Oesophageal necrosis after impaction as a proposed cause of markedly elevated serum creatine kinase activity in a juvenile cat

Abstract

Case summary

A 21-week-old, male castrated domestic mediumhair cat presented with a history of acute, severe regurgitation. No abnormalities were detected on physical examination. Initial serum biochemistry identified marked elevation in creatine kinase (CK) (905,409 U/l, reference interval [RI] 50–400), which persisted after 24 h of supportive care (32,491 U/l, RI 50–400). Serology for Toxoplasma gondii was negative. Radiography and ultrasound found severe caudal oesophageal impaction. The kitten was euthanased; a post-mortem examination confirmed oesophageal food impaction and severe, focally extensive oesophageal necrosis. The underlying cause of the oesophageal impaction was not definitively determined. Other than the oesophageal necrosis, there were no other autopsy findings to explain the elevated CK.

Relevance and novel information

Oesophageal muscle necrosis may be associated with severe elevations in CK concentrations and oesophageal disease should be considered if there is no obvious trauma, polymyopathy or cardiac disease in feline patients with markedly elevated CK.

Introduction

Creatine kinase (CK) is an enzyme responsible for the phosphorylation of adenosine diphosphate (ADP) using phosphocreatine to generate adenosine triphosphate (ATP). This biochemical process provides the essential energy required for muscle contraction. ¹ Total CK concentration ([CK]) is measured in serum of domestic animals, predominantly as a marker of skeletal and cardiac myocyte damage. ² Beyond direct trauma, various neurological conditions are associated with elevated [CK]. ³ Frequent clinical explanations for increased activity include skeletal muscle trauma – whether surgical, accidental or due to excessive restraint – as well as infectious or inflammatory myopathy, rhabdomyolysis, strenuous exercise, hypokalaemia, haemolysis artefact and neurological disease.^2,6 Furthermore, evidence indicates that cats with systemic illness or prolonged recumbency may develop moderate elevations in [CK]. ⁴

There are three isoenzymes of CK: CK-MM (muscle-type), CK-MB (myocardial-type) and CK-BB (brain-type). In human medicine, these are extensively utilised to determine the specific origin of myocyte damage, with CK-MB specifically used to diagnose myocardial infarction. ⁵ These isoenzymes have seen only limited study and application in canine and feline medicine and the specific isoenzyme is not routinely measured; rather, the total concentration of CK is reported. ⁶ CK-MM is the predominant isoenzyme found in skeletal and cardiac muscles of dogs and cats. ⁶ In humans, CK-BB is associated with leakage from smooth muscle and neural pathways, particularly the gastrointestinal tract, uterus and central nervous system. ⁵ This association may be relevant to veterinary patients if CK-BB is also present in feline smooth muscle, as it could explain serum CK elevations in patients lacking obvious skeletal myopathy.

Oesophageal anatomy in cats is different from dogs. In cats, the upper two-thirds of the oesophageal wall is composed of skeletal muscle, whereas the distal third consists of smooth muscle.^7,8 Conversely, the entire length of the canine oesophagus is composed of skeletal muscle. ⁷ These anatomical variations have direct implications for motility; for instance, generalised megaoesophagus is considered uncommon in cats, ² while acquired megaoesophagus can be segmental in cats and often forms orad to an obstruction or stricture. The feline oesophagus has not historically been considered a region capable of generating significant derangements in [CK] based on a review of current literature.

Case description

A 21-week-old, male castrated domestic mediumhair cat presented with a 4-day history of regurgitation and lethargy. The cat had been in the owner’s possession since 4 weeks of age and was the smallest in the litter but seemed healthy. The kitten had been energetic but was reported to have an ongoing behaviour of lip licking, excessive swallowing and rare vomiting. The kitten had been vaccinated and castrated without concern. The kitten was kept indoors with short periods of outdoor supervision. There were no other cats in the household.

Upon presentation, the kitten was estimated to be 8% dehydrated and had signs of possible abdominal pain. It had a body condition score of 3/9 and weighed 2.1 kg. Vital signs were normal (rectal temperature of 37.8°C, heart rate of 220 beats/min, respiratory rate of 40 with normal effort). No cardiac murmur was detected. Although hospital-induced anxiety made walking difficult to observe, no specific gait abnormalities or muscle pain were noted, though an occasional partial plantigrade stance was noted. Neurological deficits were not noted. During hospitalisation, there was ongoing regurgitation.

Laboratory investigations included a complete blood count and serum biochemistry, performed at an external laboratory and validated by a clinical pathologist. Serum and plasma were clear, without evidence of haemolysis. Results showed moderate neutrophilic leucocytosis at 24.5 ×10⁹/l (RI 5.5–19.5). Blood film analysis revealed occasional keratocytes and schistocytes, suggesting possible fragmentation injury to erythrocytes. Biochemistry revealed mild stress hyperglycaemia (9.5 mmol/l, RI 3.9–7.5), mild hypercholesterolaemia (4.5 mmol/l, RI 1.9–3.9) and mild elevation in alanine aminotransferase (ALT) activity at 352 U/l (RI 5–80). The most profound finding was marked elevation in serum CK activity at 905,409 U/l (RI 50–400). Plasma electrolytes were normal. No abnormalities were found in urinalysis (SediVue; IDEXX); specifically, no gross discolouration was noted.

Thoracic and abdominal radiographs, reviewed by a board-certified veterinary radiologist, identified a well-defined, fusiform, heterogeneously mineralised soft tissue opacity within the caudodorsal mediastinum, most consistent with ingesta. A mild, convex soft tissue bulge at the level of the gastro-oesophageal sphincter raised suspicion for a small hiatal hernia or mild focal mass effect. Additional findings included moderate generalised cardiomegaly, marked hepatosplenomegaly, mild bilateral renomegaly, small-volume pleural effusion and reduced serosal detail. The mediastinal opacity was deemed most consistent with segmental caudal oesophageal dilation secondary to food impaction and suspected lower oesophageal sphincter (LES) obstruction (Figure 1).

Figure 1

(a) Ventrodorsal and (b) right lateral recumbent radiographs of the 21-week domestic mediumhair cat showing segmental dilation of the caudal thoracic oesophagus (arrowheads) and hepatomegaly (arrowheads). Note a mild soft tissue bulge at the level of the gastro-oesophageal sphincter (asterisks), concerning for a hiatal hernia or lower oesophageal sphincter thickening/mass

Subsequent ultrasonography (Acuson Sequoia; Philips) confirmed marked hepatosplenomegaly. The liver had normal echogenicity and echotexture, while the spleen contained multiple, ill-defined, coalescing hypoechoic foci, most consistent with juvenile lymphoid hyperplasia. ⁹ The kidneys were normal in length but rounded, diffusely hypoechoic, with moderate pyelectasia (2–3 mm). Owing to their abnormal ultrasonographic appearance, fine-needle aspirates were collected from the liver, spleen and kidney. Mild free abdominal fluid was present in all quadrants, considered physiologic for the patient’s age. The stomach and small intestine were devoid of ingesta, despite recent feeding. The LES was seen in the normal anatomic location (Figure 2). Thoracic ultrasonography identified a distal oesophagus distended by content with heterogeneous, post-acoustic shadowing and reverberation (Figure 3). A sliding hiatal hernia was not definitively confirmed.

Figure 2

Subcostal ultrasound of the cranial abdomen with diaphragm (arrowheads) and normally located gastro-oesophageal sphincter

Figure 3

Subcostal ultrasound of the cranial abdomen with diaphragm (arrowheads) and the dilated caudal oesophagus

Cytological examination of ultrasound-guided liver aspirates showed moderate mixed inflammation without micro-organisms. Spleen and kidney aspirates were normal. Serology for Toxoplasma gondii (Immunofluorescent Antibody Testing IgG/IgM <1:16; VETPATH), feline immunodeficiency virus and feline leukaemia virus (SNAP; IDEXX) were all negative. Subsequent blood work 36 h later performed at the same external laboratory showed a persistently marked [CK] at 32,491 U/l.

The kitten was treated with empirical supportive care including fluid therapy (maropitant 1 mg/kg SC q24h, Prevomax; Dechra) and antiemetic therapy (Ondansetron 0.2 mg/kg IV q8h, Zofran; Pfizer). The kitten continued to regurgitate. Given the severity of the clinical signs and suspicion for primary oesophageal dysfunction, the cat was euthanased 4 days after presentation.

Post-mortem examination was performed approximately 48 h after euthanasia. There were no gross changes to the liver, spleen or general musculature. The heart was grossly normal and the weight within the expected reference interval. The primary finding was complete impaction of the distal 10 cm of the oesophagus with food, resulting in marked focal luminal dilation. The portion of the oesophagus as it passed through the diaphragm at the LES was narrowed and pale (Figure 4). Although the oesophageal hiatus appeared subjectively narrowed, the stomach was not herniated and no gastrointestinal obstruction was present. There were non-specific findings of minimal pleural and abdominal effusion as well as changes consistent with barbiturate euthanasia.

Figure 4

(a) The caudal segment of the oesophagus in the thoracic cavity is markedly distended. (b) The dissected oesophagus shows segmental reddish mucosal discolouration associated with impacted food material in situ. Bar = 3 cm

Sections from the oesophagus, heart, skeletal muscle (two sites), lungs, aorta, liver, kidneys, small intestine, large intestine, thyroid, parathyroid and stomach contents were examined. The myocardium showed one small focus of mineralisation but no other noteworthy changes. The remainder of the tissues were histologically normal. Oesophageal sections from the area affected by obstruction showed diffuse distribution throughout the tunica muscularis of swollen myocytes with vacuolation of the sarcoplasm (degeneration) and hypereosinophilic fibres with loss of cross striations (hyalinisation) and fragmentation of myofibrils (Figure 5). Necrotic myocytes were occasionally surrounded and infiltrated by macrophages and hypertrophic and hyperplastic satellite cells, the latter occasionally clumped together.

Figure 5

(a) Oesophageal tunica muscularis showing multifocal degenerative, necrotic and regenerative changes with dystrophic mineralisation. Bar = 200 µm. (b) Close up of (a); the sarcoplasm of degenerating myofibres at places contained densely basophilic granular material (mineral). Bar = 200 µm

Based on these findings, the kitten was diagnosed with oesophageal necrosis due to obstruction, which caused the regurgitation and massive elevation in [CK]. Suspicion remained for LES achalasia-like syndrome, stricture or congenital megaoesophagus leading to secondary food impaction.

Discussion

The defining feature of this case was the presence of a markedly elevated plasma [CK], a finding not previously associated with oesophageal necrosis or primary oesophageal disease in cats. Typical differentials for markedly elevated [CK] include polymyopathy, trauma, strenuous exercise, systemic illness, severe haemolysis or cardiac disease. ² In this patient, cardiac disease and ‘sick cat’ myopathy were considered but lacked clinical support, especially given the magnitude of the elevation. ⁴ This patient did not have clinical signs referable to a polymyopathy or prolonged recumbency. Although kittens aged under 2 months may have higher [CK], this kitten was significantly older and its [CK] far exceeded the mild elevations reported in younger cohorts. ¹⁰

The mild elevation in ALT activity may have resulted from primary hepatic pathology, reactive hepatopathy or hypoxic cellular injury.^2,6 Although ALT can rise secondarily to myopathy, the more specific marker, aspartate aminotransferase (AST), was not measured. However, because the liver appeared grossly normal at post-mortem examination, the inflammatory infiltrate noted on cytology was deemed likely indicative of a reactive hepatopathy rather than significant primary disease. The spleen and kidney aspirates were normal and had been collected by the emergency and critical care department because of the abnormal ultrasonographic appearance of these organs, given infectious disease was initially considered a differential diagnosis before referral.

[CK] remained elevated, although markedly improved, when re-tested 36 h after initial testing. Given the testing was performed on an external commercial instrument, it is considered unlikely to be erroneously low owing to exhaustion of the substrate. This improvement did not correlate with any clinical improvement in the patient, and neither sample was grossly haemolysed. We hypothesise that improvement may have been due to fluid therapy and improved renal excretion of excess CK.

The primary clinical sign of regurgitation allowed for localisation to the oesophagus, which was confirmed through imaging. Videofluoroscopy would have been an ideal diagnostic test but was unable to be performed. Possible differentials for the underlying cause included LES achalasia, strictures, focal megaoesophagus or hiatal hernia with intussusception. There are case reports in the literature of severe congenital oesophageal disease causing significant clinical signs. Van Geffen et al ¹¹ and Martinez et al ¹² describe cases of congenital idiopathic megaoesophagus leading to intermittent gastro-oesophageal intussusception; however, post-mortem evidence here better supported a mechanical cause. The presence of a narrowed, pale band of tissue at the LES with focal severe proximal dilatation is similar to other reports of feline LES achalasia or achalasia-like syndrome.^13,14 There is also another case report detailing a cat with secondary megaoesophagus secondary to occult oesophageal stricture; however, in that case, there was radiographic evidence of megaoesophagus. ¹⁵

The histological findings support the clinical findings: it is most likely that mechanical pressure from commercial dry food impaction led to severe oesophageal necrosis. Although most oesophageal diseases would not be expected to cause this degree of damage, the focally extensive necrosis in this case likely accounts for the massive [CK] release. The findings in this case report suggest that clinicians should exercise caution and consider oesophageal pathology when investigating unexplained [CK] elevations. Diagnostic efforts for this kitten while alive would have focused unrewardingly on polymyopathy had the localised sign of regurgitation not been present.

Conclusions

This case report details the first known instance of elevated [CK] associated with oesophageal muscle necrosis and represents the greatest magnitude of [CK] elevation reported in feline literature. Oesophageal disease should be investigated in patients with extreme [CK] elevations if clinical signs are compatible and traditional causes such as cardiac disease or generalised myopathy are absent.