
What Is Atopic Dermatitis?
More than one person in five will suffer an outbreak of atopic dermatitis at some point in their lives.
Atopic dermatitis is an extremely common form of eczema. Most often it occurs in individuals with a family or personal history of other ‘allergic’ disorders, such as food allergies, asthma and hay fever. Typically, the dermatitis starts in infancy or early childhood with recurrent outbreaks of red, itchy rashes. While outbreaks can involve any part of the skin, some areas are more commonly affected. In infants and young children, the dermatitis most often erupts on the face, scalp, and the outer surfaces of arms and legs, while in older children and adults, involvement of the folds of the elbows and knees is typical. Hands are commonly affected at any age. Some adults only have outbreaks on their hands, while others may have widespread, treatment-resistant disease.
There are treatments for atopic dermatitis, but no cures.
Many effective anti-inflammatory therapies are available for atopic dermatitis. Yet, to the frustration of patients and their caregivers, the itchy rashes come back as soon as these medications are stopped. Parents are often offered the hope that their child will likely one day ‘outgrow’ his or her eczema. But not all children do – and, as a result, many people continue to struggle with atopic dermatitis throughout their adult years.
What Causes Atopic Dermatitis?
So much suffering for so many for so long fuels an urgency to understand what is causing this condition. In addition, the prevalence of allergic diseases, including atopic dermatitis, are on the rise – especially in developed countries, such as the United States and European Union. This increase in the number of people who are being affected and the increased severity of their disease has added to this sense of urgency to understand what is behind it.
At present, there are two competing theories for the cause of atopic dermatitis. These can be thought of as the “Inside-Out” or “Immune Dysregulation Hypothesis” vs. the “Outside-In” or “Barrier-Driven Hypothesis”. It will come as no surprise to our readers that we are proponents of the latter. But since the immunological theory has been around the longest, and is still the most popular, let’s start with it.
Atopic Dermatitis Comes From The Inside: The Immune Dysregulation Hypothesis.
The fact that atopic dermatitis is often associated with other allergic disorders has fueled the prevailing view that it is caused by a ‘dysregulation’ of the immune system. This dysregulation produces a shift towards an allergic-type of immune response to foreign antigens. In this type of immune response, antigens can stimulate the production of specific antibodies of the immunoglobulin-E (Ig-E) type. These Ig-E antibodies bind to the antigens and cause mast cells to release their stores of histamine that can trigger itch in the skin and constriction of the bronchial tubes in the lungs. Simultaneously, these antigens also signal a ‘Th-2 type‘ inflammatory response in skin that results in dermatitis – the rash we can see and feel.
Are allergic diseases, like asthma and atopic dermatitis, becoming more prevalent because we are too clean?
One corollary of this “inside-to-outside” view is the so-called ‘hygiene-hypothesis’ that attempts to account for why there is so much more atopic dermatitis and asthma these days. According to this concept, our urban lifestyle, with smaller families and a lack of exposure to ‘barnyard’ life, places us in a relatively clean, ‘bug-free’ world. By failing to expose us to disease-causing microbes, this ‘too-clean’ lifestyle fails to properly train our immune systems to respond to foreign antigens the ‘right way’, by making the ‘good’ types of disease-fighting antibodies, such as Ig-G or Ig-M, and inducing a Th-1 immune response. Instead, we respond in the ‘wrong-way’, by becoming allergic and producing Ig-E and a Th-2 response.
This immune-centered concept of atopic dermatitis is supported by the benefits patients derive from anti-inflammatory treatments, like topical steroids (cortisones or ‘corticosteroids’). But cortisones have a very broad inhibitory effect on the immune system, and they can also produce other side effects unrelated to their effects on the immune system. Hence, there has been great interest in developing more specific inhibitors – ones that will only target those parts of the immune response that are ‘overactive’ in atopic dermatitis.
Several of these new generation, highly specific, immunosuppressant drugs have passed the study phase and are now available for use in the clinics.
While, these new designer-drugs seem to be quite effective, particularly in people with severe disease that has been resistant to standard treatments. But they are very expensive – to the point that for many patients, they are out of the question. Moreover, as very new drugs, their safety long-term is unknown.
Why the Inside-Out, Immune Dysregulation Theory Is ‘Leaky’.
It is ironic that the same genetic research, which led to the development of these new immunosuppressant therapies, also provided the first major crack in the Inside-Out, Immune Dysregulation hypothesis.
Studies undertaken in the search for the genes that predispose people to develop atopic dermatitis revealed, to many people’s surprise, that the strongest links are not to genes of the immune system, but rather to ones that impair the skin’s permeability barrier. We were not among the surprised, because we had predicted some years earlier that the basic problem in atopic dermatitis is a defective skin barrier. And indeed many studies, by ourselves and others, have demonstrated that the barrier is ‘leaky’ in the skin of patients with atopic dermatitis. Yet, it took these genetic discoveries to finally put the Outside-In Barrier-Driven theory firmly on the map.
A Defective Skin Barrier Is The Egg That Hatches An Itchy, Rashy Chicken
If a barrier-related gene is firmly linked to atopic dermatitis, then this suggests that the barrier defect could indeed come first. Instead of the immunological defect causing an impaired skin barrier, now, thanks to these genetic studies, it looked like an impaired skin barrier could be producing the immunological problems of atopic dermatitis. Indeed, a recent study has shown that the skin barrier is defective in babies long before they ever develop the rash of atopic dermatitis.
Atopic Dermatitis Is Caused By The Outside Getting In: The Barrier-Driven Theory
According to the Outside-In view, the fundamental problem in atopic dermatitis is an impaired skin barrier. The main purpose of the skin’s permeability barrier is to hold in our body’s precious water – to prevent its loss through evaporation into a dry atmosphere at the skin’s surface. This same barrier is charged with keeping foreign substances from entering our body through the skin.
Not only is atopic dermatitis a ‘barrier disease’, it is often triggered or worsened by external insults that put further stress the skin’s barrier system. Colonization of the skin surface by Staph. aureus is a well known trigger of atopic dermatitis. Like the barrier defect, skin colonization by bad strains of Staph. can precede the development of the first outbreak of dermatitis in babies. Again, this was not surprising to us, since we had discovered several years ago that the skin’s barrier to water loss and its barrier to infection – (its ‘permeability’ and ‘antimicrobial’ barriers) – are tightly joined.
If either one of these barrier’s – permeability or antimicrobial – is impaired, the other will not work well either.
Both the skin’s permeability barrier and its antimicrobial barriers are abnormal before the rash of atopic dermatitis appears. The fact atopic dermatitis is linked to changes in barrier-related genes, suggests that the weakness in the skin’s water barrier is most fundamental of these two barriers.
Several other external forces can trigger atopic dermatitis by further weakening the skin’s barrier. Prolonged exposure to low humidity, as occurs in our homes as they are warmed with forced air heating during winter, is one such trigger. When the humidity is low, skin must work harder to hold our body’s water inside. The skin of people prone to atopic dermatitis can’t adequately respond by tightening its barrier – it can’t build a better ‘fence’.
Another common trigger is ‘over bathing’, through the use of harsh soaps and hot water. Just as we immerse a frying pan in hot water and scour it with detergents to clean its greasy residue, over-zealous bathing practices can strip the skin of some of the natural fats (‘lipids’) it uses to construct a water-tight barrier, and trigger a flare of eczema. (For more on these triggers, sign up to receive our free booklet, “Taking Good Care Of Your Skin”). Experiencing psychological stress can trigger outbreaks by further impairing the skin’s barrier. Even exposure to air pollution can trigger eczema.
The Barrier Rules
It is essential to our survival as watery beings surrounded by a dry atmosphere that we maintain an effective barrier against dehydration. Fortunately, our epidermis is a smart organ and keeps watch over how its barrier is doing. If too much water is leaking out, it sends out signals that will set in motion efforts to repair itself. Molecular signals tell the epidermal stem cells to multiple to make more cells, and tell its daughter cells to make more lipids – all to fix the leaky barrier. Yet, because of its genetic underpinnings, the barrier in atopic dermatitis cannot be fully restored to normal. Consequently, more signaling molecules (‘cytokines’) continue to be released.
It’s A Vicious Cycle
Overtime as the barrier continues to leak, some of these signalling molecules also attract inflammatory (“T”) cells into the skin. You can think of this as a “this is an emergency, pull out all the stops” sort of move. These inflammatory cells – perhaps in a “misguided effort to help” – produce other signaling molecules that have the unfortunate effect of further impairing the skin’s barrier. For example, one of the cytokines released by inflammatory cells inhibits the skin’s production of ‘ceramides’, a type of lipid that is a key component of the skin’s barrier apparatus. In sum, a skin barrier that is unable to repair itself provokes an inflammatory response that further damages the barrier – which creates more inflammation.
Once underway, atopic dermatitis is like a snowball rolling downhill – it will keep going and grow bigger as it rolls downward.
But that’s not all – now let’s bring in allergy. When the skin’s barrier is leaky, foreign antigens in the environment can more easily penetrate to deeper layers of the skin and further provoke an immune response. Once again, the immune response produces a further weakness in the skin’s barrier, allowing an additional influx of foreign antigens and further fanning the flames.
The Implications Of The Outside-In Concept For Effective Treatment Of Atopic Dermatitis
In treating atopic dermatitis, our therapies need to start with consideration of: 1) how “big is the snowball” – or how severe is the outbreak; and 2) “how fast is it rolling” – or how ‘strong’ does the treatment need to be to stop its momentum.
With this disease perspective in mind, let us return to the issue of the new immunological treatments for atopic dermatitis – the so-called new ‘biologics’. When should they be used? Who are they for? In our view, it can be appropriate to use one of these new, ‘wonder drugs’ for more severe disease that has been resistant to standard therapies, such as topical cortisones – to put a stop to an out of control, vicious cycle of inflammation. But remember, anti-inflammatory medications alone do not correct the underlying barrier defect. While suppressing the immune component of the disease will certainly reduce inflammation and itch, they do not address the underlying cause of atopic dermatitis – a leaky skin barrier.
Most importantly, failure to address the barrier defect will inevitably lead to relapse – and the need for more anti-inflammatory medications.
For this reason, all therapeutic programs should include strategies that attempt to correct the barrier. In most cases, physicians recommend rehydration of the skin with moisturizers and other topical emollients in an attempt to rehydrate the skin and repair the barrier. In mild to moderate disease, the use of effective forms of topical barrier repair therapy alone, such as EpiCeram® emulsion, may also be sufficient to resolve the inflammation. For example, in this setting EpiCeram® has been shown to be as effective as topical corticosteroids, without any of their side effects. Antihistamines are often recommended to help relieve the itch while efforts are underway to bring the dermatitis under control. Antihistamines, too, may have the additional benefit of improving the skin’s barrier. If the dermatitis appears to be infected, an antibiotic directed against Staph. and sometimes Strep. may be prescribed.
Bottom Line: Managing atopic dermatitis is a little bit like juggling balls – you have to address the problem from several different angles and all at once – to be effective.
This juggling act includes: 1) using anti-inflammatory medications to reduce inflammation and itch; 2) treating infections, if present, with antibiotics; 3) identifying triggers and, where possible avoiding them; and, most critically, 4) improving the skin’s barrier. If simple measures like good skin care practices, barrier repair medications and low strength, topical corticosteroids have not brought relief, it’s time to see a dermatologist. Parents of children who continue to have a hard time with their eczema may benefit from consultation with a pediatric dermatologist.
Effective treatment of atopic dermatitis may seem complex at times, but its possible. Everybody deserves healthy and comfortable skin.
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