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What is HAE?

Hereditary Angioedema is a genetic disorder of the complement and contact activation systems. Most patients have a deficiency or dysfunction of C1 esterase inhibitor — a protein that regulates production of bradykinin. When the regulation fails, bradykinin accumulates locally and causes the blood vessels to leak, producing the characteristic swelling.

Because HAE is bradykinin-mediated rather than histamine-mediated, it does not respond to the medications used for typical allergic swelling. Antihistamines, steroids, and epinephrine — the standard treatments for ordinary angioedema or anaphylaxis — have little or no effect. The right diagnosis matters enormously because the right treatment is entirely different.

HAE attacks can affect the skin, the gut, and the airway. Throat involvement is potentially fatal and is the reason every patient with HAE needs both an effective acute treatment plan and, for most, a long-term prevention plan.

When to consider evaluation

  • Recurrent episodes of swelling without urticaria
  • Swelling that does not respond to antihistamines, steroids, or epinephrine
  • Recurrent unexplained severe abdominal pain
  • A family history of HAE or of unexplained sudden death from throat swelling
  • Attacks triggered by trauma, dental work, stress, or estrogen exposure
  • Episodes of facial or limb swelling that resolve spontaneously over 1–3 days

How it is diagnosed

Diagnosis begins with three blood tests: serum C4 (typically low in Type I and II HAE both during and between attacks), C1-inhibitor quantitative level, and C1-inhibitor functional assay. When indicated, genetic testing is added. A small subset of patients have HAE with normal C1-inhibitor; in these cases, additional genetic testing for FXII, plasminogen, angiopoietin-1, and other identified mutations is considered.

Family history is taken in detail, both to support the diagnosis and to identify other family members who may need testing.

Treatment options

Optimed Immunology prescribes the full range of FDA-approved HAE therapies. Each patient receives an individualized plan that includes both an acute (on-demand) treatment for breakthrough attacks and, in most cases, a long-term prophylactic therapy to prevent attacks.

Acute treatment options include intravenous C1-inhibitor (Berinert, Ruconest), subcutaneous icatibant (Firazyr), and ecallantide (Kalbitor). Long-term prophylaxis options include subcutaneous lanadelumab (Takhzyro), subcutaneous C1-inhibitor (Haegarda), intravenous C1-inhibitor (Cinryze), and oral berotralstat (Orladeyo). The right combination depends on attack pattern, severity, route preference, and lifestyle.

All prior authorizations are handled in-house. Patients receive a written action plan and education on early recognition and treatment of attacks.

What to expect at your visit

A first visit for suspected or known HAE lasts 60 minutes or longer. Dr. McNeil reviews your complete attack history, family history, and prior treatment trials. Diagnostic labs are ordered if not already complete. For confirmed HAE, the visit also covers building an acute treatment plan, considering long-term prophylaxis, and educating you on recognition of throat involvement and when to seek emergency care.

Medically reviewed

Donald L. McNeil, MD · Board Certified in Allergy & Immunology and Internal Medicine

Last reviewed: November 2025 · Sources: AAAAI · ACAAI · Immune Deficiency Foundation · FDA prescribing information · relevant clinical guidelines

This page is provided for educational purposes and does not substitute for clinical judgment or direct medical advice. Treatment decisions are individualized based on your full history, examination, and laboratory findings. If you have an emergency, call 911.

Schedule a consultation with Dr. McNeil.

If you suspect you may have HAE, an evaluation can clarify the diagnosis and identify whether treatment is appropriate.