eMedicine Specialties > Pulmonology > Infectious Lung Diseases

Coccidioidomycosis

Author: Sat Sharma, MD, FRCPC, Professor and Head, Division of Pulmonary Medicine, Department of Internal Medicine, University of Manitoba; Site Director, Respiratory Medicine, St. Boniface General Hospital
Contributor Information and Disclosures

Updated: Jun 22, 2006

Introduction

Background

Coccidioidomycosis is an infection caused by the soil-inhabiting fungus Coccidioides immitis. This fungus is endemic to certain regions of North and South America. The endemic areas in the United States include Arizona, south central California, Nevada, New Mexico, and the western half of Texas. Other endemic areas are the regions of Mexico that border the western United States. The fungus also is endemic to some Central American countries, including Guatemala, Honduras, and Nicaragua. Other areas, such as desert regions of South America (Argentina, Paraguay, Venezuela), also are endemic.

Historical perspectives

Wenicke and Posadas first described a case of coccidioidomycosis in 1892 in South America. Two years later in the United States, a patient with disseminated coccidioidomycosis was first reported in California in 1894. In 1896, Rixford and Gilchrist reported 2 cases in which they identified the infecting agent as a protozoanlike organism and named it Coccidioides immitis. Ophuls further described the life cycle and pathology of C immitis in 1905. The epidemiology of coccidioidomycosis was studied by Charles E. Smith in the Joaquin Valley after he and his colleagues developed serologic testing for coccidioidomycosis. The first effective therapy for coccidioidomycosis, intravenous amphotericin B was first used in 1957. Since the 1980s, various oral antifungal agents, including ketoconazole and itraconazole, have lead to further advances in treatment of coccidioidomycosis.

Life cycle of C immitis

C immitis is a fungus that thrives in soil and grows in either of 2 phases—the mycelial arthrospore phase in the soil or the spherule endospore phase in infected tissues. Mycelia are most prolific during the rainy season, but, at this stage, they are the least infectious. As the soil becomes dryer, the branching septated hyphae develop into arthrospores, which readily disarticulate as single fungal cells and become airborne when disturbed by wind or soil excavation. An arthrospore measures 3-5 microns, and it remains viable for long periods of time. Once inhaled, an arthrospore develops into a thick-walled spherule filled with endospores. Once released, each endospore can start the development of a new spherule and extend the infection, repeating its growth phase and continuing the cycle.

Coccidioidomycosis is not transmitted from person to person. Risk of infection is highest in dry summer months. A second period of risk usually occurs in the late fall, terminating with winter rains. Dust exposure is a critical factor for acquiring an infection. Individuals who dig in the soil or who are exposed to disrupted earth are at the greatest risk.

Pathophysiology

Following inhalation and maturity of the fungi, humoral immunity predictably begins with immunoglobulin M (IgM) antibodies, and immunoglobulin G (IgG) antibodies follow. Cell-mediated immunity, particularly T cells, becomes a key factor in determining recovery from coccidioidomycosis. A pyogenic infection develops, and, eventually, a granulomatous respiratory infection ensues. Caseation without calcification may occur. Respiratory infection usually results in endobronchiolitis. A spectrum of signs may be observed on chest x-ray films. These include (1) a nonspecific increase in pulmonary markings, (2) patchy bronchopneumonia, and (3) pleural effusion (hilar adenopathy is common).

Depending on the host's immune response, infection with C immitis may evolve into one of the clinical syndromes described below.

Primary coccidioidal pneumonia

Most patients with primary pulmonary coccidioidomycosis are asymptomatic, and the infection resolves spontaneously. In approximately 5% of patients, a persistent pulmonary focus of coccidioidomycosis may develop, manifested as a nodule, cavity, or chronic progressive pneumonia. In addition, C immitis can disseminate from the lungs and thoracic cavity to infect other areas of the body, such as bone, joints, skin, and meninges.

Nodules

In approximately 5-7% of patients with coccidioidal pneumonia, the infection evolves to form a sharply circumscribed, usually noncalcified, pulmonary nodule. Malignancy is a major concern while evaluating these nodules. In a review of 200 solitary pulmonary nodules surgically resected from patients within endemic areas, 33.5% were found to be malignant (Read, 1972).

Cavities

Another common manifestation of persistent pulmonary coccidioidomycosis is cavity formation. This occurs in approximately 5% of patients. The typical coccidioidal cavity is thin-walled, solitary, and peripheral in location. Coccidioidal cavities commonly are asymptomatic, and approximately 50% disappear within 2 years of their occurrence. The cavities may wax and wane over the years.

Chronic progressive coccidioidal pneumonia

Patients with this manifestation present with chronic systemic symptoms such as low-grade fever, weight loss, cough, chest pain, and hemoptysis. These symptoms often are indolent and simulate tuberculosis when coupled with radiographic findings of bilateral apical cavitation and fibrosis.

Dissemination

Disseminated coccidioidomycosis usually occurs within weeks to months of the primary pneumonia. In some patients with disseminated disease, no radiographic evidence of previous pulmonary disease and no history of a preceding respiratory illness may be present. Males and certain ethnic groups, such as African Americans and Filipinos, are more likely to develop disseminated disease. Patients with depressed cellular immunity, such as those with lymphoma, HIV infection, organ transplants, or those receiving high-dose corticosteroids, also are more likely to develop dissemination. Skin, bones, joints, and meninges are the most frequent sites of dissemination. The infection also may spread to bone marrow, myocardium, and kidneys.

Frequency

United States

Coccidioidomycosis affects an estimated 100,000 people each year in the United States. Coccidioidomycosis is endemic in the western hemisphere from California to Argentina. Although it usually affects only those individuals in endemic areas, coccidioidomycosis is being recognized increasingly outside of these areas, as travelers pass through endemic areas.

International

Affected areas are in the lower Sonoran areas, characterized by a semiarid climate with hot summers and alkaline soils. These areas include northern Mexico and Central and South America.

Mortality/Morbidity

• Infection is directly related to the degree of exposure to airborne arthrospores. Therefore, those exposed to large amounts of dust in endemic areas (eg, farmers, archeologists) have higher rates of infection.
• Infection rates usually are calculated from cocci skin testing, and approximately 40% of those infected develop symptomatic disease, usually pulmonary.
• The pulmonary infection in the vast majority of individuals (approximately 90%) resolves without sequelae. Approximately 10% of patients progress to harbor pulmonary sequelae of cavitary lesions and nodules. In approximately 1%, infection extends to dissemination.

Race

• Filipinos have the highest risk of dissemination, approximately 10-175 times the risk of whites. Filipinos have 10 times the risk of developing meningitis compared to whites.
• Blacks and individuals of Hispanic descent also have a higher risk of dissemination. Blacks have 5 times the risk of developing meningitis and a 5-times greater risk of death.

Clinical

History

Approximately 30-40% of individuals develop clinical symptoms after infection. The disease spectrum ranges from a mild flulike illness to subacute pneumonia.

• Most symptomatic patients have a febrile respiratory illness beginning 7-21 days after exposure (mean incubation period = 10-16 d).
• Most patients complain of cough, chest pain, fever, and fatigue.
• A study by Johnson and colleagues (1996) reported the following symptoms:
  • Cough (73%)
  • Chest pain (44%)
  • Shortness of breath (32%)
  • Fever (76%)
  • Fatigue (39%)
  • Chills (29%)
  • Erythema nodosum (26%)

Physical

More than half of the cases are subclinical. Consider coccidioidomycosis in those individuals who are at risk for infection and who develop a constellation of nonspecific signs or unusual rashes, such as erythema nodosum, erythema multiforme, toxic erythema, or arthralgias.

Signs of synovitis, bony tenderness, osteomyelitis, meningitis, hydrocephalus, lymphadenopathy, and abdominal masses or tenderness all may indicate the presence of a coccidioidal infection.

• Skin
  • A wide variety of rashes, including maculopapular lesions, erythema multiforme, and erythema nodosum, may develop.
  • Interestingly, the development of erythema nodosum is an indicator of a good prognosis.
• Pulmonary
  • Bronchitis, bronchiolitis, reactive airways disease, pneumonia, and pleural effusions may develop.
  • Frank empyemas and bronchiole pleural fistulas are possible.
  • Pleural friction rub is possible.
• Musculoskeletal
  • Nonspecific tenderness in myalgic and arthralgic areas develops.
  • One third of patients with dissemination have musculoskeletal involvement.
  • Bone lesions are unifocal in 60% of cases, and joint lesions are unifocal in 90% of cases.
  • Multiple lesions or vertebral lesions are associated with a poor prognosis.
• Hepatomegaly
• Splenomegaly
• Tachycardia
• Central nervous system
  • Acute or chronic meningitis is possible.
  • Acute hydrocephalus may be the first sign of disseminated coccidioidomycosis.
  • Hyperreflexia is possible.
  • Headache may be noted.

Causes

C immitis is a fungus present in the soil in certain endemic regions, which, when inhaled, causes coccidioidomycosis. The infection is acquired during the dry summer months or the late fall.

• Following inhalation, an initial pyogenic infection develops, followed by a granulomatous respiratory infection. In most patients, the asymptomatic pulmonary infection resolves spontaneously. However, in approximately 5% of patients, a persistent pulmonary focus or dissemination to other parts of the body (eg, bone, joints, skin, meninges) occurs. The infection also may spread to bone marrow, myocardium, and kidneys.
• Disseminated coccidioidomycosis may occur in an otherwise healthy individual, but several risk factors have been identified, as follows:
  • Male sex
  • Ethnicity (eg, African American, Filipino)
  • Pregnancy
  • Diabetes
  • Depressed cellular immunity, as in patients with lymphoma, HIV infection, organ transplants, or patients receiving high-dose corticosteroids

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