The term “precision medicine” refers to the concept of tailoring the treatment and prevention of diseases by considering the different genetic, environmental, or lifestyle factors specific to groups of people.10 Currently, precision medicine uses the genetic and molecular information of a group of patients to develop specific and optimized medications or treatments; its primary goal is to ensure that each medication or treatment is the most suitable for treating an individual, focusing also on a reduction of side effects and greater efficacy.11

Advances in new technologies in the areas of molecular and structural biology, also known as omics, will play a key role in understanding the pathophysiological mechanisms of this disease and could develop preventive strategies and personalized treatments.1,12 Precision medicine primarily focuses on human genetic information. Genetics involves the study of genes, their effects, and their relationship with inheritance. Within these areas are the "omics" sciences, which include: genomics, transcriptomics, proteomics, metabolomics, glycomics, lipidomics, epigenomics, metallomics, metagenomics, among others11,13 (Table 2). For the study of these omics and measurement of biomarkers, there are different techniques of translational immunologic approaches to measuring biomarkers in inflammatory skin conditions such as tape stripping, microneedle-based dermal biomarker patch, molecular profiling form epidermal curettage, RNA in situ hybridization staining, single-cell RNA sequencing,14 suction blistering15 and skin microdyalisis16 (Table 3).

Precision medicine recognizes the importance of individual factors such as genetics, medical history, and the patient’s environment in the development and management of AD. Personalized approaches can include selecting specific treatments based on genetic profiles, identifying and avoiding environmental triggers, and regularly monitoring treatment responses using specific biomarkers. The implementation of personalized strategies can significantly improve treatment efficacy and tolerability, as well as reduce the risk of unwanted side effects.

As previously mentioned, genetics plays a key and fundamental role in the etiopathogenesis of AD. The first genetic linkage study, which compared the inheritance of genetic markers with the presence of a clinical trait to identify AD risk genes, identified an important susceptibility locus on chromosome 3q21.17 Additionally, the FLG gene, which encodes filaggrin, is one of the best-known genes associated with AD susceptibility and severity.18 A similar association has been found with another mutation in the serine protease SPINK5.19,20 Studies conducted in Asian populations identified an association between the SPINK5 gene, which encodes a serine protease inhibitor involved in maintaining the skin barrier, and AD susceptibility.21

In recent years, multiple genetic risk factors related to AD have been identified, including ADAM33, RETN, TGFB1, CD207, TSLP, IL-13, IL-4, IL-31, IL6R, STAT3, KIF3A, and HLA-DBQ1, among others13,22–27 (Table 4). Genetic risk factors for AD have been identified through genetic linkage studies, candidate gene approaches, Genome-Wide Association Studies (GWAS), and more recently, Next-Generation Sequencing (NGS) technologies, which have contributed to a better understanding of the genetic risk basis of AD.1

GWAS is a statistical approach that compares the allelic frequency of millions of genetic variants between patients and healthy subjects to identify loci associated with clinical traits.28 These studies have identified more than 40 genes associated with AD risk, including the FLG gene, and risk loci such as SERPINB7, DSC1, and ITGB8, among others.1 In phenotype-wide association studies, a loss-of-function variant of FLG is associated with different clinical phenotypes of AD, such as asthma, allergic rhinitis, and food allergy.29 Genetic variation in the MMP ADAM33 genes and the CD14 monocyte receptor has also been associated with allergic bronchitis and asthma, respectively.30

Next-generation Exome Sequencing (WES) allows the identification of genetic variation in exomic regions, enabling the characterization of genetic factors underlying AD.1 Rare variants in FLG and other genes such as GTF2H5, EVPL, or NLRP1 have been identified in African populations.31 Another study identified a mutation in CARD11 that generates potentially correctable cellular alterations leading to AD.32

Among the new advances in genetic studies, Polygenic Risk Scores (PRS) have emerged. These scores are being used to identify patients at risk of developing AD and who are more likely to benefit from early therapeutic intervention. PRS is a quantitative measure that estimates an individual’s genetic risk burden for developing a specific disease, calculated by aggregating the risk conferred by multiple small-effect variants distributed throughout the genome.1

Recently, the development of non-invasive diagnostic tools for AD and psoriasis has helped with different conditions and guided effective therapies. Additionally, patients often experience frustration due to trial-and-error treatment approaches, which delay disease control and impact quality of life. Two companies, Mindera Health and Castle Biosciences, are pioneering non-invasive technologies to address these challenges.33 Mindera Health developed the Mind.Px™ dermal patch, which uses microneedles to collect RNA from skin samples. Machine learning and genetic biomarkers predict patient responses to specific psoriasis biologics, reducing trial-and-error treatments.34 Clinical studies (e.g., STAMP-1, STAMP-2, MATCH) demonstrated its economic and clinical benefits, showing high predictive accuracy in severe psoriasis cases, and reducing biological therapy costs.33 On the other hand, Castle Biosciences uses non-invasive skin scrapings and gene expression profiling to distinguish between psoriasis, AD, and other conditions like mycosis fungoides.33 Preliminary studies identified distinct genetic markers linked to treatment responses in patients using drugs like dupilumab and risankizumab.35 Ongoing clinical trials aim to validate these findings and optimize systemic therapy selection. These companies aim to revolutionize precision medicine in dermatology by improving diagnosis and tailoring treatment based on genetic profiles, but there still challenges to resolve, including insurance coverage, integration into clinical workflows, and patient acceptance. Successful implementation of these technologies could significantly reduce the burden of inflammatory skin diseases.

Proteomics has been useful in finding biomarkers for both treatment response and prognosis. Studies have observed elevated levels of various inflammatory protein markers in both lesional skin and serum of patients, including proteins related to immune response activation and associated with Th1, Th2, Th17, and Th22 responses.36 These methods have also been used to identify treatment response markers, measuring levels of chemokines and cytokines such as IL-22 and IL-16 before and after treatment with topical corticosteroids, showing a decrease in observed levels, and even correlating the decrease in IL-16 with clinical improvement after topical treatment.37,38 In 2023, Bakker et al. conducted a review of various studies that attempted to classify AD patients based on their immunologic biomarkers.39 Among the existing studies to date, Thijs et al. and Bakker et al., in different cohorts identified the following endotypes (Table 5): Dominant Th1/Th2/Th17 Profile, Dominant Th2/Th22/PARC Profile, and Dominant Th2/eosinophils Profile. The first two groups showed high levels of IL-4, IL-5, and IL-13 expression.40,41

For this reason, it has been suggested that they could be good candidates for targeted therapies such as dupilumab (anti-IL-4/IL-13 monoclonal antibody), tralokinumab (anti-IL-13), and Lebrikizumab (anti-IL-13),42,43 while patients in the remaining group may require drugs with a broader action profile, such as JAK inhibitors (upadacitinib, abrocitinib, baricitinib).39,41 However, more studies are still needed to evaluate the different response profiles of each of these endotypes to the existing therapeutic options.

Thus, the authors can define 2 endotypes based on cytokine expression, referred to by Dyjack et al. as Type 2-predominant inflammatory response endotype and non-Type 2-predominant inflammatory response endotype44 (Table 6). In turn, cytokine-based endotypes can be stratified by patient age. It has been observed that children with early-onset AD have a Th2/Th22/Th17 predominance,45,46 with a lack of Th1, while adults have a Th22 predominance.47 It has also been observed that adolescents have higher levels of IL-22.48

Regarding prognostic biomarkers, CCL22 expression levels in the skin have been identified as a marker that predicts clinical improvement during the use of various targeted therapies such as topical crisaborole, CsA, and fezakinumab (anti-IL-22 monoclonal antibody).49

In managing patients with AD, decision-making for selecting treatment and guiding evaluation in individual patients can be complex and often subjective.50 The introduction of highly effective drugs has led to the development of treatment algorithms based on specific treatment response targets, using algorithms to guide decisions to continue, discontinue, or modify treatment.51 The “Treat-to-Target” (T2T) strategy is defined as a targeted treatment (towards remission or reduction of disease activity) and the application of strict controls (scheduled visits with respective treatment adjustments) to achieve a proposed goal.52 Another definition of T2T could be the therapeutic strategy of defining treatment with a specific objective through defined steps with constant evaluations to determine if the proposed objectives have been achieved.53

This approach provides a framework to support treatment options made using shared clinical information, and decision-making with patients, including discussion of relevant risk/benefit issues of existing or alternative treatments.50 While T2T is well-defined in other inflammatory/immunological pathologies, there are still no clearly established consensuses for dermatological diseases. However, T2T is highly relevant in AD, which represents a therapeutic challenge due to its heterogeneous clinical presentation and significant impact of symptoms on quality of life, especially pruritus.54

A recent international consensus on T2T in AD determined that patients should be evaluated with validated measures such as the Eczema Area and Severity Index (EASI), the Maximum Pruritus Numeric Rating Scale, the Dermatology Life Quality Index (DLQI), and the Patient-Oriented Eczema Measure at 3-and 6-months, using a T2T strategy. The Committee combined clinical experience with available recommendations and guidelines, including those from Harmonizing Outcome Measures for Eczema (HOME), to develop practical T2T criteria. A unanimous agreement was reached to evaluate patients with at least 1 of 2 physician-assessed outcome measures (EASI and Physician's Global Assessment) and at least 1 of 3 patient-reported outcome measures (Pruritus Numeric Rating Scale, DLQI, and Patient-Oriented Eczema Measure). With 3 medical visits per year to achieve the ideal therapeutic transition from flare control to induction and maintenance of remission. A treatment will be considered effective if at least one physician-assessed outcome goal and at least one patient-reported outcome goal are met. If target criteria are not met, modifications should be made to optimize the current treatment (e.g., increasing the dose or frequency of systemic therapy), adding adjunctive treatment (e.g., phototherapy or another systemic therapy), or changing the current treatment.51

In conclusion, although the T2T approach can become a useful tool to simplify therapeutic goals and management of AD, its foundation is just beginning to be built. A multidisciplinary approach, including a wide range of stakeholders, including patients, is needed to better define the essential components necessary to use T2T in AD.55