Biomarkers of disease in human nails: a comprehensive review

Diagnostic, monitoring, response, predictive, risk, and prognostic biomarkers of disease are all widely studied, for the most part in biological fluids or tissues, but there is steadily growing interest in alternative matrices such as nails. Here we comprehensively review studies dealing with molecular or elemental biomarkers of disease, as opposed to semiological, pharmacological, toxicological, or biomonitoring studies. Nails have a long history of use in medicine as indicators of pathological processes and have also been used extensively as a matrix for monitoring exposure to environmental pollution. Nail clippings are simple to collect noninvasively as well as to transport and store, and the matrix itself is relatively stable. Nails incorporate, and are influenced by, circulating molecules and elements over their several months of growth, and it is widely held that markers of biological processes will remain in the nail, even when their levels in blood have declined. Nails thus offer the possibility to not only look back into a subject's metabolic history but also to study biomarkers of processes that operate over a longer time scale such as the post-translational modification of proteins. Reports on ungual biomarkers of metabolic and endocrine diseases, cancer, and psychological and neurological disorders will be presented, and an overview of the sampling and analytical techniques provided.