In recent years, however, as consumer demand for natural foods has risen, food manufacturers have been replacing synthetic additives with natural ones derived from plants, insects and other animal products. These natural substances are more likely to provoke an allergic reaction because they contain proteins that our immune systems might react to, said Dr. Ronald Simon, an allergist and immunologist at Scripps Clinic Carmel Valley in San Diego, who reviewed the literature for UpToDate, a clinical information resource used by doctors.

These natural additives include substances like a red food dye called carmine or cochineal extract, which is made from insects; a yellow dye made from the fruit of the annatto tree; psyllium, a source of dietary fiber derived from seed husks; and guar gum, which is made from a bean and is used as a binder and emulsifier in food and drugs. All of these have been implicated in rare cases of anaphylaxis.

Allergic reactions have also been reported from carrageenin, a thickener derived from seaweed; the jelling agent pectin; gelatin; and Mycoprotein, a fermented fungus used as a meat substitute and marketed under the brand name Quorn.

Our immune system recognizes these natural proteins, Dr. Simon said, “because it evolved to protect us against invading organisms and to recognize protein structures in fungi and bacteria or cancer cells.” He said the immune system is less likely to recognize a synthetic additive. (Dr. Simon acknowledged he has served as a consultant on food additives for the International Association of Color Manufacturers.)

Dr. Swerlick, the dermatologist who treated Ms. Eisenberg, agreed that reactions to synthetic additives are rare and not well understood, making them even more difficult to identify. In a 2013 paper, he described 11 patients he had seen over a five-year period, all of whom came in with chronic skin disorders that cleared up significantly when drugs containing coloring were replaced by dye-free medications. (Skeptics say that hives generally come and go and there is no proof that the removal of dyes caused the patients’ skin to clear.)

Each of Dr. Swerlick’s cases was slightly different, he said, so it was “a bit of detective work.” One 61-year-old patient had chronic skin problems on his hand, but the rash flared up suddenly, shortly after he refilled a prescription for diabetes pills and noticed that the color had changed from off-white to dark purple. The new pills, it turned out, contained a blue dye. Another patient, a 42-year-old man, had suffered from a rash for almost a year but noticed it resolved when he went on vacation and left his toothpaste, which contained a blue dye, at home.

Many of the patients had “a drug allergy list that’s 20 drugs long,” Dr. Swerlick said. “You realize they can’t be allergic to all these medications. It must be something common to all of them, like a dye. That’s one of the clues.”