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Successful Management of 3 Dogs with Colonic Pythiosis Using Itraconzaole, Terbinafine, and Prednisone

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Successful Management of 3 Dogs with Colonic Pythiosis Using Itraconzaole, Terbinafine, and Prednisone UC Davis UC Davis Previously Published Works Title Successful management of 3 dogs with colonic pythiosis using itraconzaole, terbinafine, and prednisone. Permalink https://escholarship.org/uc/item/2119g65v Journal Journal of veterinary internal medicine, 33(3) ISSN 0891-6640 Authors Reagan, Krystle L Marks, Stanley L Pesavento, Patricia A et al. Publication Date 2019-05-01 DOI 10.1111/jvim.15506 Peer reviewed eScholarship.org Powered by the California Digital Library University of California Received: 19 January 2019 Accepted: 8 April 2019 DOI: 10.1111/jvim.15506 CASE REPORT Successful management of 3 dogs with colonic pythiosis using itraconzaole, terbinafine, and prednisone Krystle L. Reagan1 | Stanley L. Marks2 | Patricia A. Pesavento3 | Ann Della Maggiore1 | Bing Y. Zhu1 | Amy M. Grooters4 1Veterinary Medical Teaching Hospital, University of California Davis, Davis, California Abstract 2Department of Medicine and Epidemiology, Gastrointestinal (GI) pythiosis is a severe and often fatal disease in dogs that School of Veterinary Medicine, University of traditionally has been poorly responsive to medical treatment. Although aggressive sur- California, Davis, California 3Department of Pathology, Microbiology, and gical resection with wide margins is the most consistently effective treatment, lesion Immunology, School of Veterinary Medicine, location and extent often preclude complete resection. Recently, it has been suggested University of California, Davis, California that the addition of anti-inflammatory doses of corticosteroids may improve outcome 4Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State in dogs with nonresectable GI pythiosis. This report describes 3 dogs with colonic University, Baton Rouge, Louisiana pythiosis in which complete resolution of clinical signs, regression of colonic masses, Correspondence and progressive decreases in serological titers were observed after treatment with Krystle L. Reagan, University of California itraconazole, terbinafine, and corticosteroids. This treatment protocol represents a Davis, VMTH, 1 Garrod Drive, Davis, CA 95616. promising treatment for dogs with GI pythiosis in which surgical intervention is not Email: [email protected] feasible. Present addresses Ann Della Maggiore, MarQueen Pet KEYWORDS Emergency and Specialty, Roseville, CA 95661 antifungal, colitis, oomycete, Pythium insidiosum Bing Y. Zhu, Small Animal Specialist Hospital, North Ryde, New South Wales 2113, Australia 1 | INTRODUCTION that most often are affected include the gastric outflow region and the ileocecocolic junction (ICCJ). The aquatic oomycete Pythium insidiosum is the causative agent of Treatment of GI pythiosis traditionally has been unrewarding, pythiosis, a severe, progressive, and often fatal disease that most likely because ergosterol (the target of most traditional antifungal 9 often affects the skin or gastrointestinal (GI) tract in dogs.1 Although drugs) generally is lacking in the oomycete cell membrane. Instead, as historically it has been diagnosed in tropical and subtropical regions,2 sterol auxotrophs, Pythium, Lagenidium, and related oomycetes incor- its geographical distribution in the United States has expanded over porate sterols from their environments or hosts rather than producing them.9 Nonetheless, improvement or resolution of clinical disease has the past 15 years to include more arid environments in California and been described after treatment with ergosterol-targeting drugs (most Arizona and less temperate climates in Wisconsin.3,4 Gastrointestinal often itraconazole and terbinafine) in a small number of dogs with pythiosis typically causes focal or multifocal segmental thickening or pythiosis as well as in a 2-year-old child.5,10-12 expansile granulomatous masses involving the stomach, small intes- Despite these limited successes, the prognosis for dogs with non- tine, colon, and, less often, the esophagus.3,5-8 Areas of the GI tract resectable GI pythiosis has for the most part remained poor, with a reported median survival time of 26.5 days.3,5 Recently, however, it was noted that the addition of anti-inflammatory doses of prednisone Abbreviations: BCS, body condition score; BUN, blood urea nitrogen; GI, gastrointestinal; ICCJ, ileocecocolic junction; PP, percent positivity. to antifungal treatment in an effort to palliate clinical signs may This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. © 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine. 1434 wileyonlinelibrary.com/journal/jvim J Vet Intern Med. 2019;33:1434–1439. REAGAN ET AL. 1435 increase the likelihood of successful treatment in dogs with non- tenesmus had resolved and the dog had gained 1.9 kg body weight. A resectable GI pythiosis, and that complete resolution of disease can repeat CBC identified resolution of the previously noted eosinophilia occur in dogs treated with corticosteroids alone.1,13 Based on this (194/μL), but mild hypercalcemia (12 mg/dL; reference range, anecdotal information, 3 dogs with nonresectable colonic pythiosis 9.6-11.2 mg/dL) was noted on serum biochemistry. A trough were treated with a combination of itraconazole, terbinafine, and itraconazole serum concentration was low at <0.3 μg/mL (Itraconazole prednisone without surgical intervention. The purpose of our report is level detection by bioassay, MiraVista, Indianapolis, Indiana). This bio- to present the clinicopathologic findings, treatment, and outcome in assay detects activity of all antifungals and interpretation is difficult these 3 dogs. because this patient also was receiving terbinafine. The itraconazole dosage was increased to 13.4 mg/kg PO q24h and the terbinafine and prednisone were continued as described above. 2 | CASE 1 At reevaluation 3 months after initiation of treatment, the dog had gained an additional 1.6 kg body weight and had no clinical A 1-year-old male neutered Labrador cross breed dog was presented signs. Abdominal ultrasound examination identified mild thickening to the University of California, Davis Veterinary Medical Teaching of the ascending colonic wall, cecum, and ileum with resolution Hospital with a 1-month history of large bowel diarrhea, hematochezia, of the previously noted masses within the colon and ileum. The tenesmus, dyschezia, and weight loss. The dog was adopted 1 month previously enlarged mesenteric and sublumbar lymph nodes were before presentation and the previous medical history was unknown. ultrasonographically normal. Anti-P. insidiosum antibody serology General physical examination showed a body condition score (BCS) of was repeated and had decreased to 27% PP. After 6 months of treat- 2 out of 9 and slight tachycardia. Body weight on presentation was ment, serology results had decreased further to 13% PP, and predni- 12.8 kg. Rectal examination elicited a pain response but no other sone was tapered to 0.16 mg/kg PO q24h. Itraconazole and terbinafine abnormalities were noted. A CBC identified eosinophilia (1855/μL; were continued at the same dosage as initially administered. Abdominal reference range, 0-1500/μL) and serum biochemistry disclosed a mild ultrasound examination and serology were repeated every 6 months decrease in blood urea nitrogen (BUN) concentration of 8 mg/dL (refer- over the course of 5 years while continuing the same doses of predni- ence range, 11-33 mg/dL). Abdominal ultrasound examination identi- sone, itraconazole, and terbinafine, during which the dog remained fied smooth, severe (1 cm), circumferential thickening of the wall of the asymptomatic and had unremarkable abdominal ultrasound assessments. descending colon over an area >7 cm in length. An additional discrete Anti-P. insidiosum antibody serology was monitored every 6-12 months eccentric mass approximately 1 × 1 cm was noted in the ileal wall. Both and continued to be 13%-26% PP. Two years after diagnosis, serology lesions were hypoechoic with decreased definition of wall layering. The monitoring became unavailable from the initial laboratory and continued mesenteric and sublumbar lymph nodes were enlarged at approxi- serologic monitoring was performed using an alternative laboratory mately 1.5 cm in diameter with normal echogenicity, and a small vol- (Pythium Laboratory, Pathobiology Diagnostic Services, Auburn Uni- ume of peritoneal effusion was detected. Cytological evaluation of the versity, Auburn, Alabama). Five years after diagnosis, the dog's anti- effusion disclosed a protein concentration of 3.2 g/dL and 181 560 P. insidiosum antibody serology was 6% PP and the dog was still nucleated cells/μL comprised 76% neutrophils and 19% eosinophils. receiving itraconazole, terbinafine, and prednisone at the same doses Serology for anti-P. insidiosum antibodies (Pythium Laboratory, Louisi- described above. ana State University, Baton Rouge, Louisiana) was positive with a per- cent positivity (PP) of 104% (values reported to be <15% in healthy dogs and >40% in dogs with pythiosis).14 Colonoscopyb identified 3 | CASE 2 hyperemic, irregular, and edematous colonic mucosa. No obvious mass effect was noted. Colonic pinch biopsy specimens were consistent with A 7-year-old male Newfoundland and Labrador cross breed dog severe eosinophilic and histiocytic
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