Hyposensitization
Encyclopedia
Allergen immunotherapy (also termed hyposensitization therapy, immunologic desensitization, hyposensibilization, or allergen-specific immunotherapy) is a form of immunotherapy
for allergic
disorders in which the patient is vaccinated with increasingly larger doses of an allergen
(substances to which they are allergic) with the aim of inducing immunologic tolerance. Allergen specific immunotherapy is the only treatment strategy which treats the underlying cause of the allergic disorder. It is a highly cost-effective treatment strategy which results in an improved quality of life
and a reduction in allergic- and allergen-related asthma
, as well as a reduction in days off school/work. Immunotherapy has been shown to produce long-term remission of allergic symptoms, reduce severity of associated asthma, as well as reduce the chances of new sensitisations to allergens developing. This is achieved via immunotherapy modulating the immune system response to allergens.
Allergen immunotherapy can either reduce the need for medication, severity of symptoms or eliminate hypersensitivity
altogether. Therapy can be administered under the tongue (sublingually) or by injections
under the skin (subcutaneous). Allergen-specific immunotherapy is the only known treatment option that is known to modify the allergy disease process (with a possible chance of curing the disease), whereas other therapies merely suppress the symptoms. Subcutaneous injection immunotherapy has been shown to be a highly efficient treatment for allergic disease, but due to a rare serious side effect of anaphylaxis
, its use is restricted to specialist centers. As a result there has been growing interest in the sublingual therapy which can be safely administered at home.
is an extremely common disorder. For example in the UK 1 in 5 people have allergic rhinitis with approximately 50 percent of those with allergic rhinitis being allergic to grass pollen. Over half of people receiving symptom based treatments report that they only get partial or a poor benefit from symptomatic based treatments. For these such patients immunodesensitisation therapy can be recommended. Subcutaneous injection based immunotherapy is one effective route but is complicated by rare but serious side effects. As a result of these rare but serious side effects the sublingual route for allergen vaccination immunotherapy is gaining increasing popularity among allergy specialists due to its lack of serious side effects.
Immunotherapy administered through cutaneous injections or sublingual
ly has substantial empirical support. Numerous research articles and several meta-analytic studies support its clinical effectiveness. Immunotherapy can lead to a substantial decline in allergen symptomatology leading to a significant improvement in quality of life for allergy sufferers. Repeated courses of immuno-desensitisation leads to further reduction in allergy disease severity. Immunotherapy is superior to antihistamines and topical steroids in reducing severity of allergy symptoms and has been found to be a cost effective treatment strategy. Immunotherapy results in less time taken off work compared to those who rely solely on symptomatic relieving medications. In the case of grass allergy immunotherapy the pollen from the grass species used has strong cross reactivity between the various grass species thus meaning that treatment leads to desensitisation to all grass species.
Sublingual specific immunotherapy has the benefit of allowing treatment to be carried out in the home environment and has been found to be a cost effective treatment strategy for allergic disorders. Sublingual immunotherapy cost effectiveness is significantly increased due to the reduced number of medical visits compared to those receiving subcutaneous injection based immunotherapy. For example those receiving subcutaneous injections make almost seven times more visits than those receiving home based sublingual immunotherapy versus those receiving subcutaneous injections who require frequent visits to doctors to receive their regular injections. Furthermore the sublingual route appears to be equally as effective as the subcutaneous route in trials of grass allergy.
is a relatively young science that originated in the 19th century. Grass pollens were identified for the first time as the likely trigger of seasonal hay fever in the 1870s. Skin allergy test
ing became an accepted assessment technique around 1910. IgE
was identified in the 1960s. The first scholarly report of immunotherapy for allergy appeared in 1911 in the medical journal, The Lancet
, but research lagged behind clinical practice. Whereas clinical lore in medicine generally supports the effectiveness of immunotherapy, sufficient research evidence on the effectiveness and mechanism of immunotherapy began to accumulate in the last 15 years of the 20th century.
Some limited research of sublingual immunotherapy in children has been conducted and shown promise as a generally well tolerated treatment strategy for allergic disorders in children.
in the body, reducing allergic symptoms. Immunotherapy, in contrast, trains the immune system to tolerate allergic triggers by means of gradual exposure to increasing amounts of the offending allergen. The benefits of allergen specific immunotherapy are long lasting unlike symptomatic based treatments. Immunotherapy is most effective for pollen, dust, and animal dander allergies, and may help those with asthma
.
Treatment started 10 – 14 weeks before the start of the grass pollen season results in a 34% reduction of rhinoconjunctivitis symptoms and a 54% increase in well days. Continued treatment over 2 years in the case of grass allergy shows progressive immunological changes resulting in progressive desensitisation to the allergen with up to an 73 percent reduction in symptomatology. About 3 in 4 patients with hay fever
experience significant improvement with immunotherapy after one year of therapy. However, with continued therapy the number of people benefiting from specific immunotherapy appears to increase to over 4 in 5 people who benefit from specific immunotherapy by the end of the 2nd year of therapy. Sometimes symptoms are reduced rather than abolished. In that case immunotherapy may allow the patient to reduce the quantity of medication required for symptom relief.
Research in children aged from 5 years old to 16 years old shows similar effectiveness in the treatment of grass allergy as seen in adults. Like in adults allergen related asthma
also decreases as well as allergic rhinitis
symptoms. Recent studies in children suggest that if immunotherapy is commenced soon after allergies first develop, it may actually reduce the risk of developing allergic reactions to other allergens, and even reduce the risk of later developing asthma.
Immunotherapy is also an essential part of managing dangerous allergic reactions (anaphylaxis
) to bee and wasp stings. In these cases, the protection against further dangerous allergic reactions to stinging insects is variously quoted at between 80 and 95%.
(IgE). This is called the 'primary antibody response.' The IgE
produced during this response binds to basophils in the bloodstream and to a similar type of cell called mast cells in the tissues. When the person again encounters the allergen, these basophils and mast cells that have bound to IgE release histamine
, prostaglandins, and leukotrienes, which causes inflammation of the surrounding tissues, resulting in allergic symptoms.
Even the most allergic individual can tolerate minuscule amounts of an allergen without experiencing symptoms. Immunotherapy commences with the subcutaneous injection of a tiny amount of offending allergen, and gradually increases the dose until the individual's immune system is essentially 'retrained' to tolerate exposure without producing an allergic response. This process is also known as specific immunotherapy.
Immunotherapy via repeated exposure to a specific allergen via either sublingual or subcutaneous route leads to a desensitisation to the allergen and thus a reduction in allergic symptomatology and use of symptomatic based treatments. The exact mechanism is not fully understood but it is accepted that immunotherapy causes modification of the immune system. This modification leads to changes in IgE synthesis and the production of IgE blocking antibodies which thus reduces the immune systems allergic response to specific allergens. There is also an increase in Th2 to the regulatory T cells. The molecular mechanism of such immunotherapy can be partly interpreted as that there occurs induction of allergen-specific IgG to neutralize the allergen instead of induction of allergen-specific IgE.
In bee or wasp venom immunotherapy, immunoglobulin subclass IgG4 has been considered to be particularly important, where IL-10
make the B cells to switch the produced immunoglobulin class from IgE to IgG4.
It has been revealed that the mechanism of this immunotherapy consists of some more other components. They include increased production of IL-10
which acts on Th2 or mast cells to become anergic and suppresses Th2 not to release cytokines and prevent histamine
from being secreted.
It was indicated that osteopontin
produced by CD14+
cells induced IL-12
in antigen presenting cells to activate Th1.
It was recently shown that a progressive expansion of circulating regulatory T cells was made during venom immunotherapy.
Subcutaneous immunotherapy (SCIT)
Immunotherapy via the subcutaneous route involves the use of small hypodermic syringes which are used to inject commercial allergen extracts. Injections are normally given into the loose tissue over the back of the upper arm, half way between the shoulder and elbow. Injections are given under the skin ("subcutaneous"). This is the least painful place to inject allergen, as there are few nerve endings in the skin. When given correctly, the injections should be only slightly uncomfortable. They are not normally painful and are usually well tolerated by adults and teenagers. Some doctors may advise you to take an antihistamine a few hours before each injection to reduce the likelihood of local discomfort and other side-effects.
Allergy injections are started at very low doses. The dose is gradually increased on a regular (and usually weekly) basis, until a "maintenance" dose is reached. This usually means four to six months of weekly injections to reach the maintenance dose. Once the maintenance dose is reached, the injections are administered less often (every two to four weeks), still on a regular basis. Maintenance injections are normally given once per month for a few years. Generally, the longer the treatment and the higher the dose, the greater the therapeutic benefit.
After successful completion of immunotherapy, long-term protection can be expected for a period of 3–5 years or more. Therapy can be repeated should symptoms begin to return or if the individual becomes exposed to new allergens that were not included in the previous treatment regimen. Because allergy vaccine injections have a strong evidence base for clinical effectiveness, this form of treatment is covered by the vast majority of insurance companies in the United States.
Intralymphatic immunotherapy (ILIT)
Intralymphatic delivery of immunotherapy is another modality which is effective in the treatment of allergic disorders.
Intralymphatic immunotherapy (ILIT) administers allergens directly into a subcutaneous lymph node; A paper in 2009 found that studies on both animals and humans demonstrated that a direct injection into lymph nodes enhanced the immune responses to protein, peptide, and naked DNA vaccines and that this increased response meant that the overall allergen dosage and therapy duration could be reduced.
A study on mice found that intralymphatic immunisation induced a more than 10-fold higher IgG2a response with 100-fold lower allergen doses than subcutaneous immunisation; and that only intralymphatic immunisation stimulated the production of the Th1-dependent subclass IgG2a, which is associated with improved protection against allergen-induced anaphylaxis.
ILIT is well tolerated and patients found it to be "practically painless" and easy to perform. Patient compliance with ILIT was improved as compared with SCIT.
Sublinguil immunotherapy (SLIT)
In some countries, particularly in Europe, there is a strong tradition of undertaking immunotherapy using oral vaccines or sublingual drops. While there has been some interesting research in this area in recent years, the effectiveness of this form of treatment is difficult to compare with standard injected immunotherapy. Double-blind, placebo-controlled studies in Europe using high-dose sublingual immunotherapy have shown benefit. Some practitioners in the United States, particularly ENT physicians, offer sublingual immunotherapy as another immunotherapy option.
Sublingual immunotherapy is a safe and effective alternative to injection based immunotherapy and can be administered in the home environment. Modest benefits have been demonstrated within the first season of therapy. Treatment needs to be continued for at least 3 years to achieve maximum effectiveness in immune desensitisation to the allergen. In the case of sublingual immunotherapy there is no need to do a titrated graduated updose and therapy is generally started at the usual clinical dose.
Transcutaneous immunotherapy (TCIT) / Epicutaneous immunotherapy (ELIT)
This emerging therapy administers allergen by a skin patch. Though relatively new, clinical trials show that TCIT, EPIT is safe and comparably effective to conventional immunotherapy.
Subcutaneous immuno-therapy (SCIT)
While itchiness, swelling, and redness at the site of injection are expected, systemic reactions such as hives or anaphylaxis
rarely occur. A July 2011 study following 773 patients that collectively received approximately 28,000 injections, the rate of systemic reaction to SCIT was about 4%. As such, patients are advised or required to wait in the clinic for 20–30 minutes so that they can be treated immediately in the case that they develop a severe systemic reaction. However, a 2008 study found that just under 50% of reported systemic reactions occurred more than 30 minutes after the injection.
Premedication with antihistamines or corticosteroids can reduce the risk of systemic reaction.
There is an established correlation between those receiving a Rushed Immunotherapy and higher rates of systemic reactions as compared to that those receiving conventional SCIT. While it may seem attractive to patients to rush SCIT, it seems as though it does lead to an increased risk to having a systemic reaction. However, this may not be the same for allergic respiratory diseases.
About 74% of systemic reactions to SCIT are mild reactions such as cutaneous or upper respiratory symptoms; about 23% are moderate reactions such as asthma with reduced lung function, and about 3% are severe, where life-threatening airway compromising or hypo-tension occurs.
Based on the highest reported symptoms of a systemic reaction, such as generalized itching, upper airway itchiness, coughs, or a shortness of breath should be reported immediately so they can be monitored or managed. These are usually managed through the use of epinephrine.
If such reactions occur, the allergy specialist will adjust the dosage to a safe level. The risk of a systemic reaction is reduced if the patient avoids exercising or overheating for a few hours before and after the procedure. Some heart and blood pressure medications such as beta-blockers are contraindicated as well.
The physician should be consulted if the patient notices a worsening of allergy symptoms or if he or she is suffering from a cold or has been undergoing a different kind of vaccination procedure. Immunotherapy does not increase the risk of contracting a cold.
Sublingual immuno-therapy (SLIT)
The side effects of sublingual desensitisation therapy are generally mild and limited to local reactions. Common side effects include oral pruritus, edema mouth, ear pruritus, throat irritation
, sneezing, mild itching and swelling of the mouth. Side effects which are less common or rare include headache
, oral paraesthesia, eye pruritus, conjunctivitis
, cough
, asthma
, pharyngitis
, rhinorrhoea, nasal congestion
, rhinitis
, throat tightness, pruritus and fatigue. In most cases these side effects diminished minutes or hours after immunotherapy and disappeared 1 – 7 days after commencement of therapy. As a precautionary measure against rare but serious side effects e.g. asthma attacks it is recommended that the first sublingual tablet containing the specific allergen for immunotherapy is administrated whilst under the observation of a medical doctor and observed for 30 minutes for any signs of serious side effects.
Sublingual immunotherapy is contraindicated in patients who have systemic diseases of the immune system, inflammatory conditions of the oral cavity with associated severe symptoms e.g. oral lichen planus
with ulcers or severe oral mycosis
or individuals with severe and uncontrolled asthma. Immunotherapy tablets are also contraindicated in individuals who are allergic to any of the addition constituents of the tablet.
Immunotherapy
Immunotherapy is a medical term defined as the "treatment of disease by inducing, enhancing, or suppressing an immune response". Immunotherapies designed to elicit or amplify an immune response are classified as activation immunotherapies. While immunotherapies that reduce or suppress are...
for allergic
Allergy
An Allergy is a hypersensitivity disorder of the immune system. Allergic reactions occur when a person's immune system reacts to normally harmless substances in the environment. A substance that causes a reaction is called an allergen. These reactions are acquired, predictable, and rapid...
disorders in which the patient is vaccinated with increasingly larger doses of an allergen
Allergen
An allergen is any substance that can cause an allergy. In technical terms, an allergen is a non-parasitic antigen capable of stimulating a type-I hypersensitivity reaction in atopic individuals....
(substances to which they are allergic) with the aim of inducing immunologic tolerance. Allergen specific immunotherapy is the only treatment strategy which treats the underlying cause of the allergic disorder. It is a highly cost-effective treatment strategy which results in an improved quality of life
Quality of life (healthcare)
Quality of Life is a phrase used to refer to an individual’s total wellbeing. This includes all emotional, social, and physical aspects of the individual’s life. However, when the phrase is used in reference to medicine and healthcare as Health Related Quality of Life, it refers to how the...
and a reduction in allergic- and allergen-related asthma
Asthma
Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...
, as well as a reduction in days off school/work. Immunotherapy has been shown to produce long-term remission of allergic symptoms, reduce severity of associated asthma, as well as reduce the chances of new sensitisations to allergens developing. This is achieved via immunotherapy modulating the immune system response to allergens.
Allergen immunotherapy can either reduce the need for medication, severity of symptoms or eliminate hypersensitivity
Hypersensitivity
Hypersensitivity refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity. These reactions may be damaging, uncomfortable, or occasionally fatal. Hypersensitivity reactions require a pre-sensitized state of the host. The four-group classification...
altogether. Therapy can be administered under the tongue (sublingually) or by injections
Injection (medicine)
An injection is an infusion method of putting fluid into the body, usually with a hollow needle and a syringe which is pierced through the skin to a sufficient depth for the material to be forced into the body...
under the skin (subcutaneous). Allergen-specific immunotherapy is the only known treatment option that is known to modify the allergy disease process (with a possible chance of curing the disease), whereas other therapies merely suppress the symptoms. Subcutaneous injection immunotherapy has been shown to be a highly efficient treatment for allergic disease, but due to a rare serious side effect of anaphylaxis
Anaphylaxis
Anaphylaxis is defined as "a serious allergic reaction that is rapid in onset and may cause death". It typically results in a number of symptoms including throat swelling, an itchy rash, and low blood pressure...
, its use is restricted to specialist centers. As a result there has been growing interest in the sublingual therapy which can be safely administered at home.
Background
Allergic rhinitisAllergic rhinitis
Allergic rhinitis, also known as pollenosis or hay fever, is an allergic inflammation of the nasal airways.It occurs when an allergen, such as pollen, dust or animal dander is inhaled by an individual with a sensitized immune system...
is an extremely common disorder. For example in the UK 1 in 5 people have allergic rhinitis with approximately 50 percent of those with allergic rhinitis being allergic to grass pollen. Over half of people receiving symptom based treatments report that they only get partial or a poor benefit from symptomatic based treatments. For these such patients immunodesensitisation therapy can be recommended. Subcutaneous injection based immunotherapy is one effective route but is complicated by rare but serious side effects. As a result of these rare but serious side effects the sublingual route for allergen vaccination immunotherapy is gaining increasing popularity among allergy specialists due to its lack of serious side effects.
Immunotherapy administered through cutaneous injections or sublingual
Sublingual
Sublingual, literally 'under the tongue', from Latin, refers to the pharmacological route of administration by which drugs diffuse into the blood through tissues under the tongue...
ly has substantial empirical support. Numerous research articles and several meta-analytic studies support its clinical effectiveness. Immunotherapy can lead to a substantial decline in allergen symptomatology leading to a significant improvement in quality of life for allergy sufferers. Repeated courses of immuno-desensitisation leads to further reduction in allergy disease severity. Immunotherapy is superior to antihistamines and topical steroids in reducing severity of allergy symptoms and has been found to be a cost effective treatment strategy. Immunotherapy results in less time taken off work compared to those who rely solely on symptomatic relieving medications. In the case of grass allergy immunotherapy the pollen from the grass species used has strong cross reactivity between the various grass species thus meaning that treatment leads to desensitisation to all grass species.
Sublingual specific immunotherapy has the benefit of allowing treatment to be carried out in the home environment and has been found to be a cost effective treatment strategy for allergic disorders. Sublingual immunotherapy cost effectiveness is significantly increased due to the reduced number of medical visits compared to those receiving subcutaneous injection based immunotherapy. For example those receiving subcutaneous injections make almost seven times more visits than those receiving home based sublingual immunotherapy versus those receiving subcutaneous injections who require frequent visits to doctors to receive their regular injections. Furthermore the sublingual route appears to be equally as effective as the subcutaneous route in trials of grass allergy.
Clinical experience and research
ImmunologyImmunology
Immunology is a broad branch of biomedical science that covers the study of all aspects of the immune system in all organisms. It deals with the physiological functioning of the immune system in states of both health and diseases; malfunctions of the immune system in immunological disorders ; the...
is a relatively young science that originated in the 19th century. Grass pollens were identified for the first time as the likely trigger of seasonal hay fever in the 1870s. Skin allergy test
Skin allergy test
Skin allergy testing is a method for medical diagnosis of allergies that attempts to provoke a small, controlled, allergic response. -Process:A microscopic amount of an allergen is introduced to a patient's skin by various means:...
ing became an accepted assessment technique around 1910. IgE
IGE
IGE was one of the largest services company buying and selling virtual currencies and accounts for MMORPG. During its peak time, it had offices in Los Angeles, China , and headquarters & customer service centre in Hong Kong. IGE was one of the main monopoly in virtual economy services, also known...
was identified in the 1960s. The first scholarly report of immunotherapy for allergy appeared in 1911 in the medical journal, The Lancet
The Lancet
The Lancet is a weekly peer-reviewed general medical journal. It is one of the world's best known, oldest, and most respected general medical journals...
, but research lagged behind clinical practice. Whereas clinical lore in medicine generally supports the effectiveness of immunotherapy, sufficient research evidence on the effectiveness and mechanism of immunotherapy began to accumulate in the last 15 years of the 20th century.
Some limited research of sublingual immunotherapy in children has been conducted and shown promise as a generally well tolerated treatment strategy for allergic disorders in children.
Benefits from immunotherapy
Current pharmacotherapies (antihistamines) do not prevent allergic reaction, but instead block the action of histamineHistamine
Histamine is an organic nitrogen compound involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by...
in the body, reducing allergic symptoms. Immunotherapy, in contrast, trains the immune system to tolerate allergic triggers by means of gradual exposure to increasing amounts of the offending allergen. The benefits of allergen specific immunotherapy are long lasting unlike symptomatic based treatments. Immunotherapy is most effective for pollen, dust, and animal dander allergies, and may help those with asthma
Asthma
Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...
.
Treatment started 10 – 14 weeks before the start of the grass pollen season results in a 34% reduction of rhinoconjunctivitis symptoms and a 54% increase in well days. Continued treatment over 2 years in the case of grass allergy shows progressive immunological changes resulting in progressive desensitisation to the allergen with up to an 73 percent reduction in symptomatology. About 3 in 4 patients with hay fever
Hay Fever
Hay Fever is a comic play written by Noël Coward in 1924 and first produced in 1925 with Marie Tempest as the first Judith Bliss. Laura Hope Crews played the role in New York...
experience significant improvement with immunotherapy after one year of therapy. However, with continued therapy the number of people benefiting from specific immunotherapy appears to increase to over 4 in 5 people who benefit from specific immunotherapy by the end of the 2nd year of therapy. Sometimes symptoms are reduced rather than abolished. In that case immunotherapy may allow the patient to reduce the quantity of medication required for symptom relief.
Research in children aged from 5 years old to 16 years old shows similar effectiveness in the treatment of grass allergy as seen in adults. Like in adults allergen related asthma
Asthma
Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...
also decreases as well as allergic rhinitis
Allergic rhinitis
Allergic rhinitis, also known as pollenosis or hay fever, is an allergic inflammation of the nasal airways.It occurs when an allergen, such as pollen, dust or animal dander is inhaled by an individual with a sensitized immune system...
symptoms. Recent studies in children suggest that if immunotherapy is commenced soon after allergies first develop, it may actually reduce the risk of developing allergic reactions to other allergens, and even reduce the risk of later developing asthma.
Immunotherapy is also an essential part of managing dangerous allergic reactions (anaphylaxis
Anaphylaxis
Anaphylaxis is defined as "a serious allergic reaction that is rapid in onset and may cause death". It typically results in a number of symptoms including throat swelling, an itchy rash, and low blood pressure...
) to bee and wasp stings. In these cases, the protection against further dangerous allergic reactions to stinging insects is variously quoted at between 80 and 95%.
Mechanism of therapeutic action
The immune system of allergy affected individuals, for reasons not fully understood, misinterprets a usually innocuous substance as a disease agent and begins producing a type of antibody against it, called immunoglobulin EImmunoglobulin E
Immunoglobulin E is a class of antibody that has been found only in mammals. IgE is a monomeric antibody with 4 Ig-like domains...
(IgE). This is called the 'primary antibody response.' The IgE
IGE
IGE was one of the largest services company buying and selling virtual currencies and accounts for MMORPG. During its peak time, it had offices in Los Angeles, China , and headquarters & customer service centre in Hong Kong. IGE was one of the main monopoly in virtual economy services, also known...
produced during this response binds to basophils in the bloodstream and to a similar type of cell called mast cells in the tissues. When the person again encounters the allergen, these basophils and mast cells that have bound to IgE release histamine
Histamine
Histamine is an organic nitrogen compound involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by...
, prostaglandins, and leukotrienes, which causes inflammation of the surrounding tissues, resulting in allergic symptoms.
Even the most allergic individual can tolerate minuscule amounts of an allergen without experiencing symptoms. Immunotherapy commences with the subcutaneous injection of a tiny amount of offending allergen, and gradually increases the dose until the individual's immune system is essentially 'retrained' to tolerate exposure without producing an allergic response. This process is also known as specific immunotherapy.
Immunotherapy via repeated exposure to a specific allergen via either sublingual or subcutaneous route leads to a desensitisation to the allergen and thus a reduction in allergic symptomatology and use of symptomatic based treatments. The exact mechanism is not fully understood but it is accepted that immunotherapy causes modification of the immune system. This modification leads to changes in IgE synthesis and the production of IgE blocking antibodies which thus reduces the immune systems allergic response to specific allergens. There is also an increase in Th2 to the regulatory T cells. The molecular mechanism of such immunotherapy can be partly interpreted as that there occurs induction of allergen-specific IgG to neutralize the allergen instead of induction of allergen-specific IgE.
In bee or wasp venom immunotherapy, immunoglobulin subclass IgG4 has been considered to be particularly important, where IL-10
Interleukin 10
Interleukin-10 , also known as human cytokine synthesis inhibitory factor , is an anti-inflammatory cytokine. In humans IL-10 is encoded by the IL10 gene....
make the B cells to switch the produced immunoglobulin class from IgE to IgG4.
It has been revealed that the mechanism of this immunotherapy consists of some more other components. They include increased production of IL-10
Interleukin 10
Interleukin-10 , also known as human cytokine synthesis inhibitory factor , is an anti-inflammatory cytokine. In humans IL-10 is encoded by the IL10 gene....
which acts on Th2 or mast cells to become anergic and suppresses Th2 not to release cytokines and prevent histamine
Histamine
Histamine is an organic nitrogen compound involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by...
from being secreted.
It was indicated that osteopontin
Osteopontin
Osteopontin , also known as bone sialoprotein I , early T-lymphocyte activation , secreted phosphoprotein 1 , 2ar and Rickettsia resistance , is a human gene product, which is also conserved in other species...
produced by CD14+
CD14
Cluster of differentiation 14 also known as CD14 is a human gene.The protein encoded by this gene is a component of the innate immune system. CD14 exists in two forms. Either it is anchored into the membrane by a glycosylphosphatidylinositol tail or it appears in a soluble form...
cells induced IL-12
Interleukin 12
Interleukin 12 is an interleukin that is naturally produced by dendritic cells, macrophages and human B-lymphoblastoid cells in response to antigenic stimulation.-Gene and structure:...
in antigen presenting cells to activate Th1.
It was recently shown that a progressive expansion of circulating regulatory T cells was made during venom immunotherapy.
Procedures
For benefits to be felt from either sublingual or injection based allergen specific immunotherapy it needs to be started 2 – 4 months before the start of the allergen season in the case of seasonal allergies. The earlier it is started the better the level of allergy protection.Subcutaneous immunotherapy (SCIT)
Immunotherapy via the subcutaneous route involves the use of small hypodermic syringes which are used to inject commercial allergen extracts. Injections are normally given into the loose tissue over the back of the upper arm, half way between the shoulder and elbow. Injections are given under the skin ("subcutaneous"). This is the least painful place to inject allergen, as there are few nerve endings in the skin. When given correctly, the injections should be only slightly uncomfortable. They are not normally painful and are usually well tolerated by adults and teenagers. Some doctors may advise you to take an antihistamine a few hours before each injection to reduce the likelihood of local discomfort and other side-effects.
Allergy injections are started at very low doses. The dose is gradually increased on a regular (and usually weekly) basis, until a "maintenance" dose is reached. This usually means four to six months of weekly injections to reach the maintenance dose. Once the maintenance dose is reached, the injections are administered less often (every two to four weeks), still on a regular basis. Maintenance injections are normally given once per month for a few years. Generally, the longer the treatment and the higher the dose, the greater the therapeutic benefit.
After successful completion of immunotherapy, long-term protection can be expected for a period of 3–5 years or more. Therapy can be repeated should symptoms begin to return or if the individual becomes exposed to new allergens that were not included in the previous treatment regimen. Because allergy vaccine injections have a strong evidence base for clinical effectiveness, this form of treatment is covered by the vast majority of insurance companies in the United States.
Intralymphatic immunotherapy (ILIT)
Intralymphatic delivery of immunotherapy is another modality which is effective in the treatment of allergic disorders.
Intralymphatic immunotherapy (ILIT) administers allergens directly into a subcutaneous lymph node; A paper in 2009 found that studies on both animals and humans demonstrated that a direct injection into lymph nodes enhanced the immune responses to protein, peptide, and naked DNA vaccines and that this increased response meant that the overall allergen dosage and therapy duration could be reduced.
A study on mice found that intralymphatic immunisation induced a more than 10-fold higher IgG2a response with 100-fold lower allergen doses than subcutaneous immunisation; and that only intralymphatic immunisation stimulated the production of the Th1-dependent subclass IgG2a, which is associated with improved protection against allergen-induced anaphylaxis.
ILIT is well tolerated and patients found it to be "practically painless" and easy to perform. Patient compliance with ILIT was improved as compared with SCIT.
Sublinguil immunotherapy (SLIT)
In some countries, particularly in Europe, there is a strong tradition of undertaking immunotherapy using oral vaccines or sublingual drops. While there has been some interesting research in this area in recent years, the effectiveness of this form of treatment is difficult to compare with standard injected immunotherapy. Double-blind, placebo-controlled studies in Europe using high-dose sublingual immunotherapy have shown benefit. Some practitioners in the United States, particularly ENT physicians, offer sublingual immunotherapy as another immunotherapy option.
Sublingual immunotherapy is a safe and effective alternative to injection based immunotherapy and can be administered in the home environment. Modest benefits have been demonstrated within the first season of therapy. Treatment needs to be continued for at least 3 years to achieve maximum effectiveness in immune desensitisation to the allergen. In the case of sublingual immunotherapy there is no need to do a titrated graduated updose and therapy is generally started at the usual clinical dose.
Transcutaneous immunotherapy (TCIT) / Epicutaneous immunotherapy (ELIT)
This emerging therapy administers allergen by a skin patch. Though relatively new, clinical trials show that TCIT, EPIT is safe and comparably effective to conventional immunotherapy.
Side effects and adverse reactions
While itchiness, swelling, and redness at the site of injection are expected, systemic reactions such as hives or anaphylaxis
Anaphylaxis
Anaphylaxis is defined as "a serious allergic reaction that is rapid in onset and may cause death". It typically results in a number of symptoms including throat swelling, an itchy rash, and low blood pressure...
rarely occur. A July 2011 study following 773 patients that collectively received approximately 28,000 injections, the rate of systemic reaction to SCIT was about 4%. As such, patients are advised or required to wait in the clinic for 20–30 minutes so that they can be treated immediately in the case that they develop a severe systemic reaction. However, a 2008 study found that just under 50% of reported systemic reactions occurred more than 30 minutes after the injection.
Premedication with antihistamines or corticosteroids can reduce the risk of systemic reaction.
There is an established correlation between those receiving a Rushed Immunotherapy and higher rates of systemic reactions as compared to that those receiving conventional SCIT. While it may seem attractive to patients to rush SCIT, it seems as though it does lead to an increased risk to having a systemic reaction. However, this may not be the same for allergic respiratory diseases.
About 74% of systemic reactions to SCIT are mild reactions such as cutaneous or upper respiratory symptoms; about 23% are moderate reactions such as asthma with reduced lung function, and about 3% are severe, where life-threatening airway compromising or hypo-tension occurs.
Based on the highest reported symptoms of a systemic reaction, such as generalized itching, upper airway itchiness, coughs, or a shortness of breath should be reported immediately so they can be monitored or managed. These are usually managed through the use of epinephrine.
If such reactions occur, the allergy specialist will adjust the dosage to a safe level. The risk of a systemic reaction is reduced if the patient avoids exercising or overheating for a few hours before and after the procedure. Some heart and blood pressure medications such as beta-blockers are contraindicated as well.
The physician should be consulted if the patient notices a worsening of allergy symptoms or if he or she is suffering from a cold or has been undergoing a different kind of vaccination procedure. Immunotherapy does not increase the risk of contracting a cold.
Sublingual immuno-therapy (SLIT)
The side effects of sublingual desensitisation therapy are generally mild and limited to local reactions. Common side effects include oral pruritus, edema mouth, ear pruritus, throat irritation
Throat irritation
Throat irritation is a common complaint in individuals of all ages. Throat irritation means different things to different people. Some people may mean a dry cough; others describe it as a scratchy feeling at the back of the throat and others simply mean a sensation of something stuck at the back of...
, sneezing, mild itching and swelling of the mouth. Side effects which are less common or rare include headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
, oral paraesthesia, eye pruritus, conjunctivitis
Conjunctivitis
Conjunctivitis refers to inflammation of the conjunctiva...
, cough
Cough
A cough is a sudden and often repetitively occurring reflex which helps to clear the large breathing passages from secretions, irritants, foreign particles and microbes...
, asthma
Asthma
Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...
, pharyngitis
Pharyngitis
Pharyngitis is an inflammation of the throat or pharynx. In most cases it is quite painful, and is the most common cause of a sore throat.Like many types of inflammation, pharyngitis can be acute – characterized by a rapid onset and typically a relatively short course – or chronic....
, rhinorrhoea, nasal congestion
Nasal congestion
Nasal congestion is the blockage of the nasal passages usually due to membranes lining the nose becoming swollen from inflamed blood vessels. It is also known as nasal blockage, nasal obstruction, blocked nose, stuffy nose, or stuffed up nose.Nasal congestion has many causes and can range from a...
, rhinitis
Rhinitis
Rhinitis , commonly known as a stuffy nose, is the medical term describing irritation and inflammation of some internal areas of the nose. The primary symptom of rhinitis is nasal dripping. It is caused by chronic or acute inflammation of the mucous membrane of the nose due to viruses, bacteria or...
, throat tightness, pruritus and fatigue. In most cases these side effects diminished minutes or hours after immunotherapy and disappeared 1 – 7 days after commencement of therapy. As a precautionary measure against rare but serious side effects e.g. asthma attacks it is recommended that the first sublingual tablet containing the specific allergen for immunotherapy is administrated whilst under the observation of a medical doctor and observed for 30 minutes for any signs of serious side effects.
Sublingual immunotherapy is contraindicated in patients who have systemic diseases of the immune system, inflammatory conditions of the oral cavity with associated severe symptoms e.g. oral lichen planus
Lichen planus
Lichen planus is a chronic mucocutaneous disease that affects the skin, tongue, and oral mucosa. The disease presents itself in the form of papules, lesions, or rashes. Lichen planus does not involve lichens, the fungus/algae symbionts that often grow on tree trunks; the name refers to the dry and...
with ulcers or severe oral mycosis
Mycosis
A mycosis is a fungal infection of animals, including humans. Mycoses are common, and a variety of environmental and physiological conditions can contribute to the development of fungal diseases...
or individuals with severe and uncontrolled asthma. Immunotherapy tablets are also contraindicated in individuals who are allergic to any of the addition constituents of the tablet.
External links
- "American Academy of Allergy, Asthma, and Immunology" information and articles of interest.
- "American College of Allergy, Asthma, and Immunology" information and articles of interest.
- "American Board of Allergy and Immunology" American Board of Allergy and Immunology
- "Allergies", from Rutgers.edu
- "Allergy shots, allergy immunotherapy" FAQs on Allergy Immunotherapy.