Severe Lactic Acidosis in Hemophagocytic Lymphohistiocytosis

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a catastrophic disease with multiple triggers, and often results in poor outcomes. We present a case of severe, persistent lactic acidosis in a rare presentation of HLH secondary to parvovirus B19 infection that improved after steroids and IL-1 inhibitor treatment. Case Description: A 79-year-old man with diabetes mellitus and cirrhosis presented after a fall, 5 days of progressive malaise, fever, nausea, vomiting, melena, and hematemesis and was to be found febrile to 101° F and hypertensive. Workup showed serum creatinine 1.28 mg/dL, lactic acid (LA) 15.9 mmol/L, pancytopenia, and VBG pH of 7.2 with severe metabolic acidosis (HCO3 9 mEq/L). IV fluids and antibiotics were started, and GI ulcer was treated on EGD. His clinical condition deteriorated with persistent lactic acidosis, shock, decreased urine output, worsening transaminitis, elevated LDH, low haptoglobin, and with concern for potential metformin toxicity, hemodialysis was initiated. Lactic acid decreased from 20 to 13 mmol/L but increased to 20 mmol/L after stopping dialysis. A viral blood panel was positive for Parvovirus B 19 IgG. With ongoing fevers, pancytopenia, elevated ferritin at 8378 ng/mL and hypertriglyceridemia, he met 7 of 9 HLH-2004 criteria (H-score 284). Soluble IL-2Ra/CD25 was elevated at 4778.9 pg/mL. Bone marrow biopsy showed hypercellularity 70% with hemophagocytic lymph histiocytosis. Treatment with dexamethasone and anakinra improved the pancytopenia, liver enzymes, and lactic acidosis. Due to refractory septic shock, he was ultimately transitioned to comfort care. Discussion: HLH is a rare, aggressive syndrome with dysregulated cytokine release, histiocyte activation, and multiorgan failure. Studies have reported an increased activity of lactate dehydrogenase A and inhibition of pyruvate dehydrogenase due to inflammatory cytokines increasing the production of lactate. The Warburg effect, where cells may preferentially use the lactic fermentation pathway even in the presence of oxygen and without significant mitochondrial dysfunction may also play a role. Lactic acidosis in patients with HLH is underrecognized, but if identified may prompt earlier treatment and improved outcomes.