Chapter 21 UVB Irradiation Therapy and Rebound
Dichotomous effect of ultraviolet B on the expression of corneodesmosomal enzymes in human epidermal keratinocytes
By M Nin et al. published in the Journal of Dermatological Science 54 (2009) 17-24
The study with the above title, not intended to handle posttopical steroid rebound, refers to Dr. Cork’s skin barrier disruption theory as a good explanation for the phenomenon of addiction or rebound after prolonged use of topical corticosteroids. But it has eventually raised a question about his theory.
First of all, let’s take a quick look at Dr. Cork’s theory.
Dichotomous effect of ultraviolet B on the expression of corneodesmosomal enzymes in human epidermal keratinocytes
By M Nin et al. published in the Journal of Dermatological Science 54 (2009) 17-24
The study with the above title, not intended to handle posttopical steroid rebound, refers to Dr. Cork’s skin barrier disruption theory as a good explanation for the phenomenon of addiction or rebound after prolonged use of topical corticosteroids. But it has eventually raised a question about his theory.
First of all, let’s take a quick look at Dr. Cork’s theory.
Corneocytes, bonded together by corneodesmosomes, provide the barrier against environmental allergens. The integrity of the barrier function is maintained as long as proteases and protease inhibitors are modulated in good balance.
Nin et al. wrote that UVB irradiation on cultured epidermal cells increased proteases (SCCE and SCTE) and decreased inhibitor (LEKTI). That is, continued UVB irradiation on AD skin lesions should result in addiction and rebound according to Dr. Cork’s theory.
However, I have not heard of rebound occurrence after UVB therapy for AD. How can we consider this fact?
Inhibition of T helper 2 chemokine production by narrowband ultraviolet B in cultured keratinocytes
By R. Hino etc. published in the British Journal of Dermatology Volume 156(2007) Issue 5, Pages 830 – 837
I thought the above paper might have a hint. This paper compared the effect of a narrow band UVB irradiation system with that of conventional UVB irradiation system. Hino et al. found that UVB irradiation increased TH1 cytokines such as IL-1α and TNFα, whereas it suppressed Th2 cytokines such as MDC and TARC.
Topical corticosteroids, while destroying the skin barrier, strongly shift the Th1/Th2 balance toward Th2-dominant immunity. On the other hand, UVB irradiation disrupts the epidermal barrier as topical steroids would do, but suppresses the Th2 immune response in the Th1/Th2 balance. I estimate this is the reason UVB irradiation does not lead to rebound.
Dr. Cork’s explanation highlighting the skin barrier disruption as the causative factor for addiction and rebound caused by the long-term use of topical corticosteroids might not be perfect in a strict sense. Putting together two different experimental results, it can be said that topical corticosteroids, if used for a long time, will act on epidermal cells to impair the skin barrier function and shift the Th1/Th2 balance to Th2-domint immunity, resulting in addiction and rebound.
However, there is an animal experimental model using mice that demonstrates the occurrence of rebound after UVB (see Chapter 26). (Some points are made that persistent light reaction or actinic reticuloid might be a rebound phenomenon due to UVB irradiation on the skin.) If rebound occurs on the human skin after UVB irradiation for AD treatment, Dr. Cork’s theory will be supported.
At any rate, Dr. Cork’s theory is important not because he shed light on the activity of proteases such as SCCE but because he explained the rebound in light of the damage on the epidermal cells. Addiction and rebound are not caused in treatment of asthma or collagen disorder where steroids are inhaled or internally applied. They are problems that occur only when steroids are topically used on the skin for a long time.
Described below is the additional information of narrow band UVB irradiation.
Nin et al. wrote that UVB irradiation on cultured epidermal cells increased proteases (SCCE and SCTE) and decreased inhibitor (LEKTI). That is, continued UVB irradiation on AD skin lesions should result in addiction and rebound according to Dr. Cork’s theory.
However, I have not heard of rebound occurrence after UVB therapy for AD. How can we consider this fact?
Inhibition of T helper 2 chemokine production by narrowband ultraviolet B in cultured keratinocytes
By R. Hino etc. published in the British Journal of Dermatology Volume 156(2007) Issue 5, Pages 830 – 837
I thought the above paper might have a hint. This paper compared the effect of a narrow band UVB irradiation system with that of conventional UVB irradiation system. Hino et al. found that UVB irradiation increased TH1 cytokines such as IL-1α and TNFα, whereas it suppressed Th2 cytokines such as MDC and TARC.
Topical corticosteroids, while destroying the skin barrier, strongly shift the Th1/Th2 balance toward Th2-dominant immunity. On the other hand, UVB irradiation disrupts the epidermal barrier as topical steroids would do, but suppresses the Th2 immune response in the Th1/Th2 balance. I estimate this is the reason UVB irradiation does not lead to rebound.
Dr. Cork’s explanation highlighting the skin barrier disruption as the causative factor for addiction and rebound caused by the long-term use of topical corticosteroids might not be perfect in a strict sense. Putting together two different experimental results, it can be said that topical corticosteroids, if used for a long time, will act on epidermal cells to impair the skin barrier function and shift the Th1/Th2 balance to Th2-domint immunity, resulting in addiction and rebound.
However, there is an animal experimental model using mice that demonstrates the occurrence of rebound after UVB (see Chapter 26). (Some points are made that persistent light reaction or actinic reticuloid might be a rebound phenomenon due to UVB irradiation on the skin.) If rebound occurs on the human skin after UVB irradiation for AD treatment, Dr. Cork’s theory will be supported.
At any rate, Dr. Cork’s theory is important not because he shed light on the activity of proteases such as SCCE but because he explained the rebound in light of the damage on the epidermal cells. Addiction and rebound are not caused in treatment of asthma or collagen disorder where steroids are inhaled or internally applied. They are problems that occur only when steroids are topically used on the skin for a long time.
Described below is the additional information of narrow band UVB irradiation.
Mr. Hino used the narrow band UVB lamp with a restricted wavelength of 310~315 nm in his study. It shows the improvement comparing to the line of broadband that partly coincides with a line of wavelength causing undesirable burning effect. Six years ago when I was still working as a dermatologist, narrowband UVB treatment was uncommon. Usual BB (broadband)-UVB irradiator was available, but not employed for AD treatment considering such risks as burning. If NB-UVB is proved to be a safe method free from addiction and rebound, it is very favorable.
However, this method will be difficult to be employed unless patients get enough explanation about the risk of addiction and rebound caused by long-term use of topical corticosteroids. If topical corticosteroids are said to be safe as long as they are used following the guideline who will dare to accept the treatment with NB-UVB?
People still have the strong image that UV is carcinogenic and should wonder why such a dangerous method has to be used instead of steroids. The same thing can be said as to immunosuppressants such as Protopic (Tacrolimus).
Neglecting the phenomenon of addiction or rebound after a prolonged use of topical corticosteroids and avoiding clear explanation on it when asked by patients will cause distrust in new treatment methods and deprive patients of the chance for treatment.
However, this method will be difficult to be employed unless patients get enough explanation about the risk of addiction and rebound caused by long-term use of topical corticosteroids. If topical corticosteroids are said to be safe as long as they are used following the guideline who will dare to accept the treatment with NB-UVB?
People still have the strong image that UV is carcinogenic and should wonder why such a dangerous method has to be used instead of steroids. The same thing can be said as to immunosuppressants such as Protopic (Tacrolimus).
Neglecting the phenomenon of addiction or rebound after a prolonged use of topical corticosteroids and avoiding clear explanation on it when asked by patients will cause distrust in new treatment methods and deprive patients of the chance for treatment.