Differences Between Allergy and Intolerance

The differences between allergy and intolerance are multiple. The first picture is caused by autoimmune mechanisms and the second isn't.

Written and verified by el biólogo Samuel Antonio Sánchez Amador.

Last update: 08 July, 2023

Allergies and intolerances are becoming more and more common in general society. It’s estimated that 30-40% of the population has at least one allergic condition and that, by 2050, half of the inhabitants of the Earth will have developed an allergic condition throughout their lives. In order to treat these conditions adequately, it’s necessary to describe the differences between allergy and intolerance.

Although they may seem the same, allergies and intolerances represent two different pathological mechanisms. Keep reading, because below we’ll show you how these conditions differ on a physiological, symptomatic, and causal level.

The importance of intolerances and allergic conditions

Where there are differences, there can also be similarities. In the first place, it’s important to emphasize that both allergies and intolerances are included in the general picture of hypersensitivity. According to the Oxford Dictionary, this term is defined as “a medical condition that causes the body to have extreme physical reactions to particular substances, medicines, light, etc.”

Although in most cases, hypersensitivity pictures are linked to a malfunction of the immune system, this isn’t always the case. Sometimes overreactions by the body are dictated by other mechanisms that escape typical protective cells (such as lymphocytes).

In the following list, we’ll show you a series of figures that perfectly exemplify the importance and epidemiology of hypersensitivity reactions in the world:

• According to the World Allergy Organization (WAO), 30 to 40% of the world’s population suffers from some type of allergic condition. By 2050, this figure can reach 50%.
• On the other hand, up to 20-30% of the world’s population has a food intolerance (intolerance to lactose, gluten, sucrose, trehalose, and more).
• Allergic conditions are the number one condition in childhood age groups in the United States.
• In this same country, more than 50 million people experience allergic conditions every year. This type of hypersensitivity is the sixth most common cause of chronic disease in the region.
• Serious allergic drug reactions affect up to 10% of the general population. In the hospital setting, they’re registered in up to 20% of the people admitted.

As you can see, allergic reactions and intolerances are very common in general society. Understanding the difference between the two medical terms is essential, as treatment and prevention vary from case to case.

What are the differences between allergy and intolerance?

Although both conditions can be included in the general term of hypersensitivity, they’re not the same thing. Below, we’ll show you the differences between allergy and intolerance by section.

1. Allergy is immune-mediated, but intolerance is not

The United States National Library of Medicine defines an allergy as a reaction of the immune system toward something that doesn’t generate a response in the majority of the population. Allergic rhinitis, food allergies, atopic dermatitis, some types of asthma, and anaphylaxis are considered allergic conditions.

The element that elicits the excessive immune reaction is known as an allergen. From a biological point of view, an allergen is an antigen that’s capable of stimulating a type I hypersensitivity reaction in atopic individuals through immunoglobulin E responses (IgE antibodies).

This type of response is associated with parasitic infections in “healthy” humans, but allergy sufferers produce IgE-type antibodies after exposure to a compound that shouldn’t be a problem. The most common allergens are pollen, mite feces, insect toxins, and skin flakes from pets.

The Oxford Dictionary defines intolerance as “the fact of not being able to eat particular foods, use particular medicines, etc. without becoming ill.” When we talk about intolerance, we almost always refer to the discomfort generated after consuming a food, but this isn’t the same as a food allergy.

Allergies are immune-mediated and respond to increased circulating antibodies, but intolerances aren’t. In general, intolerances are based on the malabsorption of a nutrient at the intestinal level, which leads to water and electrolyte imbalances due to diarrhea and unwanted bacterial fermentations (gas, abdominal pain, and cramps).

2. The pathological mechanisms are different

Another difference between allergy and intolerance lies in the physiological mechanisms that cause each of the pictures. In the following sections, we’ll show you specifically what each of them consists of.

The mechanisms of allergy

As we’ve said above, an allergy is immune-mediated. In the initial stages of the allergic picture, a type I hypersensitivity reaction occurs. In it, the allergen (an antigen) is presented by an antigen-presenting cell (APC), which performs endocytosis and expresses the molecule of interest on the surface of its membrane.

The APC presents the allergen to T helper lymphocytes, which are responsible for producing cytokines and activating B lymphocytes. These latter white blood cells produce type E antibodies or immunoglobulins. For their part, the antibodies produced bind to the surface of basophils and mast cells, responsible for mediating inflammatory responses.

This entire process is necessary for sensitization to a specific allergen to occur. The next times that Ig-E recognizes the conflict substance, a generalized immune response will occur that will manifest itself with allergy symptoms.

The mechanisms of intolerance

The mechanisms of intolerance are much more varied, as they depend on each case. Take as an example lactose intolerance, as it’s one of the most common variants at the food level.

As indicated by the Statpearls portal, this intolerance is due to the lack of the lactase enzyme in the brush edges of the intestinal mucosa. In intolerant patients, the lack of the enzyme causes dairy products to not be properly metabolized, and unabsorbed lactose reaches the environment of the large intestine.

When lactose compounds reach the colon, they’re metabolized by bacteria that are part of the microbiota, leading to fermentation that produces copious amounts of gas (hydrogen, carbon dioxide, and methane). Unabsorbed sugars also cause the osmotic pressure in the intestine to increase and water to be released (diarrhea occurs).

In this case, there’s no immune activation involved. Everything is based on chemical processes: The non-absorption of lactose, the production of gases, and the hydroelectrolyte imbalance in the intestine are the result of an enzymatic imbalance, not of the action of lymphocytes or antibodies.

3. Different symptoms

Another difference between allergy and intolerance lies in the symptoms that both conditions cause, as they’re quite different. We’ll show them to you in the following sections.

Allergy symptoms

Allergy symptoms are highly dependent on the substance involved and the area that first came into contact with the allergen. The Mayo Clinic presents the most common clinical signs according to the type of condition:

• Allergic rhinitis: Sneezing, itchy nose, eyes, and palate, stuffy nose, mucus, and conjunctivitis.
• Food allergy: Tingling in the mouth, swelling of the lips and throat, hives, and, in the most severe cases, anaphylaxis.
• Insect bite allergy: Edema at the site of injury, generalized itching or hives, cough, chest tightness, shortness of breath, and anaphylaxis.
• Allergic drug reaction: Itchy skin, hives, rash, swelling of the face, and anaphylaxis.
• Atopic dermatitis: Itchy, red skin and peeling layers.

Most allergens (pollen, mites, and skin flakes) are inhaled through the mouth and nose, so the airways are usually the most affected structures. When the immune reaction is severe, a condition known as anaphylaxis occurs. We’ll look at it more precisely in the following lines.

Symptoms of intolerance

Intolerances present with a very diverse set of symptoms, as these depend on the type of condition and the triggering substances. We’ll take as an example, again, lactose intolerance:

• Bloating or bloating
• Diarrhea
• Gases
• Sickness
• Abdominal pain
• Stomach noises
• Vomiting

As you can see, in this case, there’s no tingling in the mouth, swelling of the lips, hives, or anaphylaxis. If it were a food allergy, the immune reaction would lead to symptoms characterized by inflammatory mechanisms. As this isn’t the case, only signs limited to the digestive system are present.

4. Allergy can lead to anaphylaxis, but intolerance can’t

The term anaphylaxis refers to a severe allergic reaction. By definition, all anaphylaxis is preceded by an allergic process and sensitization, but it never occurs in patients with intolerance. This is another of the key differences between allergy and intolerance, as the first is much more serious.

Interestingly, food allergies are the leading cause of anaphylaxis in children, while allergies to medications and insect bites occupy the leading positions in adults. At a physiological level, it’s produced by the massive release of inflammatory mediators and cytokines (including interleukin).

Some of the symptoms of this serious condition are the following:

• Skin: Very obvious redness, swelling, hives, and itching
• Mouth: Itching and swelling of the tongue and lips
• Throat: Tightness and difficulty swallowing (dysphagia)
• Chest: Shortness of breath, wheezing, tightness, and shortness of breath
• Heart: Weak pulse, leading to fainting and loss of consciousness
• Digestive system: Vomiting and diarrhea
• Nervous system: Confusion, loss of consciousness, and difficulty in coordinating

Anaphylaxis is estimated to affect between 3 and 30 individuals per 100,000 people per year. Of all anaphylactic patients, 0.05 to 2% of them will end up dying. Although this condition can be treated, it’s very serious and leads to death without adequate emergency care.

To treat an anaphylactic patient, adrenaline (epinephrine) must be given urgently to reduce the body’s immune response. Oxygen is also commonly used to facilitate breathing, antihistamines, hydrocortisone, and beta-agonists to reduce airway inflammation.

5. Different treatments

The last of the clear differences between allergy and intolerance lies in the treatment. As you can imagine, an immune-mediated reaction and an intestinal fluid and electrolyte imbalance will be approached very differently.

Allergy treatment

Allergy treatment is based on preventing the immune reaction in the first instance (or reducing it if it occurs). Some of the common approaches are as follows:

• Avoid allergens: The first step is always to try not to come into contact with the allergen that overactivates the immune system. Unfortunately, sometimes this is very difficult (as in a pollen allergy).
• Use of medications: Antihistamines are very useful to treat unavoidable allergic conditions. Some of them are cetirizine (Zyrtec, Zyrtec Allergy), desloratadine (Clarinex), and fexofenadine (Allegra, Allegra Allergy).
• Immunotherapy: Immunotherapy encompasses a series of complex processes that are based on desensitization. In a controlled environment, the patient is increasingly exposed to the allergen to look for a change in their immune system.
• Adrenaline (epinephrine): In cases of anaphylaxis, the injection of adrenaline can save the life of the patient.

Treatment of intolerance

Treatment of intolerances is much more limited, as the cause isn’t as specific as an overactivation of the immune system. In these cases (especially in food intolerances), the only possible therapy is the guidance of a nutritionist and dietary replacement. Sometimes intolerance to problem compounds develops, but not in other cases.

The biggest problem when dealing with intolerances is detecting the causative agent, as it can be any ingredient in the individual’s diet (or any environmental compound, even if it’s not ingested). For this, exclusion diets are prescribed and the patient is monitored until the conflicting agent is found.

Two very different disease groups

As you can see, the differences between allergy and intolerance are multiple and clear. An allergy is an immune process, while intolerance responds to the lack of means to metabolize a substance. Keep in mind that here we’ve taken into account only food intolerances, but there are other less prevalent ones that are also important.

Be that as it may, allergies are generally considered more serious than intolerances due to the possible anaphylaxis that can develop. In any case, the key is to avoid the conflicting agent and put yourself in the hands of a doctor as soon as the first symptoms are detected.