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A comparison of skin endpoint titration and skin-prick testing in the diagnosis of allergic rhinitis.


Among the many methods of allergy diagnosis are intradermal testing (IDT IDT Integrated Device Technology, Inc. (Santa Clara, CA, USA)
IDT I Don't Think
IDT Identity Theft
IDT Interrupt Descriptor Table
IDT Integrated DNA Technologies
IDT Inactive Duty Training
IDT Instructional Design & Technology
) and skin-prick testing (SPT (Sectors Per Track) The number of sectors in one track. ). The usefulness of IDT has been called into question by some authors, while others believe that studies demonstrating that SPT was superior might have been subject to bias. We conducted a study to compare the validity of SPT and IDT--specifically, the skin endpoint titration titration (tītrā`shən), gradual addition of an acidic solution to a basic solution or vice versa (see acids and bases); titrations are used to determine the concentration of acids or bases in solution.  (SET) type of IDT--in diagnosing allergie rhinitis Rhinitis Definition

Rhinitis is inflammation of the mucous lining of the nose.

Rhinitis is a nonspecific term that covers infections, allergies, and other disorders whose common feature is the location of their symptoms.
. We performed nasal provocation testing on 62 patients to establish an unbiased screening criterion for study entry. Acoustic rhinometric measurements of the nasal responses revealed that 34 patients tested positive and 28 negative. All patients were subsequently tested by SET and SPT. We found that SPT was more sensitive (85.3 vs 79.4%) and more specific (78.6 vs 67.9%) than SET as a screening procedure. The positive predictive value Positive predictive value (PPV)
The probability that a person with a positive test result has, or will get, the disease.

Mentioned in: Genetic Testing

positive predictive value 
 of SPT was greater than that of SET (82.9 vs 75.0%), as was the negative predictive value The negative predictive value is the proportion of patients with negative test results who are correctly diagnosed. Worked example
Relationships among terms:

(as determined by "Gold standard")

True False
 (81.5 vs 73.0%). None of these differences was statistically significant; because of the relatively small sample size, our study was powered to show only equivalency. The results of our study suggest that the information obtained by the SET method of IDT is comparable to that obtained by SPT in terms of sensitivity, specificity, and overall performance and that both SET and SPT correlate well with nasal provocation testing for ragweed ragweed, any plant of the genus Ambrosia, coarse, weedy herbs belonging to the family Asteraceae (aster family), most of which are native to America. They have inconspicuous greenish flowers and soft subdivided leaves. . Therefore, the decision as to which to use can be based on other factors, such as the practitioner's training, the desire for quantitative results, the desire for rapid results, and the type of treatment (i.e., immunotherapy or pharmacotherapy pharmacotherapy /phar·ma·co·ther·a·py/ (-ther´ah-pe) treatment of disease with medicines.

Treatment of disease through the use of drugs.
) that is likely to be chosen on the basis of test results.


Allergic rhinitis Allergic Rhinitis Definition

Allergic rhinitis, more commonly referred to as hay fever, is an inflammation of the nasal passages caused by allergic reaction to airborne substances.
 is one of the most common diseases in the United States, affecting 30% or more of the general population. (1) It is a source of significant morbidity; symptoms as wide ranging as rhinorrhea, cough, sneezing To verbally tell somebody about a new and interesting Web site. See viral marketing. , itching, runny eyes, sinusitis sinusitis

Inflammation of the sinuses. Acute sinusitis, usually due to infections such as the common cold, causes localized pain and tenderness, nasal obstruction and discharge, and malaise.
, and generalized fatigue considerably diminish quality of life. Its economic costs are also considerable--not only with respect to the amount of money spent on treatments, but also with regard to the amount of time lost from school and work and decreased productivity.

The choice of treatment for allergic rhinitis is usually based on the severity of symptoms. In milder cases, decongestants Decongestants Definition

Decongestants are medicines used to relieve nasal congestion (stuffy nose).

A congested or stuffy nose is a common symptom of colds and allergies.
 or simple avoidance of the offending allergen allergen /al·ler·gen/ (al´er-jen) an antigenic substance capable of producing immediate hypersensitivity (allergy).allergen´ic

pollen allergen
 can provide relief. Patients who are unable to control their exposure or tolerate their symptoms may opt for a nonsedating antihistamine antihistamine (ăn'tĭhĭs`təmēn), any one of a group of compounds having various chemical structures and characterized by the ability to antagonize the effects of histamine.  and/or other medications, such as topical or systemic corticosteroids Corticosteroids, Systemic Definition

Corticosteroids are a group of drugs which are chemically related to the hormones produced by the adrenal glands as a response to adrenocorticotropic hormone (ACTH), but excluding the sex hormones that are produced
. Unfortunately, some patients are unable to achieve relief even with maximal pharmacologic therapy, and it is they who are most often referred for further allergy evaluation. These patients may be candidates for immunotherapy, which usually entails systematic desensitization systematic desensitization (sisˈ·t  to the offending antigens. Immunotherapy has been shown to be effective for the vast majority of patients who choose it, provided that they are diagnosed correctly. For these patients, finding the offending antigens is critical. After a careful history and physical examination, skin tests or in vitro in vitro /in vi·tro/ (in ve´tro) [L.] within a glass; observable in a test tube; in an artificial environment.

in vi·tro
In an artificial environment outside a living organism.
 tests are frequently employed. (2)

Among the factors that must be considered in evaluating the appropriateness of any given test are its safety (minimal risk of anaphylaxis anaphylaxis (ăn'əfəlăk`sĭs), hypersensitive state that may develop after introduction of a foreign protein or other antigen into the body tissues. ), sensitivity, specificity positive and negative predictive values, reproducibility correlation with symptoms, and ease of administration The allergy testing allergy testing See Patch testing, RAST, Skin testing.  modalities that are available to the clinician include in vitro testing (IVT IVT

intravenous transfusion.
), skin-prick testing (SPT), intradermal testing (IDT) (including skin endpoint titration [SET]), and nasal provocation testing (NPT NPT National Pipe Taper (pipe thread specification)
NPT Non-Proliferation Treaty
NPT Nonprofit Times
NPT Newport (Rhode Island)
NPT Nuclear Nonproliferation Treaty
NPT Neath Port Talbot

In vitro testing. Several types of IVT are available to measure a patient's serum total and allergen-specific immunoglobulin E immunoglobulin E
n. Abbr. IgE
The class of antibodies produced in the lungs, skin, and mucous membranes and responsible for allergic reactions.
 (IgE) levels. One of the earliest was the radioallergosorbent test ra·di·o·al·ler·go·sor·bent test
n. Abbr. RAST
A radioimmunoassay test to detect certain types of immunoglobulin-bound allergens responsible for tissue hypersensitivity.
 (RAST), which involved the placement of a radioactive label on an anti-IgE antibody anti-IgE antibody Allergy medicine An antibody directed against IgE. See Allergy. . During this assay, the patient's specific IgE remains bound to antigen in a test tube, where its relative abundance tan be measured. An effort to improve the sensirivity of RAST led to the development of the modified RAST (mRAST). Further advances in IVT involved the development of fluorometric or colorimetric col·or·im·e·ter  
1. Any of various instruments used to determine or specify colors, as by comparison with spectroscopic or visual standards.

 labels, which spare technicians from exposure to radiation.

Among the advantages of IVT are its safety and sensitivity. It is particularly useful in (1) patients who are taking a beta blocker, because skin testing in these patients tan be dangerous and (2) patients who are on an antihistamine, because skin testing in these patients is unreliable. (3) Patients with dermatographism can be better assessed by IVT, as can children who balk balk

the action of a horse when it refuses to obey a command to which it usually responds. See also jibbing.
 at skin testing. IVT is slightly more expensive and slightly less sensitive than SPT, but it is slightly more specific. However, results are not immediately available.

Skin-prick testing. SPT was first described in the 1920s and popularized by Pepys in the 1970s. (4) These tests are well regarded because they are specific, sensitive, convenient, and relatively safe. In addition, SFT SFT Statens Forurensningstilsyn (Norwegian Pollution Control Authority)
SFT System Fault Tolerance
SFT Shaft
SFT Secure File Transfer
SFT School Food Trust (UK)
SFT Societe Francaise des Traducteurs
 correlates well with IDT. SPT is performed by introducing a droplet droplet

very small drop of fluid.

droplet nuclei
the finite particles of matter which are transmitted from animal to animal.
 of antigen approximately 1 mm deep into the skin with a high-gauge needle. This technique allows the antigen to cause a superficial skin reaction without entering the dermis dermis: see skin. . SPT requires that a positive control (histamine) and a negative control (saline with or without glycerin glycerin /glyc·er·in/ (-in) a clear, colorless, syrupy liquid used as a laxative, an osmotic diuretic to reduce intraocular pressure, a demulcent in cough preparations, and a humectant and solvent for drugs. Cf. glycerol. ) be introduced into the skin at distinctly separate sites. (5)

In recent years, SPT has been modified to allow for the introduction of larger quantities of antigen. Needles with longer bevels can be used to deposit antigen into the dermis, and multiprong devices such as the Multi-Test instrument (Lincoln Diagnostics; Decatur, Ill.) can be used to test as many as eight antigens at once. With their longer prongs, these devices penetrate the skin somewhat more deeply than do conventional skin-prick instruments, and they arc considered by some to more closely resemble intradermal tests.

Individual skin-prick tests have been shown to correlate well with mRAST and with SET (81 to 89% for the latter). (6,7) However, studies have shown that multiprong devices do not correlate as well. (8) For example, Levine et al round a disparity in results obtained by mRAST and the Multi-Test device. (9) Although there was good agreement with respect to negative results in that study, agreement occurred in only 56 to 67% of positive tests.

Other advantages of SPT are its relative ease of use, short hands-on time, and quick results. One of the draw-backs of SPT is patient discomfort; intertester reproducibility may also be a problem. Other variables--including the specific sites being tested, the distance between test sites, and the consistency of technique--may confound results, as well. (5,9) The use of nonstandardized allergen extracts leads to further difficulties. Finally, there are several different scales used to read results.

Intradermal testing. IDT has been in use since the early part of the 20th century. (5) Dilute antigen extract is injected into the dermis, and a superficial wheal wheal (hwel) a localized area of edema on the body surface, often attended with severe itching and usually evanescent; it is the typical lesion of urticaria.

 forms. This technique causes minimal patient discomfort. IDT is very sensitive and more reproducible than SPT, primarily because a larger volume of a known antigen concentration can be introduced. Allergists disagree as to whether IDT correlates well with clinically significant allergens and with SPT. (10) Moreover, there are questions about its specificity; in patients with a negative SPT, it is hot clear whether a reaction to an IDT represents a true positive or a local skin reaction (false positive).

Disadvantages that are unique to standard IDT include the need for more rime, labor, and supplies. Also, standard IDT is potentially more dangerous than SPT if it is not performed judiciously. The greater volume of antigen that is delivered is more likely to precipitate an anaphylactic anaphylactic /ana·phy·lac·tic/ (an?ah-fi-lak´tik) pertaining to anaphylaxis.
anaphylactic (an´
 reaction. Therefore, some authors recommend that SPT be performed prior to IDT. (10,11)

Skin endpoint titration. SET is a modified method of IDT in which serially diluted antigen extracts are used to determine the minimum amount of antigen that is required to elicit a significant allergic response, quantified by comparing the size of wheal increase with that evoked by a negative control test. The endpoint response is reached upon the determination of the lowest concentration of antigen that produces a wheal (1) that is the first wheal more than 2 mm larger than the negative control wheal and (2) that is followed by a second wheal that is at least 2 mm larger than the preceding one. The endpoint signifies the degree of sensitivity and indicates a safe starting point for immaunotherapy.

As a form of IDT, SET carries the same advantages as nontitrated IDT, and it has the additional benefit of being more quantitative. However, SET is time-consuming and is somewhat uncomfortable for the patient. But these disadvantages are often outweighed by the fact that SET is the only skin test that provides a semiquantitative assessment of a patient's allergen sensitivity. A modified form of SET is currently used by the federal Food and Drug Administration to validate the potency of allergenic extracts. (12)

Tandy et al reported that the correlation between SET and mRAST was 82.2%. (13) At dilutions of 1:12,500 (dilution #4) and 1:312,500 (dilution #6), SET is roughly equivalent to SPT in terms of the volume of antigen delivered. By comparison, standard IDT uses dilutions of 1:100 (equivalent to SET dilution #1) to 1:1,000 (between SET dilutions #1 and #2). In common practice, SET is started at the #6 dilution for seasonal allergens and at the #4 dilution for out-of-season allergens; both are comparable to SPT dilutions.

Nasal provocation testing. NPT is a direct method of assessing whether a given antigen produces symptoms of allergie rhinitis when it is introduced into the nasal mucosa. Passali and Bellussi characterized NPT as a "third-level" method of investigation, to be used only when nasal allergy i s suspected. (14) They asserted that skin testing and serum assays can establish a diagnosis in most patients, but provocation can localize lo·cal·ize  
v. lo·cal·ized, lo·cal·iz·ing, lo·cal·iz·es
1. To make local: decentralize and localize political authority.

 previously primed toast cells in the "organ of shock"--that is, the nose. Their protocol involves three steps. First, anterior rhinomanometry is performed to rule out nasal stenosis. Second, lactose is insufflated into the nasal fossa and rhinomanometry is repeated. Third, Iyophilized antigen is introduced into the fossa fossa /fos·sa/ (fos´ah) pl. fos´sae   [L.] a trench or channel; in anatomy, a hollow or depressed area.

acetabular fossa  a nonarticular area in the floor of the acetabulum.
. Rhinomanometric measurements are taken 10 to 15 minutes following the introduction of the antigen.

Another method of NPT is the disk method, which involves the administration of oxymetazoline oxymetazoline /oxy·met·az·o·line/ (-met-az´o-len) an adrenergic used as the hydrochloride salt as a vasoconstrictor to reduce nasal or conjunctival congestion.

 to reduce mucosal edema edema (ĭdē`mə), abnormal accumulation of fluid in the body tissues or in the body cavities causing swelling or distention of the affected parts. . Afterward, an allergen-impregnated filter-paper disk is placed on the nasal septum. The disk releases antigen, and nasal secretions are collected at predetermined pre·de·ter·mine  
v. pre·de·ter·mined, pre·de·ter·min·ing, pre·de·ter·mines
1. To determine, decide, or establish in advance:
 intervals. The disks are weighed before and after insertion into the nose, and mediators are eluted from the disk and quantified. The disk method is very labor-intensive and time-consuming. (15,16)

A third way of performing NPT is to introduce allergen into the nares via either a suspension spray or a filter-paper disk. After 10 minutes of reaction rime, the degree of mucosal swelling is assessed by either acoustic rhinometry or anterior rhinomanometry. (10)

Nasal provocation can be eschewed in favor of bronchial bronchial /bron·chi·al/ (brong´ke-al) pertaining to or affecting one or more bronchi.

Relating to the bronchi, the bronchial tubes, or the bronchioles.
 provocation, but the upper airway test has several distinct advantages. First, the nasal mucosa is readily available. Second, controlled provocations with various stimuli are easy to perform. Third, collecting specimens and measuring mucosal responses can be easily accomplished without the risk of inducing bronchospasm bronchospasm /bron·cho·spasm/ (brong´ko-spazm) bronchial spasm; spasmodic contraction of the smooth muscle of the bronchi, as in asthma.

. (17)

Study rationale

Although SET has become the testing modality of choice for many otolaryngologists, some advocates of SPT continue to dismiss it without acknowledging its inherent benefits. As a result, SET has not always been accurately represented in recent comparative studies between it and SPT, standard IDT, IVT, and/or NPT. In some studies, SPT has been used as the gold standard. (10,18-20) However, allocation of subjects into different groups on the basis of SPT findings introduces a preselection bias into the investigation. Another factor that can hinder interpretation of results is introduced when only patients with negative SPT results are evaluated by IDT, despite the fact that one of the goals of the study is to compare SPT with IDT. Selecting a qualitative IDT technique other than the semiquantitative SET also introduces prejudice. Finally, NPT--which is the gold standard for determining the clinical relevance of a particular allergen has been used to assess differences between preselected groups on the basis of SPT results. Using NPT as the gold standard for determining the presence or absence of nasal allergy and for determining skin responses would yield more relevant information. Indeed, positive NPT results have been reported in as many as 44% of SPT-negative groups. (10) The results of previous studies of the value of IDT in the assessment of clinically relevant inhalant inhalant /in·hal·ant/ (in-hal´ant)
1. something meant to be inhaled; see inhalation (def. 3).

2. a class of psychoactive substances whose volatile vapors are subject to abuse.
 allergy are misleading and might have been biased in favor of SPT. (10,18-20)

To show that a group of patients has a clinically relevant sensitivity to any pollen, researchers can use one of two methods. One is to initiate nasal provocation with pollen grains, and the other is to correlate each patient's daily symptom scores and medication intake with daily pollen counts during the pollen season. The underlying assumption is that a patient with a clinically significant allergy to a pollen should report increased symptom severity following exposure to the pollen, either in the laboratory or in the environment.

We hypothesized that both SET and SPT correlate well with NPT. By recruiting study patients prospectively and performing all three types of test on every patient, we were able to use NPT as the gold standard without introducing selection bias into our study. Our objective was to determine if SPT should precede SET because of SPT's greater degree of sensitivity and specificity or if SPT and SET are equally reliable, in which case either could be used as a first-line assay.

Patients and methods

We recruited 62 patients aged 18 years or older who had a history of allergy to ragweed--specifically, seasonal symptoms that were temporally associated with ragweed pollination pollination, transfer of pollen from the male reproductive organ (stamen or staminate cone) to the female reproductive organ (pistil or pistillate cone) of the same or of another flower or cone. . We eliminated the chance that unpredictable priming would occur as a result of natural exposure to ragweed pollen by recruiting patients who were currently asymptomatic and by conducting out study outside the ragweed season (although we could hot eliminate the possibility of priming caused by exposure to allergens other than ragweed). We did not accept patients who had a history of asthma or nasal polyps, or those who had received immunotherapy for ragweed at any time during the preceding 10 years. For study purposes, allergy medications were discontinued as follows: oral decongestants for 3 days, most antihistamines Antihistamines Definition

Antihistamines are drugs that block the action of histamine (a compound released in allergic inflammatory reactions) at the H1
 for 3 days (except for astenfizole [3 months] and cetirizine [7 days]), topical and systemic steroids for 2 weeks, and nasal cromolyn for 1 week. All patients were free of upper respiratory infections during the week prior to testing. Out research protocol was approved by the Institutional Review Board at the University of Chicago. All study patients signed a document of informed consent prior to participating in the study.

We first obtained baseline measurements of nasal volume by acoustic rhinometry. Next, we performed a diluent diluent /dil·u·ent/ (dil´oo-int)
1. causing dilution.

2. an agent that dilutes or renders less potent or irritant.

Serving to dilute.

 provocation (0.9% saline with 0.4% phenol phenol (fē`nōl), C6H5OH, a colorless, crystalline solid that melts at about 41°C;, boils at 182°C;, and is soluble in ethanol and ether and somewhat soluble in water. ) to assess each patient's response. An abnormal response would have cast doubt on that particular patient' s future findings and would have disqualified him or her from the study; fortunately no response was abnormal. Patients were then assessed by NPT, SET, and SPT. NPT was always performed first to allocate patients into study groups. Patients were then randomly assigned to receive either SET first and SPT second or vice versa.

Immediately following provocation and before acoustic rhinometry, each patient completed a questionnaire to indicate the number of sneezes, and each made a mark on a visual analog scale to indicate the severity of his or her symptoms, including runny nose, stuffy nose, sneezing, and nose or throat itching (figure 1). All patients under went NPT to determine their clinical sensitivity to ragweed.

Clinical sensitivity was assessed with increasing amounts of ragweed pollen; dilutions progressed from 1:10,000 to 1:3,000 to 1:1,000 and finally to 1:300. Dilutions of the standardized skin-test extract were prepared in a 1/20 weight per volume (w/v) ragweed concentrate in phenolated saline. The solution was sprayed twice into each nostril nostril /nos·tril/ (nos´tril) either of the nares.

A naris.


either of the two apertures (nares) of the nose that lead into the nasal cavity.
 with a spray pump identical to those used for aqueous nasal sprays. The clinical response to the provocation was monitored by acoustic rhinometry measurements taken 10 and 25 minutes after each antigen dose. Thirty minutes were allowed to elapse e·lapse  
intr.v. e·lapsed, e·laps·ing, e·laps·es
To slip by; pass: Weeks elapsed before we could start renovating.

 between provocations. We measured the volume of the nasal cavity after each administration of a different dilution. After each challenge, we recorded the number of sneezes that occurred during the first 5 minutes.

We assumed that an NPT result was positive if we detected a 15% reduction in volume after 10 minutes by acoustic rhinometry. Although the 15% threshold was arbitrary, it was based on the fact that variability between acoustic rhinometry readings approaches 10%; therefore a 15% change would represent a real change in volume and would be a sale distance from values that might have represented artifactual ar·ti·fact also ar·te·fact  
1. An object produced or shaped by human craft, especially a tool, weapon, or ornament of archaeological or historical interest.

 changes resulting from operator-dependent factors. (21) The amount of decrease in volume is reflective of the degree of congestion The condition of a network when there is not enough bandwidth to support the current traffic load.

congestion - When the offered load of a data communication path exceeds the capacity.
 and inflammation caused by the allergie response, and thus is an indicator of response.

Both NPT-positive and NPT-negative patients under went SET and SPT to determine their sensitivity to ragweed, white ash, timothy grass, meadow fescue fescue (fĕs`ky), any of some 100 species of introduced Old World grasses of the genus Festuca. , and either marsh elder weed/white oak or dust mite/cat. Our allergen panel changed slightly over time as we modified it to identify patients who were "out of season" for this testing.

All skin tests included positive (histamine) and negative (glycerinated saline) controls. SPT was performed with a standard Multi-Test applicator ap·pli·ca·tor
An instrument for applying something, such as a medication.

n a device for applying medication; usually a slender rod of glass or wood, used with a pledget of cotton on the end.
 and 1/20 w/v standardized extracts. The wheal response was read in 20 minutes. Results were scored according to the grading system described by Van Metre et al. (22)

SET was performed with techniques approved by the American Academy of Otolaryngic Allergy and Foundation. (23) Each intradermal injection of five-fold dilution of the 1/20 w/v ragweed concentrate was delivered by a 27-gauge, 1/2-inch, beveled bev·el  
1. The angle or inclination of a line or surface that meets another at any angle but 90°.

2. Two rules joined together as adjustable arms used to measure or draw angles of any size or to fix a surface at an angle.
 hypodermic needle, starting with 0.01 ml of the #6 dilution (1:312,500). Wheal sizes were read 10 minutes later and compared with those raised by the negative control injections. Then the next strongest dilution was administered and read. We stopped SET when we reached the endpoint--that is, when successive injections raised wheals A wheal or "wheal response" is an area of edema in the upper epidermis that itches or burns. They usually indicate an insect bite, another type of allergic reaction, or injury to the skin.  whose diameters were 2 mm or more larger than the preceding wheal, including the control.

We analyzed our data by using sensitivity and specificity calculations with NPT as the gold standard. We performed a receiver-operator characteristics (ROC) curve analysis according to a method described by DeLong et al (24) with STATA statistical software. ROC analysis can help assess the utility of a diagnostic tool in clinical practice. In a ROC graph, they axis represents the true positives (sensitivity) and the x axis represents the false positives (1-specificity). ROC analysis allows one to determine a threshold value or critical point from which results can be considered positive or negative. For our analysis, variable cut-off points for SPT and SET were based on the respective grading system of each test. For SET we used variable cut-off points of 0, 1, 2, 3, 4, 5, and 6, and for SPT we used cut-off points of 0, 1, 2, 3, and 4. At each cut-off point, the accuracy rate was calculated independently and used in the construction of the ROC graph.


After we obtained data on all patients, we assigned them to one of eight groups based on their NPT, SET, and SPT results (table 1). Of the 62 patients in our study, 34 had positive NPT results and 28 had a negative test. Of the 34 NPT-positive patients, 27 had positive SET results and 29 had positive SPT results (table 2).

We then calculated the sensitivity, specificity, positive predictive value, and negative predictive value of the SET and SPT results. In addition, we calculated the probability that a test would be negative when disease was present and the probability that a test would be positive when disease was not present. Although both tests were accurate, we found that there was a trend favoring SPT; however our sample was not large enough to show statistical significance (table 3).

In the ROC analysis, the area under the curve for SET was 0.7773 and the area under the curve for SPT was 0.8361 (figure 2). Although the difference was not statistically significant (p = 0.1276), our sample size was not large enough to allow for statistically significant comparisons. Nevertheless, the two sets of area under the curve were consistent and similar. In a ROC analysis, the similarity of the shape of the curves and their closeness reflects the concordance concordance /con·cor·dance/ (-kord´ins) in genetics, the occurrence of a given trait in both members of a twin pair.concor´dant

 of the two tests in terms of negative and positive diagnoses.


In some previous articles on this subject, authors have claimed that IDT is unnecessary or even dangerous if SPT is used. (10,11) Although these authors claimed that they used NPT as the gold standard, they actually used SPT; they performed NPT or IDT only when SPT was negative. This might make sense clinically because this is how most physicians practice; most clinicians believe that IDT is the more sensitive modality. As a result, in 1993, Nelson et al recommended that IDT not be used. (10) However, they did hot take into account the many variables inherent in skin-testing methods, especially in IDT. Our data suggest that the information obtained by the SET method of IDT is comparable to that obtained by SPT in terms of sensitivity, specificity, and overall performance.

Compared with the other tests, treatment based on SET is believed to provide symptom relief much more rapidly because the endpoint is the symptom-relieving dose. (5,6) The safety of immunotherapy based on SET has been proven by the fact that the rate of associated adverse reactions is extremely low. (6) Treatment based on RAST is mathematically equivalent to SET-based treatment, and relief is rapid and safe. The results of our study suggest that bath SET and SPT correlate well with NPT for ragweed. Therefore, the decision as to which to use can be based on other factors, such as the practitioner's training, the desire for quantitative results, or the desire for rapid diagnosis, and the type of treatment (i.e., immunotherapy or pharmacotherapy) that is likely to be chosen on the basis of test results.
Table 1. Assignment of patients based on the results of nasal
provocation testing (NPT), skin endpoint titration (SET), and
skin-prick testing (SPT) results

Group    n     NPT        SET        SPT

  1     26   Positive   Positive   Positive
  2      1   Positive   Positive   Negative
  3      3   Positive   Negative   Positive
  4      4   Positive   Negative   Negative
  5     19   Negative   Negative   Negative
  6      6   Negative   Positive   Positive
  7      3   Negative   Positive   Negative
  8      0   Negative   Negative   Positive

Table 2. Results of skin endpoint titration (SET) and
skin-prick testing (SPT) in the 62 patients, using
nasal provocation testing (NPT) as the gold standard

                NPT results (no. patients)

               Positive   Negative   Total

Positive SET      27          9        36
Negative SET       7         19        26
Total             34         28        62

Positive SPT      29          6        35
Negative SPT       5         22        27
Total             34         28        62

Table 3. Comparison of selected reliability factors
with skin endpoint titration (SET) and skin-prick
testing (SPT)
               SET    SPT
               (%)    (%)

Sensitivity   79.4   85.3
Specificity   67.9   78.6
PPV *         75.0   82.9
NPV *         73.0   81.5
PNP *         21.0   15.0
PPN *         32.0   21.0

* PPV = positive predictive value; NPV = negative predictive value;
PNP = probability that a test would be negative when disease was
present: PPN = probability that a test would be positive when disease
was not present.


(1.) King HC, Mabry RL, Mabry CS. Allergy in ENT ENT ears, nose, and throat (otorhinolaryngology).

ear, nose, and throat


ear, nose and throat.

ENT Ears, nose & throat; formally, otorhinolaryngology
 Practice. New York: Thieme, 1998.

(2.) Peebles RS, Hartert TV. In vivo diagnostic procedures: Skin testing, nasal provocation, and bronchial provocation. Methods 1997;13:14-24.

(3.) Chambers DW. Cook PR, Nishioka GJ, Erhart P. Comparison of mRAST and CAP with skin endpoint titration for Alternaria Alternaria

a saprophytic fungus commonly found on the skin; also has been associated with subcutaneous infections (phaeohyphomycosis) and reputed to be one of the causes of the indeterminate syndrome of forage poisoning in farm animals. Tenuazonic acid is a toxic metabolite.
 tenuis ten·u·is  
n. pl. ten·u·es Linguistics
1. A voiceless stop.

2. A voiceless unaspirated stop in ancient Greek.
 and Dermatophagoides pteronyssinus. Otolaryngol Head Neck Surg 1997;117:471-4.

(4.) Pepys J. Skin tests for immediate, type I, allergic reactions. Proc R Soc Med 1972;65:271-2.

(5.) Gordon BR. Allergy skin tests for inhalants inhalants, 1. chemical vapors that are inhaled for their mind-altering effects.
2. in herbology, volatile herbal compounds that are delivered by holding a soaked pad to the nose and mouth, by placing the herbs in steaming water, or
 and foods. Comparison of methods in common use. Otolaryngol Clin North Am 1998; 31:35-53.

(6.) Fadal RG. Experience with RAST-based immunotherapy. Otolaryngol Clin North Am 1992;25:43-60.

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(8.) Nelson HS, Rosloniec DM, McCall LI, Ikle D. Comparative performance of rive rive  
v. rived, riv·en also rived, riv·ing, rives
1. To rend or tear apart.

2. To break into pieces, as by a blow; cleave or split asunder.

 commercial prick skin test devices. J Allergy Clin Immunol 1993;92:750-6.

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1. within the dermis.

2. intracutaneous.

Within or between the layers of the skin.
 skin testing in the diagnosis of clinically relevant allergy to timothy grass. J Allergy Clin Immunol 1996;97:1193-1201.

(11.) Allergen skin testing. Board of Directors. American Academy of Allergy and Immunology. J Allergy Clin Immunol 1993;92: 636-7.

(12.) U.S. Dept. of Health and Human Services Noun 1. Health and Human Services - the United States federal department that administers all federal programs dealing with health and welfare; created in 1979
Department of Health and Human Services, HHS
, Food and Drug Administration. Biologic products: Allergenic extracts. Implementation of efficacy review. Federal Register Jan. 23, 1985:50: 3082-3112.

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(15.) Naclerio RM. Inhibition of mediator release during the early reaction to antigen. J Allergy Clin Immunol 1992;90(Pt 2): 715-19.

(16.) Wagenmann M. Baroody FM, Kagey-Sobotka A, et al. The effect of terfenadine on unilateral nasal challenge with allergen. J Allergy Clin Immunol 1994:93:594-605.

(17.) Andersson M, Greiff L, Svensson C, Persson C. Various methods for testing nasal responses in vivo: A critical review. Acta Otolaryngol 1995;115:705-13.

(18.) Mariotta S, Mannino F. Torrelli L, et al. Prick and intradermal tests compared with specific IgE in allergic assessment. Allergol Immunopathol (Madr) 1995 ;23: 121-6.

(19.) Malling Malling may refer to:
  • Malling Rural Sanitary District, Kent, England - (1875 - 1894)
  • East Malling and West Malling, two villages in the above RSD
  • Malling, Moselle, France
  • Malling, Denmark
  • Heinrich August Malling (1807-1893), a Danish statesman and novelist.
 HJ. Diagnosis and immunotherapy of mould allergy. II. Reproducibility and relationship between skin sensitivity estimated by end-point titration and histamine equivalent reaction using skin prick test and intradermal test. Allergy 1985;40: 354-62.

(20.) Menardo JL, Bousquet J, Michel FB. Comparison of three prick test methods with the intradermal test and with the rast in the diagnosis of mite allergy. Ann Allergy 1982;48:235-9.

(21.) Gungor A, Moinuddin R. Nelson RH, Corey JP. Detection of the nasal cycle with acoustic rhinometry: Techniques and applications, Otolaryngol Head Neck Surg 1999;120:238-47.

(22.) Van Mctre TE, Adkinson NF, Jr., Amodio FJ, et al. A comparative study of the effectiveness of the Rinkel method and the current standard method of immunotherapy for ragweed pollen hay lever. J Allergy Clin Immunol 1980;66:500-13.

(23.) Fornadley JA, Corey JP, Osguthorpe JD, et al. Allergie rhinitis: Clinical practice guideline. Committee on Practice Standards, American Academy of Otolaryngic Allergy. Otolaryngol Head Neck Surg 1996;115:115-22.

(24.) DeLong ER, DeLong DM. Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: A nonparametric approach. Biometrics 1988;44: 837-45.

Anil Gungor, MD Rizwan Moinuddin, MD Steven M. Houser, MD Bulent Mamikoglu, MD Benjamin F. Aquino, MD Jacquelynne P. Corey, MD, FAAOA FAAOA Fleet Air Arm Officers Association , FACS FACS Fellow of the American College of Surgeons.

Fellow of the American College of Surgeons


fluorescence-activated cell sorter.
 Imran Akbar, BA

From the Section of Otolaryngology, Department of Surgery, Pritzker School of Medicine The Pritzker School of Medicine is the M.D. granting unit of the Biological Sciences Division of the University of Chicago. It is located on the University's main campus in the Hyde Park portion of Chicago proper, and matriculated its first class in 1927. , University of Chicago.

Reprint requests: Jacquelynne P. Corey, MD, Associate Professor, Section of Otolaryngology, Department of Surgery, Pritzker School of Medicine, University of Chicago, MC 1035, 5841 S. Maryland Ave., Chicago IL 60637. Phone: (773) 702-0382; fax: (773) 702-6809; e-mail:

The study described in this article was funded by a combined grant from the American Academy of Otolaryngic Allergy and Foundation and the American Academy of Otolaryngology-Head and Neck Surgery. Dr. Gungor, Dr. Houser, and Dr. Mamikoglu received partial support via a grant from Hoechst Marion Roissel (now Aventis Pharmaceuticals).
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Author:Corey, Jacquelynne P.
Publication:Ear, Nose and Throat Journal
Date:Jan 1, 2004
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