Skin testing has been performed as an adjunct in the diagnosis of allergic diseases for more than 130 years. Charles Blackley, an English physician, performed the first skin test in 1873.<sup>2 Blackley C.H. Experimental Researches on the Cause and Nature of Catarrhus Aestircus  London: Balliere, Tindall Cox (1873). 

Haga clic aquí para ir a la sección de Referencias</sup> He applied extracts of grass pollen to denuded forearm skin, producing a wheal in allergic individuals.

In 1911 Leonard Noon attempted to induce the production of pollen antitoxin in allergic patients by injecting these patients with pollen extract.<sup>13 Li J.T. Immunotherapy for allergic rhinitis Immunol Allerg Clin North Am 2000 ;  20 : 383-399

Haga clic aquí para ir a la sección de Referencias, 19 Noon L. Prophylactic inoculating against hayfever Lancet 1911 ; 1572-1573  [cross-ref]

Haga clic aquí para ir a la sección de Referencias</sup> Noon also attempted to determine the degree of sensitivity of allergic patients to specific allergens. He made various dilutions of antigen extracts and instilled them into the patient's conjunctiva. His endpoint was the concentration of extract resulting in conjunctival inflammation. This work resulted in the development of the Noon unit, which was the quantity of antigenic material extracted from 0.001 mg of timothy grass pollen. Presently, the Noon unit is 1 μg of antigenic material, and an extract labeled 1:10 w/v contains 100,000 NU/mL. The following relationship is important to keep in mind:

Noon unit = 0.001 mg antigen = 1/2 PNU = 0.1 mL of #4 test solution. The protein nitrogen unit (PNU) is a standardized measure of all protein present in a given extract. The #4 test solution represents an antigen dilution of 1:12,500.

Cooke expanded on Noon's work by establishing an individual's degree of sensitivity to allergens by using intradermal skin challenge tests.<sup>3 Cooke R.A. The Rx of hayfever by active immunization Laryngoscope 1915 ;  25 : 108-112

Haga clic aquí para ir a la sección de Referencias</sup> Cooke assigned patients to four groups based on their skin reactivity to antigenic exposure.

French Hansel is considered the father of otolaryngic allergy.<sup>20 Oglethorpe J.D. Evaluation of otolaryngic allergy: The American Academy of Otolaryngic Allergy Otolaryngol Head Neck Surg 1996 ;  114 : 515-524

Haga clic aquí para ir a la sección de Referencias</sup> He was the first otolaryngologist to perform skin tests in 1930 using multiple individual extracts as opposed to single concentrations of antigenic material. His early experiences, published in 1953,<sup>9 Hansel F. Clinical Allergy  St. Louis: CV Mosby (1953).  922

Haga clic aquí para ir a la sección de Referencias</sup> demonstrated that each individual antigen has a unique response in a given patient. The strength of a response to different antigens is not the same for all the antigens encountered by a given individual.<sup>20 Oglethorpe J.D. Evaluation of otolaryngic allergy: The American Academy of Otolaryngic Allergy Otolaryngol Head Neck Surg 1996 ;  114 : 515-524

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Phillips previously had demonstrated that the size of the skin wheal following intradermal skin testing correlated well with the dose of the antigen administered.<sup>21 Philips E.W. Relief of hayfever by intradermal injections of pollen extract JAMA 1926 ;  86 : 182-184

Haga clic aquí para ir a la sección de Referencias</sup> Hansel thus concluded that multiple intradermal skin tests using individual allergens with varying doses produced greater accuracy of information regarding the degree of the patient's sensitivity.<sup>22 Rinkel H.J. Management of clinical allergy. II: Ideologic factors in skin titration Arch Otolaryngol 1963 ;  77 : 42-75

Haga clic aquí para ir a la sección de Referencias</sup> This method has become the fundamental concept behind serial endpoint titration (SET). Hansel used intradermal injections of antigens in a 1:10 ratio. He tested individual antigens in varying strength while measuring the response.

Unfortunately, the 1:10 antigenic dilution resulted in abrupt whealing and a high frequency of false-positive responses. In 1937, Herbert Rinkel, an allergist working with Hansel, found that an antigenic dilution ratio of 1:5 administered in progressively increasing increments resulted in a qualitatively and quantitatively superior measure of allergic skin reactivity. The response was constant through three or four dilutions in 72% of patients, avoided false-positive reactions, and allowed for the detection of very low levels of sensitivity. It was acknowledged that a ratio of 1:3 reflected skin reactivity even more accurately, but the mathematics were more difficult than when using 1:5 dilutions.<sup>1 Anon J.B. Introduction to in vivo allergy testing Otololaryngol Head Neck Surg 1993 ;  109 : 593-600

Haga clic aquí para ir a la sección de Referencias</sup> Table 1 shows the equivalent concentrations of extract used in the currently available skin testing methodologies.

Rinkel emphasized the importance of recognizing the various types of skin responses and knowledge of factors that modify these responses when using serial dilution testing to determine the degree of sensitivity in inhalant allergies. Although these techniques of testing are commonly used today, the final treatment dose determined by these calculations (low dose immunotherapy, also known as the `Rinkel technique,') is no longer recommended or practiced.

The current terminology, SET or serial dilution titration (SDT), is preferred to avoid confusion with outdated Rinkel treatment techniques.<sup>13 Li J.T. Immunotherapy for allergic rhinitis Immunol Allerg Clin North Am 2000 ;  20 : 383-399

Haga clic aquí para ir a la sección de Referencias, 23 Trevino R.J., Veling M.C. The importance of quantifying skin reactivity in treating allergic rhinitis with immunotherapy Ear Nose Throat J 2000 ;  79 : 362-366

Haga clic aquí para ir a la sección de Referencias</sup> Other titration techniques also currently are in use (at a 1:3 dilution) by the Food and Drug Administration (FDA) for standardization of allergen extracts (see Table 1.