Fungal Diseases of the Lung

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Fungal Diseases of the Lung

Anatomic Alterations of the Lungs

When fungal spores are inhaled, they may reach the lungs and germinate. When this happens, the spores produce a frothy, yeastlike substance that leads to an inflammatory response. Polymorphonuclear leukocytes and macrophages move into the infected area and engulf the fungal spores. The pulmonary capillaries dilate, the interstitium fills with fluid, and the alveolar epithelium swells with edema fluid. Regional lymph node involvement commonly occurs during this period. Because of the inflammatory reaction, the alveoli in the infected area eventually become consolidated (Figure 18-1). Airway secretions may also develop at this time.

In severe cases, tissue necrosis, granulomas, and cavity formation may be seen. During the healing process, fibrosis and calcification of the lung parenchyma ultimately replace the granulomas. In response to the fibrosis and occasionally calcification, the lung tissue retracts and becomes firm. The apical and posterior segments of the upper lobes are most commonly involved. The anatomic changes of the lungs caused by fungal diseases are similar to those seen in tuberculosis.

Fungal diseases of the lung cause a chronic restrictive pulmonary disorder. The major pathologic or structural changes of the lungs associated with fungal diseases of the lungs are as follows:

Etiology and Epidemiology

Fungal spores are widely distributed throughout the air, soil, fomites, and animals, and even exist in the normal flora of humans. As many as 300 fungal species may be linked to disease in animals. In plants, fungal disease is the most common cause of death and destruction. In humans, most exposures to fungal pathogens do not lead to overt infection because humans have a relatively high resistance to them. Human fungal disease (also called mycotic disease or mycosis) can be caused, however, by primary or “true” fungal pathogens that exhibit some degree of virulence or by opportunistic or secondary pathogens that take advantage of a weakened immune defense system (e.g., in acquired immunodeficiency syndrome [AIDS] and human immunodeficiency virus [HIV] infection).

Primary Pathogens

Histoplasmosis

Histoplasmosis is the most common fungal infection in the United States. It is caused by the dimorphic fungus Histoplasma capsulatum. In the United States, the prevalence of histoplasmosis is especially high along the major river valleys of the Midwest (e.g., Ohio, Michigan, Illinois, Mississippi, Missouri, Kentucky, Tennessee, Georgia, and Arkansas). In fact, on the basis of skin test surveys it is estimated that 80% to 90% of the population throughout these areas shows signs of previous infection. Histoplasmosis is often called Ohio Valley Fever.

H. capsulatum is commonly found in soils enriched with bird excreta, such as the soil near chicken houses, pigeon lofts, barns, and trees where starlings and blackbirds roost. The birds themselves, however, do not carry the organism, although the H. capsulatum spore may be carried by bats. Generally, an individual acquires the infection by inhaling the fungal spores that are released when the soil from an infected area is disturbed (e.g., children playing in dirt).

When the H. capsulatum organism reaches the alveoli, at body temperature it converts from its mycelial form (mold) to a parasitic yeast form. The clinical manifestations of histoplasmosis are strikingly similar to those of tuberculosis. The incubation period for the infection is approximately 17 days. Only about 40% of those infected demonstrate symptoms, and only about 10% of these patients are ill enough to consult a physician. Depending on the individual’s immune system, the disease may take on one of the following forms: asymptomatic primary histoplasmosis, acute symptomatic pulmonary histoplasmosis, chronic histoplasmosis, and disseminated histoplasmosis.

Asymptomatic histoplasmosis is the most common form of histoplasmosis. Normally it produces no signs or symptoms in otherwise healthy individuals who become infected. The only residual sign of infection may be a small, healed lesion of the lung parenchyma or calcified hilar lymph nodes. The patient has a positive histoplasmin skin test result.

Acute symptomatic pulmonary histoplasmosis tends to occur in otherwise healthy individuals who have had an intense exposure to H. capsulatum. Depending on the number of spores inhaled, the individual signs and symptoms may range from a mild to serious illness. Mild signs and symptoms include fever, muscle and joint pain, headache, dry hacking cough, chills, chest pain, weight loss, and sweats. People who have inhaled a large number of spores may develop a severe acute pulmonary syndrome, a potentially life-threatening condition in which the individual becomes extremely short of breath. The acute pulmonary syndrome is often referred to as spelunker’s lung because it frequently develops after excessive exposure to bat excrement stirred up by individuals exploring caves. During this phase of the disease, the patient’s chest radiograph generally shows single or multiple infection sites resembling those associated with pneumonia.

Chronic pulmonary histoplasmosis is characterized by infiltration and cavity formation in the upper lobes of one or both lungs. This type of histoplasmosis often affects people with an underlying lung disease such as emphysema. It is most commonly seen in middle-aged white men who smoke. Signs and symptoms include fatigue, fever, night sweats, weight loss, a productive cough, and hemoptysis—similar to signs and symptoms of tuberculosis. Often the infection is self-limiting. In some patients, however, progressive destruction of lung tissue and dissemination of the infection may occur.

Disseminated histoplasmosis may follow either self-limited histoplasmosis or chronic histoplasmosis. It is most often seen in very young or very old patients with compromised immune systems (e.g., patients with HIV infection). Even though the macrophages can remove the fungi from the bloodstream, they are unable to kill the fungal organisms. As a result, disseminated histoplasmosis can affect nearly any part of the body, including eyes, liver, bone marrow, skin, adrenal glands, and intestinal tract. Depending on which body organs are affected, the patient may develop anemia; pneumonia; pericarditis; meningitis; adrenal insufficiency; and ulcers of the mouth, tongue, or intestinal tract. If untreated, disseminated histoplasmosis is usually fatal.

Screening and Diagnosis

Coccidioidomycosis

Coccidioidomycosis is caused by inhalation of the spores of Coccidioides immitis, which are spheric fungi carried by wind-borne dust particles. The disease is endemic in hot, dry regions. In the United States, coccidioidomycosis is especially prevalent in California, Arizona, Nevada, New Mexico, Texas, and Utah. About 80% of the people in the San Joaquin Valley are coccidioidin skin test positive. Because the prevalence of coccidioidomycosis is high in these regions, the disease is also known as California Disease, Desert Fever, San Joaquin Valley Disease, and Valley Fever. The fungus has been isolated in these regions from soils, plants, and a large number of vertebrates (e.g., mammals, birds, reptiles, amphibians).

When C. immitis spores are inhaled, they settle in the lungs, begin to germinate, and form round, thin-walled cells called spherules. The spherules, in turn, produce endospores that make more spherules (the spherule-endospore phase). The disease usually takes the form of an acute, primary, self-limiting pulmonary infection with or without systemic involvement. Some cases, however, progress to disseminated disease.

Clinical manifestations are absent in about 60% of the people who have a positive skin test result. In the remaining 40%, most of the patients demonstrate coldlike symptoms such as fever, chest pain, cough, headaches, and malaise. In uncomplicated cases, patients generally recover completely and enjoy lifelong immunity. In approximately 1 in 200 cases, however, the primary infection does not resolve and progresses with varied clinical manifestations. Chronic progressive pulmonary disease is characterized by nodular growths called fungomas and cavity formation in the lungs. Disseminated coccidioidomycosis occurs in about 1 in 6000 exposed persons. When this condition exists, the lymph nodes, meninges, spleen, liver, kidney, skin, and adrenals may be involved. The skin lesions (e.g., bumps on the face and chest) are commonly accompanied by arthralgia or arthritis, especially in the ankles and knees. This condition is commonly called desert bumps, desert arthritis, or desert rheumatism. Death is most commonly caused by meningitis.

Blastomycosis

Blastomycosis (also called Chicago disease, Gilchrist’s disease, and North American blastomycosis) is caused by Blastomyces dermatitidis. Blastomycosis occurs in people living in the south-central and midwestern United States and Canada. The infection occurs in 1 to 2 out of every 100,000 people in these areas. Cases also have been reported in Central America, South America, Africa, and the Middle East. B. dermatitidis inhabits areas high in organic matter, such as forest soil, decaying wood, animal manure, and abandoned buildings. Blastomycosis is most common among pregnant women and middle-aged African-American men. The disease also is found in dogs, cats, and horses.

The primary portal of entry of B. dermatitidis is the lungs. The acute clinical manifestations resemble those of acute histoplasmosis, including fever, cough, hoarseness, aching of the joints and muscles, and, in some cases, pleuritic pain. Unlike histoplasmosis, however, the cough is frequently productive, and the sputum is purulent. Acute pulmonary infections may be self-limiting or progressive. When the condition is progressive, nodules and abscesses develop in the lungs. Extrapulmonary lesions commonly involve the skin, bones, reproductive tract, spleen, liver, kidney, or prostate gland. The skin lesions may, in fact, be the first signs of the disease. It often begins on the face, hands, wrists, or legs as subcutaneous nodules that erode to the skin surface. Dissemination of the yeast also may cause arthritis and osteomyelitis, and involvement of the central nervous system causes headache, convulsions, coma, and mental confusion. Standardized testing procedures for blastomycosis are not available. The diagnosis of blastomycosis can be made from direct visualization of the yeast in sputum smears. Culture of the fungus also can be performed. An accurate blastomycin skin test is not available.

Opportunistic Pathogens

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