Endemic Fungi

Paras Patel

James W. Myers

INTRODUCTION

Blastomycosis, histoplasmosis, and coccidioidomycosis are the three common systemic and endemic mycoses in the United States.
Even though most symptomatic cases of blastomycosis, coccidioidomycosis, and histoplasmosis occur in patients without significant preexisting and predisposing disease, individuals with defective cell-mediated immunity are at increased risk for these mycoses if they are exposed by living or traveling in the endemic areas.

EPIDEMIOLOGY AND PATHOGENICITY

Blastomycosis, coccidioidomycosis, and histoplasmosis are caused, respectively, by the following dimorphic fungi: Blastomyces dermatitidis, Coccidioides immitis or Coccidioides posadasii, and Histoplasmosis capsulatum.
Each species grows as a mold in nature or in the laboratory at temperatures below 98.6°F (37°C). On routine fungal culture media at 77°F to 86°F (25°C to 30°C), they produce mycelial colonies that vary in texture, pigment, and growth rate.
Under the appropriate growth conditions in vitro, they convert to a distinctive form of growth that is found in tissue.
Systemic fungal infections are acquired by inhalation of the airborne conidia of dimorphic, exogenous fungi. These fungi convert to tissue forms in the lungs, which subsequently disseminate to other organs as well as skin.
The fungi that cause coccidioidomycosis and histoplasmosis are associated with dry soil, or soil mixed with guano.
The agent of blastomycosis undoubtedly exists in nature, but its habitat has not been clearly defined.
Inhalation of conidia of any of these fungi can lead to pulmonary infection, which may or may not become symptomatic.
The organism may become dormant only to reactivate later.
Some patients develop a progressive pulmonary disease, which can occasionally lead to systemic dissemination.
These infections are not contagious, and they are not transmitted among humans or animals. No “Isolation Precautions” are needed in the hospital.

Table 51-1 compares some of the epidemiologic features of these systemic mycoses.

Table 51-1 Epidemiologic Features

Features	Blastomycosis	Histoplasmosis	Coccidioidomycosis
Geographic areas of high endemicity	Highly endemic in the Mississippi and Ohio river basins, areas surrounding the Great Lakes, and the St. Lawrence River valley	Highly endemic in the Ohio and Mississippi river valleys. Approximately 50% of adults in endemic areas have been infected.	Highly endemic in the southern San Joaquin Valley of California and southern Arizona, New Mexico, Nevada, Texas, northern Mexico, and parts of Central and South America
Saprophytic form (<95°F)	Hyaline, septate hyphae	Hyaline, septate hyphae	Hyaline, septate hyphae
Existence in environment	The moist soil enriched with decaying vegetation encourages the growth of the organism.	Possible exposure events include destroying chicken coops, cutting down trees, or spelunking in caves.	Exposure to the soil of the arid lower Sonoran Desert
Predominant tissue forms	Yeast	Yeast	Spherules
Mode of transmission	Inhalation of conidia from the environmental mold	Inhalation	Inhalation
Self-limited infection	Unknown	Yes	Yes
Approximate percentage of immunocompetent patients	More than 90	More than 90	More than 90
Approximate percentage of males among patients with disease	50-90	80-90	75-90
Relative frequency of disease among AIDS patients in the endemic areas	Rare	Common	Common
Approximate percentage of infections that are asymptomatic	>50	>65	>95

CLINICAL FEATURES

Blastomycosis

The most common manifestations are pulmonary, cutaneous, and bone infections.

Infection is asymptomatic in more than 50% of infected individuals.
The most common symptoms include cough, night sweats, weight loss, chest pain, skin lesions, fever, hemoptysis, myalgia, and dyspnea.
Chest radiographs may reveal a patchy pneumonitis, a mass-like infiltrate, or nodules. Often, it is confused with lung cancer.
Chronic cutaneous blastomycosis presents as one or more subcutaneous nodules that eventually ulcerate. Skin lesions are often confused with skin cancers.
- Lesions are more common on exposed skin surfaces of body such as the face or extremities and may evolve over weeks or months into granulomatous lesions.
- Aspiration or biopsy of leading edge of the skin lesion shows the active microabscesses and the typical yeast cells.
When dissemination occurs, it may involve the genitourinary tract, central nervous system (CNS), spleen, skin, bone, and less commonly, the liver, lymph nodes, heart, and other viscera. Tables 51-2, 51-3 and 51-5 compare the features of the major endemic fungi.

Histoplasmosis Capsulatum

Most infections are asymptomatic.
Patients with symptomatic pulmonary infection usually have a self-limited illness that begins several weeks after exposure (2 weeks) to the fungus in a confined place such as a storm cellar, a chicken house, or a bat cave.
- Patients with symptomatic disease usually present with fever, chills, fatigue, nonproductive cough, and myalgias.
- Chest radiographs usually show a patchy lobar or multilobar nodular infiltrate.
- Acute pulmonary infection can be associated with joint symptoms, especially in women.
  - Erythema nodosum
  - Erythema multiforme
  - Frank arthritis is rare.
  - Immunologic phenomena
Immunocompromised patients with heavy exposure to H. capsulatum usually present with life-threatening acute pulmonary histoplasmosis.
- Cases usually present with high spiking fevers, chills, prostration, dyspnea, and cough.
- Chest radiograph reveals diffuse, reticulonodular pulmonary infiltrates.
Chronic cavitary pulmonary histoplasmosis is a form of histoplasmosis, which mainly occurs in elderly patients who have chronic obstructive pulmonary disease.
- Patients with chronic cavitary pulmonary histoplasmosis present with fever, fatigue, anorexia, weight loss, cough productive of purulent sputum, and hemoptysis.
- Radiographs reveal unilateral or bilateral upper lobe infiltrates with multiple cavities and extensive fibrosis in the lower lobes.
Pulmonary involvement with histoplasmosis has been associated with multiple complications such as mediastinal and hilar lymph nodes calcifications, granulomatous mediastinitis and fibrosing mediastinitis, and pericarditis.
- Enlarged mediastinal and hilar lymph nodes can cause pressure on adjacent structures, including the esophagus, airways, and blood vessels.
Pericarditis
- 5%
- Friction rub 75 %
- 6 weeks after a respiratory illness
- Yeast organisms uncommonly found
Acute disseminated histoplasmosis occurs mainly in immunocompromised patients such as HIV infected patients with CD4 counts lower than 150, patients with an organ transplant, or patients taking corticosteroids or tumor necrosis factor antagonists.
- Fever, chills, anorexia, weight loss, hypotension, dyspnea, hepatosplenomegaly, and skin and mucous membrane lesions. Ulcers are less common than in other forms.
- Pancytopenia, elevated alkaline phosphatase, diffuse pulmonary infiltrates on chest radiography and computed Tomography (CT), findings of disseminated intravascular coagulation, and acute respiratory failure are common.
Subacute progressive disseminated forms occur as well.
- Fever in approximately 50%
- Focal lesions in various organ systems
  - Gastrointestinal tract
    - Especially terminal ileum and cecum
  - Endovascular structures including the aortic valve and abdominal aorta. Difficult to grow in blood cultures
  - Adrenal glands. Addison disease in 10%
  - Hepatosplenomegaly, deep mucosal ulcers
  - CNS
    - Chronic meningitis. Lymphocytic, basilar location
    - Mass lesions
    - Cerebritis
Chronic progressive disseminated histoplasmosis occurs mainly in middle-aged men who have no known immunosuppressive illness.
- Fever (˜30%), night sweats, weight loss, anorexia, and fatigue
- The most common physical finding (˜50%) is an oropharyngeal ulcer that is indurated and usually deep and painless.
- Hepatosplenomegaly
- Adrenal insufficiency may occur.
- An increased erythrocyte sedimentation rate, elevated alkaline phosphatase, and pancytopenia are often noted.
- Diffuse reticulonodular infiltrates on chest radiography and CT may be seen.
- Granulomas, few yeasts on pathology specimens

Histoplasma capsulatum var. duboisii causes African histoplasmosis, which differs in clinical presentation from the typical form.

Larger yeast cells (10 microns vs. 2 microns)
More skin and bone lesions and less pulmonary
Giant cells (Tables 51-2 and 51-3)

Coccidioidomycosis

Approximately 40% of people infected with C. immitis present with a flu-like symptom of cough, fever, night sweats, pleuritic chest pain, and shortness of breath one to three weeks after inhalation of spores.
60% of people remain asymptomatic.

Table 51-2 Comparison of Common Symptoms of the Endemic Fungi

Clinical Features	Blastomycosis	Histoplasmosis	Coccidioidomycosis
Fever	Yes	Yes	Yes
Night sweats	Yes	Yes	Yes
Weight loss	Yes	Yes	Yes
Anorexia	Yes	Yes	Yes
Fatigue	Yes	Yes	Yes
Myalgia	Yes	Yes	Yes

5% of infected patients develop pulmonary lesions such as nodules or thin-walled cavities near the pleura.
Less than 1% of patients develop disseminated disease.
Cutaneous coccidioidomycosis presents with verrucous plaques, nodules, or papules.
Commonly involve nasolabial folds or the sternoclavicular area
Bones, joints, brain, spinal cord, thyroid, eye, larynx, or genitourinary tract may be involved as well.

Clinically significant illness may present as “valley fever” lasting weeks to months. Primary infections usually manifest as community-acquired pneumonia occurring 7 to 21 days after exposure.
- Chest pain, cough, and fever
- Cutaneous manifestations such as erythema nodosum and erythema multiforme
Most pulmonary coccidioidal infections resolve without complications within several weeks to many months.
- A few patients with infections develop pulmonary sequelae, and even less patients develop disseminated infection.
- Pulmonary cavities usually are peripherally located and solitary. Over time, most develop a distinctive thin-walled cavity.