Two Cases of Hereditary Angioedema with Isolated GI Manifestations

Background: Hereditary angioedema (HAE) is a rare disorder due to deficiency (type I) or dysfunction (type II) of C1 esterase inhibitor (C1inh). Case 1: A 33-year-old, otherwise healthy, woman reported a 14 year history of paroxysmal abdominal pain with vomiting and watery diarrhea. Each time the symptoms resolved spontaneously within 24-48 hours. Repeated serological and imaging studies were normal. Over the years, the patient had undergone 3 exploratory laparotomies due to severe presentations concerning for intestinal obstruction. Each time, no pathology was found other than free fluid in the pelvis. A recent similar presentation led to a CT of the abdomen revealing a single thickened loop of jejunum with proximal intestinal dilation and minimal ascites. Bloodwork was normal except for a decreased C4. Subsequent C1inh assays were diagnostic of HAE type II - C1inh quantity = 0.2 g/L [0.21-0.49 g/L] and C1inh function = <35% [80-105%]. The patient did not have any skin or pulmonary manifestations of angioedema. Six months later, she presented again with abdominal pain. Her symptoms resolved rapidly and completely with administration of C1inh replacement protein. Case 2: A 41-year-old woman with a history of endometriosis presented with 3 years of recurrent, severe abdominal pain associated with vomiting. At her second presentation she underwent an urgent diagnostic laparoscopy with no findings except for free fluid in the pelvis. She was trialed on estrogen suppressive therapy for endometriosis but the attacks escalated. On one occasion, a CT scan revealed an isolated thickened jejunal loop. Upper and lower endoscopies were normal as were studies for autoimmune disease, catecholamine excess, carcinoid syndrome and porphyria. Complement studies showed normal C3 & C4, C1inh = 0.22 g/L [0.21-0.49 g/L] and function = <35% [80-105%]. Exogenous estrogen was discontinued and her treament plan will include administration of C1inh replacement protein on her next presentation. Conclusions: This rare disorder can mimic intestinal obstruction and should be considered in patients with unexplained abdominal pain. C4 is the substrate for C1 thus should be low during attacks if C1inh is deficient or dysfunctional. Twenty percent of patients with HAE have isolated GI manifestations. Ascites may be the only sign in the late stages of an attack. Skin and life-threatening laryngeal angioedema can occur. ACE inhibitors and exogenous estrogens can exacerbate the condition by depressing endogenous C1inh levels, whereas androgen receptor agonists can be used as therapy. Many centers have C1inh replacement protein available; fresh frozen plasma can also be used to abate acute attacks.