How Allergies Happen, and Why They Appear or Vanish

Allergies feel arbitrary from the outside, yet inside the body they follow a script. The immune system, tuned to detect parasites and poisons, meets something harmless like pollen or peanut protein. It files that encounter under “danger,” creates a molecular reminder, then overreacts on the next exposure. That is the entire plot of hay fever, hives, wheezing, anaphylaxis.

What most of us call an “allergy” is a two-act play: first sensitization, then a repeat encounter that triggers release of histamine and other chemicals from mast cells.

Here is the cellular choreography. In susceptible people, a first exposure prompts T helper 2 cells to nudge B cells into making IgE antibodies. Those IgE molecules stick to mast cells and basophils like tiny tripwires. When the allergen returns, it crosslinks those IgE tripwires, the cells erupt, and histamine, leukotrienes and other mediators cause itching, swelling, sneezing, coughing, sometimes a drop in blood pressure. This classic, IgE mediated pathway explains most food allergy, pollen allergy and anaphylaxis, and it is why antihistamines and epinephrine work.

There are important variations. Some reactions are delayed and driven by T cells rather than IgE, for example certain rashes after antibiotics or contact allergy to nickel. Drug “allergies” can also be pharmacologic intolerances, as with aspirin related breathing problems. The reader who developed an adult acetaminophen reaction may have an IgE allergy, a delayed T cell reaction, or a non immune intolerance; an allergist can sort that out with history, testing and, if safe, a supervised challenge.

We inherit a tendency toward this overreaction, not an exact list of offenders. Physicians call that tendency atopy. Children of allergic parents have higher odds of allergies, asthma and eczema, especially if both parents are affected. Genome wide studies point to dozens of genes, including immune switches in the HLA region and FLG, which encodes filaggrin, a protein that helps seal the skin. Loss of filaggrin is strongly linked to eczema and higher risk of peanut allergy, probably because a leaky skin barrier gives the immune system a misleading first lesson.

That is the heart of the modern “dual exposure” idea. When the first exposures to a food happen through broken skin, as with babies who have eczema, the immune system is more likely to become sensitized. When the first exposures happen in the gut, during normal feeding, the immune system is more likely to learn tolerance. The concept feels abstract until you see the magnitude of the effect in clinical trials.

Introducing peanut into the diets of high risk infants reduced peanut allergy by about 81 percent in the landmark LEAP trial (NEJM).

That single result overturned a generation of avoidance advice. Pediatric guidelines now endorse early introduction of peanut for most infants, with extra guidance for babies with severe eczema or egg allergy. It is a sharp example of how environment can beat genetics, and it clarifies a common confusion: you inherit risk, not a peanut allergy per se. That is why a parent with spring allergies can have a child with egg allergy, and why families sometimes perceive a “skipping generation” pattern. The genes are shared, the exposures and timing are not.

Cleanliness is part of the story, but not because dirt is magic. The old hygiene hypothesis has matured into a biodiversity hypothesis, the idea that modern life reduces the microbial richness that educates early immune responses. Striking data come from neighboring traditional communities with different farming practices. Amish children who live with high microbial exposure in their homes have far lower rates of asthma than Hutterite children in more industrialized farms, along with immune signatures that suggest more robust innate training (NEJM). Pets, siblings, daycare, outdoor play and diet all nudge this early education. So do pollutants. Diesel exhaust and indoor smoke can tilt airways toward inflammation, and global warming is changing the classroom too.

Across North America the pollen season has lengthened by about 20 days and pollen concentrations have risen roughly 21 percent since 1990 (PNAS).

One last wrinkle that puzzles many families is cross reactivity. Proteins that look alike can fool IgE, which is why people with birch pollen allergy can get an itchy mouth from apples or hazelnuts, a pattern called oral allergy syndrome. It also explains why some react to chickpea, fenugreek or lentils along with peanut, all legumes that share similar protein motifs. The mystery spice in curry powder is sometimes not a mystery at all.

People often say they “developed an allergy out of nowhere.” There is always a first sensitizing exposure even if it was invisible. Adult onset can follow a change in environment, a new job, a home renovation, a respiratory infection that shifts immune tone, or, for foods, a period of avoidance followed by reintroduction.

Disappearance has a logic too. Many children outgrow milk and egg allergy as their immune systems build regulatory circuits and blocking antibodies, particularly IgG4, that compete with IgE for the same allergen. Peanut, tree nut and shellfish allergies are more stubborn, but not immutable. Roughly 1 in 5 children with peanut allergy will eventually tolerate it. Pollen allergies also wax and wane, often tracking life stages, geography and cumulative exposure.

We can also teach the system on purpose. Allergen immunotherapy, the old fashioned series of shots for ragweed or cat dander, reshapes T cells and antibodies over three to five years and reduces symptoms long after treatment stops. Sublingual drops and tablets work for some pollens and dust mites. In food allergy, carefully supervised oral immunotherapy trains the gut by giving tiny, increasing doses, trading daily discipline for a lower risk from accidental bites. The first FDA approved product, peanut powder for children, arrived in 2020 (FDA), and new biologic drugs are making this training safer.

Omalizumab, an antibody that soaks up free IgE, was recently approved to reduce the severity of reactions from accidental exposure to multiple foods, and it is being used to stabilize patients who are starting oral immunotherapy (FDA). Other biologics that block IL-4, IL-5 or TSLP are changing the trajectory of eczema and asthma, the other corners of the atopic triangle.

All this leaves reasonable questions. If exposure can prevent allergy, why do some kids get worse when exposed? Because dose, route and timing matter. Smearing peanut lotion on eczematous skin is not the same as eating peanut in infancy. If genetics matter, why do identical twins sometimes diverge? Because epigenetic marks change with environment. If I avoid a food long enough, will I lose my allergy? Sometimes, but often the risk goes up rather than down without a structured plan. The immune system is plastic, not programmable.

Practical takeaways, grounded in evidence

• For most infants, introduce common allergens in the first year, including peanut and egg, following pediatric guidance and the LEAP evidence for high risk babies.
• Protect the skin barrier in babies with eczema, ask about filaggrin related dry skin, and be cautious with topical products that contain food proteins.
• Normalize microbial diversity, outdoor play, pets if you want them, and healthy air. Avoid tobacco smoke and unnecessary indoor pollutants.
• For established allergies, discuss immunotherapy and, for food, whether oral desensitization is appropriate. Ask about new biologics that can reduce risks during training.
• Carry epinephrine for anaphylactic food allergies. Antihistamines ease itching and sneezing, they are not a substitute for epinephrine in severe reactions.

It is tempting to think of allergies as a fixed identity, the kid who is allergic to peanuts, the adult who is allergic to cats. The better frame is educational. The immune system can learn, it can forget, and it can be taught. The lesson plan starts before birth and runs through the first years of life, then keeps going. If we treat it that way, the story many families live through, the surprise, the fear, the avoidance, can be replaced with something more empowering, evidence guided exposure that builds tolerance and smarter care when avoidance is still necessary.