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

Abstract

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.

Keywords: diabetic ketoacidosis; insulin; insulin allergy; insulin hypersensitivity; insulin-dependent diabetes.

Figure 1

Glycaemic control in this patient, reflected as HbA1c trend, and continuous glucose monitoring (CGMS) before (A) and after (B) insulin pump. Time on X axis is presented as months from presentation to hospital with severe DKA and insulin (detemir) allergy.

Figure 2

Localised cutaneous hypersensitivity reactions to insulininjections. (A) Localised erythematous rashes at sites of insulin detemir injections at initial presentation. (B) Localised erythematous skin reactions occurred after test doses of glulisine, circled in blue. A few of the resolving rashes (small arrows) at previous insulin detemir sites at 3 days after hospital admission are shown. (C) Localised cutaneous reaction at insulin administration sites when patient was on insulin aspart (novorapid) subcutaneous insulin pump is shown here. Patch testing to consumables of insulin pump were negative. (D) Increasingly altered cosmesis of her abdominal skin from repeated localised allergic reactions to insulin were observed after 4 years of insulin therapy. (E) Histology by haematoxylin and eosin staining (x100 magnification) showed dermal oedema and lymphohistiocytic perivascular inflammation suggestive of hypersensitivity reaction.