Introduction

Sialadenosis is a rare, noninflammatory and nonneoplastic condition of the salivary glands in dogs, in which the affected glands become enlarged.^1,2 Clinical signs include retching, loss of appetite, and hypersalivation.^3,4 Although the etiology of sialadenosis remains unknown, treatment with phenobarbital may lead to a rapid resolution of the clinical signs, which may support the theory that it is a form of limbic epilepsy.^2,4–7

To the authors’ knowledge, development of presumptive sialadenosis, responsive to phenobarbital, has never been reported following an oropharyngeal stick injury or other cervical trauma in the dog.

Case Report

A 3 yr old female spayed Labrador retriever was presented to the surgery department of Willows Veterinary Centre and Referral Service for management of an oropharyngeal stick injury that occurred 6 wk earlier.

At the time of the initial oropharyngeal stick injury, yelping, coughing, gagging, and bleeding from the mouth were reported along with the development of a severe cervical swelling. The referring veterinarian performed cervical radiographs and an examination of the oral cavity. Two oral lacerations were noticed on the right side of the oropharynx, but a foreign body could not be identified. Subsequently, the dog was hospitalized overnight and medical management was initiated with metronidazole^a 18 mg/kg per os (PO) q 12 hr, potentiated amoxicillin^b 14 mg/kg PO q 12 hr, prednisolone^c 0.52 mg/kg PO q 24 hr, maropitant^d 2.1 mg/kg PO q 24 hr, and omeprazole^e 0.7 mg/kg PO q 24 hr. The dog initially responded to medical management, but the cervical swelling recurred when the prednisolone dose was decreased. Prednisolone was discontinued 5 days before referral.

On presentation to our referral center, 45 days after the initial stick injury, the dog was receiving potentiated amoxicillin^b, omeprazole^e, and paracetamol^f 10 mg/kg PO q 12 hr as prescribed by the referring veterinarian. On physical examination, there was marked hypersalivation, a firm 10 to 15 cm swelling in the right submandibular area, and right-sided Horner syndrome. Cardiovascular parameters, thoracic auscultation, and abdominal palpation were within normal limits. Rectal temperature was 38.8°C. In-house hematology and biochemistry testing were within normal limits. An in-house coagulation panel was performed; the prothrombin time was 19 s and hence on the upper normal limit (range 14–19), and the activated partial thromboplastin time was 142.5 s (range 75–105) and hence moderately prolonged.

Given the suspicion of a cervical foreign body, an oral and laryngeal examination and cervical computed tomography (CT) scan under general anesthesia were recommended. The dog received medetomidine^g 0.005 mg/kg IV and methadone^h 0.3 mg/kg IV as premedication, induction of general anesthesia was performed with propofolⁱ 0.9 mg/kg IV, and maintenance with isoflurane^j. Laryngeal examination under a light plane of anesthesia revealed right-sided laryngeal paralysis.

The patient was positioned into sternal recumbency for the CT scan of the head and neck. Images were acquired using a 64-slice multidetector row CT^k. Pre- and postcontrast images were acquired; postcontrast images were acquired after IV administration of iodinated contrast medium, iohexol^l 600 mg I/kg, by pressure injector.

CT findings included a 10 cm, stick-shaped foreign body in the center of a right-sided cranial cervical abscess (Figures 1, 2). A fistulous tract could be followed from the abscess to the level of the right tonsillar crypt. A right-sided epihyoid bone fracture and right medial retropharyngeal lymphadenomegaly were also present. The right mandibular salivary gland appeared hypoattenuating and enlarged with surrounding fat stranding, most suggestive of either a parenchymal mucocele or sialadenitis (Figure 2).

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Under the same general anesthetic, surgical exploration of the neck was performed through a ventral midline approach. The right-sided cervical abscess was identified just adjacent to the vagosympathetic trunk and carotid artery. After the abscess was opened, a 10 cm wooden stick was retrieved. Tissue samples were collected for culture and sensitivity testing, and lavage of the abscess cavity was performed with sterile saline. Subsequently, the right mandibular salivary gland was resected and submitted for histopathology. An active suction drain was placed in the abscess cavity before wound closure.

Postoperatively, the dog received methadone^h 0.2 mg/kg IV q 4–6 hr overnight, after which buprenorphine^m 0.02 mg/kg IV q 6–8 hr was administered for 24 hr. IV potentiated amoxicillinⁿ 20 mg/kg IV q 8 hr was administered for 36 hr followed by oral potentiated amoxicillin^b 18.2 mg/kg PO q 12 hr. Furthermore, omeprazole^o 1 mg/kg IV q 24 hr, tranexamic acid^p 10 mg/kg IV q 8 hr, paracetamol^q 10 mg/kg IV q 8 hr, meloxicam^r 0.1 mg/kg IV q 24 hr, and maropitant^d 1 mg/kg IV q 24 hr were administered.

Although cervical swelling and hypersalivation persisted postoperatively, the dog showed a good initial recovery. After 4 days, she was eating well and was bright enough to be discharged with potentiated amoxicillin^b 18.2 mg/kg PO q 12 hr, paracetamol^s 9 mg/kg PO q 12 hr, and omeprazole^t 1.45 mg/kg PO q 24 hr.

Histopathology of the right mandibular salivary gland was consistent with inflammation, necrosis, and possible sialadenitis without any evidence of neoplasia. Both aerobic and anaerobic bacterial culture of the cervical abscess tissue sample were performed and yielded a heavy mixed growth of Enterococcus spp. (sensitive to potentiated amoxicillin and resistant to fluoroquinolones) and Escherichia coli (sensitive to fluoroquinolones and resistant to potentiated amoxicillin). According to a telephone conversation with the owner, the dog had been improving since discharge with a significant decrease in swelling and hypersalivation. Based on the bacterial culture results, marbofloxacin^u 2.2 mg/kg PO q 24 hr was dispensed for 3 wk and the course of potentiated amoxicillin was also extended to achieve a duration of 4 wk in total. The owner started to administer marbofloxacin 1 wk after discharge.

Four weeks postoperatively and 3 wk following the start of marbofloxacin administration, the dog was presented to our referral center again because of hypersalivation since receiving marbofloxacin. The cervical swelling and right-sided Horner syndrome had resolved, and the hypersalivation had been managed with maropitant^d 2.1 mg/kg PO q 24 hr with limited improvement. An adverse reaction to marbofloxacin was suspected, but after discontinuation of marbofloxacin, the hypersalivation persisted and worsened over the next few weeks. The dog presented again 9.5 wk postoperatively with a complaint of hypersalivation, repeated swallowing attempts, vomiting once daily, lethargy, and a significant weight loss of 2 kg in 2 wk. At that point, the dog had not received any antimicrobial medication or other medication for 4 wk.

On physical examination, marked hypersalivation was present. No cervical swelling was detected, but mild pressure over the submandibular area triggered gagging, swallowing attempts, and regurgitation. Cardiovascular parameters, thoracic auscultation, and abdominal palpation were otherwise unremarkable. Rectal temperature was 39.3°C. In-house hematology and biochemistry indicated mild dehydration, but otherwise, the values were within normal limits.

Differential diagnoses for the clinical signs included persistent cervical foreign material, a recurrent abscess, or salivary gland disease. A follow-up CT scan and oral examination under anesthesia were recommended. The dog was anesthetized with a similar protocol as previously described. No abnormalities were detected on oral examination, and the right-sided laryngeal paralysis had resolved. A CT scan of the head and neck was obtained using the same protocol as described above. CT findings included slight enlargement and moderate heterogeneous contrast enhancement of the right parotid, zygomatic, and molar salivary glands, consistent with either sialadenitis or sialadenosis. The previous right-sided cervical cellulitis and abscess had resolved, and there was no evidence of any cervical swelling or residual foreign material.

Based on the clinical signs and CT findings, a presumptive diagnosis of sialadenosis was made and empirical treatment was started with phenobarbital^v 3 mg/kg IV q 12 hr. The dog was hospitalized on IV fluid therapy and also received maropitant^d 1 mg/kg IV q 24 hr. Twenty-four hours later, the regurgitation and hypersalivation had resolved and the dog appeared bright and was eating well. The dog was discharged on oral phenobarbital^w 2.4 mg/kg PO q 12 hr for 6 wk, with the aim to slowly taper down the phenobarbital thereafter.

Two months after the initiation of the phenobarbital treatment, based on a telephone conversation with the owner, the dog remained asymptomatic. The dose of phenobarbital had been decreased to 1.6 mg/kg twice daily 6 wk after the start of the course, and it was gradually tapered down every 6 wk until it was stopped 6 mo after initiation of treatment. At the time of writing, based on email communication with the owner, the dog had been off medication for 5 months without any recurrence of clinical signs, including no regurgitation, no cervical swelling, and no clinical signs of Horner syndrome.

Discussion

This report describes the development of presumptive sialadenosis following a chronic oropharyngeal stick injury in a dog. To the authors’ knowledge, it is the first time in the veterinary literature that presumptive sialadenosis has been reported in a dog secondary to a cervical trauma.

Oropharyngeal stick injuries can present acutely or chronically, with chronic cases denoting all injuries presented more than 7 days after the initial trauma.⁸ Accordingly, the case described here was considered a chronic oropharyngeal stick injury. The main clinical signs of chronic oropharyngeal stick injuries result from the presence of foreign material and abscess formation, with or without a discharging sinus.^8,9 In this case, the dog initially presented with a cervical swelling and hypersalivation, which were attributable to the presence of a cervical abscess, a large foreign body, and traumatized right mandibular salivary gland. At the time of the initial presentation and CT scan, there was no evidence of generalized salivary gland disease. The clinical signs initially resolved following surgical management of the cervical abscess and right mandibular sialadenectomy, but the hypersalivation subsequently returned.

Recurrence of the cervical abscess or persistence of foreign material was considered possible. However, the CT scan documented resolution of the previous cervical abscess and no evidence of further focal inflammation or persistent foreign material, and the rapid and complete response to phenobarbital was supportive of either sialadenosis or noninfectious sialadenitis as a cause for the clinical signs.^2–4

Sialadenosis is defined as a bilateral, uniform, noninflammatory, nonneoplastic condition of the salivary glands, in which the affected glands are enlarged and most often nonpainful.¹ The mandibular salivary glands are most often affected, and the etiology remains unknown.¹ Clinical signs include frequent retching or gulping, lip-smacking, loss of appetite, weight loss, exercise intolerance, and hypersalivation.^3,4 The diagnosis of sialadenosis is usually based on exclusion of other causes of salivary gland enlargement such as neoplasia, sialadenitis, sialolithiasis, and sialoceles.^2,3 Histopathology of the resected right mandibular gland showed inflammatory changes, but these were associated with the trauma to the surrounding tissues that occurred as a consequence of the stick injury. Cytology or histopathology of the remaining enlarged salivary glands was not performed. However, CT appearance of the affected glands was not consistent with neoplasia, sialolithiasis, or sialocele formation. Sialadenosis and noninfectious sialadenitis were both considered, and clinical signs, imaging features, and presumed pathophysiology overlap for these two conditions.^{5–7,10–12} Furthermore, both conditions respond to phenobarbital administration. Cytology can be considered but is not specific in cases of both sialadenosis and sialadenitis. Histopathology would have been required to make a final diagnosis of sialadenosis or noninfectious sialadenitis. In the case of sialadenosis, the affected salivary glands show minimal to no histological changes.¹

Given the very rapid and complete response to phenobarbital administration, histopathology was not performed. A presumed diagnosis of sialadenosis was therefore made.

In dogs affected by sialadenosis, surgical resection of the enlarged glands, glucocorticoids, or antibiotic administration does not improve clinical signs, but treatment with phenobarbital may lead to a rapid improvement of the clinical signs.^3,6 A full resolution of clinical signs is often noted within 1 wk, and a decrease in size of the affected salivary glands is noticeable within 2–4 wk.⁶ Although affected dogs can often be successfully weaned off the phenobarbital after an extended course, there have also been reports of relapse of the clinical signs, and some dogs may require lifelong treatment.^1,6,7 Other drugs such as oral pilocarpine have been used to treat sialadenosis in dogs, but beneficial effects were only reported inconsistently.³

In this case, near-complete resolution of the clinical signs (hypersalivation, vomiting, lethargy, and lack of appetite) occurred very rapidly, 24 hr after initiation of the phenobarbital treatment, and complete resolution of the clinical signs was reported after 1 wk. To reduce the risk of relapse, the dog received a prolonged tapering course of phenobarbital, starting at 3 mg/kg, which was similar to previous reports.² The phenobarbital was discontinued after 6 mo, and there was complete resolution of the clinical signs and no evidence of relapse 5 mo after discontinuation of treatment.

The etiology of sialadenosis and noninfectious sialadenitis remains unclear. In people, sialadenosis can be attributed to a chronic overstimulation such as in patients with bulimia or can occur in association with autonomic neuropathies (type 2 diabetes, alcoholism).⁴ In dogs, because of the response to phenobarbital, both sialadenosis and noninfectious sialadenitis have been described as an unusual form of limbic epilepsy.⁴ In some dogs, esophageal abnormalities and cricopharyngeal dysphagia have also been reported concurrently with sialadenosis or noninfectious sialadenitis.^4,5 Although the neurological pathways involved are complex and are not fully understood, this could support a link to hyperstimulation of the afferent vagal nerves. The nuclei of the solitary tract (NTS) are a series of nuclei forming a vertical column of gray matter in the medulla oblongata.¹³ Nerve fibers from the facial, glossopharyngeal, and vagus nerve run through the center of and innervate the NTS.¹³ The NTS also projects to parts of the limbic system and forms circuits that contribute to autonomic regulations.¹³ A low pH in the esophagus or pharynx activates vomiting areas such as the NTS and area postrema through afferent vagal nerves.¹⁴ In turn, the NTS is anatomically connected to the superior salivary nucleus of the medulla oblongata, which gives rise to the chorda tympani nerve, an efferent pathway that innervates the salivary glands.¹⁴ The anatomical proximity of the NTS, superior salivary nucleus, and limbic system could explain the relationship between esophageal abnormalities, afferent vagal nerve stimulation, and sialadenosis.

Sialadenosis has been described in a dog after a surgery that did not involve the cervical region, but this type of sialadenosis was transient and self-limiting and resolved after 2 hrs.¹⁵ There is one report of sialadenosis in association with an esophageal foreign body in one dog, but the authors presumed that the foreign body became lodged secondary to the esophageal dysfunction and did not cause the sialadenosis.⁶

Sialadenosis, or noninfectious sialadenitis, has never been described in relation to an oropharyngeal stick injury or other trauma in the cervical region. The presumptive sialadenosis in this case could have been unrelated to the oropharyngeal stick injury, although the timing of the clinical signs and involvement of the salivary glands ipsilateral to the stick injury suggest a correlation. Esophageal abnormalities were not observed, although a fluoroscopic swallowing study was not performed and esophageal dysmotility could therefore not be fully ruled out. The dog initially presented with a chronic oropharyngeal stick injury and large cervical abscess, and with temporary unilateral laryngeal paralysis and Horner syndrome suggestive of trauma to or inflammation of the ipsilateral vagosympathetic trunk and/or recurrent laryngeal nerve. Although it remains hypothetical, it is possible that local inflammation of the afferent vagal nerve could have led to the unilateral sialadenosis or noninfectious sialadenitis of the ipsilateral salivary glands in this case. The exact onset of the presumed unilateral sialadenosis is somewhat unclear in this case; initial clinical signs before surgical treatment of the cervical abscess included hypersalivation, which also occurs with sialadenosis, and unilateral sialadenosis could therefore have been present before surgical treatment. However, only the right mandibular salivary gland was abnormal on the initial CT scan, and this was attributed to direct trauma. Furthermore, clinical signs initially resolved after surgical treatment, which would be unusual for sialadenosis or sialadenitis. Another possibility is that either trauma from surgery or inflammation following surgery contributed to the development of postoperative unilateral sialadenosis. The fact that the sialadenosis was unilateral in this case is supportive of a focal cause. To the authors’ knowledge, there are no reports of other cases of unilateral sialadenosis in the dog. Unilateral sialadenosis is reported in people¹⁶ but without association with a focal trauma in the cervical area.

Conclusion

This case report describes presumptive sialadenosis as a suspected complication of a chronic oropharyngeal stick injury. Although this condition is rare and has not been described before in relation to trauma, it should be included as a differential diagnosis in patients presenting with hypersalivation, gagging, and decreased appetite. The diagnosis of sialadenosis requires exclusion of other causes for the clinical signs, and thorough investigations should therefore be performed. A rapid response to phenobarbital may be seen, although an extended course of treatment is usually required and relapse is possible.