D1.383 - Nonimmediate hypersensitivity reaction to Lanadelumab in a patient with Hereditary Angioedema: a case report

Hereditary angioedema (HAE) is a rare genetic disease that involves a deficiency or disfunction of C1 inhibitor, which leads to the overproduction of bradykinin and activation of bradykinin B2 receptors. Currently, lanadelumab is one of the first-line treatments for long-term prophylaxis (LTP) of HAE. 

Secondary effects of lanadelumab are local reactions (usually mild), antilanadelumab antibodies (2.8% with neutralizing antibodies, but without any perceptible clinical impact) and increased activated partial thromboplastin time. So far, no cases of delayed hypersensitivity reaction (DHR) induced by lanadelumab have been reported. 

A 47-year-old man with history of HAE due to C1-INH deficiency starts LTP with lanadelumab 300 mg every 2 weeks in September 2024. Following the third dose, he developed a well-defined erythematous and pruritic plaque that measured 12x15 cm at the injection site 24 hours after the administration. They lasted up to 2 weeks with residual hyperpigmentation and progressive expansion (Figure 1A). The same lesion appeared after the following dose (Figure 1B). Six weeks after the second reaction, skin tests were performed with lanadelumab and polysorbate 80 with delayed readings al 48 and 96 hours. Histologic findings were obtained from a skin punch.

Patch tests were negative at 48 and 96 hours. Intradermal test was positive at 1:10 dilution of lanadelumab at the 48 hours reading (Figure 2). The histologic features showed lymphocytes at the epidermodermal junction and within the epidermis, disrupting the interface. The dermis showed predominantly superficial and deep perivascular lymphocytic infiltrate with variable number of eosinophils. (Figure 3). 

We present the first case of DHR due to lanadelumab confirmed by an intradermal test with a positive delayed reading and skin biopsy. According to this case report, clinicians should be aware of this unusual reaction to this drug. It is important to study and report large local reactions with unusual appearance.