Canine and feline histoplasmosis: A review of a widespread fungus - Veterinary Medicine
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Canine and feline histoplasmosis: A review of a widespread fungus
Infection with this pathogenic fungus most commonly results from inhaling spores from contaminated soil. The infection should be treated promptly to avoid dissemination, which carries a poorer prognosis.



Table 2. Common Antifungal Treatments for Histoplasmosis in Dogs and Cats
Although canine pulmonary histoplasmosis may be self-limiting and resolve without treatment,7 antifungal therapy is recommended because of the risk of dissemination (Table 2).10,36 In people, itraconazole is the first-line treatment for mild to moderate pulmonary or disseminated histoplasmosis, and amphotericin B is the first-line treatment for severe pulmonary or disseminated histoplasmosis.67 Itraconazole or amphotericin B is considered the first-line treatment for histoplasmosis in dogs and cats.10


Even though itraconazole is reportedly the treatment of choice for histoplasmosis in dogs and cats,10,38 few reports of specific studies of its efficacy in these species exist. One report indicated good efficacy in eight cats treated with itraconazole (5 mg/kg orally b.i.d.) for 60 to 130 days, with two cats relapsing and requiring additional therapy to achieve complete remission.38 Because of marked variability in the oral absorption of itraconazole, some cats may require twice-daily dosing at 10 mg/kg.68 Different formulations of itraconazole exist (Table 2); of these, the oral suspension has the greatest bioavailability.22,68,69 Use of the intravenous formulation of itraconazole may be considered in animals that cannot be treated with an oral formulation. However, little data exist on the use of intravenous itraconazole in dogs and cats.22,69


Case example: Histoplasmosis in a Himalayan Cat
No studies evaluating fluconazole therapy in dogs and cats with disseminated histoplasmosis exist. But since fluconazole has increased penetration into the eye and central nervous system, it may theoretically be a better azole agent for patients that have neurologic or ocular involvement refractory to itraconazole.10 Results of an in vitro study showed that fluconazole had a higher minimal inhibitory concentration than itraconazole for Histoplasma species.70 However, in people, fluconazole is considered a second-line treatment for histoplasmosis,67 and in mice with experimentally induced Histoplasma species meningitis, fluconazole monotherapy was less efficacious than itraconazole or amphotericin B monotherapy.71


Successful treatment of feline histoplasmosis with varying dosages of ketoconazole has been reported.18,44,50 However, because of its reduced spectrum of activity against Histoplasma species and increased relative toxicity, ketoconazole is not a first-choice treatment.10

Voriconazole and posaconazole

Voriconazole, a triazole structurally related to fluconazole,72 and posaconazole, a triazole structurally related to itraconazole, also have activity against H. capsulatum. There are not sufficient data regarding the safety and efficacy of these newer agents in dogs and cats to warrant recommending their use. They may be considered as rescue therapy for patients in which other treatments have failed. Pharmacokinetic data for these agents in dogs are available.73,74

Amphotericin B

In dogs and cats with severe disseminated or pulmonary histoplasmosis, amphotericin B or combination therapy with amphotericin B and itraconazole may provide more effective control.10 Itraconazole treatment is started at the same time as amphotericin B and is continued for the normally recommended duration of treatment (Table 2) after amphotericin B treatment is terminated. Although typically administered intravenously, subcutaneous amphotericin B has been used to treat cryptococcosis.75

Nephrotoxicosis is an important adverse effect of amphotericin B therapy, particularly when the deoxycholate form is used. Since urine changes may precede serum elevations in urea nitrogen and creatinine, serial evaluation of urine specific gravity and monitoring for evidence of casts, protein, or hematuria should be performed.22 Because of their comparatively reduced nephrotoxicity, the lipid and liposomal forms of amphotericin B are preferred, and should be considered when amphotericin B treatment is indicated.76,77

While the lipid and liposomal forms of amphotericin B are more expensive, this increased expense must be considered in light of increased safety. The financial and health costs of toxicosis related to using the deoxycholate form may be as much or more of a burden than the additional cost of the lipid forms.78

Supportive therapies

Because of the risk of immunosuppression and subsequent dissemination of infection, glucocorticoids are generally not recommended in treating histoplasmosis. However, airway obstruction from enlarged hilar lymph nodes and inflammation associated with proliferation of the organism in the lungs can be life-threatening.10 In a study of dogs with enlarged hilar lymph nodes secondary to chronic pulmonary histoplasmosis, corticosteroid administration (prednisone 2 mg/kg orally every 12 to 24 hours) resulted in the resolution of the clinical signs of airway obstruction in less than one week, compared with 8.8 weeks in dogs treated with antifungal therapy.17 Only consider using corticosteroids if there is marked respiratory compromise and if no organisms are found on cytologic or histologic evaluation. Additional supportive therapy for pulmonary histoplasmosis may include oxygen supplementation and antibiotics, if clinically indicated.11


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