Necrolytic migratory erythema following prolonged continuous subcutaneous dasiglucagon administration: a rare dermatologic adverse event

Abstract

Summary: Clinical management of congenital hyperinsulinism (CHI) remains a significant challenge due to its complex pathophysiology and the limitations of available therapies. Dasiglucagon, a synthetic glucagon analog, represents a novel approach to managing CHI, particularly in patients where conventional therapies fail. This report discusses a rare case of prolonged continuous subcutaneous dasiglucagon use in a neonate with CHI. Despite initial stabilization of glycemic levels, the patient developed necrolytic migratory erythema (NME), a rare dermatological condition associated with hyperglucagonemia, during dasiglucagon therapy. The patient further experienced severe malnutrition, zinc and amino acid deficiencies, and sepsis. Following the discontinuation of dasiglucagon therapy due to these severe side effects, the patient's skin and nutritional status improved markedly. However, glycemic control required subtotal pancreatectomy. This report underscores the potential of dasiglucagon in CHI management but highlights the importance of close monitoring during prolonged therapy.

Learning points: NME, a rare but severe condition, appears to be associated with prolonged continuous subcutaneous dasiglucagon therapy, requiring early recognition and intervention. Close monitoring is essential during prolonged continuous subcutaneous dasiglucagon therapy to detect potential adverse effects, focusing on dermatological conditions, nutrient deficiencies or signs of infection. Multidisciplinary care is crucial to manage CHI with dasiglucagon, ensuring a comprehensive approach that addresses both glycemic control and potential side effects.

Keywords: congenital hyperinsulinism; dasiglucagon; necrolytic migratory erythema; neonatal hypoglycemia.

Figure 1

Clinical timeline, biomarker serum levels, weight by age and enteral nutritional status information. (A) Dots mark clinical events (empty) or refer to images (filled) in Fig. 2. Colored bars indicate periods. The x-axis denotes time in months. Following a diazoxide trial (orange bar), therapy with intravenous glucagon (green bar) and subcutaneous octreotide (blue bar) was initiated. In our observation, skin involvement (purple bar) was initially documented (e) a few weeks after the initiation of subcutaneous dasiglucagon (red bar), while the parents took notice of skin changes before this. Subcutaneous dasiglucagon was tapered (fading color) following sepsis (f). This was paralleled by a gradual improvement in the skin affection. Ultimately, a subtotal pancreatectomy was performed (g). (B) Serum zinc (blue), glutamine (red) and albumin (yellow) trajectories over time. Solid lines connect individual measurements, while dashed lines indicate reference ranges. Glutamine measurements are shown as an example of general amino acid levels. (C) Patient weight trajectory over time (green line), with the solid black line indicating the 50th percentile and solid gray lines representing the 5th, 25th, 75th and 95th percentiles of the reference population. (D) Enteral macronutrient intake and enteral calories per day during dasiglucagon treatment.

Figure 2

Clinical images. Clinical images refer to timepoints depicted in Fig. 1 and represent the clinical presentation before dasiglucagon treatment (A), during treatment (B), shortly before admission to the PICU (C) and shortly after subtotal pancreatectomy (D).