Q:

5/30/2013
I have a 77 year-old male who developed severe angioedema of his lips and tongue which lasted 48 hours despite antihistamines and epi and required hospital admission. He also had generalized urticaria at the time as well with hives coming on and off lasting 48 hours as well. He had no food exposures within 12 hours, no stings, no new drugs. He is on an ACE inhibitor for past 10 years. My question is can I safely rule out ACE inhibitor induced angioedema since he also had urticaria? In other words, does ACE inhibitor angioedema always occur without urticaria?

A:

Thank you for your inquiry.

You are absolutely correct that, characteristically, angioedema due to an ACE inhibitor is not associated with urticaria. However, quite interestingly, polymorphisms of the angiotensin-converting enzyme gene has been associated with angioedema occurring in the presence of urticaria, albeit chronic urticaria. (see abstract copied below).

In addition, although it violates the principle of clinical parsimony, one could not be sure that this patient’s urticaria and angioedema were due to the same process, and therefore I do not think you could rule out that the angioedema could at least have been worsened by, if not caused by, the ACE inhibitor. For these reasons, I would be reluctant to continue the ACE inhibitor in your patient.

Thank you again for your inquiry and we hope this response is helpful to you.

Association of insertion/deletion polymorphism of the angiotensin-converting enzyme gene with angio-oedema accompanying chronic urticaria but not chronic urticaria without angio-oedema or the autologous serum skin test response. Abstract Association of insertion/deletion polymorphism of the angiotensin-converting enzyme gene with angio-oedema accompanying chronic urticaria but not chronic urticaria without angio-oedema or the autologous serum skin test response.

Chronic Background urticaria is defined as the daily or almost daily occurrence of weals for more than 6 weeks. The underlying pathophysiology is reported to be mast cell activation, with release of mast cell mediators, predominantly histamine. Substance P is a neuropeptide and has the capacity to provoke histamine release from skin mast cells. Angiotensin-converting enzyme (ACE), widely expressed in skin, is one of the major peptidase for the degradation of substance P. An insertion/deletion polymorphism (I/D) in the ACE gene has been reported to be related to the levels of enzyme.

An increase in substance P levels due to an:
Objective: polymorphism in ACE gene might be related to the pathology. Thus, we aimed to investigate whether there is an association between ACE I/D polymorphism and chronic ordinary urticaria.
Methods: Ninety-five patients with chronic ordinary urticaria were recruited and divided into two groups according to autologous serum skin test status and accompanying angio-oedema. One hundred and sixty-one healthy subjects were enrolled as control group. All participants were genotyped for I/D polymorphism in intron 16 of the ACE gene by polymerase chain reaction.
Results: A statistically significant association was not found between ACE I/D  polymorphism and chronic ordinary urticaria. Further analyses of chronic ordinary urticaria patients showed that ACE I/D polymorphism was not associated with autologous serum skin test status of patients. However, the frequencies of II genotype and I allele were statistically significantly higher in chronic ordinary urticaria patients with accompanying angio-oedema with regard to angio-oedema-negative patients (II genotype: 24% vs. 9%, P = 0.0002; I allele: 58% vs. 27%, P = 0.0001) and control group (II genotype: 24% vs. 19%, P = 0.01; I allele: 58% vs. 41%, P = 0.03).
Conclusion: No evidence of an association between ACE I/D polymorphism and risk of developing chronic ordinary urticaria. However, it can be a contributing factor to susceptibility of angio-oedema in chronic ordinary urticaria.

Sincerely,
Phil Lieberman, M.D.

AAAAI - American Academy of Allergy Asthma & Immunology