Allergen Immunotherapy: How Allergy Shots Work

What Is Allergen Immunotherapy?

Allergen immunotherapy (AIT) is a medical treatment that gradually exposes the immune system to increasing doses of specific allergens, training the body to tolerate substances that previously triggered allergic reactions. It is the only treatment that addresses the root cause of allergies rather than just managing symptoms.

Allergen immunotherapy represents a fundamentally different approach to treating allergies compared to medications like antihistamines and corticosteroids. While traditional allergy medications work by blocking or suppressing the allergic response after it has already been triggered, immunotherapy works at a deeper level by actually modifying how the immune system responds to allergens in the first place. This makes it the only available treatment that can potentially cure allergic disease rather than simply controlling symptoms.

The treatment works through a process called immune tolerance induction. When you have an allergy, your immune system has mistakenly identified a harmless substance (like pollen or pet dander) as dangerous, producing IgE antibodies that trigger allergic symptoms upon exposure. Immunotherapy gradually retrains the immune system by exposing it to carefully controlled amounts of the allergen, eventually teaching it to recognize the substance as harmless. This process involves complex changes in immune cell populations, including the development of regulatory T cells that actively suppress allergic responses.

The treatment is also known by several other names, including allergy shots, desensitization therapy, hyposensitization, and allergen-specific immunotherapy (ASIT). In medical literature, you may see it abbreviated as AIT, SCIT (subcutaneous immunotherapy for injections), or SLIT (sublingual immunotherapy for tablets or drops).

History and Development

Allergen immunotherapy has over a century of clinical use. It was first developed in 1911 by Leonard Noon and John Freeman at St Mary's Hospital in London, who demonstrated that hay fever symptoms could be reduced by injecting patients with grass pollen extracts. Since then, the treatment has been extensively studied and refined, with modern formulations offering improved safety and efficacy. The development of sublingual tablets in recent decades has expanded treatment options and improved convenience for patients.

How Immunotherapy Differs from Other Treatments

Understanding how immunotherapy differs from symptomatic treatments helps explain why it requires longer treatment but offers more lasting benefits. Antihistamines block histamine receptors, preventing immediate allergic symptoms but providing no protection once the medication wears off. Nasal corticosteroids reduce inflammation but must be used continuously to maintain benefit. In contrast, immunotherapy changes the underlying immune response, providing benefits that typically persist for years after treatment completion.

What Types of Immunotherapy Are Available?

There are two main types of allergen immunotherapy: subcutaneous immunotherapy (SCIT), given as injections at a medical facility, and sublingual immunotherapy (SLIT), taken as tablets or drops under the tongue at home. Both methods are effective, though they differ in convenience, allergen availability, and treatment protocols.

The choice between subcutaneous and sublingual immunotherapy depends on several factors, including the specific allergens being treated, patient preferences, lifestyle considerations, and geographic availability. Both approaches have been proven effective in numerous clinical trials, though subcutaneous immunotherapy has a longer track record and broader range of available allergen extracts. Understanding the differences between these options helps patients and healthcare providers make informed treatment decisions.

Subcutaneous Immunotherapy (SCIT) - Allergy Shots

Subcutaneous immunotherapy involves regular injections of allergen extracts under the skin, typically in the upper arm. This method has been used for over 100 years and remains the most common form of immunotherapy worldwide. The injections must be administered in a medical setting due to the small risk of systemic allergic reactions, and patients typically wait 30 minutes after each injection for observation.

The treatment follows a two-phase approach. During the build-up phase, which lasts approximately 7-15 weeks, patients receive weekly injections with gradually increasing allergen doses. This careful dose escalation allows the immune system to adjust without triggering severe reactions. Once the maintenance dose is reached, patients transition to the maintenance phase, receiving injections every 2-4 weeks for 3-5 years. Some clinics offer accelerated schedules with multiple injections per visit, reaching maintenance doses faster but requiring longer observation periods.

A significant advantage of SCIT is the ability to treat multiple allergens simultaneously with a single injection containing several allergen extracts. This makes it particularly useful for patients with multiple allergies, such as those allergic to several types of pollen, dust mites, and pet dander. Custom-mixed extracts can be tailored to each patient's specific allergy profile based on skin testing or blood test results.

Sublingual Immunotherapy (SLIT) - Tablets and Drops

Sublingual immunotherapy represents a newer approach that has gained significant popularity since the early 2000s. This method involves placing allergen extracts under the tongue, where they are absorbed through the mucous membranes. The convenience of home administration has made SLIT an attractive option for many patients, though the first dose must be given under medical supervision to monitor for adverse reactions.

SLIT is available in two forms: tablets and drops. Tablet formulations have undergone extensive clinical trials and are approved for specific allergens including grass pollen, ragweed pollen, and house dust mites. These standardized products offer consistent dosing and well-documented efficacy. Sublingual drops are more commonly used in Europe and can contain multiple allergens, though the evidence base is generally less robust than for tablets.

Unlike injection therapy, sublingual treatment is taken daily throughout the treatment period, typically for 3-5 years. For seasonal allergens like pollen, some protocols allow for pre-seasonal or co-seasonal treatment, starting a few months before the allergy season and continuing through it. Year-round treatment generally provides better long-term outcomes for both seasonal and perennial allergens.

What Allergies Can Be Treated with Immunotherapy?

Allergen immunotherapy is effective for allergic rhinitis (hay fever), allergic asthma, and insect venom allergies. It works best for allergies to pollen (grass, trees, weeds), dust mites, pet dander (cats and dogs), mold, and stinging insect venom (bees, wasps). Food allergies are generally not treated with traditional immunotherapy.

The effectiveness of allergen immunotherapy varies depending on the specific allergen and the allergic condition being treated. The best-established evidence supports its use for respiratory allergies caused by airborne allergens and for systemic allergic reactions to insect stings. Understanding which conditions respond best to immunotherapy helps identify appropriate candidates for treatment and set realistic expectations for outcomes.

Allergic Rhinitis and Hay Fever

Allergic rhinitis, commonly called hay fever when triggered by pollen, is one of the most common indications for allergen immunotherapy. Symptoms include nasal congestion, sneezing, runny nose, and itchy eyes, which can significantly impact quality of life, work productivity, and sleep quality. Studies consistently show that immunotherapy reduces these symptoms by 20-40% compared to placebo, with many patients able to reduce or eliminate their use of allergy medications.

Immunotherapy is particularly beneficial for patients with moderate to severe allergic rhinitis that is not adequately controlled with medications, those who experience side effects from allergy medications, patients who want to reduce long-term medication use, and those with allergies that significantly impact quality of life despite treatment. The benefits typically become apparent within the first year of treatment and continue to improve over time.

Allergic Asthma

For patients whose asthma is triggered by specific allergens, immunotherapy can reduce asthma symptoms, decrease the need for controller medications, and reduce the frequency and severity of asthma exacerbations. This is particularly important because poorly controlled asthma can lead to permanent airway changes over time. However, immunotherapy should only be started in patients whose asthma is well-controlled, as treatment may be risky for those with unstable or severe asthma.

Research has shown that allergen immunotherapy may also help prevent the development of asthma in children with allergic rhinitis, a phenomenon known as the "allergic march." By treating allergies early, it may be possible to interrupt the progression from upper airway allergies to lower airway disease, potentially preventing a lifetime of asthma management.

Insect Venom Allergy

Venom immunotherapy is one of the most effective forms of allergen immunotherapy, providing 90-95% protection against severe allergic reactions to insect stings. This treatment is recommended for individuals who have experienced systemic allergic reactions (beyond just local swelling) to stings from bees, wasps, hornets, yellow jackets, or fire ants. Given the potentially life-threatening nature of anaphylaxis to insect stings, venom immunotherapy can be genuinely lifesaving.

Unlike respiratory allergy treatment, venom immunotherapy may be continued indefinitely for patients at high risk of future reactions, particularly those with a history of severe anaphylaxis or certain underlying conditions like mastocytosis. The decision to stop treatment after 5 years should be made on an individual basis with careful consideration of ongoing risk factors.

Conditions Where Immunotherapy Is Not Effective

Traditional allergen immunotherapy is generally not effective for food allergies, drug allergies, chronic urticaria (hives) without a clear allergic trigger, or allergic conditions caused by irritants rather than allergens. While oral immunotherapy (OIT) for food allergies is being studied and has shown promise for peanut allergy, it uses different protocols and is not yet widely available as standard treatment.

How Does the Treatment Process Work?

Allergen immunotherapy begins with comprehensive allergy testing to identify specific triggers. Treatment then progresses through a build-up phase (weekly doses for 7-15 weeks) and a maintenance phase (monthly doses for 3-5 years). Most patients notice improvement within the first year, with maximum benefits developing over the full treatment course.

The process of allergen immunotherapy is carefully structured to maximize effectiveness while minimizing risk. Understanding each step of the treatment journey helps patients prepare for the commitment involved and recognize what to expect at each stage. Close collaboration between patients and allergists is essential throughout the process to optimize outcomes and manage any challenges that arise.

Initial Evaluation and Testing

Before starting immunotherapy, a thorough evaluation is essential. This typically includes a detailed medical history focusing on allergic symptoms, their triggers, timing, and response to previous treatments. Comprehensive allergy testing is performed using skin prick tests, intradermal tests, or blood tests (specific IgE) to identify the exact allergens causing symptoms.

The allergist will also assess whether immunotherapy is appropriate based on the severity of symptoms, response to other treatments, presence of any contraindications, and the patient's ability to commit to the treatment schedule. This evaluation ensures that patients selected for immunotherapy are likely to benefit from treatment and can safely undergo the process.

The Build-up Phase

Once the decision to proceed with immunotherapy is made, treatment begins with the build-up phase. For subcutaneous immunotherapy, this involves weekly injections starting with very low allergen doses that gradually increase over 7-15 weeks until reaching the maintenance dose. Some practices offer cluster or rush protocols that reach maintenance doses faster through multiple injections per visit, though these require longer observation periods and may carry slightly higher risks.

For sublingual immunotherapy, the first dose is given under medical supervision, followed by daily self-administration at home. The build-up for SLIT tablets is typically faster, often reaching maintenance doses within a few days to weeks depending on the specific product. Patients are instructed to hold the tablet under the tongue without swallowing for a specific period to allow proper absorption.

The Maintenance Phase

After reaching the maintenance dose, patients continue treatment at regular intervals for 3-5 years. For SCIT, this means monthly injections, while SLIT requires daily tablet or drop administration. The extended duration is necessary to achieve lasting immune changes that will persist after treatment ends. Studies show that shorter treatment courses provide benefit while actively taking therapy but may not confer long-term protection after stopping.

During maintenance, patients are monitored for both effectiveness and adverse reactions. Dosing may be adjusted if reactions occur, and additional allergens can sometimes be added if new sensitivities develop. Regular follow-up appointments help track progress and make any necessary modifications to the treatment plan.

What to Expect During Treatment

Most patients begin noticing symptom improvement within 3-6 months of starting treatment, though maximum benefits develop gradually over the full treatment course. Early in treatment, patients may still need to use symptomatic medications during high allergen exposure periods, but the need for these medications typically decreases over time.

For seasonal allergies, improvement is often most noticeable during the second pollen season after starting treatment. By the third year, most patients experience significant symptom reduction and decreased medication requirements. The goal is not necessarily complete elimination of symptoms but rather meaningful improvement in quality of life with reduced treatment burden.

How Effective Is Allergen Immunotherapy?

Allergen immunotherapy is highly effective, reducing allergy symptoms by 20-40% for respiratory allergies and providing 90-95% protection against severe reactions in venom allergy. Importantly, benefits persist for years after completing treatment, unlike symptomatic medications that only work while being taken.

The effectiveness of allergen immunotherapy has been demonstrated in numerous high-quality clinical trials, systematic reviews, and meta-analyses. While the degree of benefit varies based on factors like the specific allergen, patient characteristics, and treatment adherence, the overall evidence strongly supports immunotherapy as an effective treatment option. Understanding what level of improvement to expect helps patients make informed decisions about pursuing this treatment.

Effectiveness for Respiratory Allergies

For allergic rhinitis, meta-analyses of randomized controlled trials consistently show symptom reductions of 20-40% compared to placebo. This may sound modest, but it represents meaningful clinical improvement for many patients, especially when combined with reduced medication needs. Quality of life improvements can be substantial, with patients reporting better sleep, improved concentration, and ability to participate in outdoor activities previously limited by symptoms.

Beyond symptom reduction during treatment, allergen immunotherapy provides sustained benefits after treatment completion. Studies following patients for 7-10 years after completing immunotherapy show that the majority maintain their symptom improvement without ongoing treatment. This contrasts sharply with symptomatic medications, whose benefits disappear immediately upon discontinuation.

Effectiveness for Asthma

In patients with allergic asthma, immunotherapy has been shown to reduce asthma symptoms, decrease medication requirements, improve lung function, and reduce bronchial hyperreactivity. The Cochrane review of allergen immunotherapy for asthma found significant benefits compared to placebo across multiple outcome measures. However, the magnitude of benefit varies considerably between studies, likely reflecting differences in patient populations and treatment protocols.

Perhaps most importantly for long-term health, immunotherapy may prevent the development of asthma in children with allergic rhinitis. The Preventive Allergy Treatment (PAT) study followed children with allergic rhinitis for 10 years and found that those who received immunotherapy were significantly less likely to develop asthma compared to those who received only symptomatic treatment.

Effectiveness for Venom Allergy

Venom immunotherapy is remarkably effective, with studies showing 90-95% protection against systemic reactions upon subsequent stings in treated patients, compared to a 60% risk of reaction in untreated individuals. This high efficacy rate makes venom immunotherapy one of the most effective treatments in allergy medicine and potentially lifesaving for patients with a history of anaphylaxis to insect stings.

Factors Affecting Effectiveness

Several factors influence how well individual patients respond to immunotherapy. Better outcomes are associated with higher doses of allergen, longer treatment duration, good treatment adherence, younger patient age at treatment initiation, monosensitization (allergy to a single allergen), and moderate rather than severe disease. Understanding these factors helps optimize treatment plans and set appropriate expectations for individual patients.

What Are the Risks and Side Effects?

Allergen immunotherapy is generally safe when administered properly. Local reactions (redness, swelling at injection site) are common but mild. Systemic reactions occur in about 0.1-0.2% of injections, with severe anaphylaxis being very rare (approximately 1 in 1 million injections). Sublingual therapy has an even better safety profile with mainly local mouth/throat reactions.

Like any medical treatment, allergen immunotherapy carries certain risks that must be weighed against potential benefits. The safety profile of immunotherapy is well-established through decades of clinical experience and numerous safety studies. Understanding the types of reactions that can occur, their frequency, and how they are managed helps patients make informed decisions and prepares them to recognize and respond appropriately to any adverse effects.

Local Reactions

Local reactions at the injection site are the most common side effect of subcutaneous immunotherapy, occurring in up to 80% of patients at some point during treatment. These reactions include redness, swelling, itching, and warmth around the injection site. They typically develop within 30 minutes of injection and resolve within 24-48 hours. While uncomfortable, local reactions are not dangerous and do not predict systemic reactions.

Management of local reactions includes ice application, oral antihistamines, and sometimes topical corticosteroids. If local reactions become large or bothersome, the allergen dose may be reduced temporarily before continuing to increase. Persistent large local reactions may require protocol modifications but rarely necessitate discontinuing treatment.

Systemic Reactions

Systemic reactions involve symptoms beyond the injection site and can include hives, nasal congestion, throat tightness, wheezing, or in severe cases, anaphylaxis. These reactions occur in approximately 0.1-0.2% of injection visits for subcutaneous immunotherapy. Risk factors include uncontrolled asthma, injections during peak pollen season, dosing errors, and certain medications like beta-blockers.

This is why subcutaneous immunotherapy is administered in medical settings with emergency equipment and trained staff available. Patients are required to wait 30 minutes after each injection for observation, as most systemic reactions occur within this time frame. When systemic reactions do occur, they are usually mild and respond quickly to treatment with antihistamines or epinephrine if needed.

Sublingual Immunotherapy Safety

Sublingual immunotherapy has an excellent safety profile, with severe systemic reactions being extremely rare. The most common side effects are local reactions in the mouth and throat, including itching, tingling, swelling of the lips or tongue, and throat irritation. These reactions are usually mild, occur primarily at the beginning of treatment, and typically resolve within the first few weeks.

Because severe reactions are so rare with SLIT, patients can take their treatment at home after the first supervised dose. However, patients are still provided with an action plan for managing reactions and should have antihistamines available. First-dose supervision is important to ensure patients tolerate the medication and understand proper administration technique.

Who Is a Good Candidate for Immunotherapy?

Good candidates for allergen immunotherapy are patients with IgE-mediated allergies confirmed by testing, symptoms not adequately controlled with medications, and the ability to commit to 3-5 years of treatment. It is most effective in younger patients and those with fewer allergen sensitivities. Uncontrolled asthma, beta-blocker use, and pregnancy are relative contraindications.

Patient selection is crucial for immunotherapy success. The treatment works best in carefully selected patients who have clear allergic disease, appropriate treatment goals, and the ability to adhere to the lengthy treatment protocol. Both patients and healthcare providers should understand the criteria that help identify ideal candidates and the factors that might limit treatment effectiveness or safety.

Ideal Candidates

The best candidates for allergen immunotherapy typically share several characteristics. They have clearly IgE-mediated allergies, meaning their symptoms are triggered by specific allergens and confirmed through skin testing or blood tests showing allergen-specific IgE antibodies. Their symptoms significantly impact quality of life despite using appropriate symptomatic medications, or they experience unacceptable side effects from these medications.

Ideal candidates are also able to commit to the treatment schedule, understanding that immunotherapy requires consistent adherence over several years to achieve lasting benefits. They have realistic expectations about treatment outcomes, recognizing that immunotherapy reduces but may not eliminate symptoms. Younger patients often respond better than older patients, and those with allergies to a smaller number of allergens tend to have better outcomes than those with multiple sensitivities.

Contraindications and Precautions

Certain conditions may make immunotherapy inadvisable or require special precautions. Uncontrolled or severe asthma is the most important contraindication for subcutaneous immunotherapy, as patients with unstable asthma are at significantly higher risk of severe systemic reactions. Asthma must be well-controlled before starting injections and should be carefully monitored throughout treatment.

Beta-blocker medications (taken for heart conditions or high blood pressure) can interfere with the treatment of anaphylaxis, making systemic reactions more difficult to manage. Patients on beta-blockers require careful risk-benefit assessment and may need medication modifications or enhanced monitoring. ACE inhibitors are of particular concern with venom immunotherapy and sublingual therapy.

Pregnancy is generally a contraindication for starting immunotherapy due to the risk of systemic reactions that could harm the fetus. However, patients who become pregnant while on maintenance immunotherapy can usually continue treatment safely, as the risk of reactions is lower once the maintenance dose is established. Autoimmune conditions and immunodeficiency may also affect treatment decisions and require individualized assessment.

Children and Immunotherapy

Children are often excellent candidates for immunotherapy, with most guidelines recommending treatment from age 5 years, though some allow treatment from age 3 in appropriate circumstances. The ability to cooperate with injections and communicate symptoms is important for safe treatment. Early treatment in children may offer particular benefits, including preventing the development of new allergies and reducing the risk of progressing from allergic rhinitis to asthma.

How Should You Prepare for Treatment?

Preparation for allergen immunotherapy includes comprehensive allergy testing, reviewing your medication list with your allergist, ensuring asthma is well-controlled if applicable, and understanding the treatment schedule and commitment required. On injection days, avoid strenuous exercise for several hours before and after treatment.

Proper preparation helps ensure safe and effective immunotherapy treatment. This includes medical preparation before starting therapy, practical considerations for each treatment session, and lifestyle adjustments that optimize outcomes. Working closely with your allergist and communicating openly about any concerns helps create the best conditions for treatment success.

Medical Preparation

Before starting immunotherapy, your allergist will review your complete medical history, including all current medications, previous allergic reactions, and any conditions that might affect treatment safety. If you have asthma, it should be well-controlled with a peak flow or spirometry measurement often documented before starting injections. Medications that might interfere with emergency treatment, such as beta-blockers, may need to be adjusted.

You should inform your allergist about any infections or illnesses, changes in medications, new symptoms, and upcoming vaccinations or dental procedures. These factors may temporarily affect your treatment schedule, as doses may need to be modified or delayed under certain circumstances.

Injection Day Guidelines

On days when you receive allergy injections, several precautions help ensure safety. Avoid vigorous exercise for at least 2 hours before and after your injection, as physical activity can increase blood flow and potentially worsen reactions. Eat before your appointment, as reactions may be more severe on an empty stomach. Bring any prescribed emergency medications, such as an epinephrine auto-injector if you have one.

Plan to stay at the clinic for 30 minutes after each injection for observation. This waiting period is when most reactions occur, and the medical staff can quickly address any problems. After leaving, remain aware of how you feel and know how to seek help if delayed reactions occur.

Managing Expectations

Understanding what to expect from immunotherapy helps maintain realistic expectations and treatment adherence. Improvement typically begins within the first year but develops gradually over the full 3-5 year course. You may still need symptomatic medications during high allergen exposure periods, especially early in treatment. Complete symptom elimination is not the goal; rather, the aim is meaningful improvement in symptoms and quality of life with reduced medication needs.

What Happens After Treatment Ends?

After completing 3-5 years of immunotherapy, most patients maintain their improved tolerance to allergens for many years, often indefinitely. Some may experience gradual return of symptoms over time and might benefit from a repeat treatment course. Follow-up appointments help monitor long-term outcomes.

One of the most significant advantages of allergen immunotherapy over symptomatic treatments is the persistence of benefits after treatment completion. Understanding the long-term trajectory after stopping immunotherapy helps patients appreciate the value of completing the full treatment course and know what to expect in the years that follow.

Duration of Benefits

Studies following patients for up to 12 years after completing immunotherapy demonstrate that the majority maintain their treatment benefits. The degree of sustained improvement varies between individuals and may depend on factors like treatment duration, adherence during therapy, and ongoing allergen exposure. Most patients continue to experience reduced symptoms and medication requirements compared to their pre-treatment state.

For venom allergy, protection rates remain high even 10-15 years after completing treatment in most patients. However, patients with certain risk factors, such as very severe initial reactions, mastocytosis, or other clonal mast cell disorders, may have higher rates of losing protection and might benefit from longer or indefinite treatment.

Monitoring After Treatment

After completing immunotherapy, periodic follow-up with your allergist helps monitor ongoing symptom control and address any changes. If symptoms begin to return, repeat allergy testing can determine whether this reflects loss of tolerance to previously treated allergens or development of new sensitivities. Some patients may benefit from a repeat treatment course if significant symptoms return years after completing their initial therapy.

Lifestyle Considerations

Completing immunotherapy does not mean you need to avoid allergen exposure. In fact, continued natural exposure to allergens likely helps maintain the tolerance developed during treatment. However, reasonable precautions remain sensible, such as reducing dust mite allergen levels in the home for those with dust mite sensitivity. The goal is normal life without excessive restrictions.