Disseminated Histoplasmosis Diagnosed on Peripheral Blood Film

A 51-year-old man was hospitalized with fever, cough and respiratory distress requiring intubation. He was initially treated for Haemophilus influenzae pneumonia based on respiratory cultures, but deteriorated, developing multi-organ failure and requiring extracorporeal membrane oxygenation. He had a 20-year history of Crohn's disease in remission on the TNFα inhibitor, infliximab, with no other comorbidities. He had recently started a new job in a waste management facility. Full blood count showed a haemoglobin of 108 g/L, platelet count of 55 × 109/L, total leukocyte count of 3.1 × 109/L, absolute neutrophil count of 2.8 × 109/L and lymphocyte count of 0.1 × 109/L. Baseline creatinine, international normalized ratio, activated partial thromboplastin time and fibrinogen were within normal limits. Liver enzymes were elevated with alanine transferase 91 U/L (reference interval [RI], < 42) and alkaline phosphatase 170 U/L (RI, 40–129). Peripheral blood film showed numerous intracellular inclusions in monocytes and neutrophils (Figure 1A–F, Wright–Giemsa, ×100 objective; 1 G, Wright–Giemsa, ×50 objective), raising suspicion for histoplasmosis and prompting further investigation. Urine histoplasma antigen was positive by enzyme immunoassay above the limit of quantification, above 20 ng/mL, and bronchial washings were culture-positive for Histoplasma capsulatum. Chest x-ray (Figure 1H) and computerized tomography (Figure 1I) of his thorax revealed diffuse patchy airspace opacity in keeping with acute respiratory distress syndrome (ARDS). Despite antifungal treatment with liposomal amphotericin B, the patient's condition deteriorated, with progressive multi-organ failure from disseminated histoplasmosis, ultimately resulting in death. H. capsulatum is a fungus present in soil containing bird or bat droppings and is common to the Ohio and Mississippi River Valleys. Histoplasmosis is clinically heterogeneous from asymptomatic infections to rapid fatal infections [1]. Pulmonary manifestations can include nodules, cavitation lesions, fibrosis and ARDS [1]. Pancytopenia in disseminated histoplasmosis is associated with the co-occurrence of viral, bacterial infections and poor outcomes [2]. Disseminated histoplasmosis may have multi-organ involvement and non-specific radiological findings, commonly leading to misdiagnosis or delayed diagnosis [2]. With climate change, there is an expansion of geographic ranges for various fungal diseases such as histoplasmosis [3]. This, along with the increase in development and utilization of immunomodulatory therapies, has increased the population of patients who are at increased risk of histoplasmosis [4]. This case highlights the importance of the peripheral blood film in the diagnosis of disseminated histoplasmosis, particularly in immunosuppressed individuals with environmental or occupational risk factors and underscores the need for early recognition and treatment of this increasingly encountered infection. J.H. and E.D. collected data and drafted the initial manuscript. B.C.-Y. and C.C.H. reviewed the manuscript and provided feedback. All authors approved the final version of the manuscript. J.H. and E.D. received summer studentship funding from BioTalent Canada. The authors have nothing to report. Informed consent was received from all participants. The authors declare no conflicts of interest The data that support the findings of this study are available from the authors upon reasonable request.

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