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      Successful Treatment of Cutaneous Curvularia geniculata, Nocardia niigatensis, and Viral Papillomatosis in a Dog During the Therapeutic Management of Immune-Mediated Hemolytic Anemia

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          Abstract

          Opportunistic infections represent a major cause of mortality in immunocompromised patients. Discontinuation or reduction of immunosuppressive medications is recommended with the development of opportunistic infections, which may cause a relapse or worsening of the immune-mediated disease. A 7.5-year-old, spayed female great Dane was diagnosed with immune-mediated hemolytic anemia with initial immunosuppressive therapy consisting of oral prednisone, ciclosporin and mycophenolate mofetil. The patient developed diffuse right forelimb pyogranulomatous fungal dermatitis with deep draining tracts 6 weeks into immunosuppressive treatment with Curvularia geniculata growth. Oral once daily terbinafine and itraconazole were initiated; ciclosporin was immediately discontinued and the mycophenolate mofetil/prednisone doses were reduced. The right forelimb skin lesions resolved after 4 weeks, but the patient presented with a diffuse severe neutrophilic dermatitis on the left forelimb; 16S rRNA sequencing identified Nocardia niigatensis. Cutaneous nocardiosis was treated with oral enrofloxacin and doxycycline; systemic immunosuppressive therapies were continued for immune-mediated hemolytic anemia control. One month later, the left forelimb lesions completely resolved but the patient developed several multifocal, exophytic warts; the clinical features and histopathology were consistent with viral papillomas. Within the following 4 weeks, the patient developed severe diffuse papillomatosis of the left forelimb, which was successfully treated with 2 weeks of every other day topical imiquimod administration. In this case, successful treatment of cutaneous opportunistic bacterial, fungal and viral infection was possible with proper treatment even though the immunosuppressive drug treatments could not be discontinued.

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          Most cited references22

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          Nocardiosis: updates and clinical overview.

          Nocardia, a gram-positive bacillus with the microscopic appearance of branching hyphae, can produce considerable disease in the appropriate host. The taxonomy of Nocardia continues to evolve; more than 50 species have been described. Early recognition and effective therapy are imperative to achieve successful outcomes. Although nocardiosis typically occurs in patients with cell-mediated immunosuppressive conditions, infection may occasionally develop in immunocompetent patients as well. This review addresses the microbiology of Nocardia, risk factors for infection, clinical presentations, and management strategies. Copyright © 2012 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.
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            Comparative review of human and canine osteosarcoma: morphology, epidemiology, prognosis, treatment and genetics

            Osteosarcoma (OSA) is a rare cancer in people. However OSA incidence rates in dogs are 27 times higher than in people. Prognosis in both species is relatively poor, with 5 year OSA survival rates in people not having improved in decades. For dogs, 1 year survival rates are only around ~ 45%. Improved and novel treatment regimens are urgently required to improve survival in both humans and dogs with OSA. Utilising information from genetic studies could assist in this in both species, with the higher incidence rates in dogs contributing to the dog population being a good model of human disease. This review compares the clinical characteristics, gross morphology and histopathology, aetiology, epidemiology, and genetics of canine and human OSA. Finally, the current position of canine OSA genetic research is discussed and areas for additional work within the canine population are identified.
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              Imiquimod and the imidazoquinolones: mechanism of action and therapeutic potential.

              A central development of the past decade has been in our understanding of the interactions between, and interdependence of, the innate and adaptive immune responses. Innate immunity recognizes 'danger' signals and activates adaptive immunity in a targeted, appropriate and effective response. Dendritic cells and macrophages have a central role in this process, and pharmacological agents that modulate the functions of these cells could have therapeutic value. The imidazoquinolone compounds, of which imiquimod, formulated as Aldara trade mark, is the best characterized to date, are such molecules. Imiquimod and its homologues act by activating macrophages and other cells via binding to cell surface receptors, such as Toll receptor 7, thereby inducing secretion of pro-inflammatory cytokines, predominantly interferon (IFN)-alpha, tumour necrosis factor (TNF)-alpha and interleukin (IL)-12. This locally generated cytokine milieu biases towards a Th1 cell mediated immune response with the generation of cytotoxic effectors, and this has been exploited clinically in the treatment of viral infections (human papillomavirus, herpes simplex virus, molluscum contagiosum) and nonmelanoma skin cancer. Imiquimod has been shown to be significantly more effective than placebo in clearing genital warts, and mechanism of action studies indicate that this is related to the ability to generate proinflammatory cytokines and a Th1 response. Intra-epithelial neoplasms of cutaneous and mucosal surfaces are associated with human papillomavirus infection and there is some evidence that immune response modifiers may have therapeutic value for these lesions. Topical immunotherapy with immunomodulators shows potential for effective and patient-friendly treatment of cutaneous viral infections. These compounds also have adjuvant properties that could significantly enhance conventional vaccine strategies.
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                Author and article information

                Contributors
                Journal
                Front Vet Sci
                Front Vet Sci
                Front. Vet. Sci.
                Frontiers in Veterinary Science
                Frontiers Media S.A.
                2297-1769
                08 August 2019
                2019
                : 6
                : 249
                Affiliations
                [1] 1Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia , Athens, GA, United States
                [2] 2Department of Pathology, College of Veterinary Medicine, University of Georgia , Athens, GA, United States
                Author notes

                Edited by: Silke Salavati, University of Edinburgh, United Kingdom

                Reviewed by: Elizabeth A. Layne, University of Wisconsin-Madison, United States; Jacques Fontaine, University of Liège, Belgium

                *Correspondence: Frane Banovic fbanovic@ 123456uga.edu

                This article was submitted to Comparative and Clinical Medicine, a section of the journal Frontiers in Veterinary Science

                Article
                10.3389/fvets.2019.00249
                6694281
                8193b2c5-7db5-47a8-938a-5f68456d10d1
                Copyright © 2019 Strzok, Siepker, Armwood, Howerth, Smith and Banovic.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 03 April 2019
                : 10 July 2019
                Page count
                Figures: 3, Tables: 0, Equations: 0, References: 22, Pages: 7, Words: 3555
                Categories
                Veterinary Science
                Case Report

                opportunistic skin infections,canine,skin,dermatology,immunosuppression

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