Case Presentation: A 15-year-old female with a past medical history of acne vulgaris on topical Dapsone and anxiety on Sertraline presented to the ER with severe shortness of breath. She was recently hospitalized for a left knee meniscal repair one month prior. She went to a theme park on the day of admission where she developed palpitations, shortness of breath, and a blue tinge to her fingertips and lips.Physical exam was significant for tachycardia and an oxygen saturation of 86%. The patient appeared anxious with fine motor tremors and diaphoresis. She had perioral and peripheral cyanosis. Her cardiac exam revealed regular rhythm without murmur as well as 2+ distal peripheral pulses with brisk capillary refill. Pulmonary exam was significant for tachypnea with subcostal and supraclavicular retractions but without abnormal breath sounds. Remainder of exam was normal.A d-dimer was quickly obtained to rule out pulmonary embolus and was negative. EKG and troponins were obtained for concern of a cardiac etiology and revealed sinus tachycardia and no elevation in troponins. Chest X-ray and COVID-19 tests were negative. CBC revealed no leukocytosis and no anemia or polycythemia. Lipase and pregnancy test were obtained and negative. Arterial blood gas was performed.Her abdominal symptoms resolved rapidly in the ER, but her dyspnea and cyanosis worsened requiring placement on 15L 100% oxygen which only increased her oxygen saturation to 90%. Her arterial blood gas was noted to be chocolate brown in color and revealed the final diagnosis of methemoglobinemia with a level of 37%.

Discussion: The patient revealed starting Dapsone two days prior to ER presentation after a 6-month pause in her treatment. Despite light topical application, her methemoglobin level rose to 37% with severe life-threatening symptoms. Dapsone causes severe oxidative stress on the red blood cells causing the alteration of hemoglobin and subsequent decreased oxygen delivery to the tissue. This causes the blood to appear chocolate-like in color. She was started on methylene blue which precipitated serotonin syndrome. It was presumed this was because of the interaction between Zoloft and methylene blue as a potent MAOI. This resolved with benzodiazepines. IV ascorbic acid was started in addition to the methylene blue to reduce the methemoglobin level without risk of causing serotonin syndrome. Her methemoglobin level slowly resolved and she was discharged with a methemoglobin level of 0.6% after 3 days.

Conclusions: Topical dapsone use for acne in teenagers can precipitate methemoglobinemia. In our anxious or depressed adolescents on SSRIs, it is important to remember that methylene blue can cause serotonin syndrome. The alternative treatment option is IV ascorbic acid or vitamin C, but contact your local poison control center for further recommendations! This patient’s anxiety was worsening her shortness of breath and she responded well to benzodiazepines for serotonin syndrome, but there is also the option of cyproheptadine to block those serotonin receptors.