History and exam

Key diagnostic factors

common

exposure to fungal spores

The fungus grows in soil and material contaminated with bat or bird droppings. Infection results from inhalation of spores that are disseminated into the atmosphere when soil and/or organic material containing the spores are disturbed. Patients who inhale a large inoculum are more likely to develop severe acute pulmonary histoplasmosis, while a low inoculum exposure is more likely to result in asymptomatic or mildly symptomatic infection.

Histoplasma capsulatum is endemic to the Ohio, Mississippi, and Missouri River valleys in the US, and to Central and South America.[3][16] Activities associated with the development of histoplasmosis pneumonia include cave exploration, close proximity to chicken roosts, demolition and excavation, and gathering wood.

risk factors that impair host defenses

These include stem cell and solid organ transplant, graft-versus-host disease, emphysema, HIV infection, neutropenia, and treatment with corticosteroids or tumor necrosis factor-alpha antagonists.

fever

Seen in up to 80% of patients with symptomatic infection.[1]

headache

Common symptom of acute and chronic infections.

dyspnea

Common symptom of acute pulmonary histoplasmosis, because of airway or vascular compression.

dry or nonproductive cough

Dry cough seen in 70% of acute symptomatic patients.[9]

pleuritic chest pain

Common symptom of acute pulmonary histoplasmosis, seen in 85% to 100% of cases.[1]

anorexia

Common symptom of acute pulmonary histoplasmosis, seen in 85% to 100% of cases.[1]

uncommon

productive cough

Patients with chronic cavitary disease typically present with a productive cough.

Other diagnostic factors

common

abdominal pain

Common symptom of acute pulmonary histoplasmosis.

fatigue

Common symptom of acute pulmonary histoplasmosis.

malaise

Common symptom of acute pulmonary histoplasmosis.

arthralgias

Common symptom of acute pulmonary histoplasmosis.

uncommon

weight loss

Common in chronic or disseminated histoplasmosis. Seen in 26% to 50% of patients.[44]

hepatosplenomegaly

Manifestation of disseminated histoplasmosis; often seen in children.[44][45]

scattered crackles on chest auscultation

May be found in some patients with mild disease.

bronchial breathing on chest auscultation

May be found in some patients with mild disease.

distant breath sounds on chest auscultation

May be heard during auscultation over a lung cavity in patients with more severe respiratory involvement.

hemoptysis

Associated with chronic pulmonary histoplasmosis.

meningitis-like symptoms

Associated with central nervous system-disseminated histoplasmosis.

skin lesions

Can be seen in disseminated histoplasmosis.

gastrointestinal symptoms

Can be seen in disseminated histoplasmosis.

sepsis-like syndrome

Can be seen in disseminated histoplasmosis.

Risk factors

strong

exposure to fungus

The fungus grows in soil and material contaminated with bat or bird droppings. Infection results from inhalation of spores that are disseminated into the atmosphere when soil and/or organic material containing the spores are disturbed. Patients who inhale a large inoculum are more likely to develop severe acute pulmonary histoplasmosis, while a low inoculum exposure is more likely to result in asymptomatic or mildly symptomatic infection.

Histoplasma capsulatum is endemic to the Ohio, Mississippi, and Missouri River valleys in the US, and to Central and South America.[3][16] Activities associated with the development of histoplasmosis pneumonia include cave exploration, close proximity to chicken roosts, demolition and excavation, and gathering wood.

emphysema

Chronic obstructive lung disease is an independent risk factor for the development of chronic pulmonary histoplasmosis.[1]

HIV infection

Patients infected with HIV with CD4 cell counts <150 cells/mm³ are at high risk for developing disseminated histoplasmosis in conjunction with pulmonary infection.[17]

treatment with tumor necrosis factor (TNF)-alpha antagonists

TNF-alpha plays an essential role in host defenses against Histoplasma capsulatum, and treatment with TNF-alpha antagonists such as infliximab and etanercept is associated with an increased risk of disseminated histoplasmosis.[14][18]

treatment with corticosteroids

Corticosteroid therapy affects the host immune response at many levels and is a recognized risk factor for acute pulmonary histoplasmosis and disseminated disease.

treatment with immunosuppressants

Immunosuppressants such as calcineurin inhibitors and antilymphocyte globulin are recognized risk factors for histoplasmosis.

neutropenia

Neutropenia resulting from cytotoxic chemotherapy is associated with a high risk of invasive fungal infections including disseminated histoplasmosis.

In non-neutropenic hosts, complement activation and chemotactic factors attract neutrophils to the invading fungal pathogen, leading to damage and growth inhibition. This mechanism is inhibited in neutropenic patients, leading to an increased risk of dissemination.

stem cell and solid organ transplant

The possibility of invasive and/or disseminated fungal infection should be considered early in the disease course of patients with underlying risk factors, including stem cell and solid organ transplant recipients.[19][20][21][22]

graft-versus-host disease

The possibility of invasive and/or disseminated fungal infection should be considered early in the disease course of patients with underlying risk factors including graft-versus-host disease, when increased immunosuppressive therapy is required.[19]

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