Can Molecular Biomarkers Unlock the Future of Personalized Dermatology?

🔍 Key Finding This review explores the role of molecular biomarkers in personalizing therapies for various dermatological conditions like hidradenitis suppurativa, psoriasis, atopic dermatitis, alopecia areata, vitiligo, and chronic spontaneous urticaria. While some biomarkers effectively guide current treatments, others primarily offer scientific insights into disease mechanisms, highlighting the need for further research to fully realize the potential of precision dermatology.

🔬 Methodology Overview

• Design: Literature review
• Data Sources: PubMed, SCOPUS, and Web of Science databases
• Search Strategy: Utilized NLM Medical Subject Headings (MeSH) and specific search strings (e.g., “(biomarkers OR serum marker) AND [disease name]”)
• Selection Criteria: Articles published within the last five years; primary data from various study designs (RCTs, cohort studies, case studies, etc.); focus on biomarkers in HS, Psoriasis, AD, AA, Vitiligo, and CSU; English language; full-text availability. Priority given to primary sources.
• Analysis Approach: Qualitative synthesis of findings related to biomarkers in each dermatological condition.
• Scope: Exploration of molecular biomarkers and personalized therapies in specific dermatological conditions.

📊 Results

• Hidradenitis Suppurativa (HS): TNF-α, IL-1β, and MMPs are key biomarkers. Adalimumab has shown efficacy in reducing HS lesion counts. Anakinra, an IL-1 antagonist, decreased inflammatory lesions and pain scores. Only 1 diagnostic, 1 monitoring, and 2 predictive HS biomarkers were identified in a systematic review of 48 potential markers.
• Psoriasis: TNF-α, IL-23, IL-17, and HLA genes are important biomarkers. IL-23 and IL-17 inhibitors, as well as TYK2/Janus kinase 1 inhibitors, have shown promise in treatment.
• Atopic Dermatitis (AD): ECP, IL-4, IL-13, TSLP, and the filaggrin gene (FLG) are relevant biomarkers. Dupilumab (IL-4 and IL-13 inhibitor), tralokinumab (IL-13 inhibitor), baricitinib (JAK inhibitor), and nemolizumab (IL-31RA blocker) have demonstrated therapeutic benefits. ~7% of AD patients developed anti-drug antibodies to dupilumab in phase 3 trials.
• Alopecia Areata (AA): Lipocalin-2, insulin, c-peptide, various cytokines, and genetic polymorphisms (CTLA-4 rs231726, PTPN22 rs2476601) are associated with AA. JAK inhibitors (ritlecitinib, brepocitinib, ruxolitinib, tofacitinib, baricitinib) have shown efficacy in hair regrowth. Intralesional vitamin D3 is also effective for localized patchy AA.
• Vitiligo: Biomarkers include cytokines, autoantibodies, oxidative stress markers, immune cells, antibodies, soluble CDs, chemokines, TYR, TYRP1, DCT, LARP7, KIF1A, MIF, sCD27, alarmins, and miRNAs.
• Chronic Spontaneous Urticaria (CSU): IgE, various cytokines, autologous serum tests, and other inflammatory markers are implicated. Omalizumab and cyclosporine are used in treatment, with IgE levels potentially predicting response. Anti-TPO antibodies are associated with increased CSU severity and duration.
• Acne: LRIG1, IGF-1, FoxO1, various cytokines, and TLR-2 are potential biomarkers. Oral isotretinoin targets FoxO transcription factors. Anti-IL-17A therapy has shown limited efficacy for inflammatory acne lesions.

💡 Clinical Impact This review highlights the potential of molecular biomarkers to personalize dermatologic treatment for conditions like HS, psoriasis, AD, AA, vitiligo, and CSU, guiding therapy selection and monitoring. While some biomarkers already inform clinical practice, further research and integration of AI, nanotechnology, and multi-omics data promise to enhance diagnostic accuracy and treatment efficacy, paving the way for truly precision dermatology.

🤔 Limitations

• Common proinflammatory markers like cytokines lack specificity for differentiating between inflammatory skin conditions.
• Some biomarkers have more scientific/laboratory value than direct clinical utility due to cost or accessibility issues.
• Conflicting results in biomarker studies, particularly in autoimmune diseases, complicate their reliability in clinical practice.
• Limited clinical evidence supporting the reliability of some informatics-derived biomarkers.
• Insufficient data on long-term safety and efficacy of some targeted therapies, like JAK inhibitors.
• Potential for patients to develop anti-drug antibodies, leading to treatment failure with biologics.
• Need for further research to validate biomarkers and establish clear clinical application guidelines.

✨ What It Means For You This research reinforces the importance of considering individual patient biomarkers when selecting dermatological therapies, moving away from a one-size-fits-all approach. Doctors can utilize this information to better predict treatment response and tailor therapies for conditions like psoriasis, eczema, and alopecia areata based on a patient’s specific inflammatory markers or genetic predispositions. Further research is needed to validate the clinical utility of some biomarkers and refine personalized treatment strategies.

Reference Tan IJ, Podwojniak A, Parikh A, Cohen BA. Precision Dermatology: A Review of Molecular Biomarkers and Personalized Therapies. Curr. Issues Mol. Biol. 2024;46:29752990. https://doi.org/10.3390/cimb46040186