Table I.

Final 25-variable set used in the validated SIS tool

Symptoms •Recurrent swelling in any part of the face, lips, tongue, larynx, extremities, genital, or throat that is nonpruritic •≥1 episode of swelling (edema) in face, lips, tongue, larynx, or throat •Acute swelling episode lasting ≥2 d •Episode of swelling (edema) in face, lips, tongue, larynx, or throat that does not respond effectively to antihistamines, corticosteroids, or epinephrine •Recurrent acute abdominal pain and swelling episodes with no fever lasting more than 24 h •Swelling (edema) after surgery or a dental procedure •Facial, throat, lip, abdominal edema after starting birth control pills or HRT (estrogen-containing) or pregnancy •≥1 emergency room visits for appendicitis

Diagnosis •Diagnosed with acquired angioedema or ACE inhibitor angioedema •Diagnosed with HAE/angioedema due to C1 inhibitor disorder/C1 esterase inhibitor deficiency

Family history •Family history of hereditary angioedema •Family history of swelling of face, lips, skin, or tongue •Family member who died of suffocation due to throat or tongue swelling (laryngeal edema)

Genetic testing result • Pathogenic variant in genes with known association with HAE ○ ANGPT1 gene mutation ○ F12 gene (coagulation factor XII) gene mutation ○ SERPING1 gene mutation ○ PLG gene variant ○ KNG1 gene

Known triggers •Allergic reaction to ACE inhibitors, causing lip swelling, edema, or abdominal pain •Allergic reaction during pregnancy that caused lip swelling or edema

Laboratory results •Low serum C4 level •Absent or greatly reduced C1 inhibitor level or function

Therapies •Acute swelling responds to bradykinin B-2 receptor inhibitor or C1 esterase inhibitor •Treated with HAE-specific medications •Long-term use of steroids

Negative symptoms •Hives or urticaria •Diagnosis of bullous SLE/lupus •Diagnosis of kidney or heart disease •Diagnosis of cellulitis

ACE, Angiotensin-converting enzyme; HRT, hormone replacement therapy.