Coccidioidomycosis is the disease process that results from infection with the fungus Coccidioides immitis or Coccidioides posadasii. This fungus grows in the soil of endemic areas to include southern California, Arizona, Nevada, New Mexico, Texas, northern Mexico and in parts of South America (Argentina and Paraguay). Persons of African or Filipino ancestry are more prone to infection. Infection occurs when the arthrospores are inhaled and reach the alveoli. Human-to-human transmission has not been reported. The various forms of human infection include acute pneumonia, chronic progressive pneumonia, pulmonary nodules/cavities, extrapulmonary nonmeningeal disease, and meningitis.
Primary pulmonary infection is often asymptomatic; however, when symptoms do manifest, they include fever, chills, malaise, nonproductive cough, dyspnea, arthralgias, pharyngitis, and skin rash. In fact, 60% of cases are either asymptomatic or mimic an upper respiratory tract infection. San Joaquin Valley fever is a symptom complex that results from primary coccidioidomycosis and is characterized by erythema nodosum, arthralgias, malaise, and fever. The primary tissue reaction is granulomatous; however, fibrosis, purulence or caseation may occur. The symptoms of primary pulmonary infection generally resolve and may be the only manifestation of infection, or they may be replaced by symptoms of chronic pulmonary infection (symptoms persist for longer than 8 weeks-more common in diabetics and the immunocompromised) or dissemination (more common in patients with AIDS or on immunosuppressive medications). Some patients manifest acute progressive pneumonia with severe parenchymal damage, and this disorder is often associated with a fatal outcome. An exudative pleural effusion may also occur with primary pulmonary disease. Chronic progressive pneumonia manifests as chronic cough, sputum production, hemptysis, and weight loss that persists for longer than three months.
Other potential sites of infection seen in extrapulmonary nonmeningeal disease include muscles, tendons, bones, joints, meninges, skin, and the organs of the female pelvis. Although pulmonary infection is more common, these other sites of infection will be discussed briefly.
Musculoskeletal coccidioidomycosis often manifests as local pain, swelling , warmth, and fever. Bone or joint infection is seen in approximately one-third of cases of disseminated coccidioidomycosis. The skull, metacarpals, metatarsals, spine, and tibia are the most commonly affected bones with lytic lesions being more common than sclerotic manifestations. Bone scans are effective for detecting involvement and are much more sensitive than plain radiographs. In 90% of cases with joint involvement, the lesions are unifocal and affect the ankles or knees most commonly.
Cutaneous manifestations are many and include rash, papules, pustules, plaques, nodules, ulcers, abscesses, or large proliferative lesions. A wart-like lesion is characteristic. Skin lesions, which mimic other fungal lesions, are common with disseminated disease. Multiple abscesses without an explanation should prompt appropriate diagnostic testing. Since the purulent material is a good source for culture, an appropriate specimen should be collected and sent. Warn lab personnel of the suspected diagnosis as they are at risk of exposure with resultant infection from spores.
Meningitis usually occurs within the first 6 months of infection, and may develop with the initial infection. The basilar meninges are the main areas of infection, and space-occupying lesions are rare. Meningeal irritation, which is characteristic of bacterial meningitis, is rare. Headache is the most common presenting complaint. Other associated symptoms may include fever, weakness, confusion, seizures, abnormal behavior, stiff neck, diplopia, ataxia, vomiting, or focal neurologic deficits. Cerebral spinal fluid (CSF) examination may reveal pleocytosis (predominantly mononuclear cells although eosinophils may also occur), a low glucose level, and an elevated protein content. The diagnosis is confirmed by CSF culture (positive in one-third of cases) or a positive CSF complement fixation test in the absence of parameningeal disease. With meningeal disease, as opposed to other sites of dissemination, the serum complement fixation titers are usually below 1:32.
The diagnosis is often made via skin tests and serology although culture is the best means. Purulent material yields the highest culture results. Skin testing (converts 10-45 days after infection) is performed using either the standard coccidioidin antigen or the spherulin antigen. Patients with erythema nodosum may have severe reactions to the skin test, and a diluted antigen should be used if skin testing is deemed necessary in these patients. It is important to note that a negative skin test does not rule out infection, and a false-negative skin test does not mean the patient is anergic. In fact, anergy is common with disseminated disease. Even in the presence of the proper symptoms, a positive skin test is only indicative of prior exposure to Coccidioides immitis. Therefore, a positive skin test should be confirmed by serologic evaluation. Coccidioides complement fixation titers (CF) are an effective means to establish the diagnosis and also provides some information as to the severity of infection. When CF titers are greater than 1:32, there is a risk of disseminated disease; however, a high titer is not always present when there is dissemination, and conversely, a high titer does not always indicate dissemination. When interpreting titers it is important to note that 95-100% of patients not afflicted with disseminated disease have titers below 1:32, and in patients with disseminated disease, 61% have titers of 1:32 or greater and 41% have titers of 1:64 or greater. Peripheral eosinophilia may occur with primary infection especially when infection is associated with either erythema nodosum or disseminated disease. An enzyme-linked immunosorbent assay for coccidioidal antigens and a polymerase chain reaction are also available to aid in establishing the diagnosis.
The chest radiograph is often abnormal, even in asymptomatic infection. Infiltrates are commonly noted and vary in size, location and duration. Pleural effusions are occasionally noted in less than 10% of cases. Pulmonary nodules, either single or multiple, often result from infection as do pulmonary cavitary lesions. Cavitary lesions may hemorrhage, rupture into the pleural space or undergo spontaneous closure. Nodular lesions rarely result in dissemination although 10 to 15% may result in cavitation. Approximately 5% of persons who have suffered infection have residual pulmonary changes, most commonly a pulmonary nodule or cavity. Bronchiectasis may result from a severe initial infection or from chronic pulmonary disease.
Therapy is variable depending on the severity of infection. Symptomatic uncomplicated primary infections generally resolve without therapy. Therapy entails either surgical resection, fluconazole, itraconazole, voriconazole, or amphotericin B. Possible indications for chemotherapy include the following: severe primary infection, greatly increased complement fixation titers (indicative of potential dissemination), persistence of symptoms for more than 6 weeks, prostration, persistently elevated serologic titers, anergic skin testing (indicative of dissemination), infancy, high risk heritage (African or Filipino), pregnancy, immunologic compromise (diabetes mellitus), or the presence of underlying diseases (asthma, emphysema, etc.) likely to be adversely affected. Infection during pregnancy is a dangerous situation. In fact, maternal mortality resulting from infection is common in endemic areas. When pregnant women have active disease, abortion or early delivery should be considered, and amphotericin B therapy should be administered. Amphotericin B appears to increase the chances of maternal survival and to be safe for the fetus if the aforementioned options are not possible. Patients with coccidioidomycosis meningits require lifelong therapy. Fluconazole may be used in dosages of 400 to 1200 mg/day and itraconazole therapeutic dosages range from 400 to 600 mg/day. Since itraconazole requires a gastric pH, it is a poor therapeutic choice in patients on proton pump inhibitors.