eMedicine Specialties > Dermatology > Fungal Infections

Coccidioidomycosis

Author: Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Coauthor(s): Linas Riauba, MD, Assistant Professor of Clinical Medicine, Department of Medicine, Section of Infectious Disease, University Hospital, University of Medicine and Dentistry of New Jersey
Contributor Information and Disclosures

Updated: Jun 12, 2009

Introduction

Background

In 1892, Alejandro Posada first defined coccidioidomycosis as a distinct disease. Coccidioidomycosis is caused by Coccidioides immitis, a dimorphic soil fungus native to the San Joaquin Valley of California, southern portions of Arizona, northern portions of Mexico, and scattered areas in Central America and South America.

C immitis propagates both as a saprophyte and as a parasite. In soil, it grows as a mold with branching septate hyphae. When the soil is disturbed, the hyphae fragment, which forms extremely hardy structures called arthroconidia, can become airborne. If inhaled by animals or humans, the arthroconidia can reach the pulmonary alveoli and transform into thick-walled multinucleate spherules, which form septa and produce hundreds to thousands of uninucleate endospores. Each endospore is capable of producing new spherules or mycelia.

Various other eMedicine articles on coccidioidomycosis are as follows:

• Coccidioidomycosis (Emergency Medicine)
• Coccidioidomycosis (Infectious Diseases)
• Coccidioidomycosis (Ophthalmology)
• Coccidioidomycosis (Pediatrics)
• Coccidioidomycosis (Pulmonology)
• Coccidioidomycosis, Thoracic (Radiology)

Pathophysiology

Almost all C immitis infections result from the inhalation of arthroconidia. Infection may be locally controlled, or it may spread within the lungs or via the bloodstream. In rare occurrences, an inoculation of C immitis causes primary cutaneous coccidioidomycosis with lymphatic extension to the regional lymph nodes; these cases resolve without treatment. In 2009, a report alleged transmission of coccidioidomycosis to a human by a cat bite.¹ This occurred in a veterinary assistant who had been bitten on the hand by a cat that was later diagnosed with disseminated disease.

A single C immitis arthroconidium may be sufficient to produce a naturally acquired respiratory infection. The size of the arthroconidium allows it to be deposited in the terminal bronchiole but probably does not allow it to reach the alveolar space by means of direct inhalation. As an arthroconidium transforms into a spherule, the resulting inflammation results in a local pulmonary lesion. Extracts of C immitis organisms react with complement, leading to the release of mediators of chemotaxis for neutrophils.

In some patients, C immitis leaves the lungs to establish disseminated lesions in distant parts of the body. To establish extrapulmonary sites of infection, the fungal elements must move from the bronchiole into the lung parenchyma and enter and leave the vascular space. In some instances, endospores in the macrophages travel through the lymphatics, reaching the bloodstream. This process is reflected in the common finding of infected hilar, peritracheal, and cervical lymph nodes in patients with extrapulmonary coccidioidal infections. T lymphocytes are of paramount importance in controlling C immitis infections.

Frequency

United States

Approximately 25,000 new, clinically evident cases of coccidioidomycosis are reported annually in the United States, with as many as 75 deaths per year resulting from the infection.

C immitis is endemic in the soil in certain regions of the Western Hemisphere, almost all of which are located between latitudes 40° north and 40° south. In the United States, C immitis is endemic in California's Central Valley and in southern parts of Arizona. It also is endemic in certain places in Utah, Nevada, New Mexico, and Texas. New infections frequently occur during the summer months after the soil dries. In Arizona, a second peak of new clinical infections occurs in October, which corresponds to a similar dry period after the summer rains in that region.

Coccidioidomycosis in Arizona increased in incidence from 1990-1995.² The number of reported cases increased from 255 (7 cases per 100,000 population) in 1990 to 623 (14.9 cases per 100,000 population) in 1995.

The number of annually reported coccidioidomycosis cases in California more than tripled from 2000-2006, rising from 2.4 cases to 8 cases per 100,000 population.³ The annual incidence was highest in Kern County (150 cases per 100,000 population), with the hospitalization rate highest among non-Hispanic blacks, increasing from 3 cases to 7.5 cases per 100,000 population.

International

In addition to regions in the United States, other areas in which C immitis has been identified include northern parts of Mexico adjacent to the Sonoran region of Baja California,⁴ Central America (Nicaragua, Honduras, and Guatemala), and South America (Argentina, Columbia, Venezuela, and Paraguay).

Coccidioidomycosis is endemic in Brazil.⁵ A serologic survey of 229 volunteers in northeast Brazil using the immunodiffusion testing method with commercial Coccidioides species antigens detected 15 individuals without a clinical diagnosis of the disease and 2 individuals in treatment for coccidioidomycosis.⁶ Most of the positive results were in men aged 18-65 years who were engaged in armadillo hunting.

Mortality/Morbidity

• Mortality rates of fulminant infection remain high despite appropriate treatment. In recently published data, of patients in Arizona the hospitalized for it, 48 died, and 12 (25%) of these patients had a concurrent diagnosis of human immunodeficiency virus infection.²
• The infection causes as many as 75 deaths per year in the United States.
• This endemic fungal infection of the southwestern United States causes morbidity and mortality among solid organ transplant recipients who reside in or visit the endemic area or who receive organs from donors infected with the fungus.⁷

Race

• Filipinos have the highest risk of dissemination or progressive pneumonitis.
• African Americans, followed by Mexicans, also appear to have an increased risk for disseminated infection, though their risk is lower than that of Filipinos.

Sex

• Pregnant women are more likely to acquire disseminated coccidioidal infection, especially in the third trimester or in the immediate postpartum period.

Clinical

History

• Most C immitis infections in patients who are immunocompetent are asymptomatic or produce only a self-limited upper respiratory tract illness.
• The first symptoms of primary infection usually appear 9-21 days after exposure.
• Weight loss is a common sign, and headache has been noted in as many as 20% of patients, even in the absence of meningeal involvement.
• The triad of fever, erythema nodosum, and erythema multiform may occur. Erythema nodosum and erythema multiform have a strong predilection for female patients. Migratory arthralgias are common.
• Occasionally, coccidioidal pneumonia is present as a diffuse process. This pneumonia can lead to respiratory failure either because of inoculation with a high concentration of the pathogen or because fungi in the bloodstream infiltrate the lung at many sites. The presentation of coccidioidal pneumonia is fulminant, mimicking that of septic shock or bacterial infection, and mortality rates remain high despite appropriate treatment.
• Since early in the HIV epidemic, most AIDS patients with it had overwhelming diffuse pulmonary disease with a high mortality rate.⁸
• Dissemination of coccidioidomycosis is more likely in pregnancy.⁹ Immunologic and hormonal alterations during pregnancy and postpartum may account for the increased frequency and severity of disease during pregnancy.¹⁰

Physical

In patients with newly diagnosed coccidioidal infections, 2 critical assessments are made: (1) an evaluation of the extent of the disease, which is based on a review of the systems and physical examination, and (2) an identification of the risk factors for future complications.

The most common clinical presentation in patients with coccidioidomycosis is acute or subacute pneumonic illness. Findings in patients with new infection include shortness of breath, cough, chest pain, fever, and fatigue.

Other findings may include the following:

• Pulmonary nodules, cavities, and pneumothorax
  • Approximately 5% of pulmonary infections result in the formation of nodules, which may be as large as 6 cm in diameter. Typically, a nodule causes no symptoms but may be indistinguishable from a neoplasm without histologic examination. Occasionally, nodules may liquefy and drain into a bronchus to form a cavity.
  • Pulmonary cavities may be present initially or in later stages of the pulmonary infectious process. Usually, cavities are peripheral and solitary and, with time, develop a distinctive thin wall. Cavities may remain asymptomatic; one half of them close within 2 years. Some cavities are associated with local symptoms of pleuritic pain, cough, or hemoptysis.
    • Mycetoma may develop in the cavities as a result of infection with either mycelia of C immitis or other fungi such as Aspergillus species.
    • The rupture of a peripheral coccidioidal cavity into the pleural space is a complication that is most common in young male patients.
  • Pneumothorax is often present. An air-fluid level in the pleural space is a clue that the process is not a spontaneous pneumothorax.
• Chronic fibrocavitary pneumonia
  • Some patients develop a chronic fibrotic pneumonia process characterized by both pulmonary infiltrates and pulmonary cavitation.
  • Chronic fibrocavitary pneumonia appears to be associated with diabetes mellitus or preexisting pulmonary fibrosis related to cigarette smoking or other causes.
  • Involvement of more than 1 pulmonary lobe is more common.
  • The lesions may cause systemic symptoms, such as fever, night sweats, and weight loss, as well as local symptoms.
• Extrapulmonary dissemination of infection
  • C immitis spreads beyond the lungs in approximately 0.6% of the infections in the general population. Most extrapulmonary disseminated infections are a result of hematogenous spread of the infectious process.
  • Several factors dramatically increase the risk of dissemination: immunodeficiency conditions, including the late stages of HIV infection¹¹ ; chemotherapy; administration of high-dose (>20 mg/d) corticosteroids; and Hodgkin lymphoma. Additionally, men are more likely to develop disseminated infection than women.
  • Supraclavicular and cervical lymphadenopathy are a common presentation and probably is the result of lymphatic drainage from the pulmonary infection site.
  • The skin is the most common site of dissemination.
    • Involvement ranges from superficial maculopapules, keratotic nodules, and verrucous ulcers to subcutaneous fluctuant abscesses.
    • The lesions have a predilection for the nasolabial fold.
    • Erythema nodosum and erythema multiforme may occur; these have a strong predilection for female patients. Erythema nodosum may manifest as painful subcutaneous nodules and are typically located on the lower extremities. Erythema nodosum may be the first sign of systemic disease. Less commonly, erythema multiforme may develop instead of erythema nodosum, resulting in the typical target lesions. The triad of fever, erythema nodosum, and arthralgias is called desert rheumatism.
    • Buot et al reported finding specific cutaneous lesions of coccidioidomycosis during placement of a ventricular cardiac shunt for chronic meningitis.¹²
  • Joint and bone infections can also occur.
    • Joint infections differ from desert rheumatism: The infections in the latter are typically associated with prominent synovial involvement and effusion, whereas the self-limited joint findings associated with early infection are not.
    • The knee is most often affected, though any joint can be involved. Other commonly infected joints include the joints of the hands and wrists, the feet and ankles, and the pelvis. Although the long bones can be affected, infection in the vertebral column is more common. Involvement of multiple vertebral bodies is typical; these infections may coalesce to produce both anterior and posterior abscesses.
    • Infection may be isolated in the synovium, or it may progress to involve the underlying bone as well. Alternatively, the bones may be involved first, with secondary extension into the joint space.
  • Coccidioidal meningitis is the most serious form of disseminated infection. Untreated, it is almost always fatal within 2-3 years of diagnosis. Meningitis usually develops soon after the symptoms of the initial infection appear (average interval, 6 wk to 6 mo). The primary area of involvement is the basilar meninges.
    • Common presenting signs and symptoms include fever, headache, vomiting, altered mental status, and typical laboratory findings (see Procedures).
    • Hydrocephalus is a common complication, especially in children. Cerebral vasculitis and focal intracerebral coccidioidal abscesses are less common complications.

Causes

• Epidemics of coccidioidomycosis have been linked to large-scale soil disturbances caused by storms, earthquakes, and excavations.
• Farmers, ranchers, construction workers, and others engaged in outdoor activities with significant exposure to soil and dust have a high risk of infection by C immitis.
• Most cases are isolated and sporadic.
• Almost all C immitis infections result from arthroconidia inhalation.
  • A single C immitis arthroconidium may be sufficient to produce a naturally acquired respiratory infection.
  • Infection may be local, or it may spread in the lungs or via the bloodstream.
• Chronic fibrocavitary pneumonia appears to be associated with diabetes mellitus or preexisting pulmonary fibrosis related to cigarette smoking or other causes.
• Stagliano et al reported on a case of fomite-transmitted coccidioidomycosis that occurred in an immune-compromised child.¹³

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