The influence of trigger factors on hereditary angioedema due to C1-inhibitor deficiency

Abstract

BackgroundHereditary angioedema (HAE) resulting from C1-inhibitor deficiency is characterized by attacks of subcutaneous and submucosal edema. Many factors have been presumed to induce edema. Our study analyzed these factors in a fairly large patient population.MethodsIn the first stage of our study, we analyzed the data recorded by 92 subjects in their patient diaries over seven years. The second phase included 27 HAE patients, who had been completing the diary entry ‘Trigger factors’ every day for seven months whether or not they had experienced an attack.ResultsDuring the initial stage, 91% of the subjects described some factor possibly related to the onset of an attack. They could identify a trigger factor – most commonly (21%) mental stress – in 30% of the 3176 attacks. We found a significant (p < 0.001) difference in the distribution of the trigger factors of the edematous attacks of different locations. The 27 participants of the second phase identified 882 potential trigger factors and recorded 365 attacks. Of these, 246 (67%) occurred on days when the patients identified a potential trigger factor. The likelihood of edema-formation associated with the latter was as follows: menstruation – 63%, infection – 38%, mental stress – 26%, physical exertion – 25%, meteorological changes – 21%, fatigue – 17%.ConclusionThis analysis of the trigger factors explored, for the first time, their potential role in inducing HAE attacks. Our findings might open new perspectives in extending the indications for edema-prophylaxis, and could contribute to a better understanding of the pathomechanism of HAE attacks.

International consensus on the diagnosis and management of pediatric patients with hereditary angioedema with C1 inhibitor deficiency

“…A multitude of factors may trigger edematous episodes in C1‐INH‐HAE at any age 33. In children, most attacks occur without a clear trigger.…”

“…These agents should be avoided in C1‐INH‐HAE patients of all ages whenever possible 14, 31, 33, 35, 36. In some cases, attacks can be prevented through counseling, lifestyle changes, and by avoiding triggering factors, most specifically contact sports and other activities involving physical tissue trauma.…”

Multiple roles of complement MASP-1 at the interface of innate immune response and coagulation

“…Bradykinin, a vasoactive pro-inflammatory peptide, has an unquestionable role in hereditary angioedema (HAE), however, several types of triggering factors are needed to provoke edematous attacks (Zotter et al, 2014). Microbial infection, trauma and menstruation are three well known triggering factors of HAE attacks.…”

A danazolkezelés hatása C1-inhibitor-hiány okozta hereditaer angiooedemás gyermekek növekedésére

“…Ez bradikinin felszabadulásához és az érpermeabilitás fokozódásához vezet, ily módon angiooedema alakulhat ki a subcutan szövetekben (például a végtagokon, az arcon, a nyakon, a törzsön és a nemi szerveken) és/vagy a submucosában (a gyomor-bél csatornában és a felső légutakban) [2,3]. A C1-INH-HAE ellátása az angiooedemás epizódok akut kezeléséből, a kiváltó tényezők kiküszöböléséből [4], továbbá rövid és/vagy hosszú távú profilaxisból áll [5]. Az oedemás epizódok akut kezelésére a bradikinin felszabadulását gátló gyógyszerek, például humán plazmából előállított, nanofiltrált C1-INH-(pdC1-INH) koncentrátum [6,7], rekombináns humán C1-INH (rhC1-INH) [8] és a kallikreingátló ecallantide [9] alkalmazhatók.…”