Fever after recent travel
HISTOPLASMOSIS
Histoplasma capsulatum is a dimorphic fungus that thrives in the soil and caves of regions with moderate climate, especially in soil containing large amounts of bird excreta or bat guano.9 Bats are natural hosts of this organism, and it is endemic in North and Central America, including parts of Mexico. Air currents can carry the microconidia for miles, thus exposing people without direct contact with contaminated sites.
The infection is usually acquired by inhalation of microconidia or small hyphal elements or by reactivation of previously quiescent foci of infection in an immunosuppressed patient. Most patients exposed to H capsulatum remain asymptomatic or develop mild symptoms, which are self-limiting. A small number develop acute pulmonary histoplasmosis or chronic cavitary histoplasmosis. Disseminated disease usually occurs only in an immunosuppressed host.
Acute pulmonary histoplasmosis presents with fever, malaise, headache, weakness, substernal chest pain, and dry cough and may be associated with erythema nodosum, erythema multiforme, and arthralgias. It may be mistaken for sarcoidosis since enlarged hilar and mediastinal lymph nodes are often seen on chest radiography.10
Progressive disseminated histoplasmosis is defined as a clinical illness that does not improve after at least 3 weeks of observation and is associated with physical or radiographic findings with or without laboratory evidence of extrapulmonary involvement.11
Fever, malaise, anorexia, weight loss, night sweats, hepatosplenomegaly, and lymphadenopathy are features of progressive disseminated histoplasmosis.
Cutaneous manifestations of disseminated histoplasmosis occur in 10% to 25% of patients with acquired immunodeficiency syndrome and include papules, plaques with or without crust, pustules, nodules, lesions resembling molluscum contagiosum virus infection, acneiform eruptions, erythematous macules, and keratotic plaques.12
TESTING FOR HISTOPLASMOSIS
2. What investigation is least likely to help confirm the diagnosis of disseminated histoplasmosis?
- Polymerase chain reaction (PCR) testing of serum, cerebrospinal fluid, and bronchoalveolar lavage specimens
- Urinary Histoplasma antigen testing
- Serologic testing
- Blood and bronchoalveolar lavage cultures
Urinary Histoplasma antigen has a sensitivity of 90% for the diagnosis of disseminated histoplasmosis in patients with acquired immunodeficiency syndrome.18 It is less useful for pulmonary forms of histoplasmosis: the sensitivity is 75% and may even be less in milder or chronic forms of pneumonia.19 False-positive reactions may occur in patients with other fungal infections such as coccidioidomycosis, blastomycosis, paracoccidioidomycosis and penicilliosis.20 Urine antigen levels can also be used to monitor therapy, since levels decrease during therapy and increase in 90% of those who have a relapse.21
Our patient’s urinary Histoplasma antigen level was greater than 23.0 ng/mL (positive is > 0.50).
Serologic testing. Immunodiffusion immunoglobulin G (IgG) testing for Histoplasma and Blastomyces was negative, as was an enzyme immunoassay for Coccidioides IgG and IgM. However, antibody tests are less useful in immunosuppressed patients,22 and thus a negative result does not rule out histoplasmosis. A fourfold rise in complement fixation antibody titer is diagnostic of acute histoplasmosis. A single complement fixation titer of 1:32 is suggestive but not diagnostic of histoplasmosis. Cross-reactions may occur with other fungal infections like blastomycosis. The immunodiffusion assay has a greater specificity but slightly less sensitivity than the complement fixation assay.19
Culture of H capsulatum is the definitive test to establish a diagnosis of histoplasmosis. Culture can be performed on samples taken from blood, bone marrow, sputum, and bronchoalveolar lavage fluid, or from lung, liver, or lymph node tissue. Cultures are positive in 74% to 82% of cases of progressive disseminated histoplasmosis.13 However, treatment should not await culture results since the fungus may take several weeks to grow.
Back to our patient
Although Histoplasma serologic studies and cultures were negative, the diagnosis of disseminated histoplasmosis was made on the basis of the patient’s immunosuppressed status, travel history, clinical features, and positivity for urine Histoplasma antigen. Though urine histoplama antigen may be falsely positive in other fungal infections such as coccidioidomycosis, paracoccidioidomycosis, and blastomycosis, clinical features and the absence of central nervous system, joint, and bone involvement suggested disseminated histoplasmosis.
