1/5

REVIEW ARTICLE

Patient-reported Outcome Measures for Angioedema: A Literature

ActaDV

Review
Anna Trier Heiberg BRIX1, Henrik Balle BOYSEN2, Karsten WELLER3, Teresa CABALLERO4–6 and Anette BYGUM7,8
1
Faculty of Health Science, University of Southern Denmark, Odense, 2HAE International (HAEi), Horsens, Denmark, 3Department of
Dermatology and Allergy, Comprehensive Allergy Centre Charité, Charité – Universitätsmedizin Berlin, Berlin, Germany, 4Allergy Department,
Hospital Universitario La Paz, 5Hospital La Paz, Institute for Health Research (IdiPaz), 6Center for Biomedical Research Network on Rare
Diseases (CIBERER U754), Madrid, Spain, 7Department of Clinical Research, Faculty of Health Science, University of Southern Denmark and
8
Department of Clinical Genetics, Odense University Hospital, Odense, Denmark
Acta Dermato-Venereologica

Angioedema and hereditary angioedema are characte-

rized by swelling of the subcutaneous and/or submu-
SIGNIFICANCE
cosal tissue, resulting in localized oedema. The rarity, This article reviews the patient-reported outcome measu-
but also the diverse clinical presentation, of these con- res available for angioedema and hereditary angioedema,
ditions can be challenging regarding diagnosis, tre- and assesses their availability in the Nordic languages.
atment, and management. Patient-reported outcome Patient-reported outcome measures have immense possi-
measures (PROMs) are data received directly from the bilities when used consistently and systematically in clini-
patient, providing the patient’s perspective on various cal practice, ultimately providing patients with better, and
subjects regarding health and well-being. PROMs can more personalized, care. This review provides an overview
be helpful tools to optimize treatment and long-term of clinically relevant PROM tools for angioedema and here-
management of conditions. A major challenge regard­ ditary angioedema and where they can be accessed.
ing the consistent use of PROMs in clinical settings in
Scandinavia is language availability; many of the vali­
dated PROMs for hereditary angioedema and angi-
urticaria can be treated with antihistamines, while non-
oedema lack translations into the Nordic languages.
responders to high-dose antihistamines often benefit
The litterature search yielded 9 different PROM tools from omalizumab as long-term prophylaxis (6, 7). Acute
for angioedema and hereditary angioedema. Five were attacks of bradykinin-mediated AE can be treated with
icatibant, which is a bradykinin B2 receptor antagonist, or
ActaDV

found suitable for use in clinical practice in Europe.

Even though several PROMs exist they are not used complement C1-inhibitor (C1-INH) concentrates, which
consistent. Accessible electronic PROMs and careful are advanced orphan drugs licensed for use in hereditary
planning is required to implement PROMs optimally in angioedema (HAE) (5, 8, 9). Long-term prophylactic
routine care processes. treat­ment is indicated in severe cases, mostly patients
Key words: hereditary angioedema; angioedema; patient-re-
with HAE. Prophylactic treatments of bradykinin-
ported outcome measure. mediated AE include complement C1-inhibitor concen-
trates, or lanadelumab, which is a human monoclonal
Accepted Mar 10, 2021; Epub ahead of print Apr 21, 2021
antibody targeted against plasma kallikrein (8, 9). Addi­
Advances in dermatology and venereology

Acta Derm Venereol 2021; 101: adv00456. tional drugs for the treatment of patients with HAE are
Corr: Anna Trier Heiberg Brix, Faculty of Health Science, University of the kallikrein inhibitors ecallantide and berotralstat, but
Southern Denmark, DK-5000 Odense, Denmark. E-mail: anbri14@stu- these are not yet available in Europe.
dent.sdu.dk
HAE is a rare genodermatosis with potentially life-
threatening swelling attacks (8–10). The pathogenesis

A ngioedema (AE) is a clinical symptom characte-

rized by self-limiting swellings of subcutaneous
or submucosal tissue, resulting in localized, often non-
of HAE types I and II is related to extensive bradykinin
release due to deficiency or lack of function of C1-INH.
HAE with C1-INH deficiency is associated with disease-
pitting, oedema. The swellings are unpredictable, and causing variants in the SERPING1 gene. A more recently
the frequency, location and severity of swellings vary described subtype of HAE is HAE with normal C1-INH,
between patients and intra-individually (1, 2). AE de- in which mutations in genes encoding factor XII, angio­
velops over several hours and resolves spontaneously poietin, plasminogen, myoferlin and kininogen-1 have
within a few days if not treated. The typical locations are been identified in some patients (11, 12).
face, lips, tongue, extremities, genitalia, upper airways The severity and unpredictable pattern of diseases
or abdomen (3, 4). with recurrent AE, along with painful and often disabling
AE can be accompanied by wheals, or may be pri- swellings, results in impaired health-related quality of life
mary (monosymptomatic) AE without wheals (3, 5). (HRQoL), which describes the patient’s emotional, social
The swelling is a consequence of increased vascular and physical well-being (13–16). Patients may have, or
permeability induced by different vasoactive mediators, may develop, anxiety and depression as important as-
such as histamine or bradykinin. Histaminergic AE and sociated disorders (17, 18).

This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta doi: 10.2340/00015555-3807
Society for Publication of Acta Dermato-Venereologica Acta Derm Venereol 2021; 101: adv00456
 2/5 A. Trier Heiberg Brix et al.

PATIENT-REPORTED OUTCOME MEASURES Angioedema tools

Validated instruments developed for AE are the Angioedema Acti-
ActaDV

In recent years there has been an increased focus on

vity Score (AAS) (21), Angioedema Quality of life Questionnaire
patients’ perspectives on their health and well-being, (AE-QoL) (22), and the Angioedema Control Test (AECT) (23)
recorded with the help of PROMs (19). PROMs capture (Table I). These instruments can be used in all forms of recurrent
data directly from the patient, without interference from AE, including HAE.
the physician (or any other healthcare professional). The AAS is a short daily, diary-type questionnaire that prospec-
tively assesses daily AE activity and can be performed in less than
They provide useful knowledge about the patients’ 1 min. If AE is present, the patient needs to answer 5 additional
own assessment of their disease situation, which can questions, each scored 0–3. Cumulative data from 4 consecutive
be used to improve disease activity, disease control and weeks provides a valid assessment of disease activity (21). The
HRQoL, enhance patient–physician communication and AAS has been translated into all Nordic languages.
Acta Dermato-Venereologica

thereby possibly increase patient satisfaction (19, 20). The AE-QoL is a short 17-item questionnaire designed to
retro­spectively assess HRQoL, with a recall period of 4 weeks.
PROMs can also be important target parameters to tailor Its results can be displayed as a total score or as 4 domain scores.
individual treatment needs and refine management of The scores each range from 0 to 100, after linear transformation
conditions. When used repetitively in the same patients, of raw values (22), with higher scores indicating higher HRQoL
PROMs can also improve the assessment of treatment impairment. Linguistically validated versions of the AE-QoL are
effectiveness. Finally, PROMs are important outcome available in Danish, Swedish, and Finnish.
The patient organization HAE Scandinavia has translated AAS
measures in clinical trials. and AE-QoL to Icelandic. However, the Icelandic versions are
The potential of a structured and consistent use of not yet validated.
PROMs to monitor, evaluate and optimize treatment and The AECT monitors disease control retrospectively, with a
HRQoL is promising, but requires work and appropriate recall period of 4 weeks or 3 months. The validation shows that
the results are largely similar between the 4-week and the 3-month
management of workflow to implement in clinical routine. recall period, and the physicians can choose which recall period
For patients with AE or HAE, 6 different outcome tools suits the individual setting (24). The AECT comprises 4 questions,
have recently become available, as reported below. is quick to complete, and can be used easily in clinical practice
as a routine tool to monitor disease control (23, 24). The AECT
is available in Danish and Swedish, and a translation process to
METHODS Norwegian is currently ongoing.
The AAS, AE-QoL and AECT are all available to physicians
This is a narrative review. A literature search for published data free-of-charge (from www.moxie-gmbh.de).
ActaDV

regarding PROMs for AE and HAE was performed in PubMed,

with the following terms “hereditary angioedema”, “angioedema”,
“HAE”, “oedema” both alone or combined with “patient-reported Hereditary angioedema specific tools
outcomes”, “PROMs”, “PROM”, “health-related quality of life” HAE-specific validated PROMs include the Hereditary Angioede-
and “HRQoL”. Studies using only generic tools, such as Eu- ma Activity Score (HAE-AS) (25) and Hereditary Angioedema
roQoL5, SF12, SF36 or VAS scale, were excluded. Studies using Quality of Life (HAE-QoL) (26).
non-validated, study-specific questionnaires to access PROMs The HAE-AS is a retrospective questionnaire with 12 questions
were also excluded. Nine different HAE/AE-specific tools were assessing disease activity, with a recall period of 1 month for 2
found, described in 9 articles (21–29), and 2 reviews of PROMs questions and 6 months for the remaining 10 questions (25).
for HAE with a different focus (15, 16). The start date was June The HAE-QoL is a retrospective questionnaire with a recall
Advances in dermatology and venereology

5, 2020, and end date of the search was November 2020. period of 6 months. It contains 25 questions grouped into 7 cate-

Table I. Patient-reported outcome measures (PROMs) for recurrent angioedema

AAS AE-QoL AECT HAE-AS HAE-QoL

Validated Yes Yes Yes Yes Yes
Time requirement, min <1 <5 <5 <5 <5
Data collection Daily prospectively 4-week recall period 4-week or 3-month recall 1-month and 6-month 6-month recall period
period recall period
Number of questions 1 if no attack. 6 if attack. 17 4 12 25
Score 0–15 0–100 0–16 0–29 25–135
Dimensions 1 4 1 1 7
Designed for Adultsa with recurrent Adultsa with recurrent AE Adultsa with recurrent AE Adultsa with HAE and Adultsa with HAE and C1-
angioedema (AE) C1-INH deficiency INH deficiency
Measures Disease activity HRQoL Disease control Disease activity HRQoL
Administered Self-administered Self-administered Self-administered Self-administered Self-administered
questionnaire questionnaire questionnaire questionnaire questionnaire
Available in the following Danish, Finnish, Norwegian, Danish, Swedish, Finnish, Danish, Swedish, Danish Danish
Nordic languages Swedish, Icelandicb Icelandicb Norwegianc
Distributed by MOXIE – https://moxie- MOXIE – https://moxie- MOXIE – https://moxie- DV-HAE-QoL Study DV-HAE-QoL Study Group.
gmbh.de gmbh.de gmbh.de Group. Bibliopro.orgd Bibliopro.orgd
a
>18 years. bTranslation was performed by patient organization HAE Scandinavia (but not linguistically validated). cStructured translation process is ongoing, linguistically
validated version will be available shortly. dFoundation of Biomedical Research of La Paz University Hospital-IdiPAZ (FIBHULP) holds the copyright.
AAS: Angioedema Activity Score; AE-QoL: Angioedema Quality of life Questionnaire; AECT: Angioedema Control Test; HAE-AS: Hereditary Angioedema Activity Score;
HAE-QoL: Hereditary Angioedema Quality of Life.

www.medicaljournals.se/acta
 Patient-reported outcome measures for angioedema 3/5

gories, assessing treatment difficulties, physical functioning and only in printed form. The paperwork and the time needed
health, disease-related stigma, emotional role and social functio- to complete the questionnaires can be a challenge to fit
ActaDV

ning, concern about offspring, perceived control over illness and

mental health (26).
into the daily life of patients and time-consuming for
HAE-AS and HAE-QoL were developed in Spain and have treating physicians. Thus, electronic versions could be
limited Nordic language availability. HAE-QoL is available a better way of collecting PROMs (36). Digitizing the
in 18 languages, with Danish being the only Nordic language. questionnaires, making it fast, easy to use, and available
HAE-QoL is available to physicians free-of-charge (from www. on the patients preferred device, is key to unlocking the
bibliopro.org/).
The Hereditary Angioedema Patient Reported Outcome (HAE value of PROMs, as useful tools in managing and opti-
PRO) (27), was developed for use in the Icatibant outcome study. mizing patient care.
In contrast to the other tools described, HAE-PRO is completed Another important issue is the language in which the
Acta Dermato-Venereologica

when the patient has an attack of HAE. After e-mail correspon- PROMs are available. Five questionnaires are available
dence with Shire/Takeda, we were not able to access the HAE in Danish, 3 out of 5 are available in Swedish, 2 out of
PRO, and the tool is not described further here.
Physicians in the USA may use the Hereditary Angioedema As- 5 are available in Finnish, but only the AAS is available
sociation (HAEA-QoL) questionnaire. Since this tool is developed in all Nordic languages; however, it is not linguistically
specifically for the medical system in the USA, it is not described validated in Icelandic. Translation and cultural adaption
further here (28). can be a time-consuming process (37–40). It is recom-
The Mean Symptom Complex Severity (MSCS) and the Treat-
mended to follow a structured process of forward and
ment Outcome Score (TOS) (29) are disease-specific, validated
tools, which provide a composite score regarding the severity of backward translation, followed by pre-testing of the
an attack at a given time (e.g. baseline, prior to administration of instrument and cognitive interviewing (cognitive debrie-
a study medication, time-period after drug administration) and fing). Reconciliation, cognitive debriefing and validation
the treatment response (TOS). The tools have been used only for ensure that the meaning and function of the PROM is
ecallantide, and are therefore not ideal for regular monitoring of
patients with HAE. The tools are complex and not suitable for
not lost during the translation process (38, 39). Each
routine use in clinical practice; therefore they are not described country may also need PROMs in languages other than
in detail here. their national language. For example, the Danish HAE
Centre serves patients from Germany, Norway, Portugal,
Hungary, Turkey, Syria and Pakistan (41); hence, to be
DISCUSSION successful with the use of the PROM tools in the entire
patient group, the range of language availability needs to
ActaDV

Diagnosis, management and treatment of AE can be com-

plicated, as AE includes several subtypes with different be expanded. Cultural adaption, along with translation,
pathophysiological backgrounds. Management of HAE is often necessary to ensure that the aim is conserved in
is a lifelong and challenging process, involving many translation, via scaling or replacing items to ensure that it
factors, including hereditary aspects. Several advanced is equivalent relevant and valid in a new culture (38–40).
orphan drugs are licensed for use in HAE and should be Each country differs in terms of how the medical system
used conscientiously in patient care, primarily with a fo- is organized, which is why the USA use their own QoL
cus on efficacy and safety, but also with a regard to drug tool for patients with HAE (28).
expense (30, 31). In order to individualize and optimize If used correctly and consistently as a monitoring tool,
Advances in dermatology and venereology

treatment of HAE, physicians need information not only it is expected that PROMs will help the refine indivi-
on the severity and frequency of attacks, but also on the dual treatment and may also reduce the annual cost of
impact of the disease on patients’ lives. The divergence medication per patient, by enabling a better overview of
in how physicians and patients with chronic illnesses treatments that provide “value for money”.
understand disease severity and activity is well known In April 2020 the Global Allergy and Asthma European
(16). To our knowledge, no disease-specific PROM for Network (GA2LEN) and HAE International (HAEi) laun-
angioedema exists for children (<18 years old). HRQoL ched a new concept: Angioedema Center of Reference
have been investigated in children with HAE (32, 33), and Excellence (ACARE), with inspiration from other
with the generic Pediatric Health-Related Quality of Life successful GA2LEN networks. To certify as an ACARE
4.0 Generic Core scales (34), with diverse results (32, unit, a total of 32 requirements in 5 domains must be
33). In addition, a children’s version of the Dermatology fulfilled (42). The use of PROMs is highlighted and, in
Life Quality Index (DLQI) is available and may be app- order to successfully certify as an ACARE centre, docu-
lied in children with recurrent AE (35). mentation of consistent use of at least 1 tool in 80% of
In order to personalize treatment, it is meaningful to the patients with recurrent AE must be present.
monitor disease activity, disease control and HRQoL on a In addition, valuable information is collected through
consistent basis. It is also important to integrate PROMs PROMs, which can be used in general quality improve-
into the electronic medical health record. The AECT has ment and research.
recently been approved in an electronic version (in Ger- In conclusion, PROMs for use in monitoring and
man), but the rest of the tools described here are available managing patients with HAE have been developed

Acta Derm Venereol 2021

 4/5 A. Trier Heiberg Brix et al.

and validated, but are not yet used on a regular basis in 12. Ariano A, D’Apolito M, Bova M, Bellanti F, Loffredo S, D’Andrea
G, et al. A myoferlin gain-of-function variant associates with
the management of HAE in the Nordic countries. The
ActaDV

a new type of hereditary angioedema. Allergy 2020; 75:

potential use of PROMs in the clinic setting has a wide 2989–2992.
range of benefits, both for patients and for the healthcare 13. Aabom A, Andersen KE, Perez-Fernández E, Caballero T,
Bygum A. Health-related quality of life in Danish patients
system. However, planning is required regarding how to with hereditary angioedema. Acta Derm Venereol 2015;
implement PROMs optimally in the local routine care 95: 225–226.
processes, preferably as an electronic version that is 14. Nordenfelt P, Nilsson M, Lindfors A Wahlgren CF, Björkander
J. Health-related quality of life in relation to disease activity
easily accessible for patients. in adults with hereditary angioedema in Sweden. Allergy
Asthma Proc 2017; 38: 447–455.
15. Caballero T, Prior N. Burden of illness and quality-of-life
ACKNOWLEDGEMENTS measures in angioedema conditions. Immunol Allergy Clin
Acta Dermato-Venereologica

North Am 2017; 37: 597–616.

Conflicts of interest. ATHB has been involved in teaching activities 16. Bygum A, Busse P, Caballero T, Maurer M. Disease severity,
for CSL Behring. HBB reports no conflicts of interest. KW reports activity, impact and control and how to assess them in pa-
grants from Shire, non-financial support from Moxie, during the tients with hereditary angioedema. Front Med 2017; 4: 212.
conduct of the included study; personal fees from Novartis, per- 17. Caballero T, Aygören-Pürsün E, Bygum A, Beusterien K, Hau-
tamaki E, Sisic Z, et al. The humanistic burden of hereditary
sonal fees from Moxie, personal fees from Shire/Takeda, personal
angioedema: results from the Burden of Illness Study in
fees from BioCryst and personal fees from CSL Behring, outside Europe. Allergy Asthma Proc 2014; 35: 47–53.
the submitted work. TC reports personal fees and other from 18. Fouche AS, Saunders EF, Craig T. Depression and anxiety in
BioCryst, personal fees, non-financial support and other from patients with hereditary angioedema. Ann Allergy Asthma
CSL-Behring, personal fees from Merck, personal fees and other Immunol 2014; 112: 371–375.
from Novartis, personal fees from Octapharma, personal fees, 19. Nelson EC, Eftimovska E, Lind C, Hager A, Wasson JH, Lind-
non-financial support and other from Shire HGT, personal fees and blad S. Patient reported outcome measures in practice. BMJ
other from Pharming NV, outside the submitted work. AB reports 2015; 350: g7818.
grants and other from CSL Behring, grants and other from Shire/ 20. Santana MJ, Feeny D. Framework to assess the effects of
using patient-reported outcome measures in chronic care
Takeda, other from ViroPharma, from HAE Scandinavia, outside
management. Qual Life Res 2014; 23: 1505–1513.
the submitted work. 21. Weller K, Groffik A, Magerl M, Tohme N, Martus P, Krause
K, et al. Development, validation, and initial results of the
Angioedema Activity Score. Allergy 2013; 68: 1185–1192.
REFERENCES 22. Weller K, Groffik A, Magerl M, Tohme N, Martus P, Krause K, et
al. Development and construct validation of the angioedema
1. Rye Rasmussen EH, Bindslev-Jensen C, Bygum A. Angi- quality of life questionnaire. Allergy 2012; 67: 1289–1298.
ActaDV

oedema – assessment and treatment. Tidsskr Nor Laegeforen 23. Weller K, Donoso T, Magerl M, Aygören-Pürsün E, Staubach
2012; 132: 2391–2395. P, Martinez-Saguer I, et al. Development of the Angioedema
2. Belbézier A, Bocquet A, Bouillet L. Idiopathic angioedema: Control Test – a patient-reported outcome measure that as-
current challenges. J Asthma Allergy 2020; 13: 137–144. sesses disease control in patients with recurrent angioedema.
3. Pall AH, Lomholt AF, von Buchwald C, Bygum A, Rasmussen Allergy 2020; 75: 1165–1177.
ER. Clinical features and disease course of primary angi- 24. Weller K, Donoso T, Magerl M, Aygören-Pürsün E, Staubach
oedema patients in a tertiary care hospital. J Asthma Allergy P, Martinez-Saguer I, et al. Validation of the Angioedema
2020; 13: 225–236. Control Test (AECT) – a patient-reported outcome instrument
4. Zingale LC, Beltrami L, Zanichelli A, Maggioni L, Pappalardo for assessing angioedema control. J Allergy Clin Immunol
E, Cicardi B, Cicardi M. Angioedema without urticaria: a large Pract 2020; 8: 2050–2057.e4.
clinical survey. CMAJ 2006; 175: 1065–1070. 25. João Forjaz M, Ayala A, Caminoa M, Prior N, Pérez-Fernández
Advances in dermatology and venereology

5. Cicardi M, Aberer W, Banerji A, Bas M, Bernstein JA, Bork K, E, Caballero T; DV-HAE-QoL study group. HAE-AS, a specific
et al. Classification, diagnosis, and approach to treatment disease activity scale for hereditary angioedema with C1-
for angioedema: consensus report from the Hereditary inhibitor deficiency. J Investig Allergol Clin Immunol 2020
Angioedema International Working Group. Allergy 2014; Jan 14 [online ahead of print].
69: 602–616. 26. Prior N, Remor E, Pérez-Fernández E, Caminoa M, Gómez-
6. Zuberbier T, Aberer W, Asero R, Abdul Latiff AH, Baker D, Traseira C, Gayá F, et al. Psychometric field study of Here-
Ballmer-Weber B, et al. The EAACI/GA²LEN/EDF/WAO guide­ ditary Angioedema Quality of Life Questionnaire for Adults:
line for the definition, classification, diagnosis and manage- HAE-QoL. J Allergy Clin Immunol Pract 2016; 4: 464–473.
ment of urticaria. Allergy 2018; 73: 1393–1414. 27. Bonner N, Abetz-Webb L, Renault L, Caballero T, Longhurst H,
7. Maurer M, Sofen H, Ortiz B, Kianifard F, Gabriel S, Bernstein Maurer M, et al. Development and content validity testing of a
JA. Positive impact of omalizumab on angioedema and patient-reported outcomes questionnaire for the assessment
quality of life in patients with refractory chronic idiopathic/ of hereditary angioedema in observational studies. Health
spontaneous urticaria: analyses according to the presence Qual Life Outcomes 2015; 13: 92.
or absence of angioedema. J Eur Acad Dermatol Venereol 28. Busse PJ, Christiansen SC, Birmingham JM, Overbey JR,
2017; 31: 1056–1063 Banerji A, Otani IM, et al. Development of a health-related
8. Bygum A. Hereditary angio-oedema for dermatologists. quality of life instrument for patients with hereditary angi-
Dermatology 2019; 235: 263–275. oedema living in the United States. J Allergy Clin Immunol
9. Busse PJ, Christiansen SC. Hereditary angioedema. N Engl Pract 2019; 7: 1679–1683.
J Med 2020; 382: 1136–1148. 29. Vernon MK, Rentz AM, Wyrwich KW, White MV, Grienen-
10. Bork K, Hardt J, Witzke G. Fatal laryngeal attacks and mor- berger A. Psychometric validation of two patient-reported
tality in hereditary angioedema due to C1-INH deficiency. J outcome measures to assess symptom severity and changes
Allergy Clin Immunol 2012; 130: 692–697. in symptoms in hereditary angioedema. Qual Life Res 2009;
11. Bork K, Wulff K, Rossmann H, Steinmüller-Magin L, Braenne I, 18: 929–939.
Witzke G, Hardt J. Hereditary angioedema cosegregating with 30. Maurer M, Magerl M, Ansotegui I, Aygören-Pürsün E, Betschel
a novel kininogen1 gene mutation changing the N- terminal S, Bork K, et al. The international WAO/EAACI guideline
cleavage site of bradykinin. Allergy 2019; 74: 2479–2481. for the management of hereditary angioedema – the 2017

www.medicaljournals.se/acta
 Patient-reported outcome measures for angioedema 5/5

revision and update. World Allergy Organ J 2018; 11: 5. who.int/substance_abuse/research_tools/translation/en/.

31. Agboola F, Lubinga S, Carlson J, Lin GA, Dreitlein WB, Pear- 38. Beaton DE, Bombardier C, Guillemin F, Ferraz MB. Guidelines
ActaDV

son SD. The effectiveness and value of lanadelumab and C1 for the process of cross-cultural adaptation of self-report
esterase inhibitors for prophylaxis of hereditary angioedema measures. Spine (Phila Pa 1976) 2000; 25: 3186–3191.
attacks. J Manag Care Spec Pharm 2019; 25: 143–148. 39. Guillemin F, Bombardier C, Beaton D. Cross-cultural adap-
32. Engel-Yeger B, Farkas H, Kivity S, Veszeli N, Kőhalmi KV, tation of health-related quality of life measures: literature
Kessel A. Health-related quality of life among children with review and proposed guidelines. J Clin Epidemiol 1993; 46:
hereditary angioedema. Pediatr Allergy Immunol 2017; 28: 1417–1432.
370–376. 40. Wild D, Grove A, Martin M, Eremenco S, McElroy S, Verjee-
33. Aabom A, Nguyen D, Fisker N, Bygum A. Health-related Lorenz A, Erikson P; ISPOR Task Force for Translation and
quality of life in Danish children with hereditary angioedema. Cultural Adaptation. Principles of Good practice for the trans-
Allergy Asthma Proc 2017; 38: 440–446. lation and cultural adaptation process for Patient-Reported
34. Varni JW, Burwinkle TM, Seid M, Skarr D. The PedsQL 4.0 as Outcomes (PRO) measures: report of the ISPOR Task Force
a pediatric population health measure: feasibility, reliability, for Translation and Cultural Adaptation. Value Health 2005;
Acta Dermato-Venereologica

and validity. Ambul Pediatr 2003; 3: 329–341. 8: 94–104.

35. Lewis-Jones MS, Finlay AY. The Children’s Dermatology Life 41. Brix ATH, Svensson TM, Sandberg M, Bygum A. Hereditary
Quality Index (CDLQI): initial validation and practical use. angioedema: the challenges of cross-border family investi-
Br J Dermatol 1995; 132: 942–949. gation and treatment. BMJ Case Rep 2020; 13: e231906.
36. Kreiberg KB, Bygum A. Reporting through smartphone app- 42. Maurer M, Aberer W, Agondi R, Al-Ahmad M, Al-Nesf MA,
lication results in detailed data on acquired and hereditary Ansotegui I, et al. Definition, aims, and implementation of
angioedema attacks. Allergy 2019; 74: 1800–1802. GA2LEN/HAEi angioedema centers of reference and excel-
37. WHO. (accessed 2020 Jul 31). Available from: https: //www. lence. Allergy 2020; 75: 2115–2123.
ActaDV
Advances in dermatology and venereology

Acta Derm Venereol 2021