SPT

In the 1970s Pepys suggested the use of a modified prick test procedure, using a 25-gauge hypodermic syringe needle, which permits 0.003 mL of the antigen to be absorbed into the epidermis when performed at a 45° angle to an approximate depth of 1 mm without inducing bleeding. Although this technique is no longer used, it highlighted the need for standardization of the amount introduced into the skin. Furthermore, a proper technique necessitates the use of separate needles for each test to avoid mixing the antigen solutions. Using the same needle or lancet wiped with dry cotton wool or cotton moistened with 75% ethanol between tests produces an unacceptable number of false-positive results and presents a potential risk of exposure to blood-borne pathogens.

To reduce the variability of the SPT procedure, several investigators have modified the test method. Morrow Brown introduced the vertical prick puncture method, which uses a single-point device measuring 1.25 mm long. A guard prevents penetration of the needle beyond a predetermined depth. No skin lifting is used and, in using this instrument, supposedly only a small amount of antigen is delivered into the skin when compared with the Pepys prick test. By using commercially available, nonreusable, and standardized devices, the procedure is considered standard (with the limitation of the extract used) and safe.

Among other devices used for SPT, the Multi-Test (Lincoln Diagnostics, Decatur, IL, USA) has been available for more than 20 years. This test consists of a plastic device containing 8 heads, 4 on each side. Each head has 9 prongs. This device allows for a quick and easy approach and it is possible to perform multiprick puncture testing within approximately 30 seconds. However, multiheaded devices present significant variability because of the pressure applied and are considered to be more painful than single devices. In general, single-point nonreusable devices are considered the preferred (standard) procedure for SPT.

Correlation of Skin Test Results with OFCs

Various studies have investigated how SPT results correlate to the outcome of OFCs, considered the gold standard for diagnosing food allergies. When correlating the size of the wheal and/or the positivity of the tests (>3 mm mean diameter) with the outcome of double-blind, placebo-controlled food challenges, significant differences in wheal sizes were noted between individuals who were allergic to egg, milk, peanut, and wheat and those who were tolerant. By contrast, reactivity to soy could not be predicted based on SPT results. Cutoff values for clinical positivity were established. Other groups reported different values in their population of patients, indicating that the SPT results should be interpreted according to a specific population, as well as to the antigen extract used.

Precautions Before Skin Prick Testing

Before any SPT is performed, a few precautions should be followed for the safety of the patient and the accuracy of the results. The following list of precautions, adapted from Ref. are standard:

• 1.
  

  No testing should be performed without a physician being immediately available to treat a patient, should a systemic reaction occur.

  
  
• 2.
  

  Emergency equipment has to be readily available.

  
  
• 3.
  

  The allergenic extracts used should be standardized whenever possible. In addition, they should be manufactured free of extraneous antigenic factors.

  
  
• 4.
  

  Test concentrations used must be appropriate for the degree of sensitivity of the patient as determined from the history.

  
  
• 5.
  

  A positive (histamine) and negative control solution should always be included.

  
  
• 6.
  

  The test should be performed on nonlesional skin.

  
  
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  Before the test, the patients should be evaluated for increased, and nonspecific, skin reactivity (dermographism).

  
  
• 8.
  

  It must be determined ahead of time whether the patient uses medications (mostly antihistamines) that might interfere with the accuracy of the skin tests.

  
  
• 9.
  

  An accurate record of the reactions and the proper timing must be kept, and each reaction must be accurately measured.

  
  
• 10.
  

  An evaluation of the patient’s allergic symptoms must be completed before any tests and close observation performed during the test.

In addition, the physician or technician performing SPT needs to be trained and needs to have repeated practice of skin prick testing to provide reproducible and reliable results.

Common Errors in Skin Prick Testing

The following errors are common and should be avoided:

• 1.
  

  When performing SPT with multiple antigens each solution should be placed 2 cm or more apart.

  
  
• 2.
  

  Insufficient or excess penetration of the skin by the puncture instrument may lead to false-negative results. This situation occurs more frequently with plastic devices or Morrow Brown needles used by unqualified personnel.

  
  
• 3.
  

  Induction of bleeding, possibly leading to false-positive results.

  
  
• 4.
  

  Spreading of allergen solutions during the test or when the solution is wiped away.

Prick-prick Test

This procedure is performed by using native antigens (eg, a fresh fruit), and is commonly used in food-related allergic reactions. One first pricks through the fresh food and then pricks the skin of the patient. Some studies reported that the SPTs were positive 40% of the time with commercial extracts and 81% of the time using fresh foods. The overall concordance between a positive prick test and a positive challenge test is 59% with commercial extracts and 92% when fresh foods were used. When a history is positive, and a commercial food antigen prick test is negative, then a prick-prick test using fresh food should be considered.

Criteria of Positivity

The wheal or the flare has been considered to assess the positivity of skin tests. For prick puncture tests, reactions generally regarded to indicate clinical allergy are usually more than 3 mm in wheal diameter and more than 10 mm in flare diameter. An alternative criterion is a ratio of the size of the test induced by the allergen to the size that is elicited by the positive control solution. Any degree of positive response, with appropriate positive and negative controls, indicates the presence of an allergic sensitization but not necessarily the simultaneous presence of an allergic disease related to the tested allergen. Therefore, an agreement between the skin test results and the clinical history is essential in the overall interpretation of the clinical significance of the SPT.

Patch Test

Patch testing may be helpful in cases of suspected non–IgE-mediated food allergies. Majamaa and colleagues tested 143 children less than 2 years of age suspected to be allergic to cow’s milk by elimination diet and an OFC. Seventy-two of the 143 children had a positive OFC, and among these 26% were found to have increased IgE to cow’s milk protein, 14% had an SPT, and 44% had a positive patch test to cow’s milk. Most of the patients with a positive patch test had a negative SPT to cow’s milk. A positive patch test suggests a delayed-type sensitivity to the tested antigen but as with all tests for food allergy the physician must evaluate whether this immunologic reaction corresponds to a clinical condition. Although patch tests might be helpful in the diagnosis of food allergy, in particular in children with eosinophilic gastrointestinal disease of atopic dermatitis, the relevance of this test in routine diagnostic testing has been questioned and cannot be generally recommended.

Scratch Test

The scratch test is characterized by a superficial epidermal abrasion, approximately 2 mm long, to which an antigen is applied. This test is simple and quick to perform, but not sufficiently sensitive or specific because of the wide interindividual variation in performing the test. The major disadvantages of scratch testing are the significant numbers of false-positive reactions, the low reproducibility, and that the test is more painful than a prick test. Therefore, the Allergy Panel of the American Medical Association (AMA) Council of Scientific Affairs recommends that scratch testing should not be performed routinely.

Intradermal Tests

Although intradermal tests are used in allergy diagnosis, in particular for the diagnosis of venom or drug allergy, this procedure should not be used in common clinical practice in the diagnosis of food allergy.