According to an analysis of the 2017 Global Burden of Disease study database, atopic dermatitis (AD) also known as atopic eczema is the leading contributor to all skin-related disability, affecting up to 2•4% of the global population (JAAD International. 2021). This burden falls particularly hard on health-care professionals, in whom occupational dermatitis affects up to 23% of people in nursing, as substantial risk factors are frequent handwashing and use of protective gloves. It therefore comes as no surprise that the COVID-19 pandemic has led to increased instances of skin irritation and disease in health-care workers because of prolonged use of personal protective equipment (PPE) and the chronic levels of stress that exacerbates AD. A survey done in Hubei (China) reported in March, 2020, by Journal of the American Academy of Dermatology measured the prevalence of skin trauma caused by continuous COVID-19 infection-prevention practices in hospital workers at 97%. This study was followed shortly in May, 2020, by a publication in British Medical Journal reporting increased cases of skin trauma in health-care workers in the UK. Frequent handwashing is a standard recommendation for reducing the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), to be undertaken by the global population. It is then possible that an increase in dermatitis will not only apply to health-care professionals.
AD is typically characterised by intense itching and chronic recurrence of circular eczematous lesions on the skin, both of which can vary with severity and length of onset. It is multifactorial, with genetic predisposition and environmental factors both known to contribute to onset of the condition. Its prevalence is dependent on familial history of AD and age, showing the highest instances in early childhood, tailing off in early adulthood and then peaking again in older populations. Lesions tend to also be age-specific in distribution, being few and diffuse in adults and occurring primarily on the hands and eyelids, but showing more acute facial or torso lesions in children.
Disruption to the skin barrier is considered the main cause for AD and there are two prevailing hypotheses regarding mechanism of action. The first is the so-called outside-in hypothesis, which proposes that weakening and subsequent disruption of the skin barrier is due to allergen induction and subsequent sensitisation of the antibody IgE. The skin is damaged from intense itching, leading to further exacerbation from allergen and microbe entry. This hypothesis supports the idea of an environmental factor in the initiation of AD, leading to inflammation as the cause of the breakdown of the skin barrier. A study published in EBioMedicine in July, 2020, by Lee and colleagues lends support to this theory, identifying fatty acid binding protein 5, a protein essential in ensuring skin barrier function, as a promoter of a T-helper-17 (Th-17) cell-induced cytokine response. The authors noted that increased expression of FABP5 led to increased epicutaneous IgE sensitisation, setting off this cascade.
The second hypothesis, the so-called inside-out hypothesis, suggests that AD occurs due to immune dysregulation, which is a consequence of skin barrier breakdown, not the cause. Filaggrin, encoded by the filaggrin gene (FLG) is a protein that binds to keratin fibres in epithelial cells that plays a pivotal role in maintaining the skin barrier. Mutations to FLG is the most common gene dysregulation known to result in AD. A review centred on filaggrin published by Annals of Allergy, Asthma & Immunology in October, 2020, reported that loss-of-function mutations or haploinsufficiency of FLG results in substantially increased risk of AD development and disease severity. FLG mutations also indicate a higher likelihood of disease persistence and subsequent development of allergic rhinitis and allergic asthma, also known as the atopic triad, or atopic march. The exact mechanisms by which this occurs, however, are yet to be fully understood.
Preventative approaches to reduce the frequency and severity of AD flare ups have focused on the avoidance of known allergens and maintenance of the skin barrier. Potential triggers include contact allergens, food, stress, fabrics, contact abrasion, and sweating. There is currently no definitive characteristic of a trigger and avoidance measures are typically discovered by individual monitoring. Adoption of a skincare routine that includes the daily use of emollients and specially formulated moisturisers to provide protection and relief from mild cases of AD is often recommended. These practices could help to enhance moisturisation, reduce skin dryness, inflammation, and itching.
Underneath the skin, the inflammatory profile of AD reflects the diverse nature of its triggers. Lesion sites can contain dendritic cells, IgE-producing B-cells, mast cells, basophils, and eosinophils. A common signalling pathway in AD is the type 2 inflammation response, including IL-4, IL-13, and IL-31, which are thought to have a role in the itch-scratch cycle. These findings have led to research focused on the inhibition of cytokine signalling as a means of treating AD symptoms.
When flare ups occur because of cytokine activity, the first line of treatment is the use of topical corticosteroid creams. The ability to apply these creams locally and intermittently is advantageous to help minimise side-effects. A few creams, such as those containing hydrocortisone, can be acquired without prescription for mild cases. Another option for alleviating itchiness is the use of antihistamines. Interestingly, although often prescribed for managing AD, studies are inconclusive on the efficacy of antihistamines for preventing flare ups. Other treatment options include UV phototherapy, orally administered corticosteroids, or immune inhibitors (eg, Janus Kinase (JAK) inhibitors).
Current Food & Drug Administration (FDA) approved JAK inhibitors ruxolitinib, tofacitinib, and baricitinib are used for the treatment of myelofibrosis and rheumatoid arthritis. Cytokines involved in the pathogenesis of AD, such as IL-31 and IL4Rα, which are implicated in pruritus, signal via the JAK-STAT pathway and research into repurposing these inhibitors to treat AD has been underway. In January, 2021, the National Eczema Association announced that the JAK inhibitors ruxolitinib, baricitinib, abrocitinib, and upadacitinib are under evaluation by the FDA for treatment of AD. In addition to topical delivery, these JAK inhibitors also offer effective oral therapy for severe widespread cases with minimal side-effects. This treatment option represents a potential game changer for managing patients with severe AD.
Because of the highly individualistic nature of AD, the need for patient education is of particular importance. Severity of disease recurrence can vary widely in an individual and it is important that there is an intrinsic ability to manage reactive behaviours, such as habitual scratching, skin and stress management, and use of topical corticosteroids and antihistamines. It is still unclear which health conditions the COVID-19 pandemic will bring, so continued innovation is needed especially in health care, where research into hypoallergenic PPE could prove valuable
AD has no known cure and its multifaceted risk and pathophysiology poses a challenge for effective treatment. Engaging continued support for research to understand the mechanisms, triggers, and ways to effectively manage and prevent AD onset is a worthwhile investment. Afterall, our skin is the largest and most effective pathogen deterrent we own.
EBioMedicine