Histoplasmosis, heart failure, hemolysis and haemophagocytic lymphohistiocytosis

Histoplasmosis is an endemic mycosis with global distribution, primarily reported in immunocompromised individuals. A 29-year old immunocompetent male presented with fever, hepatosplenomegaly and pancytopenia. His peripheral blood showed features suggestive of intravascular hemolysis and echocardiography showed features suggestive of pulmonary arterial hypertension. Bone marrow showed yeast with morphology suggestive of Histoplasma capsulatum. Further investigations revealed hyperferritinemia, hypofibrinogenemia and increased triglycerides. With a diagnosis of progressive disseminated histoplasmosis with secondary Haemophagocytic lymphohistiocytosis, he was successfully treated with amphotericin B followed by itraconazole. We report this case to highlight the atypical and rare manifestations of histoplasmosis.


Introduction
Histoplasmosis is an endemic mycosis caused by the dimorphic fungi, Histoplasma capsulatum. The mode of infection is by inhalation of microconidia that are usually found in bird or bat guano containing soil. In immunocompetent individuals, such acute infection resolves on its own while the disease may be limited to lungs or disseminate to liver, spleen and bone marrow in immunocompromised [1]. Definite diagnosis of histoplasmosis is made by demonstrating fungi on microscopy or cultures. Cultures may take up to six weeks to become positive and can lead to a significant delay in diagnosis. The treatment of choice is amphotericin B followed by oral itraconazole or itraconazole alone depending upon severity and extent of disease [2].
We report a case of histoplasmosis in a young immunocompetent male with atypical presentations.

Discussion
Histoplasmosis has widespread distribution in the western world but it is also endemic in many parts of South-East Asia. It has been reported in India since the 1950s with variable histoplasmin sensitivity rates (0-12.3%) [3,4]. Its spread and increasing incidence has largely been  [4]. Three large studies from Delhi and South India reported 80 cases of disseminated histoplasmosis in ten years. Most of the cases were reported from the Gangetic delta [5]. Histoplasmosis can also get complicated with secondary Haemophagocytic lymphohistiocytosis (HLH) as a result of a cytokine storm due to an overwhelming activation of lymphocytes and macrophages. This condition may be rapidly fatal if the cause is not discovered and treated adequately. In a review by Sonavane et al., thirty-eight cases of Histoplasmosis associated HLH have been reported worldwide, of which eight cases were from India. Most cases have been reported in the immunocompromised hosts [6]. Anemia in histoplasmosis is common and is mostly because of the bone marrow involvement and/or rarely due to secondary HLH. However, the case described above also had a component of coomb's positive hemolytic anemia. To the best of our knowledge, only two such cases have been reported but the pathophysiology of such an occurrence is still not Another important clinical feature that our patient had was pulmonary arterial hypertension. The patient had acute worsening in shortness of breath and the ECG showed S1Q3T3 pattern. CT pulmonary angiogram showed no abnormality. We could not explain pulmonary hypertension in our patient as he was asymptomatic prior to this presentation and we could not find any reports that linked histoplasmosis with pulmonary hypertension. However, an interesting finding was noted in our patient. With successful treatment, there was a significant reduction in pulmonary artery systolic pressure (53mm of Hg to 41mm of Hg) on follow up echocardiography. The diagnosis in our patient was confirmed by spotting the typical morphology of histoplasmosis on giemsa staining of bone marrow aspirate. The sensitivity of direct demonstration and culture in progressive disseminated histoplasmosis is 76% and 74% respectively [1]. For disseminated histoplasmosis, amphotericin B is given for 7-14 days followed by oral itraconazole for up to a year. Our patient stopped his treatment after four months of initiation. Considering, he was asymptomatic even after eight months of discontinuation and wasn't willing to start treatment again, we decided to follow him up closely.
Management of secondary HLH requires treatment of the primary disease; however, the chemoimmunotherapy for HLH including steroids, etoposide and cyclosporine may be required in certain cases [9].

Conclusion
Histoplasmosis is increasingly being reported from the Indian subcontinent, especially in individuals without any risk factors for the disease. We report this case to highlight the atypical and rare manifestations that can be associated with this disease.

Competing interests
The authors declare no competing interests.