At the university, Benson was surrounded by doctors — many he’d trained and then hired — who were as fascinated by difficult diagnoses as he was. When the documents arrived, he organized something he called a diagnostic flash mob. As he had for the past decade, when facing a tough diagnostic problem, he sent out a message inviting anyone who was free to help him think through the case.

A week before the young woman was scheduled to visit, Benson presented her case to his colleagues, his flash mob. One doctor pointed out that no one had identified what had caused her allergic reaction — why not? Perhaps she was allergic to something rare, suggested another. Could she have catamenial anaphylaxis, a reaction caused by a hormone of her menstrual cycle? Or what if there was no specific trigger — what if the whole system was somehow in overdrive?

Or maybe this wasn’t anaphylaxis, offered another. Maybe it’s her heart after all. Benson took notes throughout the discussion.

Possible Disorders

The following week, the young woman and her parents flew from New York to see Benson. He spent more than an hour with her, going over these episodes and her medical history. He examined her, then sent her to the lab to get a few tests. When the results came back, Benson put together a letter for her and her doctor outlining all the diagnostic possibilities he’d considered and how likely he thought each was. Like her allergist, he couldn’t find a pattern to these attacks. It wasn’t food, or some environmental exposures or even her monthly hormonal changes. And if there was no trigger to what sounded very much like an allergic reaction, Benson’s list of the likely possibilities got much shorter. And at the top of that list were diseases of mast-cell proliferation.

Allergic reactions are caused by a part of the immune system called mast cells. When these cells encounter bacteria, or something they mistake for an invader (i.e., the allergen), they release chemicals that cause blood vessels to enlarge and tissues to swell and become more permeable so that the fighter cells of the immune system can get in and destroy the invader. At their mildest, these cells cause the swollen, runny nose of allergic rhinitis. At the other end of the spectrum, they can cause the hypotension and swollen, closed airway or gastrointestinal distress of anaphylaxis.

There are unusual disorders caused by the development of too many mast cells. The most common of these is called systemic mastocytosis, in which many of those mast cells develop a mutation that makes them more excitable and more easily triggered. Once set off, these overabundant, hyperactive cells turn their biological weapons against the self, causing a severe allergic reaction.