C53-45 A Silent Collapse: Agranulocytosis and Fatal Septic Shock Likey Due to Levamisole

Agranulocytosis is a rare but devastating hematologic emergency often triggered by drugs or toxins, and its presentation in critically ill patients can be obscured by sepsis or substance use.We present a 38-year-old male with a history of nasal heroin use, who developed a sore throat, odynophagia, and low-grade fevers over several days. He delayed care until profound weakness and a “wet” cough prompted presentation to the ER, where imaging revealed near-complete whiteout of his left lung. He was intubated for respiratory failure and transferred to the ICU. On arrival, patient was ill-appearing with mottled skin, tachycardia, rhonchi over the left lung, and cold extremities. He required multiple vasopressors for septic shock, CRRT for renal failure, and bicarb infusion for lactic acidosis (lactate 18, pH 6.95). Labs showed pancytopenia, profound agranulocytosis (WBC 0.67, absolute neutrophils ≈0), extreme transaminitis (AST 16,250, ALT 3,826), hyperkalemia, hypoalbuminemia, and a high anion gap metabolic acidosis. CT confirmed dense left-lung consolidation typical of multifocal pneumonia likely aspiration-related and dilated small-bowel loops concerning for ileus. A UDS was positive for opiates and amphetamines; no other neutropenia-inducing exposures were identified. Given emerging reports linking agranulocytosis in illicit drug users to levamisole, a common adulterant in street heroin and cocaine, and the absence of other causative medications or exposures, G-CSF was initiated. Despite broad-spectrum antibiotics, stress-dose corticosteroids, and max ventilator support, his neutrophil count remained near zero and infection progressed unchecked. He suffered a cardiac arrest; after brief ROSC, family established DNR status, and he succumbed to multi-organ failure. Confirmatory toxicologic analysis for specific adulterants was not possible due to his rapid decline.This case underscores the lethality of drug-associated agranulocytosis which can present as refractory sepsis and the challenge it poses when innate immunity collapses. Clinicians must maintain a high index of suspicion for profound neutropenia in patients with substance use, recognize the potential role of untraceable adulterants, and initiate aggressive supportive care early.