Case Presentation: A 15-year-old female with a history of migraines presented with headache and confusion. On the morning of presentation, the patient endorsed a migraine-like headache that was not relieved with over-the-counter medications, blue/gray discoloration of her hands, and shortness of breath. Review of systems was positive for anxiety, chest pain, and lightheadedness and negative for fever, cough, and congestion. The patient endorsed vaping 2-3 weeks prior but denied any other drug exposures or ingestions. Home medications included fexofenadine and propranolol daily for migraine prevention, topical dapsone for acne, and an intrauterine device. On presentation, the patient was tachycardic to 140, had labored breathing with a respiratory rate of 36, and was diffusely cyanotic, most prominent periorally and on the hands and feet. Oxygen saturations were in the low 80s and did not improve with 10L supplemental oxygen via non-rebreather. A venous blood gas demonstrated respiratory alkalosis with pH 7.44, PCO2 27, HCO3 23. Chest x-ray and echocardiogram were normal, and EKG showed sinus tachycardia. Co-oximetry was notable for levels of 50% carboxyhemoglobin and 13.9% methemoglobin. Serum studies revealed a carboxyhemoglobin level of 0.5% and a methemoglobin level markedly elevated to 34.1%. Treatment with methylene blue was initiated with rapid improvement in symptoms and methemoglobin levels. Further history elicited daily application of topical dapsone 7.5% gel to the face, chest, shoulders, and back for three weeks, despite the prescription being written for application only to the face. Serum dapsone level was 13mcg/mL (steady-state plasma concentrations from patients on 200mg daily antileprotic therapy: 0.1-7.0mcg/mL, mean = 2.3mcg/mL), confirming dapsone toxicity as the etiology of methemoglobinemia.
Discussion: Dapsone 7.5% gel is approved by the FDA for topical treatment of acne vulgaris in patients at least 12 years of age, with systemic exposure thought to be ~1% of the exposure from 100mg oral dosing. While methemoglobinemia due to systemic dapsone use has been well-described, to our knowledge, only two cases of methemoglobinemia caused by topical dapsone have been reported in the literature. Graff et al report a case of a 19-month-old female with methemoglobinemia following topical application of an unknown amount of an older sibling’s 5% gel with inability to rule out concurrent oral ingestion. Likewise, Swartzentruber et al describe a 19-year-old female who developed methemoglobinemia after applying a pea-sized amount of 5% dapsone gel twice daily for seven days. Our case represents the third report of methemoglobinemia caused by topical dapsone and is notable for medication misuse as the patient was applying more than twice the prescribed amount, leading to development of methemoglobinemia.
Conclusions: This case demonstrates the importance of taking a thorough medication history, including topical medications, which are often overlooked due to perceived lack of systemic effects. It also highlights the need for clear anticipatory guidance when prescribing topical dapsone given the potential for significant morbidity and mortality associated with methemoglobinemia.