Abstract Introduction Phenazopyridine is an over-the-counter urinary analgesic used to relieve discomfort associated with urinary tract irritation. Although generally safe, it has been linked to rare cases of methemoglobinemia and, even less frequently, sulfhemoglobinemia. We report a case in which both conditions occurred concurrently in a patient with an underlying enzymatic deficiency, creating diagnostic and therapeutic challenges. Case Presentation A 71-year-old man with a history of lung transplantation, basal cell carcinoma, and squamous cell carcinoma presented to the emergency department with fatigue, shortness of breath, and frequent falls over one week. On arrival, his SpO2 was 69 percent on room air. He appeared cyanotic but had no respiratory distress. High-flow nasal cannula therapy was initiated at 60 liters per minute with 100 percent inspired oxygen, improving spO2 only to 82 percent. Co-oximetry demonstrated methemoglobin levels exceeding 30 percent. He was treated with two doses of methylene blue (1.5 milligrams per kilogram followed by 1 milligram per kilogram), which normalized his methemoglobin level. Genetic evaluation demonstrated cytochrome b5 reductase deficiency, an inherited condition which can explain the delayed improvement of methemoglobinemia in this case. The etiology of the acute methemoglobinemia was attributed to phenazopyridine use, which he had been taking, without prescription, for urinary tract discomfort. Despite treatment, his SpO2 persisted below 90 percent, though he remained hemodynamically stable and asymptomatic. Additional testing revealed elevated sulfhemoglobin levels, confirming concurrent sulfhemoglobinemia, a rare but recognized adverse effect of phenazopyridine. His oxygenation gradually normalized with supportive care, and he was discharged in stable condition. Discussion This case highlights the importance of recognizing multiple hemoglobin abnormalities in patients with unexplained hypoxemia or discordant oxygen saturation measurements. When measured oxygen saturation fails to respond promptly to methylene blue, clinicians should consider concomitant causes such as sulfhemoglobinemia or enzymatic deficiencies. Awareness of these possibilities is crucial when evaluating patients exposed to oxidant medications, including phenazopyridine. Early recognition and appropriate management can prevent unnecessary interventions and reduce morbidity. This abstract is funded by: None
Nangia et al. (Fri,) studied this question.