Feline atopic syndrome: An insight into its effects on the central nervous system through vestibular disease

Abstract

A 2-year-old male Abyssinian cat was presented with a left head tilt, lethargy, compulsive walking with a left-circling tendency, medial strabismus, a delayed pupillary light reflex, abdominal papules, and severe pruritus that began at 4 mo of age. Imaging revealed mineral opacity foci in the left ear, and magnetic resonance imaging confirmed heterogeneous signal changes, suggesting a diagnosis of otitis interna. No abnormal findings were observed on cerebrospinal fluid tests. Treatment with prednisolone, antibiotics, a hypoallergenic diet, and probiotics led to the resolution of skin issues and neurological improvement. Despite a persistent head tilt after more than 5 mo, there was no recurrence of severe neurological symptoms during the tapering off of prednisolone treatment.

Key clinical message:

This is the first case report illustrating the potential impact of feline atopic syndrome on the central nervous system. It emphasizes the importance of viewing feline atopic syndrome as more than just a skin disorder.

Otitis media/interna (OMI) is recognized as a prevalent cause of peripheral vestibular disease in cats (1,2) and has the potential to alter the fluid composition of the inner ear (3). It leads to the impairment of sensory structures in the vestibular system, affecting balance (4).

Animals with prolonged ear issues may exhibit progressive symptoms of central vestibular disease (CVD) (5). Among cats showing central vestibular signs, 93% display a subdued mental state, 90% exhibit cranial nerve deficits other than the facial and vestibulocochlear nerves, and 85% demonstrate ataxia (2).

Intracranial complications arising from OMI in cats may not be readily recognized due to the low prevalence of the disease, and 53% of affected cats do not exhibit evidence of external or middle ear disease upon otoscopic examination (6).

In addition, although 16 to 20% of cats with feline atopic syndrome are reported to have otitis externa (7), cats, unlike dogs, very rarely develop otitis media as a result of otitis externa (8). Cats may also have otitis media without otitis externa (9).

This report presents a rare case demonstrating that feline atopic syndrome is a potential cause of otitis interna. It is also the first case to show that atopic syndrome in cats may affect the central nervous system.

CASE DESCRIPTION

A 4-month-old male Abyssinian cat was brought to a veterinary hospital due to circling and falling behavior. A complete history revealed that the cat had received the second dose of feline viral rhinotracheitis, calicivirus, panleukopenia (FVRCP) vaccine and the first dose of leukemia vaccine. The cat had also received a dewormer to prevent heartworm and internal and external parasites. The initial diagnosis involved otitis externa and media based on skull radiography and otoscopy examinations and considering the presence of neurological symptoms. Otoscopic examination revealed a large amount of brown cerumen in the ear canal, along with erythema, swelling, and an opaque tympanic membrane. No abnormalities were observed on skull radiography.

Temporary improvement of neurological signs occurred when the external ear canals were cleaned. However, the cat subsequently developed a left-sided head tilt, right-jerk horizontal nystagmus, compulsive walking, and lethargy. One year later, systemic papules appeared and pruritus developed. Compulsive walking and an obtunded mentation simultaneously developed. Although prednisolone, amoxicillin-clavulanic acid, and marbofloxacin were administered for 8 mo, the systemic papules, pruritus, and neurological signs exhibited a waxing and waning pattern.

At 2 y of age, the cat was referred to the veterinary medical teaching hospital for further investigation. The cat was presented with a left head tilt, lethargy, diarrhea, and diffuse papules on the abdominal skin. Upon physical examination, the cat exhibited mild lethargy, and multiple papules and crusts were noted in the abdominal and inguinal regions (Figure 1). The cat’s visual analog scale score was 9.5 out of 10, indicating severe pruritus (10–12).

FIGURE 1.

A — At the first visit, there were papules and crusts (arrows) in the cat’s abdominal and inguinal regions. B — After 2 mo of treatment, the papules and crusts disappeared, leaving a few comedones (arrow) remaining.

Cytologic examination of the abdominal papules revealed a low number of cocci. There were no respiratory signs, and the cat’s vital signs were within normal limits. Upon microscopic evaluation of a fecal swab to identify the organism responsible for the diarrhea, dysbiosis was observed. The cat displayed a left head tilt (Figure 2), compulsive walking with a left-circling tendency, medial strabismus, and a delayed pupillary light reflex in both eyes. Otoscopic examination to investigate if otitis was causing the head tilt did not reveal any evidence of external or middle ear disease. Cytologic evaluations of swabs of the ear canal did not reveal any specific findings. A chemistry panel indicated elevated levels of aspartate aminotransferase (53 U/L; reference range: 0 to 48 U/L) and creatine kinase (402 U/L; reference range: 0 to 314 U/L). No abnormalities or notable results were detected on the complete blood (cell) count, electrolyte analysis, blood gas analysis, or coagulation panel. On skull radiography, multiple opaque foci were identified in the left auricle and external ear canal. This finding suggested the presence of mineralization in the ear canal wall, which can be observed in cases of otitis externa (13). Similar changes can occur when otitis externa becomes chronic in cats (9). For this reason, the possibility of otitis externa could not be excluded, even in the absence of clear abnormalities in the external ear canal. Therefore, the differential diagnoses included food allergy, feline atopic syndrome, OMI resulting from chronic otitis externa, a nasopharyngeal polyp/mass, and central nervous system disease.

FIGURE 2.

A — The cat exhibited a left head tilt; however, there was no evidence of external or middle ear disease as the cause of the head tilt. B — Although a slight left head tilt persisted after treatment, there was a clear improvement compared with before treatment.

Magnetic resonance imaging (MRI) with clear contrast enhancement revealed a heterogeneous signal change in the left inner ear (Figure 3), characterized by T2-weighted hypointensity, T2-fluid-attenuated inversion recovery (FLAIR) hypointensity, and T1-weighted isointensity. In addition, mild contrast enhancement of the right facial and vestibulocochlear nerves (Figure 3 A) and mild thickening and enhancement of the walls of the bilateral external acoustic meatus were observed (Figure 3 B). Results of feline cerebrospinal fluid (CSF) infectious disease polymerase chain reaction panel and microbial culture tests were normal.

FIGURE 3.

A to D — Transverse magnetic resonance images showing a heterogeneous signal change in the cat’s left inner ear (arrowhead) with T1-weighted isointensity (A) exhibiting clear contrast enhancement (B), T2-weighted hypointensity (C), and T2-fluid-attenuated inversion recovery (FLAIR) hypointensity (D). In addition, mild contrast enhancement of the right facial and vestibulocochlear nerve (white arrow in A) and mild thickening and enhancement of the walls of the bilateral external acoustic meatus (yellow arrows in B) were observed.

Combining the above results, a diagnosis of peripheral and central vestibular disease stemming from otitis interna was established. Food allergies and feline atopic syndrome remained as differential diagnoses. Treatment included the administration of an anti-inflammatory agent (prednisolone: Solondo tablet; Yuhan, Seoul, Korea), 1 mg/kg, PO q12h and antibiotics (cefixime: Cefixime capsule; Withus Pharm, Seoul, Korea, 12.5 mg/kg, PO, q12h; and marbofloxacin: Marbocyl tablet; Vetoquinol Korea, Gyeonggi, Korea, 5.5 mg/kg, PO, q24h). Dietary restriction was implemented by feeding hypoallergenic cat food (Hill’s Prescription Diet z/d Dry Cat Food; Hill’s Pet Nutrition, Overland Park, Kansas, USA). Probiotics (Lactobacillus sakei proBio65, LACTOVET freeze-dried powder; ProBionic, Jeollabuk-do, Korea), 2 × 10⁹ CFU, q24h, were prescribed to manage dysbiosis.

After 2 mo of treatment, the papules and crusts disappeared (Figure 1) and the diarrhea resolved. The visual analog scale score indicating pruritus improved to 0 out of 10. In addition, cytologic assessment revealed the absence of cocci on the skin, and dysbiosis was not observed on a repeated rectal swab. The cat displayed improved mentation. The medial strabismus had resolved and compulsive walking with a left-circling tendency had ceased. Although the left head tilt and delayed pupillary light reflex in both eyes persisted, a clear improvement was evident compared with the cat’s condition before treatment (Figure 2).

Despite the feeding of hypoallergenic cat food and probiotics for > 5 mo, new papules appeared on the abdomen. Eosinophils were detected on cytology and no infectious agents were identified. Thus, a tentative diagnosis of feline atopic syndrome was made based on the cutaneous symptoms and the response to anti-inflammatory therapy. At the time of writing, the cat was undergoing investigations to determine environmental causes, and treatment plans were being scheduled accordingly.

Despite the stepwise decrease in prednisolone over 5 mo from the start of treatment, there was no reappearance of the cat’s obtunded mentation, compulsive walking with a left-circling tendency, or medial strabismus. However, the left head tilt remained.

DISCUSSION

This study reports a case with a tentative diagnosis of feline atopic syndrome affecting both the peripheral and central nervous systems. Diagnosis was supported by clinical signs, neurological examination, MRI findings, and response to treatment. To our knowledge, this is the first reported case demonstrating the potential effect of feline atopic syndrome on the central nervous system.

Reports illustrating the connection between atopic dermatitis and the central nervous system are rare. In humans, the association between atopic dermatitis and abnormal brain structures (including decreased size of caudate nucleus, cortex, and gyrus) has been reported (14), but the precise process remains unclear. In dogs with syringomyelia, including OMI, high levels of interleukin (IL)-31 were observed in CSF samples, but there appeared to be no correlation with itching or pain (15).

In this case, there were no chronic respiratory symptoms, tumors, foreign bodies, trauma, or history of a tick infestation that could have caused OMI. Ultimately, considering that atopy might lead to increased activity of neutrophils in otitis media, likely due to the heightened reaction of pre-activated inflammatory cells to bacterial presence as shown in humans (16), the inflammatory state may also be caused by immune dysfunction in feline atopic syndrome (17). Furthermore, the inner ear communicates directly with the middle ear in cats (18), which suggests that feline atopic syndrome may be a cause of otitis interna. In addition, although progression from otitis externa to otitis media is rare in cats (8), considering that control of otitis externa in cats with allergic skin disease requires addressing the underlying allergy (9), we suggest the otitis externa that occurred at 4 mo of age in this cat persisted as an underlying condition with uncontrolled feline atopic syndrome and progressed to otitis interna over a period of more than a year.

Interestingly in this case, there were not only symptoms suggestive of peripheral vestibular disease, such as the left head tilt and compulsive inclination to circle to the left, but also symptoms raising suspicion of CVD, including the animal’s obtunded mentation, delayed pupillary light reflex, and medial strabismus in both eyes.

There is 1 published report indicating that the spread of infection from the inner ear to the central nervous system is signified by the presence of pleocytosis in the CSF, as observed in 10 of 11 cases of canine OMI (19). In humans, it was reported that the cochlear aqueduct serves as a direct path for infections and inflammation between the CSF and the inner ear (20). The neurological outcomes of acute meningitis caused by OMI are influenced by the presence of tumor necrosis factor, prostaglandins, and IL-1 (21).

Unfortunately, due to insufficient CSF volume, we were unable to conduct cytology and fluid analysis, which precluded CSF culture. In addition, MRI findings did not reveal any lesions in the brain stem or diencephalon, and thus we could not confirm intracranial inflammation. However, considering the report that 15% of cats displaying clinical signs of CVD do not have detectable lesions on MRI despite having a focal clinical localization (2), reports of decreased production of IL-1 and tumor necrosis factor associated with the use of dexamethasone in human bacterial meningitis (21), and the clinical improvement observed in the current case with anti-inflammatories (such as the cat’s improved mentation, cessation of compulsive left circling, and disappearance of medial strabismus), we suggest that the clinical signs described herein likely involved not only the peripheral vestibular system but also the central vestibular system.

Although inner-ear lavage and bacterial culture were not attempted due to a lack of owner consent, the cat was treated concurrently with anti-inflammatory drugs and antibiotics before referral. There was no improvement in neurological symptoms after > 8 mo of antibiotic and prednisolone treatment before admission to the referral hospital. Considering that neurological symptoms improved after the management of feline atopic syndrome, and that no bacteria were cultured from the CSF, we postulate that feline atopic syndrome contributed to the development of vestibular disease affecting the central nervous system.

Despite mild contrast enhancement of the right facial and vestibulocochlear nerves on MRI, the clinical signs observed were left head tilt and a left-circling tendency. The lesion in the right facial and vestibulocochlear nerves might have been less severe than the lesion in the left inner ear, considering that head tilt can occur when one side is more severely affected in cases of bilateral vestibular disease (22).

Despite treatment, the persistent left head tilt was believed to stem from permanent damage to the vestibulocochlear nerve (23). The limited regenerative capacity of vestibular and cochlear sensory cells in adult mammals (24), as evidenced in this cat, can contribute to a lasting impairment of balance function (4).

In conclusion, we report a rare case indicating that feline atopic syndrome (and/or otitis externa due to feline atopic syndrome) could be potential causes of otitis interna. It is also the first reported case demonstrating that atopic syndrome in cats may affect the central nervous system.

Comprehensive diagnostic evaluations for vestibular syndrome should be conducted in these cases. The link between feline atopic syndrome and central nervous system involvement emphasizes the importance of viewing feline atopic syndrome as more than just a skin disorder.

Funding Statement

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education (NRF-2023R1A2C1005348).