In the latest Case Record of the Massachusetts General Hospital, a 29-year-old man was seen in an outpatient clinic because of abdominal pain, fever, and weight loss. Testing for HIV antibodies was positive, and the CD4 T-lymphocyte count was 10 per cubic millimeter. Chest imaging revealed tiny nodules in both lungs.
This case illustrates the importance of offering routine HIV testing to all persons presenting for medical care, even those who do not appear to be at high risk for infection.
• What is the differential diagnosis of diffuse reticulonodular infiltrates on chest radiography in patients with AIDS?
Diffuse reticulonodular infiltrates in patients with AIDS can be due to several pathogens. Patients with Pneumocystis jirovecii pneumonia typically present with diffuse interstitial infiltrates, but they can also present with reticulonodular disease. Kaposi’s sarcoma can cause a reticulonodular pattern but is more commonly associated with bulky nodular disease. Pulmonary disease is nearly always preceded by cutaneous or oral mucosal involvement. Viral pathogens (e.g. cytomegalovirus), cancers (including lymphoma), and lymphoproliferative disorders do not cause reticulonodular disease.Fungal infection with cryptococcosis, coccidioidomycosis, penicilliosis, or histoplasmosis may cause disseminated disease in patients with AIDS and can manifest with a reticulonodular infiltrate.
• What are the clinical manifestations of disseminated histoplasmosis in patients with AIDS?
Disseminated histoplasmosis occurs in up to 30% of patients with AIDS in areas where histoplasma is endemic, and disseminated histoplasmosis is the AIDS-defining illness in up to 50% of patients with AIDS. It causes a latent infection that can reactivate years after the patient has left the endemic area, especially when CD4 T-lymphocyte counts fall below 100 per cubic millimeter. Patients typically present with indolent fever and weight loss, and diarrhea is common. Lymphadenopathy or hepatosplenomegaly may be present on examination, as well as mucosal involvement, with ulcerations in the oropharynx or anal area. Skin lesions similar to those seen in persons infected with other dimorphic fungi can be present. Results of chest radiographs are abnormal in up to 70% of patients with disseminated disease and may show interstitial or reticulonodular infiltrates, even in patients who have no pulmonary symptoms. Up to 12% of patients with AIDS and disseminated histoplasmosis have gastrointestinal involvement, most commonly in the colon or cecum.
Morning Report Questions
Q: What are the limitations of the antigen-detection test in the diagnosis of histoplasmosis?
A: The antigen-detection test is important in the diagnosis of histoplasmosis, but it has limitations. Cross-reactivity occurs in patients infected with other fungal pathogens, especially other agents of endemic mycoses (e.g., Blastomyces dermatitidis, Paracoccidioides brasiliensis, Penicillium marneffei, and Coccidioides immitis); therefore, positive results must be considered in the context of a patient’s epidemiologic history. In turn, negative results do not rule out the diagnosis of histoplasmosis; the sensitivity of the assay varies with the clinical syndrome, disease severity, tempo of disease progression, and immune status.
Q: What are the biological characteristics of Histoplasmosis capsulatum?
A: H. capsulatum is a dimorphic fungus that grows as a mold in the environment and as a yeast at body temperature. In the environment, mold spores are dispersed by activities that disrupt the soil, and the spores can then be inhaled by humans. After the fungus has been inhaled and has reached lung temperature, it converts into a small, round or oval budding yeast. Historically, this process of thermal dimorphism was exploited in the laboratory as a way to verify the identity of the isolate as H. capsulatum.