Esophageal disease (Proceedings)

Esophageal diseases, including megaesophagus, 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. Failure to consider the possibility of regurgitation in the patient presented for vomiting could lead to delays in diagnosis, treatment errors, and undesired consequences. Patients with megaesophagus are at risk of potentially life-threatening complications such as aspiration pneumonitis, so early recognition of the problem of regurgitation is important to prompt and appropriate diagnosis and treatment.

Megaesophagus overview

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.

Aspiration pneumonia is one of the most common complications of esophageal disease, including megaesophagus, in small animal patients. In a recent study (Kogan et al) of canine aspiration pneumonia, esophageal dysfunction was one of the leading underlying causes, noted in 35/88 dogs. In those 35 dogs, megaesophagus was the most common esophageal disorder, observed in 25. An important set of observations that were noted in a companion article was that fewer than half of 88 dogs with aspiration pneumonia had abnormalities of body temperature, heart or respiratory rates, and for 80 dogs in which lung sounds were described, abnormal sounds were recorded in 55/80. Cough was described in only 57% of cases. Taken together, these reports show that aspiration pneumonia is not readily excluded based on clinical signs and physical examination abnormalities; patients with risk factors for aspiration pneumonia, such as megaesophagus, should have thoracic radiographs obtained as part of their routine evaluation.

Megaesophagus can be congenital or acquired, with acquired megaesophagus a much more common disease than congenital megaesophagus. Although cats do develop megaesophagus, megaesophagus is seen more commonly in dogs.

Congenital megaesophagus

Congenital megaesophagus is seen in young to juvenile animals, and has a number of different causes. Idiopathic congenital megaesophagus is believed to reflect afferent (sensory) dysfunction of the vagal nerve leading to poor esophageal contraction in response to material in the esophageal lumen. Congenital myasthenia gravis can cause megaesophagus and reflects deficiencies in the number of acetylcholine receptors at the neuromuscular junction (typically established by examination by examination of external intercostal muscle biopsies). Congenital megaesophagus has been seen as part of a complex of other neurologic abnormalities including laryngeal paralysis and peripheral weakness and has been termed laryngeal paralysis-polyneuropathy complex; the complex has been described in related Dalmatians and Pyrenean mountain dogs. Megaesophagus can also be a consequence of obstructive disease such as vascular ring anomalies.

Regurgitation of food or fluid is the most common clinical sign of congenital megaesophagus; poor weight gain in conjunction with regurgitation is also common. Affected animals may have clinical signs of respiratory disease secondary to aspiration events.

Diagnosis of congenital megaesophagus is typically established by demonstrating esophageal dilation either by plain thoracic radiographs or contrast esophagrams. The underlying cause (e.g. vascular ring anomaly, acquired myasthenia gravis) defines treatment and prognosis. Patients with some vascular ring anomalies are surgical candidates, and the prognosis is generally considered better the sooner the surgical intervention occurs.

The prognosis for dogs with congenital idiopathic megaesophagus is fair. With time and proper supportive care, some dogs will gain esophageal function as they grow older. The prognosis for other causes of congenital esophageal dysfunction is more guarded as repeated aspiration events, and nutritional deficits, tend to characterize these animals.

Acquired megaesophagus

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 or tumors (Spirocerca lupi). Among the myopathies linked to megaesophagus are 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 nerve 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; other risk factors found in this study included 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 cause of acquired megaesophagus in dogs; esophagitis itself can be the result of a number of other diseases. Some of the more important causes of esophagitis include gastroesophageal reflux, and chronic vomiting. Gastroesophageal reflux appears to be a common event during anesthetic procedures. In a study by Wilson et al, more than half (51/90) of dogs undergoing surgical procedures with either halothane, isoflurane or sevoflurane had evidence of esophageal reflux (as assessed by continuous monitoring of esophageal pH throughout the procedure) during the anesthetic period, and most dogs experiencing esophageal reflux had low esophageal pH for prolonged periods of time. The inhalant anesthetic used, or the type of premedication administered, did not appear to alter the risk of reflux during anesthesia. While the number of clinical cases that emerge from anesthetic-related esophagitis/megaesophagus is fortunately small, the failure to consider that the dog "vomiting" post-operatively may in fact be regurgitating could result in treatment errors and more serious consequences (e.g. strictures).

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 esophogram. There is a risk of the patient aspirating contrast material during a contrast esophogram.

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 can 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 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.

References

Kogan DA, et al. Clinical, clinicopathologic, and radiographic finding in dogs with aspiration pneumonia: 88 cases (2004-2006). J Am Vet Med Assoc 2008; 233:1742.

Kogan DA, et al. Etiology and clinical outcome in dogs with aspiration pneumonia: 88 cases (2004-2006). J Am Vet Med Assoc 2008; 233:1748.