A report about a biological product for patients with atopic dermatitis.

 Have you heard of the medicine called a biological product? It is a practical application of the monoclonal antibody.
 There are various biological products available nowadays. Among them Xolair (Omalizumab) is the most promising for atopic dermatitis at present.

 Xolair was studied as a medicine for asthma. Patients with asthma often suffer from atopic dermatitis also. Some patients with asthma to whom Xolair was administered also improved their eczema. So doctors started to study the efficacy of the medicine for atopic dermatitis. Some reported Xolair was useful while the others reported not effective. There was no double blinded case-control study. The below report is the first double blinded case-control study about Xolair for atopic dermatitis though the population is small.

Immunologic Effects of Omalizumab in Children with Severe Refractory Atopic Dermatitis: A Randomized, Placebo-Controlled Clinical Trial. Iyengar SR,et al. Int Arch Allergy Immunol. 2013 Jun 27;162(1):89-93  

 The number of patients was 8 at the age of 4-22. They were divided to two groups of placebo and Omalizumab administration.
 They were all refractory patients (“All patients had severe AD that had failed standard therapy.”). Whole the treatment was discontinued one week before the first administration of the placebo or Omalizumab. The agent was administered by subcutaneous injection and the dosage of Omalizumab was 150-375mg every time. The frequency was every 2-4 weeks and the duration of treatment was 22 weeks.

 Total IgE, Free IgE, TARC and SCORAD values are picked up from the results of the article as the following table. How do you read the numerals?

 Omalizumab is an antibody to IgE. It binds to the patient’s IgE and inactivates it. The free IgE decreaseed and Th2 system also became inactivated.
 However, about the SCORAD which indicate the clinical severity of atopic dermatitis, the values decreased in both the placebo and Omalizumab groups. How should we understand the result?

 I consider there is a possibility that the placebo patients improved  by topical steroid withdrawal(TSW) for 22 weeks.

 In the article, the authors didn’t mention the result of the statistical analysis. So I did the matched Student’s t test to their results. The P value were as the following.

  At the 0.05% of the significance level, the placebo group improved while Omalizumab group didn’t improve.

 The author’s comment is as the following.
“The high rate of response to placebo has been well documented in these types of studies and, had any of the above published studies examining the clinical effects of anti-IgE included a placebo arm, a similar rate of response may have been seen.”

 Wait for a while. The phrase is likely to be skipped just carelessly but you ( the author) mentioned the patients were all refractory to the usual standard therapy, weren’t they? You admit such patients improved by the placebo treatment for 22 weeks and it is often the case with that kind of studies?

 Yes, atopic dermatitis has a tendency of natural healing. But the enrolled patients were “All patients had severe AD that had failed standard therapy.” I suppose you should not have forecasted their natural improvement before the study.

 The price of Xolair is about USD 350 per 75mg. It costs about USD 4200-21000 for 22 week treatment.
 Here I should clarify my stance about this therapy. I dare say I will buy Xolair and administer to my child if he or she suffers from the refractory atopic dermatitis. If I were a sufferer, I definitely buy the treatment. The problem about the above article is only the SCORAD result of the placebo group. The results of blood examination are clear and convincing. The significance of SCORAD is over 0.05 but I believe it will decrease if the population becomes larger.
 The cost is really high. But fortunately I can afford it. I will pay for the medicine even though there is a small risk of anaphylaxis or carcinogenicity due to immunosuppression. I take the merit heedless to the risk of this medicine.

 But I know well all the patients can’t try the treatment because of the financial problem. Don’t worry. You could also become improved only by discontinuance of the whole treatment for 22 weeks just like the patients of placebo group.

 Yes, it is the essence of the TSW. Patients feel strong anxiety to the situation of “nothing to do”. Placebo patients in the above article might have worsened temporarily but they could stand it because they thought they were through a treatment. Doctors could also stand the stressful situations because they thought they were scientifically right. Do consider. If the placebo patients remain worsened, the best scientific outcome could be obtained. Otherwise the doctors couldn’t stand seeing worsening patients without any treatment and must have recommended to resume topical corticosteroids.

 However,what a happy ending of the study! All patients became improved in the above article and the efficacy of TSW was also confirmed. A toast to the authors!

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.

14 件のコメント:

  1. Hi, I had read Dr. Fukaya's comments on "The bankrupt of the regulation of cortisol level in the skin tissue might be the essence of TSA" and I am curious as to what role the adrenal glands play in average tsw duration, if any. I am trying to figure out whether supporting the adrenal glands via diet and lifestyle changes will speed up the tsw process or not, as opposed to not supporting them. And, does the regulation of cortisol levels in the skin tissue play a more direct or important role in tsw recovery than the adrenal glands do? Thank you, Dan

    1. TSA and adrenal insufficiency are different. In most TSA patients adrenal function is normal or a little increased.
      Adrenal insufficiency mainly occurs in case systemic (oral) corticosteroids are taken for a long time in AD patients.
      But there can exist a severe adrenal insufficiency case caused by topical corticosteroids only.
      You will able to understand the relation of the two by the figure of the following article.

  2. Dr. Fukaya, thank you so much for your time and answer. I appreciate everything you have done in this area of medicine and can not thank you enough. I have read this information but still am confused. I used ts for the most part and am 4 months in tsw. Since I have not experienced adrenal failure my adrenal glands are likely fine. So, supporting them by diet will not effect tsw duration? Or, should I assume my adrenal glands are weakened to some degree and therefore support of the glands through diet will effect tsw duration? Can you clarify?

    1. You don’t need to check your adrenal function at present. You are now at 4 months after TSW and you are able to write an e-mail. Patients with adrenal failure can’t do such a work.
      As for diet, I can’t say anything. In animal experiments, starvation increases serum corticosteroids and seems to help recovery of corticosteroid-producing cells such as adrenal gland or skin. There is a fork therapy also in japan that recommends starvation for curing atopic dermatitis or TSA. On the other hand, many fatty patients can withdraw from TSA successfully without diet. TSW is so severe that such patients would become very pessimistic to life without eating their favorites. Patients with exudative rebound skin are liable to become hypo-proteinemia. Especially in infants or children, appropriate nutrition is very important for their growth under the right control of food allergy. So there are good and bad aspects in starvation in TSW or AD.

  3. Dr. Fukaya, after re-reading everything you provided I have to conclude that tsw can not be sped up in any significant way by enhancing adrenal gland function in most cases. Is that a correct assumption? Are you aware of a way to speed up tsw? Do you think moisturizer withdrawal during tsw can speed up the tsw process?

    Also, I used a tiny amount of betamethasone dipropionateointment usp 0.05% on a very small area on my lower body for approximately 18 years every other day. Then, I also used it in slightly larger amounts on my one hand for about one year every other day, and finally on 80% of both my hands for a little over the last two years 2-3 times per day, before beginning tsw on my own accord. I had severe rebound symptoms on the hands from the start of tsw, and 4 months in my skin seems to be slowly improving. It is better than before I ceased ts use. It started improving greatly when I ceased moisturizing in combination with daily dead sea salt baths and lots of sun to heal the broken skin at about month two. After reading http://www.xtosis.com/chapter23.htm I am concerned because I am 58 years of age. I have telangiectasia symptoms of itching and pain but not the appearance of telangiectasia. Do you think I will fully recover, and if so, how long would you estimate. Thank you again for everything!

    1. I agree with Dr. Sato in that moisturizer withdrawal speeds up in certain cases.
      However, it is a hard landing method. I know some patients drop out from TSW itself by selecting moisturizer withdrawal. If you are enough strong and like to shorten the TSW period, I recommend it.
      My answer to the latter half lies in the following.
      In your age, I suggest you can use moisturizer in the future after TSW. People with normal skin also use moisturizer when they become elder. I suggest you should refrain from soap in taking a shower or bath. It will remove sebaceous matter which is a natural moisturizer.

  4. Dr. Fukaya, your answers were extremely informative and have helped me put everything in perspective now. Again, I can't thank you enough for taking the time and for your detailed answers to my questions. Moisturizer withdrawal was difficult, but they only made me itch more and kept my broken skin from healing over. I was in so much pain anyway that I was able to handle it. It was well worth the week or two of worse pain to have months of lessor pain, a much better comfort level, and lower risk of infection. I had figured out that I needed to stop using moisturizers on my own, but reading about it on your site gave me the confidence that I was correct in my logic. I didn't think about some people dropping out of tsw because of the intense pain in the beginning of MW, but in retrospect I can understand why. It certainly can be a very difficult period.

    Dr. Fukaya, many thanks for all the work you've done. I am but one of many who has benefited from your efforts. Your work will benefit millions of tsw sufferers to come. Hopefully, it will save millions from tsa at some point as well. I wish you the very best of health! Thanks again, Dan

  5. Hi Dr. Fukaya, I recently had extensive blood work done and the following are my abnormal results only. I was wondering if any of these indicate anything other than my body is still fighting or recovering from tsw? I'm at month 5-1/2 and feel I am 80-90% healed. Most obvious symptoms are nearly gone such as rash, pain, itching, insomnia etc. The abnormal test results seem to be related to high histamine levels or other allergic issues caused by tsa/tsw. I have had many blood tests in past years with no abnormal results. I used ts liberally on my hands for the past two years, and very sparingly on just one small spot on my body for 20 years. If I may ask, what is your opinion?
    IMMUNOGLOBULIN E, TOTAL 431 - normal range 0-100 IU/ML "High",
    MCHC 35.8 - normal range 31.5-35.7 G/DL "High",
    NEUTROPHILS 38 - normal range 40-74 % "Low",
    EOS 24 normal range 0-5 "High",
    EOS (ABSOLUTE) 1.5 - normal range 0.0-0.4 X10E3/UL "High"

    1. High EOS is related with TSW. It is often amplified after TSW but clinically it means nothing.
      Other values are of no relation with TSW. Neutrophil must be relatively low due to high EOS.
      Most of TSW patients are very healthy generally. Don’t worry.

  6. Hi Dr. Fukaya,

    What is your opinion on the use of the "moist wound healing" method for people going through TSW? TIA

    1. It is a method for wound healing with minimum scar which has become popular recently in Japan. Are you Japanese?? It is not a specific method for eczema sufferers.

  7. Dr. Fukaya,

    I apologize, I forgot to include this with my previous question. What is the difference between moist wound healing and moisturizing? Thank you so much!

    1. Maybe I have already answered to the question by the last reply. Moist wound healing is for the deep wound and moisturizing is for the superficial skin.

    2. Thank you for very much for your response and all you do for people. I'm Native American in the state of Oregon.


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