Type III Hypersensitivity Reaction

What is Type III Hypersensitivity Reaction?

A hypersensitivity reaction happens when the body’s defensive system, the immune system, reacts too strongly to something it views as a threat which can cause problems. This usually happens to people who have been exposed to the same thing at least once before.

Hypersensitivity reactions can be grouped into four categories:

* Type I – An immediate reaction caused by specific antibodies, called IgE

* Type II – Reaction caused by other types of antibodies (IgG or IgM)

* Type III – Reaction caused by certain complexes formed when antibodies and antigens come together

* Type IV – Reaction that’s delayed and triggered by cells of the immune system

In a type III hypersensitivity reaction, the immune system responds oddly by producing what are called “immune complexes” – these are the combined forms of the harmful substance (antigen) and the body’s defense (antibody). These complexes can accumulate in different parts of the body like skin, joints, blood vessels, or parts of the kidney and trigger a response that involves other particles in the body’s defense system. This, in turn, attracts certain cells which release harmful substances at the site where the complexes are, leading to damage of the surrounding tissue.

Typical diseases involving a type III hypersensitivity reaction include conditions like serum sickness, a type of kidney inflammation that happens after a certain type of infection termed “post-streptococcal glomerulonephritis,” systemic lupus erythematosus (a long-term condition causing inflammation to joints, skin, and other organs), farmers’ lung (an allergic reaction to certain dusts), and rheumatoid arthritis (a long-term condition that causes pain, swelling and stiffness in the joints). The distinctive feature that sets type III reactions apart from others is that in type III reactions, the antigen-antibody complexes form in your blood before they make their way into tissues.

What Causes Type III Hypersensitivity Reaction?

Serum sickness is a reaction that can be caused by certain types of drugs that contain proteins from other species. These proteins can be found in medications such as antivenins (snake or spider venom antidotes), vaccines, antitoxins (substances that counteract toxins), and streptokinase (a drug that breaks down blood clots).

Why does this happen? Well, this foreign protein can act as a kind of intruder, triggering our immune system into action. Some antibodies, crafted in a lab from the blood of rabbits, horses, or mice, can also cause this immune reaction, known as a type III hypersensitivity reaction.

There are other medications, called synthetic monoclonal antibodies, that are made to mimic your body’s natural antibodies. Examples of these include Infliximab, used to treat conditions like rheumatoid arthritis and Crohn’s disease, and Omalizumab, used to manage asthma. These types of drugs can sometimes trigger a reaction that’s similar to serum sickness, known as a serum sickness-like reaction (SSLR).

Fantasy creatures?! No, insect stings, ticks, and even mosquito bites can also cause serum sickness.

Additionally, some infections, such as Hepatitis B and bacterial endocarditis (an infection of the heart’s inner lining), can provide a steady supply of intruders, giving rise to something called circulating immune complexes. This can also cause reactions similar to serum sickness.

There’s a long list of other types of drugs linked with these type III hypersensitivity reactions, including various antibiotics, anti-gout medication, epilepsy drugs, antidepressants, and more.

Risk Factors and Frequency for Type III Hypersensitivity Reaction

Serum sickness is a rare condition. One study found that, after the administration of an antivenom used for snake bite treatment, the chance of getting serum sickness was just 0.13%. Another study found that reactions to rabies treatments originating from horses and humans were extremely rare in children under the age of 10, with rates of 0.05% and 0.01% respectively. Interestingly, a literature review found that a specific drug-related serum sickness-like disease had occurrence of less than 0.2% per treatment, mainly in children under 5 years old.

The chance of developing serum sickness may depend on the dosage and the type of antigen. For instance, serum sickness related to horse-derived anti-rabies serum is more likely than that associated with the tetanus antitoxin treatment, with rates of 16.3% compared to 2.5% to 5%.

Signs and Symptoms of Type III Hypersensitivity Reaction

Immune-complex mediated disease presents itself in different ways based on the type of antigen and how the body is exposed to it. For instance, if the antigen enters the body through the veins, it could result in inflammation of the blood vessels, arthritis, and kidney disease. If inhaled, it could cause a lung condition known as hypersensitivity pneumonitis. If the antigen is injected locally, it can cause necrotizing skin lesions, a reaction often seen on the skin. Inflammation of the dermis and fat below the skin could also manifest as a purpuric rash, erythema nodosum (tender red nodules on the front of the lower legs), or erythema multiforme (target-like lesions with minimal mucosal involvement, often present in the lower legs).

Here are some common immune complex-mediated diseases and their symptoms:

• Serum Sickness: In the past, horse serum was used to treat scarlet fever and pneumonia. This serum could cause immune reactions leading to joint pain, rash, and fever. Signs of kidney involvement, such as protein in urine, might also be present. These symptoms typically appear one to two weeks after exposure to the antigen. Nowadays, serum sickness is associated with exposure to nonhuman proteins or certain antibodies, which may cause similar symptoms. A version of serum sickness can also be caused by certain drugs.
• Hypersensitivity Pneumonitis (HP): Also known as extrinsic allergic alveolitis, this is a lung condition caused by inhalation of certain antigens that trigger allergic reactions. Symptoms in the acute phase include fever, cough, and shortness of breath, which peak within 24 hours. Long-term exposure can cause weight loss and respiratory symptoms.
• Systemic Lupus Erythematosus (SLE): SLE is an autoimmune disease affecting multiple systems in the body. Symptoms can span many systems and might include fever, weight loss, fatigue, muscle and joint pain, skin rash, heart inflammation, lung and digestive issues, kidney problems, blood disorders, and neurological symptoms.
• Post Streptococcal Glomerulonephritis (PSGN): This is a kidney condition caused by immune complexes triggered by a certain type of strep bacteria. Symptoms typically appear 1-3 weeks after a strep throat infection or 3-6 weeks after a skin infection and include blood or protein in urine, high blood pressure, swelling, and decreased kidney function.

Testing for Type III Hypersensitivity Reaction

If you experience symptoms associated with serum sickness, like a fever, joint pain, and rash, your doctor might order a series of tests to figure out what’s going on. Think of these tests like clues in a puzzle – while no single one can definitively diagnose serum sickness, they can collectively give a clearer image.

Some of the tests could include a complete blood count to check for changes in your blood cells, tests related to hepatitis B, and tests that measure inflammation in your body (like ESR and CRP). Your urine could be tested to check for traces of protein, and if you have any skin lesions, these might be biopsied to look for a condition called leukocytoclastic vasculitis.

Quite similar to serum sickness, if you exhibit symptoms of a condition called ‘hypersensitivity pneumonitis’ (HP), certain tests could be carried out. Doctors might look at your blood count and antibodies in your serum. They might also request for an X-ray or a high-resolution CT scan of your chest to better understand what’s going on inside. Lastly, a procedure called ‘bronchoalveolar lavage’ can be conducted to identify any inflammation in your lungs. None of these are a surefire way to diagnose HP, but collectively they tell a bigger story.

Systemic lupus erythematosus (SLE or lupus), is another autoimmune disorder that shares some symptoms with serum sickness. If this is the suspect, additional tests could be deployed, including a complete blood count and other blood tests. Doctors may look for the presence of certain antibodies linked with lupus. Urinalysis could be carried out to check for changes in your urine, and in more severe situations, a kidney biopsy might be necessary. Any associated symptoms affecting your lungs and joints could also require additional imaging studies.

Post-streptococcal glomerulonephritis (PSGN) is a kidney disease that occurs after some types of strep infections. To diagnose this disease, testing for antibodies, blood cell counts, and checking for low complement levels might be asked for. The presence of protein or blood in your urine would provide additional pointers. In severe cases, doctors might ask for a kidney biopsy to study tissues more closely.

Finally, you might undergo specific tests if there’s a chance that you’re dealing with an immune complex-mediated disease, a group of conditions that occur when your immune system attacks normal cells in your body. These tests might include blood tests, antibody testing, urinary tests, various imaging studies like X-rays and CT scans. Skin and renal biopsies, along with culturing samples could also be performed.

Treatment Options for Type III Hypersensitivity Reaction

Type III hypersensitivity reaction is a medical term for an allergic reaction that can cause problems in the body. The way to treat it will depend on the specific symptoms you have.

The first step in treating this condition is to remove the object or substance causing the reaction. This could be a certain food, medication, or other allergen.

Medications like antihistamines and nonsteroidal anti-inflammatory drugs, which help with things like allergies and pain, can help manage the symptoms. In more severe cases, corticosteroids might be used. This type of medicine helps to control inflammation, which is the body’s way of protecting itself but can cause problems if it goes on for too long.

Avoiding contact with the specific allergen is another key part of managing this condition. This can require you to make changes to your lifestyle or environment to avoid the allergen.

Systemic Lupus Erythematosus (SLE), or lupus, is a form of hypersensitivity reaction that’s treated based on each patient’s unique condition. One medication that’s particularly important for long-term treatment of lupus is hydroxychloroquine. Other medicines for treating lupus can include antimalarials, corticosteroids, nonbiologic DMARDS, nonsteroidal anti-inflammatory drugs, and biologic DMARDs.

If you have severe symptoms or if diagnosis is unclear, you may need to go to the hospital. Both infection and autoimmune diseases, where the body’s immune system attacks its own cells, are associated with type III hypersensitivity reactions. As a result, it’s often important for you to see a rheumatologist, immunologist, or infectious disease specialist. These are doctors who specialize in autoimmune conditions, immune system disorders, and infectious diseases.

Treatment for autoimmune disorders like lupus can include a range of medications, depending on your individual needs. These can include hydroxychloroquine, NSAIDs, azathioprine, cyclophosphamide, methotrexate, mycophenolate, and tacrolimus.

What else can Type III Hypersensitivity Reaction be?

Type I and II hypersensitivity reactions (allergic reactions) both involve antibodies, which are part of the immune system, and their signs and symptoms can often be the same.

Type I hypersensitivity, also called immediate hypersensitivity, is caused by IgE antibodies. Here’s how it works: these antibodies, which are attached to certain cells, react when they come into contact with a specific allergen. This causes the cells to release substances like histamine which lead to an allergic reaction. Conditions that are commonly caused by this type of reaction include:

• Anaphylaxis (a severe and possibly life-threatening reaction)
• Bronchial asthma
• Allergic rhinitis (hay fever)
• Food allergies

Type II hypersensitivity involves IgG and IgM antibodies. These antibodies bind to cells circulating in the blood. This process can make the cells a target for destruction by the immune system. In some cases, the antibodies interfere with the normal functioning of cell receptors. Several conditions are associated with this type of reaction, such as:

• Autoimmune hemolytic anemia (a condition where the immune system destroys red blood cells)
• Autoimmune thrombocytopenic purpura (a condition where the immune system destroys platelets)
• Acute rheumatic fever (a complication of strep throat)
• Goodpasture syndrome (a rare disease that can involve rapidly worsening kidney failure)
• Myasthenia gravis (a condition that causes muscle weakness and tiredness)
• Graves’ disease (a type of hyperthyroidism)
• Pernicious anemia (a type of vitamin B12 deficiency)
• ANCA vasculitis (a type of blood vessel inflammation)

What to expect with Type III Hypersensitivity Reaction

The future health outcomes of a type III hypersensitivity reaction can vary widely, depending on the specific illness and any other existing health issues. Serum sickness, for example, usually has a very positive outcome. Its symptoms usually disappear within one or two weeks after taking the problematic medication is stopped.

On the other hand, Hypersensitivity pneumonitis can cause long-term health problems with symptoms that get worse over time. Factors that can make this condition worse include extended or intense exposure to the trigger, being older, having ‘clubbed’ fingers and toes (a condition whereby the ends of the fingers and toes swell and become rounder) and fibrotic changes in the lung (sort of like scarring of the lung tissue).

Autoimmune diseases, like Systemic Lupus Erythematosus (SLE), are often accompanied by complications including high blood pressure, kidney failure, and infections. In fact, 40% to 75% of patients with SLE may develop a condition called lupus nephritis that affects the kidneys. Unfortunately, 10% of these may progress to End-Stage Renal Disease (ESRD), a severe condition where the kidneys stop working almost entirely.

Despite these challenges, the survival rates for SLE are encouraging. The survival rates after 5, 10, and 15 years of diagnosis are approximately 96%, 93%, and 76% respectively.

Possible Complications When Diagnosed with Type III Hypersensitivity Reaction

Type III hypersensitivity reaction can lead to several complications. These complications are associated with types of conditions:

1. Serum Sickness:

• Inflammation of the blood vessels, or vasculitis
• Acute kidney injury, often triggered by kidney inflammation called glomerulonephritis

2. Hypersensitivity Pneumonitis, a condition that affects the lungs:

• Alveolitis, an inflammation of the lungs’ air sacs
• Pulmonary fibrosis, a lung disease that can lead to restrictive lung disease
• Cor pulmonale, a condition that causes right-side heart failure

3. Systemic Lupus Erythematosus (SLE), an autoimmune disease that can cause:

• High blood pressure
• Infections
• Blood clots, or thrombosis
• Glomerulonephritis, which can lead to end-stage renal disease
• Miscarriages

4. Post-streptococcal Glomerulonephritis, a kidney disorder that can develop after a strep infection:

• Acute kidney injury that requires dialysis
• Chronic kidney disease
• Proteinuria, an excessive amount of protein in the urine
• High blood pressure

Preventing Type III Hypersensitivity Reaction

Patients should keep away from contact with anything they are allergic to. Failure to do this could lead to a severe allergic reaction known as hypersensitivity. If the allergic substance is part of their job environment, they might need to consider taking safety measures at work or even changing their nature of work. If a patient has ever had an allergic reaction to a particular medication, it’s prudent to meticulously review their drug allergy list and be aware of any potential side effects. It’s crucial for patients to know the medicine’s brand and generic name. The patient must also steer clear of medications with components similar to the drug that caused the allergic reaction. This could help in preventing a similar allergic reaction. It’s important to note that repeated contact with the substance that causes the allergic reaction can lead to a more severe condition.