Principles of Skin Testing

Tutorial

  For an overview of immediate drug allergy testing, I recommend getting started by watching Immediate Drug Allergy Hypersensitivity Testing.

Concentrations typically employed for drug skin testing are 1:10, 1:100, and full strength.

Should be performed on healthy, non-pathologic skin. For example skin with altered permeability (e.g. atopic dermatitis), the amount of allergen penetrating the skin is up to 20x greater than the average volume of inoculum by SPT.

Controls

Figure 1: Controls for immediate skin testing

To increase the solubility of histamine in water, it is provided in its salt form, such as histamine dihydrochloride or histamine phosphate. In vivo, histamine dissociates into its biologically active form, called “histamine base.”

The histamine and normal saline controls used for skin testing usually also includes 0.4% phenol (also known as carbolic acid) in order to inhibit microbial growth and maintain sterility. Carbolic acid is what Joseph Lister discovered to be an effective antiseptic for surgery.

Increased skin test reactivity - Skin lesion with altered permeability (e.g. atopic dermatitis) - Stress

Decreased skin reactivity - Eczema (but finding is not consistently observed) - Some patients with cancer - Chronic renal failure or on regular hemodialysis - Patients with spinal cord injuries - Peripheral nerve abnormalities (e.g. diabetic neuropathy)

Positive Skin Test

Figure 2: Positive skin test

Immediate skin testing reading times

Immediate skin testing reading times

Immediate Reaction

Immediate skin testing starts around 5 minutes and peaks at 15 minutes, resolving around 30 minutes.

Histamine is not the only mediator of the wheal and flare response. Mast cell degranulation also leads to release of the following mediators:

  • Tryptase

  • Neurogenic Mediators (e.g. substance P, CGRP, neurokinin A)

  • Nitric oxide

  • Corticotropin-releasing hormone

Late phase reaction

Late phase reaction–if occurs–start around 1-2 hours, peak at 6-12 hours, and resolve at 24-48 hours. Not actively/systematically recorded (instruct patients to notify if does occur); however, the exact clinical significance of late phase reactions is unknown.