Allergies

TL;DR. An allergy is the immune system mounting a full defensive response against something harmless: pollen, peanut protein, cat dander, a bee sting. The mechanism is specific and worth knowing, because everything about allergy follows from it. On first exposure, the body makes IgE antibodies against the harmless protein and parks them on the surface of mast cells throughout the skin, airways, and gut. On the next exposure, the allergen bridges two IgE molecules, the mast cell dumps its contents within seconds, and histamine and other mediators produce swelling, itch, mucus, and constricted airways. When it happens locally you get hay fever or hives. When it happens systemically you get anaphylaxis, which can kill in minutes and for which the treatment is adrenaline into the thigh, immediately.

Key takeaways

• Allergic conditions affect a large and rising share of the world's population, with hay fever alone affecting hundreds of millions.
• The mechanism is IgE-mediated mast cell degranulation. Understanding it explains why antihistamines help itch and sneeze, why they are useless in anaphylaxis, and why adrenaline is.
• Adrenaline is the only first-line treatment for anaphylaxis, given intramuscularly into the outer thigh. Delay is the single biggest predictor of death.
• Early introduction of peanut prevents peanut allergy. The LEAP trial showed roughly an 80 percent reduction, reversing decades of advice to avoid allergens in infancy.
• Food intolerance is not food allergy. Lactose intolerance is an enzyme deficiency and cannot cause anaphylaxis; conflating them clogs allergy services and trivialises real allergy.
• Most people labelled penicillin-allergic are not, and the label pushes them toward worse antibiotics for life.

What it is

In short: Four types of hypersensitivity, and only the first can cause anaphylaxis, which is why a nickel rash and a peanut reaction are not comparable.

Hypersensitivity reactions come in four classical types. Allergy in ordinary usage means type I: immediate, IgE-mediated.

That table matters clinically. A nickel rash from a watch strap is a genuine allergy and cannot cause anaphylaxis, because it is T-cell mediated with no IgE involved. A rash appearing three days into an antibiotic course is a different mechanism from swelling and wheeze twenty minutes after the first dose, and only the second predicts a dangerous reaction on re-exposure.

The allergic conditions:

Don't be confused: allergy and intolerance are different in mechanism, severity, and management. Allergy involves the immune system, can be triggered by trace amounts, and can be life-threatening. Intolerance is a digestive or metabolic problem: lactose intolerance is a deficiency of the lactase enzyme, producing bloating, cramps, and diarrhoea in proportion to the dose, with no immune involvement and no risk of anaphylaxis. Coeliac disease is a third thing entirely: an immune-mediated but not IgE-mediated disease (Chapter 47). These distinctions matter in restaurants, in schools, and in emergencies.

The history

In short: Anaphylaxis was discovered in 1902 by researchers trying to immunise dogs, and a 2015 trial reversed decades of advice about avoiding allergens in infancy.

Ancient sources record fatal reactions to stings and to specific foods. Hay fever was described as a distinct condition by John Bostock in 1819, who thought it was caused by hay, and Charles Blackley demonstrated in 1873 that pollen was the cause, using his own skin as the test surface and inventing skin prick testing in the process.

1902: Charles Richet and Paul Portier, trying to immunise dogs against jellyfish toxin, found that a second, smaller dose killed the animals rapidly. They named the phenomenon anaphylaxis ("against protection"), the opposite of prophylaxis. Richet received the Nobel Prize in 1913.

1906: Clemens von Pirquet coins "allergy," meaning altered reactivity. 1966 to 1967: Kimishige and Teruko Ishizaka, and independently Gunnar Johansson and Hans Bennich, identify IgE, the missing antibody class, and the mechanism becomes clear.

1911: Leonard Noon publishes the first pollen immunotherapy, injecting small increasing doses of pollen extract. Allergen immunotherapy is therefore over a century old and remains the only treatment that changes the underlying allergy rather than suppressing symptoms.

2015: The LEAP trial reverses standard advice. For years, guidelines had recommended delaying peanut introduction in high-risk infants. LEAP randomised infants with eczema or egg allergy to early, regular peanut consumption or avoidance, and found peanut allergy at age 5 in 1.9 percent of the early-introduction group versus 13.7 percent of the avoidance group, roughly an 80 percent reduction. Guidelines worldwide changed.

What actually goes wrong

In short: Antibodies parked on mast cells are bridged by the allergen, the cells empty within seconds, and every symptom follows from what they release.

Sensitisation (the first exposure). An allergen crosses a barrier, most efficiently through inflamed skin (which is why eczema in infancy is a strong predictor of later food allergy), and is taken up by dendritic cells. In a person with an atopic tendency, the response is skewed toward T helper 2 cells producing interleukin-4 and interleukin-13, which instruct B cells to class-switch to IgE. That IgE binds high-affinity receptors on mast cells in tissue and on basophils in blood. Nothing is felt. The person is now sensitised.

Elicitation (subsequent exposures). The allergen binds and cross-links adjacent IgE molecules on the mast cell surface. This triggers immediate degranulation, releasing:

• Histamine: vasodilation, increased vascular permeability, itch, smooth muscle contraction.
• Tryptase: measurable in blood after anaphylaxis, which is how it is confirmed retrospectively.
• Leukotrienes and prostaglandins: bronchoconstriction, mucus, more vascular leak, and longer-lasting effects.
• Cytokines: recruiting eosinophils and other cells for a late-phase reaction hours later.

The consequences follow directly: vasodilation plus leak means swelling and, systemically, falling blood pressure; smooth muscle contraction means wheeze, vomiting, and cramps; sensory nerve stimulation means itch.

Why anaphylaxis kills. Two mechanisms: airway obstruction from swelling of the throat and tongue plus bronchospasm, and distributive shock, in which massive vasodilation and fluid leak out of the circulation drop the blood pressure precipitously. Up to 35 percent of the circulating volume can move into the tissues within minutes.

Why adrenaline is the answer, and antihistamines are not. Adrenaline acts on three receptors at once and reverses each mechanism: alpha-1 receptors constrict blood vessels, restoring blood pressure and reducing mucosal swelling; beta-2 receptors dilate the airways; beta-1 receptors increase cardiac output; and it stabilises mast cells against further degranulation. Antihistamines block only the histamine receptor, only some of the mediators, and take 30 to 60 minutes to act orally. Giving an antihistamine and waiting is a recognised contributor to anaphylaxis deaths.

What it does to the body

In short: From sneezing to shock, with the dangerous version killing through airway swelling and a sudden collapse in blood volume.

Allergic rhinitis: sneezing, itchy runny blocked nose, itchy watering eyes, and, consistently underestimated, impaired sleep, concentration, and school and work performance. It commonly coexists with asthma and worsens asthma control, which is the basis for the "one airway, one disease" framing.

Eczema: intensely itchy inflamed skin, disrupted barrier function, scratching that damages the barrier further, sleep loss, and secondary bacterial infection. Its role as the entry point for sensitisation makes early, effective eczema treatment a plausible allergy prevention strategy.

Food allergy: from oral itching and hives through vomiting and abdominal pain to full anaphylaxis. The commonest triggers are milk, egg, peanut, tree nuts, soy, wheat, fish, shellfish, and sesame. Milk and egg allergies are usually outgrown; peanut, tree nut, fish, and shellfish allergies usually are not.

Anaphylaxis: rapid onset, usually within minutes to an hour, involving two or more systems, or hypotension after a known allergen. Signs: widespread hives and flushing, swelling of lips, tongue, and throat, hoarseness and stridor, wheeze, vomiting and abdominal pain, faintness, collapse, and a sense of impending doom that patients report consistently. Biphasic reactions, a return of symptoms hours after apparent resolution, occur in a minority and are why observation after treatment is standard.

Is it deadly?

Anaphylaxis is, though the absolute numbers are small relative to how much fear it generates: fatal anaphylaxis is rare, on the order of a few deaths per million people per year in countries with good data. Food is the commonest trigger in children and young adults; drugs and venom dominate in older adults.

The risk factors for a fatal outcome are consistent and actionable: delayed adrenaline, coexisting asthma (especially poorly controlled), being upright or standing up during a reaction (which can cause fatal reduction in cardiac filling, so patients should be laid flat with legs raised unless breathing is easier sitting), adolescence and young adulthood (risk-taking and not carrying devices), and previous severe reactions.

The larger burden of allergy is not death but chronic morbidity: uncontrolled rhinitis, disturbed sleep, eczema, asthma exacerbations, dietary restriction, and anxiety.

Is it contagious?

No. Allergies cannot be caught.

The tendency to develop them, atopy, is inherited: a child with one atopic parent has roughly double the risk, and with two, higher still. Families also share environments, which contributes.

The hygiene hypothesis in its current form is about early-life microbial exposure rather than cleanliness as such. Growing up on a traditional farm with livestock, having older siblings, and early daycare attendance are associated with lower rates of allergy, and the mechanism appears to be immune education toward regulatory rather than allergic responses. What this does not support is avoiding vaccination or hygiene measures: infections that cause disease do not protect against allergy, and the protective exposures appear to be diverse harmless microbial ones.

Who gets it

In short: Rates rose sharply through the twentieth century, which points at environment rather than genes, and early microbial exposure appears protective.

Allergic disease rose sharply through the second half of the twentieth century in industrialised countries and is now rising in urbanising middle-income countries, a pattern strongly suggesting environmental rather than genetic causes.

Contributing factors with reasonable evidence: reduced microbial diversity in early life, antibiotic use in infancy, caesarean delivery (a modest association), reduced early allergen introduction (now reversed as advice), vitamin D status, air pollution (which appears to make pollen more allergenic as well as irritating airways), and climate change, which is lengthening pollen seasons and increasing pollen production measurably.

Age patterns: eczema and food allergy start in infancy; hay fever typically starts in childhood or adolescence; drug and venom allergy skew older. Many childhood food allergies resolve.

Geography: pollen allergies track local flora and season. Peanut allergy is far more common in Western countries than in, for example, Israel, where peanut-containing snacks are introduced very early, an observation that generated the LEAP trial.

Treatment, and how it works

In short: Adrenaline into the thigh immediately for anaphylaxis, and antihistamines for everything milder, because they treat only one of the mediators released.

Anaphylaxis

1. Adrenaline (epinephrine) intramuscularly into the outer thigh, immediately. Adult dose typically 0.3 to 0.5 mg (0.5 mg in most European guidance), repeatable after 5 minutes. The thigh is used because absorption is faster than from the arm or from subcutaneous injection. There is no dose of adrenaline that is more dangerous than untreated anaphylaxis in a person having one.
2. Call emergency services.
3. Lie the person flat with legs raised, or sitting if breathing is difficult, or on their side if vomiting or unconscious. Do not stand them up or walk them, which has caused deaths.
4. Repeat adrenaline if no improvement.
5. Then, and only then, adjuncts: oxygen, intravenous fluids, inhaled bronchodilators, antihistamines and corticosteroids for skin symptoms and possibly to reduce late-phase reactions, though neither is life-saving and steroids have limited evidence in this setting.
6. Observe for several hours because of biphasic reactions.

Ongoing management

Allergen immunotherapy

The only treatment that modifies the underlying allergy. Increasing doses of the allergen are given by injection (subcutaneous) or under the tongue (sublingual tablets or drops) over 3 to 5 years. The immune response shifts from IgE toward blocking IgG4 antibodies and regulatory T cells. It is effective for pollen, dust mite, and, particularly impressively, venom allergy, where it reduces the risk of systemic sting reactions from around 50 percent to a few percent.

Oral immunotherapy for food allergy works differently: it raises the threshold for reaction so that accidental exposure is less dangerous, rather than curing the allergy. It requires daily dosing indefinitely, and reactions during treatment are common. It is a genuine advance and it is not a cure, and patients should be clear which one they are being offered.

Prevention

• Early allergen introduction. Introduce peanut and egg in infancy, from around 4 to 6 months alongside other solids, particularly in infants with eczema, following local guidance. This is a reversal of previous advice and it is well supported.
• Treat infant eczema well, on the reasoning that the inflamed skin barrier is the sensitising route.
• Breastfeeding where possible, though evidence for allergy prevention specifically is mixed.
• Avoid tobacco smoke exposure.

What treatment costs

• Adrenaline autoinjectors: anxiety and cost, and the practical problem that they expire and are frequently not carried. Side effects when used are palpitations, tremor, pallor, and anxiety, all short-lived and vastly preferable to the alternative.
• Antihistamines: sedation with first-generation agents, which is genuinely dangerous when driving and impairs schoolwork in children.
• Intranasal steroids: nasal irritation and occasional bleeding, minimal systemic effect when used correctly, which requires spraying away from the septum.
• Immunotherapy: local reactions are common, systemic reactions occur, which is why subcutaneous injections are given in supervised settings with resuscitation facilities available.
• Biologics: injection reactions and high cost.

What the person can do

In short: Carry two autoinjectors, use them early, teach the people around you, and get a proper diagnosis rather than acting on an unvalidated test.

• Carry two adrenaline autoinjectors at all times if you have been prescribed them, and know how to use them. Ask a clinician to watch you demonstrate, since technique errors are common.
• Teach the people around you. Most people who die of anaphylaxis are with someone who did not know what to do. Schools, workplaces, friends, and partners should know where the device is and how to use it.
• Use it early. Do not wait to see whether the reaction escalates. Under-use kills; over-use in doubt is safe.
• Get proper diagnosis rather than self-diagnosing. Skin prick and specific IgE testing must be interpreted alongside history; a positive test without clinical reactions is sensitisation, not allergy, and acting on it leads to unnecessary and sometimes harmful dietary restriction. Unvalidated tests (IgG food panels, hair analysis, applied kinesiology) have no diagnostic value and generate long lists of foods to avoid.
• Get the penicillin allergy label checked. Around 10 percent of people carry it and roughly 90 percent of them tolerate penicillin on formal testing. Removing an incorrect label improves antibiotic choice, reduces resistance, and improves outcomes.
• For rhinitis, start intranasal steroids before the season begins and use them daily rather than as needed, since they take days to work fully.
• Read labels and ask in restaurants, and be aware that most fatal food reactions occur outside the home.
• Keep asthma well controlled if you have both, since asthma is the strongest predictor of a severe outcome from food anaphylaxis.

Living with it

Food allergy imposes a constant, low-grade vigilance that is easy to underestimate from outside: every meal, every social event, every school trip requires checking. Quality-of-life measures in families with food-allergic children are comparable to those in chronic physical illness, and anxiety is common and sometimes disabling in itself.

Adolescents are the highest-risk group and the hardest to support, because the behaviours that reduce risk (carrying a device, asking about ingredients, telling friends) conflict with the developmental drive not to be different. Practical approaches that work involve peers rather than lectures.

And in the other direction, over-diagnosis has real costs: children on unnecessary exclusion diets have nutritional and social consequences, and a family living in fear of an allergy that testing does not support is not made safer by that fear.

What's next

• Omalizumab and other biologics for food allergy, raising reaction thresholds without daily oral dosing.
• Better immunotherapy: modified allergens, adjuvants, and shorter courses.
• Prevention in infancy, extending the LEAP approach to multiple foods and testing whether aggressive early eczema treatment prevents food allergy, which is the current leading hypothesis.
• Understanding the rise, which remains unexplained in detail and is the question that would most change practice if answered.
• Climate: longer, more intense pollen seasons are already measurable and will make allergic rhinitis and asthma worse without any change in human biology.

Sources and notes

Mechanism and classification follow standard immunology and allergy references. IgE discovery: Ishizaka and Ishizaka, 1966 to 1967; Johansson and Bennich, 1967. Anaphylaxis: Portier and Richet, 1902. LEAP trial: Du Toit et al., NEJM, 2015 (peanut allergy at 60 months, 1.9 percent with early introduction versus 13.7 percent with avoidance). Anaphylaxis management, including the fatal risk of standing patients up: Pumphrey, Clinical and Experimental Allergy, 2000, and current resuscitation council guidelines. Venom immunotherapy efficacy: standard allergy texts and guidelines. Penicillin allergy delabelling: multiple studies finding roughly 90 percent of labelled patients tolerate penicillin on testing. Omalizumab for food allergy: OUtMATCH trial, NEJM, 2024. Hygiene hypothesis and farm effect: Strachan, BMJ, 1989, and subsequent European farm cohort studies. Fatal anaphylaxis rates: national registry analyses, which vary by country and definition.

Open questions. Why allergic disease increased so sharply is not settled. Whether treating infant eczema aggressively prevents food allergy is under trial. Whether oral immunotherapy produces lasting tolerance rather than temporary desensitisation is unresolved.

Next: the immune system making the same mistake, with a different target: you. 👉