Esophageal disease can easily sneak up on the unsuspecting clinician if regurgitation, the cardinal sign of esophageal disease, is not considered a differential diagnosis for an animal that presents for what the owner perceives as vomiting. Patients with esophageal diseases are at risk of life-threatening complications such as esophageal perforations or aspiration pneumonitis, so early identification of esophageal disease is important to prompt and appropriate treatment. Esophageal foreign bodies and esophagitis have the potential, if not identified and treated, to cause esophageal strictures or megaesophagus, which can be more difficult to treat. Failure to consider the possibility of regurgitation in the patient presented for vomiting could lead to delays in diagnosis, treatment errors, and undesired complications. The common esophageal diseases of dogs and cats, and the focus of these notes, are megaesophagus, esophagitis, and esophageal strictures. Less common, but still important, causes of esophageal disease include esophageal neoplasia and gastroesophageal intussusception. Megaesophagus Megaesophagus can be congenital or acquired, with acquired megaesophagus a more common disease than congenital. Although cats do develop megaesophagus, megaesophagus is seen more commonly in dogs. Many diseases have been associated with acquired megaesophagus, and generally fall into categories of myopathies, peripheral neuropathies, other disorders of the neuromuscular junction, or obstructive diseases such as strictures, foreign bodies, granulomas (Spirocerca lupi) or, in younger patients with regurgitation, vascular ring anomalies. Some myopathies linked to megaesophagus include inflammatory myopathies of infectious or non-infectious (immune- mediated) origin (polymyositis, systemic lupus erythematosis, dermatomyositis). Some neuropathies tied to acquired megaesophagus include polyradiculoneuritis, bilateral vagal injury, dysautonomia, and lead and thallium toxicity. Other neuromuscular junction diseases with the potential to cause megaesophagus include botulism, tetanus and anticholinesterase toxicities (e.g. organophosphates). Central nervous system disease (e.g. brain stem lesions, neoplasia, trauma) has also been associated with megaesophagus. Myasthenia gravis (MG) is considered one of the most common causes of acquired megaesophagus in dogs; dogs with MG may have megaesophagus as the only manifestation of neuromuscular junction disease, or may have more classical appendicular weakness. Gaynor et al retrospectively studied a large number of dogs with megaesophagus to identify risk factors associated with the disease. In their series of 136 dogs, the most common risk factor identified was MG, with other risk factors including esophagitis and peripheral nerve disease. Despite being commonly cited as a risk factor for acquired megaesophagus, the Gaynor study did not find any association between megaesophagus and hypothyroidism. Esophagitis is another common cause of acquired megaesophagus in dogs; esophagitis itself can be the result of a number of other diseases. The cardinal clinical sign of megaesophagus is regurgitation, which must be distinguished from vomiting by careful historical investigation. Compared to vomiting, regurgitation is a passive process that is not proceeded by prodromal signs such as lip-licking, anxiousness, and repeated heaving/retching. Regurgitation can occur minutes to hours after ingestion of food or water. Distinction between regurgitation and vomiting in some patients can be difficult, and if there is any doubt about whether a patient could be regurgitating, it may be prudent to assess esophageal function before pursuing causes of vomiting. Failure to consider that a patient presented for vomiting may actually be regurgitating could lead to delays in diagnosis, inappropriate therapy, or serious complications of untreated esophageal disease. Animals with megaesophagus may also have difficulty swallowing, excessive salivation, pain with swallowing, or if pulmonary aspiration has occurred, cough or alterations in respiratory rate and pattern. Vomiting may also be a component of the clinical presentation potentially confounding the recognition of regurgitation as an element of the animal’s clinical presentation; vomiting can accompany megaesophagus if vomiting (usually chronic) has led to esophagitis. Animals with esophagitis or aspiration may also have fever. Prolonged regurgitation is likely to lead to weight loss. Physical examination abnormalities in patients with megaesophagus can include poor body condition, distension (which can be dynamic) of the left ventral neck area, and fever and pulmonary crackles if aspiration pneumonitis is present. Patients with MG may have evidence of peripheral weakness, although this will not be appreciated in all patients. Once the problem of regurgitation is suspected, megaesophagus is often easily demonstrated on plain thoracic radiographs on which an air (or sometimes fluid)-filled esophagus is readily seen. Occasionally, animals with megaesophagus will not have an obvious air-filled esophagus apparent on thoracic radiographs, and esophageal hypomotility may be demonstrated during a contrast esophagram. There is a risk of the patient aspirating contrast material during a contrast esophagram. Once megaesophagus has been identified, revisiting the physical examination to carefully screen the patient for other signs of neuromuscular disease can be helpful in prioritizing differential diagnoses. Additional diagnostic steps often performed early in patients with megaesophagus include a CBC, biochemical profile and urinalysis to screen for inflammatory, or endocrine (hypoadrenocorticism) disease, anti-acetylcholine receptor antibodies, and if evidence supports hypoadrenocorticism, an ACTH stimulation test. A positive test for Ach-receptor antibodies confirms a diagnosis of MG, but a negative result does not exclude a diagnosis of MG as it is known that some dogs with MG can be antibody negative; this may be particularly true of focal forms of myasthenia in which only the esophagus may be affected. Other tests that may be indicated in occasional patients include ANA titers, serum CK activity, blood lead concentrations, and if there is evidence of dysfunction in other muscles, EMG and muscle biopsies for histopathological examination. Endoscopic examination of the esophagus is not commonly performed in animals with megaesophagus, but is probably underutilized. Esophagoscopy is a sensitive means of detecting esophagitis, which can lead to acquired megaesophagus. In animals whose history includes risk factors for esophagitis (e.g. recent general anesthesia) or suggests the possibility of concurrent vomiting, endoscopic examination of the esophagus and other parts of the intestinal tract may reveal lesions suggestive of esophagitis or other gastrointestinal disease and allows for biopsy of the gastrointestinal mucosa to help define the underlying cause of vomiting. Another benefit of endoscopic examination is the opportunity it provides to place gastrostomy tubes, which can be very helpful in the provision of nutritional support in addition to insuring reliable delivery of medications. Ancillary testing that can be important for some patients is sampling of the respiratory tract for cytology and microbial culture. Culture of respiratory washes (transtracheal, bronchial or bronchoalveolar lavage) is more important in those animals that have been treated for long periods of time with antibiotics, or that have received multiple different antibiotics. Treatment of megaesophagus centers on identification and treatment of underlying diseases when identified. Patients with MG should receive an acetylcholinesterase inhibitor such as pyridostigmine and are often candidates for immunosuppressive therapy with glucocorticoids and/or azathioprine. The timing of implementation of immunosuppressive treatment in the face of pulmonary aspiration is based on clinical judgment, but the author will typically try to wait when possible until there has been clinical and radiographic resolution of pneumonia before implementing immunosuppressive therapy. Some animals that exhibit good responses can be maintained with immunosuppressive drugs alone. The optimal dosage of glucocorticoids for animals with MG has not been established. Avoiding immunosuppressive dosages is advocated by some to lessen the risk of exacerbating muscle weakness. Esophagitis should be treated with H2 receptor blockers such as famotidine, and a sucralfate slurry. Metoclopramide, which increases lower esophageal sphincter tone, probably should not be given in the face of overt esophageal hypomotility. It may be reasonable to empirically treat for esophagitis while awaiting Ach receptor antibody test results, or if the owner refuses to allow diagnostic investigation for financial or other concerns. Causes of vomiting or predispositions to esophagitis should be identified and treated when possible. Resolution of megaesophagus can be appreciated in some patients with correction of underlying causes. Animals with evidence of aspiration pneumonitis are usually candidates for antimicrobial treatment, which should be broad-spectrum if treatment is done without benefit of respiratory wash cultures. Antibiotics should be continued for a week beyond radiographic resolution of pulmonary injury. The prognosis for dogs with congenital megaesophagus is fair. With time and proper supportive care, some dogs will gain esophageal function as they grow older. The prognosis associated with acquired megaesophagus varies with the underlying cause. For patients that have treatable primary disorders (e.g. MG; esophagitis), resolution of megaesophagus and associated clinical signs is possible, and the prognosis can be fair to good. The prognosis for patients with megaesophagus secondary to obstructive disease seems to be a function of the length of time that the esophagus has been obstructed; the longer the esophagus has been obstructed, the less likely there will be return of normal esophageal function. Animals with idiopathic megaesophagus often have a poor prognosis as these patients are susceptible to repeated bouts of aspiration, weight loss, and continued regurgitation, all of which can prove extremely frustrating for owners. Esophagitis and esophageal strictures Esophagitis most commonly develops in patients that have had either chemical or mechanical injury to the esophagus. For patients that develop chemical induced esophagitis, most often a consequence of prolonged exposure of the esophageal mucosa to gastric acid, pepsin or bile, a breakdown in one or more of the esophageal protective mechanisms (anatomic configuration of the lower esophageal sphincter, mucus production in the mucosa, epithelial tight junctions), or injury that overwhelms such protective mechanisms, usually precedes esophagitis. Animals that ingest caustic substances can also sustain a chemically-induced esophagitis. In dogs, one of the more common causes of esophagitis is esophageal reflux during general anesthesia, which can be associated with relaxation of the lower esophageal sphincter (LES) and reflux of gastric acid or other injurious agents (bile, lecithin) into the esophagus. Any other condition that disrupts the LES (e.g. hiatal hernias) can result in reflux esophagitis. Chronic vomiting, which can regularly bathe the esophageal mucosa with harmful gastric secretions or bile, can also predispose to esophagitis. Chemical injury from some medications, e.g. doxycycline or related drugs (best documented in cats) can cause esophagitis. Esophageal foreign bodies that are not promptly removed can cause focal esophagitis. Other less common causes of esophagitis include ingestion of caustic agents, infection (Pythium sp) and esophageal surgery. Clinical signs of esophagitis are similar to those for megaesophagus. In addition to regurgitation, the clinical presentation of animals with esophagitis can be confusing if esophagitis is secondary to chronic vomiting. Esophagitis can also be a clinically silent condition until a stricture or megaesophagus develops. Esophagitis is suspected based upon the presence of compatible clinical signs, exclusion of other causes of regurgitation (especially esophageal foreign bodies and megaesophagus), and documentation of esophageal inflammation. Esophagoscopy is the most sensitive means of detecting lesions of esophagitis, although some patients can have histologically evident esophagitis without obvious endoscopic lesions. Contrast esophagram abnormalities (mucosal irregularities, retention of contrast) can suggest the diagnosis. Treatment of esophagitis centers around identification and correction, whenever possible, of any predisposing risk factors or causes. Other important treatment aspects include limiting additional injury to the mucosa, typically by reducing gastric acid secretion through the use of H2 receptor blockers (famotidine, ranitidine) or proton pump inhibitors (omeprazole and related). The proton pump inhibitors are considered the most potent of acid suppressors, and tend to be favored in the treatment of esophagitis in people. A commonly used, though clinically unproven, approach is to administer sucralfate (often as a slurry in water) with the goal of providing a “band-aid” to the eroded/ulcerated mucosa to limit additional injury. Metoclopramide is often administered to increase the tone of the LES if there is no evidence of megaesophagus. Theoretically, feeding a higher protein diet would be of benefit because such diets stimulate the release of gastrin, which can increase tone of the LES. Treatment is typically provided well beyond resolution of clinical signs in the absence of repeated endoscopic assessment. The prognosis for patients with esophagitis varies with the underlying cause and severity of esophageal injury. Complications of esophagitis include megaesophagus, aspiration pneumonitis, and esophageal stricture formation. Clinical signs of esophageal stricture are as for other diseases noted above; regurgitation can be severe in the face of marked compromise of the esophageal lumen with some animals unable to retain even water without regurgitation. The presence of a stricture is often suggested historically by the appearance, or worsening of, regurgitation, especially following a known episode of esophagitis, or a risk factor for esophagitis (e.g. an episode of general anesthesia). Strictures are easily confirmed during esophagoscopy, or with contrast esophagrams. Advantages of the latter include the ability to establish the length of a stricture, particularly for those strictures that are too small to permit advancement of an endoscope. Treatment of esophageal strictures requires dilation of the stricture, either by balloon dilation or esophageal bougienage. In people or veterinary species, studies have not demonstrated a clear advantage of one technique over another, and the technique used is often a reflection of training, availability of equipment and/or personal preference. Repeated dilations are commonly needed to restore a functional lumen, which is the goal of dilation. Using electrocautery to create 3-4 “fracture” sites around the circumference of the stricture has been advocated as a means to reduce the amount of post-dilation esophageal injury and reduce the number of dilations needed to achieve an acceptable outcome. Since dilation usually causes additional mucosal injury, treatment of patients after dilation is the same as for esophagitis. Iatrogenic tears are a potential complication of balloon or bougienage procedures. The role of glucocorticoids in the management of patients with esophageal strictures is not well-established by evidence of efficacy in veterinary medicine, although administration of glucocorticoids either by local injection under endoscopic guidance, or systemically administered glucocorticoids, is often used by some clinicians. The author commonly places gastrostomy tubes to facilitate administration of medications, in addition to providing fluid and nutritional support, while evaluating the outcome of esophageal dilations or while waiting for esophagitis- induced megaesophagus to resolve. Patients with esophageal strictures have a good prognosis if esophageal dilation has been successful at restoration of a function lumen.