2014年6月6日金曜日

The skin produces steroids by itself

 It has been revealed that the skin (keratinocytes) itself has an ability of producing steroids. It is a proved fact.

The skin becomes thin by continuous application of steroids, temporarily hypertrophic (thicker than normal) after withdrawal and normalized after a significant period.
 The consecutive changes can be explained as follows from the thinking of cortisol production by the skin. It is not proved yet. It is my hypothesis but it can explain various phenomena about TSA.

 Topical steroids make the epidermis thin by suppressing the proliferation and differentiation of the keratinocytes.

 Physiologically, the epidermis produces steroids. The produced (inner) steroids regulate the proliferation and differentiation of the skin. However, prolonged application of topical steroids may suppress the production of the inner steroids. It is just like adrenal grand is suppressed by systemic steroids administration.

 When topical steroids were withdrawn and the inner steroids can’t be produced immediately, the epidermis becomes thickened and poorly differentiated. At that period skin can’t work as a normal organ and may react to various stimuli.

 After a significant time has passed, the skin recovers its function to produce inner steroids. That is the story of TSW from the viewpoint of steroid production by the skin itself.


From the above theory, many phenomena can be explained in an integrated way.

For example, ultraviolet rays are proved to induce the production of steroids in the skin. It is empirically known that UV therapy works on eczema and it induces no rebound. It may be because UV never suppresses inner production of steroids but increases it.

 The so called “moisturizer withdrawal therapy” is another example. The epidermis is proved to produce more cortisol in the dry atmosphere by the experiment using cultured keratinocytes(→ ref.). When the procedure of TSW prolongs and the redness of the skin continues, withdrawal from the whole topical agents sometimes works though it is accompanied by another rebound just like withdrawal from steroids. The mechanism may be the facilitation of recovery of production of inner steroids.

 Cholesterol is the primary material of all steroids. It is converted by the enzyme CYP11A1 to pregnenolone. On the other hand, CPY11A1 is an enzyme to metabolize aromatic carbonates which are contained in Coal Tar. Coal Tar has been known to be useful to make eczema subside since the time before topical steroids were on the market. If aromatic carbonates in the coal tar induce expression of CPY11A1, cortisol production in the skin is also accelerated. Vitamin D is also known to be metabolized by CPY11A1 (→ ref.) and there is medical literature topical Vitamin D works on eczema (→ ref.) . It may be of the same reason.

 Nowadays it is revealed that there are three organs which produce steroids, i.e. adrenal grand, brain and skin. The fact was elucidated only several years ago and it might not be well known to the ordinary people. The skin also produces sex hormone also. That is why women’s skin changes according to their periods.

 There are patients who used topical steroids so long a time and the epidermis seems not to produce any more steroids eternally.  I believe there are no patients who can’t recover the inner production of cortisol within the skin but you can choose the method of supplying steroids as much as needed by topical agents.

 It is so much for today. I hope your itching disappeared or decreased for a little time by reading my article
 I know you sufferers through TSW are spending a severe time day by day. But there is an exit because your skin is living and struggling to reconstruct the balance for recovery.

PS: Suppliment for Brenda Chu.
Cortisol synthesis pathway is in the following figure.
Cortisol is made from cholesterol via pregnenolone by the enzymes of CYP11A1, CYP17, 3βHSD, CYP21 and CYP11B1. Progesterone is on another pathway and doesn’t convert to cortisol.
I suppose any agent which induces expression of CYP11A1, CYP17, 3βHSD, CYP21 or CYP11B1 can be a facilitator of TSW. The examples are coal tar and topical Vitamin D above mentioned.



Please click here as for the clofibrate ointment. It is a non-steroidal agent with mild anti-inflammatory effect.

34 件のコメント:

  1. Dear Dr. Fukuya,

    I so happened left another message earlier to you (maybe on one of your older blogs) regarding this. I remember that I read your online book which mentioned skin produces its own steroid. When we're going thru TSA, as you mentioned above "I believe there are no patients who can’t recover the inner production of cortisol within the skin but you can choose the method of supplying steroids as much as needed by topical agents.".
    So, my question is, what other method is out there for TSA patients to supply steroid to their skin which TS is not an option? What about natural progesterone cream?

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    1. Please refer to the above suppliment.

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  2. Thank you doctor Fukaya! This is VERY interesting information and it explains so much about why our skin reacts the way it does.

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  3. Dear Dr. Fukaya,

    Very interesting and enlightening article. I have a few questions I hope you can answer. If a person's eczema or rash was treated with long term oral or iv steroids, but never topical steroids, would they have the same kind of rebound like we do with topical steroids if they never have used them? Why can many people use prednisone for years and not have a rebound effect on their skin upon cessation? Is it because they never had a skin issue before? Which contributes the most to the damage that steroids cause in our skin, topical steroids or oral/iv steroids?

    What approximate percentage of the population who have serious rebound from steroids have rebound from topicals, and what percentage would you estimate from oral/iv use only? Lastly, can people have the same rebound effect from using non steroid topicals? I know the first thing a typical doctor will prescribe for the skin is a topical steroid, so there seems to be very little information about how oral/iv steroids affect the skin. Thank you so much for everything you have done in research on tsa/tsw. I am extremely grateful for your research and information you provide. Dan

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  4. Hi Dr. Fukaya,

    I'm not sure if my last question was posted or if I accidentally deleted it. I was asking about the relationship of oral/iv steroids compared to topical steroids in relation to rebound effects on the skin. We have a new forum for topical steroid sufferers called NoMoreSteroids.com and we are considering using different terms instead of tsa/tsw, due to the stigma attached to the words "addiction" and "withdrawal", to spread the word about these drugs at a grassroots level here is then US. Something along the lines of "topical steroid damage", or "steroid damage", and "topical steroid recovery" or "steroid recovery".

    I assume the word steroids encompasses all three, topical, oral, and iv. We don't want to call it "topical" if all steroids cause the same skin reaction upon cessation. We are somewhat concerned the term "topical" is unnecessarily limiting (for our purposes of reaching people), since a significant portion of sufferers have been treated with systemic steroids in addition to topicals.

    Do oral steroids cause the same damage to the skin as topical steroids do? I'm confused on this because I assume most people are prescribed topicals before they are prescribed orals, so don't know if both have the same effects. I also know several people who have used prednisone for many years and stopped without a rebound effect in their skin. But, they weren't taking the oral steroids for a skin condition. I'm hoping you can shed some light on this. Thanks again for your time and everything you have done for all tsa/tsw sufferers. Dan

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    1. Please refer to the article about systemic steroids.
      http://mototsugufukaya.blogspot.jp/2013/06/paradoxical-idea-of-systemic-steroids.html
      I think the term ‘topical’ is very important. I have seen many patients with other disease such as collagen disease who were under control of oral steroids. They never develop skin manifestation of rebound. The rebound or TSA must be associated with the original disease or topical way of application.
      By systemic administration, the concentration of the skin tissue cortisol may not increase extraordinarily because blood vessel regulates inside and outside (See the following article).
      http://mototsugufukaya.blogspot.jp/2013/07/the-bankrupt-of-regulation-of-cortisol.html
      About the term ‘addiction’, I know some patients hate the nuance because it has an image of mental dependence. But there is no other word that is more suitable as far as I know.

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  5. Hi Dr. Fukaya, this is what I suspected but wasn't exactly sure how or why. Thank you so much for your clarification on this. I have a much better understanding of everything I asked you about now. Thanks again and good health to you!

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  6. Hello Dr Fukaya,

    Can you comment on the effectiveness of the newer novel treatments for atopic dermatitis such as the biologic drug Dupilumab or other pathway inhibitors like Tofacitinib?

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    1. There is an article about Xolair (Omalizumab). Please refer to it.
      http://mototsugufukaya.blogspot.jp/2013/07/a-report-about-biological-product-for.html

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    2. Thank you for your response Dr Fukuya.

      As you said, Xolair (Omalizumab) was designed for asthma and placebo patients showed some signs of recovery, however I was wondering what your thoughts on a treatment like Dupilumab (Regeneron) is since it is specifically designed for atopic dermatitis.

      Would a treatment like this take away the TSW symptoms? Could you also comment on how effective the clinical trials have been? I believe it is in phase 2 currently. Thank you for your time.

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    3. Sorry, I have not read the articles about those new medicines. I will read them in the future but not now. They are still in halfway through.

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  7. Dear Dr. Fukuya,

    Thanks for your prompt reply. You are really helpful and I am truly grateful with your help here.
    Just want to know, I am thinking to make my own vitamin D cream with Vitamin D capsules. What kind of potency do you think is appropriate to apply on?

    Thanks again!

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    1. If you like to try Vitamin D, there is a report that oral supplement was useful.
      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2659525/
      It would be easier to take. Usefulness of a therapy differs by patient. I hope you can find a good one for you.

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  8. Dear Dr Fukuya,

    I am in steroid withdrawal month 14. My progress is quite good, no more eczema now. However, prurigo suddenly exists since month 12, it appears on my legs, arms and back. The spots is just like the photo below, it will leave a dark scar. How to treat prurigo effectively? What causes the prurigo?

    Photo: http://www.atlasdedermatologieprofessionnelle.com/images/2/21/MVC-678Fbis.jpg

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    1. It looks like Pityriasis Lichenoides et Varioliformis Acuta rather than TSW. The difference with Prurigo is the necrosis on the center. I suggest consulting a dermatologist though it is not urgent.

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  9. Hi Dr Fukuya,

    I was using steroids and have TSW. Recently I began using antiseptic cream (chlorhexidine acetate 1%) on the eczema spots. It works well and heals the flare-ups. Do you recommend this? Is it harmful in the long term?

    Regards,
    Thomas

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    1. Don’t worry. It is not harmful. Please refer to the article.
      http://mototsugufukaya.blogspot.jp/2013/06/disinfectant-therapy-to-staphs-on.html

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  10. Thank you Dr Fukuya! The article is very clear and I have a better understanding.

    I have tried using other disinfectants like alcohol (isopropyl), hydrogen peroxide, and potassium permanganate but they don't work that well. Do you know the reason?

    Other than povidone-iodine 10% solution (which might cause sensitization) and electrolyzed strong acid aqueous solution (which I cannot find), what other disinfectants do you recommend?

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  11. Dear Dr Fukuya- you say the skin will eventually normalise. Is this the same for skin which has atrophied over a very long period of steroid use? Do you think it will reverse or improve if it is very atrophied? Thanks!

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    1. Hi, Blondie. I uploaded a new article about skin atrophy. Please find the answer in it.
      http://mototsugufukaya.blogspot.jp/2014/07/topical-steroids-cause-two-kinds-of.html

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    2. PS: My family name is not Fukuya but Fukaya :)

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  12. Hi Dr Fukaya
    I am in the process of going through TSW. I am currently in month 14 and am doing okay (not great). I recently have been to a doctor who suggested i may want to try Bio Identical Hormone Replacement (I also have HypoThyroidism). She suggested it could help with the steroid withdrawal. While I'm not 100%, I certainly would not want to jeopardize my progress and take a step backward, which would be completely devastating. Are there any implications in taking the Hormone replacement? I'm a bit confused about the medical theory behind it.
    Thank you in advance,

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    1. I have never heard of Bio Identical Hormone Replacement therapy. I could find the outline of it in Wikipedia. From the description in it, the therapy seems to be neither good nor bad for TSW. But as I am not familiar with the therapy, I should refrain from further comment.

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  13. thank you for responding... sorry... I think I posted this 5 times, as i wasn't sure what the message said :)

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  14. Hello doctor,

    I am from Romania and here we don't have any expert in this are as you. Could i have your email so i can ask you few taw related questions?

    Thank you!
    Regards
    Alina

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    1. Please write your questions here. I don’t reply to personal e-mails but I will answer here because many other sufferers could share the knowledge.

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  15. Hello doctor Fukaya,

    Im sorry, you are right, as i to been hovering over your blog and reading all the comments hoping to find something similar to me.

    I will tell a bit about my history with TS so you can better understand my situation.

    At about 21(i am now 31 almost) years old, i had what the doctor said it was contact dermatitis on my face, so i was given Locoid cream. It was all good until the condition come back, so i the used Locoid again, went to the doctor, he give me the same cream.

    After some years, 4 maybe 5, i can't really recall how much time i was using it, my skin was so sensitive to everything, if i went a day without punting the Locoid on, my skin would go crazy. So at that point i went to another doctor, she said that the cream was not good for long time use, so she give me Advantan milk to gradually stop using it, so i did, but the condition on my skin still came back, but at this point i was using the cream only once a week, more or less, whenever i would need it. This spring i went to yet another doctor after stopping the TS and my skin was really bad, she said that i have sensitive skin and i had a rash, she give Cutivate cream and said it is safe to use once a week and that it is used for babies. I used this untill this summer. Its now almost three months without steroids.

    After stopping with the TS, my skin gradually got worse and worse. But my symptoms are not as all i have read on blogs and in peoples storys. The skin was not dry, but very oily with bumps all over, they look like whiteheads and blackheads sometimes pimples but actual pimples, not red and not that itchy or oozing.

    Now the skin is still oily, but it feels like it is oily on the inside and dry on the outside, still bumpy and now with some red patches.

    My problem area is the skin around the eys, its almost always swollen, it has this weird texture, it feels like it is more then is has to be, and it forms a texure something looking like crocodile skin and the color is really bad, darck purple, like bruised. I look like i have been hit in the eyes everyday. And the color is like that for a number of yers, i did not know what was wrong.

    My questions are:

    1. Am i in tsw even if i don't have the usual symptoms?
    2.Is the color and texture around my eyes looking like that because of tsw? Could i have been in some sort of a widrawl since i have been using less ts(Advantan)? If so, will i ever get back to looking normal?
    3.I am getting married in a month, and thinking of going like this in front of everybody i know has put me in a state of constant depression and insomnia, i was thinking of using some ts just before the wedding, would that destroy all this months on agony?


    Thank you so much and i am sorry about the really, really long comment.
    Have a nice day,
    Alina

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    1. 1 Maybe you are addicted and your situation is of TSW.
      2 Maybe you become normal except the aging change due to withdrawal period. Your second doctor tried to taper TS but seems to have failed to support your mentality. It is often the case with such doctors.
      3 No, it never destroys. I call such usage of steroids as ‘wedding steroids’. After the ceremony, you can struggle again with TSA. It is an alternative way of TSW but not rare at all. If you were my patient, I would recommend injection of steroids before wedding only once temporarily.
      Remember you were originally healthy. Keep your mind strong. You are not a rare case at all and you are not alone.

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  16. Thank you so much doctor!
    There is nothing for me to do but be patience and hope for the best!

    Have a nuce day!

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  17. Dr. Fukaya,
    What is your thought on asthma inhalers and tsw? Do you stop your patients from taking steroid inhalers if they are bad asthmatics?

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    1. TSA occurs only on the skin. You should not stop asthma inhalers. It is very important.

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  18. Dear Dr. Fukaya,
    Thank you for the response. There is a child on itsan that was using flu tic as one inhaler with mask and developed eczema and went into tsw I do not know the details exactly, however if a person were to use a mask with steroid inhalers simply washing with soap should remove residue correct? I thank you for your experience. It is very important to understand what is affected and what is not.

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    1. Too much soap will damage the skin also. We must remember TCS and soap are both harmful to the barrier function.
      http://topicalsteroidaddiction.weebly.com/chapter-912288-dr-corkrsquos-epidermal-barrier-disruption-theory---2.html
      Maybe wiping by dry cotton etc. is enough.

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  19. Ok thank you. So if no signs of eczema for now no tsa. But for future wipe face with cotton or water or change from face mask to something else. I am thankful for your advice.

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