Thirty years ago, fewer than a half-percent of American children suffered from peanut allergies—a potentially life-threatening condition. Over the next two decades that number tripled, and today it is estimated at somewhere between two and five percent. In a world where exposure to peanuts and other allergens is increasingly likely in school cafeterias, fast-food eateries, and even the neighborhood birthday party, this is no small matter.

Happily, in the past decade, a solution has emerged. It’s called oral immunotherapy (OIT), a process of desensitizing patients to the foods they are allergic to, thus protecting them from the dangers of a severe allergic reaction. Thanks to this innovative therapy—after decades of increasing numbers of children with life-threatening peanut allergies, 2025 saw a radical decrease in those numbers (see box, right).

But ten years ago, OIT was an untested theory, and allergists and pharmacists were just beginning to explore how to turn theory into practice. Among the pioneers in that effort were pharmacist Zoe Stefanadis of Chapel Hill Compounding Pharmacy and allergist Dr. David Fitzhugh of Allergy Partners of Chapel Hill. Their joint project—launched nine years ago—was to create an effective, efficient mechanism for desensitizing those with peanut allergies. The project was an interesting challenge for both.

The Challenge

“When Dr. Fitzhugh approached me with this idea,” says Ms. Stefanadis, “I was really intrigued! My first reaction was ‘this is a natural assignment for a compounding pharmacy.’ My work, fundamentally, is problem solving; that’s what compounding is all about—and that’s what makes it such fascinating work.

“Everything we compound is, in fact, a unique solution to a specific medical problem for a specific patient,” she explains. “We add flavors to help with bitter medications—something that’s especially useful for   children and pets. Maybe the drug that’s needed is made with dyes or fillers the patient can’t tolerate. Perhaps they need to taper up or taper down, and standard drugs aren’t available in the right dosages. Or the medicine irritates the GI tract, so they need the drug in topical form. Or, or, or. . . the challenges of preparing the right medication, in the right form and dosage for individual patients with unique needs are endless.

“The peanut allergy problem was a first for me, however,” Ms. Stefanadis recalls. “The puzzle Dr. Fitzhugh presented sounded simple enough: to compound various nut flours in capsule form and in precise protein levels that gradually increased with the desensitization program. But we soon found out that we had a lot to learn to accomplish this successfully!”

The project presented a learning curve for Dr. Fitzhugh as well. “The theory behind oral immunotherapy,” he explains, “is that people with food allergies can be gradually desensitized by exposing them to minute amounts of their food allergen in a careful graded fashion.

“We’ve always dealt with food allergies, but until OIT, working with children with peanut allergies was depressing, because the only therapy was to avoid the allergen and carry an EpiPen for emergencies. And avoidance is hard.

“The growing numbers of children with food allergies has broader implications than the risk of exposure. Too often these kids are stigmatized, often separated at the ‘peanut table,’ or maybe restricted from social activities, such as a field trip or party, because their parents are worried about a serious reaction. So, there are a lot of reasons why having a food allergy can be potentially isolating for a child. And it underscores just how important these desensitization therapies are.

“The first protocols and research proposing gradual desensitization therapy,” says Dr. Fitzhugh, “were published about 15 years ago. And there were many concerns and questions about how to accomplish this, given that there was no commercially approved product for this.

“I’m part of what I would call the second wave of allergists and immunologists who began experimenting with how to design an effective program—that was about nine or ten years ago. And, before I began working with Zoe, I was personally mixing all these solutions in liquid format. That was a real challenge, because the key to the desensitization process is to make gradually increasing dosages beginning with very small, precise amounts of the peanut protein. Since I’m not a pharmacist, and lacked the tools, it was a difficult, unwieldy process. It was hard to create a solution and even harder to dose each one accurately. It quickly became clear to me that there had to be somebody who could do a better job than I could!”

At this point, Dr. Fitzhugh asked his neighbor Zoe Stefanadis if this was something she could do, and their partnership began.

“Working with a compounding pharmacy was an obvious choice,” he says. “And thanks to her problem-solving approach and talented staff, partnering with Zoe and her team became the key to a very successful program. Not only have they been able to make the precise medicines we need for a standardized program of peanut and tree nut desensitization, but they have also developed special protocols for kids who are highly allergic. It’s been a wonderful partnership, and we couldn’t have done it without them.”

The Project: Putting Theory into Practice

“Today, we make these desensitization medications routinely for allergy practices in several states,” says Ms. Stefanadis, “not only for peanut allergies, but for many tree nut allergies, including cashews, pistachios, hazelnuts, walnuts, and pecans.

“But nine years ago, the task was surprisingly challenging. Very few pharmacies had done this, so we had relatively little information to go on. Step one was to work with Dr. Fitzhugh to understand the requirements; next was to work with my technicians to develop a plan for everything from finding sources for peanut protein to packaging. It was a team effort in every way.”

“The desensitization process,” explains Dr. Fitzhugh, “is a carefully structured program of gradually increasing dosages of the peanut protein. Each dosage level is staged over a three-week period, and the first dosages are administered in office to ensure that there are no problem reactions. After 21 days at one dosage, we’ll test and then start the next level, again for three weeks. Every time we increase a dosage it’s done under observation in the office, since there’s a low but measurable chance of reacting to these dose increases. Ultimately, we typically get these kids into several grams of their respective allergens.

“So the puzzle we asked Zoe and her team to solve was to compound these many different, very small—dosages in capsule form—so the lengthy process of desensitization could be accomplished efficiently and safely.”

“That puzzle,” says Ms. Stefanadis, “could only be solved through compounding. There were many challenges. To begin with, the active ‘medicine’ was peanut protein—and I had never thought I’d refer to peanut flour as active pharmaceutical ingredient, but so it is.

“We soon learned that peanut flours have different consistencies—difficult to standardize and challenging to prepare in very small dosages. So that led us to the next problem of sourcing—where to find the peanut flour that meets the same standards of quality and consistency we require of all our medicines.

“So a first step was to find a reliable source. Next was to experiment with the best way to prepare and deliver the various dosages. In a case like this,” she explains, “standardization—consistency—is critically important. The FDA considers a 90 percent rate acceptable. But in the work we do—and especially in the case of allergies and desensitization—90 percent is not acceptable. Each of the many dosages has to be precise and consistently accurate. So standardization is essential. And packaging is important, too; for example, we use color coded capsules to distinguish between different dosage levels and ensure that the medicines are taken accurately.

“After solving each of these pieces of the puzzle,” she says, “we were able to come up with efficient formulations—for peanuts as well as other nuts, including walnuts and pistachios. And in the years since, the desensitization project has expanded. More than five allergy clinics in three states are now working with Chapel Hill Compounding to use this method of desensitization with their patients.”

Outcomes

Is OIT successful? “Indeed it is!” says Ms. Stefanadis. “I like to describe it as a careful journey where, at the end, most children can safely eat a candy bar with peanuts! It’s a ‘safe’ process in large part because of the standardization protocols we’ve developed.”

“OIT has indeed proven to be effective,” agrees Dr. Fitzhugh. “It takes time; for the average food allergen, it’s usually at least six months and sometimes a year to get to a point of acquiring adequate protection. But the feedback I hear from my patients’ parents is powerful—the relief they feel when their kids reach the point of protection is overwhelming. Being able to offer—not a cure—but a therapy that provides protection against a potentially life-threatening problem is super satisfying.

“Success rates vary,” he acknowledges. “We’ve found that selecting the right candidates is important to getting to what we consider a reasonable protected dose—which is about a thousand milligrams of food protein. In real-world terms, that’s about four whole peanuts. And about 85 percent of our patients are able to get to that dose. So it’s not 100 percent, but we’ve also gotten better at predicting who’s a good candidate. The most important factor is age; starting younger is better. So, we’re starting kids now as young as two and three.

“While OIT works best for certain patients, the success rate overall is high. Once that point of protection is reached, maintenance is all that’s required and people can comfortably fit the therapy into their life routines.”