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RESEARCH FROM LABS AROUND THE WOLD

Top 5 Scientific Discoveries About Skin Of The Decade

December 26, 2019 By Peter M. Elias, M.D. & Mary L. Williams, M.D. Leave a Comment

We have learned a lot about skin and its permeability barrier in recent years.  Here are our picks for the top 5 discoveries about skin of the past decade.  Some of these arose from work in our laboratory, and some from research by other investigators.

  • 1. Common inflammatory skin diseases, like the eczemas and even psoriasis, begin with an inherited weakness in the skin’s barrier. 

This revelation came pretty much as a surprise to everyone in the dermatologic research community – although not to us. Our work on the skin barrier had long before led us to this conclusion.  But heretofore most other research into these common disorders had focused on the role of the immune system.  The question was – which is the chicken and which the egg?  Both the barrier and inflammation were clearly involved in the disease process – but which came first? 

It was the work of the new generation of geneticists – who, in their search for the genes that underlay atopic dermatitis, (which have a strong familial bent), discovered that genes of the skin’s barrier system are commonly altered in people who suffer from these disorders. 

The pendulum of opinion in regard their causation has not completely swung from the immunological to the barrier, but it certainly is gravitating in that direction.  Work in progress includes studies to see whether preventing the development of a defective barrier through the use of barrier repair therapies can also prevent the development of atopic dermatitis and other allergic disorders. Stay tuned here.

  • 2. Skin plays host to an amazing diversity of microbes – both good and bad. 

In the past, when our knowledge of the skin’s microbial flora depended upon our ability to grow these organisms in the laboratory, we assumed there were only  limited numbers of ‘normal’ and ‘disease-causing’ microbes that lived on skin.  Now with the advent of RNA-sequencing technology, we have learned that the skin – like the gastrointestinal tract – hosts a large number of micro-organisms. 

The role of the skin’s microbiome in health and disease is beginning to be unraveled.  Stay tuned for more insights on that front.

  • 3. Air pollution provokes skin diseases and accelerates skin aging.

Air pollution has been with us for a long time, and we have long been aware that it is a problem for people with chronic lung conditions, like asthma.  But in recent years we have learned that it can also be harmful to pregnant women and their babies, to people with heart disease, and even for those with kidney and psychiatric conditions.  The close ties between air pollution and climate change are also now receiving attention.

Just in the past decade we have learned that pollution also is bad for the skin – producing flares of eczemas and acne, and accelerating skin aging. That skin is also affected by air pollution should come as no surprise.  Skin after all is bathed in the polluted air that surrounds us.  And although skin evolved robust defenses against assault by foreign chemicals, its capabilities are finite and can be overwhelmed.  Our knowledge about the effects of air pollution on skin is in its infancy.  We predict you will need to stay tuned for more here, too.

  • 4. Age-related abnormalities in the skin’s permeability barrier provoke systemic inflammation.

We learned some years ago that the skin’s barrier becomes weaker as we age – a defect that begins by age 50 in most people.  It has also been known for some time that many of the common diseases associated with aging – for example, heart disease, Alzheimer’s disease, and osteoarthritis – are associated with markers of chronic inflammation carried in the blood.  Recently, we discovered that the age-related barrier defect in the skin results in the release of inflammatory markers into the blood stream.  And conversely, correction of the skin’s barrier defect, (through the use a topical barrier-repair formulation), can reduce the load of  chronic inflammation markers in the blood. 

These results suggest that the chronic inflammation in the blood that is provoking many common age-related diseases could be arising from the skin.  If so, then correction of the age-related barrier defect might prevent some of these age-related  disorders of heart, brain and joints.  This concept will require further experimental proof, so stay tuned, once again.

  • 5. Many products that claim to moisturize the skin are actually harmful, particularly for people with ‘sensitive skin’.

This is another chapter in the age old story of ‘caveat emptor’ – buyer beware!  Unfortunately, there is little requirement for scientific truth in the claims on the packages of cosmetics and other products sold over the counter. 

In this research, we learned that many products which claim to be beneficial for moisturizing dry skin, are actually harmful.  Improvements are only temporary, and overtime  they can worsen the skin barrier and provoke more symptoms of dryness and itch – especially in those of us who have sensitive skin to begin with.   

Sunscreens In The Blood?

August 30, 2019 By Mary L Williams, M.D. Leave a Comment

Matta et al have now shown what we all should have seen coming: the chemicals of our most common and effective sunscreens do not just sit on the skin’s surface and soak up damaging ultraviolet rays before these rays can penetrate to deeper layers and injure nuclear DNA. No – these chemicals themselves can penetrate the skin’s barrier and enter the blood stream (and from whence they can theoretically go anywhere in the body). We should have seen this coming because: a) the permeability barrier is a biological construct, and as such, has its limitations and vulnerabilities; and b) previous studies have found some of these ingredients in human urine and breast milk.

[Read more…] about Sunscreens In The Blood?

What Time Is Your Skin?

February 9, 2019 By Mary L Williams, M.D. Leave a Comment

Body Time

As the Earth’s rotation creates alternating hours of light and dark, we adapt our behaviors to harmonize with this daily cycle. An internal ‘clock’ adjusts our metabolism to fit the demands of our usual daytime and nighttime activities. This makes good sense, since our metabolic needs are very different when we are sleeping and fasting, in comparison to what we need when awake, working and eating. Until recently, it was believed that this biological clock resided solely in the brain – in the hypothalamus to be precise – and that the effects of this clock on our metabolism were mediated by hormones, like melatonin and cortisol. In this traditional scheme, light entering the eye, stimulates the retina, transmitting messages along the optic nerve to regulate the activity of the cells in this central clock and their output of these hormones or their activators. That is still true – but it’s not the whole story.

Skin Can Tell Time, Too!

It turns out that nearly all cells have clocks of their own, and melatonin and cortisol released by a central clock are not the only signals to which these ‘peripheral’ clocks are tuned. Now, recent research suggests that the skin may provide the key to understanding our daily or ‘circadian’ rhythms and their importance in medical practice. Epidermis, these authors demonstrate, may be the ideal tissue to study. It possesses a robust peripheral clock, with a set of metabolic pathways having a reliable, diurnal cycle of activity – and it has the added advantage of being readily accessible.

Why is this potentially important? First, in the past physicians could evaluate the timing of a patient’s internal clock only by using difficult to administer and time-consuming assays of blood melatonin levels under standardized laboratory conditions. These assays were not practical for use in clinical settings. But, if Wu, et al, are correct, it should soon be possible to assess the status of a person’s internal clock with a single, easily obtained skin samples, such as plucked hairs or tape-stripped skin.

When Should I Take My Pills, Doctor? Have That Operation? Apply My Creams?

Information about the timing of our internal clocks could be helpful to our doctors, when they prescribe medications or schedule surgery. Other research has shown that ‘circadian’ fluctuations in metabolism impact both the effectiveness of some medications, and the outcomes of surgery. Knowing the status of a patient’s clock might be particularly important for night shift workers, in whom the normal circadian rhythm may well be disrupted. By assessing his or her skin’s clock, physicians might be able to ascertain the best time of day (or night) for a night-time worker to take medications or undergo surgery

The skin’s clock also regulates the repair mechanisms that protect against the development of the types of DNA damage from ultraviolet light linked to skin cancers. Knowing which hours of sunlight are the most risky for producing unrepaired genetic damages that could result in skin cancer for a patient, could help their dermatologist identify the best time for their light treatments – to achieve the desired therapeutic effect with the lowest risk of inducing cancer later on. Our skin’s clock also regulates melanin synthesis – the protein in skin that produces our shades of color. Timing treatments for vitiligo, (a common skin condition of decreased skin pigmentation), around the hours when melanin synthesis is peaking might increase the effectiveness of these therapies. In addition, the knowledge that these clock genes regulate pigment production could lead to new approaches to therapy for this and other pigmentation disorders. Hair is another skin product whose growth is tuned to its biological clock. Clearly, further understanding of the skin’s clocking system may have important therapeutic spin-offs for a variety of skin conditions.

Fourth, and of particular interest to our readers, is the fact that circadian rhythms are also known to modify the efficiency of our skin’s permeability barrier. Knowledge of the timing of a patient’s clock might be predictive of the best time to apply certain topical medications. If the desired effect of the drug requires it to penetrate the permeability barrier, then it might be optimal to apply it when the barrier is less efficient in keeping out foreign chemicals. Conversely, if the benefit takes place on the surface of the skin – as with topical medications directed against ectoparasites, like lice or scabies – then applying the treatment when the barrier is most robust could prevent unwanted side effects, such as neurotoxicity from the scabicide, lindane.

Our Smart Skin

This developing story of the skin’s biological clock can serve as yet another reminder that we should take the skin and what it does for us seriously. In addition, discovery of the skin’s internal clock offers yet another striking example of how the brain and epidermis are closely related, operationally. We now have learned that the skin has retained its own internal clock, which operates in synchrony and employs some of the same genes that regulate the brain’s clock. This should not be surprising if we recall that the brain and epidermis share a mutual embryonic origin. Both are branches from the same tree.

Could A High Salt Diet Actually Be Beneficial?

January 5, 2019 By Peter M. Elias, M.D. & Mary L. Williams, M.D. Leave a Comment

Varieties of salts | Photo by Mary L. Williams, MD


A High Salt Diet Is Bad, Right?

Most of us probably think salt is bad for us. Our doctors will most likely have prescribed a low salt diet if we suffer from high blood pressure or heart disease. Yet, recent studies shed a whole new light on how our bodies adjust to a high salt diet. And maybe its not all bad…

It had always been thought that if we ingest an extra load of salt, our kidneys will immediately try to restore the balance of salt and water in our blood. According to this simplistic concept – when we eat more salt, we drink more water. The imbibed water then flushes out the excess salt, allowing the levels of both salt and water to return to normal.

But some recent studies, including observations on astronauts, whose intake and outgo could be monitored carefully, show that this is not what happens when we increase our salt intake.

[Read more…] about Could A High Salt Diet Actually Be Beneficial?

Eczema and Staph Infections: the Chicken or the Egg?

December 15, 2018 By Mary L Williams, M.D. Leave a Comment

Image: Research from Around the World: Skin Colonization by Staphylococcus aureus Precedes teh Clinical Diagnosis of Atopic Dermatitis in Infancy | Meylan et al. (2017) Journal of Investigative Dermatology

Clinicians have known for decades that people with atopic dermatitis (eczema) are prone to Staph. infections (Staphylococcus aureus) on their skin. And we have also known that treatment of the infection can be critical to improving their eczema. Even when the rash is not obviously infected, nearly always Staph can be recovered from the patches of eczema.

In other words, even when the skin lesions of atopic dermatitis are not obviously infected, they are colonized, often heavily, by Staph. aureus.

The role of Staph in atopic dermatitis has become a hot topic with the recent focus on the normal skin microbiome and its disruption in disease. Like the gut, skin is normally colonized by a large number of microorganisms. Prominent among its ‘normal flora’ are several good varieties of Staphylococcus.  These ‘good’ Staph growing on normal skin are usually able to keep the ‘bad’ Staph. (Staph.aureus, that is) at bay.

The ‘bad’ Staph. are known to produce a variety of toxins and proteases (enzymes that digest proteins) that can weaken the barrier and stir up the immune system – both of which are key components in the ‘pathogenesis’ (causation) of atopic dermatitis (or ‘eczema’). This leads to the obvious question: does colonization of the skin with Staph. aureus lead to the development of eczema?

Could Staph. aureus be the ‘egg’ that hatches the atopic dermatitis ‘chicken’?

A recent study out of Lausanne, Switzerland provides evidence that this could indeed by the case. Because most cases of atopic dermatitis develop in the first 2 years of life, these authors took a cohort of 149 newborns and followed them for 2 years or until a clinical diagnosis of atopic dermatitis was established. Some of the infants were considered high risk, because of a family history of ‘atopy’ (or allergy). At birth and then at regular intervals, the skin was cultured at two sites and the infants examined for signs of eczema.

They found a positive association between colonization of the skin by Staph. aureus and the development of atopic dermatitis. And most intriguingly, that this colonization preceded the development of eczema by two months on average. They also found, conversely, that colonization with a ‘good’ strain of Staph. (Staph. hominis) declined on the atopic dermatitis skin.

These studies suggest that its not that atopic dermatitis skin provides a fertile field for the growth of Staph. aureus, but that these ‘bad’ Staph. could indeed be provoking the eczema to develop in the first place.

It has also been known for decades that not only are the lesions of atopic dermatitis colonized – even the clinically uninvolved areas of skin, as well as often the nasal mucosa, of eczema patients will harbor Staph. Aureus – without showing any signs of infection. And we’ve also known that the uninvolved skin of eczema patients is not entirely normal, either. Its often drier (low moisture content), has an impaired skin barrier, and shows subtle signs of eczema under the microscope.

These authors did not measure other skin functions, particularly the skin’s barrier function, to see whether a defective skin barrier (our prediction) is the real ‘egg’ here. In other studies we have shown that the skin’s permeability barrier is intimately linked to its antimicrobial barrier. Whatever disrupts the permeability barrier will also affect its antimicrobial barrier. These barriers are joined hand in glove.

Thus, it is entirely possible that an impaired skin barrier leads to colonization with ‘bad’ Staph. which in turn promotes the development of atopic dermatitis. Hopefully, the next large prospective study will measure both barrier function and Staph. colonization to sort out which of these two scenarios is the most likely.

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INSIDE THE SKIN BARRIER

The Skin Microbiome: Good Bugs And The Bugs That Bug Us

January 7, 2020 By Peter M. Elias, M.D.

We hear a lot about the multitude and diversity the micro-organisms – especially the bacteria - that … Read More...

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SKIN DISORDERS

Dry Skin: Who Is At Risk and What Can Be Done About It?

December 1, 2019 By Peter M. Elias, M.D. Leave a Comment

Who is at risk? Many people are prone to develop dry skin. Examples include those who have or … Read More...

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REPAIRING THE SKIN BARRIER

The How and Why of Sensitive Skin

November 1, 2018 By Peter M. Elias, M.D. 1 Comment

An alarming percentage (about 60%) of normal adults, mostly women, self-report that they regularly … Read More...

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CLIMATE AND THE SKIN

The Skin’s Many Barriers and Climate Change

October 9, 2020 By Mary L Williams, M.D.

Skin's Many Barriers And How Climate Change May Affect Them Skin has many barriers: it keeps us … Read More...

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Q & A

Q& A: Preventing Dry Skin From COVID-19 Hand Washing And Toxic Hand Sanitizers

December 1, 2020 By Peter M. Elias, M.D. & Mary L. Williams, M.D. Leave a Comment

Q: I have developed dry skin from COVID-19 because I have to wash my hands so often. Hand sanitizers … Read More...

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Research: From The Elias Lab

Top 5 Scientific Discoveries About Skin Of The Decade

December 26, 2019 By Peter M. Elias, M.D. & Mary L. Williams, M.D. Leave a Comment

We have learned a lot about skin and its permeability barrier in recent years.  Here are our … Read More...

MORE FROM THE ELIAS LAB >>

Research: From Labs Around the World

Top 5 Scientific Discoveries About Skin Of The Decade

December 26, 2019 By Peter M. Elias, M.D. & Mary L. Williams, M.D. Leave a Comment

We have learned a lot about skin and its permeability barrier in recent years.  Here are our … Read More...

MORE FROM RESEARCH AROUND THE WORLD >>

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