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If the affected mast cells are in the skin, lips, and eyelids, you get hives. If they are in the throat, you choke up and vomit. If they are in the lungs, you wheeze. You can imagine what havoc ensues in the GI tract. One measure of the severity of an allergy is a scale of 1 to 5; “level 5” indicates an extremely high antibody population in the bloodstream. The more IgE poised to respond, the more sensitive the patient is to even the smallest presence of the allergen and, in most cases, the more severe the reaction.

A level 5 allergy may trigger an anaphylactic reaction in which so many different vital functions shut down so fast that the body goes into shock. Blood pressure plummets and the patient loses consciousness. Anaphylaxis first grabbed pop culture's attention in the context of bee stings. (See exhibit A: Thomas J. in the 1991 movie
My Girl
. If your character is a quirky outsider with severe allergies, your days are numbered.)

I wish I could say that if five minutes have passed after exposure to an allergen and you are still upright, then you have dodged the bullet of anaphylaxis. But that's not the case. A reaction can start within seconds, or accumulate over a period of several hours. Some scientists believe delayed reactions result from a different antibody response—immunoglobulin G, or IgG—particularly primed to respond to such allergens as milk, wheat, and corn. After one ill-fated dinner party, I was awakened in the middle of the night by an attack I thought I'd tamed before going to bed, with a reaction much worse than the one
I'd had earlier. That's considered a biphasic reaction. In rare cases, anaphylaxis is triggered only if the allergen is combined with exercise in the three to four hours following exposure.

Anaphylactic reactions are sneaky bastards. On average they kill 150 people in America each year.

The eight most common food allergens in the United States are legally classified as milk, egg, peanuts, tree nuts, fish, shellfish, soy, and wheat. These foods account for more than 90 percent of allergies in the United States; there are about 160 known allergens, total. Corn and sesame are two other allergies with growing prevalence. Some of the least common food allergens are bananas, zucchini, potatoes, peas, turkey, and—though it seems exotic compared to the rest—avocado. All but avocado are popular in baby food form, and Gerber should probably get to work on a guacamole recipe.

The predisposition to develop allergies may be an inherited trait, but specific allergies are not. My father had allergies but outgrew almost all of them, which isn't happening in my case. He says that eating eggplant triggers an itchy throat, but we suspect this might be related to the fact that he detests eggplant. My mother experienced hives as a child, but she was never diagnosed with any specific food allergies. My younger sister doesn't have any food allergies except taro. Since her exposure took the form of tasting poi in Hawaii, she's not mourning the loss of taro from her diet.

There are a lot of gray areas in the realm of allergy. Celiac disease, often conflated with wheat allergy, is actually an autoimmune disorder of the small intestine that necessitates a gluten-free diet. But in acute cases, the severity of reaction demands zero tolerance for exposure—meaning those with
celiac face the same attending social complications as those with deadly food allergies.

Then there are the widespread intolerances to food, most notably lactose. Too many times someone describes this as a “food allergy” when speaking with a waiter or host. It's not an allergy; it's a condition of missing enzymes, translating into an inability to digest milk sugar, which causes abdominal pain.

I confess that when someone claims to have a dairy allergy, then indulges in a chocolate-chip cookie because he or she is willing to tolerate bloating and stomachaches later in the day, I get annoyed. That kind of behavior makes us all less credible. There's a reason the food allergic have taken to using the phrase “true allergy.” Millions of people have been diagnosed with food allergies. Yet the medical understanding of what causes them, and how to control or cure them, is maddeningly incomplete.

•  •  •

The mystery of allergies has been around since antiquity. Between the sixth and fourth centuries BCE, a collective of physicians that included Hippocrates of Kos composed the sixty or so treatises known as the Hippocratic Corpus, rejecting superstition to treat medicine as a science. The Corpus is known for giving us the phrase “First do no harm,” which is often conflated with the Hippocratic oath (though that exact phrase in translation is actually found in a different work of the Corpus,
Epidemics
).

Buried in this compendium of textbooks, lectures, and notes on philosophy is the observation that some patients can
eat cheese “without the slightest hurt … [while] others come off badly.” Many historians of science believe this to be the first recorded recognition of allergies. The larger passage makes clear that the cheese does not cause the suffering directly; the cheese is not spoiled or poisoned. Rather, that particular body exhibits a hardwired and self-destructive response, a “hostile humor” to cheese.

Subsequent generations of physicians were fascinated by this observation, but little research focused on the physiological roots of the phenomenon. Sir John Floyer, an English physician born in 1649, was one exception. He carefully listed the food, powders, and vapors that precipitated his asthmatic patients' difficulty in breathing.

That's not Floyer's claim to fame. He is remembered because he was the one who recommended to Sarah Ford—also known as Mrs. Michael Johnson—that she take her young son to the court of Queen Anne, where he would be touched and cured of the “King's Evil.” This proved to be a seminal event in the life of a certain Samuel Johnson. In addition to shaping the life of that literary critic, Floyer invented a watch for the purpose of measuring pulse, which he believed was a key indicator of health. But as far as allergies went, well, there wasn't even a name for the phenomenon yet.

It wasn't until 1906 that Clemens von Pirquet, an Austrian doctor engaged in research on smallpox and tuberculosis, coined the term
allergie
or
allergy
. His conflation of Greek words for
other
and
energy
evoked his theory that the disparate arrays of symptoms—i.e., edema, hives, vomiting—that he had observed in experiments were, in fact, a coherent biological reaction coordinated through the immune system: a
hypersensitivity to ingested foreign materials that increased with subsequent trials. Not all of his fellow scientists welcomed von Pirquet's insight. Quite the opposite. He started what would now be called a battle for brand recognition.

Prominent French physiologist Charles Richet publicly dismissed the word
allergy
on the grounds that the term he had created in 1902,
anaphylaxis
(rough translation: “absence of guard”), did a perfectly good job describing the issue. Richet would go on to win the 1913 Nobel Prize in Physiology or Medicine for his work with anaphylaxis, which he defined as any sensitivity developed in an organism after receiving an injection of a protein, colloid, or toxin. An expert on extrasensory perception and the occult, Richet's other coinages included
ectoplasm
and
metapsychics
. We can also thank him for figuring out that animals shiver in order to regulate body temperature.

For von Pirquet, this professional turf war was endemic of a career that always fell one step short of fame. Another French scientist, Charles Mantoux, used von Pirquet's research to develop an effective way of screening for tuberculosis infection. This procedure promptly became known as the Mantoux test. Five times von Pirquet would be nominated for the Nobel Prize, and five times he would not win.

Anaphylaxis
captured the big picture of a body's shutdown response, and the word is still used today. But von Pirquet's work in the clinics of Austria—augmented by time spent in Paris and Baltimore, Maryland, where he was offered a professorship at Johns Hopkins—rightly focused not on the antigens of invading matter but on the antibodies of the host. His point that the greatest damage was host inflicted placed him in step with an important generation of physicians including Ludwik
Fleck and Carl Weigert (who called it the “Siva effect,” invoking the self-sacrificing Hindu god). Many of our critical understandings of how allergic reactions form—only after the initial exposure, using an incubation period that shortens after subsequent exposures, and manifesting in a variety of symptoms for a variety of allergens—come from von Pirquet's findings.

By the 1920s, both the terms
allergy
and
anaphylaxis
were used in scholarly texts, and the former would eventually overtake the latter in public parlance. But professional success can't cure personal despair. In 1929, Clemens von Pirquet and his wife, Maria, committed suicide using cyanide. In his final years, the doctor had used sophisticated statistical analysis to identify correlations between volume of deaths and calendar date, laying the groundwork for what we can now identify as “seasonal” illnesses, such as hay fever. And depression.

Baron von Pirquet poisoned himself in February. Just nine months later, in November 1929, a new magazine debuted in America:
Journal of Allergy
.

Scientific interest in the allergy phenomenon had solidified under a common name, yet this did not translate to immediate medical comprehension. In the 1940s and early 1950s, physicians attributed illnesses as diverse as migraines, colitis, and multiple sclerosis to the villain of allergies. Allergies, together with hay fever and asthma, were the evil henchmen of increasing urbanization. Doctors prescribed “fresh air”; allergy sufferers were sent off to frolic in fields of ragweed. Magazine ads encouraged patients to light up a stramonium cigarette filled with jimsonweed, the dried hallucinogen also known as the devil's trumpet.

There were a few important technical and theoretical
advances during this time. Diphenhydramine, one of the first antihistamines, was invented by Cincinnati chemical engineer Dr. George Rieveschl in 1943 and approved by the Food and Drug Administration for prescription usage in 1946. Pfizer would later trademark the drug under the name Benadryl, and today it is available in a number of generic formats. Like-minded research in Europe led pharmaceutical companies to flood the market with antihistamines, which address allergic reactions directly by blocking histamine receptor sites. These are often paired with decongestant tablets that help manage attack symptoms.

Today, other available oral treatments include montelukast sodium, a leukotriene antagonist (meaning that it attacks other mediators of inflammation besides histamines) that is marketed under the name Singulair and is primarily used to treat chronic asthma. And in cases where a progressing attack interferes with the ability to swallow, a patient can use a nebulizer that converts a liquid medicine to an inhalable aerosol.

For the most acute attacks, a patient can self-administer a shot of epinephrine using an EpiPen or Twinject injector, to be followed by immediate medical care. Anyone who has been diagnosed with the potential for anaphylaxis is advised to carry an injector at all times. There's brisk business in carriers designed for the fashion savvy or, in the case of mothers buying for allergic sons, anything that doesn't resemble a tampon holder.

The 1940s also welcomed the first official “allergy clinic,” established in London at St. Mary's Hospital and headed by John Freeman, who was a pioneer in the field of immunotherapy injections. Using pollen allergies as their model, Freeman
and his colleague Leonard Noon theorized that regular subcutaneous doses of a known allergen administered in “Noon units,” extracts measured in weight per milliliter, could desensitize the patient. Today, shots are an FDA-approved therapy for allergies to pollen, pet dander, and insect stings. I collected approximately 782
I GOT MY SHOT TODAY
stickers over time, including a complete series featuring the members of New Kids on the Block. Though they have never proven particularly successful at reducing food sensitivity, and some experts doubt their overall effectiveness, they remain one of the most popular forms of treatment for children with allergies.

Much has changed in sixty years; much remains the same. A patient walking into St. Mary's in 1946 might have received, essentially, the same prick test I would have received in 1986. The prick test is as elegant a diagnostic tool as one would suspect given its name. A technician uses a lancet to create a grid of tiny subcutaneous breaks in the skin of the subject's back or forearm. Each prick point is then swabbed with the essence of one of the allergens being tested. After an appropriate waiting period, the skin is inspected for skin rash, hives, or other reaction. The bigger the wheal, the worse the allergy, but the nature of delivery ensures a reaction usually no more serious than a mosquito bite.

Like some of the simplest antihistamine compounds, this procedure endures in the modern day because it is easily available, is comparatively inexpensive, and provides fast results. But it's also traumatic. There's nothing worse than lying on your belly feeling a fiery swelling as it spreads across your back and being forbidden to scratch the itch, while a doctor says, “My goodness, look at that. That there.”

Giving patients the option of a less visceral diagnostic process, in 1974, a Swedish laboratory trademarked the RAST (radioallergosorbent test), which surveys a blood sample for the presence of specific immunoglobulin E antibodies. The yield of numeric data indicated not only the presence of allergies but also their severity, leading scientists to develop the rubric of level 1, level 2, and so on, assigned in correspondence to IgE frequency. Though RAST testing is expensive, it is now a standard diagnostic for those patients with a demonstrated capacity for anaphylactic reaction or with other factors that would complicate a skin test, such as eczema. The problem is that RAST testing, while useful, generates a lot of false positives. One of my rounds of RAST testing claimed I was allergic to both rice and pineapple—staple foods that have never caused a reaction when I've eaten them.

BOOK: Don't Kill the Birthday Girl
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