I was recently embroiled in an online discussion with several pulmonary and primary care colleagues regarding the efficacy of Allergen Immunotherapy in the treatment of asthma and the future of sublingual immunotherapy, which I think is worth sharing. Let’s start off with some Frequently Asked Questions:
Whare are “Allergy Shots”?
Allergen immunotherapy or “allergy shots” is a form of treatment aimed at decreasing sensitivity to substances called allergens which were identified by allergy testing. Allergen immunotherapy involves injecting increasing amounts of these allergens to a patient over a period of time to decrease the patient’s sensitivity to the allergens, prevent development of new allergies, and in children, prevent progression from allergic rhinitis to asthma. Allergen immunotherapy can lead to long-lasting relief of allergy symptoms after treatment is discontinued.

How does Allergen Immunotherapy work?
Allergen immunotherapy works like a vaccine. Your body responds to injected amounts of a specific allergen by developing immunity or tolerance. There are two phases to immunotherapy: a build-up phase and a maintenance phase.

When will the allergy shots start working and when can I stop my meds?
The benefits of allergen immunotherapy, in terms of reduced allergy symptoms, can begin during the build-up phase but may take as long as 12 months on the maintenance doses. It is important to continue taking allergy medications as prescribed together with the allergy shots during the build-up phase. Later, when your symptoms improve, you may discuss with your doctor whether you can discontinue some of your allergy medications.
If you do not get your allergy shots on schedule, it will take longer to reach the maintenance dose and longer for the allergy shots to work effectively.

How long do I have to take the Allergy shots?
With currently available allergen extracts, maintenance treatment is generally continued for 3 to 5 years after the build-up phase, which can take up to 6 to 9 months. The majority of inidividuals experience lasting remission but a minority may relapse after discontinuing immunotherapy, therefore the decision to stop must be individualized.

How effective is allergen immunotherapy?
Immunotherapy is successful in up to 90-95% of patients with seasonal allergies and up to 85% of patients with year-round allergies.

Asthma is a multifactorial disease. Allergic rhinitis/ sinusitis has definitively been shown to contribute to the severity of asthma in patients. One of the modalities used to treat allergic rhinitis/ sinusitis and asthma is allergen immunotherapy (IT). By no means is anyone suggesting that allergen immunotherapy be used INSTEAD OF inhaled steroids, however allergen IT does have solid data to show its efficacy when used in conjunction with other modalities.

This is topic has been addressed by the American College of Allergy, Asthma, and Immunology in its position paper on the Cost Effectiveness of Immunotherapy for Asthma.

Regarding sublingual immunotherapy, there is considerable evidence that sublingual immunotherapy for allergic rhino-conjunctivitis has been effective using high doses of grass extract. This is commercially available and used in Europe, but has yet to have FDA approval in the USA. Some studies showing efficacy are cited below:
1. Calderon M, Essendrop M. Specific immunotherapy with high dose SO standardized grass allergen tablets was safe and well tolerated. J Investig Allergol Clin Immunol. 2006;16(6):338-44. 2. Nelson HS. Advances in upper airway diseases and allergen immunotherapy. J Allergy Clin Immunol. 2007 Feb 8; [Epub ahead of print]
That being said, appropriate dosing and efficacy with multiple SL allergen combinations are still an issue.

The “sublingual immunotherapy” that is pure quackery has been used to treat “idiopathic environmental intolerance” (IEI) by means of “neutralizing” extracts administered as sublingual drops usually at such a miniscule dose that it is really only placebo. See the AAAAI position statement on this.

For a tragic example of the use of these “neutralizing sublingual drops” for treatment of IEI or “multiple chemical sensitivity syndrome” see the “Tragic Example” post on this blog.

Link: Allergen Immunotherapy Practice Parameters
AAAI Tips to Remember: What are Allergy Shots?
Table: Clinical Indications for Allergen Immunotherapy

AAAAI Rhinitis Video

After the offending allergen has been identified by allergy testing, avoidance of the allergen, whether it be a food, drug, or airborne protein like dust mites or pollen, is the next critical step. Avoidance can significantly reduce symptoms related to allergies and is of vital importance particularly in food and drug allergies.

 INDOOR ALLERGENS:

• House Dust Mites

House dust mites are the major cause of year-round itchy and runny nose, itchy watery eyes, sneezing, wheezing, and shortness of breath.

What are Dust Mites?

Dust mites belong to the family of 8-legged creatures called Arachnids. They are microscopic and eat particles of skin and dander and thrive in bedding, carpeting, upholstered furniture, clothing, closets, and car seats which are all likely to contain skin particles. They are harmful only to people who become allergic to them. People allergic to dust mites react to proteins in the bodies and digestive waste (feces) of the mites. When allergic people inhale these particles, they start itching, sneezing, or wheezing.

What can be done to avoid Dust Mites?

Taking steps to minimize dust mite exposure in the bedroom often leads to a decrease in symptoms and medication requrements. Emphasis is placed on the bedroom since people spend a third of 24 hours there and because it has the greatest number of dust mites. The mattress, pillows, and boxspring should b encased in zippered, allergen-impermeable covers, and other bedding should be washed frequently in hot water (130 degrees Fahrenheit) every week.

Dust mites grow best at 75-80% relative humidity and cannot live at under 50% humidity. The ideal relative humidity to eliminate them is 40-50%. Use a humidity gauge (hygrometer) and a dehumidifier.

Source: AAAAI Indoor Allergen Tips

• Pet Dander

More than 70% of US households have a dog or cat. An estimated 10% of the population may be allergic to animals. The number of pets in the US is estimated at more than 100 million which increases the likelihood of accidental exposure to animals by people with allergies when visiting pet owners.

The dander, or skin flakes, as well as the saliva and urine of pets, can cause an allergic reaction. Animal hair is not considered a significant allergen but the hair or fur collects pollen, dust, mold, and other allergens.

Those pets that are known to cause allergic reactions should be removed from the home of the allergic person to avoid worsening of symptoms. Keeping the animal outdoors is only a partial solution, since studies show that homes with pets kept in the yard still have higher allergen concentrations than homes without pets. A “trial” removal of a pet for a few days or even weeks is of little value since you need at least 6 months of avoidance for allergen levels to drop to levels in homes without pets.

Short of removing the pet from the house permanently, here are some tips to reduce pet dander exposure:

1. Keep the pet out of the bedroom, if possible, out of the house.

2. Have a non-allergic person bathe the pet weekly to reduce amount of dander released.

4. Remove or reduce carpet floor coverage and replace bedding and carpeting

3. Have a non-allergic person clean the pet’s litter box or cage regularly.[/ that has animal dander in it.

5. Use High Efficiency Particulate Air (HEPA) Clearners.

6. Cover Upholstery or use sofa and seat covers that can be easily cleaned or wiped down.

• Mold:

Molds are microscopic fungi which, unlike plants, are unable to produce their own food from sunlight and air. Many molds reproduce by releasing spores into the air which then settle on organic matter and grow into new mold clusters. Airborne mold spores are more numerous than pollen grains, and when inhaled, can produce allergic symptoms.

Molds can be found wherever there is moisture, oxygen, and a source of the few other chemicals they need. Growth is encouraged by warmth and high humidity. Hot spots of mold growth in the home include damp basements and closets, bathrooms (especially shower stalls), places where fresh food is stored, refrigerator drip trays, house plants, air conditioners, humidifers, garbage pails, mattresses, upholstered furniture and old foam rubber pillow.

Here are a few tips to decrease mold exposure indoors:

1. Keep humidity low, less than 50%. Use a dehumidifier or air conditioner with a hygrometer to monitor relative humidity.

2. Allow adequate ventilation. Use an exhaust fan particularly in the bathroom and kitchen or open windows to remove humidity from cooking or showers.

3. Clean visible mold from walls and ceilings. Wash the shower curtain, tiles, stall, tub, and toilet tank with mold-killing and mold-preventing solutions. (50/50 bleach and water mixture also works well)

4. Correct drainage problems near the house and correct seepage or flooding problems inside the house. Remove water-damaged carpet, if present.

5. Allergic persons should not have their bedroom on the basement level.

6. Do not carpet the bathroom and bedroom and avoid carpets on concrete floors, especially the basement. Tile, hardwood, or vinyl floors are a better choice.

7. Dry shoes and boots thoroughly before storing.

8. Empty water pans in self-defrosting refrigerators and throw out spoiling food immediately. Empty garbage containers frequently.

9. Limit the number of houseplants. Mold also grows on bark, do not store firewood indoors and avoid live Christmas trees.

10. Greenhouses, antique shops, saunas, sleeping bags, summer cottages, and hotel rooms are sources of high mold exposure. Automobile air conditioners may also harbor mold.

11. Keep compost piles away from the main house.

OUTDOOR ALLERGENS

• Pollen:

When outdoor pollens are high, remain indoors, particularly in the late morning. Pollen grains can cause significant allergic symptoms like asthma and allergic rhinitis, particularly during the spring and the fall. It is difficult to avoid pollen because it is windborne and can cover wide distances. Short of moving to a different location, here are some tips for avoiding pollen during the season.

1. The pollen count is usually highest in the late morning and early afternoon particularly during sunny, windy days.
2. The pollen count measures the concentration of a specific pollen like birch tree pollen, in the area in a specific area and time. A pollen count is a useful guide for when it is advisable to stay indoors and avoid contact with pollen.
3. Keep the windows and doors closed during the allergy season.
4. Install a room air conditioner with a special filter.The special filter (High Efficiency Particulate Air or HEPA filter) traps airborne allergens. If the house does not have central air, the best spot to put the air conditioner and filter would be the bedroom. Change the filters frequently. An allergic person should also use the car air conditioner to decrease pollen exposure when commuting. Pollen allergic persons should not have a window fan blowing into their bedroom as this will maintain outdoor pollen exposure all night.
5. Avoid working outdoors, if you must wear a special face mask. The face mask is designed to filter pollen out of the air and keep it from reaching the nasal passages.
6. Consider taking a vacation at the height of the pollen season. Preferably at a location where the pollen exposure is minimal, like the seashore.

Outdoor Mold:

Molds are microscopic fungi which, unlike plants, are unable to produce their own food from sunlight and air. They are made up of clusters of filaments and live on plant or animal matter, which they decompose for their nourishment. Molds reproduce by releasing spores into the air.

Airborne mold spores are far more numerous than pollen grains and can cause significant asthma, allergic rhinitis, and sinusitis.

A.

1. Avoid camping or walking in the woods where mold growth on rotted logs and vegetation is high.
2. Avoid cutting grass, raking leaves, and exposure to soil, compost, sandboxes, hay, fertilizers, and barns.
3. Wear a well fiting mask if outdoor work can not be avoided.

Source: AAAAI Outdoor Allergen Tips

Allergen: A substance, usually a protein such as pollen, animal dander, food, or medication, which can trigger an allergic reaction

Allergic rhinitis: refers to the sneezing, itching, and mucus production associated with an reaction to allergens in the air such as pollen, dust mites, animals, or molds. May be seasonal or year-round.

Allergies: Exaggerated reaction of the immune system when exposed to certain substances, usually related to the presence of the allergic antibody, IgE

Allergist: Physician who specializes in the diagnosis and treatment of allergy related problems including allergic rhinitis, asthma, drug and food allergy

Anaphylaxis: Severe, life-threatening allergic reaction which may result in death, requires immediate emergency medical treatment

Angioedema: refers to swelling in the deeper layers of the skin, usually associated with urticaria/ hives

Antibody: A protein in the immune system that reacts to mostly foreign substances in the body

Atopic Dermatitis: A recurring itchy skin rash also called “eczema” that often appears in the first few years of life but can persist in allergic people

Challenge test: A test used to confirm whether a person is allergic to a particular substance, performed under close supervision by a physician.

Epinephrine: also called adrenaline, injectable medication used to treat anaphylaxis by constricting blood vessels

Histamine: Chemical released by immune cells during an allergic reaction, causes swelling and inflammation

Hives: See Urticaria

Immunoglobulin E: Type of antibody involved in most allergic reactions

Immunotherapy: Series of injections that help build up the body’s tolerance to an allergen

RadioAllergosorbent Test (RAST): A blood test that measures the amount of IgE antibody in the blood to a specific allergen

Rhinitis: Swelling, congestion, and increased mucus in the nasal passages, may be due to allergies

Sinusitis: Swelling or infection in one or more of the sinuses, which are air spaces in the skull around the nose and eyes

Urticaria: also known as hives, Itchy wheals on the skin

AAAAI video 

Diagnosis or determining whether someone is suffering from allergies or not, begins with the history. The physician or health care provider is interested in knowing the pattern of the symptoms and their relation to any possible allergen exposures. For example in the case of allergic rhinitis one would ask:

• Do you sneeze or get itchy nose/ eyes during a specific season or all year round?
• Is it worse at night or during the day?
• Indoors or outdoors?
• With exposure to pets or other animals?

Tests are performed when the history points to a possible allergic reaction to a specific allergen. Skin tests and RadioAllergoSorbent blood Tests (RAST) are performed to determine the presence or measure the level of the allergic antibody, IgE, to the allergen.

It should be stressed that a positive allergy test alone does not make the diagnosis of an allergic reaction. The results of the test must be correlated with the patient’s history.

1. Skin tests the most commonly used form of allergy testing. In this test, an extract of the allergen is placed on the skin, then a superficial puncture or scratch is made at the site allowing contact between the deeper layer of the skin and the allergen.If a person is allergic to that particular allergen, an itchy wheal with surrounding redness will form within 15 minutes. If this “scratch” or epicutaneous test is negative, in the case of airborne or medication allergies, the patient may then go on to get small doses of the allergen injected under the skin, called “intradermal” skin testing. The intradermal test is not recommended for food allergens.
2. Blood Test or RAST- measures the levels of the allergic antibody IgE in the blood to specific allergens. This test is not as sensitive as the skin test, but is used if a skin test can not be performed because the patient is taking antihistamines, has a rash covering his body, or if he or she had a severe allergic reaction (anaphylaxis) to the suspected allergen.
3. Challenge Test- In the case of food or medications, even if a person has a negative skin test or blood test, there is still a chance that a person may still have an allergic reaction to the suspected allergen.In this case, challenge tests are performed where the person is given small, increasing doses of the suspected food or medication at regular intervals and under close monitoring to determine if he or she develops any signs or symptoms of an allergic reaction. These tests may be open or blinded where the person and/or the physician may or may not know whether the patient is getting the actual allergen or a placebo to avoid bias.

Allergy Cartoon video (Osaka Japanese cartoon):

AAAAI What is an Allergic Reaction video

AAAAI Rhinitis Video

Allergy refers to the exaggerated reaction of the immune system in susceptible people, when it is exposed to a protein called an allergen. An allergen can take the form of tree pollen, peanut, cat dander, stinging insect venom, penicillin, and latex, among many others. Exposure to the allergen causes immune cells to release substances such as histamine in parts of the body which lead to itching, swelling, sneezing, hives, wheezing, low blood pressure, and sometimes, even death.

Allergens do not cause symptoms in all people, only in a group of people who develop Immunoglobulin E (IgE) to the particular allergen. IgE is the molecule responsible for triggering the allergic response in most people and its detection in the blood or the skin is an important part of the process when we determine whether or not someone has allergies.

An allergic reaction results in the release of the chemical histamine into the blood and different parts of the body. Histamine causes increased production of mucus, itching, swelling, muscle spasms, and leakage and dilation of blood vessels. Where the histamine is released determines the symptoms of the allergic reaction as follows:

Eyes: watery eyes, itching, red eyes

Nose: Sneezing, itchy nose, runny nose, congestion

Lungs: Cough, wheezing, difficulty breathing (due to airway muscle spasms)

Gastro-Intestinal: Nausea, vomiting, diarrhea, abdominal spasms

Skin: Itching, hives, swelling

Circulatory System: Dizziness, Low blood pressure, palpitations, passing out