Canine oral eosinophilic granuloma treated with corticosteroid monotherapy - case report

[Granuloma eosinofílico oral canino tratado com monoterapia com corticoide - relato de caso]

ABSTRACT

Eosinophilic granuloma is a lesion commonly found in cats but is rare in dogs, manifesting as nodules or plaques in the oral cavity, especially on the soft palate and tongue, with possible genetic potential involved. Due to the scarcity of descriptions of this oral lesion in dogs, especially in Brazil, the present report aimed to describe it in a Siberian Husky, treated at the Veterinary Hospital of the University of Franca, presenting an adherent and ulcerated plaque on the soft palate. Histopathological examination detected intense eosinophilic infiltrate associated with areas of collagenolysis, absence of neoplastic cells and negative PAS staining. Corticosteroid therapy with prednisolone (2mg/kg, every 24 hours, 7 days) was instituted, with gradual weaning of 0.5mg/kg, every 7 days. Given the excellent therapeutic response, this medication was maintained as monotherapy and, within 90 days of the end of treatment, there were no signs of relapse, without the need for association with complementary therapies or other therapeutic modalities, which could cause adverse effects and additional costs. It is admitted that, despite being uncommon, due to its similar clinical appearance, eosinophilic granuloma should be included in the differential diagnosis of neoplasms and infections, aiming at appropriate therapeutic institution.

Keywords:
collagenolysis; Siberian Husky; soft palate; veterinary allergology

RESUMO

O granuloma eosinofílico é uma lesão comumente encontrada em gatos, mas rara em cães, manifestando-se nestes como nódulos ou placas em cavidade oral, especialmente em palato mole e língua, com possível potencial genético envolvido. Devido à escassez de descrições dessa lesão oral em cães, especialmente no Brasil, o presente relato teve como objetivo descrevê-la em um Husky Siberiano, atendido no Hospital Veterinário da Universidade de Franca, apresentando placa aderida e ulcerada em palato mole. O exame histopatológico detectou intenso infiltrado eosinofílico associado a áreas de colagenólise, ausência de células neoplásicas e coloração PAS negativa. Instituiu-se corticoterapia com prednisolona (2mg/kg, a cada 24 horas, por sete dias), com desmame gradual de 0,5mg/kg, sete dias. Diante da excelente resposta terapêutica, tal medicação foi mantida como monoterapia e, em 90 dias transcorridos do término do tratamento, não houve indícios de recidiva, sem haver necessidade de associação com terapias complementares ou outras modalidades terapêuticas, as quais pudessem causar efeitos adversos e custos adicionais. Admite-se que, apesar de incomum, pela aparência clínica semelhante, o granuloma eosinofílico deve ser incluído no diagnóstico diferencial de neoplasias e infecções, visando à instituição terapêutica adequada.

Palavras-chave:
colagenólise; Husky Siberiano; palato mole; alergologia veterinária

INTRODUCTION

Canine eosinophilic granuloma is a rare lesion characterized by the presence of nodules and plaques, single or multiple, on the soft palate or vegetative masses on the ventral or lateral portion of the tongue, and can also be found on the tonsils and skin (Walsh, 1993; Bredal et al., 1996; Tellado et al., 2014; Mendelsohn et al., 2019), ventral abdomen, prepuce, digit, flank, external ear canal, nasal plane, and trachea (Vercelli et al., 2005). When present in the oral cavity, the lesions can be painful and associated with dysphagia, anorexia, sialorrhea (Tellado et al., 2014; Sousa et al., 2022), and coughing during and after meals (Bredal et al., 1996), with halitosis being the main complaint from the owners (Sousa et al., 2022).

The etiology of canine eosinophilic granuloma is uncertain; however, it is suspected that the pathogenesis is related to immune responses to antigenic exposures, which include parasitic/infectious allergens (fleas, mosquitoes, fungi, bacteria, and viruses), non-infectious allergens (pollen, medications, food products), and idiopathic factors (Poulet et al., 1991; Walsh, 1993; Jang et al., 2022). Regarding breeds, Siberian Huskies and Cavalier King Charles Spaniels are the most affected (Madewell et al., 1980; Bredal et al., 1996; Vercelli et al., 2005).

The diagnosis should be based on histopathology, which reveals an intense infiltration of degranulated eosinophils, often due to collagenolysis, surrounded by collagen fibers (Sousa et al., 2022). According to Withrow and Macewen (2007), the lesions mimic the appearance of malignant neoplasms, being one of the differential diagnoses along with bacterial or fungal granulomatosis and foreign body reactions (Declercq and Vercauteren, 2019).

Immunosuppressive doses of corticosteroids are used as monotherapy to reduce lesion size and improve the patient’s general condition (Miller et al., 2013; Tellado et al., 2014). Older studies reported high recurrence rates with the use of these medications in a short period, considering them as palliative rather than curative therapy (Madewell et al., 1980; Potter et al., 1980). On the other hand, prolonged use of high doses of corticosteroids can cause severe adverse effects (Sykes et al., 2007; Jang et al., 2022). Therefore, the use of adjuvant agents such as antihistamines and immunosuppressants, as well as electrochemotherapy, has been reported as alternative therapies (Tellado et al., 2014; Jang et al., 2022).

Given the scarcity of scientific cases on eosinophilic granuloma in the palate of dogs, especially in Brazil, this report aims to describe this condition, emphasizing the clinical, therapeutic, and especially diagnostic characteristics, which are essential to rule out differentials such as neoplasms and infectious processes of the oral cavity.

CASE REPORT

A four-year-old, intact male Siberian Husky, weighing 24.5 kg, was seen at the Veterinary Hospital of the University of Franca (UNIFRAN) with a neoplasm in the soft palate, followed by a dry cough and halitosis, but with normal eating and drinking habits and only one episode of allergic dermatitis.

In the physical examination, all parameters were within the normal range for the species, and upon inspection of the oral cavity, a plaque-like, reddish, ulcerated neoplasm approximately 4cm in diameter was observed, adhered to the soft palate (Fig. 1). The time of evolution was unknown to the owner, mainly due to the difficulty in inspecting the caudal oral cavity.

Figure 1
Plaque-like neoplasm, with red and ulcerated appearance, approximately 4cm in diameter, adhered to the soft palate (arrow) of a male dog, Siberian Husky, four years old.

Hematological parameters were within normal values for the species. Thoracic X-rays and abdominal ultrasound did not show evidence of metastases. Thus, under general inhalation anesthesia, cytology of the affected area was performed using a swab, which revealed only the presence of erythrocytes and no neoplastic or inflammatory cells. Subsequently, an incisional biopsy was performed for histopathological analysis. Macroscopically, the obtained fragments were noted to be grayish brown with brownish spots and had a soft texture. Cleavage was not performed due to the thickness of the fragments, so all the material was submitted for histopathological examination.

Microscopically, intense inflammatory infiltrate composed of eosinophils was detected, distributed diffusely throughout the collagenous tissue, which appeared dissociated, with moderate macrophages and lymphocytes interspersed. Additionally, some areas showed collagen fibers bordered by degranulated eosinophils in a "flame figures" appearance, confirming the diagnosis of eosinophilic granuloma (Fig. 2). No neoplastic cells were found, and fragments were also subjected to PAS (periodic acid-Schiff) staining for the detection of fungal structures, with negative results.

The use of prednisolone at an anti-inflammatory dose significantly reduced the palatine lesion during the interval between the biopsy and the histopathological results (Fig. 3).

Following the definitive diagnosis, monotherapy with prednisolone at an immunosuppressive dose (2mg/kg, orally, every 24 hours for 7 days) was established. After the first week showed satisfactory response, a gradual tapering was initiated by reducing the dose by 0.5mg/kg every 7 days, until reaching a final dose of 0.5mg/kg, administered for seven days and then every 48 hours for six days, resulting in significant improvement.

Throughout the treatment, the patient was monitored clinically to identify any potential side effects from prolonged corticosteroid use, and to date (90 days after the end of treatment), the animal has shown no signs of recurrence of the palatine lesion (Fig. 4).

Figure 2
Photomicrograph of eosinophilic granuloma in the soft palate of a male dog, Siberian Husky, four years old. A: Extensive area of collagen degeneration (collagenolysis, *), strongly eosinophilic, amorphous, and with a "flame figures" appearance, associated with intense eosinophilic infiltrate bordering this region (arrows). Obj. 10x, HE. B: Intense inflammatory infiltrate predominantly eosinophilic, with discrete macrophages and rare lymphocytes and neutrophils intermixed (and detail, obj. 100x). A focal area with slight collagen degeneration (arrow) amidst the intense infiltrate. Obj. 40x, HE.

Figure 3
Reduction of the palatine lesion (eosinophilic granuloma), after administration of prednisolone at an anti-inflammatory dose in male dog, Siberian Husky, four years old. Note the remnants of the lesion (arrows).

Figure 4
Palatine appearance 90 days after the end of oral prednisolone treatment in male dog, Siberian Husky, four years old, with eosinophilic granuloma.

DISCUSSION

The young Siberian Husky described in this report aligns with studies that identified this breed and age group as the most affected by eosinophilic granuloma in the oral cavity, despite the rarity of the lesion (Madewell et al., 1980; Potter et al., 1980; Vercelli et al., 2005, Miller et al., 2013). The appearance and location of the lesion in the oral cavity also correspond with descriptions by Tellado et al. (2014) and Mendelsohn et al. (2019), who noted that plaque on the soft palate is one of the most common forms.

The clinical signs presented by the reported patient included halitosis and dry cough, with halitosis being the most common complaint from owners, according to Tellado et al. (2014) and Sousa et al. (2022), likely due to the ulcerative nature of the lesion with potential necrosis (Mendelsohn et al., 2019). Coughing, especially during and after meals, is also a characteristic clinical sign of eosinophilic granuloma, as noted by Bredal et al. (1996).

Although some studies indicate a significant prevalence (21%) of peripheral eosinophilia in young male Siberian Huskies with eosinophilic granuloma (Vermond and Koedam, 1989; Miller et al., 2013), the eosinophil count in the patient in question was within the established limits for the species, similar to the findings of Mendelsohn et al. (2019), where only 3 out of 22 animals showed eosinophilia in the complete blood count.

Some studies have suggested that Type I hypersensitivity reaction may play a significant role in the pathogenesis of the disease, a hypothesis supported by the predominance of eosinophils in the lesions and the positive response to glucocorticoid therapy (Vercelli et al., 2005; Mendelsohn et al., 2019). Since this hypersensitivity reaction is primarily triggered by allergens in genetically predisposed animals, the reported dermatitis in the history of the described animal may indicate that it has genetic factors contributing to the development of eosinophilic granuloma. Madewell et al. (1980) and Woodward (2006) reported cases of hereditary transmission of the condition in Siberian Huskies and Greyhounds, respectively, further emphasizing the likely genetic involvement in the disease’s etiology.

For provisional clinical diagnosis, cytological samples obtained from oral lesion scrapings are described as simpler to obtain compared to biopsies due to tissue friability and the amount of sample needed (Bredal et al., 1996). However, the swab samples obtained from the lesion in the oral cavity of the reported patient only showed erythrocytes, which prevented presumptive diagnosis. Furthermore, due to the similarity of the lesions with other tumor and infectious conditions, performing a biopsy for histopathological evaluation is essential to rule out these differential diagnoses and outline the appropriate treatment.

The histopathological findings characterized by diffuse eosinophilic infiltrate, with varying macrophages and lymphocytes intermixed, corroborated with those found in other reports of canine eosinophilic granuloma (Madewell et al., 1980; Vercelli et al., 2005). The presence of degenerated collagen fibers bordered by degranulated eosinophils in a "flame figures" appearance is commonly described in canine eosinophilic granuloma but is not pathognomonic, as it can also be found in other hypersensitivity reaction conditions and in mastocytomas (Vercelli et al., 2005; Miller et al., 2013; Rech et al., 2021). Sykes et al. (2007) described the presence of eosinophilic granuloma in the hard and soft palates of tigers (Panthera tigris) with macroscopic characteristics similar to those described in domestic dogs and cats, including flat or slightly raised circular ulcers, as well as similarities in histopathological findings.

Regarding diagnosis, the use of PAS (periodic acid-Schiff) staining aimed to detect fungal structures as a differential diagnosis (fungal granulomatosis) or as a potential allergen triggering the eosinophilic granuloma, as described by Poulet et al. (1991) and Jang et al. (2022). The absence of neoplastic cells in the analyzed tissues was also crucial for ruling out neoplasia, another differential diagnosis of canine eosinophilic granuloma, according to Withrow and Macewen (2007).

Several studies have confirmed that eosinophilic granuloma in dogs responds to corticosteroid use (Potter et al., 1980; Vermond and Koedam, 1989), and in some cases, spontaneous regression can occur without medication (Potter et al., 1980; Mendelsohn et al., 2019). Furthermore, there are numerous cases treated with corticosteroid monotherapy in which there was complete regression of the lesion without the need for adjunctive therapies (Madewell et al., 1980; German et al., 2002; Vercelli et al., 2005). Such cases are consistent with the findings in this report, where the lesion was highly responsive to anti-inflammatory therapy with prednisolone in the postoperative period following the biopsy and completely regressed with subsequent immunosuppressive therapy.

Seasonal or chronic recurrences of canine eosinophilic granuloma have been reported in the scientific literature, especially after short periods of corticosteroid therapy (Potter et al., 1980; Madewell et al., 1980; Bredal et al., 1996). However, Vercelli et al. (2005) reported a therapeutic success with prednisolone at a dose of 0.5 to 2.2mg/kg (orally, every 24 hours) for 3 to 4 weeks, with no recurrence observed in six months of follow-up after the initial treatment. The protocol used in this report followed the regimen described by the aforementioned authors, and no signs of recurrence were noted up to three months after the end of treatment.

In this context, Mendelsohn et al. (2019) described that 100% of dogs with a history of allergies had complete resolution of eosinophilic granuloma lesions after treatment, with 66.7% treated with prednisone (either alone or in combination with other medications). Although they did not find statistical significance, corticosteroid treatment was correlated with clinical resolution in the population of allergic dogs, which is consistent with the patient in this report, who had a history of allergic dermatitis.

Due to the serious adverse effects associated with prolonged use of high doses of corticosteroids (such as gastritis, enteritis, chronic renal failure, and hepatotoxicity), other therapeutic modalities like electrochemotherapy, adjunctive immunosuppressive agents (azathioprine), and antihistamines have been reported (Tellado et al., 2014; Mendelsohn et al., 2019; Jang et al., 2022). According to Tellado et al. (2014) the use of electrochemotherapy followed by intravenous administration of bleomycin for oral canine eosinophilic granuloma, although effective, resulted in gingival swelling and oral discomfort as secondary effects, which were resolved with the use of non-steroidal anti-inflammatory drugs for seven days. Azathioprine has limited use due to the risk of severe hepatotoxicity and bone marrow suppression, potentially leading to neutropenia, thrombocytopenia, or both (Jang et al., 2022). In simpler cases like the one reported in this study, the positive response to isolated corticosteroid therapy proved to be a less costly and safer alternative for the patient, provided that attention is given to monitoring for adverse secondary effects.

CONCLUSIONS

Based on the reported case, it is possible to infer that, although rare in dogs, eosinophilic granuloma has a predisposition for the Siberian Husky breed and may be correlated with allergic processes mediated by Type I hypersensitivity reactions. Histopathological diagnosis is preferred, especially to differentiate it from malignant neoplastic lesions and fungal, bacterial, or viral infections. Monotherapy with prednisolone proved effective, with no recurrence of lesions and without the need for adjunctive therapies or other therapeutic modalities with significant adverse effects or high costs.

The scarcity of scientific reports on eosinophilic granuloma in dogs, especially in Brazil, highlights the need for further studies and investigations. This should focus primarily on identifying predisposing factors, with the aim of improving preventive measures regarding allergen exposure, enhancing diagnostic ease, and developing safer therapeutic modalities. These efforts will ensure a better quality of life and survival for affected animals.

REFERENCES

• BREDAL, W.P.; GUNNES, G.; VOLLSET, I. et al. Oral eosinophilic granuloma in three Cavalier King Charles spaniels. J. Small Anim. Pract., v.37, p.499-504, 1996. DECLERCQ, J.; VERCAUTEREN, G. Necrotizing eosinophilic dermatites in three dogs. Vlaams Diergeneeskd. Tijdschr., v.88, p.91-96, 2019.
• GERMAN, A.J.; HOLDEN, D.J.; HALL, E.J. et al. Eosinophilic diseases in two Cavalier King Charles spaniels. J. Small Anim. Pract., v.43, p.533-538, 2002.
• JANG, M.; LEE, W.; PARK, S. Eosinophilic granuloma treated with prednisolone and azathioprine in a dog. J. Vet. Clin., v.39, p.192-196, 2022.
• MADEWELL, B.R.; STANNARD, A.A.; PULLEY, L.T. et al. Oral eosinophilic granuloma in Siberian Husky dogs. J. Am. Vet. Med. Assoc., v.177, p.701-703, 1980.
• MENDELSOHN, D.; LEWIS, J.R.; SCOTT, K.I. et al. Clinicopathological features, risk factors and predispositions, and response to treatment of eosinophilic oral disease in 24 dogs (2000-2016). J. Vet. Dent., v.36, p.25-31, 2019.
• MILLER, W.H.; GRIFFIN, C.E.; CAMPBELL, K.L. Miscellaneous skin diseases. In: _____. Muller and Kirk’s small animal dermatology. 7.ed. St. Louis: Elsevier, 2013. p.707-718.
• POTTER, K.A.; TUCKER, R.D.; CARPENTER, J.L. Oral eosinophilic granuloma in Siberian Huskies. J. Am. Anim. Hosp. Assoc., v.15, p.595-600, 1980.
• POULET, F.M.; VALENTINE, B.A.; SCOTT, D.W. Focal proliferative eosinophilic dermatites of the external ear canal in four dogs. Vet. Pathol., v.28, p.171-173, 1991.
• RECH, R.R.; GIARETTA, P.R.; PLOEG, R. et al. Shapes of pathology. Pesq. Vet. Bras., v. 41, p.e06894, 2021.
• SOUSA, G.R.; COSTA, D.F.L.; NASCIMENTO, M.J.R. et al. Atypical eosinophilic granuloma in a dog. J. MVZ, v.27, p.e2097, 2022.
• SYKES, J.M.; GARNER, M.M.; GREER, L.L. et al. Oral eosinophilic granulomas in tigers (Panthera tigres): a collection of 16 cases. J. Zoo Wildl. Med., v.38, p.300-308, 2007.
• TELLADO, M.N.; MICHINSKI, S.D.; OLAIZ, N. et al. Canine oral eosinophilic granuloma treated with electrochemotherapy. Case Rep. Vet. Med., v.2014, p.1-4, 2014.
• VERCELLI, A.; CORNEGLIANI, L.; PORTIGLIOTTI, L. Eyelid eosinophilic granuloma in a Siberian Husky. J. Small Anim. Pract., v.46, p.31-33, 2005. VERMOND, J.F.G.; KOEDAM, M.A. Eosinofiel granuloom in de mondholte bij een Siberische Husky. Tijdschr. Diergeneeskd., v.114, p.82-85, 1989.
• WALSH, K.M. Oral eosinophilic granuloma in two dogs. J. Am. Vet. Med. Assoc., v.183, p.323-324, 1993.
• WITHROW, S.J.; MACEWEN, E.G. Small animal clinical oncology. 4.ed. Philadelphia: Saunders, 2007.
• WOODWARD, T.M. Greater palatine island axial pattern flap for repair of oronasal fistula related to eosinophilic granuloma. J. Vet. Dent., v.23, p.161-166, 2006.

Publication Dates

• Publication in this collection
  28 Apr 2025
• Date of issue
  May-Jun 2025

History

• Received
  23 Aug 2024
• Accepted
  04 Nov 2024