Coccidioidomycosis: causes, symptoms, diagnosis, treatment, prognosis

Coccidioidomycosis is a highly contagious disease caused by Coccidioides immitis and Coccidioide posadasii, and is manifested by mostly benign, self-limiting, acute respiratory infections, as well as chronical disseminated infections in the skin, subcutaneous tissue, internal organs, and bones.


The pathogens are Coccidioides immitis and Coccidioide posadasii, which are dimorphic fungi. The fungi can reside in soils at any pH value or at any temperature in nature, but cannot be isolated in well irrigated and nutritious soils in the epidemic area. In nature, the fungi exist in the form of mold with septate hyphae. The spores can float in the wind, thereby extremely contagious. The fungi enter the lungs through inhalation or enter the skin after trauma, so coccidioidomycosis is an exogenous infection. Humans are generally susceptible, and animals can also be infected. However, human-to-human and animal-to-human transmission are absent.

Signs and Symptoms

Primary coccidioidomycosis

Coccidioides mainly invade the lung, skin, subcutaneous tissue, lymph nodes, bones, joints, internal organs, and brain.

60% of patients have no obvious clinical symptoms, but positive results are visible in coccidioidin skin test. In an incubation period of about 2 weeks after infection, some patients present symptoms of upper respiratory tract infections, such as cough, low fever, night sweats, headache, purulent sputum, and bloody sputum. Sometimes, pleurisy, massive pleural effusion, herpetic conjunctivitis, or acute arthritis are present. Few patients may present with erythema nodosum and erythema multiforme on the extremities and face. In X-ray examination, pulmonary lesions, such as pneumonia-like lesions, tuberculoid lesions, mediastinal and hilar lymphadenopathy, and pleural effusion can be found in 80% of patients.

Papular nodules occur after skin trauma, and the erosions on the surface are like syphilis chancres. Scattered, secondary nodules occur along the lymphatic vessels, and the regional lymph nodes are enlarged. A history of skin trauma may be absent. Common skin lesions are red to dark red, painless nodules or plaques, and the erosions on the surface lead to ulcers, eventually forming verrucous lesions. Cutaneous coccidioidomycosis can be healing spontaneously after scabbing.

Figure 1 A: chest X-ray showing hydropneumothorax in the right lung, low translucency area (black arrow), and right atelectasis, B: CT after closed thoracic drainage showing thin-walled cavity (white arrow) in posterior right upper lobe, alveolar recruitment after closed thoracic drainage

Progressive coccidioidomycosis

If primary coccidioidomycosis persists, pulmonary cavity, pleural effusion, air fluid levels, tuberculoid lesions, bronchiectasis, empyema, and pneumothorax may occur in 2% - 8% of patients with symptomatic primary infections. The development of the disease can cause multiple nodular cavities. Persistent high fever, fatigue, anorexia, emaciation, anemia, cough, dyspnea, cyanosis, purulent mucous sputum, and bloody sputum can be present. Some spherules can be found in the sputum. Hematogenous dissemination can cause lesions in the bone, joint, skin, and internal organs.


The lesions are acute purulent, with massive neutrophil infiltration. Sometimes there is caseous necrosis. Spherules containing endospores can be found in the abscesses. With the continuous development of endospores, the histologic reaction gradually changes from acute purulent to chronic granulomatous, with infiltration of lymphocytes, epithelioid cells, large monocytes, histiocytes, plasma cells, and foreign body giant cells. Pathogens are common in the giant cells or peripheral granuloma tissue. Epithelial cells can be hypertrophic.

Abscesses or granuloma can be seen in the lymph nodes, and pathogens can also be found. Abscess, necrosis, or cavity formation in bones, which are filled by granuloma tissue, may be visible, and pathogens are present.

In histopathology, pathogens are 20 - 200μm in size spherules containing 2 - 5μm in diameter endospores. Spherules have four forms, which indicate different developmental stages.

Premature spherules are small and round, with or without homogeneous cytoplasm in the spherules.

Maturing spherules are round or oval and thick-walled, and there may be cytoplasm near the cell wall.

Mature spherules are round, thick-walled, 20 - 200μm in diameter, and containing 2 - 5μm in diameter endospores.

Collapsed spherules are different shaped and are spherules that have released endospores, and most of them have no endospores.

HE stain can stain the endospores and cell walls but too light, and PAS stain can stain endospores but cannot stain cell walls. The best stains are Grocott methenamine silver (GMS) stain and Gridley fungus (GF) stain, which can stain endospores and cell walls, and sharp contrasts can assist in the observation.


On the basis of typical clinical presentations, coccidioidin skin test, arthroconidia found in fungal microscopy, and histopathology, the disease can be diagnosed.


Primary coccidioidomycosis can be treated with fluconazole, and primary skin infections can be treated with excision, cryotherapy, and laser.

Mild to moderate, nonmeningeal, extrapulmonary coccidioidomycosis can be treated by fluconazole ≥400 mg/d orally or itraconazole 200mg orally twice a day. Alternative treatment options include voriconazole 200mg orally or intravenously twice daily or posaconazole 400mg orally twice daily, but these treatment options have not been well studied and evaluated clinically. In severe cases, amphotericin B 0.5 - 1.0 mg/kg for 4 - 12 weeks can be administered, depending on the severity of infection. Amphotericin B lipid preparations are superior to ordinary amphotericin B. After the condition is stabilized, amphotericin B can be replaced by azoles orally once a day.

For patients with HIV or AIDS, maintenance treatment is required to prevent recurrence. The maintenance treatment regimen is fluconazole 200mg orally once daily or itraconazole 200mg orally twice daily, until the CD4 cell count > 250 /μL.

Meningeal coccidioidomycosis can be treated with fluconazole 800 - 1200 mg/d, and lifelong antifungal treatment is required.

Bone lesions can be excised. Conservative treatment may be appropriate in cavitary pulmonary lesions. If there is persistent hemoptysis, surgery should be considered.


Untreated disseminated coccidioidomycosis is often fatal, and meningeal coccidioidomycosis without long-term or even lifelong treatment is also life-threatening. The mortality rate of coccidioidomycosis in patients with advanced HIV infection exceeds 70% within one month after definitive diagnosis. It is not clear whether treatment can reduce the mortality rate of this disease.