The complexities of insulin allergy: a case and approach

Background Insulin hypersensitivity is rare, but challenging for individuals with diabetes. The prevalence of insulin allergy has decreased since the introduction of human recombinant insulin preparations. Hypersensitivity reactions range from injection site erythema and swelling, to anaphylaxis. While some reactions are to excipients (zinc, protamine, metacresol), many are to recombinant insulin itself. We present a case of type 1 hypersensitivity to various preparations of insulin in a patient with insulin-dependent type 2 diabetes mellitus (T2DM). Case presentation A 61-year-old woman with a 30-year history of insulin-dependent T2DM was referred for evaluation of reactions to insulin. She had two episodes over 5-months; both required Emergency Department visits and epinephrine administration. The first episode entailed a burning sensation of the extremities and nausea, immediately after injecting NovoRapid® insulin. The second event entailed a similar reaction but this time there was also angioedema of the upper airway with difficulty breathing and hypotension, immediately after injecting Levemir® and NovoRapid®, and taking metformin. There were no cofactors such as exercise, infectious illness, or NSAIDs use. Skin testing was performed with metformin, Lantus®, Humalog®, NovoRapid®, glulisine, insulin regular, NPH, Levemir® and the excipient protamine, as per published testing concentrations. Metacresol was not tested as its use was restricted by the hospital pharmacy. Insulin preparations with and without metacresol were included in testing however. A clinic staff served as a negative control. The patent had negative testing with protamine, but sensitization to all insulin preparations. Metformin skin testing and challenge along with latex IgE were negative. Subsequently, she underwent intentional weight loss of 70 lb, and was started on oral hypoglycemics with good effect. Conclusions Our case highlights the importance of diagnosing insulin allergy through a detailed history and focused testing. Therapeutic strategies include avoidance and insulin alternatives, alternate insulin preparations, or desensitization. In severe recurrent hypersensitivity reactions, Omalizumab or pancreatic transplantation have been effective.

RAPID DESENSITIZATION WITH INTRAVENOUS INSULIN IN A PATIENT WITH DIABETIC KETOACIDOSIS AND INSULIN ALLERGY

Objective: We report a case of insulin desensitization in a patient with known allergy to multiple insulin preparations who presented with diabetic ketoacidosis (DKA). Methods: Clinical and laboratory data, and desensitization protocols are presented. Results: A 65-year-old woman with type 2 diabetes and a documented insulin allergy presented with severe DKA. She was managed initially with intravenous (IV) fluids, sodium bicarbonate, and hemodialysis. An intradermal skin test was positive for 0.01 units/mL of human regular insulin. A rapid desensitization protocol for IV human regular insulin was initiated after pretreatment with methylprednisolone, ranitidine, montelukast, and cetirizine. An initial dilution of 1 unit of insulin in 100,000 mL of 0.9% sodium chloride was started at 5 mL/hour IV. The dilution was increased at 60-minute intervals to 1 unit/10,000 mL, 1 unit/1,000 mL, 1 unit/100 mL, 1 unit/10 mL, then 1 unit/1 mL. The dose was then increased from 1 to 7 units/hour (0.1 units/kg body weight/hour). The anion gap closed after 24 hours, and overlapping desensitization was started for subcutaneous (SC) human regular insulin starting with 0.00001 units with a gradual increase to 7 units before meals and 6 units at bedtime over 5 days. There were no anaphylactic reactions to IV or SC insulin. She was discharged with human regular insulin SC 4 times daily, oral montelukast, cetirizine, diphenhydramine as needed, and an epinephrine pen. No allergic reactions were reported at follow-up visits. Conclusion: Rapid insulin desensitization is possible to allow treatment of DKA with human regular insulin IV in patients with known insulin allergy.

SUN-693 What Else Should Be Done in Patients with Uncontrolled Type 2 Diabetes and Severe Insulin Allergy?

Introduction: Insulin allergy in patients with diabetes mellitus is a very rare condition. The immediate vital implications for the patient call for prompt diagnosis and management of insulin allergy. We present a case of a patient that was unable to tolerate the insulin desensitization process, however; he was successfully treated with antidiabetics’ medications following the AACE guidelines for the management of type 2 diabetes (T2DM).Case description:31 years old obese Caucasian male with a BMI of 35, a history of T2DM and insulin allergy who was admitted to the hospital with hyperglycemia and osteomyelitis of the right foot. Endocrinology was consulted for the management of diabetes. Laboratory results showed hemoglobin A1C 11.1%, C peptide level 2.79 with blood glucose 283 mg/dl with negative insulin specific IgG level and elevated Ig E levels. The patient was actually diagnosed with T2DM in 2001, then started on metformin, glyburide initially. Given uncontrolled diabetes he was started on insulin in 2007 however, he developed an allergic reaction to different types of insulin (including anaphylactic reaction) so he was referred to allergy and immunology for further testing and possible desensitization. He had an allergy to human, bovine and porcine insulin. Exclusion of other causes of allergy including latex, protamine, and zinc was performed by the immunologist. Trial of insulin desensitization (using NPH and regular Insulin) failed. He also developed an allergic reaction to different medications including sulfonylurea, SGLT2 inhibitors, DDP4 inhibitors, and alpha-glucosidase inhibitors. During the inpatient setting in 2019, we assessed the patient and considered different options available; bromocriptine versus amylin products versus fish insulin versus IGF1 (as of last resort). Other options were another desensitization process in the ICU setting with transitioning to an insulin pump, however, the patient refused that option. We started the patient on bromocriptine mesylate(cyclocet) with pioglitazone and the A1C improved in the next 3 months from 11.1%-->9.8%. The patient is still following up with us and plans for desensitization once the osteomyelitis of the foot is controlled. Discussion and conclusion: Insulin allergy is a rare but severe condition that calls for immediate work-up. It can be managed well in close cooperation between the endocrinologist and the immunologist. Our patient developed IgE-mediated symptoms occurring immediately after insulin injection and confirmed by intradermal skin testing. Specific immunotherapy has been reported in case reports in the literature and should be considered for these patients Following AACE guidelines for the management of T2DM with the addition of bromocriptine mesylate until desensitization was a beneficial option for our patient.

Successful Treatment of Insulin Allergy with Desensitization Therapy: A Case Report and Literature Review

Insulin therapy is an essential treatment for type 1 and uncontrolled type 2 diabetes mellitus (DM). Hypersensitivity reactions have been described since the first administration of insulin, the same as any other therapy. Despite being a rare situation nowadays, it requires careful intra-hospital monitoring and multidisciplinary management. Here, we present a case of a 57-year-old patient with type 2 DM, an average glycemic control, and both penicillin and insulin allergy. Heunderwent a desensitization protocol which allowed successfully dismiss him with intermediate-acting insulin.

Successful management of severe diabetic ketoacidosis in a patient with type 2 diabetes with insulin allergy: a case report

Background Diabetic ketoacidosis (DKA) is an acute, major, life-threatening complication of diabetes that requires immediate treatment. Allergic reaction to insulin is rare, especially when using recombinant human insulin. The clinical presentation of insulin allergy can range from minor local symptoms to a severe generalized allergic reaction such as anaphylaxis. A limited number of cases have been reported on the treatment of severe DKA in patients with type 2 diabetes with insulin allergy. Here, we describe a patient with type 2 diabetes with insulin allergy in which severe DKA resolved after the initiation of continuous intravenous (IV) recombinant human insulin infusion. Case presentation A 58-year-old man with type 2 diabetes initiated subcutaneous insulin administration (SIA) after failure of oral antidiabetic treatment. Symptoms of an allergic reaction developed, including pruritic wheals appearing within 10 min of injection and lasting over 24 h. Both skin prick and intradermal tests were positive with different types of insulin. Two days before admission, he stopped SIA because of allergic symptoms and then experienced weakness and upper abdominal pain. On admission, he was in severe metabolic acidosis with a pH of 6.984 and bicarbonate of 2.5 mmol/litre. The blood glucose level was 20.79 mmol/litre, BUN 4.01 mmol/litre, creatinine 128 μmol/litre, and urinary ketone 11.44 mmol/litre. Over 24 h, metabolic acidosis was refractory to IV fluids, bicarbonate and potassium replacement, as well as haemodialysis. Ultimately, he received continuous IV recombinant human insulin infusion at a rate of 0.1 units/kg/hour, in combination with haemodiafiltration, and no further allergic reactions were observed. On day 5, ketonaemia and metabolic acidosis completely resolved. He had transitioned from IV insulin infusion to SIA on day 14. He was discharged on day 21 with SIA treatment. Three months later, he had good glycaemic control but still had allergic symptoms at the insulin injection sites. Conclusions In this patient, SIA caused an allergic reaction, in contrast to continuous IV insulin infusion for which allergic symptoms did not appear. Continuous IV recombinant human insulin infusion in combination with haemodiafiltration could be an option for the treatment of severe DKA in patients with diabetes with insulin allergy.

Successful management of severe diabetic ketoacidosis in a patient with type 2 diabetes with insulin allergy: a case report

BackgroundDiabetic ketoacidosis (DKA) is an acute, major, life-threatening complication of diabetes that requires immediate treatment. Allergic reaction to insulin is rare, especially when using recombinant human insulin. The clinical presentation of insulin allergy can range from minor local symptoms to a severe generalized allergic reaction such as anaphylaxis. A limited number of cases have been reported on the treatment of severe DKA in patients with type 2 diabetes with insulin allergy. Here, we describe a patient with type 2 diabetes with insulin allergy in which severe DKA resolved after the initiation of continuous intravenous (IV) recombinant human insulin infusion.Case presentationA 58-year-old man with type 2 diabetes initiated subcutaneous insulin administration (SIA) after failure of oral antidiabetic treatment. Symptoms of an allergic reaction developed, including pruritic wheals appearing within 10 minutes of injection and lasting over 24 hours. Both skin prick and intradermal tests were positive with different types of insulin. Two days before admission, he stopped SIA because of allergic symptoms and then experienced weakness and upper abdominal pain. On admission, he was in severe metabolic acidosis with a pH of 6.984 and bicarbonate of 2.5 mmol/litre. The blood glucose level was 20.79 mmol/litre, BUN 4.01 mmol/litre, creatinine 128 µmol/litre, and urinary ketone 11.44 mmol/litre. Over 24 hours, metabolic acidosis was refractory to IV fluids, bicarbonate and potassium replacement, as well as haemodialysis. Ultimately, he received continuous IV recombinant human insulin infusion at a rate of 0.1 units/kg/hour, in combination with haemodiafiltration, and no further allergic reactions were observed. On day 5, ketonaemia and metabolic acidosis completely resolved. He had transitioned from IV insulin infusion to SIA on day 14. He was discharged on day 21 with SIA treatment. Three months later, he had good glycaemic control but still had allergic symptoms at the insulin injection sites.ConclusionsIn this patient, SIA caused an allergic reaction, in contrast to continuous IV insulin infusion for which allergic symptoms did not appear. Continuous IV recombinant human insulin infusion in combination with haemodiafiltration could be an option for the treatment of severe DKA in patients with diabetes with insulin allergy.