The skin is more than just a protective shield; it is a complex, immunologically active organ. When this protective barrier is compromised, conditions such as eczema (atopic dermatitis) and psoriasis can emerge or worsen. Recent research has turned the spotlight on skin barrier biomarkers biological indicators found in the skin or blood that reflect the integrity and function of the skin barrier. These biomarkers are becoming valuable tools in predicting disease severity, guiding treatment, and even forecasting flare-ups in chronic inflammatory skin conditions.
Understanding and utilizing these biomarkers could mark a significant shift from generalized to personalized dermatology, where prevention and treatment are tailored based on an individual’s unique skin biology.
What Are Skin Barrier Biomarkers?
Skin barrier biomarkers are measurable substances, such as proteins, lipids, or cytokines, that provide insights into the skin’s health and its ability to protect against external threats like allergens, microbes, and irritants. When the barrier is disrupted, it often leads to increased transepidermal water loss (TEWL), dryness, and inflammation, all hallmarks of eczema and psoriasis.
Key skin barrier biomarkers include:
- Filaggrin (FLG) mutations
- Claudins and tight junction proteins
- Interleukins (IL-4, IL-13, IL-17, IL-22, IL-31)
- Thymic stromal lymphopoietin (TSLP)
- S100 proteins (S100A7, A8, A9)
- Transepidermal water loss (TEWL) as a physiological marker
These indicators help researchers and clinicians understand not only what is happening in the skin, but also why and how severely.
Eczema and the Filaggrin Factor
Atopic dermatitis (AD) is often the first manifestation of atopy in children, and genetics play a strong role. One of the most significant discoveries in eczema research has been the identification of filaggrin gene (FLG) mutations, which result in reduced or absent filaggrin protein in the stratum corneum (Brown et al., 2008). Filaggrin is essential for skin barrier integrity, hydration, and pH regulation.
Individuals with FLG mutations often have earlier onset, more persistent, and more severe eczema, and are more prone to secondary infections due to barrier breakdown (Palmer et al., 2006). Detecting FLG mutations through genetic or protein-based tests may help predict not only severity but also the likelihood of developing eczema in infants with a family history.
Cytokine Profiles in Psoriasis Severity
Psoriasis is driven by immune dysregulation, especially the overactivation of Th17 and Th1 pathways. Cytokines such as IL-17, IL-23, TNF-α, and IL-22 are elevated in psoriatic lesions and play a central role in keratinocyte proliferation and chronic inflammation (Lowes et al., 2008).
Measurement of these cytokines, whether in blood or skin tissue, can provide a real-time snapshot of disease activity. Elevated IL-17A, for example, correlates with plaque thickness and erythema, and levels drop significantly with biologic treatments like secukinumab or ixekizumab (Langley et al., 2014). Thus, these biomarkers not only indicate severity but also track treatment response.
Predicting Flares and Monitoring Progress
Skin barrier biomarkers are increasingly being studied for their predictive potential. For instance:
- Elevated TSLP and IL-33 levels may signal an impending flare in atopic dermatitis
- Increased TEWL can precede visible signs of skin breakdown
- High serum IL-31 is associated with intense itching in eczema patients (Raap et al., 2012)
Regular monitoring of these biomarkers could allow for preemptive treatment adjustments, reducing the frequency and intensity of flare-ups.
Non-Invasive Testing: A Growing Frontier
Traditionally, biomarker analysis required invasive skin biopsies or blood tests. However, newer techniques are emerging:
- Tape stripping collects stratum corneum proteins painlessly for biomarker analysis
- Wearable sensors can measure TEWL or skin hydration in real-time
- Microarray and transcriptomic profiling are enabling comprehensive skin barrier assessments from tiny samples (Bakker et al., 2021)
These innovations could make routine biomarker testing a part of standard dermatologic care, especially for chronic inflammatory conditions.
Toward Personalized Dermatology
The integration of skin barrier biomarkers into clinical practice paves the way for precision medicine in dermatology. Rather than relying solely on visual inspection and subjective symptoms, dermatologists can use quantifiable data to:
- Predict who is at risk of severe eczema or psoriasis
- Choose therapies based on inflammatory pathway activity
- Monitor therapeutic response objectively
- Identify early signs of relapse
This personalized approach has the potential to improve outcomes, reduce side effects, and increase patient satisfaction.
Skin barrier biomarkers are transforming how we understand and manage chronic inflammatory skin conditions like eczema and psoriasis. By providing a molecular-level view of disease severity and progression, they offer a new layer of precision in diagnosis, treatment, and prevention. As technology evolves and non-invasive testing becomes more accessible, these biomarkers will likely become cornerstones of personalized skin care, improving lives for millions living with these burdensome conditions.
References
- Bakker, D. S., Ariens, L. F. M., van der Schaft, J., van den Bogaard, E. H., & van de Kerkhof, P. C. M. (2021). Tape strips in dermatological research. British Journal of Dermatology, 184(5), 837–845. https://doi.org/10.1111/bjd.19764
- Brown, S. J., & McLean, W. H. I. (2008). One remarkable molecule: filaggrin. Journal of Investigative Dermatology, 128(3), 520–529. https://doi.org/10.1038/sj.jid.5701051
- Langley, R. G., Elewski, B. E., Lebwohl, M., Reich, K., Griffiths, C. E. M., Papp, K., … & Blauvelt, A. (2014). Secukinumab in plaque psoriasis—results of two phase 3 trials. New England Journal of Medicine, 371(4), 326–338. https://doi.org/10.1056/NEJMoa1314258
- Lowes, M. A., Bowcock, A. M., & Krueger, J. G. (2008). Pathogenesis and therapy of psoriasis. Nature, 445(7130), 866–873. https://doi.org/10.1038/nature05663
- Palmer, C. N., Irvine, A. D., Terron-Kwiatkowski, A., Zhao, Y., Liao, H., Lee, S. P., … & Smith, F. J. D. (2006). Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nature Genetics, 38(4), 441–446. https://doi.org/10.1038/ng1767
- Raap, U., Wichmann, K., Bruder, M., Ständer, S., Wedi, B., & Kapp, A. (2012). Correlation of IL-31 serum levels with severity of atopic dermatitis. Journal of Allergy and Clinical Immunology, 118(3), 930–932. https://doi.org/10.1016/j.jaci.2006.04.019
