Regurgitation: oesophagitis and megaoesophagus

Regurgitation is a symptom caused by the retrograde movement of food or secretions from the pharynx, or more often from the oesophagus, into the oral cavity. It is a passive phenomenon, with very few prodromal signs. Once regurgitated, the ingesta can be ejected from the mouth, swallowed or inhaled.

Differentiation between vomiting and regurgitation

Differentiating between vomiting and regurgitation is not always easy. The collection of a detailed history is fundamental and special attention must be paid to the owner’s description, to statements such as “my pet vomits”, or “my pet coughs before vomiting”; further investigations may be required when considered necessary. From a diagnostic point of view distinguishingbetween the two events is crucial, so it is very important to "guide" the owner through specific questions in order to collect the information required.

The presence of regurgitation may be indicative of different oesophageal diseases, such as oesophagitis, gastroesophageal reflux, motility disorders (megaoesophagus, etc.), obstructive lesions such as foreign bodies, stenosis, vascular abnormalities, tumours, but also hiatus hernia or gastroesophageal intussusception.

The subject matter of this work comprises inflammatory diseases of the oesophagus (oesophagitis) and motility disorders, with a special emphasis on megaoesophagus.

OESOPHAGITIS

The term oesophagitis is indicative of inflammation of the oesophageal mucosa (and at times even of the submucosa). The causes of inflammation of the oesophagus are diverse and in chronic cases oesophageal stricture and megaoesophagus may be present.

Causes
The most frequent cause of oesophagitis lies in the prolonged contact of the oesophageal mucosa with gastric acid following episodes of continued vomiting, excessive acid production (e.g. in the presence of neoplasms) or of gastroesophageal reflux disease (following general anaesthesia, hiatus hernia, gastric cardia abnormalities, etc.).Typically,normal oesophageal peristalsis causes the gastric acid to return rapidly into the stomach; in the presence of decreased peristalsis or of persistent excess stomach acid the gastric acid flows instead back into the oesophagus, causing severe damage to the mucosa and submucosa. In chronic cases this triggers a vicious cycle of inflammation and vomiting which is difficult to stop and which may result in the formation of oesophageal strictures.

Gastroesophageal reflux is not a frequent finding in anaesthetized animals, but when present it can often be severe and may also result in stenosis.^1,2,3 Animals of both sexes can be affected by this complication; in females, recent studies have shown that there is no correlation between increased reproductive hormone levels⁴ and the formation of strictures.

Foreign bodies (bones,⁵ fish hooks⁶ and toothpicks⁷) may often be the cause of oesophagitis and of consequent strictures. Prolonged oesophageal exposure to medications may result in local inflammation and consequent irritation and in cats the administration of tetraciclines has particularly been blamed.^8,9 Some animals may ingest caustic agents from the environment, or lick them directly from their own skin during grooming (cats), with ensuing oral and oesophageal lesions. The extent of the  injury is mainly determined by the nature of the caustic agent being ingested.

Some neoplasms, such as gastrinomas, may be responsible for an excessive production of gastric acid that can pass from the stomach to the oesophagus, causing inflammation.

Infections of the oesophagus may be present with some rare diseases (e.g. pythiosis and spirocercosis) and in immunocompromised animals (subjects treated with steroids, cyclosporine, azathioprine, etc.), with consequent irritation. Less often, imflammation may also result from the presence of oesophageal cancers.

Clinical signs

Clinical signs vary depending on the type of local damage and on the extent and degree of the inflammation present.¹⁰ If the inflammation is minimal the subject may be entirely asymptomatic. In the presence of moderate to severe inflammation the more frequently observed clinical signs are hypersalivation, anorexia, odynophagia (extension of the head and neck during swallowing due to pain), dysphagia, often regurgitation (sometimes with the presence of fresh blood), weight lossand cachexia.

Diagnosis
The presence of oesophagitis can usually be suspected following the collection of a good medical history.¹¹ Blood levels (CBC and biochemical profile) are rarely altered.

Chest radiographs are not sensitive enough to allow the identification of a state of inflammation. Barium contrast studies (oesophagograms) may show signs of barium retention in the oesophagus, mild oesophageal dilatation or alterations of the oesophageal mucosa. Liquid barium is usually administered first and is then followed by food mixed with barium. On rare occasions the liquid barium may pass through the stenotic area without allowing the detection of the stricture.

Fluoroscopy, which is a dynamic examination, may show partial obstructions that may have been missed by radiographic examination.

Endoscopy (without the need for a biopsy) is the most sensitive and specific exam for the diagnosis of oesophageal diseases. In animals with mild inflammation endoscopy may only reveal a mild tissue erythema, but in animals with severe inflammation it may allow the detection of erythema, erosions and sometimes even of ulcers. If gastroesophageal reflux is present the lesions are more evident in the distal oesophagus, close to the gastric cardia (lower oesophageal sphincter).

Treatment
The treatment of oesophagitis requires the elimination of predisposing factors (e.g. hiatus hernia, foreign bodies, etc.), the use of appropriate medications and of a diet with small and frequent meals, low in fat and high in protein, so as to increase the tone of the gastric cardia and minimize reflux.¹²

The drug more commonly used in the treatment of oesophagitis is sucralfate.¹³ The dose varies according to the weight of the animal (dogs <20 kg: 0.5 gr/dog; dogs >20 kg: 1gr/dog; cats: 250 mg/cat PO) and the drug is administered three times a day on an empty stomach. Sucralfate selectively binds to proteins of the eroded mucosa forming a barrier over the exposed areas so as to protect them from further damage caused by stomach acid.

H2-receptor antagonists (ranitidine, famotidine, cimetidine) inhibit the production of stomach acid and may effectively reduce oesophageal reflux. These medications may be administered either orally or parenterally. Parenteral administration is the route of choice for all patients who, because of vomiting, cannot take medications by mouth. In human medicine H2-receptor antagonists apparently also have a prokinetic activity (e.g. ranitidine, nizatidine) and appear to be more effective than drugs which do not have this effect (cimetidine, famotidine).¹⁴

Proton pump inhibitors (omeprazole, lansoprazole) are also effective as single agents, but their efficacy in reducing the production of stomach acid and oesophageal reflux improves when used in combination with H2-receptor antagonists.

Metoclopramide can be administered either orally or parenterally (subcutaneously, intravenously). Metoclopramide is less effective than cisapride in reducing oesophageal reflux and promoting gastric emptying, but cisapride has been withdrawn from the market in several countries because of cardiovascular side effects.

Other centrally acting antiemetics (e.g. maropitant, ondansetron, chlorpromazine, etc.) may be used to inhibit vomiting.

In animals that cannot feed themselves adequately because of the presence of vomiting or of oesophageal strictures the recommendation is to bypass the oesophagus and further reduce oesophageal irritation by means of a gastric feeding tube (e.g. PEG, etc.). Oesophageal and rhinoesophageal tubes are not recommended.

Systemic steroids are often used to reduce the risk of strictures, but their efficacy has never been demonstrated. It would seem, however, that the use of local steroid injections during endoscopic dilatation procedures for severe oesophageal strictures may improve the efficacy of the expansion and reduce the number of subsequent dilatations needed.¹⁵

In the above cases the use of antibiotics is controversial as their contribution to oesophageal healing has not yet been shown. When used, the recommendation is to use broad-spectrum antibiotics that may also be effective against the anaerobic bacteria which are commonly found in the oral cavity.

In the presence of strictures, dilatation procedures and endoscopic bougienage are necessary. In such cases surgery is rarely indicated and should be considered only as a last resort.

A good practice to prevent inflammation and consequent oesophagitis is to administer water after giving oral medications (especially tablets).

Treatment duration is variable and depends on the degree of inflammation present. An endoscopic evaluation performed a few days/weeks after the start of the treatment is strongly recommended as it allows to monitor the results achieved.

Prognosis
The prognosisis dependent on the severity of the oesophagitis. In mild/moderate cases medical treatment and an appropriate diet usually allow for an excellent prognosis, while in severe cases the prognosis is guarded; this in view of the possible presence of oesophageal strictures that are not always resolved with multiple endoscopic dilatations. The success rate reported for these cases is between 77 and 88%.^1,3,7

In most cases,the early treatment of oesophagitis allows for the resolution of clinical signs and prevents the formation of oesophageal strictures.

MEGAOESOPHAGUS

The term megaoesophagus is used to describe oesophageal dilatation. There are various different causes of such dilatation, including factors such as hypomotility, loss of normal peristalsis and obstruction.^16-18 Megaoesophagus may be congenital or acquired and this latter type can be distinguished into primary (idiopathic) or secondary forms.¹⁹

Etymology
From the Greek mega (large) and issofagos (oesophagus).

Pathogenesis
Megaoesophagus (congenital and acquired) can be caused by changes in the visco-elastic capacity of the oesophagus, by a lack of vagal response in the intraluminal distension of the oesophagus or by dysfunction of the afferent vagal fibres of the deglutination reflex.^17,20-23

Congenital megaoesophagus has a hereditary basis in the Wire Fox Terrier and the Miniature Schnauzer. Congenital megaoesophagus also occurs frequently in the German Shepherd dog, Great Dane, Labrador, Newfoundland, Shar-Pei and Irish Setter: although a genetic defect has been strongly suspected in these breeds, one has never been demonstrated. Congenital megaoesophagus can affect both purebred and mongrel dogs. The clinical signs may appear from 3 months to 1 year of age. Although congenital megaoesophagus is very rare in cats, the breed most predisposed to this condition seems to be the Siamese.

Acquired megaoesophagus is divided into idiopathic and secondary forms. Acquired megaoesophagus has been found in all breeds although some seem to be more predisposed (German Shepherd dog, Great Dane, Irish Setter). 

There are various causes of secondary megaoesophagus, some of which are rare.

Myasthenia gravis, the underlying cause in almost 25% of cases,^24,25 is an immune-mediated disease in which the production of antibodies against nicotinic receptors for acetylcholine (Ach) results in interruption of neuromuscular transmission and, therefore, muscle weakness. Myasthenia gravis is distinguished into congenital (rarer) and acquired forms. In its turn the acquired form is divided into two types: generalised and local. Most dogs with the generalised form have muscle weakness and megaoesophagus. In the focal form the muscle weakness predominantly affects the oesophagus, pharynx and facial muscles.

The diagnosis of myasthenia gravis is made on the basis of measurements of antibodies against the Ach receptors in the blood. It is important to appreciate that the concentration of anti-Ach antibodies is much lower in the local form than in the generalised one and, indeed, the examination may give negative results in animals with generalised acquired myasthenia gravis.²⁶ Furthermore, in the case of congenital myasthenia gravis there is a deficiency of receptors for Ach and so antibodies are often not detectable in the blood in animals with this condition.²⁶

Other disorders that can cause secondary megaoesophagus include endocrine diseases such as hypoadrenocorticism²⁷and hypothyroidism,^28,29 dysautonomia,^30,31 toxic substances,^32,33 vascular defects,³⁴ inflammation of the oesophagus and neoplasms such as thymoma,^35-38 etc. (see below).

Idiopathic megaoesophagus is rare and often fatal. It occurs spontaneously in animals from 5 to 12 years of age which present with a dilated, hypomotile oesophagus. The aetiopathogenesis is unknown but appears to be related to a lack of opening of both the upper and lower oesophageal sphincters during oesophageal distension as a result of a defect in afferent sensory innervation or in the function of the oesophageal muscles.³⁶

Clinical signs

The most common clinical sign is regurgitation. Pet owners often confuse regurgitation with vomiting, but it is crucial to distinguish between the two in order to make the correct diagnosis and, consequently, to be able to give the right treatment. Regurgitation is characterized by passive evacuation of fluids, saliva and undigested food from the oesophagus, while vomiting is accompanied by nausea and abdominal contractions.

Halitosis, ptyalism, regurgitation and weight loss are clinical signs of the megaoesophagus itself. Cough and dyspnoea are frequent complications caused by aspiration pneumonia secondary to the accidental inhalation of oesophageal matter into the lungs. In the case of secondary acquired megaoesophagus other clinical signs may be present, depending on the underlying pathology, and include generalised weakness, muscle tenderness, problems with locomotion and gastrointestinal signs.

Diagnosis
The diagnosis of megaoesophagus is made by imaging. X-raysof the neck and chest can show the dilated oesophagus containing air, fluids or ingesta. Often, however, a radio-opaque barium mealis needed to be able to exclude stenosis, obstructions or foreign bodies or, when the oesophagus appears normal, to evaluate possible hypomotility in the absence of oesophageal dilatation. Fluoroscopyis an excellent technique for evaluating oesophageal motility, but when it is not possible, radiography with a contrast agent (oesophagograms) during and immediately after ingestion of a radio-opaque meal can be used.

Signs of aspiration pneumonia include alveolar and interstitial infiltrates; the right, middle lobe is the area of the lung most frequently involved.³⁹ Oesophageal motility is better evaluated by fluoroscopy, scintigraphyandmanometry, but unfortunately these techniques are available in only very few veterinary referral centres. Oesophagoscopy is rarely necessary and should only be used in suspected cases of oesophagitis, stenosis, obstruction, foreign bodies or neoplasm.

Once the presence of megaoesophagus has been confirmed, it must then be determined whether the condition is primary or secondary.  Subjects with primary megaoesophagus often present with a very dilated oesophagus with no peristaltic movements; in cases of secondary megaoesophagus there is less dilatation and some residual motility. A recent study⁴⁰ showed a small, but statistically significant increase in the diameter of the oesophagus in non-myasthenic animals compared to myasthenic ones, but this finding is of limited importance in veterinary practice.

Further examinations that may be useful are a complete blood count, blood biochemistry profile (including electrolytes and creatinine kinase), urinalysisand, depending on the clinical signs, assays of anti-acetylcholine antibodies,an ACTH stimulation test, athyroid screenand other tests if indicated (e.g.electromyography, muscle biopsies).

Treatment
It is important to treat any underlying pathologies and severe complications, such as aspiration pneumonia and dyspnoea, which could further worsen the patient’s condition.

In animals with secondary megaoesophagus the causative disorder must be identified and treated  (e.g. myasthenia gravis with pyridostigmine or neostigmine; hypoadrenocorticism with corticosteroids and mineralocorticoids). Treatment can lead to an improvement in the clinical signs (even achieving a complete remission of the megaoesophagus) but over a variable time. It is extremely important to ensure that these patients have an adequate nutritional supply and that their vomiting and regurgitation is treated to avoid further problems.

Since there is a high risk of recurrence when drug treatment is suspended, the animal must be monitored closely and the owner encouraged to report any changes.

The type of diet chosen depends heavily on the patient’s clinical presentation and capacity to swallow. A liquid diet usually passes more easily through the oesophagus under the effect of gravity.

If the patient does not tolerate feeding by mouth, possible options are introduction of a gastric tube, percutaneous endoscopic gastrostomy (PEG) or various surgical techniques. Gastric tubes can be maintained for quite a long time (we have left a PEG tube in situ for several months in a patient with myasthenia gravis, without complications).  Oesophageal tubesare contraindicated since they can worsen the regurgitation and increase the risk of aspiration pneumonia.

Drugs to reduce the production of gastric juices (e.g. ranitidine, omeoprazole) can be used, particularly in the case that oesophagitis is suspected to be the principal cause of the megaoesophagus. 

The use of prokinetic drugs (metoclopramide, cisapride, etc.) is not advised, not only because of problems related to their action (metoclopramide) or limited availability (cisapride), but also because of a lack of documented evidence of their efficacy. Metoclopramide acts at the level of serotoninergic receptors in smooth muscles, but the canine oesophagus is formed entirely of striated muscle. Cisapride is not commercially available in various countries and it probably slows the transit of food through the oesophagus.¹⁹

Prognosis
The prognosis of animals with congenital megaoesophagus is poor, with the possibility of recovering oesophageal function varying between 20 and 40%.¹⁹ Some animals can improve with growth, particularly if the oesophagus has not irreversibly lost its elasticity.

In some cases of acquired secondary megaoesophagus, oesophageal function can be restored if the underlying cause (e.g. Addison’s disease, oesophagitis) is treated effectively, whereas in other cases (e.g. myasthenia gravis) this does not always occur.  

The prognosis of idiopathic megaoesophagus depends heavily on how early the diagnosis is made and on the response to treatment. 

The commonest reasons for treatment failure are aspiration pneumonia, persistent regurgitation, which causes debilitation of the patient, and the lack of food intake which leads to cachexia and death (usually by euthanasia because of the patient’s poor quality of life).

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