Venom Immunotherapy: What is it and How Does it Benefit Patients

Venom allergies are a serious concern for many individuals, especially those who have encountered severe reactions to stinging insects. Understanding the nature of these allergies and the potential for life-threatening reactions is crucial for effective management and treatment. In this blog, we delve into the world of venom immunotherapy (VIT), exploring its purpose, mechanisms, and benefits for patients.

Brief Overview of Venom Allergies

Stinging Insects That Cause Venom Allergies:

There are four stinging insects responsible for the most severe allergic reactions to venom: yellow jackets, hornets, honeybees, and fire ants.

Yellow Jackets:

Yellow jackets are aggressive, territorial, and are known to sting repeatedly once provoked. There are six different species of yellow jacket located across the U.S. that can sting and cause an allergic reaction. Yellow jackets tend to create two types of nests, aerial and ground nests. Ground nests are more common and can be difficult to see. Four types of yellow jackets create ground nests, while only one, the Aerial Yellow Jacket, creates aerial nests. They also tend to live in large colonies of up to 4,000 workers and they are most active in the late summer and fall.

Hornets:

Hornets are aggressive, territorial, and are known for their large nests and painful sting. There are two species of hornet, the Yellow Hornet and the White-Faced Hornet. Although they look different, both species can repeatedly sting their victim. Hornets create both aerial and paper nests that should be avoided as much as possible to not be stung.

Honeybees:

Honeybees are social insects and are critically beneficial to the natural world because of their role in pollination of plants. Honeybees are found worldwide, and their nests are typically found in hollow trees, rock crevices, or under objects where they hide from predators. Honeybees are non-aggressive and are typically more concerned about caring for their hive and pollination than potential victims. The best way to avoid a honeybee sting is to not bother their hive or swat/attack them if they come near.

Fire ants:

There are six species of fire ant currently in the U.S., two imported species and four native species. Fire ants are social insects and don’t typically attack humans unless their nests are disturbed or threatened. When provoked, all fire ant species but one swarms their victim, and each fire ant will sting multiple times. The best way to avoid a fire ant sting and venom reaction is to avoid their nests and/or have them removed by a certified professional. 

How to Avoid Stinging Insects:

There are some simple ways to avoid stinging insects, whether you have an allergy or not. Of course, as described above, the best way to avoid being stung is to not disturb the stinging insects’ nest. The other simple ways to avoid being stung include:

• Keeping picnic foods well-covered
• Move slowly and don’t “flail or swat” your arms
• Keep insecticides readily available
• Check the exterior of your property regularly for nests
• Always have infestations removed by professionals
• Wear close fitting clothing that covers the extremities

It is important to note that allergies to stinging insects can develop over time after repeated exposure to their venom. As people age into adulthood, their allergies tend to get worse with more severe reactions.

Understanding Severe Allergic Reactions to Venom:

The most severe reaction a person can have to an allergy would be anaphylaxis or anaphylactic shock. Anaphylaxis is an acute, life-threatening hypersensitivity disorder and is defined as a generalized, rapidly evolving, multi-systemic allergic reaction.⁸ The first hour after initial symptom onset is the most crucial when treating anaphylaxis. The worse and more rapid the onset of symptoms, the more severe the reaction will be.

Stinging insect (Hymenoptera) venom is one of the most common causes of allergies in adults, with almost 7% of the U.S. population at risk of a severe reaction from their next sting.³

Venom Immunotherapy & Managing Severe Allergic Reactions:

Venom immunotherapy, or VIT, leads to protection from a severe allergic reaction in 77-84% of cases for honeybee and 91-96% for vespid venoms.¹¹ Although VIT has a complex diagnosing and treating process, the protective effect from VIT can last for years with continuing treatment.

What is Venom Immunotherapy (VIT)? 

Definition and Purpose of Venom Immunotherapy:

Venom immunotherapy (VIT) is the most effective treatment for people with bee and vespid venom allergies that is proven to modulate the immune system, resulting in a success rate for patients of between 80-95%.¹¹ During treatment, doses of insect venom are administered increasingly to induce immunological tolerance through subcutaneous injections over several weeks and potentially up to five years.³ While allergen immunotherapy (AIT) exists to reduce allergy symptoms over time by increasing a patient’s tolerance, VIT is meant to prevent fatal or life-threatening allergic reactions to stinging insect venom.⁶

Dr. Steven Kernerman, a board-certified physician by the American Board of Allergy, Asthma, and Immunology and the American Board of Internal Medicine, and provider at Spokane Allergy & Asthma Clinic says, “After being diagnosed with a bee or wasp allergy, you can pretty much start on venom immunotherapy as soon as can be arranged. If there are no insurance restrictions, this can mean within days of being tested and having the diagnosis confirmed.”

History and Development of Venom Immunotherapy:

The first case of immunotherapy in connection with venom allergies was published in 1925 where one patient was reported to be desensitized to bee stings after treatment.¹² The history of venom immunotherapy is extensive in comparison to immunotherapy for other allergies, specifically food allergies, although allergen immunotherapy was born from a controlled trial of hay fever immunotherapy in 1911.³

The initial trials and cases of VIT used the whole crushed body of a wasp, which continued for many years until it was shown to be ineffective. The current modality of VIT was developed in 1978, where the venom is extracted directly from the insect’s venom sacs. This version of VIT is highly effective in treatment.³

At HollisterStier Allergy, we offer various venom extracts to be used for venom immunotherapy, including:

• Honeybee Venom (Apis mellifera)
• White-faced Hornet (Dolichovespula maculata) Venom Protein
• Yellow Hornet (Dolichovespula arenaria) Venom Protein
• Wasp Venom (Polistes spp.) Protein
• Yellow Jacket Venom Protein (equal parts: germanica, V. maculifrons, V. pensylvanica, V. vulgaris, and V. squamosal)
• Mixed Vespid Venom Protein (contains Yellow Jacket, White-Faced Hornet, and Yellow Hornet)
• Venomil® Single-Dose Diagnostic (2mL vial)

VIT stands out in comparison to other allergy treatment options because it treats the cause of the allergy while other options treat the allergic reaction.

Mechanisms of Venom Immunotherapy

Immunotherapy works through an assortment of complex immunological mechanisms that alter the immune response to the incoming allergen. The first mechanism of action is the desensitization of mast cell and basophil, followed by changes in the T-cells, and lastly alterating in B-cell, IgE mast cell, basophil, and eosinophil responses to the presented allergen.³ 

Diagnosing a Venom Allergy for VIT:

When it comes to diagnosing and managing stinging insect allergies, the guidelines stipulate a cautious approach. According to Jakob et al., diagnostic testing is reserved for patients who have a documented history of anaphylactic responses to stinging insect venom. This selective approach ensures that resources are directed towards patients with the most risk, while simultaneously minimizing unnecessary procedures and potential risks associated with them.⁷

Treatment decisions, particularly regarding VIT, are similarly stringent and tailored to individuals who have previously demonstrated evidence of an IgE-mediated sensitization to Hymenoptera venom.⁷ This targeted strategy not only ensures the effective allocation of resources, it also reduces the likelihood of unnecessary treatment burdens for potential patients.

According to HollisterStier Allergy’s venom immunotherapy package insert, prick testing should be done before intradermal testing to determine appropriate concentration for intradermal testing. Skin testing (prick and intradermal) provides information to assist in identifying those patients who are to be classified as extremely sensitive and who may not tolerate the Suggested Dose Schedule.

How VIT Works in the Body:

VIT is a pivotal treatment in managing stinging insect venom allergies, offering a multi-phased approach to desensitization. As outlined by Niedoszytko et al., the therapy comprises two primary phases: the buildup phase and the maintenance phase. During the buildup phase, incremental doses of allergen are administered until the maintenance does is achieved. This phase can vary in duration, ranging from a single day to several weeks, depending on the protocol.⁹

Once the maintenance dose is reached, the risk of systemic reactions to subsequent stings significantly diminishes, offering patients a reduction of a possible reaction from 70% down to 3%. The maintenance phase is critical to ensure the long-term prevention of anaphylactic reactions and typically spans from three to five years, while being tailored to the severity of the patient’s allergic reaction.⁹

There is also the option for medical providers to offer their patients with rush or ultra rush VIT, which can be a safe and effective treatment option for patients who may be higher-risk or don’t have the availability for traditional VIT.¹⁶ According to Sturm, Eva, et al., in a study of a group of high risk patients receiving rush VIT, incidences of systemic reactions was low and epinephrine use was never necessary. This study concluded that the regiment proved to be safe and convenient for patients. Rush and ultra rush VIT are both accelerated versions of the traditional VIT, with rush VIT having a build-up phase over a course of several days and ultra rush VIT reaching maintenance dose within hours. Rush or ultra rush VIT may be best for higher-risk patients to reduce the possibility of a strong systemic reaction to treatment.¹⁴

Venom Immunotherapy Standardization:

Due to the detailed and rigid guidelines that go into diagnosing and treating stinging insect venom allergies, all venom extracts used in venom immunotherapy are standardized. Standardization is based on measurements of enzymatic activity of the protein for each species.

The FDA requires venom manufacturers to run the following tests for licensure to manufacture:

• Hyaluronidase
• Phospholipase A
• Protein
• Sterility
• Safety
• Moisture
• Mannitol

Benefits & Risks of Venom Immunotherapy

VIT is a pivotal treatment for those at high risk of anaphylaxis or life-threatening systemic reactions due to Hymenoptera venom allergy.¹³ For these individuals, VIT provides a tangible pathway towards mitigating the frequency and severity of allergic reactions. Through treatment, patients experience a notable enhancement in their quality of life. Moreover, the long-term effectiveness and durability of VIT offers patients sustained relief and peace of mind.

However, there are some potential risks and complexities that are possible with venom immunotherapy. Some patients may encounter severe side effects during treatment, which is influenced by various factors including baseline serum tryptase concentration (BTC) and the presence of bee venom allergy.¹⁰ Individuals with bee venom allergy require heightened vigilance and surveillance through the VIT process to ensure their safety and general well-being.

While VIT can transform the lives of those plagued by severe stinging insect venom allergies, it’s important to understand potential treatment risks and the benefits.

Venom immunotherapy (VIT) stands as a beacon of hope for individuals plagued by severe allergic reactions to stinging insects. Through its gradual approach of desensitization and modulation of the immune response, VIT offers not only relief but also long-term protection against life-threatening anaphylaxis.

While it’s essential to recognize the potential risks and considerations associated with VIT, its proven efficacy in reducing the frequency and severity of allergic reactions underscores its importance in the realm of allergy management. With ongoing research and advancements, VIT continues to pave the way towards improved quality of life for those with venom allergies, promising a future where the threat of anaphylaxis diminishes, and individuals can live without fear of the sting.