Your female patients may experience HAE differently

Hormonal triggers in women: Puberty, contraception and menopause

 

Around 50% of female patients will experience their first HAE attack before the age of 12, and 90% by the age of 23.1 A known trigger of HAE attacks is changes in female hormones. 

 

As such, your female patients may report varying frequency and severity of attacks throughout different stages of life, such as puberty and adolescence.1,2 

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Your female patients should also be aware that, in addition to common HAE attack triggers, there are additional moments in their life that can affect HAE attacks, such as ovulation, contraception use or menopause.2,3

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Early initiation of oral oestrogen-containing contraceptives is increasingly common and can increase kallikrein production and bradykinin, which is responsible for vasodilation and vascular permeability responsible for angioedema.4

 

Therefore, you should avoid prescription of these contraceptives as they may trigger attacks.1 Instead, it is recommended that females with HAE use progesterone-only pills.2,3 For your patients with HAE who are entering menopause, oestrogen preparations for hormone replacement therapy should not be used.3 Be sure to discuss life stage changes and the therapeutic options available for each stage with your female patients and update their management plan accordingly.

 

 

Considerations during family planning, pregnancy and breastfeeding

 

Fertility is not impacted in women who have been diagnosed with HAE.5 It is important to provide information to your female patients before they plan to start a family and to discuss with them how their HAE symptoms may change during pregnancy. In vitro fertilisation may increase the frequency and severity of patient’s attacks due to increased oestrogen production.4 

 

Patients should be informed that the hormonal, anatomical and physiological changes that occur during pregnancy can mitigate or aggravate HAE attacks depending on the individual.1,5 Patients may feel anxious about passing HAE to their children, and genetic counselling should be offered if appropriate.4

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A treatment plan should be created with the patient, which shows them how to proceed during pregnancy and childbirth. 


Labour and delivery only rarely induce an attack,1 but it is important to discuss the use of short-term prophylaxis during labour with patients. Breastfeeding can also increase attack frequency; however, it is still recommended by WAO/EAACI guidelines due to the benefits to the infant.1
 

Considerations for children

Impact of HAE on children and caregivers

 

Patients with HAE are likely to experience their first symptoms as children,6 and most first attacks in children manifest with skin angioedema. It is important to consider abdominal symptoms of HAE, which often go unrecognised in children, in whom abdominal pain is common.1 While laryngeal attacks should always be considered a medical emergency, it is important to know that, particularly in children, asphyxia can occur rapidly due to smaller airway diameters.1
 

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If patients display symptoms at an early age, this may be associated with a more severe disease course, increased HAE attacks, increased hospitalisations and a greater impact on mood and quality of life.6

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The burden of disease often extends beyond the child themselves and impacts the child’s caregivers, who are often their parents.7 All family members, acting as caregivers or not, might also have a HAE diagnosis themselves.7 

 

Caregivers often take on tasks such as scheduling and transporting children to medical appointments, preparing medication and contributing to treatment decisions, constituting a significant emotional, physical and financial burden.7

 

Parents of children with HAE can be referred to the ‘Information for parents’ webpage. As in adults, HAE attacks in children can occur spontaneously or in response to triggers. Infections are more common triggers of attacks in children. It is recommended that children receive their vaccinations to help reduce HAE attack frequency.1

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Guidelines recommend that restrictions of suspected triggers should be individualised, along with the use of prophylaxis where necessary, with the aim of avoiding any limitations in activities and lifestyle.1 

 

 

Treatment options for children

 

For children with HAE there are on-demand, and long-term prophylactic (LTP) treatments available. As with adults, children should have an individualised treatment plan, which can be designed with them.1 It is key to support and advise their families, teachers and carers about the risk of HAE attacks and how they should best be managed.1

 

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On-demand treatment

The two therapies that are recommended for children are C1-INH (IV) and the bradykinin B2 receptor antagonist, icatibant, which can both be self-administered. On-demand medication for at least 2 attacks should be available at home, school and whilst travelling, including school trips.1 
 

 

Prophylaxis

In patients younger than 12 years of age, the preferred LTP therapy is plasma-derived C1-INH.1 In Europe, intravenous C1-INH is approved for children ≥6 years (depending on manufacturer/indication). The recommended LTP treatments in adolescents ≥12 years old are the same as those in adults. 


As with adults, there are some special situations, such as before medical, surgical, and dental procedures, where short-term prophylaxis should be considered for children. For these cases, STP with C1-INH is recommended. In case of STP failure and breakthrough attacks, patients should always have on-demand treatment available.1

Considerations for the elderly

There are no guideline recommendations specific to the treatment of adults ≥65 years old; however, several factors should be considered for older patients with HAE including:8

 

  • Patients may be more likely to experience treatment-related adverse events due to physiological and pharmacokinetic changes as they age
  • Older patients are more likely to have comorbidities, leading to polypharmacy and increasing the risk of drug-related disease and drug-to-drug interactions
  • Venous access may prove challenging in patients with comorbidities such as type II diabetes or obesity 
  • Comorbidities may also affect the clinical course of HAE, especially in women

References

  1. Maurer M, Magerl M, Betschel S, Aberer W, Ansotegui IJ, Aygören-Pürsün E, et al. The international WAO/EAACI guideline for the management of hereditary angioedema-The 2021 revision and update. Allergy. 2022;77(7):1961–90.
  2. Bouillet L, Longhurst H, Boccon-Gibod I, Bork K, Bucher C, Bygum A, et al. Disease expression in women with hereditary angioedema. Am J Obstet Gynecol. 2008;199(5):484.e1-4.
  3. Caballero T, Farkas H, Bouillet L, Bowen T, Gompel A, Fagerberg C, et al. International consensus and practical guidelines on the gynecologic and obstetric management of female patients with hereditary angioedema caused by C1 inhibitor deficiency. J Allergy Clin Immunol. 2012;129(2):308-20.
  4. Hsu FI, Lumry W, Riedl M, Tachdjian R. Considerations in the management of hereditary angioedema due to C1-INH deficiency in women of childbearing age. Allergy, Asthma & Clinical Immunology. 2022;18(1):64.
  5. Banerji A, Riedl M. Managing the Female Patient with Hereditary Angioedema. Women's Health. 2016;12(3):351-61.
  6. Tachdjian R, Kaplan AP. A Comprehensive Management Approach in Pediatric and Adolescent Patients With Hereditary Angioedema. Clin Pediatr (Phila). 2023;62(9):973-80.
  7. Raasch J, Glaum MC, O'Connor M. The multifactorial impact of receiving a hereditary angioedema diagnosis. World Allergy Organ J. 2023;16(6):100792.
  8. Bernstein JA, Schwartz L, Yang W, Baker J, Anderson J, Farkas H, et al. Long-term safety and efficacy of subcutaneous C1-inhibitor in older patients with hereditary angioedema. Ann Allergy Asthma Immunol. 2020;125(3):334-40.e1.
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