Background: Hereditary Angioedema (HAE) is a life-threatening genetic condition that causes severe recurring episodes of swelling, most commonly to the limbs, face, intestinal tract, and airway. HAE is an extremely rare condition, with a prevalence of only 1 in 10,000 patients.1 Patients with HAE often present with excruciating abdominal pain, severe nausea, and vomiting owing to swelling in the intestinal wall. There are 3 different types of HAE:
  • Type 1—due to a biochemical imbalance from the deficiency of C1 inhibitors in the body.1
  • Type 2—due to an accumulation of non-functional C1 inhibitors.1
  • Type 3—least common type; not fully understood; thought to be related to estrogen dependency; presents with no changes to the C1 inhibitors in the body.2
Common triggers of HAE attacks include stress, anxiety, surgery, trauma, and exposure to medications such as ACE inhibitors and NSAIDs. There are several treatment options classified as C1 inhibitors that are FDA-approved for HAE Types 1 and 2, e.g. Berinert, Cinryze, and Haegarda.1

Patient Case: KR, a woman aged 32 years, presented to a primary care clinic with abdominal edema. She reported having experienced many episodes of hand, foot, and neck edema over the past 17 years. Despite multiple procedures, including exploratory surgeries, celiac artery stenosis corrective surgery, and 7 bile duct stent placements, her condition persisted. At one point, she had been told that her problem was psychosomatic, and was referred for a psychiatric evaluation.

Her physician suspected HAE, and ordered genetic testing to confirm the diagnosis. Originally, it was thought that she had HAE type 1, but it was later determined that she had type 3. With KR’s diagnosis confirmed, meetings of her health care team, including her primary care physician, nurse care manager, local pharmacist, health plan, and specialty pharmacy, were convened to review her care. Despite the fact that HAE is a complicated disorder with very few treatments available, the pharmacist played a vital role in the team-based care model to improve the patient’s quality of life.

Team-Based Care: As medication experts, pharmacists are integral to team-based care, providing the requisite knowledge for medication therapy management, as well as initiating, modifying and monitoring drug therapy to benefit patient care. KR was ultimately referred to a Patient Centered Medical Home (PCMH) with a patient-centric care model. In the PCMH model, active communication between all providers and caregivers is supported to improve patient outcomes. KR quickly surfaced as a very high priority for the pharmacist to ensure that her medication regimen was appropriate, safe, effective, and as cost-effective, as possible.  

A significant challenge with C1 inhibitor therapy is cost. Originally, Cinryze, Berinert, tranexamic acid, and Deblitane were prescribed in high amounts to treat KR’s HAE. Upon reviewing her medication regimen, the pharmacist identified that the doses were excessive, and worked with the physician to implement the appropriate modifications. Additionally, danazol was prescribed to help calm her attacks, as HAE type 3 is primarily due to a hormonal imbalance.  

Interprofessional collaboration resulted in the best clinical solution for KR. Her health plan, the specialty pharmacy, primary physician, nurse case manager, and local pharmacist were able to work together to  reduce the cost of her medications by $720,000 per year, and improve her overall quality of life, as well as raising awareness for HAE.  

Conclusion
This case underscores the importance of inclusion of the pharmacist in team-based care. It demonstrates the pharmacist’s ability to add value as a member of the health care team by determining appropriate therapy in the case of a rare, complex condition such as HAE; in significantly reducing costs of care; and by improving patient quality of life.
 
Matthew A. Fowler, BS  is a 2019 PharmD Candidate at Campbell University College of Pharmacy and Health Sciences in Buies Creek, North Carolina.

Cari W. Pao, PharmD, MBA, MSHCM, is Senior Clinical Director, Health Outcomes Team for Walgreen Co.

Bethany Spadaro, RPh, CDE, BCGP is a clinical pharmacist in Rhode Island.

References
  1. US Hereditary Angioedema Association—The Disease. US Hereditary Angioedema Association—HAEA website. https://www.haea.org/HAEdisease.php. Accessed June 18, 2018
  2. Miranda AR, de Ue APF, Sabbag DV, Furlani W de J, de Souza PK, Rotta O. Hereditary angioedema type III (estrogen-dependent) report of three cases and literature review. Anais Brasileiros de Dermatologia. 2013;88(4):578-584. doi:10.1590/abd1806-4841.20131818.