IMPORTANT DESCRIPTION OF TSW IN THE UNITED STATES AND UNITED KINGDOM 2021.4.29

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(Dr. Sato) There was an important description regarding TSW. I haven't had a chance to read it recently, but I found a statement of "steroid withdrawal syndrome" in the 2019 9th edition of the world-famous American dermatology textbook (Fitzpatrick's Dermatology, p. 377). The following is a translation of this part.

 

[The U.S.]

Side effects of topical glucocorticoids can be divided into local effects and systemic effects by suppression of the hypothalamic-pituitary-adrenal axis.

Local side effects include the development of striae, skin atrophy, perioral dermatitis and rosacea acne. Regular, long-term use of topical glucocorticoids can also cause steroid withdrawal syndrome, particularly on the face. The symptoms are characterized by intense erythema formation, swelling, and sense of burning when topical glucocorticoids are stopped applying.

 

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(Dr. Sato) In January 2021, the National Eczema Association and the British Dermatological Association issued a joint statement on withdrawal of topical steroids in the United Kingdom. Here are the key points:.

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[The U.K.]

Topical corticosteroids are effective treatments for eczema and other inflammatory skin lesions but, like other treatments, can have side effects. Many people with eczema are concerned about the possible effects of overusing or stopping topical corticosteroids. It can be misleading if people use different words or disease names to express their influence. We would like to clarify the terms used in this document and respond appropriately to the above concerns. 

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We use the term “redness” for a whole range of colors, from pink, red, and purple to a slight darkening of the original tones. 

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① Result of overuse of topical corticosteroids

Side effects result from long-term, daily use of potent topical corticosteroids. (usually for more than 12 months.) The terms of erythroderma (Red Skin Syndrome) and Topical Steroid Addiction are used to describe several different pathologies that can result from excessive use of topical corticosteroids. — If people experience the following problems, they should seek advice from their health care professional. In most cases, topical corticosteroids should be stopped.

 

a. atrophy, b. rosacea, c. acne, d. perioral dermatitis

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② Allergic reaction to topical corticosteroids

Some patients with eczema are allergic to topical corticosteroids. Inflammation for topical corticosteroids can be stronger than the anti-inflammatory effects of steroids, resulting in no improvement in skin condition. This is sometimes referred to as Topical Steroid Addiction (because it looks like more topical corticosteroids are needed to achieve the same effect). The cause of deterioration may be the preservatives and other constituents in the steroid cream rather than the steroid itself. A patch test can determine the cause. Allergies to corticosteroids themselves are relatively rare and may be overcome by switching to a different type of topical corticosteroid.

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③ inability to control underlying inflammation

Some people continue to use topical corticosteroids correctly, but their eczema is simply too severe for topical corticosteroids to control, and inflammation persists or worsens. In this case, immunosuppressive drugs are usually needed.

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④ What Happens With Discontinuation of Topical Corticosteroid Therapy

●Rebound erythema

Topical corticosteroids are known as vasoconstrictors. It closes the small skin vessels, causing the skin to turn pale. If treatment is stopped, the blood vessels rebound and widen. Redness and swelling develop. This usually calms down over time.

 

●Redness on the face

Rosacea, acne, and perioral dermatitis caused by overuse of topical corticosteroids worsen when treatment is stopped. This is because steroids suppress inflammation.

 

●Rapidly worsening redness, pain, itching, desquamation, lymphadenopathy

 These may be recurrent or worsening of the underlying eczema after the anti-inflammatory steroids are gone. Alternative anti-inflammatory immunosuppressive treatments and drugs are needed.

 

●Adrenal insufficiency

 This is serious but very rare. Extensive, very strong topical corticosteroids are applied for years, and some are absorbed into the bloodstream. This can suppress the natural production of steroid hormones by the adrenal cortex of internal organs.

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⑤ Topical Steroid Withdrawal as one of the treatment approaches for eczema

Interest in the use of topical corticosteroids has led some people to try to cure their eczema without topical corticosteroids. At first, eczema tends to worsen.

​But some people have found that after a while, the rash settles and can be managed with simple emollients or non-drug treatments and lifestyle changes with reducing stress-induced exacerbations. If eczema persists or recurs and the person does not want to use topical corticosteroids again, dermatologic treatment options include the following.

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● The repair and prevention of natural skin defenses by treating dry skin with continued use of moisturizers

● Cold bath and bandage during exacerbation

● Using Protopic, etc.

● phototherapy

● The use of oral or injectable drugs that suppress the immune system, which affects the whole body. These can have more serious side effects than topical corticosteroids and are usually prescribed to people with more severe eczema that cannot be treated with topical corticosteroids.

 

 

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【Comment from Dr. Kenji Sato on the treatment of steroid withdrawal syndrome in the United States and the United Kingdom】

 

―About statements of the U.S.ー

I am pleased that "steroid withdrawal syndrome" has been raised as a problem and that it has been evaluated as a "local side effect" of topical steroids.

However, it is unfortunate that it is limited to facial phenomena and does not mention what occurs the whole body, and that it has not been evaluated as a first-stage treatment for steroid-dependent dermatosis.

 

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ーAbout statements of the U.K.ー

This is what I’ve always thought for a long time that the terms symptoms that occur when withdrawing from topical steroids and conditions that require withdrawal from topical steroids were used in the United States and other countries without clear distinction. Although “red skin syndrome” can be used for both, I don't consider it to be appropriate words because it has not been shown to be related to steroids. "Steroid withdrawal syndrome” refers to the former, but that is inadequate in the sense that it does not explain the condition that causes corticosteroids to be stopped using. “Topical steroid addiction” may mean the latter, but in Japanese it also means “preferred use”. In fact, I won't use this word in the sense that I have to use it even if I don't like it (it also means “desire” in English). In my opinion, “steroid dependent dermatosis” is appropriate and the description of the U.K. is good because they show efforts to use the meaning of words correctly.

This statement says that redness involves a series of red shades from pink to red to purple and a slight darkening of existing skin colors. I recognize that the color change of the reddish colors is changed by constriction and dilatability of capillary and change of oxygen concentration. However, darkening is thought to be caused by pigmentation, so we need to consider it separately.

Adrenal insufficiency, such as Addison's disease, can occur generalized pigmentation. Skin inflammation causes pigmentation only in the inflamed area. In 2017, cortisol production in the skin, experiment on mice, was first demonstrated. The same experimental methods are not directly proven in humans because they are not adaptable to humans, but human skin, like rats, has the same metabolic enzymes as the adrenal cortex of internal organs, and ACTH (adrenocorticotropic hormone) in the skin has also been proven. There is a α-Melanocyte-stimulating hormone (an αMSH) gene in the ACTH gene, and I believe that when there is stress on the skin, ACTH is secreted, cortisol is produced, and α-Melanocyte-stimulating hormone is activated, causing pigmentation only at the part of inflammation.

Since systemic (oral or intravenous) administration of steroid hormones as drugs causes adrenal suppression in the internal organs, topical steroids should suppress cortisol production in the skin which has the same metabolic system.

If topical steroids are discontinued while cortisol production in the skin is suppressed by topical steroids, the topical steroids will be inactivated and the skin will be devoid of steroids, and it will not be able to resist stress, resulting in the appearance of severe inflammatory symptoms.

I believe that this symptom is just expression of steroid withdrawal syndrome in words. I think that not describing the importance of pigmentation implies ignoring the importance of steroid hormone metabolism in the skin.

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The statement "1. result of excessive use of topical corticosteroids" is true, and "2. allergic reaction to topical corticosteroids" has been confirmed by me, but only in a few cases. The possibility of "3. inability to control the underlying inflammation" is conceivable, but so far I have no case definitely.

At this point, I’m considering the possibility that continuous use of topical steroids may increase the activity of enzymes that inactivate artificial steroids, resulting in the steroids becoming less effective.

Regarding "4. What happens when topical corticosteroid therapy is discontinued," the descriptions of "rebound erythema" and "facial redness" are considered to explain correctly about some of the symptoms of steroid withdrawal syndrome.

The rest of the article contrasts in the preceding paragraph the production of steroid hormones in the skin with what happens when topical steroids suppress cortisol production.

Other than that, I will compare the situation caused by the production of steroid hormones in the skin and the suppression of cortisol production by topical steroids.

"5. Topical steroid withdrawal as one of the treatments for eczema" describes the first approval of TSW for intractable atopic dermatitis. I recognize it is a great progress for intractable atopic dermatitis. However, I suppose they should write about NMT in more detail where it says "We can deal with eczema through drug-free treatment and lifestyle changes reducing stress-induced exacerbations.".