Skin microdialysis (SMD) is a versatile sampling technique that can be used to recover soluble endogenous and exogenous molecules from the extracellular compartment of human skin. Due to its minimally invasive character, SMD can be applied in both clinical and preclinical settings. Despite being available since the 1990s, the technique has still not reached its full potential use as a tool to explore pathophysiological mechanisms of allergic and inflammatory reactions in the skin. Therefore, an EAACI Task Force on SMD was formed to disseminate knowledge about the technique and its many applications. This position paper from the task force provides an overview of the current use of SMD in the investigation of the pathogenesis of chronic inflammatory skin diseases, such as atopic dermatitis, chronic urticaria, psoriasis, and in studies of cutaneous events during type 1 hypersensitivity reactions. Furthermore, this paper covers drug hypersensitivity, UVB-induced- and neurogenic inflammation, and drug penetration investigated by SMD. The aim of this paper is to encourage the use of SMD and to make the technique easily accessible by providing an overview of methodology and applications, supported by standardized operating procedures for SMD in vivo and ex vivo.

Background Autoimmune chronic spontaneous urticaria (CSU) is due to mast cell (MC)‐activating autoantibodies, which are screened for by the autologous serum skin test (ASST) and basophil tests (BTs). Many CSU patients are positive in only one of these tests. How often this occurs and why is currently unknown. Objectives To characterize the prevalence of mismatched ASST and BTs in CSU patients, and to investigate possible reasons for these mismatches. Methods We determined the rates of ASST+/BT‐ and ASST‐/BT+ mismatches in published CSU studies. We assessed sera from 48 CSU patients by ASST, two BTs (basophil histamine release assay, BHRA; basophil activation test, BAT), a MC histamine release assay (MCHRA) and by ex vivo skin microdialysis (SMD). Results The ASST/BT mismatch rate in published CSU studies was 31% (ASST+/BT‐: 22%, ASST‐/BT+: 9%). In our patients, the ASST/BHRA and ASST/BAT mismatch rate was 35.4% (ASST+/BHRA‐: 18.8% and ASST‐/BHRA+: 16.7%) and 31.3% (ASST+/BAT‐: 6.3% and ASST‐/BAT+: 25.0%), respectively, and the two BTs were significantly correlated (P=0.0002). The use of heterologous MCs, in vitro and in situ, instead of basophils produced similar results (MCHRA mismatch: 47.9%, ASST+/MCHRA‐: 18.8%, ASST‐/MCHRA+: 29.2%; SMD mismatch: 40.0%, ASST+/SMD‐: 10.0% and ASST‐/SMD+: 30.0%), and the MCHRA was highly correlated with SMD results (P=0.0002). Conclusions The ASST and BTs show divergent results in a third of CSU patients. Mismatches cannot be explained by the choice of basophil assay, the type of heterologous cells exposed to CSU serum in vitro (basophils vs mast cells), nor the experimental setting of heterologous skin mast cells (in vitro vs in situ). Thus, serum‐induced whealing, in CSU patients, seems to involve autologous skin signals modulating MC degranulation.

Microdialysis is a well-established technique for sampling of small molecules from the human skin, b...

Patients with acute spontaneous urticaria who did not develop chronic spontaneous urticaria and patients with acute spontaneous urticaria who progressed to having chronic spontaneous urticaria had similar autoantibody profiles and basophil histamine release assay results. Our results suggest that the presence or absence of autoantibodies does not define a patient with chronic spontaneous urticaria.