Case Presentation: A 38-year-old female presented to the emergency department with profuse vomiting, fever, chills, lightheadedness, dizziness, and the inability to tolerate oral intake. She had been in her usual state of health until two hours after returning from a doctor’s appointment where she received methylene blue intravenously. Past history included hypothyroidism, postural orthostatic tachycardia syndrome, c-ANCA vasculitis, migraine, and anxiety. Social history included marijuana/prior tobacco use. Medications included amitriptyline, hydrocortisone, levothyroxine, liothyronine, midodrine, potassium chloride, compounded semaglutide, tizanidine, NADH-ascorbic acid bicarbonate, turmeric, sumatriptan as needed. Sumatriptan was not taken within three weeks of infusion. Patient was started on monthly methylene blue infusions by an environmental medicine specialist with the goal of treating the patient’s vasculitis symptoms, which included fatigue and arthralgias. This was her 5th infusion. Within two hours of infusion the patient developed four episodes of large volume non-bloody emesis prompting ED visit, where she was found to have a temperature of 40.3 C, tachycardia and hypotension (82/44 mmHg). Examination was only remarkable for dry mucous membranes and tachycardia. The patient was alert and oriented and had no infusion site erythema.Cell count, serum chemistries, lactate, amylase and lipase were normal. Urine and blood cultures, rapid COVID and influenza tests were all negative. Chest X-ray and abdominal CT were unremarkable. Erythrocyte sedimentation rate (ESR) was elevated at 40 mm/hr. In the absence of antibiotic treatment, with vigorous intravenous hydration and withholding of serotonergic medications, the patient’s condition rapidly improved overnight. At discharge the patient was hesitant to discontinue methylene blue treatments given the relief she was experiencing for her arthralgias. She was advised to avoid using amitriptyline and sumatriptan on days preceding infusion and to discuss the benefits and risks of continuing infusions with her doctor.
Discussion: The present case discusses an unusual presentation of serotonin syndrome in a patient treated with off-label methylene blue infusions for autoimmune vasculitis. While methylene blue may be used in the treatment of certain conditions and is a dye for diagnostic procedures, its use has expanded to non-FDA approved conditions. Here we report a potentially life-threatening case where intravenous methylene blue infusion led to a serious reaction that included hypotension and an acute inflammatory response in the absence of infection. The only remarkable lab finding included an elevated ESR. This finding is consistent with previous studies that have reported a correlation between ESR and serotonin syndrome severity.1 The patient’s rapid improvement in the absence of treatment is consistent with the 5 hour half-life of methylene blue.2
Conclusions: We caution providers regarding use of intravenous methylene blue and reinforce the need to take thorough medication histories and consider potential drug interactions.