Case Presentation: A 56-year-old woman presented with dyspnea; cyanosis and paresthesia of her lips, fingers, and hands; and headache. She had known cavitary pulmonary lesions, discovered incidentally on a CT scan obtained for assessment of nephrolithiasis. Extensive evaluation had yielded no evidence of infection or malignancy. An autoimmune etiology was suspected, and prednisone had been started two weeks prior to presentation. Dapsone had also been started, for Pneumocystis jiroveci pneumonia (PJP) prophylaxis. Bactrim had not been started for PJP prophylaxis due to allergy. Vital signs were normal except for oxygen saturation of 86% on room air. Cardiopulmonary exam was unremarkable. She had mild cyanosis of her lips, fingers, and hands. She had stable, mild anemia. Basic chemistries were normal. Troponin and BNP were not elevated. Respiratory pathogen testing was negative.Chest CTA showed no evidence of pulmonary embolism or aortic aneurysm/dissection. Cavitary lesions of the right lung were slightly smaller compared with one month prior. There was no pneumonia, pleural effusion, pneumothorax, cardiomegaly, or pericardial effusion.Additional laboratory testing showed elevated methemoglobin percentage of 9.8% (normal 0-3%). Methylene blue 90 mg IV was given for treatment of suspected dapsone-induced methemoglobinemia and associated symptomatic hypoxia. The patient’s hypoxia and presenting symptoms rapidly resolved, and repeat methemoglobin percentage decreased to the normal range. Atovaquone was substituted for dapsone for continued PJP prophylaxis.
Discussion: Methemoglobin is an altered state of hemoglobin in which the heme iron is oxidized to the ferric state. The ferric hemes of methemoglobin do not bind oxygen, causing functional anemia and associated tissue hypoxia.Most cases of methemoglobinemia are acquired, resulting from increased methemoglobin formation induced by various substances. The most commonly implicated medications include dapsone, other antimalarial agents, and topical anesthetics.Symptoms of methemoglobinemia are those of tissue hypoxia, including cyanosis, dyspnea, headache, lightheadedness, fatigue, irritability, and lethargy. The severity of symptoms correlates with the methemoglobin level, and may be exacerbated by underlying anemia, heart disease, or lung disease. The classic presentation includes cyanosis in the setting of a normal arterial oxygen partial pressure, and symptoms that do not improve with administration of oxygen alone.In addition to supportive care and discontinuation of the suspected offending medication, management is with methylene blue, which is rapidly effective. However, methylene blue can precipitate severe hemolysis in individuals with G6PD deficiency, and it can cause serotonin syndrome in individuals taking a serotonergic medication, such as a selective serotonin reuptake inhibitor. IV ascorbic acid is an alternate treatment. However, in contrast to methylene blue, ascorbic acid often requires multiple doses and may take 24 hours or more to lower methemoglobin levels.
Conclusions: Diagnostic assessment of dyspnea with hypoxia, and management of the frequently causative acute and chronic cardiopulmonary illnesses, are core skills for the hospitalist. This case highlights methemoglobinemia — an unusual, acquired, reversible blood dyscrasia which results in hypoxia not of primary cardiopulmonary etiology.