1. Hereditary angioedema: an update on causes, manifestations and treatment
Hilary J Longhurst, Konrad Bork Br J Hosp Med (Lond) . 2019 Jul 2;80(7):391-398. doi: 10.12968/hmed.2019.80.7.391.
Hereditary angioedema is a rare genetic disorder caused by deficiency of C1 esterase inhibitor (C1-INH) and characterized by recurrent episodes of severe swelling that affect the limbs, face, intestinal tract and airway. Since laryngeal oedema can be life-threatening as a result of asphyxiation, correct diagnosis and management of hereditary angioedema is vital. Hereditary angioedema attacks are mediated by bradykinin, the production of which is regulated by C1-INH. Hereditary angioedema therapy relies on treatment of acute attacks, and short- and long-term prophylaxis. Acute treatment options include C1-INH concentrate, icatibant and ecallantide. Self-administration of treatment is recommended and is associated with increased quality of life of patients with hereditary angioedema. Advances in diagnosis and management have improved the outcomes and quality of life of patients with hereditary angioedema.
2. Icatibant for the treatment of hereditary angioedema
Lisa M Lundquist, Sabrina W Cole Ann Pharmacother . 2013 Jan;47(1):49-55. doi: 10.1345/aph.1R423.
Objective:To review the pharmacology, pharmacokinetics, clinical trials, and safety of icatibant, a recently approved bradykinin B(2) receptor antagonist for treatment of acute attacks of hereditary angioedema (HAE).Data sources:Articles indexed in MEDLINE (1948-June 2012), International Pharmaceutical Abstracts (1970-May 2012), and Cumulative Index to Nursing and Allied Health Literature (1981-June 2012) were identified using the search terms icatibant, bradykinin B(2) receptor antagonist, and hereditary angioedema. Additional references were identified from the reference lists of the articles identified.Study selection and data extraction:English-language articles were reviewed.Data synthesis:Icatibant was evaluated in 3 Phase 3 clinical trials and found to be a safe and effective option for treatment of acute HAE. Icatibant was compared to placebo in 2 clinical trials (FAST-1 and FAST-3) and to tranexamic acid in the FAST-2 trial. Patients receiving icatibant in FAST-1 did not experience a significant improvement in median time to clinically significant relief of the index symptom (p = 0.14), whereas patients receiving icatibant in FAST-3 experienced a significant improvement in median time to at least 50% reduction in symptom severity (p < 0.001). When icatibant was compared to tranexamic acid in FAST-2, the median time to clinically significant relief of the index symptom was shorter for patients receiving icatibant (p < 0.001). The most common adverse events associated with the administration of icatibant were injection-site reactions, which were mild to moderate and transient. These data suggest that icatibant is a safe and effective treatment for acute attacks of HAE. Although direct comparisons of recently approved alternatives for treatment of acute attacks are lacking, there are administration advantages of icatibant over other agents. Additionally, the cost of icatibant is comparable to that of the C1 esterase inhibitor Berinert and less expensive than ecallantide.Conclusions:Available efficacy data support that icatibant should be considered a safe and effective treatment for acute attacks of HAE. Additionally, limited treatment options for this rare condition, ease of administration, and comparable cost profile support its consideration for formulary inclusion.
3. ACE inhibitor-mediated angioedema
Vincenzo Montinaro, Marco Cicardi Int Immunopharmacol . 2020 Jan;78:106081. doi: 10.1016/j.intimp.2019.106081.
Angioedema (AE) occurring during ACE inhibitor therapy (ACEi-AE) is a rare complication involving between 0.1 and 0.7% of treated patients. AE can also complicate other therapeutic regimens that block the renin-angiotensin aldosterone system. Other drugs, such as immune suppressors, some type of antidiabetics or calcium antagonists, can increase the likelihood of ACEi-AE when associated to ACEi. There is a clear ethnic predisposition, since African-Americans or Hispanics show a higher prevalence of this condition compared to Caucasians. At least in African-Americans the genetic predisposition accounts for a general higher prevalence of AE, independently from the cause. People that experience ACEi-AE may have some recurrence when they are switched to an angiotensin-receptor blocker (ARB); however, epidemiological studies on large cohorts have shown that angiotensin receptor blockers (ARB) do not increase the likelihood of AE compared to other antihypertensives. Clinical manifestations consist of edema of face, lips, tongue, uvula and upper airways, requiring intubation or tracheotomy in severe cases. Attacks last for 48-72 h and require hospital admission in most cases. Intestinal involvement with sub-occlusive symptoms has also been reported. The pathogenesis of ACEi-AE depends mainly on a reduced catabolism and accumulation of bradykinin, which is normally metabolized by ACE. Genetic studies have shown that some single nucleotide polymorphisms at genes encoding relevant molecules for bradykinin metabolism and action may be involved in ACEi-AE, giving a basis for the ethnic predisposition. Treatment of ACEi-AE is still a matter of debate. Corticosteroids and antihistamines do not show efficacy. Some therapeutic attempts have shown some efficacy for fresh frozen plasma or C1 inhibitor concentrate infusion. Interventional studies with the specific bradykinin receptor antagonist icatibant have shown conflicting results; there might be a different ethnic predisposition to icatibant efficacy which has been proven in caucasian but not in black patients.
