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Histoplasmosis is an infectious disease caused by a thermal dimorphic fungus Histoplasma capsulatum. In immunocompetent individuals with low level of exposure, the infection is self-limited whereas high level of exposure presents as flu-like illness, fever, chills, headache, myalgia, anorexia, cough and dyspnea. Progressive, disseminated form of the disease is seen in immunocompromised individuals. However, a few cases of disseminated disease have also been reported in immunocompetent hosts, usually 1 case in 2000 adults.

We report the case of chronic progressive disseminated histoplasmosis in an immunocompetent individual from a nonendemic region of Mumbai, India, probably as a result of prolonged exposure and delayed presentation. In our patient, the first diagnosis was suggested by a peripheral blood smear, which is not a classical biological diagnostic method for fungal infection.

A sixty-year-old housewife presented with history of intermittent fever, nonproductive cough, pallor, weight loss, malaise and fatigue. On examination her oral temperature was 100°F, blood pressure was 140 / 80 mm of Hg, pulse rate was 106/ min. pallor was present. She had received packed cell transfusions in the past.

Routine laboratory tests showed pancytopenia. (WBC count: 3.28x10^9 / L, Hb: 9.6 gm / dl, platelet count was 75 x 10^9 / L). There was absolute lymphopenia with shift to left in granulocytes.                       ( Metamyelocytes 1%,  Myelocytes 1 % Neutrophils 73 %, Eosinophils 6% , Lymphocytes 14 % and Monocytes 5 % ). Absolute lymphocyte count was 197 cells / cumm. (Normal range: 1500-4000 cells / cumm).

Peripheral smear ( Figure B, C and D)  showed occasional neutrophils and monocytes ( <1%) with multiple phagocytic vacuoles filled with oval shaped yeast like organisms, retracted from poorly stained cell wall with eccentric chromatin, suggestive of Histoplasma capsulatum. Patient was advised bone marrow examination, sputum routine examination and CD4 / CD8 counts and fugal culture. Tests for human immunodeficiency virus (HIV), HbsAg and HCV were negative.

Sputum examination, (Figure F)  revealed oval, narrow-based budding yeast cells suggestive of Histoplasma capsulatum. PAS stain revealed these yeast-like cells as bright eosinophilic structures. . Ziehl - Neelsen stain done on sputum smear showed no acid fast bacilli.

Bone marrow aspirate stained with Leishman stain (Figure A and E ) was cellular but showed suppressed erythropoiesis and megakaryopoiesis. Large number of histiocytes, some foamy, filled with tiny intracytoplasmic yeasts were seen. These were oval, 2–3 µ in size with a slightly eccentric nucleus and a clear zone around the nucleus, morphologically suggestive of H. capsulatum. Isolation of organism from peripheral blood by culture was not successful. Here, the following conditions were ruled out – HIV, malignancy, immunosuppressive or immuno-modulating therapy or any other contributory immunosuppressive conditions like tuberculosis, chronic renal and hepatic failure not due to histoplasmosis.

In this case, the diagnosis of disseminated histoplasmosis was made first on peripheral blood smear before culture reports were available, highlighting the importance of peripheral blood smear for early diagnosis of disseminated histoplasmosis in highly suspicious case even in patients who are known to be immunocompetent.