Chapter 4 Reports in Japan – 2
Topical steroid withdrawal syndrome [Feature article] Internal disease anticipated from skin conditions, II. Skin disorder physicians should pay attention to.
By Mitsukuni Enomoto published in the Treatment:Vol.79,No.12(1997)
This article intended for internal medicine doctors was written for the magazine, Treatment, in 1997 by Dr. Enomoto, who first reported in Japan on systemic rebound phenomenon after topical corticosteroid (TCS) cessation to outline his clinical observation in the past. This one, being intended for non-dermatologist physicians, is easier to understand than his previous study in 1991.
----- Excerpt -----
Stopping TCS for patients having long been treated with TCS may cause systemic exfoliative dermatitis accompanied by 38℃ or higher fever in a few days after stoppage, which is the rebound phenomenon. Patients usually go into remission in several months without using steroids. But there are a few cases that exhibit symptoms similar to systemic steroid withdrawal syndrome including joint/muscle pain, twitch, oligouria, tachycardia and heart malfunction. These symptoms were also observed in patients with normal serum cortisol levels, and were considered TCS withdrawal syndrome.
----- End of excerpt -----
The above phrase is very important in that Dr. Enomoto pointed out the relationship with serum cortisol levels. He examined the adrenal gland function in each of the seven cases introduced in the present article. His paper in 1991 also indicated that 5 out of 7 cases exhibited adrenocortical insufficiency, which was represented by just a small decline in the ACTH loading test value and did not accompany clinically observed symptoms.
The report by Dr. Enomoto in 1991 was noticed by some doctors of great insight and cited in a general description for the TCS side effects. However, littlie attention was paid to the fact that systemic rebound can occur even without adrenal gland dysfunction. Dr. Enomoto stressed this point in his article in 1997.
I also found in the past that adrenal gland function was rather high wihen serum cortisol measured high during the rebound period after TCS discontinuation. However, daily rhythm was sometimes observed to be abnormal. Serum cortisol levels are normally higher in the early morning, but it often peaks around noon as to patients with atopic dermatitis, which might be attributable to their abnormal sleep cycle. Therefore, there were some cases where measurements for the blood taken in the early morning were low.
Occasionally, in patients treated with systemic steroids for a long time, it was found that endogenous adrenocortical steroid production capability was suppressed. In this case, substitution therapy is required. (Fatigue and weakness are typical initial symptoms for those patients when they are first seen after suspending systemic steroids.)
It took more than 2 years for my patients (not many in number) to recover from systemic steroid induced adrenocortical insufficiency. Such patients had been mostly using TCS too, and TCS had to be stopped first, and then systemic steroids were gradually reduced. Systemic steroid cessation is also accompanied by rebound flare on the skin. That is, patients must undergo steroid withdrawal twice. Specifically, systemic steroids been having administered for a patient (synthetic steroid with long half-lives such as betamethasone is often used) is to be replaced with cortisol of a physiologically required amount. Drug holidays are to be increased, according to each patient’s pace, from the initial frequency of once a week to twice a week and then every 2 days. Patients are required to visit the hospital every month or every 2 months to check the recovery of adrenocortical function by means of a rapid ACTH test. Cortisol concentration in blood initially remains at “0” even with ACTH loading, but gradually responds and shows the desired values. While withdrawal does not progress enough under the substitution therapy, serum cortisol measurement remains “0” and there’s no other way than a rapid ACTH test to confirm adrenocortical function recovery.
I respect Dr. Enomoto as an excellent dermatologist, who dared to report what he observed as it was.
----- Excerpt -----
To facilitate the understanding of topical steroid withdrawal syndrome (TSWS), it would be helpful to describe rosacea-like dermatitis, which is the local side effect of TCS. Applying Class III (strong in potency) topical steroids on the face for 1 to 2 months may cause side effects including mild skin atrophy, dilation of capillary, acne, pustilation. In such a case, we have to persuade patients to discontinue topical steroid usage, which induces rebound phenomenon. Rebound severity depends on types of steroids, application periods and primary disorders. In serious cases, eruption expands through the whole face in 1 to 2 weeks after cessation. Affected skin is highly exudative and exudate seeps through scratched wounds. Some patients complain about a burning sensation, pain or sleeplessness and usually need to be hospitalized. Such erythema peaks in 4 to 6 weeks and begins to disappear and the skin returns to normal conditions in 2 to 3 months. During this period, patients are forced to endure hardship. These severe rebound symptoms, in addition to the rosacea-like dermatitis, are the reasons long time steroid use is not recommended.
TSWS is the systemic version of the above symptoms and accompanied by symptoms similar to the systemic steroid withdrawal syndrome in addiction to the rebound flare. Although it is expected such symptoms have been observed in many dermatological clinics or departments, there is no report on it.
(snip)
When treating intractable diseases such as atopic dermatitis and psoriasis, there is a tendency that topical steroids are administered for a long time, because there are no alternative effective drugs. As a result, patients get addicted and suffer from rebound after cessation, which gives patients quite a hardship.
To avoid addiction, it is important to identify and remove root causes or exacerbating factors for the disease as far as possible. If there is no other way than to use TCS, proper measures should be taken, including intermittent administration and a less potent type of application for a certain period. If steroid usage has to be stopped due to the unfortunate occurrence of side effects, tapering doses or combining topical and systemic steroids must be considered as a way to avoid severe rebound. Not all the patients suffer from the rebound after TCS discontinuation. Also, some patients develop only exfoliative dermatitis without systemic symptoms. TCS withdrawal has yet to be studied further.
----- End of excerpt -----
Dr. Enomoto wrote in the last paragraph that tapering doses or combining topical and systemic steroids must be considered as a way to avoid severe rebound, while he also wrote in the initial part that systemic exfoliative dermatitis goes into remission in several months without using steroids. Therefore, I understand he is not totally denying “cold turkey” which means stopping steroids at once.
He is worried about renal function deterioration or heart failure. There are in fact some withdrawal cases where clinical presentations similar to heart failure are observed with severe systemic symptoms such as swollen legs. However, I have never seen patients who actually developed heart failure. If there was a risk of serious renal function deterioration or heart failure, we should have heard of many patients who are carried into the emergency room due to heart failure after stopping TCS “cold turkey” by themselves not under the support of doctors. I guess we don’t have to worry about this.
Anyway, what is great with him is that he noticed and announced that systemic symptoms developed after topical steroid discontinuation have no relation with adrenal function and are not a “withdrawal syndrome” but a “topical steroid withdrawal syndrome.”
Topical steroid withdrawal syndrome [Feature article] Internal disease anticipated from skin conditions, II. Skin disorder physicians should pay attention to.
By Mitsukuni Enomoto published in the Treatment:Vol.79,No.12(1997)
This article intended for internal medicine doctors was written for the magazine, Treatment, in 1997 by Dr. Enomoto, who first reported in Japan on systemic rebound phenomenon after topical corticosteroid (TCS) cessation to outline his clinical observation in the past. This one, being intended for non-dermatologist physicians, is easier to understand than his previous study in 1991.
----- Excerpt -----
Stopping TCS for patients having long been treated with TCS may cause systemic exfoliative dermatitis accompanied by 38℃ or higher fever in a few days after stoppage, which is the rebound phenomenon. Patients usually go into remission in several months without using steroids. But there are a few cases that exhibit symptoms similar to systemic steroid withdrawal syndrome including joint/muscle pain, twitch, oligouria, tachycardia and heart malfunction. These symptoms were also observed in patients with normal serum cortisol levels, and were considered TCS withdrawal syndrome.
----- End of excerpt -----
The above phrase is very important in that Dr. Enomoto pointed out the relationship with serum cortisol levels. He examined the adrenal gland function in each of the seven cases introduced in the present article. His paper in 1991 also indicated that 5 out of 7 cases exhibited adrenocortical insufficiency, which was represented by just a small decline in the ACTH loading test value and did not accompany clinically observed symptoms.
The report by Dr. Enomoto in 1991 was noticed by some doctors of great insight and cited in a general description for the TCS side effects. However, littlie attention was paid to the fact that systemic rebound can occur even without adrenal gland dysfunction. Dr. Enomoto stressed this point in his article in 1997.
I also found in the past that adrenal gland function was rather high wihen serum cortisol measured high during the rebound period after TCS discontinuation. However, daily rhythm was sometimes observed to be abnormal. Serum cortisol levels are normally higher in the early morning, but it often peaks around noon as to patients with atopic dermatitis, which might be attributable to their abnormal sleep cycle. Therefore, there were some cases where measurements for the blood taken in the early morning were low.
Occasionally, in patients treated with systemic steroids for a long time, it was found that endogenous adrenocortical steroid production capability was suppressed. In this case, substitution therapy is required. (Fatigue and weakness are typical initial symptoms for those patients when they are first seen after suspending systemic steroids.)
It took more than 2 years for my patients (not many in number) to recover from systemic steroid induced adrenocortical insufficiency. Such patients had been mostly using TCS too, and TCS had to be stopped first, and then systemic steroids were gradually reduced. Systemic steroid cessation is also accompanied by rebound flare on the skin. That is, patients must undergo steroid withdrawal twice. Specifically, systemic steroids been having administered for a patient (synthetic steroid with long half-lives such as betamethasone is often used) is to be replaced with cortisol of a physiologically required amount. Drug holidays are to be increased, according to each patient’s pace, from the initial frequency of once a week to twice a week and then every 2 days. Patients are required to visit the hospital every month or every 2 months to check the recovery of adrenocortical function by means of a rapid ACTH test. Cortisol concentration in blood initially remains at “0” even with ACTH loading, but gradually responds and shows the desired values. While withdrawal does not progress enough under the substitution therapy, serum cortisol measurement remains “0” and there’s no other way than a rapid ACTH test to confirm adrenocortical function recovery.
I respect Dr. Enomoto as an excellent dermatologist, who dared to report what he observed as it was.
----- Excerpt -----
To facilitate the understanding of topical steroid withdrawal syndrome (TSWS), it would be helpful to describe rosacea-like dermatitis, which is the local side effect of TCS. Applying Class III (strong in potency) topical steroids on the face for 1 to 2 months may cause side effects including mild skin atrophy, dilation of capillary, acne, pustilation. In such a case, we have to persuade patients to discontinue topical steroid usage, which induces rebound phenomenon. Rebound severity depends on types of steroids, application periods and primary disorders. In serious cases, eruption expands through the whole face in 1 to 2 weeks after cessation. Affected skin is highly exudative and exudate seeps through scratched wounds. Some patients complain about a burning sensation, pain or sleeplessness and usually need to be hospitalized. Such erythema peaks in 4 to 6 weeks and begins to disappear and the skin returns to normal conditions in 2 to 3 months. During this period, patients are forced to endure hardship. These severe rebound symptoms, in addition to the rosacea-like dermatitis, are the reasons long time steroid use is not recommended.
TSWS is the systemic version of the above symptoms and accompanied by symptoms similar to the systemic steroid withdrawal syndrome in addiction to the rebound flare. Although it is expected such symptoms have been observed in many dermatological clinics or departments, there is no report on it.
(snip)
When treating intractable diseases such as atopic dermatitis and psoriasis, there is a tendency that topical steroids are administered for a long time, because there are no alternative effective drugs. As a result, patients get addicted and suffer from rebound after cessation, which gives patients quite a hardship.
To avoid addiction, it is important to identify and remove root causes or exacerbating factors for the disease as far as possible. If there is no other way than to use TCS, proper measures should be taken, including intermittent administration and a less potent type of application for a certain period. If steroid usage has to be stopped due to the unfortunate occurrence of side effects, tapering doses or combining topical and systemic steroids must be considered as a way to avoid severe rebound. Not all the patients suffer from the rebound after TCS discontinuation. Also, some patients develop only exfoliative dermatitis without systemic symptoms. TCS withdrawal has yet to be studied further.
----- End of excerpt -----
Dr. Enomoto wrote in the last paragraph that tapering doses or combining topical and systemic steroids must be considered as a way to avoid severe rebound, while he also wrote in the initial part that systemic exfoliative dermatitis goes into remission in several months without using steroids. Therefore, I understand he is not totally denying “cold turkey” which means stopping steroids at once.
He is worried about renal function deterioration or heart failure. There are in fact some withdrawal cases where clinical presentations similar to heart failure are observed with severe systemic symptoms such as swollen legs. However, I have never seen patients who actually developed heart failure. If there was a risk of serious renal function deterioration or heart failure, we should have heard of many patients who are carried into the emergency room due to heart failure after stopping TCS “cold turkey” by themselves not under the support of doctors. I guess we don’t have to worry about this.
Anyway, what is great with him is that he noticed and announced that systemic symptoms developed after topical steroid discontinuation have no relation with adrenal function and are not a “withdrawal syndrome” but a “topical steroid withdrawal syndrome.”