Answer Clinical Challenge 4

The correct answer is Hereditary Angioedema (HAE Type III)

Many congratulations to Ed Giles, Arun Urs, Kornilia Nikaki and Dominic Dell Olio, for getting the correct answer.

Self-remitting abdominal pain without clear organic aetiology that is recurrent and lasts >6 hours is a clinical criterion for HAE defined by the European working group (Hereditary and acquired angioedema: problems and progress: proceedings of the third C1 esterase inhibitor deficiency workshop and beyond. J Allergy Clin Immunol. 2004;114:S51–S131). This patient had experienced an episode of a facial angioedema some years ago. On further exploring, it was known that other family members had history of facial angioedema, partially associated with angiotensin converting enzyme inhibitor intake.

HAEs are subdivided into 3 types: Type I HAE is characterized by low levels and reduced functional tests of C1 esterase inhibitor, whereas type II HAE shows normal levels but reduced function of C1 esterase inhibitor. Type III HAE, which affects nearly exclusively females in an oestrogen-dependent fashion (precipitation or worsening of symptoms during pregnancy, treatment with oral contraceptives, or hormonal replacement therapy) shows normal levels as well as normal function of C1 esterase inhibitor. The oestrogen dependency is explained by the fact that the expression of FXII is increased by oestrogens via oestrogen-responsive elements in the promoter region.

This patient, C3 and C4 levels as well as the level of C1 esterase inhibitor in functional testing were normal. Thus, the diagnosis was hereditary angioedema with normal C1 inhibitor levels. The patient improved spontaneously after symptomatic therapy within 2 days. Avoidance of oestrogen-containing oral contraceptives was recommended and no episodes were observed in the next several months. A clinical relapse after 6 months was again associated with the intake of an oral contraceptive.