Pulmonary Histoplasmosis: A Clinical Update.

Histoplasma capsulatum, the etiological agent for histoplasmosis, is a dimorphic fungus that grows as a mold in the environment and as a yeast in human tissues. The areas of highest endemicity lie within the Mississippi and Ohio River Valleys of North America and parts of Central and South America. The most common clinical presentations include pulmonary histoplasmosis, which can resemble community-acquired pneumonia, tuberculosis, sarcoidosis, or malignancy; however, certain patients can develop mediastinal involvement or progression to disseminated disease. Understanding the epidemiology, pathology, clinical presentation, and diagnostic testing performance is pivotal for a successful diagnosis. While most immunocompetent patients with mild acute or subacute pulmonary histoplasmosis should receive therapy, all immunocompromised patients and those with chronic pulmonary disease or progressive disseminated disease should also receive therapy. Liposomal amphotericin B is the agent of choice for severe or disseminated disease, and itraconazole is recommended in milder cases or as "step-down" therapy after initial improvement with amphotericin B. In this review, we discuss the current epidemiology, pathology, diagnosis, clinical presentations, and management of pulmonary histoplasmosis.

CD4+CTLs in Fibrosing Mediastinitis Linked to Histoplasma capsulatum.

Although fibrotic disorders are frequently assumed to be linked to TH2 cells, quantitative tissue interrogation studies have rarely been performed to establish this link and certainly many fibrotic diseases do not fall within the type 2/allergic disease spectrum. We have previously linked two human autoimmune fibrotic diseases, IgG4-related disease and systemic sclerosis, to the clonal expansion and lesional accumulation of CD4+CTLs. In both these diseases TH2 cell accumulation was found to be sparse. Fibrosing mediastinitis linked to Histoplasma capsulatum infection histologically resembles IgG4-related disease in terms of the inflammatory infiltrate and fibrosis, and it provides an example of a fibrotic disease of infectious origin in which the potentially profibrotic T cells may be induced and reactivated by fungal Ags. We show in this study that, in this human disease, CD4+CTLs accumulate in the blood, are clonally expanded, infiltrate into disease lesions, and can be reactivated in vitro by H. capsulatum Ags. TH2 cells are relatively sparse at lesional sites. These studies support a general role for CD4+CTLs in inflammatory fibrosis and suggest that fibrosing mediastinitis is an Ag-driven disease that may provide important mechanistic insights into the pathogenesis of idiopathic fibrotic diseases.

False-negative Histoplasma antigen in acute pulmonary histoplasmosis: the value of urinary concentration by ultrafiltration and heat denaturation of serum proteins in detection of Histoplasma antigen.

We report an infant with localized pulmonary histoplasmosis in whom Histoplasma antibody assays, quantitative Histoplasma urine and serum antigen concentrations, and histopathologic findings of a mediastinal mass were nondiagnostic. A provisional diagnosis of histoplasmosis was established by using laboratory methods that increase the sensitivity of the antigen assay using ultrafiltration of urine and ethylenediaminetetraacetic acid/heat denaturation of serum proteins.

Aspergillus galactomannan antigen in the bronchoalveolar lavage fluid for the diagnosis of invasive aspergillosis in lung transplant recipients.

BACKGROUND: The clinical utility of Platelia Aspergillus enzyme immunoassay (EIA) for galactomannan (GM) antigen detection in bronchoalveolar lavage (BAL) for the diagnosis of invasive aspergillosis (IA) in lung transplant recipients is not known. METHODS: BAL fluid samples from consecutive lung transplant recipients who underwent bronchoscopy were prospectively analyzed for GM. RESULTS: A total of 333 BAL samples from 116 patients were tested. Invasive aspergillosis was documented in 5.2% (6/116) of the patients. Samples analyzed included 9 BALs from two patients with proven IA, 19 BALs from four patients with probable IA, and 305 BALs from 110 patients without IA. At the index cutoff value of > or =0.5, the sensitivity was 60%; specificity was 95%, with positive and negative likelihood ratios of 14 and 0.41, respectively. Increasing the index cutoff value to > or =1.0 yielded a sensitivity of 60%, a specificity of 98%, and the positive and negative likelihood ratios of 28 and 0.40, respectively. Two of six patients with IA receiving antifungal prophylaxis had false-negative results. CONCLUSIONS: A Platelia EIA index cut-off > or =1.0 in the BAL fluid in a lung transplant recipient with a compatible clinical illness may be considered as suggestive of IA.