Eczema, also known as atopic eczema or atopic dermatitis (AD), affects a considerable world population, with 101.27 million adults and 102.78 million children experiencing this condition. The overall prevalence rates were 2.0% [95% confidence interval (CI) 1.4–2.6] and 4.0% (95% CI 2.8–5.3) in adults and children, respectively.

Furthermore, this chronic inflammatory condition significantly burdens health services globally [1, 2]. Socioeconomic status (SES) influences the severity of AD and access to medical care, which are critical to managing the disease effectively. For families in low socioeconomic strata, the direct and indirect costs associated with AD, from health care expenses to days lost by caregivers, can exacerbate the socioeconomic challenges they face. Furthermore, disparities in access to health care, particularly in urban and disadvantaged areas, suggest a complex interaction between the severity of AD and available healthcare resources, underscoring the need for more inclusive healthcare strategies that can mitigate these disparities. Therefore, understanding the socioeconomic impact of AD is crucial for developing comprehensive management plans that extend beyond medical treatment to address the social determinants of health that affect patient outcomes [3].

Notably, the presentation of this disease is highly heterogeneous and sometimes unpredictable [4]. This condition manifests itself differently between racial and ethnic groups, which requires an individualized diagnostic and therapeutic approach. Typically, AD presents as erythematous and pruritic plaques. Still, the appearance of AD varies: Asian patients may present with more defined lesions and greater lichenification, whereas those of African descent often present with more extensor surfaces than flexor surfaces, with notable papules and periorbicular accentuation. In dark-skinned individuals, erythema may appear purplish or go unnoticed, complicating evaluations with standard severity scoring systems. In addition, postinflammatory pigment changes are more pronounced in dark skin. Recognizing these variations is crucial for accurate diagnosis and effective management of AD in diverse populations [5].

For a long time, it has been widely reported that, depending on the severity of this pathology, alterations are associated with different aspects of the quality of life (QoL), mental health, and labor productivity of patients, both in adult and pediatric populations [6–10]. In addition, the presence of AD is associated with other atopic comorbidities, such as asthma, allergic rhinitis, food allergies, and eosinophilic esophagitis. In addition, many other nonatopic comorbidities, such as psychiatric disorders (generalized anxiety disorders, depressive disorders, and suicidal ideations), infections, and cardiovascular diseases, are associated with AD (Figure 1) [11]. Although these comorbidities may be specific to pathology, lifestyle changes, particularly smoking, can affect the frequency of these comorbidities [12].

The causes of AD are complex and multifactorial. For a long time, it was considered the first atopic manifestation, marking the beginning of the so-called “atopic march”, which eventually led to asthma and allergic rhinitis [13]. However, the current understanding highlights the mutation in filaggrin (FLG) as the genetic factor associated with the highest risk of AD. Despite this, the importance of variants that influence the skin and the immune system is recognized [14].

The pathogenesis of this disease is dependent on three main interrelated factors: immune dysregulation, dysfunction of the epithelial barrier, and pruritus.

Immune dysregulation in the acute phase is mediated by innate immune cells, such as T-helper cell type 2 (Th2) lymphocytes, type 2 innate lymphoid cells, dendritic cells, and basophils, which generate Th2-type cytokines [interleukins (ILs) 4, 5, 13, 31]. In addition, epidermal keratinocytes can amplify the Th2-type response, producing alarmines such as thymic stromal lymphopoietin (TSLP), IL-23, and IL-33.

In the chronic phase of the disease, in addition to the Th2-type response, Th1, Th22, and Th17 lymphocytes are involved in the release of IL-4, IL-13, and IL-22, which inhibit the expression of FLG, increasing the deterioration of the epithelial barrier and perpetuating the pathophysiology of the disease [15].

As mentioned above, dysfunction of the epithelial barrier has an immunological implication. Still, in the same way, it has been widely associated with genetic components, mainly mutations in the FLG gene. FLG is a protein produced by the epidermal keratinocytes of the upper layer and promotes the production of moisturizing factors and a lipid matrix. This protein acts as an adhesive, holding the keratinocytes of the horny layer together. The mutation in this gene has been described mostly in the white population, and it can have a highly variable presentation in 10–50% of patients with AD. A decrease in the lipid matrix leads to a decrease in the production of antimicrobial peptides, which changes the skin microbiome. This phenomenon is called dysbiosis and predisposes patients to complications associated with AD, such as impetigo and epidermal abscesses. Alterations in epidermal barrier function allow allergens to penetrate the skin, generate allergic sensitization, and perpetuate the clinical picture of patients [16].

Pruritus is one of the fundamental components that results in mechanical disruption of the epithelial membrane. This process is generated by the production of pruritogens released in the acute phase of the disease by the inflammatory cells involved. The main molecules involved are IL-4, IL-13, TSLP, and histamine. These bind to receptors on C-type sensory nerve fibers and Aδ nerve fibers in the dermis and epidermis, which perceive itching and pain [17]. Importantly, these effects are generated not only by the aforementioned inflammatory process but also by the scratching process. This results in hypersensitization of the nerve fibers secondary to the itch-scratch cycle. They act on IL-4Rα, expressed in peripheral nerves, transmitting chronic itching through the Janus kinase (JAK) 1 signaling pathway [16].

Recent epidemiological studies indicate substantial variation in the global prevalence of AD, influenced by factors such as age, sex, geographic location, and race. The global prevalence is approximately 2.0% in adults and 4.0% in children. Women are generally more affected than men, with prevalence rates of 2.8% in women (impacting an estimated 108.29 million) and 2.4% in men (95 million) [2, 18]. Notably, the incidence of AD in industrialized countries has doubled or tripled in recent decades, likely due to increased exposure to environmental pollutants [19].

A 12-month, international cross-sectional web-based survey by Barbarot et al. [20] conducted across regions in the Americas, Europe, and Asia reported that the prevalence of AD in these areas ranges from 2.1% to 4.9%. Similarly, Silverberg et al. [21], focusing on children aged 6 months to 18 years in regions including the Americas, Europe, the Middle East, and Eurasia, observed a prevalence range of 2.7% to 20.1%, reflecting significant regional variability.

In Europe, the financial impact of moderate-to-severe AD is substantial. A systematic review found that the total costs, including direct medical expenses and productivity losses, can reach up to €20,695 per person annually for adults with uncontrolled moderate-to-severe AD symptoms. Key contributors to these expenses include:

Direct medical costs: These expenses cover prescription medications, specialist visits, and other healthcare services.

The clinical manifestations of AD vary depending on age, sex, race, and geographic location. The characteristic dermatological findings of AD include pruritus (itching), xerosis (dry skin), and eczema. Eczema in AD progresses through different stages—acute, subacute, or chronic—each with distinct clinical features and severity levels classified as mild, moderate, or severe [16].

Acute stage: Typically involves intense itching and red, inflamed skin.

For a better understanding of the morphological presentation of AD, it was classified into three phases according to the age of presentation and the topography of the lesions (Table 1) [33].

The diagnosis of AD is made primarily through clinical evaluation and specific diagnostic criteria, such as those developed by the American Academy of Dermatology (AAD) and other specialized organizations. An accurate assessment of disease activity and burden is essential, which is best measured via composite scores that assess both objective and subjective symptoms, such as SCORing Atopic Dermatitis (SCORAD) [34].

The diagnosis of AD remains primarily clinical, but with the increasing availability of new therapies, there is a need to update and consolidate current diagnostic criteria to ensure that they reflect recent developments in treatment. Recent sources highlight the importance of correct identification and management of AD, which includes not only attention to skin symptoms but also to comorbidities and complicating factors that can influence the course of the disease [35].

One stands out in the different clinical criteria we can currently use since it had been used previously; however, the following article highlights the sensitivity and specificity of the Hanifin and Rajka (HR) criteria compared with the others. This article discusses the variability and challenges associated with the diagnostic criteria for AD used in clinical trials. Notably, the HR criteria are the most commonly used criteria, appearing in 69.2% of the tests that specify diagnostic criteria. Other criteria, such as the UK’s refinement of the HR criteria, the Japanese Dermatological Association (JDA) criteria, and the AAD criteria, are also mentioned but are used less frequently. Variability in the diagnostic criteria, which may affect the comparability of the results of the trials and introduce biases in the inclusion of patients, the need to standardize the diagnostic criteria in the clinical trials of AD is emphasized to improve the interpretability and inclusiveness of the results, especially for racial and ethnic minorities. Vakharia et al. [36] suggested that initiatives such as the Harmonizing Outcome Measures for Eczema (HOME) group should work toward establishing an international consensus on the diagnostic criteria for AD.

In general, the HR criteria are currently the most important and widely used in clinical trials, but there is a clear need for a more standardized approach to improve the consistency and reliability of research results in AD [36].

Effective AD management must have a comprehensive and individualized approach that addresses the disease’s symptoms and underlying causes. Central to this approach is educating patients about factors that can trigger or exacerbate AD symptoms, such as environmental irritants, allergens, stress, and weather changes. By identifying and avoiding these triggers, patients can reduce the frequency and severity of flare-ups. Maintaining the integrity of the skin barrier is also crucial; regular use of emollients supports skin hydration and barrier function. Topical treatments, including corticosteroids and calcineurin inhibitors, are primary therapies for reducing inflammation and alleviating symptoms during acute episodes. In more severe or persistent cases, systemic immunosuppressants and emerging biologic therapies, such as monoclonal antibodies (mAbs) and JAK inhibitors (JAKis), offer promising alternatives. Although evidence varies, complementary and alternative medicine (CAM) therapies have also gained interest for their potential benefits. Patient education and self-care programs, like “eczema schools”, empower individuals and their families with knowledge and skills to manage AD effectively, improving QoL. This section explores the multifaceted strategies involved in treating AD, emphasizing the importance of a holistic approach integrating medical therapies with patient education and proactive skin care.

Recent developments in understanding the pathogenesis of AD have catalyzed the introduction of biologic treatments and targeted therapies, providing promising options for patients with moderate-to-severe disease. These therapies specifically address type 2 inflammation pathways, which are central to AD pathophysiology, offering targeted efficacy with improved safety profiles.

AD is a chronic inflammatory disease with a complex pathophysiology that involves epithelial barrier dysfunction, immune dysregulation, and pruritus, which contributes to its high degree of clinical heterogeneity. The global prevalence of AD continues to increase, particularly in industrialized countries, underscoring the need for a multidimensional approach to its management.

The development of new therapies, such as those mentioned above, especially in moderate to severe cases, not only offers significant improvements in clinical symptoms but also addresses associated comorbidities, improving the QoL of patients. However, challenges persist, such as the need to standardize diagnostic criteria and long-term safety assessment, as well as the accessibility of these emerging treatments.

The treatment of AD is in a transition phase toward precision medicine, where the identification of specific markers and the development of targeted therapies promise to personalize and optimize the management of this condition. The integration of new therapeutic strategies with a multidisciplinary approach, which also considers psychosocial factors and patient education, will be key to improving the results of each patient.