2013年6月7日金曜日

Paradoxical idea of systemic steroids use for withdrawal from topical steroids

It must sound very paradoxical or even cheating. But as far as I know, the most effective method to subside rebound flare after withdrawal from TSA is temporary systemic steroid injection.

This method is not what I thought up. It is an old and traditional method for severe rosacea etc. Many of elder dermatologists know this method in fact.

More than 20 years ago ( before 1990s ), doctors used systemic steroids ( injection and oral ones) more often than nowadays. The history of steroid treatment is not so long. Dermatologists didn’t hesitate to use systemic steroids for severe dermatitis at that time. After injecting systemic steroids, the patient didn’t need to use topical steroids for a while because the efficacy of systemic steroids was so strong. I think elder doctors learned the manner from their own experience. ” Eczema > topical steroids > systemic steroids > improve” was a very simple and common procedure for those elder doctors.

From the mechanism of TSA, this manner can be explained as the followings. The essence of TSA is an iatrogenic barrier dysfunction. Epidermis becomes thin by suppression of proliferation of keratinocytes and corneodesmosome destruction due to increased protease etc. Topical steroids affect more directly to epidermis than systemic ones. That is why topical steroids are likely to cause so-called steroid addiction.

I should insist that I am never saying side effects of systemic steroids are less than topical ones.
Of course side effects of systemic steroids are severer than topical ones generally. Only from the viewpoint of steroid addiction systemic steroids are less harmful than topical ones. That is why some patients can escape from severe rebound phenomenon by utilizing systemic steroids.

Never forget that systemic steroids are far more harmful than topical ones when they are continued to use for a long time. The use of systemic steroids must be only temporary.  I recommend injection rather than oral ones. It is because patients can’t inject by themselves while patients can take oral medication more easily. Bad sensation when patients accept injection also works. Most patients accept steroid injection only when they surely need temporary relief ( for example when they didn’t anticipate so severe rebound after withdrawal ). Such patients will never accept steroid injection again easily. They are right.

Young doctors don’t know this experiencial manner. They believe topical steroids are absolutely safer than systemic steroids and speak ill of such elder doctors. As a result of ignoring existence of TSA, not only side effects of corticosteroids have been described insufficiently, but also ideas for countermeasure against them were abandoned.

Some patients might become confused because I, who must have been a commentator of TSA, look like recommending using systemic steroids. No, I never recommend the use of them. I am only introducing and explaining for logical understanding. But remember there is such an alternative way of withdrawal. It is a temporary strategic retreat so to speak.

It might sound also paradoxical but I have never told patient to stop steroids even when the patient was really addicted. It is my manner.
Self-decision is not only a patient’s right but also the patient’s obligation. I never decide. I only offer information.
But after the patient made a decision, I followed him or her with all my knowledge and ability giving respect to their precious decision. I saw many steroid-phobic patients. But on the other hand, I even followed some patients who couldn’t stop topical steroids. I prescribed as much steroids as they needed and waited until their circumstances changed.

Patients with eczema are surrounded with various circumstances. They must make a living also. Under some circumstance one can’t stop using steroids. It is OK. I will be of any help for such a patient also. That was my manner.

From such a viewpoint, systemic steroid use was also one option for the future withdrawal.

The following article is about the safety of temporary steroid injection.

A prospective observational study evaluating hypothalamic-pituitary-adrenal axis alteration and efficacy of intramuscular triamcinolone acetonide for steroid-responsive dermatologic disease. Reddy S, Ananthakrishnan S, Garg A. J Am Acad Dermatol. 2013 Mar 29. pii: S0190-9622(13)00187-4. doi: 10.1016/j.jaad.2013.02.005. [Epub ahead of print]

 The following figure is for explanation to Joey at the comment of Feb 4 2015.

Sorry, the comment column is not available now. But the author believes readers can find some hints to overcome their own situations by the previous comments.

19 件のコメント:

  1. Hi doctor - what do you think about the use of protopic for steroid cream withdrawal? Thanks! Eve

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  2. I have not enough experience of seeing Protopic or Elidel (calcineurin inhibitors:CI) users. But as a result I searched by literature, I don’t recommend to use them for the purpose of TSW.

    In Japan, dermatologists including me had great expectations to Protopic arround 2000. Everyone counted on Protopic as a relief until the patient could escape from TSA.
    It seemed to be useful at first. Most patients, though not all, could transfer from TS to CI without rebound.

    [Safety and Efficacy of 1 Year of Tacrolimus Ointment Monotherapy in Adults With Atopic DermatitisSakari Reitamo etc. for the European Tacrolimus Ointment Study Group. ARCH DERMATOL/VOL 136, AUG 2000:999-1006]

    But an unexpected thing happened. It was revealed that Protopic treatment, without any preceding TS therapy, can cause rosacea. In such cases withdrawal from CI also caused rebound. That report was a nightmare.

    [Tacrolimus-induced rosacea-like dermatitis: a clinical analysis of 16 cases associated with tacrolimus ointment application.Teraki Y, Dermatology. 2012;224(4):309-14]

    The accurate mechanism is not clear but my explanation is as the follows.

    1 Rosacea is caused by excessive TLR activation and LL37 release.

    2 TLR is one of innate immune systems and activated by TS or CI which suppresses strongly the advanced immune system (i.e. TS and CI can cause rosacea).

    3 Rosacea contains the epidermal barrier impairing mechanism thorough KLK5 (a protease which breaks the corneodesmosome) activation in itself.

    So the flow chart of CI > rosacea > addiction (rebound) can be drawn. CI itself don’t cause addiction or rebound directly. But some of CI users develop rosacea and some of rosacea patients due to CI develop rebound (addiction).

    I explained the above flowchart in the following article also.
    “The difference between (steroid induced) rosacea and TSA”
    http://mototsugufukaya.blogspot.jp/2013/06/the-difference-between-steroid-induced.html

    So the replacement from TS to CI is just a replacement at last. CI is not a savior of TSA.

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  3. Thanks doctor. So, in your opinion, the only things that can make TSW easier are cyclosporine and systemic steroids? Eve

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  4. I am afraid my opinion is rather old.
    But more than ten years ago, I have already experienced the failure case of CyS and oral steroids.
    http://mototsugufukaya.blogspot.jp/2013/06/a-case-of-withdrawal-from-ts-oral.html
    What I feel recommendable is only the administration of systemic steroids by injection under a skilled doctor who recognize TSA well. I have never experienced failure because patients can’t inject by themselves.
    Remember that I never deny the possibilities of successful cases by CyS, oral steroids or CI. I only mention there exist some failure cases.
    There are many minor countermeasures, phototherapies: http://mototsugufukaya.blogspot.jp/2013/06/phototherapy-narrow-band-uvb-therapy.html
    , olopatadine:
    http://www.xtosis.com/chapter27.htm
    ,stronger neo-minophagen C (SNMC) and so on. I hope my hyaluronan lotion could become one of such alternatives: http://drfukaya.ocnk.net/page/4

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  5. Hi Dr fukaya, I would be extremely grateful if you could answer a few
    questions:

    1. After the supression of the injected steroids, does it rebound even worse? Does the injection prolong tsw?

    2. How long is temporary? How many injections do you administer so that it does not worsen the addiction?

    3. What is the average time that the injection is effective? (providing the patient has not ever had any injections before)

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    1. >After the supression of the injected steroids, does it rebound even worse? Does the injection prolong tsw?

      I can’t declare but the answer is "No" from my experiences.

      >How long is temporary? How many injections do you administer so that it does not worsen the addiction?

      Mostly one time only. The dose is triamcinolone acetonide 40 mg (intramuscular injection). As staphs are rich on the skin surface of atopic patients, I recommend sterilization by povidone-iodine at the injection site (not by usual alcohol cotton) for preventing subcutaneous abscess formation.

      >What is the average time that the injection is effective? (providing the patient has not ever had any injections before)

      About one month. Patients can prepare for the situation after one month at that period.

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    2. , If I was in my first month this post probably may have convinced me to consider this option. I'm in month 3 now and just started on imuran so hoping to clear up within the next few weeks.

      Thank you very much for answering my questions, greatly appreciated

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  6. Hi Dr. , my 15 years old daughter is iin topical steroid withdrawal for 15 months, she still suffers bad, house bonded all the time, no school no friends, red skin , dry and itches a lot.we used ts on her probably from when she was 3 or 4 years old,not a lot, and then the last three years she can not be without steroid more than one week, so we started withdrawal 15 month ago, when she was 14 years old.So my question from your experience how long it can take teenagers to heal, are they any different from the adult time frame-30 % of time usage?Will that be helpful to take her to the ocean during summer when she will be in her 20 month off ts, or she will still be miserable? thank you so much

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    1. Sea bathing is useful for some patients with atopic dermatitis ot TSA. I recommend you to try it. About clinical course, there are many patterns and I can’t or shouldn’t predict it.
      I guess you are exhausted. I suggest you should not be too pessimistic or optimistic. Always smile and stay strong before your daughter as a parent.

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  7. Hello Dr. Fukaya,

    Some of the parents in the support group are very concerned about adrenal crisis in the children since they are not adults and feel that giving hydro-cortisone pills will help prevent adrenal breakdown during the first stages of withdrawal.

    Is there a difference in children and adults with topical steroid withdrawals and could the HC pills be an option or have you seen no difference in children either way?

    Recent findings of 2001 FDA reports by the moms show that the FDA wanted black box labels on topical steroids and as little as two weeks use could cause addiction, many childhood complications, Adrenal suppression and even death. Thank you...

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    1. I have never experienced childhood patients with adrenal suppression. All the patients with adrenal suppression I have experienced were adult and have taken oral steroids for many years. Though adrenal suppression in childhood patient due to topical steroids can occur as in the Dr. Sneddon’s case, such a case is very rare.
      http://topicalsteroidaddiction.weebly.com/chapter-2312288drsneddonrsquos-message.html
      So I suggest parents not to give oral steroids to children easily.

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  8. Dr. Fukaya,

    The method of starting out TSW with a steroid injection intrigues me, but I'm not sure if my doctors would be willing to administer it (they deny the existence of TSA and have rather large egos). My dermatologist has prescribed me prednisone, however. What kind of dosage and tapering schedule of prednisone would best mimic the effects of a one-time steroid injection for a 70 kg female? Thank you.

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    1. 1 ampule of Triamcinolone Acetonide (40mg) equals to 10 tablets of prednisone.
      As the absorption from intestine is not so accurate as injection, 3 tablets per day X 5 consecutive days is estimated to be substituted. But remember that patients are liable to be psychologically addicted to oral administration because it is easy to take tablets. I suggest you must withdraw from oral steroids completely in the future. Good luck.

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  9. I am suffering extensively from my TSW- 1 year now. I was recovering well, but it seems as though I have become over-colonized with Staph to the point where it is even in my nostrils. My derm has put me on Bactrim and Rifampin and wanted also for me to take a tapering dose of Prednisone (starting with 60 mg) to control the inflammation and get my skin under control from the Staph for the course of 16 days. I am just so worried to be put on an oral steroid because I have suffered a lot and do not want it to happen all over again with a possible dependence on oral steroids. She assured me the tapering dose is harmless and after reading this blog, my fears have lessened, but I really just have to ask again whether you think it wise that I follow through with her instructions for the oral steroids. I thank you in advance for your help. Bless you.

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    1. I can't assess your situation but systemic steroid administration is for the purpose of supporting patients leading to the final withdrawal from topical steroids.
      Sometimes it is for the mental support because it weakens the severity of rebound. But systemic steroids never solve the problem fundamentally.
      So I agree with your dermatologist if she suggested under the understanding that it is only the temporarily relief. But I don’t agree if she said as if it is absolutely necessary.
      Hyperpigmentation after TSW will be weaken or disappear only as time passes. Steroids will not help it.

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  10. Dear Dr Fukaya,

    Thank you so much for getting back to me. It is so comforting to hear the opinion of someone who knows about TSW. My skin is no longer red and burning as in the initial stages of withdrawal but now it seems as though all that remains is my atopic dermatitis that is severe and infected with Staph. After much consideration, I decided to follow through with all the medications. I have to ask, is rebound possible with a tapering dose? She assured me it is unlikely but when I initially took the first dose and then stopped it for 4 days out of fear, it seemed as though my skin flared up even more severely and abruptly. Thank you again for your insight.

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  11. Hi Dr. Fukaya,

    We had this post in our ITSAN public forum today from one of our beloved TSW vets and I wanted to run it by you as I'm concerned that many red skin syndrome sufferers will take this as an okay to use oral steroids and I don't think that is the intention of this post. Can you comment and clarify in this with someone who does not know what level their cortisol is? Thanks!

    "Hi everybody! I havent been reading or posting to ITSAN or Fb for a while now. Im three years and a half into TSW and I can say my life is pretty normal now, skin is much better, I look healthy again:). SInce I also had a bad (clinically proven) adrenal suppression, which was discovered 2 years into TSW and was treated with substitution cortisol pills- 20mg per day-10 plus 5 plus 5mg) I thought it would be good to share my experience with this. I was taking the pills for one year and I had a testing of hormons after 6 and 12 months. After 6 months my adrenals were still supressed, but after 12 months cortisol levels were back to normal again (I could also feel that- I wasnt tired anymore, skin condition was stable...). Actually that happened last december (2014) so im completely off cortisol (after weaning off slowly of course) for almost 2 months now and there has been NO WORSENINGS! I didnt even notice when exactly I stopped taking the pills, it went so smoothly:) My skin is great. SO for anyone who is afraid that substitution therapy fot adrenal supression will make them addicted again- that is not the case. Plus it helps a lot, before I started taking cortisol I thought I was dying- I was loosing weight, I was tired all the time, couldnt even go for a walk, skin wasnt getting any better, even worse, joints were in pain...Think about your situation and get tested for cortisol, if you feel that after a year or two TSW is not getting better. WIsh you all the best,
    Spela"

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    1. If the comment case is of real adrenal suppression like the case in the following URL, systemic (oral) steroids are absolutely necessary.
      http://mototsugufukaya.blogspot.jp/2013/06/a-case-of-withdrawal-from-ts-oral.html
      However, there is a doubt that the comment case was of real adrenal suppression. The comment case spent 2 years before diagnosis of adrenal suppression. If the patient was really of adrenal suppression, he or she could have died. Or at least he or she must have been hospitalized by ambulance.
      Cortisol level has a circadian rhythm. It is low in the midnight and high in the morning. So blood is usually taken in the early morning for testing. But in most patients at TSW, because of insomnia, the cycle shifts to late hours. So sometimes the cortisol level of TSW is very low even in the morning and misdiagnosed as having adrenal suppression. (I added the figure in the end of this article. Please refer to it.)
      Anyway, the comment case is a successful one as TSW. My suggestion is that if the cortisol level in patient with TCW was low in the morning, it doesn’t always mean he or she is of adrenal suppression. The diadnosis should be done by symptoms. Please refer to the symptoms of real adrenal suppression.
      http://en.wikipedia.org/wiki/Adrenal_insufficiency
      Administration of oral cortisol is absolutely necessary in cases with real adrenal suppression while it is sometimes useful but not absolutely necessary in most patients with TSW. The demerit is psychological dependence. Sometimes patients can’t do without oral steroids because they become too afraid of worsening. Such people can’t stop oral steroids even in 10 years after withdrawal though eczema has almost subsided or very subtle.

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    2. PS:
      The real adrenal insufficiency due to TCS is like the case of Dr. Sneddon. It is very very rare.
      http://topicalsteroidaddiction.weebly.com/chapter-2312288drsneddonrsquos-message.html
      In most of patients at TSW, the adrenal function is increasing because of stress. If a patient worries about adrenal insufficiency, the patient’ s cortisol level must be high. The real insufficiency patient can’t ask such a thing because of general fatigue etc.

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