CGR 10: WHEN HER ITCH TURNED BLUE AND HER BLOOD A CHOCOLATE BROWN HUE: ACQUIRED METHAEMOGLOBINAEMIA SECONDARY TO OMALIZUMAB IN TREATMENT‐RESISTANT CHRONIC IDIOPATHIC URTICARIA

Abstract

We report the first case of methaemoglobinaemia caused by omalizumab. Having suffered for 3 years from treatment-refractory chronic idiopathic urticaria, resistant to high dose antihistamines, montelukast, dapsone and frequent bursts of systemic corticosteroids, a 50-year-old female patient presented for a graded challenge of omalizumab, the humanised monoclonal antibody targeting immunoglobulin E (IgE). She had previously received 150 mg subcutaneous omalizumab monthly for a nine month period with a near complete clinical response. However, light-headedness around 8 h after each injection prompted discontinuation. Recurrence of urticaria and its associated poor quality of life inspired a graded challenge scheduled over three days (Day 1 - 50 mg, Day 2 - 100 mg, Day 3 - 150 mg). Eight hours after the second dose of omalizumab our patient became symptomatic with a headache and light-headedness. Cyanosis coupled with hypoxia, that failed to correct with supplemental oxygen prompted an arterial blood gas, which identified methaemoglobinaemia (27%, normal range 0-2%). The patient was treated with intravenous methylene blue given her cardiopulmonary compromise. Dapsone, a well-recognised cause of methaemoglobinaemia was deemed as the causative agent and was ceased immediately and indefinitely. Despite an initial improvement of urticarial symptoms, these returned within three months. Given the previous efficacy of omalizumab, another trial was scheduled at the patient's request. She was rechallenged with 150 mg but more severe methaemoglobinaemia (38%) developed. This time, ascorbic acid and multiple doses of methylene blue were administered due to a protracted clinical course over more than 72 h. This case provides strong temporal evidence that omalizumab can cause a dose-related acquired methaemoglobinaemia, with symptoms developing between 6 and 12 h following administration. To our knowledge, this is the first reported case of the potentially fatal condition, methaemoglobinaemia associated with omalizumab, or any monoclonal antibody.