6  Immediate Drug Allergy

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

Skin Testing

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

Skin Prick Testing

Figure 6.1: Skin prick testing

Intradermal Testing

Figure 6.2: Intradermal testing

Controls

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.

Positive Skin Test

Figure 6.3: Positive skin test

Figure 6.4: Immediate skin testing reading times

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

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.

Concentrations

Oral Challenge

Rapid Desensitization

Figure 6.5: Rapid Desensitization

Figure 6.6: Rate (mg/min) by time for 1-bag vs 3-bag rapid desensitization protocols

Figure Generated from protocol comparison from (Lee et al. 2020)

Biomarkers

Tryptase

Figure 6.7: Tryptase Gene

Figure 6.8: Tryptase Secretion

Figure 6.9: Tryptase Secretion

Figure 6.10: Acute and Baseline Tryptase

Tryptase is a natural serine protease

average tryptase, average tryptase HAT, average tryptase ISM, average tryptase ASM

Elevated basal tryptase >= 11.5 ng/mL Can get basal tryptase at 24 hrs after anaphylaxis event

Anaphylaxis >= 20% increase from basal tryptase + 2 ng/mL

TPSAB1 increased: HaT, SM CNV (alpha tryptase) alpha or beta tryptase constitutively released (measure of MC burden)

TPSB2 Beta preformed granule release during anaphylaxis/severe MC activation

Total Tryptase = a + B by ImmunoCAP (R) In vitro assay half-life ~90 minutes peak at 1 hr stored primarily in MC

Figure 6.1: Skin prick testing Figure 6.2: Intradermal testing Figure 6.3: Positive skin test Figure 6.4: Immediate skin testing reading times Figure 6.5: Rapid Desensitization Figure 6.6: Rate (mg/min) by time for 1-bag vs 3-bag rapid desensitization protocols Figure 6.7: Tryptase Gene Figure 6.8: Tryptase Secretion Figure 6.9: Tryptase Secretion Figure 6.10: Acute and Baseline Tryptase

Lee, Jae-Ha, Mira Moon, Young-Chan Kim, Soo Jie Chung, Jihyun Oh, Dong-Yoon Kang, Suh-Young Lee, Kyung-Hun Lee, James Yun, and Hye-Ryun Kang. 2020. “A One-Bag Rapid Desensitization Protocol for Paclitaxel Hypersensitivity: A Noninferior Alternative to a Multi-Bag Rapid Desensitization Protocol.” The Journal of Allergy and Clinical Immunology: In Practice 8 (2): 696–703. https://doi.org/10.1016/j.jaip.2019.10.014.