Disseminated Histoplasmosis in Immunocompetent Individuals- not a so Rare Entity, in India

Abstract

Introduction: Histoplasmosis is a rare fungal disease caused by dimorphic fungi Histoplasma capsulatum. The causative fungus persists in soil, infects through inhalation and manifests in three main types-acute primary, chronic cavitary and progressive disseminated histoplasmosis. Disseminated Histoplasmosis (DH) is defined as a clinical condition where the fungus is present in more than one location. Among the forms of histoplasmosis, DH is the rarest and mostly found in an immuno-compromised individual. Here we are presenting our experiences of the series of cases of DH in immuno-competent individuals who have been diagnosed in our institute in last 5 years.

Materials and methods: This is a single centre retrospective observational study, conducted in Institute of Haematology and Transfusion Medicine, which is a referral centre for Eastern India, from May 2009 to April 2014. Only cases with DH in otherwise healthy immuno-competent individuals were included in the study. The histoplasmosis was confirmed either by presence of Histoplasma in biopsy specimen from an extrapulmonary organ or by positive growth in fungal culture.

Result: Total seven patients met the inclusion criteria. Five out of 7 patients were male. The mean age was 35 years. Five of the 7 patients presented with fever for a long duration. Six patients complained of significant weight loss before diagnosis. On examination, one patient had skin nodules, five patients had hepato-splenomegaly, and two patients had lymphadenopathy. The laboratory investigations revealed anaemia in six out of 7 patients, and pancytopenia in 3 patients. Two patients had features of the hemophagocytic syndrome in the bone marrow. All patients were treated with conventional amphotericin B deoxycholate and azole antifungal. One patient with adrenal involvement died in hospital. The patient with skin nodule had recurrent relapses. The other patients had resolution of symptoms and were clinically cured.

Conclusion: DH is not an uncommon aetiology of fever of prolonged duration even in immuno-competent individual and should be kept as a differential diagnosis. Targeted investigation through early bone marrow biopsy and fungal culture may help in the diagnosis of DH. Imaging study to exclude adrenal involvement prevents case fatality. Cytopenia may be due to a secondary hemophagocytic syndrome, which improves with anti-fungal therapy. Treatment with either amphotericin B or itraconazole gives excellent outcome though therapy may have to be given for a prolonged period in case of relapses.

Figure 1

Intracellular histoplasma seen within macrophage, bone marrow aspiration smear, Romanowsky stain and PAS stain. oil immersion view, 100x.

Figure 2

Treatment Regimens Used.

Figure 3

Treatment Outcome