Recent patents in allergy and immunology: Transepidermal water loss for anaphylaxis monitoring

Description of the invention and potential applications

Food allergy is a major health burden with increasing prevalence globally.¹ The gold-standard diagnostic test for food allergy is the oral food challenge, but utilization of such challenges is limited by the risk of anaphylaxis and attendant cost as well as logistical barriers.² Recently, we described the application of transepidermal water loss (TEWL) monitoring during oral food challenges as a means to predict food anaphylaxis before it is clinically evident.³

Our pending patent application covers the use of TEWL as a novel anaphylaxis monitoring modality and is schematically illustrated in Figure 1. TEWL offers a painless, non-invasive measurement approach that requires only a skin application of a monitor device.⁴ TEWL has an established history of use in single time-point or longitudinal studies of baseline skin barrier function in atopic disorders⁵ but has not been used in a continuous monitoring protocol during food challenges. Prior attempts to develop anaphylaxis monitoring approaches, such as using facial thermography, have not led to widespread adoption.⁶

Figure 1: Schematic of the proposed role of TEWL in predicting anaphylaxis.

Transepidermal water loss (TEWL) can be measured continuously during oral food challenges (OFCs). A rise in TEWL occurs before clinical evidence of anaphylaxis, usually around the time of the first objective symptom. While the precise mechanism is not yet known, we hypothesize that the TEWL change is driven by vascular or cutaneous barrier changes related to anaphylaxis, symbolized here as a degranulating mast cell.

In our study, we demonstrated that TEWL measurement on the volar forearm presents a reliable baseline value. Using this location, we determined that TEWL increases during food allergy reactions but does not change during non-reactive oral food challenges. This finding held across various foods and the magnitude of the TEWL change correlated with the change in tryptase during reactions. Crucially, the rise in TEWL occurred before clinical evidence of anaphylaxis, usually around the time of the first objective symptom. We obtained continuous measurement-capable tewameters (Tewameter VT310, Courage + Khazaka gmbh) to measure TEWL continuously during oral food challenges. We determined that using TEWL as a continuous, real-time monitor could detect food anaphylaxis during food challenges with high specificity when combined with a single objective allergy symptom and predict food anaphylaxis approximately 38 minutes prior to its diagnosis.

Path Taken to the Invention

In 2018, we began a project collecting biosamples from all consenting clinical oral food challenge patients in the University of Michigan food allergy clinics. We included TEWL in those samples, in part to evaluate the baseline net epithelial barrier status of challenge patients. We incidentally measured TEWL over an urticarial lesion, noting that the value was higher than the surrounding skin, and later replicated this finding. We therefore hypothesized that TEWL might increase during anaphylaxis due to urticaria or other direct skin effects of allergic reactions. We began measuring TEWL during food challenges and recognized that TEWL increased during anaphylaxis without any visible skin changes in the vicinity of the measurement site. After establishing a proper baseline measurement site that was accessible throughout the food challenge and gave reliable data (the volar forearm in this case), we proceeded to collect data as above. As more reactions accumulated, we came to understand that the increase in TEWL we had observed might be usable as an anaphylaxis monitoring approach.

Conclusions

Human studies have identified TEWL as a likely anaphylaxis monitoring modality. Enhancing the safety of oral food challenges via early anaphylaxis detection is a key potential outcome of this work. To follow up on these results, we initiated an ongoing pilot clinical trial, NCT05696236 - Predicting Peanut Anaphylaxis and Reducing Epinephrine (PrePARE), to determine whether the TEWL observations can be deployed to stop food anaphylaxis early and reduce its severity. In addition, we are working to better define the mechanisms that cause the observed TEWL changes during anaphylaxis. Overall, we expect that the use of TEWL will enhance not just the ability to predict anaphylaxis in real time, but ultimately may facilitate greater understanding of the processes that underpin anaphylaxis.