Histamine Skin Prick Tests: From Established Diagnostic Technique to Advanced Experimental Biomarker

Abstract

Introduction: Skin prick tests have a long history as diagnostic and pharmacodynamic biomarker. Besides visual assessments of the wheal and flare, objective blood flow measurements using laser Doppler imaging (LDI) and laser speckle contrast imaging (LSCI) have been reported. In light of these advancements, an up-to-date characterization of the histamine-evoked response is worthwhile. Methods: A single-centre study was completed in healthy males. Two parameters were addressed: (1) dermal blood flow (DBF) within a 7.65-mm ring encircling the skin prick site (DBF_ring), and (2) surface area of the flare (AREA_flare). First, the dose response was assessed using placebo (0.9% sodium chloride) or histamine (histamine dihydrochloride 1, 3, or 10 mg/mL) skin pricks on the volar surface of subjects’ (n = 12) forearm. The DBF_ring was measured by LDI, and the AREA_flare by LDI and by ruler. Secondly, the inter-arm and inter-period reproducibility of the DBF_ring and AREA_flare, as evoked by histamine (10 mg/mL) and measured by LDI and LSCI, was examined (n = 14). Lastly, the effect of aprepitant (125 mg), ketotifen (1 mg), and a single (5 mg) and fourfold (20 mg) dose of desloratadine and levocetirizine on the histamine-induced (10 mg/mL) DBF_ring and AREA_flare was evaluated with LSCI (n = 13 or 12). Results: All three histamine doses induced a time-dependent vasodilation. Ruler recordings did not conclusively correlate with LDI assessments of the AREA_flare. The DBF_ring and AREA_flare were reasonably reproducible when measured by using LDI or LSCI, with negligible bias between arms and study periods and poor to moderate within-subject reproducibility (0.23 ≤ ICC ≤ 0.71). While the fourfold dose of desloratadine (p = 0.0041) and the single and fourfold dose of levocetirizine (p < 0.0001) managed to reduce the AREA_flare, only the fourfold dose of levocetirizine (p = 0.0052) reduced the DBF_ring. Conclusion: Caution is warranted when translating years of clinical experience with histamine skin prick tests to objective recordings of the associated changes in skin perfusion. Ruler and LDI assessments of the AREA_flare do not consistently correlate, and the reproducibility and histamine dependency of the measurements are not obvious. While 10 mg/mL histamine may be a good choice for qualitative diagnostic evaluations, a lower dose may be better suited to use as a quantitative biomarker.