Animal Allergens, AP Horse Hair and Dander

1. General

Always have injectable epinephrine and a tourniquet available when tests are being made. (See ADVERSE REACTION section.) Generally 50 to 60 scratch, prick or puncture tests can be applied safely at one sitting. Patients whose history suggests severe sensitivity should have only 5 to 10 tests applied at a time and these tests applied to the volar surface of one arm. These tests should not all be of the same type of antigen; that is, all grass pollens, all weed pollens, all danders, etc. One or two tests from several classes of antigens should be applied at a time. As soon as a large wheal begins to develop, wipe the antigen from it with a damp cotton sponge. After 10 minutes wipe off all the antigens with a damp cotton sponge, followed by a dry cotton sponge. Be careful not to wipe antigen from a positive reaction onto an adjacent test site.

2 Information for Patients

Patients should be instructed in the recognition of adverse reactions to diagnostic testing. Patients should be made to understand the importance of a 30 minute observation period, and be warned to return to the office promptly if symptoms occur after leaving.

3. Drug Interactions

Patients on non-selective beta blockers may be more reactive to allergens given for testing or treatment and may be unresponsive to the usual doses of epinephrine used to treat allergic reactions.6
Certain medications may lessen the skin test wheal and erythema responses elicited by allergens and histamine for varying time periods. Conventional antihistamines should be discontinued at least 5 days before skin testing. Long acting antihistamines should be discontinued for at least 3 weeks prior to skin testing.9 Topical steroids should be discontinued at the skin test site for at least 2-3 weeks before skin testing.9, 10 Tricyclic antidepressants such as Doxepin should be withheld for at least 7 days before skin testing.11 Topical local anesthetics may suppress the flare responses and should be
avoided in skin test sites.12

4. Carcinogenesis, mutagenesis, Impairment of Fertility

Long-term studies in animals have not been conducted with allergenic extracts to determine their potential for carcinogenicity, mutagenicity or impairment of fertility.

5. Pregnancy

4,5
Pregnancy Category C. Animal reproduction studies have not been conducted with allergenic extracts. It is also not known whether allergenic extracts can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Allergenic extracts should be given to a pregnant woman only if clearly needed.

6. Nursing Mothers

There are no current studies on secretion of the allergenic extract components in human milk or effect on the nursing infant. Because many drugs are excreted in human milk, caution should be exercised when allergenic extracts are administered to a nursing woman.

7. Pediatric Use

Wheal sizes in response to allergen skin testing can be smaller in infants than in adults. The skin response to histamine parallels that for allergens; therefore, appropriate positive control skin tests should always be performed.1

8. Geriatric Use

Skin test wheal size decreases with age. The decrease in allergen-induced skin test reaction parallels that to histamine; therefore, appropriate positive skin test controls should always be performed.1

ANIMAL ALLERGENS, AP HORSE HAIR AND DANDER ADVERSE REACTIONS

OVERDOSAGE

See ADVERSE REACTIONS Section.

DOSAGE & ADMINISTRATION

1. General
Parenteral Drug Products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

2. Scratch, Prick or Puncture Testing Methods
There are two general methods of skin testing. (1) The skin is scarified first, and the extract is then applied. (2) A drop of extract is put onto the skin, and a prick or puncture is made through the drop. Avoid touching tip of dropper to skin. Either method is satisfactory, but the second requires that the instrument be cleansed between tests or that separate needles be used.

The extracts for scratch, prick or puncture testing are supplied in dropper vials and should be kept in a rack or box in rows of 10 vials corresponding to the rows of tests to be applied to the skin.

All skin tests should be validated by appropriate positive control tests (e.g., histamine) and negative control tests (e.g., Glycerin, Albumin Saline with Phenol (0.4%), or Buffered Saline with Phenol). The negative control test should be the same material as is used as a diluting fluid in the tested extracts. Diluting fluid is used in the same way as an active test extract.

Test sites should be examined at 15 and 30 minutes. To prevent excessive absorption, wipe off antigens producing large reactions as soon as the wheal appears. Record the size of the reaction. Delayed reactions may rarely occur from tests, so it may be helpful to examine the test sites in 24 hours.

Use of Scarifiers and Spacing. Make scarifications at least 2.5 cm apart. Use more space between pollen tests to prevent smearing into adjacent sites. Hold the scarifier between the thumb and index finger, press the sharp edge of the instrument against the skin and twirl instrument rapidly. The scratch should disrupt only the outer layers of epidermis but should not produce immediate oozing of blood. The amount of pressure needed to produce a satisfactory scratch will vary between patients according to the thickness or fragility of their skin. Experience will indicate the proper amount of pressure to exert in making the scratch. If the scarifier is kept sharp and the scratch made quickly, discomfort to the patient is minimized.

Use of Prick Test Needles. The skin is cleaned and single drops of each extract applied to the properly identified test sites. A small, sterile disposable needle, such as a 1/2-inch 26 gauge needle (with the bevel up), a bifurcated vaccinating needle, or a Prick Lancetter™ is inserted through the drop superficially into the skin, the skin lifted slightly and the needle withdrawn. No bleeding should be produced. After about 1 minute the extract may be wiped away.

3. Most Satisfactory Sites for Testing
Prior to testing, clean the skin area to be tested with ether or alcohol and allow to dry. Use a sterile instrument for each patient. The back or the volar surface of the arms are the most satisfactory sites for testing. Skin of the posterior thighs or abdomen may be used if necessary. Avoid very hairy areas where possible, since the reactions will be smaller and more difficult to interpret. The most satisfactory areas of the back are from the posterior axillary fold to 2.5 cm from the spinal column, and from the top of the scapula to the lower rib margins. The best areas of the arms are the volar surfaces from the axilla to 2.5 or 5 cm above the wrist, skipping the anti-cubital space.

4. Use of Antigen Mixes
The use of complicated mixes of unrelated pollens for testing is not recommended since in the case of a positive reaction, it does not indicate which pollen(s) are responsible, and, in the case of a negative reaction, it fails to indicate whether the individual pollens at full concentration would give a positive reaction.

5. Reading Skin Test Reactions
A positive reaction consists of an urticarial wheal with surrounding erythema (resembling somewhat a mosquito bite reaction) larger than the control site. The smallest reaction considered positive is erythema with a central papule at least 5 mm in diameter. In some instances with no reaction at the control site, erythema may be considered an indication of sensitivity. In general, the size of wheal and erythema response correlates directly with the patient’s sensitivity to that allergen.

Standardized Products
(a) Mites:
The skin test concentration of 30,000 AU/mL in dropper vials is used for scratch, prick or puncture testing. Puncture tests performed on 12 highly sensitive subjects showed the following:

The sum of a skin response is the sum of the longest diameter and the mid-point orthogonal diameter.

(b) Cat Hair and Cat Pelt: The skin test concentration of 10,000 BAU/mL (10-19.9 Fel d 1 Units/mL) in dropper vials is used for prick or puncture testing. Puncture tests performed on 15 highly sensitive subjects showed the following:

The sum of a skin response is the sum of the longest diameter and the mid-point orthogonal diameter.

(c) Ragweed pollen (Short Ragweed or Giant and Short Ragweed Mixture) Antigen E Assayed: Short Ragweed extract at 1:20 w/v in 50% glycerin containing approximately 100 to 300 units of Antigen E/mL or Giant and Short Ragweed Mix at 1:20 w/v in 50% glycerin containing approximately 50 to 150 units of Antigen E/mL are usually used for scratch, prick or puncture testing.
Refer to the following table to determine the skin test sensitivity grade. The corresponding ∑E (sum of the longest diameter and the mid-point orthogonal diameters of erythema) is also presented.

A positive skin reaction to any allergen must be interpreted in light of the patient’s history of symptoms, time of the year, known exposures, and eating habits.
THE SKIN TESTS ARE IN NO WAY A SUBSTITUTE FOR A CAREFUL ALLERGIC HISTORY. THEY SERVE AS ADDITIONAL INFORMATION TO AID IN IDENTIFYING CAUSATIVE ALLERGENS IN PATIENTS WITH ALLERGIC DISORDERS.

6. Geriatric Use

The dose is the same in patients of all age groups. Because the wheal size in response to allergen skin testing decreases with age, appropriate histamine positive control skin tests must be performed.1

7. Pediatric Use

The dose is the same in patients of all age groups. Wheal size in response to allergen skin testing can be smaller in infants than in adults. Appropriate histamine positive control skin tests must be performed.1

HOW SUPPLIED

STORAGE

The expiration date of the diagnostic extracts is listed on the container label. The extract should be stored at 2° - 8°C and kept at this temperature range during office use.

LIMITED WARRANTY

REFERENCES

1. Middleton, Elliott, Jr., C.E. Reed, E.F. Ellis (ed.) Allergy Principles and Practice. Fourth Edition, Vol. 1. C.V. Mosby. 1993.
2. Sheldon, J.M., R.G. Lovell, K.P. Mathews. A Manual of Clinical Allergy. W.B. Saunders. 1967.
3. Tuft, L., H.L. Mueller. Allergy in Children. W.B. Saunders. 1970.
4. DuBuske, L.M., C.J. Ling, A.L. Sheffer. Special problems regarding allergen immunotherapy. Immunol. Allergy Clin. North Am. (USA). 12(1): 145-175, 1992.
5. Weinstein, A.M., B.D. Dubin, W.K. Podleski, S.L. Spector, R.S. Farr. Asthma and pregnancy. JAMA. 124(11): 1161-1165, 1979.
6. Jacobs, Robert L., Geoffrey W. Rake, Jr., et.al. Potentiated anaphylaxis in patients with drug-induced beta-adrenergic blockade. J. Allergy Clin. Immunol. 68(2): 125-127, August 1981.
7. Lockey, Richard F., Linda M. Benedict, Paul C. Turkeltaub, Samuel C. Bukantz. Fatalities from immunotherapy (IT) and skin testing (ST). J. Allergy Clin. Immunol. 79(4): 660-677, 1987.
8. Turkeltaub, Paul C., Peter J. Gergen. The risk of adverse reactions from percutaneous prick-puncture allergen skin testing, venipuncture, and body measurements: Data from the second National Health and Nutrition Examination Survey 1976-80 (NHANES II). J. Allergy Clin. Immunol. 84(6): 886-890, Dec. 1989.
9. Pipkorn, Ulf. Pharmacological influence of anti-allergic medication on In Vivo allergen testing. Allergy. 43: 81-86, 1988.
10. Andersson, M., U. Pipkorn. Inhibition of the dermal immediate allergic reaction through prolonged treatment with topical glucocorticosteroids. J. Allergy Clin. Immunol. 79 (2): 345-349, February 1987.
11. Rao, Kamineni S., et al. Duration of suppressive effect of tricyclic anti-depressants on histamine induced wheal and flare reactions on human skin. J. Allergy Clin. Immunol. 82: 752-757, November 1988.
12. Pipkorn, Ulf, M. Andersson. Topical dermal anesthesia inhibits the flare but not the wheal response to allergen and histamine in the skin prick test. Clin. Allergy. 17: 307-311, 1987.
13. Turkeltaub, Paul C., Suresh, C. Rastogi, Harold Baer. Office of Biologics Research and Review skin test method for evaluation of subject sensitivity to standardized allergenic extracts and for assignment of allergy units to reference preparations using the ID₅₀EAL method (Intradermal Dilution for 50 mm Sum of Erythema Determines the Allergy Unit). Methods of the Allergenic Products Branch Office of Biologics Research and Review, FDA, Bethesda, MD 20892. Revised May 9, 1986.
14. Food and Drug Administration. Biological products; Allergenic extracts classified in Category IIIB; Final order; Revocation of licenses. Federal Register. 59(220): 59228ff, November 16, 1994.