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Coccidioidomycosis diagnosed in South Carolina.

Abstract: Primary care physicians in the Eastern United States rarely consider coccidioidomycosis in the differential diagnosis of pulmonary infections or febrile illnesses. However, the mobility of the population mandates consideration of this diagnosis, particularly in patients with fever and cough that do not resolve rapidly and in patients with adenopathy on chest radiography. In this report, we describe two unrelated cases encountered during a single week in a South Carolina internal medicine practice. These cases highlight the importance of obtaining travel histories from patients with atypical pulmonary infections. Early consideration of coccidioidomycosis confers several benefits, including allaying patient anxiety by more timely diagnosis, minimizing the empiric use of antibioties, and reducing the need for extensive and possibly invasive diagnostic testing.

Key Words: coccidioidomycosis, endemic disease, travel

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Coccidioidomycosis (valley fever) is caused by the dimorphic fungus Coccidioides immitis. The disease is endemic in the southwestern United States, including parts of California, Arizona, Nevada, New Mexico, and Texas. (1) However, cases of coccidioidomycosis among travelers have been reported outside of endemic areas. For example, 23 patients with coccidioidomycosis were seen at the Cleveland Clinic between 1980 and 1998. (2) In New York State, 161 patients with hospital discharge diagnoses of coccidioidomycosis were identified between 1992 to 1997. (3) Exposure to this organism is presumably increasing due to the growing mobility of the US population. As more people travel to and from the southwestern United States, a corresponding increase in the number of cases of coccidioidomycosis should be expected outside that region. (4) In this report, we describe two unrelated cases seen within a single week in a South Carolina internal medicine practice.

Case Reports

Patient 1

A 33-year-old black male presented to our office with several days of fever and mild headache. A viral illness was suspected, and no treatment was given. Two days later, he called the practice because a cough had developed, and azithromycin was prescribed: however, the patient discontinued the drug because of gastrointestinal side effects. Four days later, he returned to the office with low-grade fever, mild cough, and a single episode of blood-tinged sputum. Physical examination was unremarkable except for a temperature of 101.2F. A chest radiograph revealed right hilar and paratracheal adenopathy and a faint right upper lobe infiltrate (see Figure). White blood cell count was 14,000 with a normal differential, and erythrocyte sedimentation rate was 65 mm/h. A comprehensive chemistry panel and angiotensin converting-enzyme level were normal. A test for HIV antibodies was negative, and a tuberculin test was nonreactive.

The patient returned to the office several days later to review the test results, at which time additional history was obtained. The patient, a mechanic in the US Army had spent 1 week at a military base in southern California and had returned 10 days before the initial office visit. Coccidioidomycosis was now suspected. On a serum specimen obtained about 10 days after onset of symptoms, a complement fixation test was positive at 1:8, and immunodiffusion for IgM and IgG were both negative (Mayo Medical Laboratories, Rochester, MN). A second serum specimen, obtained 4 weeks after onset of symptoms, detected IgM antibodies against C immitis by immunodiffusion (Coccidioidomycosis Serology Laboratory, University of California, Davis). Although the patient was asymptomatic by this time, an infectious disease consultant recommended that the patient be treated with a 3-month course of fluconazole, 400 mg daily.

Patient 2

A 54-year-old white male returned home to South Carolina after a trip to Arizona. Shortly after his return, he had fever, night sweats, malaise, and a nonproductive cough. He saw his primary care physician, who obtained a chest computed tomography scan after noting abnormalities on a chest radiograph. The computed tomography scan revealed consolidation in the right upper lobe and paratracheal and right hilar adenopathy. Exposure to an endemic mycosis was not considered. A positron emission tomography scan was considered worrisome for malignancy. Therefore, the patient was referred to a surgeon who performed bronchoscopy and mediastinoscopy with lymph node biopsy. C immitis was isolated from cultures of the mediastinal lymph node, prompting referral to an infectious disease consultant in our practice. At the beginning of the visit, the patient inquired whether he might have had "valley fever." Because he had become asymptomatic by the time of the referral, this consultant elected not to initiate antifungal treatment.

Discussion

Primary care physicians in the Eastern United States rarely consider coccidioidomycosis in the differential diagnosis of pulmonary infections or febrile illnesses. However, the mobility of the US population mandates consideration of this diagnosis, particularly in patients with fever and cough that do not resolve rapidly, and in patients with adenopathy on chest radiography. Our two unrelated cases, encountered during a single week in a South Carolina internal medicine practice, serve to remind primary care physicians of the importance of obtaining a travel history from patients with atypical pulmonary infections. In the first case, the key travel history was not obtained until the third visit. In the second case, the patient underwent costly imaging and an invasive procedure because of this omission.

The clinical presentation of coccidioidomycosis is variable. Up to two thirds of people who are infected with C immitis remain asymptomatic or have trivial symptoms. Among those who have significant symptoms, most present with some combination of cough, fever, dyspnea, chest pain, and fatigue. (5) Because adenopathy is noted frequently on chest radiography, the differential diagnosis includes tuberculosis, other fungal infections, lymphoma, and sarcoidosis. Five percent of patients have residual pulmonary lesions (eg, pulmonary nodule or cavity), and some have diffuse pneumonia. (1) A small proportion of patients have extrapulmonary dissemination.

Certain risk factors predispose patients to progression to severe disease. These include HIV infection, corticosteroid and other immunosuppressive therapies, pregnancy (especially in the second and third trimester), and diabetes. In addition, certain racial groups (Filipino, black. Native American, Hispanic, and Asian) appear to be at higher risk for extrapulmonary disease than whites. (1)

Coccidioidomycosis is diagnosed definitively by culture, but obtaining appropriate specimens for culture may be difficult. Serologic testing for C immitis can be done by immunodiffusion, enzyme immunoassay, or complement fixation. (6) Immunodiffusion can detect both IgM and IgG antibodies, and complement fixation is used to detect IgG antibodies. (5) In primary infection, IgM antibodies appear within 1 to 3 weeks. Complement fixation testing detects IgG antibodies within 4 to 12 weeks of infection. (4) Complement fixation is the preferred serologic test for persistent infection, high or increasing titers suggest more extensive or worsening disease. (5) Most serologic tests for C immitis are specific when results are positive, but they may yield falsenegative results and should be repeated later in the illness if coccidioidomycosis is suspected. (7)

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Authorities recommend antifungal therapy for patients with severe symptoms or risk factors for disease progression. However, the treatment of uncomplicated primary respiratory coccidioidomycosis is controversial. A practice guideline issued by the Infectious Disease Society of America includes the following statement regarding treatment of uncomplicated respiratory cases:

"For many, if not most, patients, management may rely on periodic reassessment of symptoms and radiographic findings to assure resolution without antifungal treatment. On the other hand, some authorities propose treatment of all symptomatic patients." (8)

This statement is accompanied by a CIII evidence rating, which indicates that there is poor evidence to support a recommendation for or against treatment and that recommendations are based on expert opinion rather than clinical trials. (9) This ambiguity was reflected in the treatment of our two cases: although symptoms had resolved in both patients by the time the diagnosis was confirmed, the first patient subsequently received fluconazole and the second did not. The consultant in the first case was influenced by the fact that the patient was black (a risk factor for progression).

Conclusion

These two cases illustrate that primary care clinicians outside the southwestern United States will occasionally encounter coccidioidomycosis as a nonendemic infection among returning travelers. Early consideration of coccidioidomycosis will help to minimize the empiric use of antibiotics, reduce the need for extensive and possibly invasive diagnostic testing, and allay patient anxiety when the diagnosis is confirmed in a timely fashion.

References

1. Chiller TM, Galgiani JN, Stevens DA. Coccidioidomycosis. Infect Dis Clin N Am 2003;17:41-57.

2. Desai SA, Minai OA, Gordon SM, et al. Coccidioidomycosis in nonendemic areas: a case series. Respir Med 2001;95:305-309.

3. Chaturvedi V, Ramani R, Gromadzki S, et al. Coccidioidomycosis in New York State. Emerg Infect Dis 2000;6:25-29.

4. Panackal AA, Rajjeh HA, Cetron MS, et al. Fungal infections among returning travelers. Clin Infect Dis 2002;35:1088-1095.

5. Galgiani JN. Coccidioides immitis. Principles and Practice of Infectious Diseases. 5th ed. Mandell GL, Bennett JE, Dolin R (eds). Philadelphia. Churchill Livingstone, 2000, pp 2746-2757.

6. Crum NF, Lederman ER, Stafford CM, et al. Coccidioidomycosis: a descriptive survey of a reemerging disease: clinical characteristics and current controversies. Medicine 2004;83:149-175.

7. Galgiani JN. Coccidioidomycosis: a regional disease of national importance. Ann Intern Med 1999;130:293-300.

8. Galgiani JN, Ampel NM, Catanzaro A, et al. Practice guidelines for the treatment of coccidioidomycosis. Clin Infect Dis 2000;30:658-661.

9. Sobel JD. Practice guidelines for the treatment of fungal infections. Clin Infect Dis 2000;30:652.
Maturity is a bitter disappointment for which no remedy exists, unless
laughter can be said to remedy anything.
--Kurt Vonnegut


J. Blake Long, MD, Allan S. Brett, MD, and Joseph A. Horvath, MD

From the Department of Medicine, University of South Carolina School of Medicine, Columbia, SC.

Reprint requests to Allan S. Brett, MD, Department of Medicine, USC School of Medicine, 2 Medical Park, Suite 502, Columbia, SC 29203. Email: allansb@gw.mp.sc.edu

None of the authors has any commercial or proprietary interest in any drug, device, or equipment mentioned in this manuscript. There was no financial support for this work. The authors have no financial conflicts of interest relevant to this work.

Accepted February 8, 2005.

RELATED ARTICLE: Key Points

* Primary care clinicians outside the southwestern United States will encounter coccidioidomycosis among travelers returning from endemic areas.

* Early consideration of coccidioidomycosis will minimize the empiric use of antibiotics, reduce the need for extensive and possibly invasive diagnostic testing, and allay patient anxiety by a more timely diagnosis.

* Treatment of uncomplicated coccidioidomycosis remains controversial.
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Article Details
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Title Annotation:Case Report
Author:Horvath, Joseph A.
Publication:Southern Medical Journal
Geographic Code:1U5SC
Date:Sep 1, 2005
Words:1710
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