An Overview of Novel Therapies for Acute Hereditary Angioedema

Abstract

Hereditary angioedema is an episodic swelling disorder with autosomal dominant inheritance. Attacks are characterized by nonpitting edema of external or mucosal body surfaces. Patients often present with swelling of the extremities, abdominal pain, and swelling of the mouth and throat, which can at times lead to asphyxiation. The disease is caused by a mutation in the gene encoding the complement C1-inhibitor protein, which leads to unregulated production of bradykinin. Long-term therapy has depended on the use of attenuated androgens or plasmin inhibitors but in the US there was, until recently, no specific therapy for acute attacks. As well, many patients with hereditary angioedema in the US were either not adequately controlled on previously available therapies or required doses of medications that exposed them to the risk of serious adverse effects. Five companies have completed or are currently conducting phase III clinical trials in the development of specific therapies to terminate acute attacks or to be used as prophylaxis. These products are based on either replacement therapy with purified plasma-derived or recombinant C1-inhibitor, or inhibition of the kinin-generating pathways with a recombinant plasma kallikrein inhibitor or bradykinin type 2 receptor antagonist. Published studies thus far suggest that all of these products are likely to be effective. These new therapies will likely lead to a totally new approach in treating hereditary angioedema.

Effect of tranexamic acid on melasma: a clinical trial with histological evaluation

“…Tranexamic acid can decrease the activity of mast cells, for example, mast cell activation after ischaemia and reperfusion injury is almost completely abolished by TXA treatment 19,20 . In our study, the number of mast cells also decreased after TXA treatment.…”

“…18 Tranexamic acid can decrease the activity of mast cells, for example, mast cell activation after ischaemia and reperfusion injury is almost completely abolished by TXA treatment. 19,20 In our study, the number of mast cells also decreased after TXA treatment. These findings suggest that the effect of TXA may be partly due to its inhibitory effects on mast cells which may affect vascularization and dermopathy.…”

Perioperative Management for Patients with Hereditary Angioedema

“…20,21 Pain associated with gastrointestinal attacks is usually slowly progressive over a day and can last for three to five days. 22 Upper airway edema is documented by 50%-79% of patients and has an estimated 15%-33% mortality rate when untreated resulting most commonly from airway obstruction during laryngeal edema. [23][24][25][26] Studies show that asphyxiation can occur in 20 minutes to 14 hours after the onset of edema in patients, and it has occurred in patients with no previous history of respiratory symptoms nor previous angioedema.…”

Icatibant for the Treatment of Hereditary Angioedema

“…Hereditary angioedema (HAE) is a rare, potentially life-threatening autosomal dominant disease caused by C1 esterase inhibitor (CI-INH) deficiency. 1–4 HAE is characterized by recurrent edema of the skin (extremities, face, genitals); edema of the gastrointestinal track resulting in abdominal pain, nausea, vomiting, and diarrhea; and edema of the larynx. The prevalence of HAE is estimated to be between 1:10,000 and 1:50,000 in general populations.…”