Rare HAE diagnosis explains years of severe abdominal pain in man
Case report shows how genetic testing solved patient’s recurring bowel issues
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A 56-year-old man’s recurring abdominal pain and bowel issues were finally traced back to a rare genetic condition, hereditary angioedema (HAE), according to a recent case report.
Despite the patient’s age and lack of family history, genetic testing identified a mutation in the SERPING1 gene, and his symptoms were successfully managed with the approved targeted therapies Takhzyro (lanadelumab) and Firazyr (icatibant).
The case, published in the journal BMJ Case Reports, highlights how HAE can masquerade as a surgical emergency. Because the swelling occurred internally in the bowel wall rather than in more visible areas like the face or hands, the patient underwent multiple hospitalizations and even a partial bowel removal before doctors found the true cause.
“This case also underscores the importance of early diagnosis and intervention in patients with [angioedema], particularly those presenting with [gastrointestinal] symptoms,” researchers noted in their report, titled “Recurrent bowel angioedema in a patient with C1 esterase inhibitor deficiency.”
The mechanics of internal swelling
Angioedema occurs when fluid leaks from blood vessels into nearby tissues, causing sudden swelling that can affect the skin, airways, or digestive tract.
In HAE, inherited genetic mutations lead to a deficiency or dysfunction of the C1 esterase inhibitor (C1-INH) protein.
C1-INH helps regulate pathways involved in inflammation and swelling. When C1-INH levels are low or dysfunctional, the signaling molecule bradykinin can accumulate, increasing blood vessel permeability and allowing fluid to leak into surrounding tissues, leading to swelling attacks.
In acquired angioedema, C1-INH deficiency develops later in life rather than being inherited. It is often associated with other medical conditions, including certain autoimmune disorders or cancers.
While many people associate angioedema with swelling of the face, lips, or throat, HAE can also cause severe abdominal attacks when swelling occurs in the bowel wall. These episodes can be mistaken for other gastrointestinal conditions, such as bowel obstruction, and may lead to repeated hospitalizations and unnecessary procedures if the underlying cause isn’t recognized.
The case report described a patient who had a complex medical history, including high blood pressure, high cholesterol, and treated cerebral aneurysms. However, his most debilitating symptoms were gastrointestinal. He had an unexplained episode years earlier involving swelling and inflammation of the small intestine that resolved on its own.
Six months before his HAE diagnosis, he was hospitalized with abdominal symptoms and found to have a bowel obstruction, leading to surgery and a partial removal of the small bowel. Afterward, he developed wound complications that required a second operation.
Two months later, he went back to the hospital with pain in the lower left side of his abdomen. Doctors found a blood clot in his lungs (a pulmonary embolism) and another clot in a vein that drains blood from the intestines, along with marked swelling and thickening of the bowel wall. He was started on a blood thinner.
The patient was hospitalized again two months later for nausea, vomiting, and recurrent abdominal pain. A CT scan showed swelling and thickening of the wall of the small intestine, which clinicians suspected was bowel angioedema. Importantly, the scan did not show signs that the bowel was losing its blood supply or that it was being damaged by poor circulation.
Blood tests revealed low C1-INH levels and reduced function. Due to his age and lack of family history, clinicians suspected acquired angioedema caused by an underlying condition, but tests found no evidence of malignancy or another secondary cause.
Genetic testing and family screening
The patient underwent genetic testing that confirmed a likely disease-causing mutation in the SERPING1 gene, supporting a diagnosis of HAE. His 20-year-old daughter was then screened and also tested positive for the mutation and low C1-INH levels, allowing her to seek treatment before experiencing similar severe episodes.
Because his bowel angioedema episodes were recurring and severe, the patient began preventive therapy with Takhzyro and was monitored every three months. For acute attacks, he was prescribed Firazyr as an on-demand medication.
After one year of treatment, the patient reported no further attacks or hospitalizations and a significant improvement in his overall quality of life.
The researchers emphasized the need for HAE to be on the radar for patients with recurrent abdominal pain, even if they show no signs of external swelling.
“This case underscores the importance of considering hereditary and acquired [angioedema] in the differential diagnosis of recurrent abdominal pain and bowel [edema] despite late onset and lack of concomitant facial or peripheral angioedema,” the researchers wrote.
