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J Vet Clin 2022; 39(4): 192-196

https://doi.org/10.17555/jvc.2022.39.4.192

Published online August 31, 2022

Eosinophilic Granuloma Treated with Prednisolone and Azathioprine in a Dog

Moonseok Jang1 , Wanghui Lee1,2 , Seongjun Park1

1College of Veterinary Medicine, Chungnam National University, Daejeon 34134, Korea
2Department of Companion Animal, Yeonsung University, Anyang 14011, Korea

Correspondence to:*parksj@cnu.ac.kr

Received: April 18, 2022; Revised: July 8, 2022; Accepted: July 13, 2022

Copyright © The Korean Society of Veterinary Clinics.

A two-year-old, intact male, 45 kg Doberman Pinscher was referred with dermal nodular lesions affecting the left hindlimb. The cytological examination revealed eosinophilic inflammation. Skin biopsy specimens showed canine eosinophilic granuloma (CEG). The dog was administered oral prednisolone (1.5 mg/kg/day) and azathioprine (2 mg/kg/day). After one week, the skin lesions diminished dramatically, but the dog presented with severe watery diarrhea. The prednisolone dose was reduced by 0.9 mg/kg/day. The lesions and diarrhea improved markedly after one week. Prednisolone was tapered by 25% of the previous dose every week to 0.2 mg/kg/day. Azathioprine was also reduced to therapy every other day. After seven weeks of combination treatment, the medications were withdrawn, but the dog had a recurrence one week later. Azathioprine (2 mg/kg/EOD) was reintroduced for two weeks. There was no relapse after all the medications had been withdrawn. This case indicates that CEG can be managed with prednisolone and azathioprine. Azathioprine may be an effective adjunctive immunosuppressive agent, and may be considered as a well-tolerated prednisolone sparing agent to treat CEG.

Keywords: eosinophilic granuloma, prednisolone, azathioprine, dog.

Eosinophilic skin disease in dogs results from uncontrolled tissue damage following insults by parasites, allergens, infectious agents (fungi, bacteria, and viruses), or drugs. This clinical presentation includes eosinophilic furunculosis, canine acute eosinophilic dermatitis (CAEDE, Wells-like syndrome), eosinophilic granuloma, eosinophilic vasculitis, and necrotizing eosinophilic dermatitis (10). Canine eosinophilic granuloma (CEG) is an uncommon skin disease. Skin lesions are most frequently located in the oral cavity and infrequently involve other cutaneous sites, such as the nasal planum, ventral abdomen, thorax, metatarsus, prepuce, flank, digit, eyelid, external ear canal, and cheek region (6,9,13). The common clinical types of skin manifestations are papular, nodular, or plaque lesions. Lesions are typically firm, nonpruritic, erythematous, and ulcerated. Affected dogs are healthy without signs of systemic involvement. A marked breed predilection for Siberian husky dogs and cavalier King Charles spaniels suggests potential hereditary factors (13). Although the pathogenesis of CEG is unclear, immunological responses to antigenic exposure, including infectious and noninfectious allergens, are suspected (10). CEG is clinically managed with corticosteroid monotherapy (8). Treatment should be continued until the lesions have resolved completely to reduce the risk of recurrence. Prolonged use of high corticosteroid doses may have serious adverse effects, such as polyuria/polydipsia, diarrhea and vomiting, and hepatotoxicity. Therefore, some effective adjunctive immunosuppressive agents may be considered.

This case report describes the successful management of a case of CEG with prednisolone and azathioprine.

A two-year-old, intact male, 45 kg Doberman Pinscher presented with a seven-month history of dermal nodular lesions affecting the left hindlimb. The owner reported a partial reduction in the size of the lesions subsequent to the prednisolone (0.5 mg/kg/day) and antibiotics treatments (amoxicillin-clavulanate, cephalexin) for three months, but the granulomas recurred after withdrawing the drugs. The granulomas were removed by surgical excision. The referring veterinarian also used afoxolaner (NexGard spectra, Merial) to exclude an ectoparasites infestation. On the other hand, the lesions developed again within three weeks. Therefore, the dog was referred to the Chungnam National University Veterinary Teaching Hospital.

The clinical evaluation revealed two ulcerated nodular lesions that measured 25 mm and 5 mm on the left lateral thigh region (Fig. 1). The physical feature was no presence of palpably enlarged peripheral lymph nodes. Imprinting smear revealed eosinophilic inflammations, and occasionally macrophages and neutrophils containing intracellular cocci were seen. Hematological analysis showed no abnormalities. For a histopathological examination, two skin biopsy specimens were collected from the lesions using 6 mm and 4 mm biopsy punches.

Figure 1.Ulcerated nodules measuring 25 mm located in the lateral thigh region (left) and measuring 5 mm located in the metatarsal region (right).

The skin biopsy revealed moderate to severe infiltrates of eosinophils with fewer macrophages in the dermis (Fig. 2). Large clusters of eosinophils surrounded hyalinized dermal collagen fibers, and occasionally flame figures were observed. The diagnosis was an eosinophilic granuloma. Oral prednisolone (Solondo, Yuhan) was instituted at 1.5 mg/kg/day for the first week. In conjunction with prednisolone, azathioprine (Immuthera, Celltrion pharm) also was initiated at 2 mg/kg/day and oral cephalexin (20 mg/kg twice daily for 28 days). After one week, the lesion started to diminish dramatically, but the dog showed severe watery diarrhea. The prednisolone dose was reduced by 0.9 mg/kg/day, and dioctahedral smectite (Smecta, Daewoong pharm) was prescribed. The lesions and diarrhea improved markedly after one week. The prednisolone dose was tapered by 25% of the previous seven weeks’ dose every week to 0.2 mg/kg/day. Azathioprine therapy was also reduced to every other day (EOD). After nine weeks of combination treatment, the medications were withdrawn totally. On the other hand, a small area of erosion and erythema with purulent exudates developed again one week later. Azathioprine 2 mg/kg/EOD and cephalexin (Falexin, Dongwha pharm) 20 mg/kg twice daily were reintroduced for two weeks. The bacterial culture and antibiotics sensitivity test revealed Pseudomonas straminea (susceptible to doxycycline and cefovecin). Doxycycline (Kukje pharm) was prescribed at 10 mg/kg twice daily with azathioprine 1 mg/kg/EOD for two weeks. There was no relapse after all medications had been withdrawn over the two-month follow-up period (Fig. 3).

Figure 2.Photomicrograph of an eosinophilic granuloma. Focal granuloma is cuffed by large numbers of eosinophils with fewer macrophages (left). The dermis contains a moderate to severe infiltrate of degranulated eosinophils and degenerated collagen fibers, so-called “flame-figure” (right) (H&E, 400×).

Figure 3.Skin lesions of the lateral thigh region (left) and the metatarsal region (right) after eight weeks of prednisolone and azathioprine treatment.

CEG is an unusual skin disease with an uncertain etiology. Type I cell-mediated hypersensitivity reaction appears to play a role in the pathogenesis (13). This theory is supported by the predominance of eosinophils in these lesions and their positive response to glucocorticoid therapy (7). The triggers for such hypersensitivity reactions may be inhaled or ingested allergens, including seasonal allergens (pollens and molds), insects (mosquitoes), food, or exposure to irritants (fungi and bacteria) (7). No evidence of any of these possible causes was obtained in this case. On the other hand, the granuloma was located superficial to the deep dermis, and the nodules were found in the lateral thigh, suggesting a possible reaction to contact with an irritant.

Eosinophilic skin diseases in dogs include eosinophilic furunculosis, eosinophilic vasculitis, acute eosinophilic dermatitis (Wells-like syndrome), necrotizing eosinophilic dermatitis, and eosinophilic granuloma (2). This dog’s histopathologic presentation differed from the other eosinophilic diseases. Eosinophilic furunculosis was excluded due to a lack of folliculocentric eosinophilic inflammation (4). The blood vessels were intact in the skin biopsies, and there was no histopathological evidence of vascular damage ruling out eosinophilic vasculitis (3).

Eosinophilic granulomas have similar clinical lesions to Wells-like syndrome and necrotizing eosinophilic dermatitis, including erythematous papules, plaques, and nodules with yellow exudate and ulceration (2,3,13). In contrast to eosinophilic granuloma, Wells-like syndrome is frequently encountered with marked erythroderma of the ventrum, hypoalbuminemia, and gastrointestinal signs before the development of skin lesions. In addition, it has eosinophilic infiltration without degranulation (2). Necrotizing eosinophilic dermatitis typically shows significant areas of necrosis and features of vasculitis on histopathology (1). The dog fulfilled the conditions for distinct granulomas with marked central eosinophilic degranulation and multifocal areas of collagen degeneration, referred to as “flame figures” (2,5,13).

Most CEG cases in dogs have been treated based on the clinical presentation. Conventional therapy consists of symptomatic treatment and control of the suspected causes, such as parasitic, infectious, or allergenic agents. Therapeutic drugs may include glucocorticoids, antihistamines, or other hyposensitization therapies (7). Other treatments yielding various results include CO2 laser therapy and surgical incision (6). In this case, several treatments were conducted with anti-inflammatory therapy and surgical removal before referral. Because these treatments could not control the disease, immunosuppressive therapy was initiated as an alternative.

Several choices to control CEG have been reported, including glucocorticoid with prednisolone sparing drugs, particularly for chlorambucil and azathioprine (7,11,12). Chlorambucil is a cell cycle nonspecific alkylating antineoplastic and immunosuppressive agent (6). It targets B-cells and is considered a slow-acting agent that may require two weeks to reach therapeutic efficacy (14). The drug has previously been shown to be an effective steroid-sparing agent in a case of CEG of the digits (6). Azathioprine is an immunosuppressant used in both human and veterinary medicine (15). Azathioprine is a purine analog. A metabolite of azathioprine, 6-thioguanin nucleotides (6-TGNs), competes with endogenous purines for DNA and RNA synthesis and inhibits proliferation and T-cell-dependent antibody synthesis (14). On the other hand, the use of azathioprine is limited by the risk of hepato-toxicosis and bone marrow suppression. The hepatotoxic effect has been attributed to the accumulation of another metabolite, 6-methyl mercaptopurine (6-MMP). Bone marrow suppression, including neutropenia, thrombocytopenia, or both, is a commonly listed adverse effect of azathioprine. On the other hand, no prevalence studies have been reported in dogs (15). Hepatotoxicosis is defined by increases in alanine aminotransferase (ALT) activity more than two times the upper limit of the reference range. The clinical signs include vomiting, lethargy, and jaundice. In a retrospective study, hepatotoxicosis was observed in five out of 34 dogs (15%) treated with azathioprine within a median onset of 14 days (15). Therefore, it is recommended to monitor the serum liver enzymes on one or more occasions between one and four weeks after starting azathioprine in dogs (15). In the present case, the dog was monitored to obtain biochemical evidence of hepatotoxicosis, but no specific findings were identified, even with a combination of prednisolone.

The dog experienced the successful management of eosinophilic granuloma with oral glucocorticoid and azathioprine. The use of azathioprine may be an effective adjunctive immunosuppressive agent, and may be considered a well-tolerated prednisolone-sparing agent for the treatment of CEG. Nevertheless, the underlying etiology remains obscure. Therefore, further research will be needed to allow more effective treatment recommendations.

This work was supported by research fund of Chungnam National University.

  1. Declercq J, Vercauteren G. Necrotizing eosinophilic dermatitis in three dogs. Vlaam Diergeneeskd Tijdschr 2019; 88: 91-96.
    CrossRef
  2. Emery CB, Affolter VK, Outerbridge CA, Lam ATH, White SD. A case of atypical multifocal nodular eosinophilic dermatosis in a Labrador retriever dog. Vet Dermatol 2020; 31: 321-e82.
    Pubmed CrossRef
  3. Gross TL, Ihrke PJ, Walder EJ, Affolter VK. Nodular and diffuse diseases of the dermis with prominent eosinophils, neutrophils, or plasma cells. In: Gross TL, Ihrke PJ, Walder EJ, Affolter VK, editors. Skin diseases of the dog and cat: clinical and histopathologic diagnosis. 2nd ed. Oxford: Blackwell Science Ltd. 2005: 342-372.
    CrossRef
  4. Gross TL, Ihrke PJ, Walder EJ, Affolter VK. Pustular and nodular diseases with adnexal destruction. In: Gross TL, Ihrke PJ, Walder EJ, Affolter VK, editors. Skin diseases of the dog and cat: clinical and histopathologic diagnosis. 2nd ed. Oxford: Blackwell Science Ltd. 2005: 450-453.
    CrossRef
  5. Kim JH, Jung JY, Kang SC, Lee YR, Lee JY, Hwang EK, et al. Eosinophilic granulomas in two dogs. Korean Soc Vet Sci 2011; 51: 69-72.
    CrossRef
  6. Knight EC, Shipstone MA. Canine eosinophilic granuloma of the digits treated with prednisolone and chlorambucil. Vet Dermatol 2016; 27: 446-e119.
    Pubmed CrossRef
  7. Mendelsohn D, Lewis JR, Scott KI, Brown DC, Reiter AM. Clinicopathological features, risk factors and predispositions, and response to treatment of eosinophilic oral disease in 24 dogs (2000-2016). J Vet Dent 2019; 36: 25-31.
    Pubmed CrossRef
  8. Miller WH, Griffin CE, Campbell KL. Miscellaneous skin diseases. In: Miller WH, Griffin CE, Campbell KL, editors. Muller and Kirk’s small animal dermatology. 7th ed. St. Louis: Elsevier. 2013: 707-711, 714-718.
  9. Norris JM. Cutaneous eosinophilic granuloma in a crossbred dog. Aust Vet Pract 1994; 24: 74-78.
  10. Poulet FM, Valentine BA, Scott DW. Focal proliferative eosinophilic dermatitis of the external ear canal in four dogs. Vet Pathol 1991; 28: 171-173.
    Pubmed CrossRef
  11. Scott DW. Cutaneous eosinophilic granulomas with collagen degeneration in the dog. J Am Anim Hosp Assoc 1987; 19: 529-532.
  12. Sykes JM 4th, Garner MM, Greer LL, Lung NP, Coke RL, Ridgley F, et al. Oral eosinophilic granulomas in tigers (Panthera tigris)--a collection of 16 cases. J Zoo Wildl Med 2007; 38: 300-308.
    CrossRef
  13. Vercelli A, Cornegliani L, Portigliotti L. Eyelid eosinophilic granuloma in a Siberian husky. J Small Anim Pract 2005; 46: 31-33.
    Pubmed CrossRef
  14. Viviano KR. Update on immununosuppressive therapies for dogs and cats. Vet Clin North Am Small Anim Pract 2013; 43: 1149-1170.
    Pubmed CrossRef
  15. Wallisch K, Trepanier LA. Incidence, timing, and risk factors of azathioprine hepatotoxicosis in dogs. J Vet Intern Med 2015; 29: 513-518.
    Pubmed KoreaMed CrossRef

Article

Case Report

J Vet Clin 2022; 39(4): 192-196

Published online August 31, 2022 https://doi.org/10.17555/jvc.2022.39.4.192

Copyright © The Korean Society of Veterinary Clinics.

Eosinophilic Granuloma Treated with Prednisolone and Azathioprine in a Dog

Moonseok Jang1 , Wanghui Lee1,2 , Seongjun Park1

1College of Veterinary Medicine, Chungnam National University, Daejeon 34134, Korea
2Department of Companion Animal, Yeonsung University, Anyang 14011, Korea

Correspondence to:*parksj@cnu.ac.kr

Received: April 18, 2022; Revised: July 8, 2022; Accepted: July 13, 2022

This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

A two-year-old, intact male, 45 kg Doberman Pinscher was referred with dermal nodular lesions affecting the left hindlimb. The cytological examination revealed eosinophilic inflammation. Skin biopsy specimens showed canine eosinophilic granuloma (CEG). The dog was administered oral prednisolone (1.5 mg/kg/day) and azathioprine (2 mg/kg/day). After one week, the skin lesions diminished dramatically, but the dog presented with severe watery diarrhea. The prednisolone dose was reduced by 0.9 mg/kg/day. The lesions and diarrhea improved markedly after one week. Prednisolone was tapered by 25% of the previous dose every week to 0.2 mg/kg/day. Azathioprine was also reduced to therapy every other day. After seven weeks of combination treatment, the medications were withdrawn, but the dog had a recurrence one week later. Azathioprine (2 mg/kg/EOD) was reintroduced for two weeks. There was no relapse after all the medications had been withdrawn. This case indicates that CEG can be managed with prednisolone and azathioprine. Azathioprine may be an effective adjunctive immunosuppressive agent, and may be considered as a well-tolerated prednisolone sparing agent to treat CEG.

Keywords: eosinophilic granuloma, prednisolone, azathioprine, dog.

Introduction

Eosinophilic skin disease in dogs results from uncontrolled tissue damage following insults by parasites, allergens, infectious agents (fungi, bacteria, and viruses), or drugs. This clinical presentation includes eosinophilic furunculosis, canine acute eosinophilic dermatitis (CAEDE, Wells-like syndrome), eosinophilic granuloma, eosinophilic vasculitis, and necrotizing eosinophilic dermatitis (10). Canine eosinophilic granuloma (CEG) is an uncommon skin disease. Skin lesions are most frequently located in the oral cavity and infrequently involve other cutaneous sites, such as the nasal planum, ventral abdomen, thorax, metatarsus, prepuce, flank, digit, eyelid, external ear canal, and cheek region (6,9,13). The common clinical types of skin manifestations are papular, nodular, or plaque lesions. Lesions are typically firm, nonpruritic, erythematous, and ulcerated. Affected dogs are healthy without signs of systemic involvement. A marked breed predilection for Siberian husky dogs and cavalier King Charles spaniels suggests potential hereditary factors (13). Although the pathogenesis of CEG is unclear, immunological responses to antigenic exposure, including infectious and noninfectious allergens, are suspected (10). CEG is clinically managed with corticosteroid monotherapy (8). Treatment should be continued until the lesions have resolved completely to reduce the risk of recurrence. Prolonged use of high corticosteroid doses may have serious adverse effects, such as polyuria/polydipsia, diarrhea and vomiting, and hepatotoxicity. Therefore, some effective adjunctive immunosuppressive agents may be considered.

This case report describes the successful management of a case of CEG with prednisolone and azathioprine.

Case Report

A two-year-old, intact male, 45 kg Doberman Pinscher presented with a seven-month history of dermal nodular lesions affecting the left hindlimb. The owner reported a partial reduction in the size of the lesions subsequent to the prednisolone (0.5 mg/kg/day) and antibiotics treatments (amoxicillin-clavulanate, cephalexin) for three months, but the granulomas recurred after withdrawing the drugs. The granulomas were removed by surgical excision. The referring veterinarian also used afoxolaner (NexGard spectra, Merial) to exclude an ectoparasites infestation. On the other hand, the lesions developed again within three weeks. Therefore, the dog was referred to the Chungnam National University Veterinary Teaching Hospital.

The clinical evaluation revealed two ulcerated nodular lesions that measured 25 mm and 5 mm on the left lateral thigh region (Fig. 1). The physical feature was no presence of palpably enlarged peripheral lymph nodes. Imprinting smear revealed eosinophilic inflammations, and occasionally macrophages and neutrophils containing intracellular cocci were seen. Hematological analysis showed no abnormalities. For a histopathological examination, two skin biopsy specimens were collected from the lesions using 6 mm and 4 mm biopsy punches.

Figure 1. Ulcerated nodules measuring 25 mm located in the lateral thigh region (left) and measuring 5 mm located in the metatarsal region (right).

The skin biopsy revealed moderate to severe infiltrates of eosinophils with fewer macrophages in the dermis (Fig. 2). Large clusters of eosinophils surrounded hyalinized dermal collagen fibers, and occasionally flame figures were observed. The diagnosis was an eosinophilic granuloma. Oral prednisolone (Solondo, Yuhan) was instituted at 1.5 mg/kg/day for the first week. In conjunction with prednisolone, azathioprine (Immuthera, Celltrion pharm) also was initiated at 2 mg/kg/day and oral cephalexin (20 mg/kg twice daily for 28 days). After one week, the lesion started to diminish dramatically, but the dog showed severe watery diarrhea. The prednisolone dose was reduced by 0.9 mg/kg/day, and dioctahedral smectite (Smecta, Daewoong pharm) was prescribed. The lesions and diarrhea improved markedly after one week. The prednisolone dose was tapered by 25% of the previous seven weeks’ dose every week to 0.2 mg/kg/day. Azathioprine therapy was also reduced to every other day (EOD). After nine weeks of combination treatment, the medications were withdrawn totally. On the other hand, a small area of erosion and erythema with purulent exudates developed again one week later. Azathioprine 2 mg/kg/EOD and cephalexin (Falexin, Dongwha pharm) 20 mg/kg twice daily were reintroduced for two weeks. The bacterial culture and antibiotics sensitivity test revealed Pseudomonas straminea (susceptible to doxycycline and cefovecin). Doxycycline (Kukje pharm) was prescribed at 10 mg/kg twice daily with azathioprine 1 mg/kg/EOD for two weeks. There was no relapse after all medications had been withdrawn over the two-month follow-up period (Fig. 3).

Figure 2. Photomicrograph of an eosinophilic granuloma. Focal granuloma is cuffed by large numbers of eosinophils with fewer macrophages (left). The dermis contains a moderate to severe infiltrate of degranulated eosinophils and degenerated collagen fibers, so-called “flame-figure” (right) (H&E, 400×).

Figure 3. Skin lesions of the lateral thigh region (left) and the metatarsal region (right) after eight weeks of prednisolone and azathioprine treatment.

Discussion

CEG is an unusual skin disease with an uncertain etiology. Type I cell-mediated hypersensitivity reaction appears to play a role in the pathogenesis (13). This theory is supported by the predominance of eosinophils in these lesions and their positive response to glucocorticoid therapy (7). The triggers for such hypersensitivity reactions may be inhaled or ingested allergens, including seasonal allergens (pollens and molds), insects (mosquitoes), food, or exposure to irritants (fungi and bacteria) (7). No evidence of any of these possible causes was obtained in this case. On the other hand, the granuloma was located superficial to the deep dermis, and the nodules were found in the lateral thigh, suggesting a possible reaction to contact with an irritant.

Eosinophilic skin diseases in dogs include eosinophilic furunculosis, eosinophilic vasculitis, acute eosinophilic dermatitis (Wells-like syndrome), necrotizing eosinophilic dermatitis, and eosinophilic granuloma (2). This dog’s histopathologic presentation differed from the other eosinophilic diseases. Eosinophilic furunculosis was excluded due to a lack of folliculocentric eosinophilic inflammation (4). The blood vessels were intact in the skin biopsies, and there was no histopathological evidence of vascular damage ruling out eosinophilic vasculitis (3).

Eosinophilic granulomas have similar clinical lesions to Wells-like syndrome and necrotizing eosinophilic dermatitis, including erythematous papules, plaques, and nodules with yellow exudate and ulceration (2,3,13). In contrast to eosinophilic granuloma, Wells-like syndrome is frequently encountered with marked erythroderma of the ventrum, hypoalbuminemia, and gastrointestinal signs before the development of skin lesions. In addition, it has eosinophilic infiltration without degranulation (2). Necrotizing eosinophilic dermatitis typically shows significant areas of necrosis and features of vasculitis on histopathology (1). The dog fulfilled the conditions for distinct granulomas with marked central eosinophilic degranulation and multifocal areas of collagen degeneration, referred to as “flame figures” (2,5,13).

Most CEG cases in dogs have been treated based on the clinical presentation. Conventional therapy consists of symptomatic treatment and control of the suspected causes, such as parasitic, infectious, or allergenic agents. Therapeutic drugs may include glucocorticoids, antihistamines, or other hyposensitization therapies (7). Other treatments yielding various results include CO2 laser therapy and surgical incision (6). In this case, several treatments were conducted with anti-inflammatory therapy and surgical removal before referral. Because these treatments could not control the disease, immunosuppressive therapy was initiated as an alternative.

Several choices to control CEG have been reported, including glucocorticoid with prednisolone sparing drugs, particularly for chlorambucil and azathioprine (7,11,12). Chlorambucil is a cell cycle nonspecific alkylating antineoplastic and immunosuppressive agent (6). It targets B-cells and is considered a slow-acting agent that may require two weeks to reach therapeutic efficacy (14). The drug has previously been shown to be an effective steroid-sparing agent in a case of CEG of the digits (6). Azathioprine is an immunosuppressant used in both human and veterinary medicine (15). Azathioprine is a purine analog. A metabolite of azathioprine, 6-thioguanin nucleotides (6-TGNs), competes with endogenous purines for DNA and RNA synthesis and inhibits proliferation and T-cell-dependent antibody synthesis (14). On the other hand, the use of azathioprine is limited by the risk of hepato-toxicosis and bone marrow suppression. The hepatotoxic effect has been attributed to the accumulation of another metabolite, 6-methyl mercaptopurine (6-MMP). Bone marrow suppression, including neutropenia, thrombocytopenia, or both, is a commonly listed adverse effect of azathioprine. On the other hand, no prevalence studies have been reported in dogs (15). Hepatotoxicosis is defined by increases in alanine aminotransferase (ALT) activity more than two times the upper limit of the reference range. The clinical signs include vomiting, lethargy, and jaundice. In a retrospective study, hepatotoxicosis was observed in five out of 34 dogs (15%) treated with azathioprine within a median onset of 14 days (15). Therefore, it is recommended to monitor the serum liver enzymes on one or more occasions between one and four weeks after starting azathioprine in dogs (15). In the present case, the dog was monitored to obtain biochemical evidence of hepatotoxicosis, but no specific findings were identified, even with a combination of prednisolone.

Conclusions

The dog experienced the successful management of eosinophilic granuloma with oral glucocorticoid and azathioprine. The use of azathioprine may be an effective adjunctive immunosuppressive agent, and may be considered a well-tolerated prednisolone-sparing agent for the treatment of CEG. Nevertheless, the underlying etiology remains obscure. Therefore, further research will be needed to allow more effective treatment recommendations.

Acknowledgements

This work was supported by research fund of Chungnam National University.

Conflicts of Interest

The authors have no conflicting interests.

Fig 1.

Figure 1.Ulcerated nodules measuring 25 mm located in the lateral thigh region (left) and measuring 5 mm located in the metatarsal region (right).
Journal of Veterinary Clinics 2022; 39: 192-196https://doi.org/10.17555/jvc.2022.39.4.192

Fig 2.

Figure 2.Photomicrograph of an eosinophilic granuloma. Focal granuloma is cuffed by large numbers of eosinophils with fewer macrophages (left). The dermis contains a moderate to severe infiltrate of degranulated eosinophils and degenerated collagen fibers, so-called “flame-figure” (right) (H&E, 400×).
Journal of Veterinary Clinics 2022; 39: 192-196https://doi.org/10.17555/jvc.2022.39.4.192

Fig 3.

Figure 3.Skin lesions of the lateral thigh region (left) and the metatarsal region (right) after eight weeks of prednisolone and azathioprine treatment.
Journal of Veterinary Clinics 2022; 39: 192-196https://doi.org/10.17555/jvc.2022.39.4.192

References

  1. Declercq J, Vercauteren G. Necrotizing eosinophilic dermatitis in three dogs. Vlaam Diergeneeskd Tijdschr 2019; 88: 91-96.
    CrossRef
  2. Emery CB, Affolter VK, Outerbridge CA, Lam ATH, White SD. A case of atypical multifocal nodular eosinophilic dermatosis in a Labrador retriever dog. Vet Dermatol 2020; 31: 321-e82.
    Pubmed CrossRef
  3. Gross TL, Ihrke PJ, Walder EJ, Affolter VK. Nodular and diffuse diseases of the dermis with prominent eosinophils, neutrophils, or plasma cells. In: Gross TL, Ihrke PJ, Walder EJ, Affolter VK, editors. Skin diseases of the dog and cat: clinical and histopathologic diagnosis. 2nd ed. Oxford: Blackwell Science Ltd. 2005: 342-372.
    CrossRef
  4. Gross TL, Ihrke PJ, Walder EJ, Affolter VK. Pustular and nodular diseases with adnexal destruction. In: Gross TL, Ihrke PJ, Walder EJ, Affolter VK, editors. Skin diseases of the dog and cat: clinical and histopathologic diagnosis. 2nd ed. Oxford: Blackwell Science Ltd. 2005: 450-453.
    CrossRef
  5. Kim JH, Jung JY, Kang SC, Lee YR, Lee JY, Hwang EK, et al. Eosinophilic granulomas in two dogs. Korean Soc Vet Sci 2011; 51: 69-72.
    CrossRef
  6. Knight EC, Shipstone MA. Canine eosinophilic granuloma of the digits treated with prednisolone and chlorambucil. Vet Dermatol 2016; 27: 446-e119.
    Pubmed CrossRef
  7. Mendelsohn D, Lewis JR, Scott KI, Brown DC, Reiter AM. Clinicopathological features, risk factors and predispositions, and response to treatment of eosinophilic oral disease in 24 dogs (2000-2016). J Vet Dent 2019; 36: 25-31.
    Pubmed CrossRef
  8. Miller WH, Griffin CE, Campbell KL. Miscellaneous skin diseases. In: Miller WH, Griffin CE, Campbell KL, editors. Muller and Kirk’s small animal dermatology. 7th ed. St. Louis: Elsevier. 2013: 707-711, 714-718.
  9. Norris JM. Cutaneous eosinophilic granuloma in a crossbred dog. Aust Vet Pract 1994; 24: 74-78.
  10. Poulet FM, Valentine BA, Scott DW. Focal proliferative eosinophilic dermatitis of the external ear canal in four dogs. Vet Pathol 1991; 28: 171-173.
    Pubmed CrossRef
  11. Scott DW. Cutaneous eosinophilic granulomas with collagen degeneration in the dog. J Am Anim Hosp Assoc 1987; 19: 529-532.
  12. Sykes JM 4th, Garner MM, Greer LL, Lung NP, Coke RL, Ridgley F, et al. Oral eosinophilic granulomas in tigers (Panthera tigris)--a collection of 16 cases. J Zoo Wildl Med 2007; 38: 300-308.
    CrossRef
  13. Vercelli A, Cornegliani L, Portigliotti L. Eyelid eosinophilic granuloma in a Siberian husky. J Small Anim Pract 2005; 46: 31-33.
    Pubmed CrossRef
  14. Viviano KR. Update on immununosuppressive therapies for dogs and cats. Vet Clin North Am Small Anim Pract 2013; 43: 1149-1170.
    Pubmed CrossRef
  15. Wallisch K, Trepanier LA. Incidence, timing, and risk factors of azathioprine hepatotoxicosis in dogs. J Vet Intern Med 2015; 29: 513-518.
    Pubmed KoreaMed CrossRef

Vol.39 No.4 August, 2022

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