Esophageal disorders: what have we been missing? (Proceedings)
Dysphagia is defined as difficult or painful swallowing. It may be due to obstruction, motility disturbance, or pain. Although dysphagia most commonly indicates a disorder involving the oral cavity or pharynx, esophageal disorders can cause this clinical sign as well. Oropharyngeal dysphagia can generally be differentiated from esophageal dysphagia on the basis of history. Characteristic signs of oropharyngeal disorders include acute gagging, exaggerated swallowing movements, and increased frequency of swallowing. Food is frequently dropped from the mouth within seconds of prehension. In contrast, patients with esophageal dysphagia do not exhibit exaggerated swallowing motions and food is not dropped from the mouth. If clinical signs are acute and persistent or progressive, a morphologic lesion (e.g., foreign body, mass, inflammation) should be suspected. Intermittent occurrence of clinical signs is usually consistent with a motility disturbance.
The causes of oropharyngeal dysphagia are listed in Box 1-2. A careful review of the history and observation of the patient as it eats will confirm the presence of dysphagia, identify its primary anatomic location (oropharyngeal in most cases), and help determine a diagnostic plan. Typically patients with oropharyngeal dysphagia eat readily but have trouble swallowing the food normally. If the tongue is not functioning normally, there may be problems with prehension and mastication as well. Affected patients may extend, ventroflex, or throw their heads back during exaggerated efforts to swallow. Additional signs that may be observed include salivation (related to inability to swallow and/or secondary to pain), nasal discharge secondary to passage of liquid food into the nasopharynx and nasal cavity, and coughing resulting from aspiration of food retained in the pharynx. Weight loss of failure to grow may also occur in some cases.
The initial step in diagnosis is to differentiate among oral, pharyngeal, and cricopharyngeal dysphagias. Signalment, clinical course (i.e., acute and persistent versus gradual onset), and physical findings are reviewed first. Clinical signs associated with cricopharyngeal achalsia are generally initially observed at the time of weaning onto solid food and, if not this early, almost always by 1 year of age. Dogs with congenitally short or cleft palate will also exhibit signs at a very young age. Young to middle-age patients are most prone to lodgment of foreign bodies in the mouth and pharynx and accidental ingestion of caustic materials (such as petroleum products or alkalis), and signs of dysphagia are acute and persistent until definitive treatment is administered. Older dogs with an insidious onset of clinical signs are more likely to be afflicted with neoplasia (e.g., glossal neoplasia, pharyngeal tumors such as squamous cell carcinoma, fibrosarcoma, melanoma, tonsillar carcinoma, retropharyngeal mass causing compression). Weight loss and reluctance to eat are generally present in chronic cases. Presence of systemic signs, such as weakness that worsens with exercise, with or without cough and dyspnea, suggests myasthenia gravis. Signs of myasthenia gravis may be limited to pharyngeal dysfunction. Weakness may also be caused by polymyositis or central nervous system disease. Dysphagia occurring in conjunction with dementia suggests cerebral disease as the underlying problem. Rabies vaccination history and potential for exposure (environment) must always be determined early in the evaluation of any patient with dysphagia.
Thorough physical examination will successfully identify the cause of dysphagia in some cases. Physical signs may also alert the clinician to the presence of any significant complications (e.g., pneumonia) and help determine specific tests that should be done to establish a definitive diagnosis. Physical examination should include a thorough evaluation of the head (temporal muscle atrophy, pain associated with muscles of mastication, ocular areas for inflammation or proptosis of one of the eyes to suggest retrobulbar mass or cellulites), oral cavity, external pharyngeal and cervical soft tissue areas for any mass effect, lymphadenopathy, or draining tract; recognition of any pain related to opening of the mouth (e.g., masticatory muscle myositis, retrobulbar inflammation, temporomandibular joint disease); and a neurologic examination. Specific neurologic tests include evaluation of cranial nerves IX (glossopharyngeal) and X (vagus) by checking the swallow and gag reflexes, respectively, evaluation of cranial nerve XII (hypoglossal) via observation and palpation of the tongue, and evaluation of gait and strength. Focal lesions of the medulla oblongata and diffuse neuromuscular disease may cause ataxia, conscious proprioception deficits, and limb weakness. Patients that exhibit any evidence of systemic signs (e.g., weakness, polyuria/polydypsia [PU/PD], muscle pain) in conjunction with dysphagia should initially be evaluated by complete blood count (CBC) (infection, inflammation, anemia of chronic disease), biochemical profile (including creatine phosphokinase [CPK] for polymyositis), and urinalysis. For example, a biochemical profile and urinalysis may confirm that lingual ulceration or necrosis is due to uremia.
Sedation or general anesthesia is often required for thorough examination of the oral cavity, pharynx, and larynx. The dental arcade, tongue (including frenulum area), palate, tonsils, and tonsillar crypts should be carefully evaluated for the presence of inflammation, mass or foreign body. Biopsies of masses should be deep to determine diagnosis and prognosis accurately. A superficial biopsy may fail to harvest neoplastic cells from a cancerous mass because the changes at the surface may be limited to inflammation and necrosis. Electrocautery can be used to control postbiopsy hemorrhage. It is important to evaluate the nasopharynx (for significant inflammation, foreign body, mass) and the proximal esophagus as well. On occasion I have found foreign bodies such as long blades of grass, peanut shells, or small needles lodged in the nasopharynx and not extending caudal to the free border of the soft palate (i.e., not readily visible on initial oral examination). Use of a flexible endoscope thqt is small enough to allow retroflexion over the soft palate greatly facilitates examination of the nasopharynx. Survey pharyngeal radiographs may be indicated as part of the preliminary work-up if history or physical examination suggests that a mass, foreign body, or injury (e.g., hyoid bone fracture) may be present. Contrast radiographic studies with fluoroscopy while observing swallowing of both liquids and food are required for differentiation of pharyngeal and cricopharyngeal dysphagia.
An acetylcholine receptor antibody titer test should be run if there is any possibility of myasthenia gravis (signs of focal myasthenia gravis may be limited to pharyngeal dysfunction and regurgitation). A Tensilon (edrophonium chloride) test could also be done, but the clinician should observe carefully for and be prepared to treat cholinergic overstimulation if it occurs. If central nervous system disease is suspected, testing may include cerebrospinal fluid analysis, nuclear scintigraphy, and/or computed axial tomography or magnetic resonance imaging (MRI).
Causes of Oropharyngeal Dysphagia
Neoplasis (benign or malignant)
Myasthenia gravis (focal or generalized)
Megaesophagus is one of the most common causes of regurgitation in dogs. Megaesophagus refers to a specific syndrome characterized by a dilated hypoperistaltic esophagus and should be differentiated from other causes of esophageal dilation (e.g., foreign body, vascular ring anomaly, mucosal stricture, neoplasia) which may or may not be characterized by abnormal peristalsis. Significant complications of regurgitation include aspiration pneumonia and chronic wasting disease.
Esophagitis occurs more commonly than is usually recognized in clinical practice. This seminar will emphasize diagnosis and management of esophageal hypomotility and esophagitis in dogs and cats.
Regurgitation refers to a passive, retrograde movement of ingested material to a level proximal to the upper esophageal sphincter. Usually this occurs before ingested material reaches the stomach. Regurgitation is a clinical sign of many disorders and should not be considered a primary disease. The term reflux refers to movement of gastric or duodenal contents into the esophagus without associated eructation or vomiting. This process may or may not produce symptoms.
Regurgitation is usually a clinical sign of an esophageal disorder (a list of causes appears in Table 1). The esophagus is a tremendously dilatable muscular tube that acts via a series of well-coordinated peristaltic contractions to move ingesta from the mouth to the stomach. Regurgitation in most cases results from abnormal esophageal peristalsis, esophageal obstruction, or asynchronous function of the gastroesophageal junction.
It is essential that the clinician make a clear differentiation between regurgitation and vomiting at the outset. Failure to recognize the difference between regurgitation and vomiting often leads to inappropriate testing (i.e., tests most useful for diagnosis of abdominal disorders are generally performed), misdiagnosis, and the use of ineffective treatment protocols. Therefore, the first diagnostic step is to obtain an accurate history. This is best accomplished by a clinician who maintains a high index of suspicion regarding the possible occurrence of regurgitation and who subsequently asks clear questions of the client about their pet's clinical signs.
Thoracic radiography for survey evaluation of the esophagus is the most important screening procedure in the diagnosis of a regurgitation disorder. Radiographs are evaluated for evidence of esophageal dilation and the presence of a foreign body or thoracic mass. Remember that transient dilation may occasionally occur and can be related to aerophagia, anxiety, dyspnea, anesthesia, and vomiting. Knowledge of the history is important in differentiation of potentially transient causes from those that are more long-standing. If survey radiographs fail to provide a definitive diagnosis, a barium esophagram (with fluoroscopy if available) should be performed. A liquid barium suspension (10 to 20 ml prior to each exposure) is best for evaluating for esophageal dilation. A mixture of food and barium is superior for evaluating esophageal motility because in some patients with slightly to moderately decreased contractility peristalsis may be adequate for liquid but clearly unable to propel solids aborally in a normal manner.
Table 1 Causes of Regurgitation
Megaesophagus - idiopathic
A baseline CBC and biochemical profile should be run in all patients with megaesophagus to look for evidence of underlying problems. Specific tests to evaluate for systemic disorders such as hypoadrenocorticism (ACTH stimulation), systemic lupus erythematosis (antinuclear antibody), and serum lead levels are done if the history and/or physical examination indicate that these primary disorders may exist. Myasthenia gravis should be considered in any patient with megaesophagus (see section which follows on focal myasthenia gravis). The test of choice is an acetylcholine receptor antibody titer. Acetylcholine receptor antibody titers can be run at the Comparative Neuromuscular Laboratory in La Jolla, CA (Dr. Diane Shelton). Blood samples should be allowed to clot at room temperature, then centrifuged as soon as possible. The serum should be removed and refrigerated. At least 1 ml (preferably 2 ml) of serum should be shipped on a cold pack by overnight express. Contact the laboratory for forms and sample submission instructions.
The address is:
Comparative Neuromuscular Laboratory
Basic Science Building, Room 1057
UC San Diego
La Jolla, CA 92093-0612
If radiographs reveal any suggestion of esophageal stricture, foreign body, mass, or diverticulum, fiberoptic endoscopy provides the most rapid and cost effective method of making a definitive diagnosis.
Megaesophagus Secondary to Acquired Myasthenia Gravis
Myasthenia gravis (MG) occurs as both an acquired, autoimmune disorder and a congenital, familial one. Acquired MG is an autoimmune disorder of neuromuscular transmission resulting from the actions of autoantibodies against nicotinic acetylcholine receptors at neuromuscular junctions. Megaesophagus associated with generalized MG (clinical signs include premature fatigue during exercise, manifest by a spastic pelvic limb gait followed by tetraparesis and then collapse; tachypnea and dyspnea, and sialosis) has been well documented. More recently a focal form of MG, in which megaesophagus occurs in the absence of detectable generalized weakness, has been recognized. The primary clinical sign is regurgitation. Other clinical signs that may occasionally be observed include pharyngeal and laryngeal muscle weakness (dysphagia and dyspnea), weakness of the facial muscles, and a decreased palpebral reflex.
A diagnosis of focal MG is established by demonstration of circulating antibodies against canine acetylcholine receptors by immunoprecipitation RIA. This test should run in all patients with acquired megaesophagus.
Treatment may include drug therapy but a specific feeding program is always instituted (see next section on general treatment measures). Pharmacologic management includes anticholinesterase drugs, azathioprine, and possibly corticosteroids. Refer to recent textbooks on esophageal disease for details on selecting a protocol and monitoring schedule.
The course of focal MG is variable. Although some dogs progress to the generalized form of MG this generally occurs within the first few weeks after onset of clinical signs (Shelton). There have been some favorable results in patients that receive azathioprine as the cornerstone drug. The serum antibody titer should be rechecked at 4 to 6 week intervals. Treatment is continued until the titer returns to the normal range. Radiographs are also made periodically to monitor esophageal size. Esophageal function may return to normal. The time course to remission may take days to months. Owners should be warned that the disease may recur.
General Management Principles for Megaesophagus
The main objectives of treatment for regurgitation disorders are to remove the initiating cause as early as possible, minimize chances for aspiration of esophageal content, and maximize nutrient intake to the GI tract. In most cases, idiopathic megaesophasgus is incurable, and treatment involves an individually tailored feeding regimen with the patient eating in an elevated position. Esophageal foreign bodies and intraluminal strictures can often be managed successfully with fiberoptic endoscopy techniques and bougienage or balloon dilation respectively. Medical management is indicated for such secondary causes of esophageal dilation as myasthenia gravis, hypoadrenocorticism, systemic lupus erythematosis, and anterior mediastinal lymphosarcoma in cats. Surgery may be indicated for selected foreign body, stricture, granuloma, and tumor cases.
Megaesophagus patients are best fed with the upper body in an elevated position of at least 45 degrees (more if possible). It is important that proper positioning be clearly demonstrated to the client so that there is no misunderstanding. Whenever possible the elevated position should be maintained for a full 10 minutes after ingestion of food is completed. Various props to aid in the elevation process have been used successfully, including ladders, stairs, ramps, tables, and chairs. Since the esophagus is virtually never completely empty in a megaesophagus patient it is often helpful to hold the animal in an elevated position for 5 to 10 minutes at a time sometime between meals and at bedtime (I ask all of my clients to at least do the bedtime elevation in an effort to empty the esophagus as much as possible prior to an expected period of prolonged recumbency).
Megaesophagus patients are ideally fed 2 to 4 times daily. This depends, of course, on the caregiver's time constraints. I have had the best success feeding soft moist to solid (chopped) canned food consistency. I only recommend trying gruels if the semi-moist consistency is not well tolerated. Some patients do well when fed a series of "meatballs" fashioned from canned food. Others can tolerate dry food fairly well. A key point is that each patient is an individual and clients should be instructed to experiment with various food consistencies in order to determine the best approach for their own pet.
Specific pharmacologic agents (e.g., prokinetic drugs such as metoclopramide, calcium channel antagonists such as nifedipine) have been tried but none has been shown to be consistently effective in improving clinical signs in canine patients with megaesophagus. I recommend that a prokinetic agent only be used if there is a concurrent gastric hypomotility disorder (clinical signs will include vomiting if this disorder is present).
Many patients with idiopathic megaesophagus can be managed successfully for months to years. I have known many dedicated owners who have managed to find the time required to care for their pets. As a result of this experience I try to offer as much encouragement as possible at the time of diagnosis. The most worrisome complications that can occur are aspiration pneumonia and significant weight loss. The prognosis is guarded to poor in patients that suffer recurrent episodes of pneumonia.
An option in cases where frequent regurgitation remains an ongoing problem with or without aspiration events, is to place a gastric feeding tube (e.g., percutaneous endoscopy-guided gastrostomy tube [PEG]). All food and water can then be administered through the feeding tube (some patients have been maintained for as long as 3 or more years in this way). Periodic tube replacement will be necessary. Low profile feeding tubes often work best for long term tube feeding. This method of management has been highly successful for some dogs that continue to regurgitate frequently despite excellent efforts to manage them with an elevated feeding program.
Inflammatory diseases of the esophagus occur more commonly than they are recognized. Inflammatory changes can range from mild mucosal inflammation that may or may not be grossly evident, to moderate to severe ulceration and transmural involvement. Any disorder that causes acute or chronic frequent vomiting has the potential for causing esophagitis. This especially includes causes of severe vomiting, such as intestinal foreign bodies, gastric foreign bodies, acute pancreatitis, parvovirus enteritis, and gastrinoma. Dogs with parvovirus enteritis that are debilitated and recumbent are especially at risk. Vomited fluid that is retained in the esophagus is not cleared adequately in weak and recumbent patients. As a result the esophageal mucosa is bathed with gastric acid and activated enzymes that will cause mucosal injury.
Other causes of esophagitis include esophageal foreign bodies, chemical and thermal injuries, injury from lodged medication (doxycycline capsules in cats can become lodged and cause esophagitis and even stricture formation), gastroesophageal reflux, and anesthesia related reflux.
Diagnosis of Esophagitis
The clinical signs of esophagitis vary considerably, depending on the degree of inflammation present. The clinician must maintain a high index of suspicion because in many cases only subtle clinical signs may be evident. With mild esophagitis there may be increased swallowing motions, salivation, and inappetence. In more severe cases there may be gulping, regurgitation, dysphagia due to pain, total anorexia, and signs that suggest esophageal pain, such as reluctance to move, standing with the head extended, reluctance to lie down, and trembling. Heartburn pain in humans can be quite intense, and it is suspected that a similar situation exists in animals. Esophageal hemorrhage may occur in severe cases. Signs such as increased attempts at swallowing, salivation, and regurgitation, and inappetence that occur within 1 to 4 days of an anesthetic procedure strongly suggest reflux esophagitis. Chronic reflux esophagitis occurs most commonly in patients with hiatal hernia disorders.
Radiographic survey and contrast studies are often normal in patients with mild to moderate esophagitis. Survey films may show increased esophageal density in moderate to severe esophagitis. There may also be various degrees of esophageal dilation, since esophageal inflammation may inhibit motility. Persistent contrast in the thoracic esophagus or esophageal dilation, or both, suggest the possibility of gastroesophageal reflux.
A definitive diagnosis of esophagitis is most often made by endoscopic visualization of the esophageal mucosa. Variable degrees of mucosal erythema or isolated patches of eroded mucosa may be seen. However, as also occurs in humans, some animals with esophagitis do not have gross esophageal abnormalities, and in these cases symptom patterns in conjunction with positive response to therapy are the key components to a presumptive diagnosis.
Treatment of Esophagitis
Mild reflux esophagitis is often asymptomatic and generally resolves without therapy. If clinical signs suggestive of reflux esophagitis occur within several days of an anesthetic procedure, treatment should be instituted, regardless of whether endoscopy is available for definitive diagnosis. Treatment in this situation usually includes an H2-receptor antagonist or a PPI, the cytoprotective drug sucralfate, and a promotility drug (metoclopramide or cisapride). The duration of therapy will typically be 7 to 14 days. A longer duration will be required if clinical signs persist.
PPIs are drugs that completely inhibit gastric acid secretion in response to all modes of stimulation. PPIs include omeprazole (Prilosec), lansoprazole (Prevacid), esomeprazole (Nexium), pantoprazole (Protonix), and rabeprazole (Aciphex). Omeprazole is the PPI that has been used most frequently in animal patients. PPIs decrease acid secretion by inhibiting H+, K+ ATPase (commonly called the proton pump), thereby blocking the final, common step in the secretion of gastric acid. PPIs control both basal and meal-stimulated acid secretion. Therefore, the acid suppression achieved by a PPI is more complete and longer lasting than can be attained with an H2-receptor antagonist. The recommended dosage for omeprazole is 0.3 mg/lb once daily.
H2-receptor antagonists are used to decrease gastric acid production, thereby decreasing acid volume available for reflux. H2-recptor antagonists also reduce the volume of gastric acid that is produced. There is no adverse effect on resting or stimulated LES pressure levels. Cimetidine (2.5 to 5 mg/lb orally every 6 to 8 hours), ranitidine (1 mg/lb [dog], 1.5 mg/lb [cat] orally every 12 hours), or famotidine (Pepcid, 0.25 to 0.5 mg/lb orally every 24 hours, or every 12 hours if there is severe esophagitis) is generally used for 2 to 3 weeks in dogs and cats with acute reflux esophagitis. Since 1987 I have preferred to use famotidine (Pepcid) because of its long dosage interval and the fact that it is associated with fewer side effects. Another H2-receptor antagonist that can be tried is nizatidine (Axid). The dosage is 1.25 to 2.5 mg/lb orally every 24 hours. Ranitidine and nizatidine also have a gastric prokinetic effect. Long-term therapy should be used in hiatal hernia patients with chronic reflux esophagitis if corrective surgery either is not performed or is unsuccessful.
Esophagitis Associated with Frequent Vomiting
Clinicians are especially cautioned to be more attentive to patients that might have esophagitis secondary to frequent or severe vomiting (e.g., caused by GI foreign bodies, parvoviral enteritis, acute pancreatitis, or renal failure). Esophagitis can easily develop in these situations, and it no doubt adds significantly to the discomfort that the patient is already experiencing. In these cases, both sucralfate and an H2-receptor antagonist are used to treat esophagitis. I use famotidine (Pepcid) injectable at 0.25 mg/lb IV BID. An antiemetic drug such as chlorpromazine (Thorazine) is injected to help decrease the frequency of vomiting. Sucralfate is given orally, in suspension form so as to better coat the esophagus, usually 30 to 60 minutes after antiemetic therapy has been administered.
The duration of therapy in patients with reflux esophagitis depends on the cause and degree of inflammation. For moderate to severe esophagitis, 4 to 8 weeks of therapy or more may be required to achieve full healing of the esophagus. For esophagitis related to frequent or severe vomiting, treatment is usually administered 5 to 7 days, and only longer if clinical signs or endoscopic findings warrant.
Tams TR: Diseases of the esophagus. In Tams TR, ed: Handbook of Small Animal Gastroenterology, ed 2, Philadelphia, 2003, WB Saunders.
Willard MD and Carsten EW: Esophagitis. In Bonagura JD and Twedt DC, eds: Current Veterinary Therapy XIV, St. Louis, 2009, Elsevier.