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Arquivo Brasileiro de Medicina Veterinária e Zootecnia

versão impressa ISSN 0102-0935versão On-line ISSN 1678-4162

Arq. Bras. Med. Vet. Zootec. v.55 n.2 Belo Horizonte abr. 2003

https://doi.org/10.1590/S0102-09352003000200005 

Generalized systemic cryptococcosis in a dog after immunosuppressive corticotherapy

 

Criptococose sistêmica generalizada em cão após corticoterapia imunossupressora

 

 

C.S. HonshoI; S.Y. MineII; A.P. OriáII; N. BenatoII; A.A. CamachoIII, *; A.C. AlessiIII; J.L. LausIII

IEstudante de pós-graduação da Escola de Veterinária da Unesp – Jaboticabal
IIResidente da Escola de Veterinária da Unesp – Jaboticabal
IIIEscola de Veterinária da Unesp Via de acesso Prof. Paulo Donato Castelane, s/n 14884-900 - Jaboticabal, SP

 

 


ABSTRACT

A male Boxer dog aged 2 years and 11 months was referred to the veterinary hospital with a history of a gastrointestinal disorder of two months duration, with apathy, hyporexia, progressive weight loss and visual deficit. Ataxia and vocalization were observed during hospitalization. The animal had been treated previously with antibiotics and immunosuppressive doses of corticoids to control chronic inflammatory bowel disease. The dog died five days later. Gross and microscopic observations indicated systemic cryptococcosis. The alimentary tract, eyes, brain, kidneys, pancreas and lymph nodes were involved.

Keywords: dog, generalized criptococcosis, Criptococcus neoformans, corticotherapy


RESUMO

Um cão da raça Boxer, macho, com 2 anos e 11 meses de idade foi encaminhado ao hospital veterinário com histórico de distúrbio gastroentérico de dois meses de duração, apatia, hiporexia, emagrecimento progressivo e deficiência visual. Ataxia e vocalização foram observadas posteriormente. O animal estava sendo tratado em outra clínica veterinária com antibióticos e doses imunossupressoras de corticóides, direcionados ao controle de provável enterite alimentar. A morte ocorreu após cinco dias. As observações macro e microscópica revelaram tratar-se de criptococose sistêmica, atingindo trato digestório, olhos, SNC, rins, pâncreas e linfonodos. O presente relato enfatiza a infecção fúngica criptocócica quanto aos seus aspectos grastrointestinais iniciais a serem considerados no diagnóstico clínico, ressaltando a imunossupressão induzida pela corticoterapia.

Palavras-chave: cão, criptococose generalizada, Cryptococcus neoformans, corticoterapia


 

 

INTRODUCTION

Cryptococcosis is an important systemic mycosis affecting dogs and cats worldwide. Among the different species of the genus Cryptococcus, Cryptococcus neoformans var. neoformans or var. gattii is the major agent causing the disease in humans and animals (Jacobs, Medleau, 1998). Cryptococcus is a saprophytic fungus which has been predominantly isolated from soil and pigeon feces (Stampley, Barsanti, 1988; Grogan, Hart, 1997; Jacobs, Medleau, 1998).

Cryptococcosis usually occurs in large-sized immunosuppressed dogs aged on average three years, and not linked to sex (van der Gaag et al., 1991; Wolf, Troy, 1992). Little is known about the route of infection, although many investigators believe that the respiratory tract may be the major point of entry by inhalation of the agent, with later hematogenous or lymphatic dissemination (Berry et al., 1990; Grogan, Hart, 1997; Malik et al., 1997; Jacobs, Medleau, 1998; Nelson, Couto, 1998; Malik et al., 1999).

In contrast to cats, in which involvement of the respiratory tract is more intense, in dogs involvement of the central nervous system (CNS) and of the eyes represents the major finding (van der Gaag et al., 1991; Wolf, Troy, 1992; Smith, 1994; Jacobs, Medleau, 1998; Sherding, 1998). On the other hand, lungs, skin, kidneys and, less commonly, the stomach, intestine, lymph nodes, pharynx, oral cavity, liver, spleen, heart, muscle and bones may also be involved (van der Gaag et al., 1991; Wolf, Troy, 1992; Sherding, 1998; Malik et al., 1999).

The definitive diagnosis is based on the identification of the agent by cytology and culture of the nasal exudate, cerebrospinal fluid and tissues such as skin, nails and lymph nodes, or by histopathological examination. The hematological and biochemical findings usually are not suggestive. At necropsy, the organs most often found to be infected are the eyes, CNS and respiratory tract (nasal sinuses and lungs).

The objective of the present report was to describe the major clinical manifestations of cryptococcosis in dogs with neurological and ophthalmological involvement, with emphasis on gastroenteric alterations as an uncommon form of presentation of the disease and on immunosuppression after corticotherapy.

 

CASE DESCRIPTION

A male boxer dog aged 2 years and 11 months was referred to the hospital with a clinical history suggestive of a gastrointestinal disorder. The dog had been treated previously with antibiotics and systemic corticoids and had, as declared by the owner, a recent loss of vision. Clinical examination revealed an apathic animal with a clinical history of hyporexia, progressive weight loss, liquid diarrhea with melena and sporadic hematochezia, in addition to cough and sneezing. Physical examination revealed a general state of cachexia, severe dehydration, and the presence of ulcerations in the oral cavity. Rectal palpation revealed the presence of several nodules measuring 0.5 to 1.0cm in diameter and of an extramural nature in the final portion of the organ.

Hematologic and biochemical examination and urinalysis yielded normal results for the species, except for isosthenuria observed by urinalysis. Feces parasitology examination and serology for toxoplasmosis and leptospirosis were negative.

Ophthalmic examination revealed a reduced response to light, intraocular pressure of 3 mmHg for both eyes, discrete episcleral congestion with moderate conjunctival hyperemia, and discrete corneal edema. Mild rubeosis iridis and the presence of a white color granuloma measuring approximately 1mm in diameter were also observed in the iris of the right eye. In the posterior segment there was diffuse vitreal exudation in the right eye, as well as peripapillary hemorrhage, retinal elevation in various areas suggestive of granulomatous chorioretinitis, and the presence of small pigmented nodules scattered in the tapetal transition of the left eye (Figure 1A). Treatment was topical prednisolone acetate (Pred fort – Allergan-Frumtost – Allergan-lok Produtos Farmacêuticos Ltda.) and 0.3% flurbiprophen (Ocufen – Allergan-Frumtost – Allergan-lok Produtos Farmacêuticos Ltda.) instillation at six-hour intervals and 1% atropine sulfate (Atropina 1% - Allergan-Frumtost – Allergan-lok Produtos Farmacêuticos Ltda.) instillation at 12-hour intervals.

 

 

Support treatment with fluid therapy and chemotherapy with sulfadiazine and trimetropim (Bactrim – Roche – Produtos Roche Químicos e Farmacêuticos S/A.) at the dose of 20mg/kg were started and the corticotherapy was discontinued. After four days, the patient returned presenting a worsening of clinical signs and symptoms, with episodes of vomiting, feces of liquid consistency and reddish color, vocalization, tetraparesis, anisocoria, and increased number of ulcers, with death occurring 24 hours later.

Necroscopic examination showed that the gastric mucosa had countless ulcers with raised borders ranging in diameter from 2 to 5mm, and that the mucosa of the small intestine had ulcers as large as 1 cm in size. The rectal mucosa presented countless nodules about 1.5cm in diameter with bloody content. The mesentery was thickened and all mesenteric lymph nodes were enlarged (Figure 1B). The pancreas was also enlarged. The liver was dark brown in color with a rugose aspect and granulated upon palpation. Several other whitish nodules were detected in the kidney - 0.5-1.0cm in diameter - (Figure 1C) and brain (1-3mm in diameter). Examination of the thoracic cavity showed pulmonary hepatization and in the heart a whitish region about 2cm in diameter in the right ventricle epicardium and infiltrating to the myocardium (Figure 1D). Fragments of these organs were collected and fixed in 10% formalin and later processed for histology by paraffin embedding. Histological sections were obtained and stained with hematoxylin-eosin (HE), period acid Schiff (PAS) and Gomori methenamine (GMS).

Histopathological examination of the kidneys showed thickening of the Bowman capsules with edema, glomerular degeneration and a mild mononuclear inflammatory infiltrate (Figure 1E). The lungs were emphysematous, with thickening of the alveolar walls which were infiltrated by large numbers of encapsulated microorganisms, many of them of small size and with a budding aspect, characteristic of C. neoformans. These features were clearly demonstrated by PAS staining and GMS. Other organs such as intestine (Figure 1F), liver, stomach, pancreas, lymph nodes, brain (Figure 1G-H), cerebellum and spinal cord presented the same type of lesion, i.e., the massive presence of fungi and a slight mononuclear infiltrate. In the intestine there was necrosis and the presence of large amounts of fungi. Fungi were also observed free in the intestinal lumen due to desquamation of the luminal epithelium.

 

DISCUSSION

In dogs, cryptococcosis mainly attacks immunosuppressed animals aged one to seven years and of large size (Wolf, Troy, 1992), as observed in the present case.

Involved animals may manifest clinical signs ranging from nonspecific ones such as anorexia, apathy and progressive weight loss to ocular and CNS involvement. The clinical neurological signs observed were depression, ataxia and visual deficit, evolving to obnubilation, vocalization and limb paresis (van der Gaag et al., 1991; Wolf, Troy, 1992; Smith, 1994; Jacobs, Medleau, 1998; Sherding, 1998). In addition to these clinical signs, the patient presented bloody diarrhea and vomiting characterizing also gastrointestinal involvement (Malik et al., 1999). The ocular changes observed in the eye fundus were characteristic of cryptococcosis, as described in the literature.

The diagnosis of cryptococcosis was based on the necropsy findings, with the detection of the infectious agent upon histopathological examination. The lesions were extensive and reached various organs including the CNS. The immature forms and the buds indicated that the fungus was in frank multiplication, perhaps as a consequence of the severe immunosuppressed state of the animal.

Blood count and biochemical exams were not conclusive and agreed with data reported by Wolf and Troy, (1992), Nelson and Couto (1998) and Sherding (1998).

Corticotherapy may have been a major cause of the worsening and dissemination of the infection as described by Malik et al. (1999), and probably, the isosthenuria detected by urinalysis was also due to the use of a corticosteroid.

It was not possible to establish the primary focal point of disease but, on the basis of the chronology of the clinical signs, it is believed that the disease may have started in the gastrointestinal tract, with later dissemination through the hematogenic route (van der Gaag et al., 1991; Malik et al., 1999). Indeed, necropsy and histopathology showed that the most evident gross and microscopic changes were confined to the entire gastrointestinal tract, although lesions also occurred in organs such as the lungs, CNS and eyes (Jacobs, Medleau, 1998). Thus, the initial gastroenteric clinical signs suggest that the point of entry of the infection may have been the gastrointestinal tract. Unfortunately the dog died before a definitive diagnosis was reached and therefore it was not possible to promote specific antifungal treatment (Berry et al., 1990; Wolf, Troy, 1992; Smith, 1994; Grogan, Hart, 1997; Sherding, 1998; Jacobs, Medleau, 1998; Nelson, Couto, 1998; Kerwin et al., 1998).

 

CONCLUSION

The present report of cryptococcosis in a dog focuses and emphasizes on fungal infection with respect to its early gastrointestinal aspects to be considered in the light of the clinical diagnosis, and the immunosuppression induced by corticotherapy.

 

ACKNOWLEDGEMENTS

To M. I. Y. Campos, E. Campos Filho, and F. A. Ardison for excellent technical assistance.

 

REFERENCES

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Recebido para publicação em 24 de dezembro de 2001
Recebido para publicação, após modificações, em 11 de outubro de 2002

 

 

* Corresponding author: E-mail: camacho@fcav.unesp.br

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