Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.

A 35-year-old man is evaluated for a 2-week history of nonproductive cough and fever. He has a 20-year history of asthma. Three weeks ago, he visited friends in Indiana. He has no dyspnea, hemoptysis, or worsening of his baseline asthma symptoms. His only medication is an albuterol inhaler as needed.

On physical examination, temperature is 38.0 °C (100.4 °F), blood pressure is 130/70 mm Hg, pulse rate is 88/min, and respiration rate is 16/min. Crackles are heard in both lungs.

Laboratory studies show a normal leukocyte count and serum creatinine level.

Chest radiograph reveals patchy pulmonary infiltrates with mild hilar lymphadenopathy.

Which of the following is the most appropriate management?

A: Lipid amphotericin B
B: Fluconazole
C: Itraconazole
D: No treatment

MKSAP Answer and Critique

The correct answer is D: No treatment.

This patient has mild pulmonary histoplasmosis, which is self-limiting and requires no treatment in a healthy host. In those who become ill, the incubation period is 7 to 21 days, and most have symptoms by day 14. Histoplasmosis is common in states bordering the Ohio River Valley and the lower Mississippi River. Infection may be asymptomatic, but the diagnosis should be considered in any patient with pulmonary and systemic symptoms following potential exposure in a geographically endemic area. In most symptomatic patients, disease is mild and resolves without therapy within 1 month. In a few patients, particularly those with immunocompromise (such as HIV infection) or other concurrent illnesses, severe pneumonia with respiratory failure may result.

Histoplasmosis may also cause chronic infection, including pulmonary and mediastinal masses, cavitary lesions, central nervous system involvement, pericarditis, and arthritis and arthralgia. Antifungal treatment is indicated for severe or moderately severe acute pulmonary, chronic pulmonary, disseminated, and central nervous system histoplasmosis or for those patients whose symptoms do not improve within 1 month. Evidence of effectiveness, however, is lacking to support this recommendation.

If treatment is indicated for acute pulmonary histoplasmosis, the treatment of choice is itraconazole. Lipid formulations of amphotericin B are indicated for more severe forms of pulmonary histoplasmosis. Fluconazole has been used for treatment of histoplasmosis, but it is less effective than itraconazole. Fluconazole resistance has also been noted in some patients who have not responded to therapy.

Key Point

• Mild forms of histoplasmosis do not require treatment, whereas more severe forms may be treated with amphotericin B or one of the newer triazole antifungal agents.

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