Insulin Hypersensitivity: A Rare Obstacle Benjamin

Today’s Visit<br>

Previous reactions to other insulins<br>

Previous insulin therapy<br>

Other History<br>

Current Medications<br>

Current Allergy List Aspirin (N/V)
Basaglar (itching at injection site)
Codeine (tongue swelling)
Darvocet (N/V)
Iodine (hives)
Lantus (severe itching, shortness of breath overnight)
Levemir (nodule at injection site, pruritis)
Lisinopril (abdominal discomfort)
Macrodantin (anaphylaxis)
Maxzide (hives)
Metoprolol (wheezing)
Morphine (N/V, tongue swelling, confusion)
Neurontin (blurred vision)
Penicillin (hives)
Pentazocine lactate (N/V)
Percocet (tongue swelling)
Red Dye (tongue swelling)
Rosuvastatin (N/V)
Shellfish (anaphylaxis/hives)
Sulfa (N/V)
Tresiba (cramping, lower extremity edema, difficulty swallowing)<br>

CGM Data<br>

Relevant Labs and Objective Values<br>

Overview of Insulin Allergies<br>

Overview: Haastrup MB, et al. Insulin allergy can be successfully managed by a systematic approach. Clinical and Translational Allergy. 2018;8(1). doi:https://doi.org/10.1186/s13601-018-0223-x Sola-Gazagnes A. Insulin allergy: A diagnostic and therapeutic strategy based on a retrospective cohort and a case-control study. Diabetologia. 08/2022;65(8):1278-1290. doi: 10.1007/s00125-022-05710-9.<br>

Pathophysiology: Type I Hypersensitivity:
IgE-mediated allergic reaction
Mast cell degranulation releases inflammatory mediators
Result: Angioedema, skin reactions, and more
Insulin’s Role:
A component within insulin must be the source
What components are candidates? Riaz Ahmad Bhutta. Elementary Immunology:Type 1 Hypersensitivity Reaction, Anaphylaxis, Atopy, and Treatment.; 2006:Chapter 11.<br>

Clinical Presentation Haastrup MB, et al. Insulin allergy can be successfully managed by a systematic approach. Clinical and Translational Allergy. 2018;8(1). doi:https://doi.org/10.1186/s13601-018-0223-x<br>

Possible Antigen Sources Schernthaner G. Immunogenicity and allergenic potential of animal and human insulins. Diabetes Care. 1993 Dec;16 Suppl 3:155-65. doi: 10.2337/diacare.16.3.155. PMID: 8299472. Chu YQ, et al. Allergic shock and death associated with protamine administration in a diabetic patient. Clin Ther. 2010 Sep;32(10):1729-32. doi: 10.1016/j.clinthera.2010.09.010. PMID: 21194595.<br>

Possible Antigen Sources<br>

Insulin Preparations: Components<br>

Insulin Preparations: Components<br>

Structuring a Protocol No current treatment guidelines for insulin allergies
Recent study shows a workflow for management:
Step 1: Determine allergy sensitivity.
Step 2: Evaluate the severity of symptoms.
Step 3: Are any alternative agents feasible?
Step 4: What change of insulin is possible?
Step 5: Monitor for efficacy and safety. Haastrup MB, Henriksen JE, Mortz CG, Bindslev-Jensen C. Insulin allergy can be successfully managed by a systematic approach. Clinical and Translational Allergy. 2018;8(1). doi:https://doi.org/10.1186/s13601-018-0223-x<br>

What options are available if an insulin switch is poorly tolerated? Yuan T, et al. Continuous Subcutaneous Insulin Infusion as an Effective Method of Desensitization Therapy for Diabetic Patients with Insulin Allergy: A 4-year Single-center Experience. Clin Ther. 2016 Nov;38(11):2489-2494.e1. doi: 10.1016/j.clinthera.2016.09.018. Epub 2016 Oct 26. PMID: 27793354. Mishra S, Connors L, Tugwell B. Role of omalizumab in insulin hypersensitivity: a case report and review of the literature. Diabet Med. 2018 May;35(5):663-666. doi: 10.1111/dme.13591. PMID: 29381818.<br>

Therapy Discussion<br>

Important Considerations<br>

Critiquing Current Therapy<br>

Evidence-Based Steps Aetna.com. Published 2023. https://www.aetna.com/cpb/medical/data/1_99/0038.html<br>

Future Considerations<br>

Takeaways Insulin allergies are rare. There is no correlating factor with strong evidence to be labeled a true risk factor.
Insulin hypersensitivity presents as immediate or delayed. Reactions are either local to the injection site or systemic and are mediated by mast cell degranulation.
Driving mediators of insulin allergy include direct reaction to insulin structure, presence of protamine, and/or excipients.
There are methods to diagnose insulin allergy via “prick” tests covered under insurance. These can determine specific insulin agent sensitivity.
The first-line option for treatment is identifying the most likely antigen-inducing reaction, then switching to an agent without said antigen.
If switching is unsuccessful, move to insulin desensitization. This can be done subcutaneously or through a pump.
Our patient today has tolerated Basaglar since 10/2023. An upward titration would benefit BG and A1c control without any evidence of increasing risk for allergic reactions.<br>

References Haastrup MB, Henriksen JE, Mortz CG, Bindslev-Jensen C. Insulin allergy can be successfully managed by a systematic approach. Clinical and Translational Allergy. 2018;8(1). doi:https://doi.org/10.1186/s13601-018-0223-x
Sola-Gazagnes A. Insulin allergy: A diagnostic and therapeutic strategy based on a retrospective cohort and a case-control study. Diabetologia. 08/2022;65(8):1278-1290. doi: 10.1007/s00125-022-05710-9.
Riaz Ahmad Bhutta. Elementary Immunology:Type 1 Hypersensitivity Reaction, Anaphylaxis, Atopy, and Treatment.; 2006:Chapter 11. https://labpedia.net/elementary-immunology/chapter-11-type-1-hypersensitivity-reaction-anaphylaxis-atopy-and-treatment/
Schernthaner G. Immunogenicity and allergenic potential of animal and human insulins. Diabetes Care. 1993 Dec;16 Suppl 3:155-65. doi: 10.2337/diacare.16.3.155. PMID: 8299472.
Chu YQ, Cai LJ, Jiang DC, Jia D, Yan SY, Wang YQ. Allergic shock and death associated with protamine administration in a diabetic patient. Clin Ther. 2010 Sep;32(10):1729-32. doi: 10.1016/j.clinthera.2010.09.010. PMID: 21194595.
Yuan T, Zhao W, Wang L, Dong Y, Li N. Continuous Subcutaneous Insulin Infusion as an Effective Method of Desensitization Therapy for Diabetic Patients with Insulin Allergy: A 4-year Single-center Experience. Clin Ther. 2016 Nov;38(11):2489-2494.e1. doi: 10.1016/j.clinthera.2016.09.018. Epub 2016 Oct 26. PMID: 27793354.<br>

References Mishra S, Connors L, Tugwell B. Role of omalizumab in insulin hypersensitivity: a case report and review of the literature. Diabet Med. 2018 May;35(5):663-666. doi: 10.1111/dme.13591. PMID: 29381818.
Aetna.com. Published 2023. https://www.aetna.com/cpb/medical/data/1_99/0038.html
How to Switch Insulin Products. pharmacist.therapeuticresearch.com. https://pharmacist.therapeuticresearch.com/Content/Segments/PRL/2016/Dec/How-to-Switch-Insulin-Products-10473<br>