Differentiating superficial fungal infection from eczema using a heated dynamic-headspace skin VOC sampler: a...

Superficial fungal infections and eczematous dermatitis frequently present with overlapping clinical features, such as erythema, scale, and pruritus, which often lead to empiric treatment and delayed diagnosis. Existing confirmatory tests, such as potassium hydroxide microscopy, fungal culture, and polymerase chain reaction, can be limited by operator dependence, turnaround time, availability, and cost. These challenges create a need for a rapid, non-invasive method to distinguish fungal infection from eczema at the point of care. We hypothesize that these conditions generate distinct skin volatile organic compound signatures because fungal lesions reflect organism-specific metabolic pathways, whereas eczematous lesions are shaped primarily by barrier dysfunction, oxidative stress, and altered microbial communities. Specifically, dermatophytes, Candida species, and Malassezia species are expected to contribute characteristic alcohols, esters, ketones, and other metabolites, while eczema is expected to be enriched in lipid peroxidation products and inflammatory barrier-related volatiles. A heated dynamic headspace sampling approach offers a practical strategy to capture these compounds by enriching semi-volatile molecules under controlled conditions while reducing interference from ambient contaminants. In parallel, advances in sorbent-based sampling, gas chromatography mass spectrometry, and portable differential mobility spectrometry support a translational pathway from biomarker discovery to clinical triage. If validated, skin volatile profiling could eventually serve as a rapid adjunctive triage approach to support confirmatory testing and guide early management decisions in selected clinical settings.