British journal of Dermatology (1992) 127. 542-548.
Correspondence Clobetasol propionate 0()S% cream in the treatment of vulvar lichen sclerosus: effect on the immunohistological profik SIR. Lichen sclerosus et atrophicus (LSA) is a chronic dermatosis which predominantly affects the genital areas, and vulvar LSA is a common management problem for gynaecologists and dermatologists. Currently employed treatments, including mild or moderate potency topical steroids and testosterone propionate 2% ointment, usually fail to control disease activity completely, often providing only partial symptomatic relief of vulvar pruritus and dryness.' ' Clobetasol propionate ()-{)S% cream, a very potent fiuorinated topical steroid, has recently been reported t{) improve vulvar LSA both clinically and histoiogically. without producing significant side-effects."' This is in keeping with our experience. Preliminary data from a trial in which 20 cases of vulvar LSA were treated with clohetasol propionate showed that the clinical and histological cure rate was markedly higher than that oiitained in a control group treated with topical 2% testosterone.'' However, longer followup is required to confirm this therapeutic efTect. Moreover, in some cases, dramatic clinical improvement is not associated with a comparable improvement in bistological cbanges. Tbe aetiology of LSA is unknown hut there is increasing evidence that the skin immune system is involved in disease activity.*"' An activated HLA-DR + T-cell dermal infiltrate, associated with dendritic CD)a* accessory cells, and an increased number of epidermal CDla ' Langerbans cells (LCs) is found in untreated vulvar LSA,' Tbese findings suggest that LSA should be included in tbe group of immunomcdiated dermatoses. It is possihle tbat the epidermal atrophy and dermal fibrosis present in LSA are related to skin immune system activation via lympbocyte production of cytokines capable of modulating keratinocyte proliferation and fibroblast collagen syntbesis."'' We have recently conducted a study in order to establish whether a i-montb period of treatment with clobetasol
propionate could modify the ahove-mentioned immunobistological pattern. An immunohistochemicai analysis of vulvar biopsies was performed in 10 women before and after clobetasol treatment (twice daily for 1 month and once daily for 2 months). In seven cases, twice-weekly maintenance therapy was continued for an additional J months, followed by a furtber biopsy ((S montbs from tbe start of treatment). A panel of monoclonal antibodies against T cells (anti-CD3. -CD4. -CD8). class II antigens (anti-HLA-DR). Langerhans cells and related dendritic cells (anti-CDla) was employed, using the alkaline phospbatase anti-alkaline phosphatase (APAAP) method. Immunohistological evaluation after 5 montbs treatment showed a dramatic reduction of the dermal lympboid infiltrate in all cases; only scattered CDi^/CD4^ cells were found in the upper and mid-dermis (Fig. I). The numher of epidermal dendritic CDI a* cells/100 basal cells appeared reduced (pretreatment 22-7± 1-9: after 3 montbs f)-f>± l-O). and HLA-DR staining was confined to dermal vessels and to a
80 70
S 50 01
S a 40 ^ 30 20 10 0 CD3
HLA-DR •*
Epidermol CDla+/ 100 bosol keratinocytes
Figure \. Effect of clobetesol treatment on the immunohistocbemicai profile. • , Before treatment: K, 3rd month: El. 6tfi month.
S42
2. Aiiti-HL'\-I)K MAb. Bclbrc Ireatment—the majority of cells in the dermal lympfiocytic infiltrate express class II antigens. In the epidermis, dendritic cells are strongly stained.
British Journal of Dermatology (1992) 127
CORRESPONDENCE
o i. Anli-HLA-I)R MAb. After d iiioiillis clobelasol treatment only endolbetial staining is found in the dermis.
lew epidermal LCs (Figs 2 and i). In the seven cases who used maintenance treatment, the Immunohistological pattern at 6 months remained essentially the same, with regard to numbers of dermai lymphocytes and expression of class II antigens. However, the number of CDla^ epidermal LCs was increased (i 4-1 ± 1 -9), almost reaching the level found in normal vulvar epidermis {16-5±i 7) (four biopsies performed as controis from uninvolved perilesional skin). hi conclusion, treatment with a very potent topical steroid such as clohetasol propionate not only improves the clinical and histological features of vulvar LSA. but also modifies the immunobistochemical parameters of skin immune system activation. These preliminary data suggest that, after a treatment course of 3 montbs. maintenance tberapy is advisable to provide iwtter long-term control of this disease. Department of Dermatoiogy. 'Department of Obstetrics and Gynaecology. University of Florence. Italy
543
5 Bracco GL, Sonni [„ Carll F et ul. A critical evaluation of clinical and histological eflects of topical treatment of lichen sclerosus witb 2% testosterone, 2% progesterone. U-05% clobetasol and cream-base. Eleventh Congress of the International Soeietfi for the Study of Vulvar Diseases flSSVD). September. 1991. 6 Dickie R|. Horne CHW. Sutherland HW et al. Direct evidence of localised immunological damage in vulvar lichen sclerosus et atrophicus. / Clin Pathol 19«6; 55: IJ95-7, 7 Carii P. Cattaneo A. Pimpinelli N el al. Immunohistochemical evidence of skin immune system involvement in vulvar lichen sclerosus et atrophicus. DermaUAogira 1991: 182; 18-22, 8 Pittelkow MR. Shipley (ID, Wille I] Jr pr al. Growth regulation of human prokeratinocytes by T(1F-a and ICF-p. / Invest Dermatol 19K6: 86: 500, 9 Freundlich B. Bomalski |S. Neilson R. Jimenez SA. Regulation of fibroblast proliferation and collagen synthesis by cytokines. Immunology Today 1986: 7: 303-7.
Potent topical steroid obtained from a Chinese herbalist SIR. We present a case ofa patient obtaining a potent topicai steroid witbout prescription from a Chinese berbalist. A 5year-old Cbinese boy with a i-year history of atopic eczema vi/as accompanied to a follow-up clinic by bis father. His father reported tbat whilst tbe 1% bydrocortisone ointment wbich had been prescribed for his son on his previous attendance had been of iittie value, tbere bad been a remarkable improvement in his eczema over a J-month period after obtaining a nonprescription remedy from a Chinese berbalist. However, it was apparent from the packet (Fig. 1) that he had received tbe potent topical steroid Huocinolone acetonide 0 0 2 5%. He had not been warned of the potential side-effects of using tbis type of preparation and bad used it twice a day on his son's face. The
P.CARLI •A.CATTANEO B.GIANNOITI
Correspondence: Dr P.Carli. CUnica Dermatologica II. via della Percfola 58. 50121. I'lorence. Italy
References 1 Ridley CM. Lichen sclerosus et atrophicus. In: The Vulva (Ridley CM. ed.). Edinburgh: Churchill Livingstone, 1988: 172-88. 2 Cattaneo A. Bracco C. Maestrini C. et al. Lichen sclerosus and squamous hyperplasia of the vulva. A clinical study of medical trt-titmcnt, / Reprod Med 1991: 36: 301-5. i Carli P. Cozza A, Bracco C et al. Testosterone al 2% nel lichen sclernatrofico vulvare. Valutazione immunoistologica e dubbi sulla etficacia terapeutica. (,' Ital Dermatol Venereol 1991: 126: 61-3, 4 Dalziel KL. Millard PR, Wojnarowska F, The treatment of vulval lichen sclerosus with a very potent topical .steroid (clobetasol propionate 0 05%) cream, Br } Dermatol 1991: 1 2 4 : 4 6 1 ^ ,
1 igure 1.
eczema bad indeed improved, and fortunately tbere was no evidence of steroid-induced cutaneous damage. There are many medicinal compounds used by practitioners of traditional Chinese medicine. In Western countries, although many Cbinese and Asian residents will self-medicate
Correspondence Clobetasol propionate 0()S% cream in the treatment of vulvar lichen sclerosus: effect on the immunohistological profik SIR. Lichen sclerosus et atrophicus (LSA) is a chronic dermatosis which predominantly affects the genital areas, and vulvar LSA is a common management problem for gynaecologists and dermatologists. Currently employed treatments, including mild or moderate potency topical steroids and testosterone propionate 2% ointment, usually fail to control disease activity completely, often providing only partial symptomatic relief of vulvar pruritus and dryness.' ' Clobetasol propionate ()-{)S% cream, a very potent fiuorinated topical steroid, has recently been reported t{) improve vulvar LSA both clinically and histoiogically. without producing significant side-effects."' This is in keeping with our experience. Preliminary data from a trial in which 20 cases of vulvar LSA were treated with clohetasol propionate showed that the clinical and histological cure rate was markedly higher than that oiitained in a control group treated with topical 2% testosterone.'' However, longer followup is required to confirm this therapeutic efTect. Moreover, in some cases, dramatic clinical improvement is not associated with a comparable improvement in bistological cbanges. Tbe aetiology of LSA is unknown hut there is increasing evidence that the skin immune system is involved in disease activity.*"' An activated HLA-DR + T-cell dermal infiltrate, associated with dendritic CD)a* accessory cells, and an increased number of epidermal CDla ' Langerbans cells (LCs) is found in untreated vulvar LSA,' Tbese findings suggest that LSA should be included in tbe group of immunomcdiated dermatoses. It is possihle tbat the epidermal atrophy and dermal fibrosis present in LSA are related to skin immune system activation via lympbocyte production of cytokines capable of modulating keratinocyte proliferation and fibroblast collagen syntbesis."'' We have recently conducted a study in order to establish whether a i-montb period of treatment with clobetasol
propionate could modify the ahove-mentioned immunobistological pattern. An immunohistochemicai analysis of vulvar biopsies was performed in 10 women before and after clobetasol treatment (twice daily for 1 month and once daily for 2 months). In seven cases, twice-weekly maintenance therapy was continued for an additional J months, followed by a furtber biopsy ((S montbs from tbe start of treatment). A panel of monoclonal antibodies against T cells (anti-CD3. -CD4. -CD8). class II antigens (anti-HLA-DR). Langerhans cells and related dendritic cells (anti-CDla) was employed, using the alkaline phospbatase anti-alkaline phosphatase (APAAP) method. Immunohistological evaluation after 5 montbs treatment showed a dramatic reduction of the dermal lympboid infiltrate in all cases; only scattered CDi^/CD4^ cells were found in the upper and mid-dermis (Fig. I). The numher of epidermal dendritic CDI a* cells/100 basal cells appeared reduced (pretreatment 22-7± 1-9: after 3 montbs f)-f>± l-O). and HLA-DR staining was confined to dermal vessels and to a
80 70
S 50 01
S a 40 ^ 30 20 10 0 CD3
HLA-DR •*
Epidermol CDla+/ 100 bosol keratinocytes
Figure \. Effect of clobetesol treatment on the immunohistocbemicai profile. • , Before treatment: K, 3rd month: El. 6tfi month.
S42
2. Aiiti-HL'\-I)K MAb. Bclbrc Ireatment—the majority of cells in the dermal lympfiocytic infiltrate express class II antigens. In the epidermis, dendritic cells are strongly stained.
British Journal of Dermatology (1992) 127
CORRESPONDENCE
o i. Anli-HLA-I)R MAb. After d iiioiillis clobelasol treatment only endolbetial staining is found in the dermis.
lew epidermal LCs (Figs 2 and i). In the seven cases who used maintenance treatment, the Immunohistological pattern at 6 months remained essentially the same, with regard to numbers of dermai lymphocytes and expression of class II antigens. However, the number of CDla^ epidermal LCs was increased (i 4-1 ± 1 -9), almost reaching the level found in normal vulvar epidermis {16-5±i 7) (four biopsies performed as controis from uninvolved perilesional skin). hi conclusion, treatment with a very potent topical steroid such as clohetasol propionate not only improves the clinical and histological features of vulvar LSA. but also modifies the immunobistochemical parameters of skin immune system activation. These preliminary data suggest that, after a treatment course of 3 montbs. maintenance tberapy is advisable to provide iwtter long-term control of this disease. Department of Dermatoiogy. 'Department of Obstetrics and Gynaecology. University of Florence. Italy
543
5 Bracco GL, Sonni [„ Carll F et ul. A critical evaluation of clinical and histological eflects of topical treatment of lichen sclerosus witb 2% testosterone, 2% progesterone. U-05% clobetasol and cream-base. Eleventh Congress of the International Soeietfi for the Study of Vulvar Diseases flSSVD). September. 1991. 6 Dickie R|. Horne CHW. Sutherland HW et al. Direct evidence of localised immunological damage in vulvar lichen sclerosus et atrophicus. / Clin Pathol 19«6; 55: IJ95-7, 7 Carii P. Cattaneo A. Pimpinelli N el al. Immunohistochemical evidence of skin immune system involvement in vulvar lichen sclerosus et atrophicus. DermaUAogira 1991: 182; 18-22, 8 Pittelkow MR. Shipley (ID, Wille I] Jr pr al. Growth regulation of human prokeratinocytes by T(1F-a and ICF-p. / Invest Dermatol 19K6: 86: 500, 9 Freundlich B. Bomalski |S. Neilson R. Jimenez SA. Regulation of fibroblast proliferation and collagen synthesis by cytokines. Immunology Today 1986: 7: 303-7.
Potent topical steroid obtained from a Chinese herbalist SIR. We present a case ofa patient obtaining a potent topicai steroid witbout prescription from a Chinese berbalist. A 5year-old Cbinese boy with a i-year history of atopic eczema vi/as accompanied to a follow-up clinic by bis father. His father reported tbat whilst tbe 1% bydrocortisone ointment wbich had been prescribed for his son on his previous attendance had been of iittie value, tbere bad been a remarkable improvement in his eczema over a J-month period after obtaining a nonprescription remedy from a Chinese berbalist. However, it was apparent from the packet (Fig. 1) that he had received tbe potent topical steroid Huocinolone acetonide 0 0 2 5%. He had not been warned of the potential side-effects of using tbis type of preparation and bad used it twice a day on his son's face. The
P.CARLI •A.CATTANEO B.GIANNOITI
Correspondence: Dr P.Carli. CUnica Dermatologica II. via della Percfola 58. 50121. I'lorence. Italy
References 1 Ridley CM. Lichen sclerosus et atrophicus. In: The Vulva (Ridley CM. ed.). Edinburgh: Churchill Livingstone, 1988: 172-88. 2 Cattaneo A. Bracco C. Maestrini C. et al. Lichen sclerosus and squamous hyperplasia of the vulva. A clinical study of medical trt-titmcnt, / Reprod Med 1991: 36: 301-5. i Carli P. Cozza A, Bracco C et al. Testosterone al 2% nel lichen sclernatrofico vulvare. Valutazione immunoistologica e dubbi sulla etficacia terapeutica. (,' Ital Dermatol Venereol 1991: 126: 61-3, 4 Dalziel KL. Millard PR, Wojnarowska F, The treatment of vulval lichen sclerosus with a very potent topical .steroid (clobetasol propionate 0 05%) cream, Br } Dermatol 1991: 1 2 4 : 4 6 1 ^ ,
1 igure 1.
eczema bad indeed improved, and fortunately tbere was no evidence of steroid-induced cutaneous damage. There are many medicinal compounds used by practitioners of traditional Chinese medicine. In Western countries, although many Cbinese and Asian residents will self-medicate
