Hypersensitivity Reactions

Hypersensitivity reactions happen when your immune system attacks something that it mistakenly thinks is harmful. These can be your own cells and tissues or foreign substances, like pollen, food or medications.

There are four types of hypersensitivity reactions, which can range from mild allergies to life-threatening emergencies. Hypersensitivities can also cause long-term conditions, like autoimmune diseases.

It might not seem like an itchy poison ivy rash, lupus and asthma have much in common. But they all happen because your immune system makes a mistake. Your body typically protects you from things that might cause harm. It recognizes unique labels on your own cells and anything that comes from outside your body. These labels — called antigens — let it know when something is harmful so it can destroy it.

But sometimes, immune cells or antibodies mistakenly cause your body to attack antigens that aren’t harmful. This can lead to allergic reactions or damage to healthy tissue.

Types of hypersensitivity reactions

There are four types of hypersensitivity reactions:

• Type I, or IgE-mediated reactions (IgE is an antibody that causes allergic reactions)
• Type II, or cytotoxic hypersensitivity
• Type III, or immune complex hypersensitivity
• Type IV, or cell-mediated hypersensitivity

Type I hypersensitivity reactions

Type I hypersensitivities are what we think of as “true” allergies. When something foreign — like pollen, food or medication — first enters your body from the outside, you become sensitized to it. Your body decides it’s harmful (an allergen) and creates IgE antibodies that wait on mast cells.

If the antibodies encounter an allergen a second time, they cause your mast cells to release histamine and other inflammatory chemicals that lead to allergic reactions. This reaction happens quickly (usually within minutes) after the second exposure. Type I hypersensitivity reactions are also called IgE-mediated reactions.

Examples of type I hypersensitivity reactions include:

• Allergic rhinitis, also called seasonal allergies or hay fever
• Food allergies
• Drug allergies
• Allergic asthma
• Anaphylaxis — a severe, whole-body, and potentially life-threatening reaction

Type II hypersensitivity reactions

Type II hypersensitivity reactions, or cytotoxic hypersensitivity, often destroy healthy cells and tissue. In most type II reactions, an antibody recognizes something on your cells’ surface that it thinks is harmful. This could be part of your body or something foreign (like a part of a medication) that’s attached to your cells. It signals your immune system to attack your own cells. In some cases of type II hypersensitivity, your cells aren’t destroyed. Instead, antibodies cause problems by attaching to your cells when they shouldn’t. This can block the cells from getting signals they need to work properly or activate cells when they shouldn’t be activated.

Examples of type II hypersensitivity reactions include:

• Hemolytic blood transfusion reactions (like when you receive a blood type that doesn’t match your own)
• Rh incompatibility
• Autoimmune hemolytic anemia
• Rheumatic fever
• Goodpasture syndrome
• Myasthenia gravis

Type III hypersensitivity reactions

Type III hypersensitivity reactions happen when antibodies attach to antigens floating freely in your blood (not attached to a cell). This creates antigen-antibody complexes (or immune complexes). These settle into your blood vessels and tissues, where they attract immune cells. The immune cells try to destroy them, causing inflammation.

Type III hypersensitivities often cause or contribute to autoimmune diseases. They’re also called immune complex hypersensitivity.

Examples of type III hypersensitivity reactions include:

• Lupus
• Rheumatoid arthritis
• Serum sickness
• Arthus reaction

Type IV hypersensitivity reactions

Type IV hypersensitivity reactions, also called cell-mediated hypersensitivities, are a bit like delayed allergic reactions. They usually develop over 48 to 72 hours after exposure, but can also take longer.

Unlike the other three types, antibodies don’t cause them. They happen as part of your adaptive immune system. Your body’s T-cells recognize an antigen, destroy healthy cells and cause inflammation. Most type IV hypersensitivities cause skin reactions.

Examples of type IV hypersensitivity reactions include:

• Contact dermatitis (like poison ivy reactions and some types of latex allergies)
• Certain types of drug reactions, like Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN)
• Autoimmune diseases, like Type 1 diabetes and multiple sclerosis

Many types of infectious diseases can also lead to type IV hypersensitivities, like tuberculosis (TB). Skin tests for these diseases are positive if you have a delayed hypersensitivity skin reaction.

Symptoms of hypersensitivity reactions

Symptoms of hypersensitivity reactions depend on the specific type and reaction. It’s possible to have symptoms from multiple types of hypersensitivity reactions at the same time.

Symptoms of type I

In general, symptoms of type I reactions may include:

• Runny nose and sneezing
• Coughing
• Itchy eyes
• Vomiting
• Difficulty breathing or swallowing
• Hives
• Swelling of your face, lips, tongue or throat
• Sudden drop in blood pressure

Symptoms of type II

Different kinds of type II reactions cause a wide variety of symptoms. Fever, tiredness and weakness are common in cytotoxic reactions.

Symptoms of type III

Symptoms common to many (but not all) forms of type III reactions include:

• Joint pain and stiffness
• Rashes and itching
• Fatigue and weakness
• Headaches
• Fever
• Hair loss
• Shortness of breath

Symptoms of type IV

Type IV reactions can be mild or severe and almost always affect your skin.

Skin changes may include:

• Pain
• Rash
• Peeling, flaking or scaling
• Red to purple or darker than your natural skin tone
• Oozing fluid or pus
• Itching

You can also have fever, body aches and other symptoms.

Causes

An immune system overreaction causes all types of hypersensitivities. Antibodies cause types I, II and III. T-cell activation causes type IV. Antibody-mediated hypersensitivity reactions (types I, II and III) happen in two steps:

1. Sensitization: Something foreign (antigen) enters your body. Your immune system makes antibodies against it. Sensitization can also happen if your body accidentally makes antibodies against its own antigens.
2. Effect: The next time your body encounters the antigen, it triggers your immune system to attack it or try to flush it out.

What triggers hypersensitivity?

Antigens from outside your body (extrinsic) or ones that are part of your body (intrinsic) can trigger different types of hypersensitivity reactions.

Common triggers include:

• Pet dander, pollen, dust mites and other allergens
• Food
• Prescription drugs
• Plants like poison ivy or poison oak
• Bee stings or bug bites
• Infectious diseases (viruses, bacteria, fungi and parasites)
• Antivenom for snake bites
• Vaccines
  

How doctors diagnose this condition

Hypersensitivity causes a wide range of diseases and reactions. So, how your provider diagnoses you will depend on your symptoms and medical history. You might need blood tests, imaging, allergy skin tests or other tests to get an accurate diagnosis.

How is it treated?

Treatment for hypersensitivity reactions depends on the specific type of disease or reaction. For instance, providers often treat type I reactions with antihistamines, inhaled medications (for asthma) and, in the case of severe reactions, epinephrine. Treatments for type II, type III and type IV reactions usually include corticosteroids and immunosuppressants.

Your treatment may be based on:

• How severe your reaction is: For example, Stevens-Johnson syndrome often requires treatment in a hospital. But other type IV reactions, like a case of poison ivy, don’t.
• How urgently you need treatment: For instance, anaphylaxis or severe asthma attacks are medical emergencies that need immediate treatment. Seasonal allergies, another type I reaction, rarely cause serious reactions. You can usually treat them at home.
• Whether your condition is acute or chronic: Some hypersensitivities cause sudden, severe symptoms. Some cause ongoing or recurring conditions, like autoimmune diseases.
• Whether you know what’s causing the reaction: Your provider will likely have you immediately stop any medications or treatments that are causing a reaction. Avoiding known allergens is the best way to prevent reactions in the future.

When should I see my healthcare provider?

Talk to a healthcare provider if you have ongoing symptoms like fatigue, weakness and joint pain. Reach out to them if you’re having trouble managing allergies, asthma or autoimmune disease.

It might be helpful to ask your provider:

• What might’ve caused this reaction?
• How can I avoid it in the future?
• What do I do if I have another reaction?
• What are my treatment options?
• How do I take this medication?
• How do I take care of myself at home?

When should I go to the ER?

Call 911 or go to the emergency room if you have symptoms of a serious reaction, including:

• Difficulty breathing
• Chest pain
• Swelling of your face, lips, tongue or throat
• Sudden and severe low blood pressure
• A wound that’s very painful, not healing or getting larger
• Large bubbles or blisters that are red, brown, dark green or black
• Ulcers or sores filled with foul-smelling fluid

Make sure you let your provider know if you’ve taken any new medications or if there’s anything else you can think of that could’ve caused a reaction.

What can I expect if I have a hypersensitivity reaction?

Most hypersensitivity reactions have a good prognosis (outcome). But what you can expect depends on your specific reaction or disease. Chronic conditions, like most autoimmune diseases or asthma, are manageable. But their treatment is usually lifelong.

The most severe and deadly hypersensitivity reactions, like toxic epidermal necrolysis, are very rare.

Can this be prevented?

The thing about hypersensitivities is that researchers don’t know who will get them or what they’ll react to. You often can’t prevent the first reaction to an allergen or trigger, but in some cases (like food or medication allergies), you can prevent subsequent reactions in the future by avoiding the trigger. Other hypersensitivity reactions, like autoimmune diseases, can’t be avoided because they’re a reaction to proteins that are part of your body.