A 7-year-old neutered male Saint Bernard weighing 54 kg (118.8 lb) was referred to the Mississippi State University Animal Health Center for evaluation because of a 6-month history of coughing, intermittent cyanotic appearance as described by the owner, gagging, change of phonation, and excessive panting. Additional history included intermittent episodes of vomiting, diarrhea, and retching throughout the dog's life. The dog was current on vaccinations and was housed indoors with 1 other dog. The most recent episode of vomiting was prior to initial evaluation, but the owner could not specify the date and was not concerned with this clinical sign. The referring veterinarian had begun treatment approximately 2 weeks prior with prednisone (0.4 mg/kg [0.18 mg/lb], PO, q 12 h), hydrocodone (0.1 mg/kg [0.05 mg/lb], PO, q 12 h), and theophylline (9 mg/kg [4.1 mg/lb], PO, q 12 h), resulting in some initial clinical improvement; however, clinical signs returned and persisted despite ongoing treatment. No further diagnostic tests or treatments were initiated prior to referral for suspected laryngeal paralysis. Discontinuation of these medications was recommended at the initial evaluation, with the prednisone requiring a tapering dose of a 25% decrease weekly.
On initial physical examination, the dog was bright, alert, and well hydrated, with a body condition score of 3 of 5. Rectal temperature was 39.1°C (102.4°F), and pulse was 88 beats/min. Findings on auscultation of the heart and lungs were unremarkable, with no pulse deficits or arrhythmias noted. The dog was panting and had pigmentation of the oral mucosa, which may have resulted in what the owner reported as cyanosis. There was no stridor heard during the examination, so laryngeal paralysis was a less likely differential diagnosis.
Results of a CBC, serum biochemistry analysis, and urinalysis were unremarkable. Total thyroxine concentration (1.7 μg/dL) was within the reference range. Right lateral, dorsoventral, and ventrodorsal radiographs of the thorax were obtained, revealing a moderate bronchial pattern throughout the lung fields indicative of chronic inflammatory, allergic, or infectious bronchitis. A single lateral radiographic view of the cervical soft tissue was unremarkable.
A laryngeal examination performed under a light plane of anesthesia with administration of propofol (3 mg/kg [1.36 mg/lb], IV, titrated to effect) and doxopram (2.2 mg/kg [1 mg/lb], IV) revealed no evidence of laryngeal paralysis; however, there was marked thickening and erythema of the epiglottis and arytenoids (Figure 1). In addition, small areas of gross ulceration of the surrounding pharyngeal mucosa were observed. An endotracheal tube was placed, and anesthesia was maintained with isoflurane in oxygen; bronchoscopy with a 1-m flexible endoscope and a bronchoalveolar lavage were performed. The only abnormalities noted on bronchoscopy were changes in the distal trachea similar to those observed in the larynx and surrounding pharyngeal tissues. The bronchoalveolar lavage fluid was submitted for cytologic evaluation and bacterial culture. There were no abnormalities seen in the bronchoalveolar lavage fluid, and the culture was negative. Following the bronchoscopy, fluoroscopy of the trachea was performed to determine whether any tracheal collapse or dynamic pathological changes were present that may have been missed during bronchoscopy. Findings included an area of soft tissue opacity in the area of the esophagus adjacent to the diaphragm believed to be due to gastric refluxate residing within the esophageal lumen. Because of these findings, esophagoscopy was performed and revealed diffuse hyperemia, erosions, and ulcerations throughout the esophagus with a focally more severe area adjacent to the lower esophageal sphincter. Once the dog was fully recovered from anesthesia, additional esophageal fluoroscopy and a barium swallow esophogram were performed. Results of these tests were consistent with gastroesophageal reflux. Barium passed normally into the esophagus and into the stomach, but following repeated swallows, the bolus immediately refluxed back into the distal esophagus for several seconds before moving back into the stomach. Retention of barium along the esophageal mucosal folds was also noted, consistent with the suspected esophagitis visualized on esophagoscopy (Figures 2 and 3). A tentative diagnosis of laryngeal dysfunction as a result of gastroesophageal reflux was made on the basis of the intermittent dysphagia, dysphonia, and panting.
Photograph of the larynx of a 7-year-old neutered male Saint Bernard evaluated because of a 6-month history of coughing, gagging, change in phonation, excessive panting, and chronic intermittent vomiting and diarrhea. Note generalized erythema of the soft palate and epiglottis; also note the ulcerative area on the left side of the larynx (thick arrow) with smaller pinpoint ulcerative lesions of the pharynx (thin arrows).
Citation: Journal of the American Veterinary Medical Association 240, 9; 10.2460/javma.240.9.1100
Right lateral esophogram of the dog in Figure 1. Notice that the proximal aspect of the esophagus is coated in residual barium throughout the length.
Citation: Journal of the American Veterinary Medical Association 240, 9; 10.2460/javma.240.9.1100
Right lateral esophogram of the dog in Figure 1. Notice that the distal aspect of the esophagus has streaking of barium coating the lumen (arrows); the barium bolus is present in the stomach.
Citation: Journal of the American Veterinary Medical Association 240, 9; 10.2460/javma.240.9.1100
The patient in this report had been vomiting intermittently for several years. Following our recommendation for a full gastroduodenoscopy to evaluate the cause of the chronic vomiting, the dog's owner elected empiric and palliative treatment. Although the role of Helicobacter infection in dogs has not been established, it is considered the primary cause of chronic gastritis in humans.1,2 The patient was prescribed a 2-week course of combination antimicrobial and antacid treatment, including bismuth PO every 8 hours, metronidazole (10 mg/kg [4.5 mg/lb], PO, q 24 h), amoxicillin (16 mg/kg [7.3 mg/lb], PO, q 12 h), sucralfate (1 g, PO, q 12 h in a slurry), famotidine (0.5 mg/kg [0.23 mg/lb], PO, q 12 h for the first 4 days), and omeprazole (0.37 mg/kg [0.168 mg/lb], PO, q 24 h). This was considered the most effective treatment on the basis of guidelines for the treatment of Helicobacter infections and GERD in human patients.2
The owner reported complete resolution of clinical signs within a week after discharge; however, the dog began vomiting small amounts of bile-tinged fluid after the medications were discontinued. Another 2-week course of the original treatment was administered with only minimal improvement, at which time the owner consented to additional diagnostic procedures to investigate the cause of the chronic vomiting.
On readmission to the teaching hospital, preanesthetic blood testing, including measurement of PCV and total solids and serum biochemical analysis, was performed and results were again unremarkable. All of the dog's respiratory clinical signs had resolved; thus, the diagnostic tests were focused on the gastrointestinal signs. Abdominal radiographs revealed gas-filled loops of intestines and a large amount of feces within the colon. Abdominal ultrasonography revealed uniformly thickened and hypoechoic gastric mucosa with discernible layering intact; the remainder of the abdominal ultrasonographic findings were within normal limits. Anesthesia was induced with propofol, and laryngoscopy revealed normal laryngeal tissues. The previously noted ulceration and hyperemia of the arytenoids and epiglottis had resolved. The dog was intubated and maintained on isoflurane anesthesia. Esophagoscopy revealed a mildly dilated lower esophageal sphincter, but no erythema or inflammation of the mucosal surface was noted. Gastroduodenoscopy was performed with a 1- and 1.6-m endoscope to obtain 10 to 12 biopsies of the gastric and duodenal walls, each through a 3-mm biopsy channel. The gastric mucosa, pylorus, and duodenum appeared grossly normal. A moderate amount of gastric fluid and ingesta was noted, despite the fact that food had been withheld for > 12 hours. All biopsy samples were evaluated by a board-certified pathologist. Biopsies of the gastric wall revealed an unremarkable gastric mucosa with colonization of spiral bacteria, suspected to be Helicobacter sp. Biopsies of the duodenal wall revealed severe lymphocytic and plasmacytic enteritis. A diagnosis of inflammatory bowel disease and Helicobacter gastritis was made. The endoscopic evaluation of the dog's larynx and esophagus demonstrated that the laryngitis and esophagitis had resolved with treatment. The combination antimicrobial and antacid treatment described for the presumed Helicobacter infection was continued. Prednisone treatment (1 mg/kg [0.45 mg/lb], PO, q 12 h) as well as a commercially available novel protein diet of venison and potato was initiated. The patient had complete resolution of all clinical signs related to respiratory and gastrointestinal disease at the time of follow-up 4 months later.
Discussion
To our knowledge, there are no reports of GERD as a causative factor in laryngeal disease in the veterinary literature, although there has been documentation of the association of secondary gastroesophageal disease with primary airway abnormalities in brachycephalic breeds.3 Gastroesophageal reflux is the most common cause of esophagitis in animals and humans,4 and there has been increasing evidence demonstrating an association between gastroesophageal reflux and laryngeal dysfunction in human medicine since the 1960s.5–7 The cause of this dog's intermittent episodes of increased respiratory effort and excessive panting was extensively investigated in an attempt to rule out any disease that may have been causing the chronic laryngeal signs. This involved a direct laryngeal examination and investigation into the lower airways, including bronchoscopy and a bronchoalveolar lavage. Lower airway disease was excluded as a causative factor because of the findings on bronchoscopy and bronchoalveolar lavage; however, there was evidence of laryngeal irritation and inflammation. Gastroesophageal reflux disease is associated with chronic laryngitis in up to 60% of affected human patients.8,9 This is referred to by different names, including reflux laryngitis, extraesophageal reflux, and laryngopharyngeal reflux.8,9
Gastroesophageal reflux was diagnosed in the patient in this report via an esophogram documenting refluxate entering the esophagus, esophagoscopy, and gastroduodenoscopy.6,7 The most consistently recognized indicator of a diagnosis of GERD involves a clinical response to empirical treatment with an antacid, and in this dog, the clinical signs initially resolved with administration of famotidine and omeprazole. Also, after 4 weeks of antacid treatment, this dog's laryngeal inflammation and esophagitis had resolved on the endoscopic examination.
The dog in the present report had coughing, dysphagia, change in phonation, and excessive panting, which were originally thought to be related to laryngeal paralysis. This diagnosis was subsequently ruled out on a direct laryngeal examination. This dog developed some of the extraesophageal clinical signs of GERD, including hoarseness, dysphonia, chronic cough, dyspnea from laryngospasm, and dysphagia.10 One possible cause for this dog's dyspneic episodes was laryngospasm, which is a sudden prolonged closure of the vocal cords in response to a noxious stimulus. Previous studies5,11 indicate that laryngospasm may be associated with acidification of the pharynx. Typical symptoms in humans with GERD include heartburn and regurgitation,12 but the sensation of chest pains and heartburn may be impossible to elucidate in animals.
There are 2 pathophysiologic mechanisms suspected to be responsible for causing extraesophageal clinical signs associated with GERD: aspiration of microscopic gastric contents with direct tissue exposure and heightened vagal reflexes.6,13,14 The accumulation of gastric contents in the distal esophagus is thought to stimulate acid-sensitive receptors, which can lead to a vagal reflex, causing noncardiac chest pains, coughing, and bronchoconstriction.14
Several animal studies5,9,10 have investigated the role of refluxed gastric substances in laryngeal disease. One experimental study9 in dogs specifically identified pepsin and common bile acids as the most injurious agents affecting laryngeal tissue. That study9 showed that exposure of vocal cords to gastric juices resulted in the appearance of thickened and inflamed tissues with ulcers and granulation tissue. These findings support the idea that these disease processes may be important in veterinary patients.
A confounding factor in the clinical signs in the dog in the present report was the presence of chronic intermittent vomiting and diarrhea, which were later attributed to inflammatory bowel disease. These clinical signs were mild at initial evaluation when the dog was being administered the prescribed steroids from the referring veterinarian, but the vomiting worsened once the steroid treatment was discontinued. Regardless of the short period of increased vomiting, the dog's respiratory clinical signs and the gross appearance of the larynx improved with antacid treatment. The use of antacids is the mainstay of treatment for laryngeal disease associated with GERD, and the clinical response to this treatment is the most consistently recognized indicator of a GERD diagnosis.8,12 Later, the dog also responded clinically with less vomiting and diarrhea to treatment aimed at a Helicobacter infection and inflammatory bowel disease. Treatment for both GERD and inflammatory bowel disease resulted in resolution of the dog's clinical signs. It is important to note that esophagitis can occur from chronic vomiting or from gastroesophageal reflux, as can laryngeal changes. However, only mild intermittent vomiting episodes were reported at initial evaluation when the laryngeal changes were marked, and microaspiration of acidic gastric contents is known to produce the observed laryngeal pathological changes.6,9,13 The severity of laryngeal changes noted in the dog's laryngeal tissues were unlikely to have occurred from a few isolated episodes of vomiting.
A single clinical report does not fully elucidate the relationship between laryngeal dysfunction and GERD, and further studies are necessary to establish a causative relationship. This potential association could be important in evaluating patients with concurrent respiratory and gastrointestinal clinical signs. Consideration of the finding that the dog in the present report did not respond clinically until the underlying gastroesophageal reflux was treated with the appropriate antacid treatment may be important in the treatment of these patients. The present report may be helpful in designing future studies examining the basis of this disease process in veterinary patients.
ABBREVIATION
| GERD | Gastroesophageal reflux disease |
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