Dust in the Wind — Cutaneous and Parotid Effects of Disseminated Coccidioidomycosis
Case Presentation
With Comment By Mary-Louise Scully, MD, Sansum-Santa Barbara Medical Foundation Clinic, Santa Barbara, Calif., and Associate Editor, Travel Medicine Advisor.
A 52-year-old African American male from Ridgefield, California, developed fever, cough, and flu-like symptoms; a chest X-ray was compatible with pneumonia. After a course of antibiotics failed to improve his symptoms, serology for possible coccidioidomycosis was obtained and found to be positive. The patient began fluconazole therapy with gradual resolution of his clinical symptoms. Follow-up serology demonstrated a complement fixation titer of 1:32 at 4 weeks and 1:16 following 8 weeks of treatment. At 10 weeks, the patient complained to his primary physician about multiple symptoms he attributed to the fluconazole and, therefore, treatment was discontinued. Four weeks later, the patient presented with a painless mass in the right parotid gland with associated adenopathy and several scattered skin lesions on his chest. The patient underwent fine needle aspiration of the parotid gland and a skin biopsy, both of which demonstrated mature spherules with endospores on pathology, and both consistent with a diagnosis of coccidioidomycosis. In addition, a culture specimen of the parotid fine needle aspirate grew out Coccidioides immitis.
Comment
Coccidioidomycosis is caused by inhalation of the spores (arthroconidia) of Coccidioides immitis, a dimorphic fungus that is endemic within the southwestern United States, primarily Arizona, central California, southern New Mexico, and western Texas. C. immitis is also endemic in many parts of Mexico such as Sonora, Chihuahua, Durango, Nuevo Leon, and Coahuila. Other endemic areas include northeastern Venezuela, Comayagua Valley in Honduras, the Motagua River Valley in Guatemala, and Patagonia and Rio Hondo in Argentina. Cases have also been reported in Bolivia, Paraguay, and Columbia.1
Travel to endemic areas may result in infection. In 2001, an English and German male were each hospitalized in their respective countries with coccidioidal pneumonia after attending a World Model Airplane Championship in Lost Hills, California, where 32 nations were represented. Follow-up revealed that 10% of the participants had either clinical illness and/or serology indicating coccidioidomycosis as a result of dust exposure at the same event.2
Increased incidence of coccidioidomycosis is typically associated with windstorms, droughts, earthquakes, or construction and excavation that results in soil disruption.
Some infectious etiologies to consider among travelers or immigrants who present with a painless parotid mass or enlargement would include tuberculosis, actinomycosis, fungal pathogens such as Coccidioides immitis, and gastrointestinal Chagas disease (parotid hypertrophy). Melioidosis, caused by Burkholderia pseudomallei, is a known cause of acute suppurative parotitis, especially among children from Southeast Asia.3 Acute suppurative parotid gland infection can account for up to 40% of pediatric cases. It may be bilateral in about 10%, and associated with rupture or permanent facial nerve palsy.
It is estimated that 100,000 infections due to C. immitis occur each year, most of which are subclinical. The most common clinical presentation is an acute or subacute respiratory or pneumonic illness, sometimes termed Valley Fever. Cough, pleuritic chest pain, fever, and flu-like symptoms are common symptoms. Occasionally, the patient will complain of arthralgias and myalgias, which led to the alternate term “desert rheumatism,” for this illness. The presence of rash (erythema multiforme or erythema nodosum) or eosinophilia in patients with flu-like illness in an endemic area can be the clues to prompt testing for coccidioidomycosis. Pulmonary sequelae such as nodules or peripheral thin-walled cavities can be seen after acute illness in about 5% of patients. Diffuse pneumonia with bilateral reticular nodular or military infiltrates can occur following inhalation of a large inoculum of spores or more often as a manifestation of fungemia related to an underlying immunodeficiency state.
Disseminated infections may develop in 0.5%-1.0% of infected patients. Patients at higher risk of disseminated disease are immunocompromised hosts, pregnant females, diabetics, and persons of African or Filipino descent. Common sites of extrapulmonary coccidioidomycosis are meninges and spinal cord, bone and joints, and skin and subcutaneous soft tissue. Other sites of dissemination have been reported in almost every organ including the eye, larynx, thyroid, prostate, kidneys, endocrine glands, and the peritoneal cavity. A recent review of head and neck manifestations of disseminated coccidioidomycosis noted freuent skin and laryngeal involvement.4 Disseminated coccidioidomycosis of the central nervous system and meningitis are by far the most serious, potentially life threatening manifestations of extrapulmonary coccidioidomycosis.
A diagnosis of coccidioidomycosis can be made by fungal culture, staining of tissue specimens, and specific serological testing. Skin testing is no longer employed, as commercially available skin test antigens are not available. Serological tests primarily utilize 2 antigens to detect antibodies. The first is a tube-precipitin antigen, which detects antibodies in the course of primary coccidioidomycosis and is considered an IgM test. The second is a complement fixing (CF) antibody, which increases later in the course of infection. The serum titer of the CF antibody is felt to correlate roughly with the extent of the infection. More importantly, when a reliable reference laboratory (such as University of California, Davis) is used for testing, the CF titer can be used serially to monitor resolution of infection (decreasing titers) and to assess worsening infection or reactivation after treatment has been discontinued (increasing titers). An ELISA test is commercially available; it uses a proprietary antigen to detect antibodies to both tube-precipitin and CF antibodies. Although this ELISA is highly sensitive for diagnosis of coccidioidal infection, the CF titer is the appropriate test to follow for management of serious or disseminated infections.
No prospective, controlled trials on management of primary coccidioidomycosis have been done. Some physicians follow patients clinically without treatment, whereas others opt to treat all symptomatic patients. With the availability of the less toxic oral azoles such as fluconazole and itraconazole, more clinicians are no doubt treating early infection, compared to the time when Amphotericin B was the only available medication. Clearly, concurrent risk factors such as HIV infection, organ transplant recipients, those on high-dose corticosteroids, as well as the more serious infections should prompt treatment. The IDSA Practice Guidelines for the treatment of coccidioidomycosis (www.IDSociety.org) list some indicators for severity of primary infection as weight loss of greater than 10%, night sweats persisting longer than 3 weeks, infiltrates involving more than one-half of one lung or portions of both lungs, prominent or persistent hilar adenopathy, concentrations of complement fixing (CF) antibody to C. immitis of greater than 1:16, inability to work, and symptoms that persist for greater than 2 months.5 Again, most experts feel that pregnant patients, diabetics, and patients of African or Filipino descent warrant early treatment based on their higher risk of disseminated disease. In pregnancy, amphotericin B should be used for treatment due to possible teratogenic effects of azoles.
Disseminated nonmeningeal disease is generally treated with either fluconazole or itraconazole. In a randomized, prospective trial comparing both drugs (fluconazole 400 mg/day vs itraconazole 200 mg, twice each day), neither drug showed statistical superiority at 8 months, though there was a trend toward slightly greater efficacy in skeletal disease using itraconazole at the doses studied.6 For practical purposes, itraconazole is less often used because of more frequent drug interaction issues and potential problems with drug absorption. With itraconazole use, it may be prudent to check serum drug levels to make sure the drug is being properly absorbed. Duration of treatment in disseminated nonmeningeal disease will vary depending on a patient’s response to treatment, but is often continued for 6 months after the disease becomes inactive; sometimes this can mean several years.7 Disseminated disease in patients with ongoing immunosuppression, such as solid organ transplant recipients, often requires secondary prophylaxis for life, as relapses are common.8
Newer antifungal agents, including voriconazole, posaconazole, and caspofungin, may have a future role in the treatment of coccidioidomycosis. Ongoing research efforts are focusing on specific fungal proteins for possible use in a recombinant vaccine. An excellent resource for both clinical and research aspects of coccidioidomycosis is the Valley Fever Center for Excellence, with online access at www.vfce.arizona.edu.
References
1. Rios-Fabra A, et al. Fungal Infection in Latin American Countries. Infect Dis Clin North Am. 1994;8(1):129-154.
2. CDC. Coccidioidomycosis Among Persons Attending the World Championship of Model Airplane Flying-Kern County, CA. MMWR. 2001;50:1106-1107.
3. Lumbiganon P, et al. Clinical Manifestations of Melioidosis in Children. Pediatr Infect Dis J. 1995;14:136-140.
4. Arnold MG, et al. Head and Neck Manifestations of Disseminated Coccidioidomycosis. Laryngoscope. 2004;114:747-752.
5. Galgiani JN, et al. Practice Guidelines for the Treatment of Coccidioidomycosis. Clin Infect Dis 2000;30:658-661.
6. Galgiani JN, et al. Comparison of Oral Fluconazole and Itraconazole for Progressive, Nonmeningeal Coccidioidomycosis. Ann Intern Med. 2000;133:676-686.
7. Chiller TM, et al. Coccidioidomycosis. Infect Dis Clin North Am. 2003;17:41-57.
8. Blair JE, et al. Coccidioidomycosis in Solid Organ Transplantation. Clin Infect Dis. 2001;33:1536-1544.
A 52-year-old African American male from Ridgefield, California, developed fever, cough, and flu-like symptoms; a chest X-ray was compatible with pneumonia. After a course of antibiotics failed to improve his symptoms, serology for possible coccidioidomycosis was obtained and found to be positive.
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