A case report and systematic literature review: insulin-induced type III hypersensitivity reaction.

Insulin-induced type III hypersensitivity reactions (HSRs) are exceedingly rare and pose complex diagnostic and management challenges. We describe a case of a 43-year-old woman with type 1 diabetes mellitus (DM), severe insulin resistance, and subcutaneous nodules at injection sites, accompanied by elevated anti-insulin IgG autoantibodies. Treatment involved therapeutic plasma exchange (TPE) and intravenous immunoglobulin (IVIg) as bridge therapy, followed by long-term immunosuppression, which reduced autoantibody levels and improved insulin tolerance. Given the limited treatment guidelines, we conducted a comprehensive literature review, identifying 16 similar cases. Most patients were females with a median age of 36.5 years; 63% had type 1 DM, and 44% had concurrent insulin resistance (56% with elevated autoantibodies). Treatment approaches varied, with glucocorticoids used in 67% of cases. Patients with type 1 DM were less responsive to steroids than those with type 2 DM, and had a more severe course. Of those patients with severe disease necessitating immunosuppression, 66% had poor responses or experienced relapses. The underlying mechanism of insulin-induced type III HSRs remains poorly understood. Immunosuppressive therapy reduces anti-insulin IgG autoantibodies, leading to short-term clinical improvement and improved insulin resistance, emphasizing their crucial role in the condition. However, the long-term efficacy of immunosuppression remains uncertain and necessitates continuous evaluation and further research.

Case Report: Insulin hypersensitivity in youth with type 1 diabetes.

Objective: Immediate type I, type III, and delayed type IV hypersensitivity reactions to insulin are rare, but potentially serious complications of exogenous insulin administration required for the treatment of type 1 diabetes (T1D). Methods: We present four cases of insulin hypersensitivity reactions occurring in youth with T1D and a literature review of this topic. Results: Insulin hypersensitivity reactions included types I, III, and IV with presentations ranging from localized urticaria, erythematous nodules, and eczematous plaques to anaphylaxis with respiratory distress. Reactions occurred in youth with newly diagnosed T1D and in those with long-standing T1D who were using both injection and insulin pump therapy. Multidisciplinary care involving pediatric endocrinology and allergy/immunology utilizing trials of many adjunct therapies yielded minimal improvement. Despite the use of various treatments, including antihistamines, topical therapies, immunosuppressant medications, desensitization trials, and intravenous immune globulin, cutaneous reactions, elevated hemoglobin A1c levels, and negative effects on quality of life remain persistent challenges. One patient became one of the youngest pancreas transplant recipients in the world at age 12 years due to uncontrollable symptoms and intolerable adverse effects of attempted therapies. Conclusion: Although rare, insulin hypersensitivity reactions negatively affect glycemic control and quality of life. These cases demonstrate the varying severity and presentation of insulin hypersensitivity reactions along with the limited success of various treatment approaches. Given the life-sustaining nature of insulin therapy, further studies are needed to better understand the underlying pathophysiology of insulin hypersensitivity and to develop targeted treatment approaches.

Case report: Insulin desensitization as the only option for managing insulin allergy in a Sudanese patient.

Introduction: Allergic reactions to insulin have become very rare with the introduction of human insulin. Anaphylaxis is a life-threatening condition that results from immediate IgE-mediated hypersensitivity. Desensitization to human insulin was reported to control immediate hypersensitivity reactions to insulin. Here, we describe the history and challenges of managing our patient and the development of an insulin desensitization protocol in a resource-limited setup. Case Summary: A 42-year-old Sudanese woman with poorly controlled type 2 diabetes on maximum antidiabetic medications required insulin therapy to achieve reasonable glycemic control. She developed progressive and severe immediate hypersensitivity reactions to insulin, including anaphylaxis. Serum sample analysis demonstrated insulin-specific IgE antibodies. The patient's poor glycemic control and the need for breast surgery indicated insulin desensitization. A 4-day desensitization protocol was delivered in an ICU bed for close observation. Following successful desensitization and 24-h observation, our patient was discharged on pre-meal human insulin, which was tolerated well to the current date. Conclusions: Although insulin allergy is rare, once encountered, it is very challenging in patients who have no other treatment options available. Different protocols for insulin desensitization are described in the literature; the agreed protocol was implemented successfully in our patient despite the limited resources.

Effective treatment of diabetes, improved quality of life and accelerated cognitive development after pancreas transplantation in a child with type 1 diabetes and allergy to manufactured insulin preparations.

BACKGROUND: Insulin hypersensitivity reactions are rare but serious and significantly affect the treatment of diabetes in children. METHODS: A 13-year-old girl with type 1 diabetes, hypoglycemic unawareness, and treatment refractory allergy to available insulin preparations underwent a solitary pancreas transplant. Before the pancreas transplantation, she was receiving a continuous subcutaneous infusion of rapid-acting insulin with an increasing need for antihistamines and steroids, negatively impacting her cognitive and social development. Her diabetes was poorly controlled, and her quality of life was progressively worsening. RESULTS: Following the transplant, she recovered well from surgery and achieved euglycemia without needing exogenous insulin. She had two biopsy proven episodes of acute cellular rejection, successfully treated. Her cognitive development also accelerated. Notable improvement was noted both in her personal quality of life and her family's overall well-being. CONCLUSIONS: This is the youngest pancreas transplant recipient with over 1-year graft survival reported in the literature. Pancreas transplant alone in a teenager without indications for kidney transplantation could be considered a last resort treatment for diabetes when continuing insulin therapy presents a high level of morbidity. A pancreas transplant is a feasible treatment modality for patients with refractory insulin allergy.

Nursing a patient with latent autoimmune diabetes in adults with insulin-related lipodystrophy, allergy, and exogenous insulin autoimmune syndrome: A case report.

BACKGROUND: Latent autoimmune diabetes in adults (LADA) is a special type of type 1 diabetes mellitus. During the early stages, patients with LADA are treated with oral antidiabetics. However, insulin treatment is still required as islet function gradually declines. Once patients have developed insulin allergy, clinical treatment and nursing care become very challenging. CASE SUMMARY: Here, we report a case of LADA with insulin-related lipodystrophy, allergy, and exogenous insulin autoimmune syndrome during insulin treatment, thus making it very difficult to effectively control glucose levels with insulin. We attempted subcutaneous injection and an insulin pump to desensitize the patient's response to insulin, and finally assisted the doctor to select the appropriate insulin treatment for the patient. We describe the management of this patient from a nursing viewpoint. CONCLUSION: We summarize the nursing experience of a case with complex insulin allergy requiring desensitization treatment. Our approach is very practical and can be applied to similar patients needing insulin desensitization.

Serious diabetic ketoacidosis induced by insulin allergy and anti-insulin antibody in an individual with type 2 diabetes mellitus.

Diabetic ketoacidosis (DKA) is one of the most serious acute metabolic complications of diabetes mellitus, and is characterized by hyperglycemia, metabolic acidosis and increased total ketone body concentrations. The main mechanism of DKA is a lack of insulin in the body. It has been reported that some immunological response is associated with insulin therapy. Herein, we report a case of serious DKA, which was induced by insulin allergy and anti-insulin antibody. This case clearly shows that DKA can be induced by insulin allergy and anti-insulin antibodies in individuals with type 2 diabetes treated with insulin. Furthermore, we should know that as the required insulin dose might be very high under severe insulin resistance and serious DKA in such cases, we should increase the insulin dose appropriately while monitoring pH, base excess and other factors.

Insulin Allergy to Detemir Followed by Rapid Onset of Diabetic Ketoacidosis: A Case Report and Literature Review.

The management of diabetes mellitus in an insulin-dependent patient is challenging in the setting of concomitant antibody-mediated-insulin hypersensitivity. We report a case of a 62-year-old woman with pre-existing type 2 diabetes mellitus of 10 years duration who developed type 3 hypersensitivity reaction to insulin analogue detemir, and subsequently, severe diabetic ketoacidosis (DKA). She was C-peptide negative and was diagnosed with insulin-dependent diabetes. Despite increasing dose adjustments, insulin-meal matching, and compliance with insulin, she experienced episodes of unexpected hyperglycaemia and hypoglycaemia. The development of rash after detemir initiation and rapid progression to DKA suggests an aberrant immune response leading to the insulin allergy and antibody-induced interference with insulin analogues. Glycaemic control in the patient initially improved after being started on subcutaneous insulin infusion pump with reduced insulin requirements. However, after a year on pump therapy, localised insulin hypersensitivity reactions started, and glycaemic control gradually deteriorated.

Rapid Desensitization for Insulin Allergy in Type 1 Diabetes Using an Insulin Pump: A Case Report and Literature Review.

OBJECTIVE: Insulin allergy, although uncommon, poses a significant challenge in those with type 1 diabetes mellitus (T1D) as insulin replacement is a necessity. Our objective is to describe a patient in whom rapid desensitization to insulin aspart was achieved using an insulin pump. METHODS: A 40-year-old woman with newly diagnosed T1D developed pruritic wheals over the abdomen after being injected with insulin glargine U-300 (Toujeo) and insulin aspart. Type 1 insulin hypersensitivity was confirmed through intradermal testing and positive insulin-specific immunoglobulin E levels. RESULT: The patient underwent rapid desensitization with an insulin pump. Half the anticipated daily basal requirement was initially subcutaneously administered before initiating low-dose insulin via the pump (0.000025 units/h) and increasing the dose every 30 minutes to reach her basal requirements within 5 hours. Subsequent larger bolus insulin doses did not produce any local or anaphylactic reactions. No pretreatment with corticosteroids or antihistamines was provided. CONCLUSION: Previous protocols for insulin desensitization span over days and often involve routine premedication. The case we presented suggests that insulin desensitization can be achieved over several hours using an insulin pump. A subcutaneous basal insulin cover should be provided prior to desensitization to avoid hyperglycemia necessitating an insulin bolus. Routine premedication may not always be necessary depending on reaction severity.

The effect of liraglutide on insulin allergy in a patient with glucocorticoid-induced diabetes and multiple sclerosis.

Glucocorticoid use may trigger secondary diabetes or exacerbate hyperglycemia in patients with diabetes mellitus (DM). Liraglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist used for the treatment of patients with type 2 diabetes. Few reports mention liraglutide as a treatment for steroid-induced DM (SIDM). Here, we report a patient with SIDM and multiple sclerosis, for whom switching to liraglutide combined with metformin therapy improved glucose levels and ameliorated the symptoms of insulin allergy. Liraglutide may be useful for treating SIDM with insulin allergy.

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.

Insulin Adverse Events.

The negative consequencies of diabetes treatment are traditionally regarded as caused by a disastrous treatment rather than adverse events of the insulin preparations. However, hypoglycemia, changes at the injection site (lipatrophy, lipoma), insulin allergy, obesity and increased risk of certain forms of cancer can easily be regarded as adverse events of the drug, and needle-phobia, psychological problems, increased risk of suicide are adverse events related to insulin and its administration. Also macroangiopathy and even microangiopathy to some extent can be regarded as adverse events as the most crucial part of the treatment of Type 1 diabetes is the insulin treatment. There is still room for improvments of insulin as a drug. We need insulins with more predictable absorption and kinetics, leading to more stable near-normal blood glucose, less risk of hypoglycemia, less effect in periphery and more effect on the liver, and less risk of vascular complications, obesity, cancer.

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 Modified Desensitization Therapy with Analog Insulin in an Individual with Severe Allergy to Multiple Insulin Preparations: A Case Report.

We present a case of a 27-year-old female with T2 DM who developed allergic reactions after commencement of insulin therapy. Trial with different types of insulin resulted in a series of allergic reactions ranging from urticarial rash to development of angioedema, bronchospasm and anaphylactic shock. She was successfully treated with a modified insulin desensitization protocol using rapid-acting insulin.

Successful modified desensitization therapy with analog insulinin an individual with severe allergy to multiple insulin preparations: A case report / Journal of the ASEAN Federation of Endocrine Societies

@#We present a case of a 27-year-old female with T2 DM who developed allergic reactions after commencement of insulin therapy. Trial with different types of insulin resulted in a series of allergic reactions ranging from urticarial rash to development of angioedema, bronchospasm and anaphylactic shock. She was successfully treated with a modified insulin desensitization protocol using rapid-acting insulin.

Effect of Liraglutide on Type B Insulin Resistance Syndrome and Insulin Allergy in Type 2 Diabetes: A Case Report.

INTRODUCTION: The appearance of anti-insulin antibodies or an allergy to insulin occasionally causes clinical problems with glycemic control in insulin users. METHODS: In the present report, we describe a therapeutic approach that was employed for a man with type 2 diabetes who had insulin allergy, anti-insulin antibodies, and anti-insulin receptor antibodies that developed during his insulin treatment. RESULTS: We started the patient on liraglutide, a glucagon-like peptide-1 receptor agonist, and attained glycemic control without incurring any side effects. Two years after liraglutide induction, his blood glucose was being maintained at a healthy level by liraglutide monotherapy. CONCLUSION: Liraglutide may be a therapeutic option for patients with insulin allergy, anti-insulin antibodies, and type B insulin resistance syndrome, as it represents an alternative strategy to insulin.

Long-acting insulin allergy in a diabetic child.

Insulin allergy has been uncommon since the introduction of human recombinant insulin preparations; the prevalence is 2.4%. Insulin injection could elicit immediate reactions, which are usually induced by an IgE-mediated mechanism, within the first hour after drug administration. In the present study, we describe the case of a child who experienced immediate urticaria after long-acting insulin injection. A 9-year-old girl affected by type I diabetes mellitus referred a history of three episodes of urticaria 30 min after insulin subcutaneous injection. During the first week of insulin therapy, she developed generalized immediate urticaria twice after long-acting insulin glargine first and then once after insulin degludec administration. Symptoms resolved within a few hours after treatment with oral antihistamine. She tolerated rapid insulin lispro. Her personal allergological history was negative. Skin prick tests with degludec, glargine and detemir were performed, showing negative results. Intradermal 1:100000-diluted tests were immediately positive for both degludec and glargine but not for detemir. In light of these findings, detemir was administered without any reaction. Our results show that detemir is tolerated by patients with clinical hypersensitivity reactions to degludec and glargine. Although reactions could be attributable to additives allergy, such as zinc or metacresol, this was excluded since all three preparations contain the same components. So, insulin itself acted as offending allergen. Detemir differs from degludec and glargine in a few aminoacids. Therefore, it is possible that the conformational rather than the linear epitope may be responsible for the reaction. This result suggests integrating intradermal tests in the diagnostic flowchart for insulin allergy. Insulin allergy should always be suspected in patients with immediate symptoms after drug injection. As allergologic work-up, prick by prick test and intradermal test to insulin preparations should be performed. In case of negative results of cutaneous tests, insulin analogs may be administered.

Type III Hypersensitivity Reaction to Subcutaneous Insulin Preparations in a Type 1 Diabetic.

Management of type 1 diabetes in patients who have insulin hypersensitivity is a clinical challenge and places patients at risk for recurrent diabetic ketoacidosis (DKA). Hypersensitivity reactions can be due to the patient's response to the insulin molecule itself or one of the injection's non-insulin components. It is therefore crucial for clinicians to quickly recognize the type of hypersensitivity reaction that is occurring and identify potentially immunogenic additives for the purpose of directing therapy as various insulin preparations have differing ingredients. We present the case of a 23-year-old diabetic female with common variable immunodeficiency (CVID) and autoimmune enteropathy who developed a type III hypersensitivity reaction to multiple formulations of subcutaneous insulin after years of use and the challenges of devising a long-term management strategy.

Human insulin and its analog injection-induced localized lipoatrophy: 6 case reports and systemic review / 中华临床营养杂志

Objective To investigate clinical and pathological characteristics of insulin-induced localized lipoatrophy and treatment.Methods We retrospectively analyzed clinical manifestation, skin biopsy pathology, treatment regimen and follow-up of 6 diabetic patients with insulin-induced localized lipoatrophy in Peking Union Medical College Hospital from January, 2010 to March, 2016, with systemic review of related literatures.Results Among 6 cases with insulin-induced localized lipoatrophy, 5 patients were with insulin allergy.5 patients were with positive insulin-autoimmune antibody, which was similar to the ratio reported in the systematic review (18 out of 19).Insulin-induced lipoatrophy could be caused by various types of preparations of insulin and insulin analogs.Subcutaneous biopsy, performed on the atrophied area, revealed the decrease of the number and volume of adipocytes and tissue fibrosis, probably accompanied with lymphocytes, eosinophils or mast cells infiltration.Lipoatrophy could sometimes be relieved by changing injection sites, types of insulin preparations or drug-delivery way, sometimes by application of systemic/local glucocorticoid or local cromolyn sodium.Conclusions Insulin-induced localized lipoatrophy is a rare adverse reaction of insulin preparations.It might be related to immune response of local tissue and heterogeneous pathological manifestations.The lipoatrophy might be improved by changing injection sites, changing the type of insulin preparations or drug-delivery way, and with possibility to carry out targeted immunosuppressive therapy according to the biopsy pathology in the future.

Current Situation and Treatment Strategies of Insulin Allergy / 中国药师

Objective: To analyze the current situation and treatment strategies of insulin allergy at home and abroad to provide reference for medical staffs to diagnose and treat the anaphylaxis.Methods: The literatures on insulin allergy in recent ten years were searched to analyze the present situation statistically and summarize the treatment strategies.Results: In recent ten years, the cases of insulin allergy were reported repeatedly.The insulin allergy mainly affected skin and its accessories, causing local allergic reactions (redness itching, induration and so on).General allergic reactions occurred rarely, but were life-threatening in severe situations.Conclusion: Medical staffs should grasp the ability of diagnosis and treatment of insulin allergy to ensure the medical safety and effectiveness for patients.

Continuous Subcutaneous Insulin Infusion as an Effective Method of Desensitization Therapy for Diabetic Patients with Insulin Allergy: A 4-year Single-center Experience.

PURPOSE: This article summarizes our experiences in the application of continuous subcutaneous insulin infusion (CSII) as a method of rapid desensitization therapy for diabetic patients with insulin allergy that was subsequently switched to a regimen of multiple-dose injections for long-term insulin therapy. METHODS: The clinical data of 11 diabetic patients with insulin allergy in Peking Union Medical College Hospital from April 1, 2008, through December 31, 2011, were retrospectively analyzed. FINDINGS: All 11 conditions were diagnosed by case history, skin testing, determination of serum specific anti-insulin IgE, and reaction to withdrawal of insulin. Seven patients accepted the traditional injection method of desensitization, and 5 patients accepted CSII with the protocol designed for this study (1 patient accepted CSII after failure by the formal method). Six of the 7 patients who accepted the traditional method and all 5 patients who accepted CSII had successful results. All 5 patients in the CSII group switched to a regimen of multiple dosage injections. In a survey of 28 nurses, both experienced nurses and practical nurses preferred to use CSII as the method of desensitization. IMPLICATIONS: It is feasible and effective for diabetic patients with insulin allergy to use CSII as a method of rapid desensitization with subsequent switching to a regimen of multiple-dose injections for long-term insulin therapy.