Resolution of esophageal dysmotility following treatment of nasal disease in a dog

Abstract

A 2-year-old Rottweiler dog was evaluated for cough, regurgitation, and nasal discharge, and was subsequently diagnosed with sinonasal aspergillosis and secondary esophageal disease. Following treatment of sinonasal aspergillosis, all clinical signs resolved. To the authors’ knowledge, this is the first report of resolution of esophageal dysfunction following treatment of sinonasal aspergillosis.

Megaesophagus (ME) is characterized by diffuse esophageal dilation resulting from esophageal hypomotility (1). Most canine ME cases are idiopathic as there is no underlying etiology identified despite aggressive diagnostic evaluation. Reported secondary causes of ME in dogs include myopathies, neuromuscular junction diseases, peripheral neuropathies, central nervous system lesions, infectious diseases, toxicities, endocrinopathies, obstructive diseases, esophageal neoplasia, and paraneoplastic causes (2–10). Treatment and prognosis for ME is variable, depending on the underlying causative factor as well as response to treatment and disease management. In the case of idiopathic canine ME, management options are limited, there is no cure, and most dogs are euthanized or die due to interminable regurgitation or aspiration pneumonia. The reported median survival time in this group of dogs is only 30 to 90 d (11–13). Secondary ME is potentially reversible if the underlying disease is promptly identified and addressed. This underscores the importance of recognizing causes of secondary, reversible ME.

Case description

A 2-year-old spayed female Rottweiler dog was presented to the Emergency Service of The Ohio State University Veterinary Medical Center (OSU-VMC) in January of 2015 for evaluation of a cough, regurgitation, and left-sided nasal discharge, which had been present for approximately 2 wk. There was no history of previous illness, toxin ingestion, or travel outside of Ohio, USA. Physical examination revealed fever (39.7°C), pulmonary crackles over the right lung fields, and bilateral yellow mucoid nasal discharge. No nasal depigmentation, facial deformity, or pain was detected on palpation. Airflow through both nares was present but subjectively reduced. The findings from the remainder of the physical examination including neurological examination were unremarkable.

A complete blood (cell) count showed a neutrophilia [12.0 × 10⁹/L; reference interval (RI): 2.6 to 10.8 × 10⁹/L] with a mild left-shift (0.2 × 10⁹/L; RI: 0 to 0.1 × 10⁹/L), monocytosis (1.3 × 10⁹/L; RI: 0.1 to 1.1 × 10⁹/L), and eosinophilia (1.5 × 10⁹/L; RI: 0 to 1.2 × 10⁹/L). Serum biochemistry and urinalysis were unremarkable. Survey thoracic radiographs (Figure 1) revealed a diffusely gas dilated thoracic esophagus and an unstructured interstitial pattern within the ventral aspect of the right cranial, middle, and caudal lung lobes, consistent with aspiration pneumonia and ME. Plasma cortisol concentration was 46.9 nmol/L before and 408.3 nmol/L 1 h after intravenous administration of cosyntropin (Mylan Institutional, Rockford, Illinois; USA), 5 μg/kg body weight (BW), ruling out hypoadrenocorticism. Serology for anti-acetylcholine receptor antibodies was negative [0.25 nmol/L (RI: < 0.6 nmol/L)] (Comparative Neuromuscular Laboratory, La Jolla, California, USA) and based on this finding, focal myasthenia gravis was considered unlikely. Sedatives were not utilized during the diagnostic process.

Figure 1.

Left lateral thoracic radiograph obtained during the initial examination revealing megaesophagus and aspiration pneumonia.

The dog was treated based on the diagnosis of aspiration pneumonia, consisting of intravenous poly-ionic fluids, enrofloxacin (Baytril 100; BayerDVM; Portland, Maine, USA), 10 mg/kg BW, IV, q24h, and clindamycin (Cleocin phosphate; Pfizer, New York, New York, USA), 11 mg/kg BW, IV, q12h. For management of megaesophagus and possible reflux esophagitis, the dog received omeprazole (Dexcel Pharma Technologies, Yokneam, Israel), 0.8 mg/kg BW, PO, q12h and sucralfate (Teva Pharmaceuticals; North Wales, Pennsylvania, USA) as a slurry (1 g PO, q12h), both without food and separate from other medications, and dietary management (vertical feedings and altered food consistency). Throughout hospitalization, the dog became brighter, had a good appetite, and the body temperature normalized. Regurgitation persisted throughout hospitalization and was observed frequently by the attending clinicians. The dog was transitioned to oral antibiotics and was discharged after 48 h.

Following discharge, the owner reported the dog had an improved energy level and decreased frequency of cough, though the dog continued to regurgitate and often gagged around the time of feeding. The dog continued to be fed its regular adult maintenance kibble moistened and pureed into meatball form and remained elevated during feeding and 15 min after. The nasal discharge persisted following hospital discharge, and shortly thereafter the dog began experiencing epistaxis from the left nare.

The dog was presented to the OSU-VMC Internal Medicine Service 3 wk after initial hospitalization. She remained on antibiotics, omeprazole, and sucralfate at presentation. The dog was non-febrile and had normal bronchovesicular sounds over all lung fields. There was mucohemorrhagic discharge from the left nare and she still had subjectively reduced bilateral airflow. Pain was noted on facial palpation. There was no depigmentation or facial deformity and eyes retropulsed normally. The mandibular lymph nodes were bilaterally enlarged. Fine-needle aspiration of both mandibular lymph nodes was obtained; cytology revealed moderate lymphoid and plasma cell hyperplasia with no neoplastic or etiologic agents identified. Survey thoracic radiographs were performed and showed resolving aspiration pneumonia. Megaesophagus was not apparent.

The dog underwent general anesthesia and computed tomography (CT) of the skull was performed with an 8-detector helical CT scanner (GE Lightspeed Ultra 8-Slice; General Electric, Waukesha, Wisconsin, USA) (Figure 2). There was moderate loss of the turbinates within the left rostral to mid nasal cavity and mild to moderate non-contrast enhancing, soft tissue attenuating material within the left nasal cavity. There were small gas attenuations within this material. Similar non-contrast enhancing material was within the left dorsal nasal concha, extending caudally into the left frontal sinus. There was ill-defined lysis of the left frontal bone medial to the globe and the outer aspect of the left frontal bone was thickened and sclerotic. There were multiple small, bony protuberances with thin stalks extending into both tympanic bullae. The left mandibular and medial retropharyngeal lymph nodes were enlarged. These findings were consistent with fungal rhinitis and sinusitis.

Figure 2.

Transverse CT image of the sinonasal cavity revealing soft tissue consistent with fungal rhinitis within the left frontal sinus.

Esophagoscopy was performed with a 9.4-mm flexible endoscope (GIF XQ140; Olympus America, Center Valley, Pennsylvania, USA) following the CT scan. The mucosa was grossly normal in color with no erosions. There was gastric fluid in the dependent portion of the esophagus and 1 episode of gastric reflux was observed, these were removed with suction/aspiration to allow for complete mucosal evaluation. Rhinoscopy using an 8.5-mm flexible endoscope (GIF P140; Olympus) revealed highly vascularized and inflamed mucosa throughout the left nasal cavity and nasopharynx. There were white fungal plaques covering the mucosal lining. The left nasal cavity was debrided with cup forceps and biopsies submitted for histopathology. Hematoxylin and eosin (H&E) stain showed widespread severe chronic lymphofollicular and suppurative rhinitis with ulcerations, erosions, epithelial hyperplasia, hemorrhage, fibrin, and woven new bone. No infectious agents were observed. Given clinical suspicion of aspergillosis, Grocott’s methenamine silver (GMS) and periodic-acid Schiff (PAS) stains were performed with no significant microscopic findings.

Following this procedure, omeprazole, sucralfate, and elevated feedings were continued. The dog continued to regurgitate and have occasional episodes of coughing and gagging around the times of eating. Clear to white mucoid nasal discharge persisted from the left nare but she had no episodes of epistaxis until 2 wk following this procedure. The dog was then presented in February of 2016 for reevaluation. She had normal vitals, mucoid nasal discharge from the left nare, and pain on facial palpation. Because of strong clinical suspicion of sinonasal aspergillosis, despite histopathology results, the owner elected to perform rhinoscopy, sinuscopy, and clotrimazole treatment.

The dog underwent general anesthesia the following day. She was positioned in sternal recumbency with the head and neck extended, and her fur clipped and surgically prepared. Stab incisions were made in the soft tissue structures over each frontal sinus followed by trephination using a 3.2-mm Steinmann pin. A 3.0-mm rigid endoscope (Storz) was introduced into each sinus and fungal plaques were observed in the left frontal sinus. This sinus was debrided with a curette. Many septated hyphae were seen on squash preparations of this tissue, consistent with Aspergillus spp. As previously reported (14–16), the patient was prepared for topical clotrimazole treatment by placing Foley catheters in each trephine hole, the rostral aspect of both nares, and the nasopharynx. Rolled cotton gauze was packed around the nasopharyngeal catheter as well. Over the course of 60 min, the dog had 30 mL of 1% clotrimazole cream infused into each frontal sinus and 60 mL of 1% clotrimazole solution infused into the nasal cavities. The dog was rotated every 15 min in an effort to ensure the clotrimazole contacted all surfaces. At the end of the procedure the cuffs of the Foley catheters were deflated, all catheters and packing material were removed, and the dog was extubated with a smooth anesthetic recovery. Overnight, the patient was stable apart from experiencing 2 episodes of regurgitation. The following morning she was febrile (40.4°C) with normal bronchovesicular sounds auscultated. Survey thoracic radiographs were performed and were consistent with aspiration pneumonia with no apparent megaesophagus. The dog was treated with oral enrofloxacin and clindamycin at the previous doses and was discharged the following morning.

Shortly after hospital discharge the dog had markedly reduced nasal discharge and the regurgitation resolved. However, 4 wk later epistaxis returned and the dog was re-evaluated in March of 2016 and the owner elected to have another treatment. The procedure was repeated as outlined above and the dog recovered without complications. Following discharge there was minimal nasal discharge and no epistaxis. The dog was re-evaluated in August of 2016 and had normal vitals on presentation. She was overweight with an otherwise unremarkable physical examination. Survey thoracic radiographs and a 4-phase barium esophagram were performed. There was no evidence of megaesophagus or esophageal dysmotility. At the time of manuscript submission the dog remained clinically normal.

Discussion

Secondary causes of canine ME and esophageal dysmotility have been well-described (2–10) and have not previously been associated with nasal disease, or sinonasal aspergillosis specifically, in dogs. In this report, we demonstrated Aspergillus spp. in the frontal sinus of a dog with concurrent ME and esophageal dysmotility, and resolution of ME and esophageal dysmotility following treatment of aspergillosis. The findings observed in the dog herein suggest that sinonasal disease should be included in the differential diagnostic categories of secondary ME in dogs, similar to cats, when clinical signs indicate a high suspicion of nasal involvement.

The reason for the correlation between sinonasal disease and ME is unknown. One potential explanation is the previously documented association between gastroesophageal reflux and upper airway obstruction (17,18). There is still debate as to whether upper airway obstruction causes gastroesophageal reflux or the gastroesophageal reflux results in upper airway obstruction, with evidence pointing to both options being possible (17,19–22). The mechanism by which upper airway obstruction may result in development of gastroesophageal reflux is due to the development of a thoracoabdominal pressure gradient sufficient to disrupt the normal function of the lower esophageal sphincter (23,24). In 1 study looking at this phenomenon in dogs, there was a correlation between degree of negative inspiratory pressure and severity of gastroesophageal reflux (24). Ultimately, if esophagitis develops from gastroesophageal reflux caused by the airway obstruction, this can result in secondary esophageal dysmotility and/or ME (25).

The dog in this study did not have evidence of complete airflow obstruction or aerophagia based on physical examination and serial imaging. However, if the mechanism resulting in this phenomenon is obstructive, the exact degree of airway obstruction required to achieve gastroesophageal reflux with secondary esophageal dysmotility/ME remains unknown. In this report, it is still a possibility that a partial obstruction and altered airflow dynamics resulted in the secondary dysmotility and ME. There were no gross abnormalities noted on esophagoscopy or biopsies of the esophagus; however, it has previously been documented that both of these tests (mucosal appearance and esophageal histopathology) are not sufficient to allow for confirmation or exclusion of esophagitis as a diagnosis (26,27).

There are other examples of upper airway disease and its relationship to secondary esophageal disease, including ME, in the veterinary literature. Recently, there were reports of upper airway obstruction in the form of nasopharyngeal polyps and nasopharyngeal stenosis causing ME in cats (5–7). Following extraction of the polyps and balloon dilatation of the stenosis the ME resolved in these patients, suggesting once again an obstructive mechanism. In contrast to these previous reports on feline patients, this is to the author’s knowledge, the first report of this syndrome occurring in a canine patient. As a result, in animals presenting with concurrent signs related to nasal disease and esophageal dysfunction, consideration should be given to the possibility of a cause-effect relationship between the 2 processes. This will ensure all possibilities and treatment options are examined for the patient’s benefit and long-term outcome.

The clinical description of the dog reported here is largely consistent with that of the typical presentation and signalment associated with sinonasal aspergillosis in dogs, with the exception of the clinical signs related to esophageal dysfunction (28). It was presumed that the dog in this description suffered from sinonasal aspergillosis as a primary process with the airway obstruction leading to esophageal dysfunction as described, and subsequently the related complications (namely, regurgitation and aspiration pneumonia). An alternative explanation, is that the dog initially suffered from primary esophageal disease, which resulted in aspiration pneumonia and caused airway inflammation. The resulting airway inflammation then allowed for an opportunistic sinonasal fungal infection. In canine sinonasal aspergillosis, there has been difficulty in establishing a link between infection and an immunocompromised state and the reason for many sinonasal aspergillosis cases remains unknown (29,30). There are reports in the literature of secondary sinonasal aspergillosis in dogs related to structural and inflammatory processes (e.g., facial trauma, foreign bodies, and dental disease), which may support this possibility (31,32). However, the secondary infection explanation was considered less likely in this case, given the resolution of clinical signs after nasal disease treatment.

Another explanation for multiple organ systems involved would be systemic aspergillosis. In humans, aspergillosis and other fungal infections (candidiasis) have been reported to infect the esophagus primarily (33,34). This is typically an invasive form of the fungus in which the individual also suffers from a systemic, immunocompromised condition (35). Esophageal biopsy and histopathological examination would have been required to exclude Aspergillus within the esophageal wall in the patient reported here. However, esophageal infection was considered unlikely in the dog described here based on gross appearance of the esophagus during endoscopy, the relative rarity of disseminated or invasive aspergillosis in both human and veterinary medicine, and resolution of disease without the use of systemic antifungals. The dog reported here responded to topical clotrimazole instilled into the upper airways alone.

Interestingly, during the initial evaluation of this dog, a diagnosis of aspergillosis was not made conclusively, although the diagnostic findings were largely supportive. We consider the lack of diagnosis of aspergillosis on initial evaluation most likely a diagnostic failure rather than lack of disease presence. If sinuscopy had been performed on initial evaluation, it may have increased the chances of a diagnosis at the earlier time points in this dog’s clinical course. It is also interesting that the ME was only present during the initial evaluation, despite the persistence of signs of esophageal dysfunction until complete resolution of the nasal disease. There are multiple reasons why this may have been observed and, the most likely explanation may be that it has to do with a variable degree of nasal obstruction present during the course of treatment. At the initial evaluation, the dog had not received any therapies to treat the upper respiratory, lower respiratory, or esophageal clinical signs and/or disease. Following initial evaluations, multiple treatments were instituted that may have affected the degree of nasal obstruction and subsequently the degree of radiographically apparent esophageal dysfunction. First, during the routine rhinoscopy a nasal flush was performed as standard procedure which may have cleared obstructive mucus and debris from the nasal passages. Second, treatments were directed at aspiration pneumonia. Aspiration pneumonitis can affect the upper airways and presumable this secondary upper airway inflammation decreased following initiation of treatment. Third, the antibiotics administered for aspiration pneumonia may have treated secondary infections in the nasal passage and resulted in decreased obstructive debris and inflammation. And lastly, and potentially most importantly, the dog was prescribed therapies aimed at the management of esophagitis at the initial visit. As mentioned, this is central to the upper airway obstructive theory and may have improved the degree of ME and esophageal dysmotility.

Spontaneous resolution of ME in dogs has been demonstrated in dogs with myasthenia gravis, hypoadrenocorticism and primary hypothyroidism following treatment (2,9,10). ACh receptor antibody titers were normal, making myasthenia gravis an unlikely explanation. Adrenocorticotropic hormone (ACTH) stimulation testing eliminated the possibility of atypical hypoadrenocorticism. Testing for thyroid dysfunction was not performed in this case due to the concerns for the influence of pneumonia on the thyroid axis and euthyroid sick syndrome. The remainder of known secondary causes of acquired ME were not specifically tested for in this case. However, it is unlikely that ME in the dog secondary to those differentials, or hypothyroidism, would resolve spontaneously without treatment.

This is the first reported case of sinonasal aspergillosis and secondary ME and esophageal dysmotility in the veterinary literature. Importantly, it adds to the literature linking upper respiratory disease with an esophageal manifestation similar to what has been reported in the feline species, notably in this case for the first time in a dog. From a clinical perspective, it is also one of few known disease processes associated with resolution of ME and esophageal dysmotility following treatment. This is extremely important in a disease in which diagnosis of primary, idiopathic ME often results in euthanasia of the animal due to prognosis, complications, and/or owner concerns with disease management. In this case, the dog’s age at presentation, concurrent nasal discharge, as well as waxing and waning diffuse ME were key to increasing our suspicion that this was likely a secondary case of ME and made primary, idiopathic ME less likely. Based on the findings of this case, should a dog present with ME and concurrent sinonasal disease, treatment of the sinonasal disease should be considered, as long-term prognosis can be good if the sinonasal disease is treatable and the ME is a secondary process. CVJ