Book Description

Background: Hereditary angioedema (HAE) due to C1-inhibitor deficiency, type I and II, is a rare disease with an estimated prevalence of 1/50,000. Angioedema in the larynx can be life threatening and angioedema in the abdomen and skin can give severe and disabling pain. Data on patients with HAE in Sweden were scarce before our study. Aim: To study the prevalence of HAE, and to investigate clinical manifestations, treatments, and Health-Related Quality of Life (HR-QoL) in adults and children in Sweden. Method: In studies, I and II, all patients received a written questionnaire followed by a phone interview with questions about clinical manifestations, medication, sick leave and QoL. In study III the patients completed EuroQol 5 Dimensions 5 Levels (EQ-5D-5L) questionnaires for both the attack-free state (EQ5D today), and the last HAE attack (EQ5D attack). Questions were also asked about sick-leave. In study IV all adults received questionnaires with EQ-5D-5L and RAND-36, Angioedema Quality of Life instrument (AE-QoL), and Angioedema Activity Score (AAS) form, and questionnaires on sick leave and prophylactic medication. Results: We identified 146 patients, 110 adults and 36 children with HAE, type I (n=136) or II (n=10), giving a minimal HAE prevalence of 1.54/100,000. For adults, the median age at onset of symptoms was 12 years and median age at diagnosis was 22 years. Median age at onset of symptoms for children was 4 years and at diagnosis 3 years. During the previous year, 47% of adults experienced at least 12 attacks, 21% 4-11 attacks, 11% 1-3 attacks, while 22% were asymptomatic. For children, the corresponding figures were about the same. The median number of attacks in those having attacks was 14 in adults and 6 in children last year. Adult females reported on average 19 attacks the previous year versus nine for males. Irrespective of location nine out of 10 reported pain. Trigger factors were experienced in 95 % of adults and 74 % of children. Plasma-derived C1-inhibitor concentrate (pdC1INH) had a very good effect on acute attacks. Long-term prophylaxis with androgens and pdC1INH reduced the annual attack frequency by more than 50 %. Of the children’s parents, 73% had been on parental leave to care for the child due to HAE symptoms. Health and QoL were generally rated as good. In study III 103 of 139 responded and reported an EQ5D today score that was significantly higher than the EQ5D attack score. Attack frequency had a negative effect on EQ5D today. Children had significantly higher EQ-5D-5L than adults. Forty four percent had been absent from work or school during the latest attack. In study IV 64 of 133 adults responded. The most affected HR-QoL dimensions in EQ-5D-5L were pain/discomfort and anxiety/depression, in RAND-36 energy/fatigue, general health, health transition, pain, and in AE-QoL fears/shame and fatigue/mood. Females had significantly lower HR-QoL in RAND-36 for general health and energy/fatigue. There was an association between AAS and EQ-5D-5L/RAND-36 (except physical function) /AEQoL. There was no significant difference in HR-QoL in patients with and without prophylactic medication. Conclusion: The minimal prevalence of HAE type I and II in Sweden is 1.54/100,000. Median age at onset was 12 years. Adult females had twice as many attacks as males, adults had also twice as many attacks as children. For acute treatment, pdC1INH had a very good effect. For long term prophylaxis, androgens and pdC1INH had good effect. The most affected HR-QoL dimensions in EQ-5D-5L were pain/discomfort and anxiety/ depression, in RAND-36 energy/fatigue, general health, health transition and pain, and in AE-QoL fears/shame and fatigue/mood. Children reported better HR-QoL than adults. AE-QoL is more disease-specific in HAE than the generic instruments EQ-5D-5L and RAND-36. However, the latter highlights the pain aspect, whereas AE-QoL does not. Patients with high disease activity should thus be considered for more intensive treatment to improve their HR-QoL.