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      Pulmonary histoplasmosis presenting with a halo sign on CT in an immunocompetent patient

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          Abstract

          To the Editor: Histoplasmosis is a common endemic mycosis. Although most infections in immunocompetent individuals are self-limiting, some patients develop severe pneumonitis or other types of chronic pulmonary infection. Specific imaging findings depend on the organisms involved, the underlying condition of the patient, and his condition after immune depleting procedures. The disease process in immunocompetent patients is usually limited to a solitary nodule on chest X-rays or CT scans, but enlarged hilar or mediastinal lymph nodes can also be observed.( 1 ) We report here the case of an immunocompetent patient with histoplasmosis who presented with a halo sign on CT. A 47-year-old man presented with dry cough, chest pain, fatigue, and fever, having started 15 days prior. He reported neither comorbidities nor a contact with environments with mold. The patient was negative for HIV by ELISA. Laboratory tests revealed leukocytosis, elevated C-reactive protein levels (33 mg/L), and hypertransaminasemia (three-fold higher than the upper limit of normal). CT scanning revealed a pulmonary nodule with a halo sign in his left lower lobe (Figure 1) and left para-hilar lymph nodes. Histological examination of a pulmonary biopsy sample obtained during bronchoscopy showed nonspecific inflammatory alterations. Cultures for mycobacteria and fungi were negative. Serology by counterimmunoelectrophoresis was positive for histoplasmosis. Figure 1 A CT scan at the level of the lower lobes showing a nodule surrounded by ground-glass attenuation (halo sign) in the left lower lobe. Treatment was initiated with itraconazole (400 mg/day). After 30 days, a CT scan showed that the size of the nodule was reduced by half. The patient showed progressive improvement of clinical symptoms and a reduction of the para-aortic adenopathy. Treatment was maintained for one year, during which the patient remained asymptomatic, the nodule completely disappeared, and the lymphadenopathy resolved. However, histoplasmosis by counterimmunoelectrophoresis remained positive. We reported the case of an immunocompetent patient who presented with a halo sign and lymphadenopathy caused by histoplasmosis, showing a good clinical response after one year of treatment with itraconazole (400 mg/day). Histoplasma capsulatum is a major endemic human fungal pathogen that can cause a broad variety of clinical presentations, ranging from mild, focal pulmonary disease to life-threatening systemic infections.( 1 ) In one study, open lung biopsies of 155 patients with undiagnosed lung lesions showed that infectious etiologies were responsible for 19% of the lesions, the most common diagnosis in this group being histoplasmosis (41%).( 2 ) The halo sign is characterized by a ground-glass opacity surrounding a nodule, mass, or round area of consolidation.( 3 ) This sign is frequently an early indicator of invasive pulmonary aspergillosis in immunocompromised patients,( 4 ) but it might also indicate other invasive fungal diseases. Our patient required treatment with high doses of itraconazole for one year. Azoles, such as itraconazole and voriconazole, and amphotericin B have significant activity against H. capsulatum. However, approximately 10% of the patients hospitalized due to histoplasmosis die,( 5 ) despite the lack of antifungal resistance among recovered isolates.( 6 ) In conclusion, a halo sign on CT might indicate active histoplasmosis, which may require long-term treatment, even in immunocompetent patients.

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          Pulmonary fungal infection: imaging findings in immunocompetent and immunocompromised patients.

          Histoplasmosis is the most common endemic mycosis in North America, and is followed by coccidioidomycosis and blastomycosis. Although the majority of these infections in immunocompetent persons are self-limited, some patients can develop severe pneumonitis or various forms of chronic pulmonary infection. Cryptococcoci, Aspergillus, Candidas, and Mucorals are ubiquitous organisms, which may affect immunocompromised patients. Specific imaging findings can be expected, depending on the organisms involved, underlying patients' conditions (immune status), and specific situations after immune depleting procedures.
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            Histoplasmosis in HIV-positive patients in Ceará, Brazil: clinical-laboratory aspects and in vitro antifungal susceptibility of Histoplasma capsulatum isolates.

            This study contains a descriptive analysis of histoplasmosis in AIDS patients between 2006 and 2010 in the state of Ceará, Brazil. Additionally, the in vitro susceptibility of Histoplasma capsulatum isolates obtained during this period was assessed. We report 208 cases of patients with histoplasmosis and AIDS, describing the epidemiological, clinical, laboratory and therapeutic aspects. The in vitro antifungal susceptibility test was carried out by the microdilution method, according to Clinical and Laboratory Standards Institute, with H. capsulatum in the filamentous and yeast phases, against the antifungals amphotericin B, fluconazole, itraconazole, voriconazole and caspofungin. In 38.9% of the cases, histoplasmosis was the first indicator of AIDS and in 85.8% of the patients the CD4 cell count was lower than 100 cells/mm(3). The lactate dehydrogenase levels were high in all the patients evaluated, with impairment of hepatic and renal function and evolution to death in 42.3% of the cases. The in vitro susceptibility profile demonstrated there was no antifungal resistance among the isolates evaluated. There was a significant increase in the number of histoplasmosis cases in HIV-positive patients during the period surveyed in the state of Ceará, northeastern Brazil, but no antifungal resistance among the recovered isolates of H. capsulatum. Copyright © 2012 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.
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              Antibody Therapy for Histoplasmosis

              The endemic human pathogenic fungus Histoplasma capsulatum is a major fungal pathogen with a broad variety of clinical presentations, ranging from mild, focal pulmonary disease to life-threatening systemic infections. Although azoles, such as itraconazole and voriconazole, and amphotericin B have significant activity against H. capsulatum, about 1 in 10 patients hospitalized due to histoplasmosis die. Hence, new approaches for managing disease are being sought. Over the past 10 years, studies have demonstrated that monoclonal antibodies (mAbs) can modify the pathogenesis of histoplasmosis. Disease has been shown to be impacted by mAbs targeting either fungal cell surface proteins or host co-stimulatory molecules. This review will detail our current knowledge regarding the impact of antibody therapy on histoplasmosis.
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                Author and article information

                Contributors
                Role: Infectious Disease Specialist
                Role: Pulmonologist
                Role: Radiologist
                Role: Radiologist
                Journal
                J Bras Pneumol
                J Bras Pneumol
                Jornal Brasileiro de Pneumologia : Publicaça̋o Oficial da Sociedade Brasileira de Pneumologia e Tisilogia
                Sociedade Brasileira de Pneumologia e Tisiologia
                1806-3713
                1806-3756
                Jun-Aug 2013
                Jun-Aug 2013
                : 39
                : 4
                : 523-524
                Affiliations
                Hospital Nipo-Brasileiro de São Paulo, São Paulo, Brazil
                Hospital Nipo-Brasileiro de São Paulo, São Paulo, Brazil
                Hospital Nipo-Brasileiro de São Paulo, São Paulo, Brazil
                Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
                Hospital Nipo-Brasileiro de São Paulo, São Paulo (SP) Brasil
                Hospital Nipo-Brasileiro de São Paulo, São Paulo (SP) Brasil
                Hospital Nipo-Brasileiro de São Paulo, São Paulo (SP) Brasil
                Universidade Federal do Rio de Janeiro, Rio de Janeiro (RJ) Brasil
                Article
                S1806-37132013000400019
                10.1590/S1806-37132013000400019
                4075861
                24068277
                4f9c28bb-b97b-46cf-955d-579c0f429afd

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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                Page count
                Figures: 1, References: 6, Pages: 2
                Categories
                Letter to the Editor

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