Hemophagocytic Lymphohistiocytosis Complicating Melioidosis.

A 50-year-old Caucasian female living in remote northern Australia presented to hospital with a 2-day history of lower limb pain, back pain, and confusion. Her past medical history was notable for hazardous alcohol use and an aortic valve replacement 3 months previously. On arrival to hospital, her respiratory rate was 40 breaths per minute, heart rate was 114 beats per minute, and blood pressure was 137/67 mm of Hg. Her hemoglobin was 133 g/L, her leukocyte count was 7.0 × 109/L, and her platelets were 211 × 109/L. A chest X-ray revealed right upper lobe consolidation and she received empirical intravenous meropenem and azithromycin. She rapidly deteriorated and required intubation for respiratory failure. Blood cultures collected on admission subsequently grew Burkholderia pseudomallei, confirming a diagnosis of melioidosis. She had a tumultuous course in the intensive care unit; on day one, she required vasopressor support to maintain adequate tissue perfusion, and on day 3, she developed thrombocytopenia (platelets 72 × 109/L) and anemia (hemoglobin 113 g/L). A repeat chest X-ray and computerized tomography scan of the lungs revealed extensive consolidation and a loculated right-sided pleural effusion which required thoracentesis (Figure 1). Despite continued meropenem, she failed to improve, and by day 21, she had developed marked pancytopenia (hemoglobin 68 g/L, leukocytes 1.2 × 109/L, and platelets 14 × 109/L). Her neutropenia did not improve despite granulocyte colony-stimulating factor and a bone marrow aspirate revealed hemophagocytosis (Figure 1). She was persistently febrile, her serum ferritin was 1,220 μg/L, and fibrinogen was 0.9 g/L, consistent with a diagnosis of hemophagocytic lymphohistiocytosis (HLH). She continued to deteriorate despite ongoing antibiotic therapy and died on day 41 of her admission.

Figure 1.

(A) Anteroposterior chest X-ray showing extensive consolidation (arrow). (B) Coronal computerized tomography images confirming extensive pneumonia and revealing a large right-sided pleural effusion (arrow). (C) A histiocyte with arrow pointing to mature erythrocyte phagocytosed within the cytoplasm. At least six mature erythrocytes are seen within this cell. This figure appears in color at www.ajtmh.org.

Secondary HLH can occur in association with a number of conditions, including infections, malignancy, immunodeficiency, and rheumatological diseases. The diagnosis can be established by molecular testing or by fulfillment of specified clinical and laboratory criteria.[1] Hemophagocytic lymphohistiocytosis is associated with a poor prognosis, with mortality rates greater than 40%.[2] Viruses are more likely to trigger HLH than bacteria; however, a number of bacterial infections have been implicated[2]; melioidosis should be added to the list. Melioidosis, a disease endemic in northern Australia,[3] is commonly associated with cytopenias,[4,5] particularly in the setting of trimethoprim/sulfamethoxazole therapy. However, if cytopenias are severe or persistent, an alternative pathology should be considered.