Undiagnosed Hereditary Angioedema in Pregnancy – Case Study

Case Description

A pregnant 23-year-old woman (nullipara, gravida 2) with anxiety and a history of cocaine use visited the hospital at 9 weeks gestation for episodic abdominal pain, nausea, vomiting, and intermittent unilateral swelling of the hands and feet over the past 2–4 days. She reported a non-itchy rash appearing before the onset of symptoms. There is no family history of swelling.

During the course of her pregnancy, she visited her gynecologist or the emergency department for similar symptoms four more times, each time being evaluated to exclude pregnancy complications and reassured that her symptoms would resolve after delivery.

Postpartum Infection?

The woman delivered a healthy baby girl at term (via C-section under spinal anesthesia) and was discharged from the hospital 2 days post-delivery. However, on the 11th day postpartum, she returned with swelling and erythema of the cesarean incision wound. She was diagnosed with cellulitis and treated with i.v. ceftriaxone followed by oral antibiotics for 2 weeks.

A few days later, the patient returned with abdominal pain and swelling of the left labia and right thigh. CT scans showed inflammatory changes around the incision and retroperitoneum, without visible abscess. Her symptoms further worsened, leading to vomiting, diarrhea, abdominal distension, and pain. She developed volume depletion and tachycardia, did not respond to an ondansetron bolus and fluids, and was admitted to the obstetric ward for suspected cesarean wound infection. Her condition improved over the course of a week with antibiotic treatment and vacuum-assisted wound closure.

Intestinal Disease?

Over the following 9 months, she experienced episodes of abdominal pain, nausea, vomiting, and intermittent swelling. During this time, she visited the emergency department 6 times, was hospitalized once, and saw 5 different specialists who conducted extensive evaluations. Proposed diagnoses included gastroenteritis, nonspecific colitis, and various gastrointestinal infections.

Hereditary Angioedema!

Ten months postpartum, a test for C4 and C1 inhibitor levels was performed, repeatedly detecting low levels (C1-INH: 0.18 and 0.37 U/ml; C4: 0.06 and 0.07 g/l). The patient was referred to an allergist and clinical immunologist, and genetic testing revealed a previously unknown missense mutation in exon 8 of the SERPING1 gene, leading to a diagnosis of Type 1 HAE. The patient is now treated with prophylactic C1-INH and icatibant for breakthrough swellings, with good response.

Discussion and Conclusion

Abdominal symptoms are most common in pregnant women with HAE, but they are often nonspecific and can resemble common pregnancy-related symptoms. Although the described patient exhibited classic HAE signs, several factors likely contributed to the delayed diagnosis – pregnancy, a history of cocaine abuse, absence of facial swelling, negative family history, and her age. Most patients develop HAE in childhood or adolescence. In a retrospective analysis of 125 pregnant women with symptomatic HAE, 71% of cases were not diagnosed before pregnancy, with correct diagnosis often occurring years after pregnancy. Pregnancy can either increase or decrease the frequency and severity of HAE attacks.

HAE should be considered for any patient with unexplained abdominal pain and recurrent episodes of angioedema (particularly if unilateral) without urticaria.

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Sources:
1. Chair I., Lacuesta G., Nash C. M., Cook V. A challenging diagnosis: hereditary angioedema presenting during pregnancy. CMAJ 2022 Sep 26; 194 (37): E1283–E1287, doi: 10.1503/cmaj.220604.
2. González-Quevedo T., Larco J. I., Marcos C. et al. Management of pregnancy and delivery in patients with hereditary angioedema due to C1 inhibitor deficiency. J Investig Allergol Clin Immunol 2016; 26 (3): 161–167, doi: 10.18176/jiaci.0037.