A UK national audit of hereditary and acquired angioedema

Abstract

Hereditary angioedema (HAE) and acquired angioedema (AAE) are rare life-threatening conditions caused by deficiency of C1 inhibitor (C1INH). Both are characterized by recurrent unpredictable episodes of mucosal swelling involving three main areas: the skin, gastrointestinal tract and larynx. Swelling in the gastrointestinal tract results in abdominal pain and vomiting, while swelling in the larynx may be fatal. There are limited UK data on these patients to help improve practice and understand more clearly the burden of disease. An audit tool was designed, informed by the published UK consensus document and clinical practice, and sent to clinicians involved in the care of HAE patients through a number of national organizations. Data sets on 376 patients were received from 14 centres in England, Scotland and Wales. There were 55 deaths from HAE in 33 families, emphasizing the potentially lethal nature of this disease. These data also show that there is a significant diagnostic delay of on average 10 years for type I HAE, 18 years for type II HAE and 5 years for AAE. For HAE the average annual frequency of swellings per patient affecting the periphery was eight, abdomen 5 and airway 0·5, with wide individual variation. The impact on quality of life was rated as moderate or severe by 37% of adult patients. The audit has helped to define the burden of disease in the UK and has aided planning new treatments for UK patients.

Keywords: C1 esterase inhibitor, complement; SERPING1; acquired angioedema; hereditary angioedema; primary immunodeficiency; secondary immunodeficiency.

Figure 1

Pathways leading to the generation of bradykinin. C1 inhibitor (C1INH), in red, blocks the conversion of HMW kininogen to bradykinin while the effect of ACE inhibitors is to impede the breakdown of bradykinin. High molecular weight kininogen (HMW kininogen), bradykinin B2 receptor, angiotensin converting enzyme (ACE), angiotensin converting enzyme inhibitors (ACE inhibitors).

Figure 2

Distribution of responses from UK centres. The locations of the 14 centres across the United Kingdom are shown and the sizes of the circles are proportional to the numbers of data sets from each centre. Purple circles show centres returning adult patient data and blue where data from children were also submitted.

Figure 3

Hereditary angioedema (HAE) and acquired angioedema (AAE) diagnoses. The percentages of 376 patients within the different diagnostic categories.

Figure 4

Diagnostic delay. Diagnostic delay is shown with the number of years from the onset of symptoms to the time of diagnosis on the x-axis and the frequency in numbers of patients on the y-axis. Where patients have negative values this is due to a diagnosis being made before the onset of symptoms, usually because the diagnosis had been made previously in another family member, which was the case in 3·2% of the 249 patients.

Figure 5

Acute treatment and long-term prophylaxis. (a) Numbers of patients who have C1 inhibitor (C1INH) available at home, in accident and emergency departments or are taking C1INH prophylaxis (total 343). (b) Numbers of adult patients taking each of the currently available oral prophylactic medications (total 335). (c) Long-term prophylaxis in children. Numbers of paediatric patients taking each of the currently available oral prophylactic medications (total 37).

Figure 6

Analysis of annual peripheral, abdominal and airway attack frequency (total 323). (a) Peripheral attack frequency. (b) Abdominal attack frequency. (c) Airway attack frequency. The mean annual attack frequency is shown with individual patients on the x-axis and the frequency of attacks on the y-axis; s.d. (d) Average annual attack frequency. The mean overall attack frequency per patient per year at the three main sites of swelling.

Figure 7

Employment status. The numbers of patients represented in the different employment categories (total 213).

Figure 8

Comparison of the impact on quality of life in adults and children. (a) Impact on quality of life in adults. Patient's rating of the impact of the disease on their quality of life for adults (total 223). (b) Impact on quality of life in children. Parent's rating of the impact of the disease on their quality of life for children (total 29).