Physiology of ACEI-AAG
A brief word on diagnosis
- Lack of allergic trigger (in contrast, ACEI-AAG may occur after minor trauma)
- Starts with focal swelling (e.g. isolated swelling of tongue or lips, often asymmetric)
- Evolves over hours (slower progression than histamine-mediated angioedema)
- Absence of urticaria or itching
- Failure to respond to antihistamines, steroid, epinephrine
Steroids, antihistamines, and epinephrine are ineffective for ACEI-AAG.
As with management of acute angioedema in patients with C1-inhibitor deficiency, administration of antihistamines, corticosteroids, or epinephrine is not associated with benefit and is not recommended
– International consensus on hereditary and acquired angioedema, Lang 2012.
Disease-modifying treatments: Fresh Frozen Plasma (FFP), Icatibant (FIRAZYR), C1-inhibitor concentrate
Purified C1-inhibitor concentrate has been effective in case reports (Nielsen 2006). This agent appears to be more popular in Europe, with inclusion in the French guidelines for management of ACEI-AAG (Nosbaum 2013). Only one case report describing the use of C1-inhibitor concentrate exists in the English literature. Currently the evidence supporting FFP appears more robust, but there is an ongoing phase III study of C1-inhibitor concentrate so this may change (NCT01843530).
Recent Bas et al. study compares Icatibant vs. Steroid/Antihistamine
Industry-driven research agenda
- Angioedema due to ACE inhibitors (ACEI-AAG) may be life-threatening, and will probably become more common with expanding use of ACE inhibitors.
- ACEI-AAG is due to excessive bradykinin. This is not responsive to treatments for allergic angioedema (e.g., epinephrine, steroid, antihistamines).
- Until recently, case reports suggested that fresh frozen plasma (FFP) or Icatibant may be effective for ACEI-AAG. FFP contains enzymes which metabolize bradykinin, whereas Icatibant blocks bradykinin receptors (figure above).
- Bas et al. performed a prospective RCT comparing Icatibant to steroid/antihistamine. As expected, Icatibant was superior.
- Icatibant is extremely expensive and not widely available. Alternatively, FFP is universally available at a fraction of the cost. Further information is needed to determine the relative efficacy of these therapies.
- If Icatibant is unavailable, consider early administration of 2-4 units FFP.