When stress writes on the skin: the secret circuit that makes eczema explode

For years we dismissed it with a phrase somewhere between insight and resignation: 'I got it from stress'. Now, however, that those skin rashes (the so-called 'rash') are closely linked by a cause-and-effect relationship to severe stress, such as before an exam at university or an important presentation at work, is no longer just a feeling. Research published in Science shows that stress can 'set fire' to the skin, inflaming it through a biological circuit that starts in the head. To analyse this phenomenon in more depth, Jiahe Tian and colleagues from Fudan University in Shanghai, (China) analysed clinical data from 51 patients with eczema, together with complementary mouse models, to examine the relationship between stress and inflammatory immune responses in the skin.

Brain and skin are connected by a direct line. And when we are under pressure, that red line can turn into an inflammatory short circuit. And there is a precise moment when stress stops being invisible. It is no longer just a looping thought or a gnawing at the pit of the stomach, but starts writing on the skin. That gets red, itchy, inflamed. And behind that outburst there is a biological circuit, a thread stretched between two worlds that are anything but separate. On the one hand, the mind under pressure, on the other, the skin that is inflamed. In between, a dialogue between nerve signals and immune cells. When stress increases, that dialogue rises in tone. It becomes faster, more intense. And, at a certain point, it explodes.

It all starts in the sympathetic nervous system, the one that activates uncontrollably when we go into 'alert' mode. Heartbeats speed up, muscles contract, the body prepares to react (or flee). But it doesn't end there. Certain neurons (a very specific population: the Pdyn+) extend their zone of influence to the skin and when they perceive stress, they release a kind of chemical message, a molecule (the CCL11.E) that functions as a recall for certain cells of the immune system. These neurons in particular 'recruit' eosinophils (immune system cells known for their role in allergies) through the CCL11-CCR3 signalling pathway and activate them via the beta-2 adrenergic receptor. For their part, eosinophils respond to that signal like following the light of a lighthouse in the dark of night and, once in the skin, do what they do best: release inflammatory substances. Result? The skin becomes red, itching increases, eczema 'patches' appear on the hands, elbows, affecting more or less extensive areas.

Those who suffer from atopic dermatitis have experienced this mechanism first-hand many times, the result of this close, almost intimate dialogue between the nerves and the immune system. And conducting the orchestra is stress, which transforms an emotion into a highly visible physical reaction. But that's not all. It triggers a well-known vicious circle: stress 'ignites' the itch, the itch leads to scratching, in this way the inflammation increases more and more and damages the skin. These negative emotions written on the skin then become immediately visible to the world and this generates new waves of stress. In short, it is a system that feeds on itself, causing increasing discomfort to the mind and body. But the study published in Science has finally unmasked this circuit, giving it names, molecules, receptors. And when a pathological phenomenon finally has a face, it also becomes a possible therapeutic target. In short, in the future, we could intervene before inflammation explodes, interrupt that signal, switch off that pathological direct line between brain and skin. Until now, stress was considered a difficult factor to measure and even more difficult to treat.

This research overturns the perspective because it identifies precise targets on which to intervene: the signal between neurons and eosinophils, the CCL11 molecule, and receptors (such as β2) that amplify the inflammatory response. This means that in the future we might not just treat the symptoms, i.e. intervene downstream, but block the effect of stress on the skin upstream. There is, however, another, even more immediate key. If stress can produce a direct biological effect, then managing it becomes an integral part of the cure, resorting for the time being to techniques such as mindfulness, physical activity and regular sleep that can influence the mechanisms that trigger inflammation. The skin, after all, confirms itself as what it has always been: a border to the outside world but also the mirror of what is going on inside us, sometimes telling loud and clear, with an immediate and disturbing language. The skin is not just a covering, but an 'intelligent' organ, traversed by nerve fibres and immune cells that communicate with each other.