Congenital Megaesophagus

Congenital megaesophagus occurs in purebred and mixed-breed dogs. It is known to be inherited in the wirehaired fox terrier as an autosomal-recessive trait and in the miniature schnauzer as either an autosomal-dominant or autosomal-recessive trait with partial penetrance. Congenital megaesophagus occurs with increased prevalence in Great Danes, German shepherds, Labrador retrievers, Newfoundlands, Chinese shar-peis, and Irish setters. Although not proved, the predilection for megaesophagus in these breeds, in addition to reports of entire litters of German shepherds, Great Danes, Newfoundlands, and shar-peis being affected, suggests a hereditary basis for megaesophagus. For this reason owners are advised not to use affected dogs or those closely related to affected dogs for breeding. Clinical signs usually occur by 3 months of age; however, dogs with mild symptoms may not be presented until 1 year of age.

Although the pathogenesis of congenital megaesophagus is unclear, esophageal function studies of affected dogs indicate defects in the vagal afferent innervation of the esophagus. Other studies have confirmed that vagal efferent innervation in affected dogs is normal but that esophageal motor function is decreased, possibly secondary to abnormal biomechanical properties of the esophageal muscle.

Acquired Megaesophagus

Acquired megaesophagus can occur in any breed; however, the breeds at a significantly increased risk for developing the disease include some of the same breeds discussed previously (i.e., German shepherds, golden retrievers, Irish setters, and Great Danes). Secondary megaesophagus can be caused by any disorder that inhibits esophageal peristalsis either by disrupting esophageal neural pathways or by causing esophageal muscular dysfunction. Numerous central and peripheral neuropathies, diseases of the neuromuscular junction, and myopathies have been reported to cause megaesophagus (see Web Box 47-2). Most of these diseases are uncommon, and an exhaustive search to rule out all is unrealistic. However, several diseases routinely should be considered.

Myasthenia gravis (MG) is the most common cause of acquired megaesophagus in the dog. It occurs rarely as a congenital disease and more frequently as an acquired disease; both can cause megaesophagus. Acquired MG is an autoimmune disorder that interferes with normal neuromuscular transmission. Production of autoantibodies against nicotinic ACh receptors decreases the number of receptors available for normal neuromuscular transmission, resulting in skeletal muscle weakness. Two forms of acquired MG, generalized and focal, have been identified. Generalized MG causes exercise-related generalized muscle weakness that worsens after exercise and improves with rest. Most dogs with generalized MG also have megaesophagus. Focal MG causes weakness that affects predominantly esophageal, pharyngeal, or facial muscles. Affected dogs usually have symptoms of megaesophagus.

Diagnosis of MG is made by measuring increased antibody titers to ACh receptors, but serum ACh receptor antibody concentrations tend to be lower in focal MG than in the generalized form. ACh receptor antibodies are negative in up to 15% of generalized MG and up to 50% of focal MG in humans (Dewey, 1997). Seronegative myasthenics exist in the veterinary population as well. Approximately 2% of dogs with generalized myasthenia gravis are seronegative. The percentage of dogs with seronegative focal myasthenia gravis has not been determined (Shelton, 2002). Immunocytochemical staining, which localizes the immune complexes at the neuromuscular junction after incubation of patient serum with normal canine muscle, is a second diagnostic method that is also relatively inexpensive and easy to perform. This test is not specific for antibodies against the ACh receptors; thus a positive result is not definitive. However, it is a useful screening test.

Many dogs diagnosed as having “idiopathic” megaesophagus are likely to have focal MG. In a study by Shelton and associates (1990), serum samples from 152 dogs with idiopathic megaesophagus were tested for ACh receptor antibodies. Results confirmed that 40 of 152 (26%) had antibody titers diagnostic for MG. Another 17 cases (11%) that did not have positive titers had positive immunocytochemical staining of immune complexes. Of those affected, 48% had clinical improvement or remission of clinical signs with treatment.

Occasionally megaesophagus is observed in dogs with primary, secondary, or atypical hypoadrenocorticism. Impaired muscle carbohydrate metabolism and depletion of muscle glycogen stores resulting from glucocorticoid deficiency and decreased catecholamine activity have been suggested as possible causes. Megaesophagus has been reported to resolve with prednisone treatment in dogs with glucocorticoid-deficient hypoadrenocorticism (Bartges and Nielson, 1992).

Hypothyroidism historically has been cited as a possible cause of megaesophagus. However, a definitive association between hypothyroidism and megaesophagus has not been proved. In a case-controlled study by Gaynor, Shofer, and Washabau (1997) of 136 dogs with acquired megaesophagus, 272 control dogs from the general hospital population, and 151 control dogs that underwent thyroid-stimulating hormone response tests, no association between megaesophagus and hypothyroidism was found. In one retrospective study of 29 hypothyroid dogs, four had megaesophagus; one dog showed clinical improvement in esophageal symptoms when treated with thyroid supplement. Radiographic evidence of a dilated esophagus persisted in all four dogs (Jaggy et al, 1994). There is an association between MG and hypothyroidism, most likely caused by a common immune-mediated disorder. Therefore thyroid function still should be evaluated in dogs with megaesophagus until MG has been ruled out definitively.

Dysautonomia, an idiopathic condition that results in clinical signs attributable to failure of the sympathetic and parasympathetic nervous systems, is becoming a more common cause of megaesophagus. Dysautonomia typically affects young dogs from rural environments with the freedom to roam. Clinical signs are consistent with autonomic dysfunction and include vomiting, regurgitation, weight loss, dysuria, decreased anal tone, mydriasis with absent pupillary light reflexes, decreased tear production, and dry mucous membranes. More than 60% of patients with dysautonomia have radiographic evidence of megaesophagus; 71% of those have concurrent lung disease (Detweiler et al, 2001). Radiographic evidence of megaesophagus with dysautonomia is indistinguishable from that seen with other causes of megaesophagus; however, gastric motility should be normal with causes other than dysautonomia.

Another condition that should prompt evaluation for megaesophagus is laryngeal paralysis. Many dogs with laryngeal paralysis also have concurrent esophageal dysfunction. Laryngeal paralysis may be a risk factor for acquired megaesophagus because both diseases have a common pathogenesis involving the vagus nerve. The vagus nerve may be the only affected nerve, or it may be affected as part of a diffuse polyneuropathy. Similarly, dogs with histories of chronic or recurrent gastric dilation with or without volvulus should be evaluated for megaesophagus. In these cases LES obstruction or esophagitis secondary to vomiting is the proposed mechanism for acquired megaesophagus.