Case In Point: Fever and a chest wall mass in a young man

The case

A 21-year-old African American US Army soldier presented with fever, chills, drenching night sweats, and nonproductive cough of 4 weeks' duration. In addition, he had recently detected a painless right breast mass. His past medical history was unremarkable. He was stationed at Fort Irwin, California, where he was working as a telephone repairman.

On physical examination, the patient had a temperature of 37.2°C (98.9°F), blood pressure of 128/76 mm Hg, pulse rate of 99 beats per minute, respiration rate of 16 breaths per minute, and oxygen saturation of 99% on room air. He appeared thin, but not cachectic, and was in no acute distress. The patient's heart, lung, and abdominal examination findings were unremarkable.

A firm, nontender, 3-cm subcutaneous mass overlay the right breast. Testicular, skin, and neurologic examination findings were normal. Multiple small (less than 1 cm), nontender lymph nodes were palpable in the axillae and groin.

Laboratory studies revealed a white blood cell count of 11.9/µL, with 30% eosinophils. Hemoglobin level was 11.4 g/dL, and the platelet count was normal. A comprehensive chemistry panel was notable only for an elevated alkaline phosphatase level (262 U/L; normal range, 38 to 126 U/L). Results of blood cultures; tests for serum Cryptococcusantigen, urinary Histoplasmaantigen, and HIV antibody; and purified protein derivative skin testing were negative.

The patient's initial chest radiograph demonstrated bilateral interstitial micronodules in a miliary pattern, as well as right-sided paratracheal fullness. A CT scan of the chest confirmed the presence of diffuse, 1- to 2-mm, micronodules in all lobes (Figure 1). The CT scan also showed a lobular parenchymal mass lesion (2.4 3 1.1 cm) in the right middle lobe and a right anterior chest wall mass.

A fine-needle aspirate of the right breast mass yielded fungal spherules filled with endospores, consistent with coccidioidomycosis, which was subsequently confirmed by fungal culture (Figure 2). A serology panel for Coccidioides immitis was also positive and revealed IgG complement fixation titers at a dilution greater than 1:256.

Results of cerebrospinal fluid analysis were normal. A bone scan showed multiple regions of increased osteoblastic activity, including the left scapula, the right anterior fifth rib, and midthoracic vertebral regions.

Therapy was initiated with amphotericin B, but because of worsening renal function, amphotericin B lipid complex was substituted. Increasing neck pain, however, prompted further imaging, which revealed a lytic lesion of the C1 vertebral body and a paraverte- bral mass (7.8 3 3.8 cm). Despite continued intravenous antifungal therapy, progressive enlargement of the paravertebral mass necessitated surgical debridement. Nine months later, the patient continued to receive amphotericin B lipid complex for persistent cervical disease, with plans for long-term, perhaps lifelong, antifungal therapy.

Discussion

C immitisis a dimorphic fungus endemic in the southwestern United States, Mexico, and South America. This fungus causes a spectrum of disease, ranging from incidentally discovered, asymptomatic pulmonary infection to potentially fatal multiorgan dissemination.

The propensity of coccidioidomycosis to mimic a wide variety of diseases and defy easy diagnosis has been previously noted.¹ The radiographic manifestations of pulmonary coccidioidomycosis are diverse and include lobar consolidation (75%), hilar or mediastinal adenopathy (20%), pleural effusion (20%), solitary or multiple nodules (5%), and cavitary lung disease (5%).^2,3 Miliary disease is very uncommon and is characterized by innumerable, tiny (1 to 5 mm) pulmonary opacities on a chest radiograph, hematogenous dissemination, and subsequent granuloma formation.^3,4

Although the miliary form of coccidioidomycosis occurs primarily in patients with identifiable immune defects, there are rare exceptions. Crum and associates⁵ found that 1 (0.4%) of 223 patients with coccidioidomycosis presented with a miliary disease pattern.

Arsura and Kilgore⁶ found 8 seemingly immunocompetent patients who had miliary coccidioidomycosis, which represented 1% of 739 admissions. Of these 8 patients, however, 2 were pregnant, 2 were HIV-negative injection drug users, and 2 were African American--groups that may be more prone to disseminated coccidioidomycosis. Five patients required mechanical ventilation, and 3 died despite intensive therapy and supportive care.⁶ Other reports of miliary coccidioidomycosis have also noted very high mortality rates.⁷

Given the poor prognosis associated with miliary coccidioidomycosis, timely diagnosis and treatment are essential. The differential diagnosis includes other infections (tuberculosis, histoplasmosis, and cryptococcosis), pneumoconiosis (silicosis), systemic inflammatory disorders (sarcoidosis), and malignancy (lymphangitic carcinoma, alveolar cell carcinoma, and lymphoma).^2,4 Differentiation on radiographs is impossible, and cultures and/or histology is usually required.

Clues to the diagnosis of disseminated coccidioidomycosis in our patient included an infectious prodrome, peripheral eosinophilia, hilar adenopathy, characteristic pattern of organ involvement (lungs, bones, soft tissues), residence in an area in which C immitisis endemic, and African American ethnicity. (African American and Filipino persons have been shown to be at higher risk for dissemination.)

C immitislives in the soil, and infection is most likely to be seen in persons whose work or hobbies involve digging (such as construction workers, military trainees, and archeologists). Climatic factors, such as temperature, soil moisture, and wind, influence the growth and release of the barrel-shaped mycelial form (arthroconidium) of the fungus into the air, which can then be inhaled. Unsuspected exposure, including that associated with travel, may be sufficient for the development of infection and may pose a diagnostic challenge to physicians in areas in which this fungus is not endemic.

Conclusion

Pulmonary coccidioidomycosis is an endemic fungal disease with varied clinical and radiographic presentations. Although dissemination is not uncommon, miliary pulmonary disease is rare and portends an especially poor prognosis. Once considered, the diagnosis of coccidioidomycosis should be pursued by performing appropriate serologic testing and confirmed by histology and culture. Physicians must remember to take a careful travel history and should consider regional fungal infections, such as coccidioidomycosis, in the differential diagnosis of unusual pulmonary disease, including disease associated with a miliary pattern or with extrapulmonary manifestations.

References:

REFERENCES

1. Oldfield EC, Olson PE, Bradshaw DA. Coccidioidomycosis presenting as neoplasia: another great imitator disease.

Infect Dis Clin Pract.

1995;4:87-92.
2. Snyder LS, Galgiani JN. Coccidioidomycosis: the initial pulmonary infection and beyond.

Semin Respir Crit Care Med.

1997;18:235-247.
3. Batra P. Pulmonary coccidioidomycosis.

J Thorac Imaging.

1992;7:29-38.
4. Fraser R. Pulmonary mycoses. In: Fraser R, Müller NL, Colman N, Pare PD, eds.

Fraser and Pare's Diagnosis of Diseases of the Chest.

4th ed. Philadelphia: WB Saunders Co; 1999:713-715.
5. Crum NF, Lederman ER, Stafford CM, et al. Coccidioidomycosis: a descriptive survey of a reemerging disease. Clinical characteristics and current controversies.

Medicine (Baltimore).

2004;83:149-175.
6. Arsura EL, Kilgore WB. Miliary coccidioidomycosis in the immunocompetent.

Chest.

2000;117:404-409.
7. Goldstein E. Miliary and disseminated coccidioidomycosis.

Ann Intern Med.

1978;89:365-366.