Case Presentation: A 58-year-old man with a history of Lyme disease was diagnosed with babesiosis two weeks earlier, confirmed by positive Babesia Polymerase Chain Reaction (PCR), and treated with a 10-day course of azithromycin and atovaquone. He returned with fatigue and exertional dyspnea, and labs indicated worsening pancytopenia. Suspecting hemolysis and bone marrow suppression from Babesia, he was restarted on Azithromycin and Atovaquone. While repeated Babesia PCR remained positive, multiple peripheral smears showed no parasites. After a blood transfusion, his symptoms improved. Laboratory tests showed low bicarbonate (16 mmol/L) and markedly elevated lactic acid (11 mmol/L), with normal PH on blood gases. He was hemodynamically stable, asymptomatic, with no hypoperfusion, hypoxemia, signs of sepsis or end-organ damage. Despite fluid resuscitation, lactic acid remained significantly elevated (9.1–12 mmol/L). Further investigations, including methemoglobinemia, Creatine Kinase, Erythrocyte Sedimentation Rate, C-Reactive Protein, Folate, Vitamin B12, Copper, and pan-CT scans, were unremarkable, and D-lactate level was normal.Persistent pancytopenia and hyperlactatemia prompted a bone marrow biopsy, revealing B-cell Acute Lymphoblastic Leukemia (ALL) with 75% blasts. Next-generation sequencing (NGS) identified an IDH1 mutation. The patient was started on Hyper-CVAD chemotherapy regimen (cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride (Adriamycin), dexamethasone (Cycle A) & Methotrexate, Cytarabine (Cycle B)), leading to resolution of metabolic acidosis within 36 hours. Due to the immunosuppressive therapy, a 6-week course of Azithromycin and Atovaquone was given to eradicate babesiosis, and follow-up Babesia PCR was negative. He is doing well continuing outpatient chemotherapy, with ongoing evaluation for an allogeneic transplant.
Discussion: Lactic acidosis results from increased lactate production, reduced metabolism, or both. Type A lactic acidosis is linked to tissue hypoperfusion, while Type D arises from excess D-lactate due to bacterial overgrowth. Type B, however, occurs without hypoperfusion and, in the context of malignancy, represents a rare but critical oncologic emergency known as the Warburg effect (WE)(1).
Conclusions: We present a case involving the Warburg effect (WE), a rare cause of type B lactic acidosis characterized by “aerobic glycolysis.” Typically, cells rely on mitochondrial oxidative phosphorylation for energy in aerobic conditions. However, in WE, malignant cells prefer lactic fermentation over oxidative phosphorylation, even when oxygen is abundant. This metabolic shift, common in cancer cells, supports rapid cell proliferation and tumor growth by generating glycolysis intermediates essential for cell division(1). Targeting the Warburg effect is an emerging cancer treatment strategy(1). The Warburg effect, commonly observed in lymphoma and occasionally in acute leukemia, chronic lymphocytic leukemia, chronic myelomonocytic leukemia, multiple myeloma (2, 3, 4, 5), and some solid tumors (6), emphasizes the importance of recognizing type B lactic acidosis as an oncologic emergency. Early diagnosis and targeted treatment for both lactic acidosis and the underlying malignancy are crucial, as the prognosis is often poor. This case highlights the need to consider malignancy as a potential cause of lactic acidosis in patients without clear signs of sepsis, hypoperfusion, or hypoxemia.