Children & young people
Background information
In a family where one parent has HAE it is important to test the children for HAE, as each child has a 50% chance of inheriting the condition.
HAE can also occur in children whose parents do not have HAE. The cause is said to be a ‘spontaneous mutation’ of the gene that causes HAE.
Diagnosis
Pointers to a diagnosis of hereditary angioedema (HAE) are:
- Family history – other family members have had similar symptoms
- Recurrent episodes of swelling (without hives) lasting more than 24 hours and unresponsive to antihistamines
- Recurrent unexplained abdominal pain
- Symptoms starting in childhood and worsening in adolescence.
Investigations
For diagnosis of HAE types I and II:
- Serum C4 levels – usually low in untreated HAE
- If C4 is low, measure C1 INH level and function
- If C4 is normal but HAE is suspected, measure C1 INH levels and function, and if normal, repeat C4 levels during an attack and assess C1 INH level and function if abnormal
- Genetic testing may be done in some cases where there is doubt.
Type III HAE
- C4 and C1 INH levels are normal
- Diagnosis is from the clinical picture
- Kininogenase activity measurement and genetic analysis for F12 gene mutation may be considered.
Testing children for HAE
The age at which children should be tested for HAE is a matter of personal choice for the family.
Symptoms of HAE are less common in babies and very young children but swellings do occur and very occasionally may be severe.
Routine blood tests (see ‘investigations’ section above) can be done from the age of 1 year.
Prior to 1 year of age most blood tests may be less accurate. However, genetic testing is possible and may be done on blood taken from the umbilical cord at birth. Genetic testing can also be done for HAE 3 (HAE with normal C1 inhibitor) in the rare cases where the parent is known to have the mutation.
Variations in symptoms
Angioedema symptoms may start at a very early age, or they may not show until adolescence or even later in life. Symptoms tend to get more severe with the hormonal changes of adolescence.
Treatment of children follows the same structure as for adults, that is:
- Avoidance of precipitating factors
- Treatment of acute attacks
- Short and long term preventative treatment
A child’s HAE management will need regular review throughout childhood to accommodate changes in symptoms and the growing independence of the child.
Precipitating factors
Many attacks have no obvious triggers. However the following things are potential triggers for HAE attacks:
- Infected teeth and other foci of infection
- H. pylori (a bacteria that can be present in the stomach)
- Dental treatments
- Minor trauma
- Intubation for anaesthetics
- Hormone changes
- Puberty
- Physical or psychological stress
Preventative treatment
Many children have few attacks and do not require preventative treatment. However, where attacks are disruptive to school or play, it may be helpful to try a regular treatment with a view to reducing the number and severity of attacks.
Tranexamic acid liquid or tablets are given once, twice or three times daily, according to the age and size of the child. They work well for some children but have little effect on others.
Some children only need preventative treatment for a short period of time; for example, if the excitement of a party is likely to trigger an attack, a few days of tranexamic acid may prevent this.
If tranexamic acid is unhelpful, C1 inhibitor injections can be given on a regular basis to prevent attacks.
Some high risk procedures such as major dental work or an operation, ideally require an injection of C1 inhibitor before the procedure to minimize the chance of triggering a swelling in the hours or days that follow.
Danazol, Oxandrolone and similar ‘attenuated androgens’ are usually not given to children.
Acute attack medication
Every child needs a plan for treatment of acute attacks, even if they have not yet had their first attack and even if they are on regular prophylaxis.
Acute attacks in children are treated with C1 inhibitor.
The dose is 500 units (1 vial) if the child is under 25kg, 1000 units (2 vials) if 25-50 kg and 1500 units (3 vials) if 50-75 kg.
As the child grows, the dose of C1 inhibitor may need to be increased.
The child should have their own supply of C1 inhibitor, at home and at school/nursery, along with a ‘to whom it may concern’ letter, giving details of HAE and its treatment.
Icatibant is used as an alternative to C1 inhibitor and is currently undergoing trials for use in children. It is unlicensed for children but is used in exceptional cases.
Home therapy
In order to prevent disruption to the family routine, and to ensure that the child is able to participate in all activities, acute treatment is often given by a parent who has been trained to do this, or if the child is older, by the child themselves, under parental supervision.
If a parent is affected by HAE, they will often have been trained to self administer C1 inhibitor. This is very helpful when training to give C1 inhibitor to a child but is not essential.
Most centres will have facilities for training adults to self administer or to administer C1 inhibitor to another adult. Many children’s centres have facilities to train adults to treat their children, and to train children to self administer.
Some centres organise training via their haemophilia service (haemophilia is a condition affecting boys, who are trained to give intravenous injections to control the condition).
Many centres can organise a nurse to visit the home to provide family training sessions.
Training for C1 inhibitor should never be rushed and most people prefer to have several training sessions before giving their own or their children treatment. For this reason, it is helpful to arrange training well in advance of any likely requirement.
The age at which children train depends on the child and the wishes of the family. Children from the age of eight years can start training, although many prefer to wait until 11-13 years.