Far more common are nonallergic reactions to aspirin and other NSAIDs that are caused not by the chemical structure of the medication but by how it does the job it is meant to do. NSAIDs interrupt the chemical chain that leads to an inflammatory response; that’s how they relieve pain. But for reasons that are not well understood, in some people this chemical chain changes, and those alterations cause the opposite to happen. Instead of reducing swelling, NSAIDs in these patients increase it, causing tissues, particularly in the respiratory tract, to become inflamed and swollen. Many of these reactions look just like an allergic response. Patients may get hives, itchy eyes and a runny nose. Or swelling of the eyes, lips or throat. Unlike true allergic reactions, which are usually limited to a single medication, this reaction can occur when any of the painkillers that affect this part of the chemical chain are taken.

For most of these reactions — both allergic and nonallergic — simply avoiding the medication, or the class of medication, is sufficient to prevent the consequences. But there is one type of nonallergic reaction to NSAIDs for which avoiding the drug is not enough. In what’s called aspirin-exacerbated respiratory disease (AERD), the hypersensitivity reaction these medications trigger is an essential clue to an underlying progressive disease process that can and should be treated.

AERD is characterized by the confluence of three disorders that together are known as Samter’s triad: First, patients have a hypersensitivity to aspirin and other NSAIDs; second, they have asthma that is often poorly controlled, even on the usual medications; third, they have nasal polyps. Although the disorder was first described early in the 20th century, it is still the focus of much research and is only beginning to be understood.

A Clue in the Nose

Jerschow suspected that the patient had AERD. Her recent hospitalization proved that she had a severe hypersensitivity reaction to NSAIDs. And she had poorly controlled asthma too. But did she have nasal polyps? Not that she knew of, the patient said. How was her sense of smell? the doctor asked. Over the past year or so, the patient reported, she’d lost her sense of smell — and much of her sense of taste. She was a good cook, but without the ability to smell or taste, it was hard to tell how a dish turned out. Jerschow wasn’t surprised; loss of smell is seen in over 95 percent of patients with AERD.

Jerschow put the nasal speculum into the woman’s nose. Were there polyps? Jerschow wasn’t sure. She sent the patient to an ear, nose and throat specialist who scoped her upper airways. She did indeed have polyps. She had AERD.

It’s a common disorder; up to 15 percent of those with severe asthma have AERD. The abnormality in the inflammatory pathway these patients develop somehow drives the entire process. It causes their hard-to-control asthma. It propels the development of nasal polyps. And it underlies these patients’ upside-down response to NSAIDs.

Finding a Helpful Treatment

Strangely, the treatment for AERD is aspirin, the oldest member of the NSAID family. It’s not clear why, but a daily dose of aspirin, titrated as high as is tolerated without triggering symptoms, can both improve asthma control and slow down the regrowth of nasal polyps.

The patient tried taking aspirin for several months, but nothing improved. In the five years since she was given this diagnosis, she has tried several medications. Some helped her sense of smell and taste, but none allowed her to start running — much less racing. A couple of months ago, the patient started a new medicine called Dupilumab. It’s a drug that targets a key step in the abnormal pathway to inflammation and swelling. She already feels much better. She’ll know she’s really back to her old self once she’s tough enough for her next Tough Mudder.