Hereditary angioedema (HAE) typically results in recurrent, painful edema episodes in various parts of the body. The most commonly affected areas are the face, extremities, airways, and gastrointestinal tract. 

The pathophysiology of HAE can be traced to decreased plasma levels of C1-inhibitor, which results in a cascade of biochemical reactions that causes vascular permeability. This gives rise to edema and inflammation, which can sometimes be life-threatening.

When abdominal attacks occur, they are often misdiagnosed as symptoms of an acute abdomen with other causes. The typical gastrointestinal symptoms of an acute attack are severe abdominal pain, nausea, and vomiting, as well as diarrhea. If the attending physician fails to take a detailed medical history or misses the possible connection with pre-existing HAE, unnecessary invasive investigations may be carried out, including exploratory laparotomy.


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As published in Allergy & Asthma Proceedings, Cao and colleagues conducted a study to further describe abdominal symptoms of an acute attack in patients with HAE. In addition, they wanted to study its frequency and severity. To do so, they recruited 107 patients with HAE (both type 1 and type 2) who had been seen at the Peking Union Medical College Hospital in China from 1983 to 2017. 

Read more about HAE etiology

A patient was said to have HAE based on the twin evidence of medical history (recurrent angioedema with the absence of urticaria) and laboratory findings (low plasma C4 and C1-inhibitors in type 1 and increased levels but decreased function of C1-inhibitors in type 2). 

The research team provided a questionnaire for the participants to fill out, asking them to recall instances of edema attacks, including frequency, locations, and duration. Participants were asked to identify the severity of their edema attacks on a scale of 0 to 10 (0 being the least severe and 10 being the most). 

The results demonstrated that 72% of patients reported experiencing gastrointestinal symptoms during their edema attacks. In addition, the mean score of the severity of abdominal symptoms was 7.6. Interestingly, all the patients who had gastrointestinal edema had type 1 HAE. 

“Our results showed that abdominal edema occurred twice as frequently as the life-threatening laryngeal edema but with a similar severity score,” Cao and colleagues wrote. “[Emergency department] physicians and gastroenterologists should consider HAE when patients experience recurrent and unexplained abdominal pain, especially when ascites is reported by ultrasound and disappears after pain relief.”

In summary, a large percentage of patients with HAE experience gastrointestinal symptoms during edema attacks; physicians should therefore have a high index of suspicion when patients with a history of HAE present with symptoms of an acute abdomen. 

A Typical Scenario 

In Clinics and Research in Hepatology and Gastroenterology, Mumneh and colleagues presented a short case study of a patient with HAE presenting with severe abdominal pain. 

The report details the case of a 20-year-old patient who was referred to gastroenterology for a 3-year history of recurrent abdominal pain and distension. The symptoms were sometimes accompanied by facial swelling and swelling in the hands. 

A detailed history of the patient’s symptoms revealed that these episodes occurred once every 2 months and lasted for 1 to 2 days. The patient revealed that the swelling was sometimes severe enough for him to visit the emergency department, during which he was typically prescribed corticosteroids and antihistamines. These drugs did little to resolve his symptoms. 

“In between episodes, a work-up involving an upper [gastrointestinal] endoscopy and an abdominal ultrasound was unremarkable,” Mumneh et al wrote. 

During one emergency department visit, he had an emergency cholecystectomy performed; this was done despite normal gallbladder pathology. Eventually, laboratory findings revealed low C1-inhibitor levels and function, as well as low C4. These results, combined with the patient’s clinical and family history, led to a diagnosis of HAE. 

This short case study illustrates the difficulties of identifying the correct source of gastrointestinal symptoms in a patient with yet undiagnosed HAE. It is common enough for physicians to fail to connect the symptoms of an acute abdomen with HAE in a patient with an existing history of the disease; figuring out the cause of gastrointestinal symptoms in a patient without a history of HAE would require remarkable intuition and some familiarity with this disease, since it is very low on the list of differential diagnoses. 

Read more about HAE patient education 

Nevertheless, a few facts about the case could prompt physicians to consider a diagnosis of HAE: the failure of antihistamines to elicit an adequate response should rule out spontaneous histaminergic angioedema; in addition, swelling in the face and hands is another clue that the disease extends beyond the gastrointestinal system.

“It is important for gastroenterologists to recognize this type of abdominal attack and to evoke the diagnosis of bradykinin-mediated angioedema,” Mumneh and colleagues wrote. “If [hereditary angioedema] is identified, long-term management should be in collaboration with an allergist and/or immunologist with the option of prescribing the newer improved therapies.” 

References

Cao Y, Liu S, Zhi Y. Recurrent and acute abdominal pain as the main clinical manifestation in patients with hereditary angioedemaAllergy Asthma Proc. 2021;42(2):131-135. doi:10.2500/aap.2021.42.210001

Mumneh N, Tick M, Borum M. Angioedema with severe acute abdominal pain: think of hereditary angioedemaClin Res Hepatol Gastroenterol. 2021;45(4):101702. doi:10.1016/j.clinre.2021.101702