Urticaria and Angioedema BSACI guideline
Powell et al. 2015
Appendix
Appendix A1: Patient information sheet - chronic urticaria and angioedema in
adults
What is it?
Urticaria is an itchy, lumpy, red rash, often called hives, weals or nettle rash
Angioedema is a swelling deep under the skin, often affecting the face or lips. It usually
occurs with urticaria, but can occur on its own.
What is the difference between acute urticaria and chronic urticaria?
Acute urticaria lasts for any period up to 6 weeks. It is usually a response to a viral
infection but can be due to an allergy.
Acute intermittent urticaria lasts for less than 6 weeks but then recurs from time to
time.
Chronic urticaria persists for more than 6 weeks. Individual spots usually last less than
24 hours, but may occur frequently.
Why does it happen?
Chronic urticaria is not an allergy. It occurs when mast cells in the skin are triggered to
release a chemical called histamine. Spontaneous urticaria is diagnosed when possible
triggers have been excluded. Urticaria can occur in response to physical factors, such as
cold, stress or scratching and rubbing (in which case it is called dermographism).
How common is urticaria and angioedema? Urticaria is a common condition, affecting
around 1 in 5 individuals at some stage of their lives. Chronic urticaria is less common,
affecting around 1 in 200 adults.
How is it diagnosed?
1
Urticaria and Angioedema BSACI guideline
Powell et al. 2015
The diagnosis is made on the history and pattern of the rash. Usually, no tests are needed,
although your doctor may wish to perform allergy tests to exclude this as a cause of the
rash. Individuals with angioedema without urticaria may require blood tests.
How is it treated?
Chronic urticaria is not associated with severe allergic reactions (anaphylaxis) and
adrenaline autoinjectors are not required. The itching can result in difficulty sleeping and
sometimes in concentrating on tasks and hence may impact on quality of life.
It is important to identify triggers that can be avoided such as cold water, stress and tight
clothes. A regular dose of a non-drowsy antihistamine is often effective. This therapy
may need to be taken for many months, occasionally years. It is safe to do this. Higher
doses of antihistamines than are used in conditions such as hay fever may be necessary
for effective control of symptoms. In some cases other medicines will need to be added.
A short course of oral steroids may be needed if the swelling or rash is particularly
distressing.
Topical creams such as 1-2% menthol in aqueous cream may offer additional benefits.
Concurrent medications
Certain blood pressure tablets called ACE inhibitors can cause or aggravate angioedema
(with or without associated urticaria) and you may need to discuss changing to an
alternative treatment with your GP.
NSAIDs such as ibuprofen, diclofenac and aspirin can aggravate urticaria and your doctor
will discuss this with you.
2
Urticaria and Angioedema BSACI guideline
Powell et al. 2015
How long will it last?
Urticaria improves with time, but this may take a while. Lifestyle stressors may need
attention with psychological support.
Patient support
There is no UK support group for this condition. Clinic contact number………
3
Urticaria and Angioedema BSACI guideline
Powell et al. 2015
Appendix A2: Patient information sheet - chronic urticaria and angioedema in
children
What is it?
Urticaria is an itchy, lumpy, red rash, often called hives, weals or nettle rash
Angioedema is a deep swelling in the skin, often affecting the face or lips. It usually
occurs with urticaria, but can rarely occur in isolation.
What is the difference between acute and chronic urticaria?
Acute urticaria lasts for any period up to 6 weeks. It is usually a response to a viral
infection, but may also be due to an allergy
Acute intermittent urticaria lasts for less than 6 weeks, then recurs from time to time.
Chronic urticaria lasts for more than 6 weeks. Individual spots usually last less than 24
hours and occur on most days.
Why does it happen?
Chronic urticaria is not an allergy. It occurs when mast cells in the skin are stimulated to
release a chemical called histamine. In some children it arises in response to physical
factors, such as cold, scratching, rubbing (in which case it is known as dermographism)
or stress. Often, no cause can be found, in which case it is known as spontaneous
urticaria.
How common is urticaria and angioedema?
Urticaria is a common condition, affecting around 10% of children at some point. Chronic
urticaria is less common, affecting around 0.5% of children
How is it diagnosed?
4
Urticaria and Angioedema BSACI guideline
Powell et al. 2015
The diagnosis is made on the history and pattern of the rash. Usually, no tests are needed,
although your doctor may wish to perform allergy tests to exclude this as a cause of the
rash. If your child suffers with angioedema alone, your doctor may perform some blood
tests.
How is it treated?
Chronic urticaria is not associated with severe allergic reactions (anaphylaxis) and
adrenaline autoinjectors are not required. It can, however, cause difficulty sleeping and
problems concentrating at school (impact on quality of life). Effective management is
therefore important.
Exposure to things which make the rash worse, such as cold weather, should be avoided,
wherever possible.
A regular dose of a non-drowsy antihistamine is the best treatment. The medicine may
need to be taken for many months or even years. The dose of the antihistamine may need
to be increased, or other medicines added. A short course of steroids may be needed if the
swelling or rash is particularly severe.
How long will it last?
Urticaria improves with time, but this may take a while. After 3 years, a third of children
with chronic urticaria are better. Most children are disease free after 7 years.
5
Urticaria and Angioedema BSACI guideline
Powell et al. 2015
Table B1: Levels of evidence [149]
Level of
Definition
evidence
1++
High quality meta-analyses, systematic reviews of RCTs, or RCTs with a very
low risk of bias
1+
Well-conducted meta-analyses, systematic reviews, or RCTs with a low risk of
bias
1Meta-analyses, systematic reviews, or RCTs with a high risk of bias
2++
High quality systematic reviews of case control or cohort or studies
High quality case control or cohort studies with a very low risk of confounding
or bias and a high probability that the relationship is causal
2+
Well-conducted case control or cohort studies with a low risk of confounding
or bias and a moderate probability that the relationship is causal
2Case control or cohort studies with a high risk of confounding or bias and a
significant risk that the relationship is not causal
3
Non-analytic studies, e.g. case reports, case series
4
Expert opinion
Table B2: Grades of recommendations [134;149]
Grade of
Type of Evidence
recommendation
A
At least one meta-analysis, systematic review, or RCT rated as 1++,
and directly applicable to the target population;
or
A body of evidence consisting principally of studies rated as 1+,
directly applicable to the target population, and demonstrating overall
consistency of results
B
A body of evidence including studies rated as 2++, directly applicable
to the target population, and demonstrating overall consistency of
results;
or
Extrapolated evidence from studies rated as 1++ or 1+
C
A body of evidence including studies rated as 2+, directly applicable
to the target population and demonstrating overall consistency of
results;
or
Extrapolated evidence from studies rated as 2++
D
Evidence level 3 or 4;
or
Extrapolated evidence from studies rated as 2+
E
Recommended best practice based on the clinical experience of the
guideline development group
6
Urticaria and Angioedema BSACI guideline
Powell et al. 2015
Table B3: Evidence table for the use of leukotriene receptor antagonists in chronic
urticaria
Source
Sanada 2005
[150]
Interventions
Montelukast 10mg
added for at least 1
week
Conclusions
12/25 improved
These were younger and
had CIU for a shorter
duration
White 2005
[151]
Design & Sample
Non randomised
uncontrolled n=25
with antihistamine
uncontrolled
chronic urticaria
RPC n=48,
crossover design
24 hour observation
Di Lorenzo
2004 [122]
RDBPC n=160
4 parallel groups
Nettis 2004
[152]
RDBPC n=81
3 parallel groups
Bagenstose
2004 [81]
RDBPC n=95
cetirizine refractory
CIU
Desloratadine,
desloratadine+montelukast, montelukast
alone or placebo
6 weeks treatment
desloratadine alone,
desloratadine+montelukast, or placebo
Zafirlukast + cetirizine
vs placebo + cetirizine
3 weeks treatment
Fexofenidine showed
greater weal and flare
suppression and faster
onset of action, compared
with montelukast
Combined treatment no
better than desloratadine
alone
Nettis 2003
[84]
N=20 with delayedpressure urticaria,
DBPC.
Loratadine alone
compared to loratadine
+ montelukast. 15 days
treatment
Erbagci
2002 [153]
RSBPC cross-over
study n=30
refractory CIU.
Reimers
2002
[129]
Pacor 2001
[82]
RDBPC n=52,
cross-over design
Cross-over treatments:
i) montelukast +
cetirizine prn; ii)
placebo + cetirizine
prn for 6 weeks each
6 weeks active, then 6
weeks placebo
treatment
Montelukast vs
cetirizine vs placebo; 4
weeks treatment
Nettis 2001
[154]
RDBPC n=51
patients with
positive ASA or
food additive
challenges
N=27 parallel
groups
Montelukast vs
fexofenadine 180mg;
27 days treatment
Symptoms and QoL
improved with combined
treatment more than with
desloratadine alone
Improvements in urticaria
scores with zafirlukast
only in subgroup with
positive ASST
Combined treatment more
effective than loratadine
alone. 8/10 had complete
suppression on pressure
challenge.
Improvement in urticaria
activity scores with
combined therapy
No improvement with
zafirlukast compared to
placebo
More symptom-free days
in montelukast group and
improved sleep quality
Similar improvements in
chronic urticaria for both
groups. 6/9 patients with
a positive ASST on
montelukast became
negative.
7
Urticaria and Angioedema BSACI guideline
Powell et al. 2015
Table B4: Evidence table on the use of ciclosporin in chronic urticaria
Source
Baskan
2004 [155]
Di
Gioacchino
2003 [156]
Grattan
2000 [87]
Design & Sample
N=20 open design
patients with history of
chronic severe
spontaneous urticaria
and positive ASST
N=40 RDBPC patients
with history of chronic
severe spontaneous
urticaria and positive
ASST
N=30 RDBPC patients
with history of chronic
severe spontaneous
urticaria and positive
ASST
Interventions
Ciclosporin
4mg/kg/day for either
4 or 12 weeks
Conclusions
Improvements in
urticaria only in first
month of treatment
Ciclosporin
5mg/kg/day for 8
weeks then
4mg/kg/day for 8
weeks
vs Cetirizine 10mg
daily; follow up for 9
months
Ciclosporin
4mg/kg/day for 4
weeks vs placebo
All took cetirizine
20mg daily
Study unblinded after 2
weeks as 16/20 in
cetirizine group
developed a severe
relapse. All patients
placed on ciclosporin.
16/40 in remission at 9
months
8/19 responded to
ciclosporin and 0/10 to
placebo at 4 weeks
26% of responders still
clear at 6 months
8