar epithelium replaces the normal squamous epithelium in the distal esophagus. BE is a consequence of gastroesophageal reflux disease (GERD) and by itself is often asymptomatic. There is nothing in this patient's clinical picture to suggest BE or GERD.

Patients with infectious esophagitis may be asymptomatic or may have odynophagia or dysphagia. Infectious esophagitis is typically caused by Candida albicans, herpes simplex virus, and cytomegalovirus. These infections typically occur in patients who are immunosuppressed owing to medications (such as glucocorticoids, azathioprine, or tumor necrosis factor-α inhibitors) or congenital or acquired immunodeficiencies. Use of swallowed aerosolized glucocorticoids may put an immunocompetent patient at risk for some of these infections. Candida infection is characterized by small, white, raised plaques on upper endoscopy, and esophageal brushings confirm the diagnosis. Pill-induced esophagitis is a much more likely diagnosis for this immunocompetent patient taking doxycycline than is Candida esophagitis.

Eosinophilic esophagitis (EoE) is defined as esophageal squamous mucosal inflammation caused by eosinophilic infiltration. EoE is usually seen in young men who present with dysphagia and a food-bolus obstruction. This patient does not have symptoms characteristic of EoE.