Hereditary angioedema (HAE) is a rare genetic disorder affecting about 1 in 67,000 individuals and may lead to increased morbidity and mortality.1,2 HAE is characterized by recurring episodes of subcutaneous and/or submucosal edema without urticaria due to an excess of bradykinin.2,3 Autosomal dominant inheritance is present in 75% of patients with HAE and is classified into 2 main types.2 Type I HAE is caused by deficiency of C1 esterase inhibitor, accounting for 85% of cases.2 Type II HAE is marked by normal to elevated levels of C1 esterase inhibitor but with reduced activity.2
Cutaneous and abdominal angioedema attacks are the most common presentation.1 However, any location may be affected, including the face, oropharynx, and larynx.1 Only 0.9% of all HAE attacks cause laryngeal edema, but 50% of HAE patients have experienced a laryngeal attack, which may be lethal.1 An angioedema attack can range in severity, depending on the location and degree of edema.3 In addition, patients with HAE often are diagnosed with anxiety and depression secondary to their poor quality of life.4 Thus, long-term prophylaxis of attacks is crucial to reduce the physical and psychological implications.
Previously, HAE was treated with antifibrinolytic agents and attenuated androgens for short- and long-term prophylaxis.1 These treatment modalities are now considered second-line since the development of novel medications with improved efficacy and limited adverse effects (AEs).1 For long-term prophylaxis, subcutaneous and IV C1 esterase inhibitor has been proven effective in both types I and II HAE.1 Another option, lanadelumab, a subcutaneously delivered monoclonal antibody inhibitor of plasma kallikrein, has been proven to decrease the frequency of HAE attacks without significant AEs.5 Lanadelumab works by binding to the active site of plasma kallikrein, which reduces its activity and slows the production of bradykinin.6 This results in decreasing vascular permeability and swelling episodes in patients with HAE.7 Data, however, are limited, specifically regarding patients with type II HAE and patients aged ≥ 65 years.5 This article reports on an older male with type II HAE successfully treated with lanadelumab.
Case Presentation
An 81-year-old male patient with hypertension, hypertriglyceridemia, and aortic aneurysm had recurrent, frequent episodes of severe abdominal pain with a remote history of extremity and scrotal swelling since adolescence. He was misdiagnosed for years and was eventually determined to have HAE at age 75 years after his niece was diagnosed, prompting him to be reevaluated for his frequent bouts of abdominal pain. His laboratory findings were consistent with HAE type II with low C4 (7.8 mg/dL), normal C1 esterase inhibitor levels (24 mg/dL), and low levels of C1 esterase inhibitor activity (28% of normal).
Initially, he described having weekly attacks of abdominal pain that could last 1 to several days. At worst, these attacks would last up to a month, causing a decrease in appetite and weight loss. At age 77 years, he began an on-demand treatment, icatibant, a bradykinin receptor blocker. After initiating icatibant during an acute attack, the pain would diminish within 1 to 2 hours, and within several hours, he would be pain free. Previously, pain relief would take several days to weeks. He continued to use icatibant on-demand, typically requiring treatment every 1 to 2 months for only the more severe attacks.
After an increasing frequency of abdominal pain attacks, prophylactic medication was recommended. Therefore, subcutaneous lanadelumab 300 mg every 2 weeks was initiated for long-term prophylaxis. The patient went from requiring on-demand treatment 2 to 3 times per month to once in 6 months after starting lanadelumab. In addition, he tolerated the medication well without any AEs.