Disease name and synonyms

Histoplasmosis – Progressive disseminated (PDH)

Fungi responsible (links to these)

Histoplasma capsulatum

Disease description

Spectrum varies from an acute to a subacute course. Acute PDH maybe a rapidly fatal course with diffuse interstitial or reticulonodular lung infiltrates in association with respiratory failure, shock, coagulopathy and multiorgan failure. Subacute PDH usually presents with weight loss, fever and hepatomegaly in association with focal abnormalities such as lymphadenopathy, meningitis, oral or gastrointestinal ulceration, and adrenal insufficiency.

Frequency and global burden

The global number of disseminated histoplasmosis cases in AIDS worldwide has been estimated to be 100,000 annually.

Underlying problems and at risk patients

AIDS, extremes of age, immunosuppression

Diagnostic testing

The best test is a histoplasma antigen test in urine, which is positive in over 90% of cases. A Wright’s stain on a blood film or bone marrow aspiration may demonstrate intracellular yeasts. Skin, mucosal or lymph node biopsy will also have characteristic intracellular yeasts visible with fungal stains. These yeast forms can be mistaken for Penicillium marneffei, which can produce a similar illness. Culture is usually positive (50-75%) but is slow and can take 10-20 days, occasionally longer. The laboratory should be warned of the possibility of Histoplasma as it is a class 3 pathogen.

Treatments

Intravenous liposomal amphotericin B (Ambisome) 3mg/Kg is the treatment of choice for PDH, for 2 weeks, followed by itraconazole 200-400mg daily, assuming no drug interaction with rifampicin. For subacute cases, only itraconazole is necessary, unless meningitis. Therapeutic drug monitoring is recommended. Early therapy with anti-retroviral therapy in new AIDS cases is helpful and recommended.

IDSA Clinical Practice Guidelines 2007

Outlook and prognosis

Some patients are extremely ill when they first present. Overall mortality of PDH is85-100% without treatment and reduced to <25% with treatment. Around 80,000 deaths annually are predicted when using the most conservative estimates available.