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SOURCE

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Source: Carver PL. Invasive fungal infections. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 10th ed. New York, NY: McGraw-Hill; 2017. http://accesspharmacy.mhmedical.com/content.aspx?bookid=1861&sectionid=146073167. Accessed February 23, 2017.

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DEFINITION

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  • Systemic fungal infection.

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ETIOLOGY

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  • Inhalation of dust-borne Histoplasma capsulatum

  • Acute histoplasmosis may occur in epidemics when soil disturbed.

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PATHOPHYSIOLOGY

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  • Aerosolized H. capsulatum is inhaled and settles in lungs.

  • Tissue granulomas form over 2–4 months.

    • Foci become encapsulated and calcified over several years.

  • Low-inoculum exposure results in benign disease course.

  • Higher-inoculum exposure results in acute, self-limited illness.

    • Fever.

    • Chills.

    • Headache.

    • Myalgia.

    • Nonproductive cough.

  • Chronic pulmonary histoplasmosis.

    • Progressive disease over period of years.

      • Cavitation.

      • Bronchopleural fistulas.

      • Involvement of both lungs.

      • Pulmonary insufficiency.

      • Death.

  • Immunocompromised hosts.

    • Progressive, disseminated histoplasmosis.

  • Acute disseminated histoplasmosis.

    • Infants and young children: fatal in 1–2 months if untreated.

    • Adults: untreated patients ill for 10–20 years, with long asymptomatic periods.

  • Histoplasmosis in HIV-infected patients.

    • Progressive disseminated histoplasmosis (PDH) serves as the first manifestation of AIDS in 50% of HIV-infected patients.

    • Symptoms include fever, weight loss, chills, night sweats, enlargement of spleen, liver, or lymph nodes, and anemia.

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EPIDEMIOLOGY

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  • Localized along Ohio and Mississippi River valleys in United States.

  • Found in nitrogen-enriched soils, particularly those contaminated by avian or bat guano.

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RISK FACTORS

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  • Immunosuppression (eg, AIDS)

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CLINICAL PRESENTATION

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  • Immunocompromised hosts.

    • Adults with AIDS present with acute form of disseminated disease that resembles syndrome seen in infants and children.

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SIGNS AND SYMPTOMS
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  • Chronic pulmonary histoplasmosis.

    • Chronic pulmonary symptoms.

    • Apical lung lesions.

  • Acute disseminated histoplasmosis.

    • Infants and young children.

      • Unrelenting fever.

      • Anemia.

      • Leukopenia or thrombocytopenia.

      • Enlargement of liver, spleen, and visceral lymph nodes.

      • Gastrointestinal (GI) symptoms: nausea, vomiting, diarrhea.

    • Adults.

      • Long asymptomatic periods interrupted by.

        • Weight loss.

        • Weakness.

        • Fatigue.

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DIAGNOSIS

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MEANS OF CONFIRMATION AND DIAGNOSIS
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  • Serologic testing.

    • Complement fixation.

    • Immunodiffusion.

    • Enzyme immunoassay (EIA)

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LABORATORY TESTS

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  • Culture.

    • Identification of mycelial isolates from clinical cultures can be made by conversion of mycelium to yeast form (requires 3–6 weeks) or by more rapid (2 hours) and 100%-sensitive DNA probe that recognizes ribosomal DNA.

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IMAGING

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  • Chest radiograph.

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DIAGNOSTIC PROCEDURES

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  • Bone marrow biopsy and culture is the best method to establish diagnosis in AIDS patients with progressive disseminated histoplasmosis.

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DIFFERENTIAL DIAGNOSIS

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DESIRED OUTCOMES

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  • Resolution of clinical abnormalities.

  • Prevention of relapse.

  • Eradication of infection.

    • Chronic suppression for immunosuppressed patients.

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TREATMENT: GENERAL APPROACH

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