Clinical signs, treatment, and prognostic factors for dogs with histoplasmosis

Abstract

OBJECTIVE To determine the clinical manifestations of histoplasmosis in a large sample of dogs, compare outcomes achieved with fluconazole versus itraconazole, and identify variables available at the time of diagnosis with prognostic value. DESIGN Retrospective case series with nested cohort study. ANIMALS 79 dogs with confirmed histoplasmosis evaluated at 2 veterinary teaching hospitals from 1999 through 2015. PROCEDURES Medical records were reviewed and data extracted regarding clinical signs at evaluation, physical examination findings, clinical laboratory values, other diagnostic test results, treatments, and outcomes. Data were compared between antifungal agents used (fluconazole or itraconazole) and between other variables. RESULTS Various breeds were represented. Working and herding breeds had mostly disseminated histoplasmosis, and toy breeds had mostly the gastrointestinal form. The diagnosis was often achieved with noninvasive techniques, such as cytologic evaluation of rectal scrape samples (n = 24) or blood films (15). Clinical remission was achieved in 16 of 25 (64%) dogs receiving fluconazole and 17 of 24 (71%) dogs receiving itraconazole. No differences were identified between antifungal agents in survival, clinical remission, or disease relapse rates. Identified negative prognostic factors included Great Pyrenees breed, dyspnea, need for oxygen supplementation, icterus, palpable abdominal organomegaly, anemia, thrombocytopenia, hypercalcemia, high serum alkaline phosphatase activity, and hyperbilirubinemia, whereas diarrhea was a positive prognostic factor. CONCLUSIONS AND CLINICAL RELEVANCE Findings suggested that histoplasmosis should be considered in a sick dog of any breed in an endemic area. Clinical signs may be nonspecific. Diagnosis may often be possible with noninvasive and inexpensive tests. Either fluconazole or itraconazole may be an effective treatment option.

Ultrasonographic findings of gastrointestinal histoplasmosis in dogs

“…Abdominocentesis was not performed in every case with peritoneal effusion, but when available, it was most commonly a transudate attributed to the patient's hypoalbuminemia. Consistent with preexisting literature, in our study two dogs had presence of Histoplasma yeasts within the effusion 4,24,25,26 …”

“…No dog with available thoracic radiographs had pulmonary parenchymal abnormalities or respiratory clinical signs. This is consistent with the gastrointestinal form of histoplasmosis documented in dogs that does not concurrently have respiratory signs or radiographic changes 4,27 . Sternal lymphadenopathy was most likely reactive from abdominal disease.…”

Clinical pharmacokinetics and outcomes of oral fluconazole therapy in dogs and cats with naturally occurring fungal disease

“…For the purpose of this study, a successful treatment outcome was defined as achieving clinical remission of fungal disease with fluconazole therapy, and treatment failure was defined as inability to achieve remission. Clinical remission was defined as resolution of all previous clinical signs of fungal disease on physical or ophthalmic examination or radiography; inactive ophthalmic lesions or static radiographic changes (taken 1 month apart) were also considered remission (Mazepa et al., 2011; Reinhart et al., 2012; Wilson et al., 2018).…”

“…In veterinary medicine, it was first studied for cryptococcosis in cats, and many dosing recommendations have been extrapolated from that initial research (Malik, Wigney, Muir, Gregory, & Love, 1992). It is now routinely used to treat blastomycosis, coccidioidomycosis, and histoplasmosis in dogs and cats (Arbona, Butkiewicz, Keyes, & Shubitz, 2020; Ludwig, Hanzlicek, KuKanich, & Payton, 2018; Mazepa, Trepanier, & Foy, 2011; Reinhart, KuKanich, Jackson, & Harkin, 2012; Wilson, KuKanich, Hanzlicek, & Payton, 2018). Recommended doses of fluconazole range from 5 to 10 mg/kg PO every 12–24 hr for dogs and 10 mg/kg or 50 mg/cat every 12–24 hr (Arbona et al., 2020; Ludwig et al., 2018; Malik et al., 1992; Mazepa et al., 2011; Papich, 2011; Reinhart et al., 2012; Wilson et al., 2018).…”

“…It is now routinely used to treat blastomycosis, coccidioidomycosis, and histoplasmosis in dogs and cats (Arbona, Butkiewicz, Keyes, & Shubitz, 2020; Ludwig, Hanzlicek, KuKanich, & Payton, 2018; Mazepa, Trepanier, & Foy, 2011; Reinhart, KuKanich, Jackson, & Harkin, 2012; Wilson, KuKanich, Hanzlicek, & Payton, 2018). Recommended doses of fluconazole range from 5 to 10 mg/kg PO every 12–24 hr for dogs and 10 mg/kg or 50 mg/cat every 12–24 hr (Arbona et al., 2020; Ludwig et al., 2018; Malik et al., 1992; Mazepa et al., 2011; Papich, 2011; Reinhart et al., 2012; Wilson et al., 2018). However, minimal pharmacokinetic (PK) data are available to support dosing recommendations, and the majority of available PK data come from healthy animals which may not predict the appropriate dosages for diseased animals (Craig, Ramzan, & Malik, 1994; Humphrey, Jevons, & Tarbit, 1985; Malik et al., 1992; Vaden, Heit, Hawkins, Manaugh, & Riviere, 1997).…”