Khattar, G

Abstract Background Sulfhemoglobinemia is a rare but potentially life-threatening dyshemoglobinemia resulting from the irreversible incorporation of sulfur into the heme moiety, producing hemoglobin species incapable of oxygen transport. Its clinical presentation often mimics methemoglobinemia, with cyanosis and oxygen saturation (SpO2) readings discordant from arterial partial pressure of oxygen (PaO2). Phenazopyridine, an over-the-counter urinary analgesic, has been implicated as a rare cause, in 3 previously documented cases. Prompt recognition is essential to avoid inappropriate therapy, particularly methylene blue, which can precipitate hemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Case Presentation A 71-year-old man with Parkinson’s disease, Crohn’s disease, and chronic anemia presented with unexplained cyanosis and SpO2 readings in the 70-80% range, despite a normal PaO2 of 180 mmHg and absence of respiratory symptoms. He had self-initiated phenazopyridine for dysuria three days prior. CT angiography of the chest and echocardiography with bubble study were unremarkable. Attempts to quantify methemoglobin and carboxyhemoglobin were unsuccessful due to analyzer errors. Laboratory evaluation revealed acute anemia (hemoglobin 5.7 g/dL), indirect hyperbilirubinemia, and low haptoglobin consistent with hemolysis. He was managed supportively with high-flow oxygen, and transfusion of two packed red blood cell units. Although initial G6PD levels were normal, testing during hemolysis can yield false negatives. Given this and the risk of methylene blue-induced oxidative stress, conservative management with ascorbic acid was chosen. The patient’s SpO2 improved gradually, and he was discharged on hospital day three. Send-out tests later confirmed sulfhemoglobinemia (1.1%), elevated cytochrome b5 reductase activity, and normal methemoglobin. Discussion This case underscores the diagnostic and therapeutic challenge of differentiating sulfhemoglobinemia from methemoglobinemia. Both disorders produce functional hypoxia with SpO2-PaO2 dissociation, but sulfhemoglobin cannot revert to hemoglobin and requires erythrocyte turnover for resolution. While methylene blue is the standard therapy for methemoglobinemia, it is ineffective for sulfhemoglobinemia and contraindicated in G6PD deficiency. In our patient, supportive care and transfusion facilitated recovery. Using the Naranjo Adverse Drug Reaction Probability Scale, the causality score was 7, indicating a highly probable relationship between phenazopyridine exposure and sulfhemoglobinemia. A high index of suspicion for G6PD deficiency as well as dyshemoglobinemia with a multidisciplinary collaboration are essential for diagnosis and management of unexplained cyanosis. This abstract is funded by: None

Abstract Introduction Drug-induced pneumonitis is an important mimic of disseminated infection in immunocompromised hosts. Lenalidomide, an immunomodulatory agent widely used in multiple myeloma, has been associated with organizing and eosinophilic pneumonitis, and occasionally sarcoid-like granulomatous inflammation. The coexistence of acute fibrinous injury and granulomatous inflammation is exceptionally rare. We present a case of lenalidomide-associated acute fibrinous and granulomatous pneumonitis presenting with a miliary pattern following autologous stem cell transplant. Case Presentation A 44-year-old woman with kappa light-chain multiple myeloma, chronic kidney disease stage V, presented with 10 days of fever (to 105 °F), dry cough, hemoptysis, dyspnea and hypoxia requiring high flow oxygen. She had been on maintenance therapy with lenalidomide, daratumumab, and weekly dexamethasone after undergoing an autologous stem cell transplant for multiple myeloma, last administered one week before symptom onset.. CT chest (Figure 1-1) showed innumerable randomly distributed micronodules with ground-glass opacities and septal thickening, suggesting disseminated infection. Laboratory results revealed eosinophilia (950/µL), neutropenia, and profound hypogammaglobulinemia. Empiric piperacillin-tazobactam, doxycycline, and fluconazole were started for possible bacterial and/or fungal infection (history of positive Coccidioides IgM). Two bronchoscopies demonstrated multifocal hypervascular airway lesions. BAL differential showed 15 % eosinophils and > 30 % lymphocytes; cultures, Fungitell, and comprehensive testing for bacterial, fungal, mycobacterial, viral, and parasitic pathogens were negative. Cryobiopsy revealed acute fibrinous and granulomatous pneumonitis with negative GMS and acid-fast stains. Following withdrawal of lenalidomide and daratumumab, the patient’s symptoms and CT findings improved without further antimicrobial therapy within the same hospitalization (Figure 1-2). She received an 8-week prednisone taper with inhaled pentamidine prophylaxis. Follow-up CT showed complete clinical and radiographic resolution (Figure 1-3), confirming a grade 3 drug-induced pneumonitis. A bronchoscopy will be repeated to assess the endobronchial vascular lesions. Discussion Lenalidomide related lung injury typically manifests as organizing or eosinophilic pneumonitis. The presence of both fibrinous and granulomatous inflammation suggests a mixed hypersensitivity and immune-complex reaction possibly potentiated by immune reconstitution after autologous transplant. The miliary pattern and BAL eosinophilia closely mimic disseminated fungal or mycobacterial infection. A Naranjo Adverse Drug Reaction Probability Scale score of 7 supported a highly probable causal relationship. Awareness of this pattern is essential, as prompt drug cessation and corticosteroid therapy are curative and prevent progression to fibrotic lung injury. This abstract is funded by: None