Allergenic Extracts - Mixed

Company: Stallergenes-Greer

U.S. Vet. Lic. No.: 294

Active Ingredient(s):

Pollens: Pure dry pollens are defatted in ether and extracted in an aqueous buffered solution. Grass pollen, which is a common cause of canine inhalant dermatitis, is more prevalent in late spring and early summer. The weeds, notably the ragweeds, are prolific producers of pollen and can cause animal allergies especially in the late summer and early fall periods. Tree pollens can also cause canine allergies although the pollination season for each species is relatively short.

Fungi: Fungal antigens are extracts of the cells and spores of pure culture fungi (molds) including yeasts, or of rusts and smuts, collected from their natural environments. Aqueous extracts of fungi are prepared from defatted material extracted in an aqueous buffered solution. Airborne fungi are an important cause of animal allergy, especially since they are present in the house throughout the year. Outdoors, fungi can also be found in large numbers from May to December with peak periods varying according to genus and climate conditions.

Dust: Screened dust from private homes is extracted in an aqueous buffered solution and dialyzed to remove irritants. House dust extract is concentrated to an extract ration of 1:1 w/v to achieve adequate Protein Nitrogen Units (PNU). House dust is a common cause of canine inhalant dermatitis because of its ubiquity in the home and its heterogeneous composition.

Epidermals, Miscellaneous Inhalants, and Foods: Epidermal extracts are made individually from the hide, hair, or feathers and contain the natural dander. Epidermals, other inhalants, and foods* are prepared using defatted materials obtained from sources as near the natural inhalant or edible food as possible.

*A small group of foods, primarily cereal grains, are extracted with fluid containing 0.1% sodium formaldehyde sulfoxylate (SFS), an anti-oxidant. This results in a light-colored extract which avoids the tattoo effect which may occur after skin testing with oxidized extracts. Extracts containing SFS are labeled for diagnostic use only.

Insects: Insects are made from the whole bodies of the insects collected from their natural habitats or are grown in laboratory colonies, such as the dust mites, Dermatophagoides farinae and D. pteronyssinus.

Allergenic Extracts - Mixed Indications

1. Diagnostic: Greer allergen extracts are aids in the skin test diagnosis of animal allergies. Compatible clinical signs and history are necessary to establish the diagnosis.

2. Therapeutic: Greer ALLERGENIC EXTRACTS are indicated for immunotherapy (hyposensitization) to aid in alleviating the symptoms associated with allergic dermatitis. A program of reducing or avoiding exposure to the offending allergen, if possible, should be initiated before or concurrent with hyposensitization treatment. Concomitant antibiotic therapy and an appropriate bathing program should be given where significant secondary bacterial infection of the skin is evident. Food extracts are not recommended in immunotherapy, but may be useful diagnostically.

Allergens interact with immunoglobulin E (IgE) to stimulate the release of mediators such as histamine from the surface of mast cells and cause skin induration and erythema reactions upon skin testing, along with other allergic symptoms which are indicative of the subject's hypersensitivity to the antigen. The allergy skin test is useful to confirm the diagnosis of allergic dermatitis. Upon a course of immunotherapy, there is generally an increase in immunoglobin G (IgG) antibodies which have been surmised to complex with the circulating antigen before it can reach the IgE present in the tissues and trigger the allergic response. Clinical improvement, however, does not correlate well with increased levels of IgG antibodies, and IgG levels vary during long-term therapy. Thus, other mechanisms following immunotherapy are probably involved in the relief of symptoms upon further exposure to the antigen.

Test Procedure: Intradermal Skin Testing:

Discussion: The signs of atopic disease may be seasonal or perennial depending upon the animal's sensitivities. Selection of the appropriate seasonal allergens for testing should be tailored to the region of the country where the animal resides. In addition, allergens which are encountered year-round in the home (e.g., house dust, mites, and molds) and in the external environment should be included in the testing scheme, where suspect. Although food extracts may be helpful in affirming or ruling out suspected food allergies, they are not recommended for definitive differential diagnosis; elimination diets remain the best method of diagnosis for food allergies. Positive intradermal skin test information or other specific allergen test results should be weighed along with clinical signs and patient history before a decision on treatment is made.

1. Materials Needed:

a. Sterile 1 mL tuberculin type syringes with 3/8 to 1/2 inch, 26- or 27-gauge needles.

b. Allergen at 1,000 PNU/mL or 1:1,000 w/v (final concentration).*

c. Negative control (saline diluent).

d. Positive control: The available histamine phosphate 0.275 mg/mL should be diluted 1:10 to yield 0.0275 mg/mL.

*The following allergens may give more consistent results when tested at concentrations lower than 1,000 PNU/mL:

2. Suggested Procedure: Before testing, the veterinarian may wish to sedate or tranquilize the patient. Care must be taken to avoid sedatives with antihistaminic activity such as acetylpromazine. Xylazine may be used.

a. Prepare the test area (usually the lateral thorax) by clipping and gently cleansing the testing site with a moist towel if necessary. Sites may be marked for easy reading.

b. Using a separate syringe for each solution, load separate 1 mL tuberculin syringes with 0.1 mL of control solutions and the test allergen extracts.*

c. Ensure that all air bubbles have been expelled from the loaded syringe, because the injection of air bubbles may force dermal cells apart and create false reactions.

d. The injection sites should be at least 2.5 cm from each other and the injections should be atraumatic.

e. After gently stretching the skin around the test site, the needle is inserted into the skin at an angle of approximately 10° with the bevel upwards.

f. Stop inserting the needle when the entire bevel is buried in the skin (ideally the bevel should be visible through the superficial layers of the skin).

g. Inject 0.05 mL of the control solution or allergen extract forming a bleb in the skin. Gently remove the needle to prevent traumatic hemorrhage.

h. Retain the remaining 0.05 mL of control solution or allergen extract in case the wheal is unsatisfactory due to the movement of the patient or poor injection technique.

i. The skin test should be completed as soon as possible to allow simultaneous comparison of the allergen wheal against the controls.

*Mixes for skin testing should not contain more than eight (8) related antigens (up to 8 grass pollens, weed pollens, tree pollens, or molds, etc. As examples of preferred mixes, see the standard Greer Stock Mixes in the catalog.). If unrelated antigens or more than eight (8) antigens are included, specific antigens may be masked or diluted by others in the mix, causing a false negative test.

3. Interpretation:

a. The skin test site is read 15 minutes after injection. The wheal is best observed by oblique or side lighting in a darkened room. Immediate (IgE mediated) reactivity will cause a wheal within 15 minutes. 24 to 48 hour reactions are occasionally seen for reasons not known at this time.

b. A wheal diameter significantly greater than the negative control denotes a positive reaction. A strong positive reaction may be approximately the size of the histamine response. Graded responses may be determined subjectively, or an objective scale of 1+ to 4+ may be used with 3+ being the size of the positive control.

c. See Overdose section below if adverse reactions occur.

Immunotherapy:

Discussion: The optimum dosage and route of administration of allergens has not been clearly established and currently many dosage schedules are in use. Subcutaneous or intradermal injections can be administered, but the subcutaneous route is more routinely employed.

It is recommended that if clinical signs of atopy are present and the animal skin tests are positive to a particular allergen or allergens, which cannot be avoided, then hyposensitization immunotheray is indicated. However, in animals whose seasonal involvement is short, or for an old animal, an alternate-day short-acting oral corticosteroid or an antihistamine may be the treatment of choice.

Hyposensitization is accomplished by injecting therapeutic allergens in a low enough dosage to be tolerated, with a slightly increased dosage at each subsequent treatment interval, attempting to reach, but not to exceed, a maximum tolerated dose as determined by increasing the dosage until signs of overdose are seen and then reducing to the maximum tolerated dose. At this point, the patient is kept at the maintenance dosage level with injections repeated at 20- to 40-day intervals.

During the course of therapy, a few patients may develop allergy to other antigens, even though allergy to the original antigens are controlled. Thus, additional testing and treatment may become necessary.

Boosters may be administered if symptoms recur after treatment.

A suggested treatment schedule is offered below, however, the final choice of the dosage and length of treatment will depend upon the sensitivity and responsiveness of the patient.

Treatment: Antigen selection is based on (a) the degree of reaction to a specific allergen test (size of wheal) (b) the clinical signs relative to patient history. However, if the patient exhibits numerous sensitivities (at the time of the first testing or at a later date), the veterinarian may administer two (2) vaccines alternately. Allergens may be administered singly, or combined into a vaccine mixture.* The allergens selected for the vaccine (treatment vial) should be limited to not more than 12. If a new antigen is added to an existing vaccine, the administration of the vaccine should proceed as if it were a new vaccine (start at day 0).

*If the patient has flea sensitivity also, the veterinarian may treat with Flea Antigen Extract. Food extracts are not recommended for treatment since their efficacy in immunotherapy has not been established.

The injection usually is administered subcutaneously with a 1.0 mL sterile tuberculin syringe, using a 3/8 to 1/2 inch, 25- to 27-gauge needle. If intradermal injections are administered, the dose should not exceed 0.2 mL per site or adverse reactions may occur.

Dosages for immunotherapy usually start at 0.1 mL of a dilution that is 1/100 to 1/10 of the concentrate. If it is suspected that the patient is extremely sensitive, lower doses or more dilute solutions may be used initially with gradually increasing doses similar to the suggested dosage schedule. If the patient can tolerate higher dosages, the schedule may be accelerated (such as starting at a higher dose or concentration, or by administering doses every 2 days rather than every 3 days) to reach a maintenance dose of 1.0 mL of the concentrate in fewer days. Dosages more dilute (less concentrated) than the purchased strengths may be made by appropriate one-to-ten dilutions in the office with a commercial saline, buffered saline, or glycero-saline diluent containing phenol preservative, 0.5 mL of extract to 4.5 mL of diluent.

Suggested Dosage Schedule:

*Maintenance dose if tolerated; otherwise maintain at the tolerated level of a lower volume or a lower concentration.

(For smaller or more sensitive animals, the starting dosage concentrations may be 1/10 those in the above table, beginning with 200 PNU/mL).

Thereafter: Keep the maintenance dose schedule at approximately 20-day intervals until relief is evident, at which time the interval may be increased to greater than 20 days, or the schedule may be modified to administer the doses preseasonally if the allergy is seasonal. If the relief wanes, the intervals may be shortened. A maximum period of immunotherapy has not been determined. Occasionally patients may have to undergo treatment indefinitely. If relief upon immunotherapy does not occur within nine (9) months to one (1) year, the treatment should be stopped and the animal re-evaluated.

Contraindication(s):

1. Diagnostic: Diagnostic skin testing is contraindicated in patients on corticosteroids or drugs with antihistamine activity which will cause inhibition of the histamine-mediated skin test reaction. These drugs should be withdrawn for a period sufficient that the patient exhibits a positive skin test response to a control skin test with histamine. The withdrawal time for antihistamines is based on their biological half-life. The withdrawal time for corticosteroids is about one week for each month of continual corticosteroid administration.

Animals with severe skin problems should not be skin tested.

2. Therapeutic: Because of the potential for de novo sensitization, allergens are not indicated for hyposensitization treatment unless specific allergen hypersensitivity has been identified by means of intradermal skin testing, or in vitro specific allergen sensitivity testing, accompanied by compatible clinical signs, history, and a differential diagnosis to rule out other etiologic conditions.

Precaution(s): Extracts should be stored at 2-8°C. Do not freeze.

Caution(s): Do not inject intravenously.

Have the following available:

1. Epinephrine diluted 1:1,000.

2. A fast-acting, water-soluble corticosteroid injection such as hydrocortisone, prednisolone, or dexamethasone.

3. An injectable antihistamine such as diphenhydramine.

Keep the animal under observation for at least 30 minutes after the administration of a testing or treatment dose. Animals prone to severe reactions should be given diphenhydramine or another appropriate antihistamine 30 minutes prior to the treatment dose administration.

Extracts in 50% glycerin should be diluted with an aqueous diluent before use to avoid pain or stinging due to the high concentration of glycerin.

Overdose: If symptoms of overdosage occur (see Side Effects section below), treatment employing (a), (b) or (c) below, or a combination thereof can be effective in combating an adverse reaction.

a) The immediate intramuscular injection of epinephrine at a dosage of 0.01 mL/kg at a 1:1,000 dilution, or in the case of a severe reaction, administer a 1:10,000 dilution intravenously in increments of 0.5 mL to 1.0 mL to a total dosage of 0.5 mL to 5.0 mL. Epinephrine administration can be repeated every 15 to 30 minutes as needed.

b) Intravenous injection of an appropriate corticosteroid such as prednisolone sodium succinate 35 mg/kg, or dexamethasone sodium phosphate 5 mg/kg.

c) Intravenous injection of an antihistamine such as diphenhydramine hydrochloride in a dosage of 1.0 to 2.0 mg/kg, slowly.

Side Effects

Adverse reactions are very rarely seen and usually consist of an exacerbation of clinical signs if too large a dose is given. However, in the event of an overdose or alternatively, exquisite sensitivity of the animal, the patient may exhibit restlessness, panting, generalized hives, vomiting, circulatory collapse, and/or diarrhea (see Overdose section above for treatment).

There are also several normal reactions that may occur and the owner should be advised of these prior to administration of the allergen. Temporary pain and discomfort may be experienced at the time of injection, with some stiffness and soreness occurring later. A small area of ulceration may occur where intradermal administration is employed.

References

Available upon request.

Presentation: Greer ALLERGENIC EXTRACTS for veterinary use are available as sterile aqueous solutions labeled on a PNU/mL basis (10,000, 20,000 and 40,000 PNU/mL for pollens* and fungi; 10,000 and 20,000 PNU/mL for epidermals, foods, miscellaneous inhalants and insects; and at 10,000 PNU/mL for house dust). On a weight/volume concentration, extracts are formulated at 1:10, 1:20, 1:40, or 1:50 w/v for most pollens,* fungi, epidermals, foods and inhalants; and 1:20 and 1:100 for insects. Special dust (HMRU mix) is 1:1, 1:2, and 1:5 w/v. House dust is 1:1 and 1:2 w/v and 10,000 PNU/mL. House dust mites, Dermatophagoides farinae and D. pteronyssinus are 1:100 w/v singly or mixed. Extracts usually are supplied in volumes of 5, 10, 30, and 50 mL. Intradermal tests are 1,000 PNU/mL or 1:1,000 w/v in 5 mL vials only. Individual prescription mixes are also available upon request. * Short ragweed (Ambrosia artemisiifolia) pollen extracts have potency states in terms of antigen E units/mL as well as a PNU/mL or w/v concentration.

Glycerinated extract concentrations are available for certain extracts. The dosages are the same as aqueous extracts. Glycerin 50% concentrates should be diluted before use and are not appropriate as concentrates for diagnostic skin testing. While glycerin 50% enhances, stability, when given in a concentrated solution it will sting upon injection.

CPN: 1110001.2