Hyaluronic acid of around 100 thousand dalton (molecular weight)

I have referred to the fact that a special size of hyaluronic acid is effective for the purpose of preventing TSA. Here I will write the details.

The above illustration is keratinocytes and hyaluronan particles (blue, round). A keraticocyte has many spikes on its cell surface. Red round one is HAS3 ( hyaluronic acid synthetase 3 ) which produces hyaluronic acid. CD44 is the receptor of hyaluronic acid. Hyaluronan particles are produced from HAS3 by the keratinocyte itself and stimulate CD44 of its own. CD44 signals reach CDC42 and actin filaments ( brown lines ) are constructed. Actin filaments are the frame of the spikes. Without actin filaments the keratinocyte can’t elongate its spikes.
The spike formation is very important because EGF (epidermal growth factor, diamond-shaped light green one) can’t attach to its receptor without spikes. EGF stimulates keratinocyte to lead to cell division and proliferation.

When topical corticosteroids are applied to the skin, HAS3 becomes inactive. There are few hyaluronan particles in the space between keratinocytes. Spike formation of keratinocyte becomes poor and EGF can’t work anymore. It means the epidermis becomes thin (epidermis atrophy ) and the barrier disfunction occurs.

Even if the HAS3 is inactive, external supplementation of HA (HAFi, blue round) can stimulate CD44, elongates spikes and activates the EGF pathway. That is the mechanism by which external application of hyaluronan works.
Not all size of hyaluronic acid has this ability of stimulating keratinocytes. Only around 100 thousand dalton size of hyaluronan works.
 The reason why only this size has the ability is explained in the above figure. CD44 ( HA receptor sends signal only when two molecules get close to each other. Hyaluronan attaches first one CD44 and then another to let the two get closer. A signal is sent from CD44 to the keratinocyte as a result.If the hyaluronan is too small, it can’t reach another CD44. If too big, hyaluronan can reach another CD44 but can’t draw it near. The appropriate size is around 100 thousand dalton.
Around 100 thousand dalton hyaluronic acid is mystical. It increases in the amnion fluid transitorily.

 A fetus before 16 weeks has no skin on it. At the period of around 16 weeks, the skin is created.
Hyaluronan of 100 thousand dalton increases in the amnion fluid only at that time temporarily. It grows the fatus skin and changes the outer cells to the epidermis.
What is the most mystical is that the hyaluronan is produced by the kidney of the fetus itself. It is made in the kidney of the fetus and urinated to the amniotic fluid. A fetus grows its skin by itself.
So external application of 100 thousand dalton hyaluronan is just like soaking damaged skin to the amniotic fluid at the period of 16 weeks. hyaluronan repairs the damaged skin.

I thought it must be useful for TSA or possible TSA patients who use TS. So I began to look for the commercially available hyaluronic acid solution of this size. Soon I found I had thought too lightly. All available cosmetics containing hyaluronic acid adopted only more than 1 million dalton sized one. Molecular size is associated with viscosity. The more the molecular size is, the stronger moisturizing capacity becomes. 100 thousand dalton hyaluronan is less viscous than that of 1 million dalton and no cosmetics company in Japan adopted the former.
I was disappointed but soon I spread my search worldwide. Then I could find three items.
One is of South Africa.

The brand name is Hydrating HA Serum. It seems to be provided to only medical doctors (Maybe people can purchase it in clinics). The price is about ZAR 430.

Though HAiF is written to be added in the website, the concentration is unknown. I asked to the company by e-mail if I could import it to Japan. The answer was as the following.

Dear Mototsugu
 Thank you for your enquiry. Unfortunately Lamelle Research Laboratories does not export products as we do not have an exporters code. Lamelle is in the process of obtaining a code and only then will be able to export products. Please accept my apologies for the inconvenience.
Kind regards
Brand Manager Lamelle Research Laboratories

There seemed to be some governmental regulation which doesn’t exist in Japan.
Another is Avene’s Eluage. Avene is a brand name of Pier Fabre group which has a patent of addition of HAiF to topical steroids.

I found the concentration of HAiF of Eluage by the following article. The concentration is 1 % (half of Barnes’s report). Eluage contains retinalaldehyde also. Retinalaldehyde is also reported useful for suppressing eczema by Prof. Saurat in Geneva university (Dr Barnes’s boss). So I guess they have connections.

The third one is from United States. The brand name is Bionect.
Bionect seems to be produced according to entirely other concept than Barnes’s HAiF. There is no term of HAiF (50-300 thousand Dalton hyaluronan) on its website. I could identify its molecular weight from the brand name of original material HYALASTINE. The MW is 50-100 thousand dalton and the concentration is 0.2%. The price is about USD 100 per 30g tube.

I could find above three products containing HA of around 100 thousand dalton. But the postage seemed expensive when imported from overseas to Japan. If it was reasonable I could inform it through my Japanese blog to Japanese patients. Patients could import it directly from overseas.But I resigned.
I decided to produce it all by myself. I could find raw material of HA of 50-100 thousand dalton in Kikkoman company website (Brand name is FCS-SU). It is easy to produce 2% aqueous solution from it. So now I am a seller of hyaluronan cosmetics since two months ago.

My hyaluronan solution
I am selling 2% 30 ml at a price of JPN 3,000 and 2% 150ml at  JPN 10,000. I think it is enough reasonable. Bionect 0.2% 30ml costs about USD 100. The concentration of mine is ten times thick but one third in price.
And what is important is that mine is simple aqueous solution while other products must contain various ingredients as usual cosmetics. Most patients with AD or TSA don’t tolerate usual cosmetics because they contain various stimulants.

Some readers might be disappointed or amazed because now I am promoting my production as a seller. Anyway, please read to the last.
I am proud because I can recommend something for patients now. I couldn’t recommend anything before ten years ago because the mechanism of TSA was entirely unclear. What I could do for my poor patients was guiding the way to withdrawal. That was all. I felt myself powerless.
So I am now proud to introduce the above hyaluronic acid solution to patients.

Another reason why I feel my idea nice is that it might become a small source of income for some patients. When I saw my TSA patients, mostly I didn’t prescribe anything. I used to hand the prescription document written as JPN 10,000 ($ 100 ) by me to the patient.
“I think what you need now must be this one. Go to the pharmacy to exchange this prescription paper with the money.”
Of coarse it is a joke. A cynical joke. But patients smiled. I prescribed smile. I knew any little smile would be more helpful than medication at the hard rebound period.
I also told as the following.
“You should not come to dermatologists too often. It costs expensive. What is the most important during withdrawal is care to money. Patients are likely to become poor when they could get their healthy skin back at last. The side effect of topical steroid is addiction while the side effect of withdrawal is poverty.”
Patients smiled because they thought it was also my joke. But I was serious in fact.

Let’s go back to the subject, I can provide 10 bottles of 2% 30ml at a price of  JPN 21,000 and 10 bottles of 2% 150ml at a price of  JPN 73,500. I will send them by EMS. Charge list of EMS from Japan to overseas is at the following website.
You first purchase one small hyaluronic acid from me and try to use it. If you become satisfied with it, you can become a provider in your country. It will help your damaged income recover a little. If your skin becomes healthy, it is the strongest promotion material for you.
Clinical studies about this size of hyaluronic acid have rapidly advanced recently. Todd in US reported its usefulness for rosacea.
Efficacy and Tolerability of Low Molecular Weight Hyaluronic Acid Sodium Salt 0.2% Cream in Rosacea. Todd E et al. JDD 2013 Vol.12(6)
Anti-aging effect for normal aged people is also reported as the following in 2011. So you can introduce and recommend my hyaluronic acid lotion to the aged people in your neighborhood.
Efficacy of cream-based novel formulations of hyaluronic acid of different molecular weights in anti-wrinkle treatment. Pavicic T et al. J Drugs Dermatol. 2011 Sep;10(9):990-1000.
    Please send an e-mail [ info=tclinic.jp ]  (replace = to @) to me if you become interested to try. I will send one small (2% 30ml) hyaluronic acid at the price of JPN 3,150 

On line shop is open at the following site. http://drfukaya.ocnk.net/

 I must add and insist that my hyaluronic acid doesn’t suppress strong eczema or flare of rebound. It is the most appropriate for possible TSA patients who are using steroids. It decreases the risk of TSA.
 After withdrawal from TS (after strong flare storm of rebound) patients’ skin is likely to become dry and very very sensitive for a while. At that period patients can’t use most topical application including even simple white petrolatum. My hyaluronic acid is appropriate at that period. It seems to be possible for such patients to use my hyaluronic acid without irritation. Hyaluronic acid will thicken and strengthen such a sensitive skin to recover.
 For young patients including babies it is OK. There is no possible risk.

Inhibition of Putative Hyalurosome Platform in Keratinocytes as a Mechanism for Corticosteroid-Induced Epidermal Atrophy.
 Barnes L et al, J Invest Dermatol. 2012 Dec 6. doi: 10.1038/jid.2012.439. [Epub ahead of print]

Hyaluronate fragments reverse skin atrophy by a CD44-dependent mechanism. Kaya G et al, PLoS Med. 2006 Dec;3(12):e493.

Hyaluronic acid, an important factor in the wound healing properties of amniotic fluid: In vitro studies of re-epithelialisation in human skin wounds. Nyman E et al, J Plast Surg Hand Surg. 2013 Apr;47(2):89-92.

The Hyaluronan Receptor for Endocytosis (HARE) activates NF-κB mediated gene expression in response to 40-400 kDa, but not smaller or larger, hyaluronan. Pandey MS et al, J Biol Chem. 2013 Mar 24. [Epub ahead of print]

Hyaluronic acid targets CD44 and inhibits Fc epsilonRI signaling involving PKCdelta, Rac1, ROS, and MAPK to exert anti-allergic effect. Kim Y et al, Mol Immunol. 2008 May;45(9):2537-47.


46 件のコメント:

  1. Dear Dr. Fukaya,
    Thanks for the insight mechanism of action about Hyaluronan. I was just curious: with a size of 50-100 thousand dalton, is the molecule able to penetrate the outer skin? thanks.

  2. Thank you for the interesting academic question.

    Maybe you are confusing the penetration through the whole skin (into the dermis beneath the basal membrane) and the penetration through the corneal layer (into the epidermis over the basal membrane). The penetration to the dermis (the former) is limited to 500 dalton in MW by the dense basal membrane but the penetration to the epidermis (the latter) is possible in much larger MW. For example, house dust mite allergens are large proteins of about 10-200 thousand Dalton but they enter into the epidermis and effect to the Langerhans cells.

    You could recognize the penetration of my hyaluronan if you apply it to your skin and compare with the usually available one million Dalton hyaruronan lotion. My hyaluronan will be absorbed rapidly to the skin (it means penetration into the epidermis through the corneal layer) and the skin surface will become dry soon while the latter will remain long on the skin. The latter must be more proper as a moisturizer than the former and it is just the reason why any cosmeceutical company had not adopted the former. So I think the penetration through the corneal layer become poor over about one million Dalton in MW.

  3. Thank you so much for your patience and detailed explanation. I appreciate it. I really enjoyed reading your blogs. You sounds more like a researcher than a doctor to me :-)

    Also, I read somewhere else (may not be reliable) that HA molecule is able to absorb water of more than 400 times of its own weight, so i think, 2% solution means that amount of water in the solution is only about 50 times of HA. Could it be possible that your HA solution goes into skin and takes more water from already dried skin?

  4. The water-holding capacity of a material is a different problem. One gram (wet) skin tissue contains 0.5-1.0 mg of hyaluronan. The water-holding capacity of hyaluronan is more than 400 ml/g as you mention. If the hyaluronan in the skin monopolizes the water in the skin, 20-40% of the skin must consist of only hyaluronan and its water. But it is not so.
    In the human tissue, every molecule is moving dynamically and the hyaluronan molecule is also produced and resolved every moment. Do you know the half-life of the hyaluronan in a living body? It is only 0.5-1.5 days. Hyaluronan in our skin is always produced and resolved. Maybe there is not enough time for hyaluronan to hold water up to its full capacity.
    The externally applied hyaluronan is dried on the surface by the body temperature and the air. One drip of my 2% hyaluronan lotion is about 0.5ml in volume and spreads to about 200cm2 in area. So the applied hyaluronan is about 0.05mg/cm2. The percentage of initial density has no sense because it will be dried on the surface soon. The dry hyaluronan molecule enters between the cracks of the corneal layer. The related factors are molecular weight and PH. The smaller MW is, the more easily the molecule enters. As the PH on the skin surface is acidic, a molecule of acidic PH (for example VitaminC) can’t easily pass through it. Hyaluronan is neutral in PH.
    After entering into the space between keratinocytes, hyaluronan molecules will hold some water but the amount must not be filled up. Anyway it will work busily like other molecules.

  5. Thanks for your explanation, Dr. Fukaya. I'm glad to learn some skin biology from you :)You said Hyaluronan is neutral, i guess it must be sodium salt of hyaluronic acid. It makes sense.
    I will purchase from your after checking if there's any issue with custom. Thanks again.

  6. Dear Dr. Fukaya,
    I don't know if you heard of this question before or if you are interested in answering, but would using the Hyaluronic acid solution help with increasing/decreasing skin healing time during topical steroid withdrawal? Or would the skin cells over time will recover regardless of external application of the Hyaluronic acid .

    1. There is a natural healing mechanism in living creatures.　Hyaluronic acid of around 100 thousand dalton accelerates the mechanism in epidermis.It is like a short-cut key. It is reported that traumatic injuries also cure faster by application of the hyaluronic acid.
      On the other hand, remember that hyaluronic acid does not suppress immune response. If the inflammation is active and strong, the hyaluronic acid appears to be ineffective at all.
      Any medication is only a tool including topical steroids. Please understand the mechanism of various drugs and utilize them as you like by your own judge. I am giving information for your judge here in the blog.

      PS: Patients can put any question here in the comment space. It is inefficient and even hard for me to answer to all questions sent to my personal e-mail box. So sorry for no reply. And it is impossible to answer to questions about each individual illness from the limited information. But I am willing to reply here to you about general information.

  7. Dear Dr. Fukaya! Thank you for your blog. Thank you for your posts. I do not write comments usually, because of my poor english((. I'm in TSW about 16 months,and i want to buy the lotion! But i have a question, can i use the lotion even if my skin on face still red,itchy, and some days oozes?But mostly dry. And another question is, i live in Asia, Kazakhstan, it is near Russia. What place of delivery and cost should i write?

    1. Maybe it is possible to send it to Kazakhstan. But please remember my HA lotion is not for suppressing the active dermatitis itself. It is for prevention of skin atrophy due to TS.
      Some patients feel irritation even by my lotion while the others not. It depends on case by case. So you can try it anyway.
      As Kazakhstan is not the available area of EMS, I will send it by usual international mail. Please order thorough the "inquiries" form of the web-shop.

  8. Dear Dr. Fukaya. Thank you for your answer.I think for me it is better to try and to know, maybe it will help with some atrophy signs on my skin! Thanks again!

  9. Hello Dr. Fukaya, I've been reading your blog and find it very interesting. I am wondering if hyaluronan solution will reverse skin atrophy that is already apparent?

    1. Yes, it surely reverses already apparent skin atrophy.

  10. thank you. I just ordered some :)

  11. Hi Dr. Fukaya. I don't have ezema, rosacea, etc. I used to be normal until 2012 of September when I got fungal itch infection on my upper mouth area near above the upper lip (peri-oral area), the fungal itch and inflammation never went away on that area for two weeks so I went to the doctor. He prescribed me elocon 0.1% cream to put on that area. I put the thick paste on for 7 days, and it severely damaged the peri-oral area, as well as some of the area on the tip of my upper lip. It became reddened, has burning constant sensation, striae, many small blood vessels (telangectasia), the skin is severely damaged with creases, the skin became hyper-sensitive/hyper-reactive.Since the skin is still reddened with rosacea-like symptoms, not knowing any better, I went to another doctor, and she misdiagnosed it as atopic/contact dematitis. And she prescribed me Advantan ointment and told me to use it for 1 week off and wait for a few more weeks and to use again to get rid of the redness. I used it for 1 week and then wait for a few more weeks and use it for 1 week again. I stopped it because it has shown no improvement, but instead feels that it is irritating my skin. So I went to a dermatologist and he misdiagnosed it as fungal dermatitis so was prescribed a hydrozole cream (hydrocortisone 1%) cream and told me to use it for 2 times per day for 2 or 3 months, or until symptoms go away, and he also got me antibiotic doxycycline tablets to take for a month or two. I used the cream for 3 weeks but still it was irritating my skin, and I felt something is wrong so I stopped, and I took all the doxycycline tablets. But still no use and after 3 months I went back and he prescribed me clomatrizole 1% (without any hydrocortisone), but still no use for 3 weeks, only further irritate my skin so I stopped and never went back to the doctor. After two months I tried to see if the hydrozole cream (hydrocortisone 1%) cream will get rid of my condition, by applying it for 1-2 weeks but stopped immediately, but after that I know that these creams only served to further irritate and aggravation my condition and make it really hyper-reactive with burning sensation, so now I never ever use it again (the last time I used it was around April 2013).

  12. So now after 8 month have passed since the last time I use the hydrocortisone 1%, it was more or less still the same condition as it was after I used the elocon 0.1% cream for 7 days that damaged my skin in the beginning. Same redness/reddened, the burning sensation, striae, telangectasia, the atropic skin with creases (skin not properly normalized, like fine wrinkles, the skin just not properly restructured), the skin is very hyper-sensitive/hyper-reactive to anything. The area that's been damaged is the skin just above the upper lip (peri-oral) and on the very tip of the upper lip, and on some area of the upper mouth. When I move, stretch my mouth, talk, blushing my teeth, or eating, smilling/laughing, opening my mouth or when I'm exposed to higher temperature changes the areas gets aggravated with intense redness and you can see dilated blood vessels, and it feels irritated, and has a mild heat sensation. The skin just don't normalize back to it's original condition. At best when it 's cool and at most relaxed state, you can still see some of the redness, the telangectasia, and striae. The skin just don't heal correctly. there's creases, lines (it's seems the connective tissue beneath the skin is not connected well enough to make a bond, as it separates by a deeper layer not filling up to cover the top skin leaving it seeming like cracks/fissures/valleys between the thin skin, and under that layer is redness and you can see some dilation of blood vessels). The skin don't completely joined as you can see in between the skin, thin valleys of depth line between the skin, and it is extremely fragile and hyper-reaactive.

    So Dr Fukaya, will the hyaluronan repair lotion help reverse some of the steroid atrophy symptoms on the area of my upper mouth just above the upper lip (perioral area) such as the redness, burning sensation, irritation, and hyper-reactive/sensitivity?

    1. I can’t say anything. My hyaluronan lotion protects the skin from atrophy due to topical steroids. But my lotion will not suppress rebound or inflammation. It has no such a strong power. On the other hand, many sufferers prefer to use my lotion because no other topical agent is so mild in stimulus. After all nobody can’t judge before you use my lotion practically.

    2. Thanks Dr. Fukaya. I've already ordered your lotion. However, I wanted to know will the lotion thicken and strengthen the already atrophied skin? Because I think the damage the steroid have made have thinned the skin so much that it caused those Rocasea-like symptoms. I hope if the skin gets thicker it will lessen the redness, irritation/mild burning sensation, and hyper-reactivity/sensitivity.

    3. Patients with rosacea are very sensitive and even my lotion can’t be tolerated.
      If your skin is tolerated to use my lotion, it surely thickens the atrophic skin due to topical steroids. Anyway, if you have already got it, please try it. If your skin is sensitive, save my lotion until your skin become less sensitive and re-try it.

  13. Thanks. I can use it, but after I apply the lotion it dries out very quickly and irritate my skin very much, as it leaves a very thin layer/film of the dried out lotion that can be peeled off. Because it dries out all the moisture from the skin and tightens my skin so much that it irritates my skin causing to damage skin.
    Can I wash it off after the lotion quickly absorbs into my skin (after a few minutes)?
    Does it make any difference (efficacy difference) how long the lotion should be left on my skin or is it ok if I wash it off after a few mins (5-10 mins) when it dries out (after the lotion quickly absorbs into my skin)?

    1. Oh, it is wasteful. The thin film is the dried hyaluronan itself. You can apply much smaller amount and extend to more area of the skin. Or add some water to the dried film (it is soluble) and extend to more area of skin. The lotion is not moisturizer but a kind of nutrition.

    2. So it shouldn't be washed off after it dries out? Because this dried out thin film of the lotion just stays on the skin and make my skin very uncomfortable and irritates my skin, as it tightens my skin to the point that I cannot stretch my skin. If I do allow it to stay longer, it damages my skin. You're saying that the thin dried out hyaluronan layer is supposed to be left on the skin. Even though it will dry out your skin and damage your skin. Because sooner or later that thin layer of dried out hyaluronan is gonna come off from the skin as the skin moves or stretches, and that thin film will crack eventually and come off. But problem is that if you leave it long enough it will damage the skin. You advised on adding water on the dried out film. Washing it off using water would be similar. I don't know whether that thin dried out hyaluronan film is supposed to be left on the skin to be effective at thickening the skin. However if it supposed to be left on the skin, then it is going to damage the skin if left long enough. Even smaller emount does the same thing, it dries out all the same.

    3. Please extend the lotion to much wider area.　Hyaluronan penetrates almost all to the skin if applied appropriately thin. If difficult, please dilute with water.I am not suggesting you should stand the discomfort of the film. I am suggesting you are applying too much (too thick).

    4. Thanks for answering. Adding some water after it dries out relieves a bit of the dryness. Just wondering, have anyone who have used your lotion for awhile (say 1 - 3 month) report that they have thickened back their skin?

    5. Your complaint of stiffness after application of my lotion is rather common.　Sorry but this lotion is not meant for comfort just after application. After a few weeks, there are many patients who report thickness of the skin in Japan. Some report a lot of dirt rolled off as they scrubbed themselves. As the dirt originates from the thickened epidermis, it is a good sign.

    6. Thank you. Does the lotion also thickened the dermis? Well, having the steroid damaging and thinning the dermis as well as the epidermis. If so, how the lotion only penetrates as far as the epidermis will have any effect on the dermis? Is there some chain of events that leads from hyaluronan stimulating the epidermis and triggering something underneath the layer, thus the dermis then starts a chain of events leading to it to proliferate and thicken the dermis?

    7. No. It has no effect on the dermis. It improves epidermis atrophy only. Maybe it is because hyaluronan can’t penetrate through basal membrane due to its large molecular weight.
      About dermis atrophy due to steroids, I recommend PRP (platelet rich plasma) therapy though it is expensive. You can see the before/after photos on my Japanese blog.

  14. hi doctor, ive been using ts for about 1 year and 10 months. heavily on my face. the eczema started just before the steroid use. ive been on tsw for 4months now. the main thing im worried about is the incredibly thin skin right under my eyes and eyelids and forehead, emphasis on the eye thing. its much darker than my normal tone and very wrinkly. i know for a fact that it is atrophy, im just wondering if its permanent. im very worried bout it, i would appreciate your much appreciated knowledge on this. thanks Moh

    1. Don’t worry. The atrophy is not permanent because the period you applied TS is not long.
      Patients often become tired and depressive in several months after TSW. It is the usual course.

    2. that is such a relief!!! thanks
      how long would you say it would take to become normal(the atrophy), including the tsw? depressive and tired are just the few things i feel to be honest.

    3. Honestly speaking, I also can’t estimate because there are so many different cases.
      Please refer to my article below.
      When there is no definite answer, we doctors encourage patients to become optimistic. Because it is only what we doctors can do and the situations of the patients often become really better by it.

    4. i understand Doc. i read thw whole articles and it explains things very clearly. As long as the damages arent permanent, i'll find ways to cope. really appreciate you opinion, thanks :)

      btw have you got any links to patients you've treated before and after photos .

    5. As I am a cosmetic surgeon now, I have some techniques to recover permanent atrophy.　I recommend PRP　(platelet rich plasma) therapy around the eyes.
      This is for aged individuals but skin (dermis atrophy) due to steroids is very similar to the aged atrophy. You can see before and after photos in my Japanese blog.
      The first neck photos in the article are atrophy due to topical steroids.
      As the technique is expensive which is always the case with cosmetic ones and your period of application of steroid is not so long, I suggest you wait until natural healing reaches the end (Maybe one year or two at longest). I referred the article (photos) here only for keeping your optimism.

  15. Hi Dr fukaya Please forgive me if these questions have already been answered. .
    1.Does skin atrophy develop during tsw I.e. when condition worsens from flares etc. OR does it develop in the periods your using topical steroid creams?
    If strong topical steroid applicstoon predestines skin to a a state of atrophy, can this lotion prevent it from developing.
    2.For the example in the provided link of your patients neck, are you able to roughly indicate how long a similar case of improvement from such atrophy would tAke from just applying your lotion once a day.
    3. Is there any possibility of an addictive effect from using Hyaluric acid? Will it affect in anyway our bodies natural production of it.I.e. if we use it say for 6 month and suddenly stop, will the skin Or natural production of Hyaluric acid be impacted in anyway from suddenly stpping usage.
    I look forward to hearing back from you.
    Yours sincerely

    1. 1 Skin atrophy develops only when TS is applied. Flare rebound is the result of it and atrophy doesn’t proceed however the flare is intense. The skin lotion will prevent atrophy when it is applied with TS.
      2 I can’t indicate because there are so many variances in TSW course.
      3 No. Addiction is a very special phenomenon occurring in TS and more rarely in calcineurins.

  16. Dear Dr Fukaya,

    I have a 2 1/2 year old daughter who developed eczema 6 months ago after moving from tropical climate (humidity often above 75%) to a very dry climate (humidity level sometimes less than 20%). The eczema got worse every month and spread from the flexures to involve the whole body. I used 0.5% hydrocortisone ointment (about 1.5 tubes) and advantan ointment (1/2 tube) together with paraffin wet wraps in order to control the eczema for about 3-4 months under direction from doctors but found that even with tapering, I could not quit the topical steroid and the skin will weep and get inflammed just one day after stopping and even a light scratch will cause bleeding and more inflammation.

    My friend introduced me to the concept of TSA and I utilized plain paraffin wet wraps daily and managed to quit TS for two months now with only four or five light applications to help get over bad flare. I also explored food allergies and through elimination diet found that nut, egg, soy, dairy, red meat, fish and tomato seems to flare her.

    I decided to take a month long holiday back to tropical climate hoping for some help with healing but I became less strict with diet on holiday and that resulted in a bad flare. I saw a dermatologist who gave her oral antibiotics for staph, stellisept (antibacterial wash), TS (desonide) and wants me to start protopic.

    I am not so happy to start drugs again and then came across your blog. Your discussion on moisturiser withdrawal was very interesting. I notice that now moisturiser seems to make her worse and decided to quit moisturiser two days ago and I have seen immediate improvement! Currently the only thing I am doing is wiping her down with dilute apple cider vinegar solution hoping to keep staph under control now that she just finished oral antibiotics. I am keen to try the acidic water but have yet to find a source for it.

    I still have some questions. Currently her skin is very very dry and still very very sensitive. Moisturiser, synthetic materials, chemicals, contact with pets or outside environments easily cause her to flare up. I carry a wet towel with me constantly to wipe her down the moment I see the itch starting again.

    1. Can hyaluronic acid product help during the sensitive period?
    2. I return to extremely dry climate in three weeks. It will be the peak of summer where temperature will often be above 40 deg and very dry. If I am not moisturizing her skin, how do I prevent a bad flare from happening when I suddenly move to very dry climate?
    3. Should I start moisturiser again before and after the trip to keep skin humidity level up? I am worried because her skin is so sensitive now. Even to white parrafin.
    4. A lot of information states water is drying but I am finding the wet towels give a lot of relief of itch but maybe it is what is keeping her skin so dry. I was even thinking to try avene thermal spring water spray.
    5. Can the "beauty water" from water ionizer help as a spray?

    Thank you for reading this and I hope you are able to reply. I am very afraid the return journey will cause her to have a very serious flare.

    1. 1 Maybe yes. Some can’t tolerate to even my lotion but the proportion is small. Please try it anyway.
      2 Patients reactive to dryness often worsen in the winter season. So I suppose returning in the summer season is better. Anyway I recommend you come back to the humid area if the child becomes worsened. Such a life will not long for so many years. The skin of the child will be usually strengthened in several years.
      3,4,5 You can use simple water spray for the child because it seems to be the best in your experience. You don’t need to use expensive or special one. Usually the humidity becomes the least in the airplane. As you can’t take liquid bottles in the airplane with you, I recommend you ask some help from cabin attendants.

  17. Dear Dr Fukaya,

    Your advice and quick response has been invaluable. Your methods have succeeded when many other expensive doctors and conventional medicine has failed. My daughter had a mini flare today and is very itchy but her skin is still improving everyday with no steroids and no emollient. I thank you sincerely. Pls continue your good work and be a beacon of light for those suffering the condition and the caregivers.

    Yours sincerely,

  18. Dear Dr Fukaya,

    A very happy new year to you. A doctor friend recommended the use of Atopiclair on my daughter. Non steroidal.


    There have been mixed reviews. Do you have any thoughts on this? Are the ingredients generally regarded as safe with no rebound effects? The product appears to contain hyaluronic acid as well as other active ingredients. In that regard, your product appears to be better as yours has simpler ingredients.

    All these creams are proving to be very costly and I'm hesitant to try until I am sure the ingredients are regarded as safe.


    1. I don’t know anything about Atopiclair except the information in its website.
      As far as search in Pubmed, it is well confirmed the usefulness as the monotherapy.
      The gradient includes hyaluronic acid but the MW must be different from mine and usual large sized because there is no description about it.
      The rebound will not occur because it contains no steroids.

  19. I have managed to find a local source of your skin repair lotion and should receive it in one to two days. A friend is delivering the acid water tonight and recommends my daughter drink the alkali water too. I hope this all helps us.

    1. Acid water is recommendable as a disinfectant. But sometimes it makes the skin dry. So if the skin becomes dry and worsens, I recommend not using it.
      Drinking alkali water is not effective for eczema or TSW. But you can drink it because it is produced at the same time when you make acid water.

  20. Unfortunately my daughter has had a bad flare again and her arms (from shoulder to wrist) and knees are very red and look burnt. I applied steroid today (desonide) because I couldn't bear the look of the persistent rash any longer. One application has only had minimal effect on the redness. I'm quite discouraged and tired and feel like using a short course of steroid (3days?)to kick off the redness.

    The good news is that your lotion arrived today and I applied it on top of the steroid and added a layer of moisturizer on top. Yes I started moisturizer again because without it, her flexures crack and get very sore. The lotion appears to be non irritating to her skin. I hope it can minimize the side effects of the steroid.

    Would a short course of topical steroid be very detrimental? I don't believe we have TSA at this point since we have not been on it for a long time (I may be wrong). However we were probably addicted a few months back. Sadly, we have had more flares and worsened eczema in this humid climate and different environment. It has spread to her face.

    I am not sure what my next step is. I know my derm is going to be frustrated that I am not choosing to use protopic.

    What is your opinion on Protopic? I am hesitant to use it due to the lack of long term data on it's safety. At least with steroids, there is long term data and we know the side effects.

    Managing children's eczema is difficult. By not applying steroid on their skin, it's as if I am letting my child suffer unnecessarily. I really wonder what my child would prefer I do. It's much harder since it isn't my own skin.

    One day after trying the acid water, she flared. Perhaps it's too strong on her skin. I'm back to using apple cider vinegar. I hope that is a strong enough disinfectant.

    I hope a short course of steroid will not lead us back to the addiction path. I don't think I have a choice at this point because she just isn't recovering from this flare.

    What a setback :((

    1. Look at the eyes of your daughter. Is she fine? Does she laugh by her eyes? If so, it is OK. Your way of child-rearing is correct. Recover self-confidence and stay proud as a parent. It is absolutely your next step.
      Never look at the skin but only look at the eyes of the daughter. If you are sad, she gets also sad. She feels sorry to you more than you feel sorry to her. Keep smile.
      As for temporary use of steroid, protopic or moisturizer, it is not a serious problem as you have noticed already. The point is that you should not apply too long. That is all.
      Stay strong.

  21. Dear Dr Fukaya,

    I thank you sincerely for your steadfast care and dedication to eczema sufferers. Here is an update on our condition. It is now day 3 after I started desonide on her. She is much improved of course but I also know the effects aren't going to last. This break, however, has also been good for me, the caregiver.

    Now that I have completed the course, I am desperate to try to maintain her skin condition. One thing I keep reading about in good eczema treatment involves disinfectant, antimicrobial or probiotic therapy. Obviously, the role of staph aureus in progression of the disease is high.

    She completed a course of oral cephalexin two weeks ago. However, that has not stopped the eczema from flaring after we stopped. I believe the use of paraffin made her itch in this humid climate and that continued to drive the eczema. I have since switched moisturizers. The use of acidic water on my daughter appeared to be too strong. The dermatologist gave an antiseptic wash (stellisept) but made no mention about whether the wash can be used long term. This too appears drying. At this moment I use a weak apple cider vinegar wash only.

    My observation is that areas of her skin behind her knees and at the elbows appear to be slightly spotty. I believe staph is persisting as a problem. Today I applied retapamulin 1% antibiotic ointment on the flexures in hopes it will keep her condition stable.

    I have always been giving probiotics but have found limited success.

    Do you have any opinions on use of a topical antibiotic? What about antibiotic resistance? It appears a pubmed article states low resistance with use of retapamulin. It is the only one I have on hand. I'm not sure if other preparations are preferable eg fucidic acid or bactroban.

    Desperately searching for a cure. Or at the very least, better management. I have been one crazy mother trying to get on top of this horrible condition!

    I have been using your hyaluronic acid lotion on her skin twice daily. I tried it on my face too. It seems to be marvelous on my skin. I can't say about my child because we are using desonide too but thank you. I do believe your product is good.

    Yours sincerely,

    1. The first thing I suggest you is staying strong as already written. The second thing you should learn is not to do anything. It is harder than doing something but as a caregiver of atopic child the stance is often very important.
      You should not hesitate to use antibiotics when the child developed sepsis signs
      but you don’t need to use antibiotics when the child is not really infected. Disinfectant therapy is useful in some patients
      but it seems not useful in case of your child as you have already experienced.
      It is the same as for use of TCS use. Even if you didn’t use TCS when the child worsened, the child would have recovered in several weeks or months. I never blame you for your applying TCS to your child. Never misunderstand my words. What is necessary in you is to learn that aggravation of eczema automatically improves as time passes especially the cause was obvious and removed like this time.
      Stay strong. Learn to do nothing but carefully observe and judge the child really needs medical care. Exercise your intuition as a parent and always add a choice of “nothing to do”. You seem to be smart and enough knowledgeable. Yes, I respect you as a good caregiver. I thank you instead of your child.

  22. Thank you for your encouragement, dedication and wisdom. I think I know now what I need to do. For months I have been trying to understand this disease and trying every way to manage the condition as safely as possible for my child, sometimes even hoping on hitting the magic button and finding a cure. Perhaps my endless research is coming to an end. The answer for my personal circumstance lies in balance. Life must go on for everyone and cannot halt because of this terrible condition. When I do reach for the drugs in order to reset our lives to being more manageable and to allow for less suffering for the child, I hope I can do so with less guilt. You are right, in my line of work, do nothing is always an option, and sometimes it is the best option. I have done my best for this child and I pray for the wisdom to know when and how to manage when I need to.

    I thank you again. Your dedication is an inspiration to me. Thank you for your amazing blog and for sharing your time and knowledge with us.


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