Hereditary angioedema should be considered in the differential diagnosis of patients with episodes of unexplained abdominal pain, nausea, vomiting, and/or diarrhea, according to a clinical review published in the Journal of Clinical Gastroenterology.

Recognizing and properly diagnosing people with isolated abdominal pain “may significantly improve morbidity and mortality for these individuals,” the authors said, especially since highly effective targeted therapies exist for the condition such as on-demand treatment for attacks, short-term prophylaxis, and long-term prophylaxis. Options include icatibant, ecallantide, and intravenous plasma-derived or recombinant human C1 inhibitor. 

Due to its rarity, hereditary angioedema may not be part of the differential diagnosis of people with recurrent, unexplained abdominal pain, especially if they do not also experience skin swelling. However, abdominal pain can occur in up to 93% of patients with hereditary angioedema. Moreover, in almost half (49%) of all hereditary angioedema attacks with abdominal symptoms, the only symptom is isolated abdominal pain.

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“Under-recognition of [hereditary angioedema] in patients presenting with predominant gastrointestinal symptoms is a key factor contributing to the delay in diagnosis, increasing the likelihood of unnecessary or exploratory surgeries or procedures and the potential risk of related complications,” the authors wrote.

They recommend that patients’ medical histories are taken carefully and that this should be followed by a physical examination, imaging studies, and laboratory tests to reach the correct diagnosis.

Hereditary angioedema is a rare genetic autoimmune disease resulting from a deficiency of C1 inhibitor. It is caused by mutations in the gene coding for C1 inhibitor, resulting in truncated or misfolded proteins.

Symptoms include repeated episodes of severe swelling of subcutaneous tissues in the face, hands, arms, legs, buttocks, and genitals. Abdominal symptoms include distension, cramping, nausea, vomiting, and diarrhea.


Staller K, Lembo A, Banerji A, Bernstein JA, Shah ED, Riedl MA. Consider hereditary angioedema in the differential diagnosis for unexplained recurring abdominal pain. J Clin Gastroenterol. Published online August 15, 2022. doi:10.1097/MCG.0000000000001744