Hereditary Angioedema (HAE)

Hereditary angioedema (HAE) is a rare, autosomal dominant, inherited disorder characterized by recurrent episodes of severe swelling that occurs in the face, extremities, gastrointestinal tract, and airways. It is caused by mutations in the SERPING1 gene or the F12 gene.¹ 

Mutations in the SERPING1 gene cause deficiency or dysfunction of the plasma protein, C1-esterase inhibitor. C1-esterase inhibitor deficiency or dysfunction results in increased vascular permeability, excessive release of bradykinin (an inflammatory mediator), and leakage of fluid from the vasculature into the surrounding tissues.¹ 

Mutations in the F12 gene cause problems with the production of coagulation factor XII, which is essential for effective blood clotting. Factor XII also drives inflammatory processes and the production of bradykinin. Mutations in the F12 gene produce factor XII proteins that demonstrate increased activity levels, resulting in the increased production of bradykinin, which causes increased vascular permeability and recurrent swelling episodes.¹

Episodes of swelling may have certain triggers, including mental stress, infections, surgical or medical procedures, major or minor trauma, physical exertion, fatigue, weather changes, and hormonal changes during menstruation, pregnancy, or puberty. These triggers provoke systemic inflammatory processes that cause excessive release of bradykinin.²

Swelling throughout the gastrointestinal tract during abdominal attacks occurs in approximately 80% of patients with HAE. These abdominal attacks cause symptoms like pain, abdominal distension, cramping, nausea, vomiting, and diarrhea. Due to the overlap of these symptoms with other causes such as appendicitis, cholecystitis, and small bowel obstruction, many patients with HAE have undergone unnecessary exploratory laparotomies, hysterectomies, or cholecystectomies.² 

Patients often raise questions about diet and potential food triggers for recurrent abdominal attacks. While some sources claim that no restrictions are necessary for patients with HAE,³ others recommend anti-inflammatory diets to avoid foods that cause inflammation, such as refined carbohydrates, soda, and red meat.⁴ 

Food Triggers for Hereditary Angioedema Attacks 

A study published in 2018 reported that hypersensitivity reactions and food are relevant triggers of HAE attacks. The researchers surveyed 27 women and 15 men with HAE regarding their attack triggers. Of these patients, 79% reported triggers, and 36% of these triggers were related to food. Suspected food triggers for abdominal angioedema episodes included tomatoes, bread, shrimp, pineapple, strawberries, milk, kiwis, tree nuts, garlic, cheese, apples, onions, leeks, bananas, citrus fruits, fish, green salads, alcohol, and chicken. None of these foods resulted in positive skin prick or ImmunoCAP tests to be classified as food allergens, indicating that these inflammatory processes are not mediated by immunoglobulin E. It appears that histamine-releasing foods capable of initiating angioedema through unidentified mechanisms may be the culprit.⁵

Another study analyzed the possibility of comorbid HAE and celiac disease in 22 children diagnosed with HAE. Four of the 22 children with HAE also had celiac disease. The researchers noted that the prevalence of celiac disease in this HAE cohort was higher than that in the general population (18.1% vs 1.2%). It is reasonable to screen patients with HAE for celiac disease if abdominal attacks or neurological symptoms persist despite adequate management.⁶

Hereditary Angioedema Nutrition 

Eating a balanced, nutritious diet high in whole, unprocessed foods is recommended for patients with HAE.^4,7 Avoidance of store-bought products containing flavor enhancers, additives, preservatives, and food coloring is also suggested.⁷ 

Because patients with HAE may have different food triggers, they can schedule a consultation with a dietician or nutritionist for professional recommendations on maintaining a diet that is safe and nutritious. Dieticians and nutritionists can guide patients with HAE through elimination diets and the reintroduction of different foods to better identify potential dietary triggers.⁷

References

1. Hereditary angioedema. MedlinePlus. Updated April 1, 2009. Accessed June 30, 2022.
2. Zotter Z, Csuka D, Szabó E, et al. The influence of trigger factors on hereditary angioedema due to C1-inhibitor deficiency. Orphanet J Rare Dis. 2014;9:44. doi:10.1186/1750-1172-9-44
3. Frank MM. Hereditary angioedema treatment & management: diet and activity. Medscape. Updated August 30, 2018. Accessed June 30, 2022.
4. Marks JL. Speaking hereditary angioedema (HAE): a glossary of terms used to describe symptoms, tests, treatments, and more. Everyday Health. Accessed June 30, 2022.
5. Steiner UC, Kölliker L, Weber-Chrysochoou C, et al. Food as a trigger for abdominal angioedema attacks in patients with hereditary angioedema. Orphanet J Rare Dis. 2018;13(1):90. doi:10.1186/s13023-018-0832-4
6. Csuka D, Kelemen Z, Czaller I, et al. Association of celiac disease and hereditary angioedema due to C1-inhibitor deficiency. Screening patients with hereditary angioedema for celiac disease: is it worth the effort? Eur J Gastroenterol Hepatol. 2011;23(3):238-244. doi:10.1097/MEG.0b013e328343d3b2
7. Angioedema and diet. Angioedema News. Accessed June 30, 2022.

Reviewed by Kyle Habet, MD, on 6/30/2022.

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Maria Arini Lopez, PT, DPT, CSCS, CMTPT, CIMT

Maria Arini Lopez, PT, DPT, CSCS, CMTPT, CIMT is a freelance medical writer and Doctor of Physical Therapy from Maryland. She has expertise in the therapeutic areas of orthopedics, neurology, chronic pain, gastrointestinal dysfunctions, and rare diseases especially Ehlers Danlos Syndrome.