Histoplasmosis overview

# Overview
Histoplasma capsulatum was first described by Samuel Taylor Darling in 1906. Histoplasmosis is typically acquired via inhalation of airborne microconidia, often after disturbance of contaminated material in the soil. In majority of the patients the infection is asymtomatic and resolves with host's immune response. In few patients inhalation of large amount of inoculum can result in an acute pulmonary infection with symptoms resembling pneumonia. Histoplasmosis can be classified with respect to the involved organ system. Patients with immunosupression, hematological malignancies, immunosuppresive therapy and infants are at a higher risk of developing disseminated histoplasmosis infection. The incidence of histoplasmosis is estimated by the Centers of Disease Control (CDC) to be around 500,000 every year in the United States. Majority of the patients are asymptomatic and few develop acute pulmonary histoplasmosis presenting with fever, cough and dyspnea. Few patients develop symptoms such as skin rash and symmetrical joint pain. Severe form of disseminated histoplasmosis presents with features of sepsis, acute respiratory distress syndrome and disseminated intravascular coagulation. Mild to moderate cases of acute pulmonary histoplasmosis will often resolve without treatment; however, treatment is indicated for moderate to severe acute pulmonary, chronic pulmonary, disseminated, and central nervous system (CNS) histoplasmosis. Typical treatment of severe disease first involves treatment with amphotericin B, followed by oral itraconazole. In many milder cases, itraconazole alone is sufficient.

# Historical perspective
Histoplasma capsulatum was first described by Samuel Taylor Darling in 1906, who coined the term to describe the "plasmodium-like" organisms in the histocytes. In 1912, Henrique da Rocha-Lima, a Brazilian tropical disease specialist, reported findings from a comparison between Leishmania and Histoplasma and concluded that Histoplasma more closely resembled a yeast than a protozoan. In the late 1940s, William A. DeMonbreun, the first person to culture the organism, suggested that the disease may be prevalent in the United States, not only the tropics, due to mild and carrier forms.

# Classification
Histoplasmosis can be classified with respect to the involved organ system. This can include pulmonary, nervous system, cardiovascular system and mediastinum. Histoplasmosis can also be classified according to the severity in to mild, moderate and severe, according to disease duration into acute, sub-acute, chronic and recurrent and according to the progression of the disease into localized or disseminated histoplasmosis.

# Pathophysiology
Histoplasmosis is typically acquired via inhalation of airborne microconidia, often after disturbance of contaminated material in the soil. In majority of the patients the infection is asymtomatic and resolves with host's immune response. In few patients inhalation of large amount of inoculum can result in an acute pulmonary infection with symptoms resembling pneumonia. In patients with immunosuppression, they are unable to mount an adequate T-cell mediated immune response resulting in uncontrolled growth of the organism with spread to the surrounding tissue and increasing the morbidity and mortality of the infection.

# Causes
Histoplasmosis is caused by Histoplasma capsulatum a fungus commonly found in bird and bat fecal material. It belongs to the recently recognized fungal family Ajellomycetaceae. It is dimorphic and switches from a mold-like (filamentous) growth form in the natural habitat to a small budding yeast form in the warm-blooded animal host. It is most prevalent in the Ohio and Mississippi River valleys.

# Differentiating Histoplasmosis from other Conditions
Patients with acute and chronic pulmonary histoplasmosis present with features similar to pneumonia. Therefore it must be differentiated from conditions presenting with cough, fever and dyspnea such as tuberculosis, sarcoidosis and other fungal infections.

# Epidemiology and Demographics
The incidence of histoplasmosis is estimated by the Centers of Disease Control(CDC) to be around 500,000 every year in the United States. In the United States, an estimated 60% to 90% of people who live in areas surrounding the Ohio and Mississippi River valleys (where Histoplasma is common in the environment) have been exposed to the fungus at some point during their lifetime.

# Screening
There is no standard screening recommended for histoplasma infection.

# Risk Factors
Risk factors for histoplasmosis infection include living in or traveling to the Central or Eastern United States. Patients with immunosupression, hematological malignancies, immunosuppresive therapy and infants are at a higher risk of developing disseminated histoplasmosis infection.

# Natural History, Complications and Prognosis
Histoplasmosis is an endemic fungal infection and infection occurs by inhalation of the microconidia present in the soil. The average incubation period is around 2 to 3 weeks. Majority of the patients are asymptomatic and few develop acute pulmonary histoplasmosis presenting with fever, cough and dyspnea. In immunocompetent patients the infection is self limiting and symptoms resolve in 2 to 3 weeks. However patients in immunocompromised state can have complications due to the spread of infection to other organs and develop disseminated histoplasmosis. Prognosis of disseminated histoplasmosis is poor and is associated with increased mortality.

# Diagnosis

## History and Symptoms
Majority of the patients are asymptomatic and few develop acute pulmonary histoplasmosis presenting with fever, cough and dyspnea. Few patients develop symptoms such as skin rash and symmetrical joint pain. Severe form of disseminated histoplasmosis presents with features of sepsis, acute respiratory distress syndrome and disseminated intravascular coagulation.

## Physical Examination
Physical examination findings in pulmonary histoplasmosis include erythema nodosum and rales on auscultation. In patients with disseminated histoplasmosis features similar to sepsis such as hypotension, altered mental status will be present.

## Laboratory Findings
There are no specific laboratory findings associated with acute histoplasma infection. Diagnosis is confirmed by the demonstration of the yeast cells from tissue samples or body fluids, culture and antigen detection.

## Chest X-Ray
Chest X-Ray in patients with pulmonary histoplasmosis will demonstrate hilar lymphadenopathy and pulmonary nodules.

## CT
Findings on CT are often related to complications of histoplasmosis and include: Calcified mediastinal and hilar lymph nodes and bronchial occlusion with intrabronchial broncholith.

# Treatment

## Medical therapy
Mild to moderate cases of acute pulmonary histoplasmosis will often resolve without treatment; however, treatment is indicated for moderate to severe acute pulmonary, chronic pulmonary, disseminated, and central nervous system (CNS) histoplasmosis. Typical treatment of severe disease first involves treatment with amphotericin B, followed by oral itraconazole. In many milder cases, itraconazole alone is sufficient. Asymptomatic disease is typically not treated.

## Surgical therapy
Surgical intervention is not recommended for the management of histoplasmosis.

# Prevention

## Primary Prevention
Prevention of histoplasma infection is to avoid activities that disturbing material (for example, digging in soil or chopping wood) where there are bird or bat droppings are present, cleaning chicken coops, exploring caves, leaning, remodeling, or tearing down old buildings. Minimizing the exposure to infective microconidia is the best preventive measure to reduce the risk of histoplasma infection.

## Secondary Prevention
Secondary preventive measures to be followed by patients are the same as primary preventive measures.