Imported African histoplasmosis by Histoplasma capsulatum var. duboisii in an HIV-2 infected patient

Objectives: African histoplasmosis caused by the fungus Histoplasma capsulatum var. duboisii, is a rare endemic mycosis occuring in western and central regions of sub-Saharian Africa. For unknown reasons, although HIV infection and H. capsulatum var. duboisii coexist in Africa, this coinfection remains rare. In Europe, diagnosed cases of African histoplasmosis are all imported. We describe a case of African histoplasmosis on a Portuguese war veteran co-infected with HIV-2 who fought in Guiné-Bissau in 1963-65 and Angola in 1972. Methods: We report a case of a 76-year-old man, diagnosed with HIV-2 infection in the previous year (under combined antiretroviral therapy) presenting an ulcerated skin lesion on the right tight (image 1), just above the knee. He was diagnosed pulmonary tuberculosis the year before and was finishing one year treatment. The solitary skin lesion begun as a small non-pruriginous eritematous papule, evolving in 6 month to a painless 3-4cm ulcer with raised borders surrounded by a hiperpigmented halo. There were no adenopathies or bone lesions. Respiratory samples and blood cultures were systematically negative for Histoplasma capsulatum. He was treated with IV liposomal Amphotericin-B for one month, followed by oral itraconazol (now on the first month), with a favourable clinical outcome. Results: Histopathology of skin biopsy revealed a superficial ulceration with underlying granulomatous infiltrate with many giant cells, where numerous round mononucleated yeasts measuring 7-8µm were evident and highlighted with PAS and Grocott stain (image 2, left side). Skin biopsy was observed on a wet mount with KOH and revealed numerous round yeasts that were also seen on Gram stain, measuring 7-8µm. Culture of skin biopsy on two Sabouraud dextrose agar (with and without cicloheximide) showed growth of a filamentous fungus compatible with Histoplasma capsulatum (image 2, right side), with large thick-walled spherical macroconidia with finger-like projections (tuberculate conidia) that arise from short conidiophores, and small oval microconidia arising on short stalks from undifferentiated hyphae. Reversion to the yeast fase has not been succeed yet. Identification was further confirmed by sequencing of genomic DNA fragments using the universal fungal primers ITS1 and ITS4. The sequences obtained were compared with sequences deposited in the GenBank and the result was: Histoplasma capsulatum var. duboisii (99% homology). Conclusion: With banalization of business or leisure trips, endemic mycosis are becoming frequently diagnosed in countries outside their natural geographic endemic areas and only a high index of suspicion makes the diagnosis possible. Apart from trips, nowadays in Portugal 4% of the resident population is immigrant, mostly from Brasil (25.5%) but also from Angola and Guiné-Bissau (9.2%), being the former an endemic country of American histoplasmosis and the later of both American and African histoplasmosis. We consider histoplasmosis a probable underdiagnosed disease that should be suspected mainly in immunodeficient HIV positive individuals with a past history of travel or residence in an endemic area