Atopic dermatitis (AD), commonly referred to as eczema, is a chronic, relapsing disease characterized by skin that is dry, itchy, inflamed, and prone to infection. It ranks 15th among all nonfatal diseases globally and carries the highest disease burden. Although the cause of AD is unknown, the following factors are associated with it:
- human genetic mutations (especially filaggrin),
- skin barrier disruption,
- inflammation-triggering allergens, and
- imbalances in the skin microbiome.
Knowing these factors forms the basis for most of the new targeted therapeutic approaches.
AD is associated with numerous comorbidities, including asthma, allergic rhinitis, food allergy, and non-atopic comorbidities like allergic contact dermatitis, anxiety, depression, suicidal thoughts, infections, and cardiovascular diseases. The symptoms and characteristics of AD, such as severe and persistent itch, prolonged and relapsing nature, chronic inflammation, and high risk of atopic or allergic comorbidity, may directly explain the elevated risk of mental disorders in these patients. Sleep disorders caused by itching may further strengthen the impact on sufferers’ mental health. Thus, the quality of life (QoL) is often markedly impaired in both adults and children with AD, including their families, owing to associated issues and tremendous efforts towards treatment.
Considering this overwhelming burden of AD on the physical, mental, and social health of patients and their families, there is an immediate need to develop new targeted therapies. The better the understanding of the pathogenesis of AD, the greater the development of more targeted topical and systemic medications that promise to be more efficacious and safer than the options currently available. Thus, future research should focus on long-term efficacy and safety and creation of best management options on an individual basis.
Although most patients with mild-to-moderate dermatitis respond well to topical corticosteroids, there still remains an urgent need for newer topical agents due to safety concerns associated with the prolonged use of topical steroids, especially on sensitive skin (e.g., the face), and due to the black box warning regarding use of topical calcineurin inhibitors towards the theoretical risk of malignancy. On the other hand, for patients with moderate-to-severe disease, systemic corticosteroids have been the only systemic agents that are approved by the Food and Drug Administration (FDA) despite their long-term use safety concerns and tendency to cause rebound effect upon discontinuation. Further, the use of phototherapy and immunosuppressants such as cyclosporine, methotrexate, mycophenolate mofetil, and azathioprine as an alternative to systemic steroids is limited by safety risks, the need for frequent laboratory monitoring, and variable therapeutic benefits.
Newer therapies:
Microbiome-targeted therapy: The human skin is home to diverse ecosystems like bacteria, viruses, and fungi, collectively known as the skin microbiome that are thought to play a vital role in offering protection from disease-causing microorganisms, boosting barrier protection, and aiding immune defenses. Severe cases of eczema are commonly treated with broad-spectrum antibiotics, which wipe out most of the bacteria, including beneficial species, thus causing an imbalance in the skin microbiome. Therefore, the goal of microbiome-targeted therapy is to kill only the disease-associated bacteria like Staphylococcus aureus, as in the case of AD, and avoid increasing the risk of developing antibiotic resistance by some strains. Research has found that certain strains of Staphylococcus hominis and Staphylococcus epidermis produce potent antimicrobial molecules known as lantibiotics in healthy human skin. These beneficial strains are far less common on the skin of people with AD. The lantibiotics work synergistically with LL-37, an antimicrobial molecule produced by the human immune system, to selectively kill Staphylococcus aureus, including methicillin-resistant strains (MRSA), and also block the production of Staphylococcus aureus toxins. Thus far, two independent phase 1 clinical trials demonstrated lantibiotics treatment to be safe, to show a significant decrease in Staphylococcus aureus, and to improve the symptoms in most patients; this is encouraging news for those hoping to develop microbiome-targeted therapy.
Emerging topical and systemic therapies: These therapies primarily target the type 2 immune pathway system. The FDA has lately approved 2 newer targeted medications for both children and adults, crisaborole 2% ointment (a nonsteroidal topical agent) and dupilumab (a monoclonal antibody blocking IL-4 available as a subcutaneous injection), with many others in the pipeline. Janus kinase inhibitors like tapinarof, an aryl hydrocarbon receptor agonist, are some new topical agents undergoing further trials. In addition to these approved drugs, other biologics targeting IL-13, IL-31, IL-33, OX40, and thymic stromal lymphopoietin are currently undergoing trials and showing outstanding efficacy and no serious long-term safety concerns.
Multidisciplinary management approach: AD is a disease leading to significant somatic suffering and psychological disturbance with a higher risk of mental disorders compared to those without AD. Hence, for successful management, a multidisciplinary approach, including psychological and social assessments along with the medical treatments of physical symptoms, should be addressed, thus emphasizing on the complete well-being of sufferers and their families.
Although, AD is one of the common skin diseases globally, it is less talked about socially. The condition causes physical discomfort, emotional distress, embarrassment, social stigma, and daily activity limitation. Thus, there is a profound need for enhanced and expanded research regarding the treatment and control of AD. We at Bioviser, with our team of experts, combine our deep industry experience with our knowledge to support your medical writing needs in the field of science and technology. Informed and thoughtful changes of public policy could reduce the future socioeconomic toll of AD on patients and their families.
