Atopic dermatitis: skin barrier, microbiome and new treatments

Why is atopic dermatitis at the heart of scientific news?

Atopic dermatitis (or atopic eczema) is the most common chronic inflammatory skin disease: it affects around one in five children and almost one in ten adults in Western countries. Long summarised as "dry, itchy skin", it is now understood as a complex disease at the crossroads of three major mechanisms: an impaired skin barrier, a type-2 immune inflammation and a disrupted skin microbiome.

This new understanding has transformed care. Since 2017, a generation of targeted treatments — biologics and JAK inhibitors — has changed the outlook for moderate-to-severe disease, which for years had no satisfactory solution.

The skin barrier: the central role of filaggrin

The outermost layer of the epidermis works like a protective wall. Filaggrin, a key protein, contributes to the cohesion of this wall and to the production of natural moisturising factors. Loss-of-function mutations in the filaggrin gene (described as early as 2006) are one of the main predisposing factors for atopic dermatitis.

When the barrier fails, the skin loses more water (increased transepidermal water loss) and lets allergens, irritants and microbes penetrate more easily. This "outside-in" phenomenon sustains inflammation and scratching. That is why restoring the barrier with emollients remains the foundation of every treatment, even in the era of targeted molecules. For a complete patient-oriented overview, see our guide Everything about atopic dermatitis.

The skin microbiome: dysbiosis and Staphylococcus aureus

The skin hosts a balanced microbial ecosystem. In atopic dermatitis this balance breaks down: microbial diversity decreases and one bacterium, Staphylococcus aureus, takes over, especially during flares.

This staphylococcus produces toxins that worsen inflammation, promote scratching and weaken the barrier further — a genuine vicious circle. Current research is exploring approaches to rebalance the microbiome ("beneficial" bacteria, postbiotics), but these remain experimental. To date, it is mainly the control of inflammation that indirectly restores a healthier microbiome.

Type-2 inflammation: the molecular key

At the core of the disease lies a so-called "type-2" inflammation, driven by specific immune messengers. Three of them play a major role:

• interleukin-4 and interleukin-13 (IL-4 and IL-13): they sustain inflammation and further damage the skin barrier;
• interleukin-31 (IL-31): often nicknamed the "itch cytokine", it is a direct driver of pruritus;
• TSLP and other alarm signals released by damaged skin, which trigger the inflammatory cascade.

Identifying these messengers was decisive: it became possible to block them one by one, rather than dampening the whole immune system.

Biologics: dupilumab, tralokinumab, lebrikizumab, nemolizumab

Biologics are antibodies given by subcutaneous injection, designed to neutralise one inflammatory messenger precisely.

• Dupilumab: the first of its class, it blocks both IL-4 and IL-13. Approved since 2017, it has shown efficacy in adults and children with moderate-to-severe disease, with several years of experience.
• Tralokinumab and lebrikizumab: they specifically target IL-13.
• Nemolizumab: it targets the IL-31 receptor and focuses above all on itch, often the most disabling symptom.

These treatments have a broadly favourable safety profile, without heavy blood monitoring. The most characteristic side effect of dupilumab remains conjunctivitis, generally manageable. Biologics are particularly suited to chronic and widespread disease.

JAK inhibitors: a new oral and topical generation

JAK inhibitors act "upstream", on an intracellular signalling pathway shared by several cytokines. They come in two forms:

• oral (upadacitinib, abrocitinib, baricitinib): their action is fast and powerful, especially on itch, which is sometimes relieved within a few days;
• topical (ruxolitinib cream): useful for more localised disease.

This power comes with a trade-off: the oral forms require baseline testing and monitoring (blood tests, vigilance for infections and certain cardiovascular and thrombotic risks). Their prescription is therefore supervised and individualised, after medical assessment.

Where does research stand?

Several promising avenues are emerging:

• prevention: the early use of emollients in at-risk infants has been studied, with still-mixed results;
• microbiome therapies: rebalancing the skin flora to limit S. aureus;
• new targets (such as the OX40 pathway or TSLP), under evaluation;
• personalised medicine: identifying markers to choose the right treatment from the outset.

Diet and lifestyle also raise high expectations; we review them in our guide Diet and atopic dermatitis. In children, management has specific features detailed in the guide Childhood atopic dermatitis.

In summary

Atopic dermatitis perfectly illustrates the recent progress of skin medicine. By understanding the trio of skin barrier – microbiome – type-2 inflammation, research has produced targeted treatments that genuinely change the lives of patients with moderate-to-severe disease.

Emollients and barrier care remain essential every day; biologics and JAK inhibitors now offer effective options when topical treatments are no longer enough. The choice is an individualised medical decision.

The Clínica Valorian analysis

What stands out is the shift in perspective: atopic dermatitis is no longer an inevitability that is temporarily "soothed", but a disease whose mechanisms we understand better and better. In our practice, we always combine a rigorous restoration of the skin barrier with a precise assessment of severity and its impact (sleep, quality of life, itch) before considering a targeted systemic treatment.

The goal is not only to clear the lesions, but to make the skin durably comfortable, choosing, for each person, the best-suited and best-tolerated option.