Abstract #1398759: Rituximab Therapy for Refractory Insulin Allergy in Type-1 Diabetes Mellitus

Abstract

Hypersensitivity reactions to insulin have decreased significantly since the introduction of human insulin preparations, but up to 3% of diabetic patients can still be affected with both immediate and delayed reactions described. There were previous reports of rituximab use in severe, refractory insulin allergies in Type-1 Diabetes Mellitus (T1DM) prior to omalizumab treatment. Here, we describe another case of T1DM with severe insulin allergy that was successfully treated with rituximab monotherapy. A 40-year-old female presents to an Endocrinology clinic for care of her T1DM. She was diagnosed with T1DM at age 37, initially treated with multiple daily injections of insulin glargine and aspart, which were switched to pod pump therapy 6 months later. Within 2 years, she experienced painful and itchy rashes with erythema and wheals at the pod insertion sites that developed within 1 to 4 hours of pod placement. Barrier adhesives, topical and oral antihistamines, and topical glucocorticoids were ineffective. Over the next 12 months, she was trialed on insulin aspart, lispro, regular, and glulisine with similar results despite using syringe and pen injectors. Skin reactions lasted several days, with nodules and surrounding lipodystrophy. Inhaled human insulin was implemented but discontinued due to cough. She was referred to our drug allergy clinic, where testing that included a positive immediate intradermal insulin lispro test and negative m-cresol skin test was performed. Serum insulin-specific IgG antibody testing was positive, but IgE antibody was negative, suggesting the reaction was related to tissue-bound IgE. Skin biopsy revealed sub-lobular panniculitis. She was empirically started on metformin, dapagliflozin, and liraglutide to reduce insulin needs, with only mild improvement achieved. However, 4 doses of rituximab 100mg weekly as intravenous infusion significantly reduced her skin reactions with a durable response out to 18 months, when the injection site reactions recurred. Rituximab treatment was repeated weekly for 4 weeks. Her skin reactions improved again after this second round of immunotherapy, and the patient continues to do well 30 months afterward. Suspected patients with insulin allergy should have a thorough evaluation including immediate and delayed skin testing, serum IgE assessment, skin biopsy, and exclusion of other skin disorders. Treatment approaches include changing insulin preparations, changing injection technique and rotating sites, antihistamines, or even desensitizing with an insulin pump. Our case reinforces that systemic immunotherapy can be a viable option in refractory cases.