Paula J. Busse, MD, is a leader in the clinical care of patients with hereditary angioedema (HAE). And when it comes to fighting for her patients, Dr. Busse, Professor of Medicine (Clinical Immunology and Allergy) at the Icahn School of Medicine at Mount Sinai, is all in.

HAE is a rare and challenging genetic disease whose symptoms include swelling in the abdomen, extremities, face, and airway, the latter of which can be life-threatening if not properly treated. The number of those affected by the disorder is just a few thousand in the United States, and as a result there are very few physicians who specialize in treating the condition.

As explained in a 2020 review article in The New England Journal of Medicine co-authored by Dr. Busse, HAE causes vasodilation, which leads to fluid accumulation in tissues, producing angioedema. Angioedema of the gastrointestinal tract can cause severe abdominal pain and potential intestinal obstruction. Airway swelling can lead to death by asphyxiation. Swelling in the hands or feet can be painful and significantly limit activities of daily living.

HAE is an autosomal-dominant genetic disorder. In around 80 percent of patients, a plasma protein known as C1-inhibitor (C1-INH) is both dysfunctional and present in deficient levels; this is known as HAE type 1. In those with HAE type 2, C1-INH is dysfunctional but at appropriate levels. A very rare third type of HAE is found in those with normal C1-INH and functional levels, secondary to defects in other genes (some of which have been identified), causing HAE-like symptoms.

Allergic reactions can cause angioedema, but those reactions are induced by histamine. In HAE, the angioedema is induced by bradykinin, a peptide that promotes vascular dilation with subsequent fluid extravasation to tissues. Bradykinin-mediated HAE is distinct from histamine-mediated angioedema and does not respond to antihistamines or corticosteroids, which are used for allergies. If not differentiated by the clinician, the result can be treatment that is ineffective—a perilous prospect if the airway is involved.

Evolving Guidelines

There are two major sets of guidelines for the clinical care of the patient with HAE, and Dr. Busse has helped develop both. One stems from work by the United States Hereditary Angioedema Association, a U.S.-based patient organization on whose medical advisory board Dr. Busse sits. Working together, the advisory board created guidelines for treatment of HAE in 2013 that were updated in 2020. Dr. Busse, who was the first author of this report, notes that the revised guidelines reflect advancements in the understanding of HAE and significant changes in its clinical management.

The other set of guidelines, for which Dr. Busse was a co-author, is an international effort from the World Allergy Organization and European Academy of Allergy and Clinical Immunology. Published in 2022, the guidelines addressed slight differences in treatment philosophies and access to therapies between U.S. and European clinicians. “At this point there are two guidelines, the U.S. and the international,” Dr. Busse explains, “but the gap between them on treatment recommendations has narrowed with the latest publication.”

The cost of HAE medications can be expensive and prohibitive. One dose of a C-1 inhibitor is several thousand dollars. “Many emergency rooms are not going to carry these drugs, although we have it on formulary here at Mount Sinai,” Dr. Busse notes. Because of the high cost, she often needs to fight for her patients, spending hours on the phone debating the merits of health care coverage with reluctant insurers.

“I spend quite a bit of time working to get patients assistance, for example through the Hereditary Angioedema Association. There is an emotional hardship for some of these patients and their families because they can’t get medications or appropriate care,” she says. “Some of these patients don’t have the insurance to see a specialist like myself, so they go to other physicians, who perhaps have mismanaged them because they don’t have the expertise, and that can lead to morbidity and even mortality. That is pretty upsetting to me.”

Dr. Busse’s approach to the clinical care of patients with HAE is to be a leading expert on the disease and to keep fighting for them. “I have been able to get some companies to donate their medications and I spend a lot of time getting prior authorizations for these patients’ medications,” Dr. Busse recalls.

Her weapon of choice for these battles? The phone.