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      Disseminated cryptococcosis presenting initially as lower limb cellulitis in a renal transplant recipient – a case report

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          Abstract

          Background

          Cellulitis is an unusual presentation of disseminated cryptococcosis, a serious infection seen predominantly in immunocompromised hosts. Disseminated cryptococcosis carries significant morbidity for transplant recipients, especially of the pulmonary and central nervous systems, and carries a high mortality risk.

          Case presentation

          We report a 59-year-old renal transplant recipient who presented with bilateral lower leg cellulitis without other symptoms or signs. Failure of conventional therapy for cellulitis prompted a skin biopsy confirming cryptococcal cellulitis. Additional evaluation to exclude disseminated disease revealed Cryptococcus neoformans in blood cultures and cerebrospinal fluid (CSF). Treatment included reduction in immunosuppression regimen and targeted treatment for cryptococcal disease with liposomal amphotericin B and flucytosine followed by fluconazole consolidation and maintenance therapy. Treatment with liposomal amphotericin B and flucytosine followed by fluconazole consolidation and maintenance therapy achieved a good clinical response. Our patient achieved significant reduction in leg cellulitis and recovered without serious complication.

          Conclusions

          This case suggests that cutaneous cryptococcosis in immunosuppressed patients warrants a low threshold for investigation for disseminated disease even in the absence of other symptoms or signs.

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          Most cited references24

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          Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america.

          Cryptococcosis is a global invasive mycosis associated with significant morbidity and mortality. These guidelines for its management have been built on the previous Infectious Diseases Society of America guidelines from 2000 and include new sections. There is a discussion of the management of cryptococcal meningoencephalitis in 3 risk groups: (1) human immunodeficiency virus (HIV)-infected individuals, (2) organ transplant recipients, and (3) non-HIV-infected and nontransplant hosts. There are specific recommendations for other unique risk populations, such as children, pregnant women, persons in resource-limited environments, and those with Cryptococcus gattii infection. Recommendations for management also include other sites of infection, including strategies for pulmonary cryptococcosis. Emphasis has been placed on potential complications in management of cryptococcal infection, including increased intracranial pressure, immune reconstitution inflammatory syndrome (IRIS), drug resistance, and cryptococcomas. Three key management principles have been articulated: (1) induction therapy for meningoencephalitis using fungicidal regimens, such as a polyene and flucytosine, followed by suppressive regimens using fluconazole; (2) importance of early recognition and treatment of increased intracranial pressure and/or IRIS; and (3) the use of lipid formulations of amphotericin B regimens in patients with renal impairment. Cryptococcosis remains a challenging management issue, with little new drug development or recent definitive studies. However, if the diagnosis is made early, if clinicians adhere to the basic principles of these guidelines, and if the underlying disease is controlled, then cryptococcosis can be managed successfully in the vast majority of patients.
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            Invasive fungal infections among organ transplant recipients: results of the Transplant-Associated Infection Surveillance Network (TRANSNET).

            Invasive fungal infections (IFIs) are a major cause of morbidity and mortality among organ transplant recipients. Multicenter prospective surveillance data to determine disease burden and secular trends are lacking. The Transplant-Associated Infection Surveillance Network (TRANSNET) is a consortium of 23 US transplant centers, including 15 that contributed to the organ transplant recipient dataset. We prospectively identified IFIs among organ transplant recipients from March, 2001 through March, 2006 at these sites. To explore trends, we calculated the 12-month cumulative incidence among 9 sequential cohorts. During the surveillance period, 1208 IFIs were identified among 1063 organ transplant recipients. The most common IFIs were invasive candidiasis (53%), invasive aspergillosis (19%), cryptococcosis (8%), non-Aspergillus molds (8%), endemic fungi (5%), and zygomycosis (2%). Median time to onset of candidiasis, aspergillosis, and cryptococcosis was 103, 184, and 575 days, respectively. Among a cohort of 16,808 patients who underwent transplantation between March 2001 and September 2005 and were followed through March 2006, a total of 729 IFIs were reported among 633 persons. One-year cumulative incidences of the first IFI were 11.6%, 8.6%, 4.7%, 4.0%, 3.4%, and 1.3% for small bowel, lung, liver, heart, pancreas, and kidney transplant recipients, respectively. One-year incidence was highest for invasive candidiasis (1.95%) and aspergillosis (0.65%). Trend analysis showed a slight increase in cumulative incidence from 2002 to 2005. We detected a slight increase in IFIs during the surveillance period. These data provide important insights into the timing and incidence of IFIs among organ transplant recipients, which can help to focus effective prevention and treatment strategies.
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              Epidemiological evidence for dormant Cryptococcus neoformans infection.

              To date, the time of acquisition of a Cryptococcus neoformans infectious strain has never been studied. We selected a primer, (GACA)(4), and a probe, CNRE-1, that by randomly amplified polymorphic DNA (RAPD) analysis and restriction fragment length polymorphism (RFLP), respectively, regrouped strains from control samples of C. neoformans var. grubii environmental isolates according to their geographical origins. The two typing techniques were then used to analyze 103 isolates from 29 patients diagnosed with cryptococcosis in France. Nine of the 29 patients lived in Africa a median of 110 months prior to moving to France; 17 of the patients originated from Europe. Results showed a statistically significant clustering of isolate subtypes from patients originating from Africa compared to those from Europe. We conclude that the patients had acquired the C. neoformans infectious strain long before their clinical diagnoses were made.

                Author and article information

                Contributors
                katrina.chakradeo@health.qld.gov.au
                paulchia@graduate.uwa.edu.au
                Cheng.Liu@health.qld.gov.au
                david.mudge@health.qld.gov.au
                janath.desilva@health.qld.gov.au
                Journal
                BMC Nephrol
                BMC Nephrol
                BMC Nephrology
                BioMed Central (London )
                1471-2369
                27 January 2018
                27 January 2018
                2018
                : 19
                : 18
                Affiliations
                [1 ]ISNI 0000 0004 0430 0107, GRID grid.460765.6, Department of Medicine, , Mackay Base Hospital, ; Bridge Road, Mackay, Australia
                [2 ]ISNI 0000 0004 0437 5432, GRID grid.1022.1, Griffith University School of Medicine, , Griffith University, ; Gold Coast, Australia
                [3 ]ISNI 0000 0004 0474 1797, GRID grid.1011.1, College of Medicine and Dentistry, , James Cook University, ; Townsville, Australia
                [4 ]Department of Anatomical Pathology, Royal Brisbane and Woman’s Hospital, Brisbane, Australia
                [5 ]ISNI 0000 0004 0380 2017, GRID grid.412744.0, Queensland Renal Transplant Service, , Princess Alexandra Hospital, ; Brisbane, Australia
                Author information
                http://orcid.org/0000-0001-6091-5948
                Article
                815
                10.1186/s12882-018-0815-7
                5787248
                29374464
                aa8692a1-7936-4d22-bb2b-dbbf299c7e9e
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 27 October 2016
                : 17 January 2018
                Categories
                Case Report
                Custom metadata
                © The Author(s) 2018

                Nephrology
                case report,crypotococcosis,cryptococcus neoformans,cellulitis,renal transplant
                Nephrology
                case report, crypotococcosis, cryptococcus neoformans, cellulitis, renal transplant

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