TopMD conducts clinical trial of CLn Bodywash for marketing purposes

CLn Bodywash, the “bleach bath in a can,” sounds like a product that we all need—a quick and easy way to cleanse your skin of Staphylococcus aureus and other nasty bacteria associated with eczema. But the marketing campaign arranged by CLn’s maker, Dallas-based TopMD, could be better.

For a start, they could arrange a decent clinical trial.

CLn must be classified as a cosmetic and not a medical product, because the FDA didn’t require tests before CLn hit the stores.

You would think the usual way to proceed with a medical product would be:

1)    clinical trial to prove safe and effective
2)    manufacturing and marketing

But TopMD scientists recently published the results of a clinical trial for CLn in the journal Pediatric Dermatology, about nine months after I first heard the product was for sale.

Of course dilute bleach baths are a known household treatment to manage skin bacteria. CLn is a portable bleach bath and isn't going to be any more hazardous than what thousands of people are already doing in their bathtubs. But is it any better? Is it worth paying money for?

I think that some marketing analyst decided that doctors around the US were reluctant to buy or recommend CLn because it hadn’t undergone a clinical trial. Now it has—with the shiny label “peer-reviewed,” although the journal it was published in is low-impact, and the “peer” who deemed the study worthy of publication could well have been a single graduate student.

The study might possibly qualify as a “phase 0” trial. It’s conducted on 18 subjects all of whom are given the product. There’s no control group that receives a placebo.

This is a problem, because both the doctors conducting the trial and the patients both want the product to work. So the reported results are bound to look better than they really are. Scientifically, this study is far from the final word on whether CLn is truly effective.

The way to avoid this problem is to have a double-blind randomized control trial where, at the very least, half of the patients get CLn and half get something that looks like it but isn’t, and nobody knows which is which until the results have been recorded.

For an example of how this might be done, at least in a way that looks good from a marketing perspective, you can see that the makers of DermaSilk clothing appear to get it right in their studies, the most recent of which was published online this week.

That the recent CLn study was motivated by marketing is clear from one of its measures. Participants were asked “Would you recommend CLn to a friend?” This is not a data point you see in too many scientific papers.

The company’s press release quotes UC San Diego’s Dr. Larry Eichenfield, chief of pediatric and adolescent dermatology at Children's Hospital, San Diego—a world leader in the field. Eichenfield says “I am excited to read the study by Dr. Ryan et al showing the benefits of TopMD's sodium hypochlorite-based body wash.”

The release doesn’t mention that Eichenfield sits on TopMD’s medical board.

I like the idea of CLn, and I think it’s probably a valuable product. I’m happy they sent me a free bottle to review back in October, and I’m keeping it in case I need it. But I wish they could present some more convincing evidence that it works. Are they afraid that it doesn’t? If not, why not use a control group in the study?

Your cream or ointment is probably contaminated. But it doesn't have to be

Unless you’re scrupulously careful about keeping your ointments and creams pristine, they are most likely contaminated with pathogenic microbes such as Staphylococcus aureus, a new study reports.

S. aureus, of course, is the nemesis of eczema patients, causing long-lasting, painful skin infections.

There’s about a 30% chance the cream inside an open jar or tube is contaminated with some microbes, although the actual number of organisms is likely relatively small. The chance is twice as high that microbes are teeming on the rim of the container, say Michael Lundov and colleagues at the University of Copenhagen, who conducted the study.

I probably don't need to point out that if your cream or ointment is in a tube, the only way it comes out is past the rim.

The authors used industry standard techniques to culture bacteria, fungi, and yeast from 32 different hand cream products collected from 20 patients. They transferred small samples of the creams to agar plates and counted the number of microbial colonies that grew.

"It is important that the patients exercise care in using creams and limit contact between the opening/edge of the container and their skin," the authors say.

They did not include a control from an unopened jar or tube, which would be interesting because it would indicate how sterile their method was. In the paper they report only that colonies grew in 20 of the 32 tests, but they count the presence of very small numbers of colonies as an indication the hand cream was contaminated. So things may not be as bad as they appear.

What can you do to prevent contamination? In biology, it’s common to take a large quantity of a reagent and parcel it out into small “aliquots.” Then you use one aliquot at a time so you don’t run the risk of contaminating the whole batch. Now, I don’t want to do that with my jumbo jar of Eucerin, but the authors suggest that I might want to use a sterile-ish spoon to take cream out each time I use it—presumably without then putting the spoon back in. I know this method is practical because Nikki, a Twitter user, told me she does this at home.

Good luck keeping your ointments and creams bug-free!

Staph aureus opens the door to skin infection by other viruses

If you have eczema, I'm sure you never thought it was a good thing that your skin was colonized by Staphylococcus aureus, the cause of so many runaway infections. If that weren't bad enough, scientists have now shown that S. aureus produces a toxin that enables other viruses to more easily infect skin cells.

The work, done by a group led by Donald Leung at National Jewish Health Center in Denver, was presented this week at the annual meeting of the American Academy of Allergy, Asthma, and Immunology in Orlando, Florida.

S. aureus produces a number of toxic substances, but one stands out in particular: "alpha-toxin." The researchers pretreated normal human skin cells with a variety of toxins, and then incubated the cells with two viruses: vaccinia and herpes simplex. Only alpha-toxin increased the amount of virus infecting the cells, compared to a control experiment. Alpha-toxin increased viral load of herpes in the skin cells by threefold, and that of vaccinia tenfold.

This may explain, the authors say, why patients with eczema are much more susceptible in general to viral skin infections than "normal" people. Eczema patients, for whatever reason, host a semi-permanent population of S. aureus, which is pumping out alpha-toxin and opening the door for its viral relatives.

[added later] It's well-known that people with eczema are more likely to develop warts, which are caused by viruses. Maybe if there were a way to neutralize S. aureus alpha-toxin, we could cut down on the number of times we get viral skin outbreaks and warts too.

Staph aureus throws a party in untreated eczema patches

We are not alone. Wherever we go, we carry our personal microbiological party along with us--in our gut, in our intestine, and naturally on our skin. We're crawling, even the healthiest of us, with ten bacteria, viruses, protozoa, etc. for every cell in our body.

New research has revealed an interesting difference between the skin microbiomes of patients who do and don't use pharmaceuticals to control their eczema. A recent study in the journal Genome Research finds that Staphylococcus aureus has pooped the party--it dominates the population of bacteria in untreated skin. On the skin of patients who use steroids, calcineurin inhibitors such as Protopic, or antibiotics, S. aureus shares its living quarters much more equitably with its bacterial cousins.

The authors of the paper, led by Heidi Kong and Julia Segre at NIH, used a technique called "16S ribosomal RNA bacterial gene sequencing" to catalog the bacterial population in two body locations at which eczema commonly occurs--the insides of the elbows and the backs of the knees--in 12 kids with eczema and 11 healthy controls.

(They used this type of sequencing because the method usually used to assay bacteria, which is to swab and try to grow a culture, may favor the growth of certain species over others. 16S sequencing provides a snapshot of all bacteria species present at any one time.)

S. aureus dominates flareup regions in patients who don't treat eczema. (Fig 3A.  from Kong et al.)

In the controls and the eczema patients before flareups, the bacterial populations were quite similar, with the eczema patients hosting populations in which S. aureus owned twice as much market share as it did in the controls.But during flares, the main finding was that in the patients who didn't treat their eczema (to be specific: they hadn't taken an oral antibiotic for the previous 4 weeks, or applied a topical treatment in the previous week), 90% of the bacterial population was Staphylococcus, compared to 20% for the patients who had treated their skin.

The scientists observed other shifts in the bacterial population on untreated skin, too. Several other species increased their relative numbers--especially Staphylococcus epidermidis, often thought to be a "commensal"--which I take to mean relatively harmless--species on healthy skin. It appears that S. aureus and S.epidermidis have some kind of symbiotic relationship--the two are helping each other out, or one is parasitic on the other in some way.

Very interesting research, although there's not much for an eczema patient to take away. Naively, one might think that this shows it is better to treat one's eczema than not. But there was nothing about the eczema in untreated skin being worse; the number of patients in the study is small; and there's a lot of variation (of course) among the data for the patients who treated their skin. What did they treat it with? We don't know. Could it be that applying a steroid helps keep down the S. aureus population? That would be weird indeed, because S. aureus folliculitis is a known side effect of strong steroid use. I'll go out on a limb and say that antibiotics are probably better than steroids for keeping S. aureus down in the short term.

One small frustrating point is that the 16S sequencing technique doesn't seem to provide absolute numbers. I'll exaggerate to make the point: Maybe there are 100 bacteria total in your elbow to start, 20 of which are S. aureus, and during a flare there are now 100,000 bacteria, but 90,000 of them are S. aureus. Or maybe there are 90 billion S. aureus out of 100 billion during a flare. This paper doesn't give you any idea of the scale.

Staph: a weakness for iron

I don't know why I did that, but I had to get it out of the way; write a post about red wine and the symmetry of itching. Now, here's what I intended to write about: a story that appeared in today's New York Times about new research on Staphylococcus aureus. Scientists at Vanderbilt University have found that S. aureus has evolved to plague humans, and that it's specialized to extract iron from our hemoglobin.

Now I expect that the problem that eczema patients have with S. aureus is more to do with cracks in the skin barrier and surface pH (S. aureus likes it alkaline, and eczematous skin obliges; normal skin is acidic). But I am intrigued by the role iron seems to play. Pathogenic microbes, it appears, need iron to live, and they don't get it by eating spinach or red meat or drinking red wine. They get it from us. They get it from our blood.

In another recent paper I covered, the authors mention that the skin is an iron-poor environment, and S. aureus actually has an iron sensor that, when there isn't any iron, helps the bacteria adhere to skin. Maybe this is to help it infiltrate the skin and get into the blood.

What the scientists find in this latest paper is that S. aureus is much better at binding hemoglobin from humans than hemoglobin from mice. The bacteria grow better when they feed on the human version, rather than the mouse version. And they have a receptor for hemoglobin, called IsdB, which is essential to hemoglobin capture. Without IsdB, S. aureus is crippled.

This is interesting, but for you and me possibly the most important result of the paper is that the authors show how useful a transgenic mouse model--an animal that has one copy of the gene for mouse hemoglobin, and one copy of the gene for human hemoglobin-- is in the study of S. aureus. If you study S. aureus using "normal" mice, the pathogen doesn't have access to iron like it does in humans, so it may be behaving differently in other ways too. Scientists using this new transgenic mouse will be more confident that their results are relevant for humans.

In particular, I wouldn't be surprised if a number of studies in the Atopic Dermatitis Vaccine Network (which is focused on MRSA) adopt this transgenic mouse as their model animal.

Moisturizer alcohol burn bad; acid moisturizer good

Voov had another dermatology appointment today. Nothing urgent; just a checkup to see how she's doing on her restricted diet. The new development is that we are not to apply steroids unless she's having a significant flare. Hidden B has, it turns out, been putting Derma-Smoothe on Voov every second night (Hidden B and I trade kid duties on alternate nights) and every morning. "I can't tell what's a significant flare," she says. "They all look significant to me."

I, on the other hand, don't think Voov's skin has been bad for quite some time. So, on my shifts, I haven't been putting any Derma-Smoothe on. This is what happens even in a two-doctorate family: we don't know exactly what we're supposed to be doing with our kid.

I mentioned that recently I got suckered into buying some generic moisturizing "creme" at CVS. It sits right next to the Eucerin, comes in the same kind of jar, and costs half as much. Why do I have to learn this lesson over and over again? The CVS creme sucks. It's slippery and actually burns my skin, although the ingredient list is virtually identical to Eucerin's. (Not perfectly identical, though, and I'd guess that the CVS version has more alcohol.)

Anyway, Hidden B found Eucerin on sale at Target and got me two jars. So I chucked out the CVS stuff. Burn begone.

This month's Journal of Allergy and Clinical Immunology has an article you'd find interesting. (Editor's summary here.) Let me recap it for you.

Two amino acids that naturally occur on normal human skin can slow the growth and reduce the infectious potential of the bacterial pathogen Staphylococcus aureus, a group of Irish scientists have shown in laboratory experiments.  

S. aureus colonizes the skin of 5% of people without eczema, and 90% of people with eczema; it infects broken skin and secretes molecules that cause and prolong inflammation.

Normal skin controls S. aureus with antimicrobial agents and an acidic pH (about pH 5.5, compared to normal cellular pH of about 7.4). I am not sure what acids are responsible for this low pH; however, two products of the breakdown of the molecule filaggrin (see here and here), "UCA" and "PCA," are amino acid components of "natural moisturizing factor" known to hydrate the skin and possibly contribute to its acidity.

The scientists explored whether UCA and PCA could, in a test tube, inhibit the growth of S. aureus. The answer was yes. UCA and PCA also reduced bacterial production of proteins necessary for S. aureus to colonize skin and evade the immune system. The interesting thing is that the scientists found the same inhibitory effects when they used hydrochloric acid instead of UCA and PCA. So the acidity of amino acids, rather than some other chemical property, is responsible for much of the bacteria-controlling effect.

However, there is one area in which UCA and PCA appear to have special properties: they greatly reduce bacterial production of one iron-sensing protein that helps S. aureus stick to skin cells. Hydrochloric acid does not do this.

If anything from this research might prove useful in the future to eczema patients, it would be that chemists might consider adding UCA and PCA to moisturizers to provide antibacterial control. There is evidence (referenced in the paper) that acidic moisturizers help suppress S. aureus.