Australas J. Dermatol 1992; 33: 177-178
REPORT OF MEETING A Review of the 1992 Annual Meeting of the British Society for Investigative Dermatology In the last week of September the annual scientific meeting of BSID was held in Sheffield. Forty-six papers were presented. Four guest lectures were given, and forty posters were on display. The first session was devoted to the p53 tumour suppressor gene and its role in psoriasis and nonmelanotic skin cancer. The session was dominated by four papers from the team of the new 34 year old professor Dermatology at Newcastle, J.L. Rees. The p53 gene product is a nuclear phosphoprotrein which is thought to have a central role in the negative regulation (inhibition) of cell growth and division, acting at the Gl phase of the cell cycle. Mutations in the p53 gene, which can be detected by a mutant p53 monoclonal antibody, are the commonest genetic event yet identified in human neoplasia. Mutant p53 is present in up to 50% of SCC and BCC and 20-30% of Bowen's Disease and actinic keratosis. Furthermore as p53 mutation is equally prevalent in skin cancers of renal transplant recipients it was suggested that virus (eg. HPV) may not be an important cause of skin cancer in these patients. The second session related to psoralen phototherapy (not PUVA). The take home messages were: P-UVB is more effective in psoriasis than UVB alone. The dose of 8-MOP better correlates with serum levels when calculated on the basis of surface area at 25mg/m' (linear correlation), than when calculated on weight at 0.6mg/kg (low serum levels in patients less than 50kg). The dose response curve for topical 8-MOP and oral 8-MOP are parallel. Thus the lower UVA dose required for bath PUVA represents the higher cutaneous concentration of psoralen and not a qualitative difference between the two procedures. Narrow-band phototherapy (311-313nm) is more effective than broad-band phototherapy (280-340nm) in the treatment of psoriasis, but it is also more tumorogenic in hairless mouse skin. Neither the level of endogenous pigmentation nor the amount of acquired pigmentation
interferes with the perception of minimal erythema dose (MED) in Caucasians. In Negroes however, the MED overestimates by a factor of two the erythemal sensitivity when correlated against cutaneous vasodilatation and cellular damage. The guest lecture at the end of this session was given by Dr J.J. Nordlund from Cincinatti on the pathogenesis of vitiligo, and his experience of 25 years of research in this condition. His main points were: That vitiligo may affect any pigment cell in the body, including the retina and the leptomeninges. That the skin is functionally aberrant in vitiligo, as evidenced by diminished contact sensitivity. That association with other autoimmune diseases is fortuitous and no greater than the national average in the USA. That the aetiological defect is in the translocation of tyrosinase in the melanocyte which leads to cell death and the secondary development of autoantobodies. Hence the immune system is not involved in the pathogenesis. The inheritance of vitiligo involves at least three genes and does not follow a simple Mendelian trait. That acrofacial vitiligo is merely an early manifestation of generalised disease and not a variant. That generalised spontaneous repigmentation is a rare event. Finally, the PUVA given for prolonged periods is an effective treatment. The third session was devoted to cutaneous appendages and the introductory lecture was given by Dr A.G. Messenger in the place of the late Professor F.J.G. Ebling, for whom a minutes silence was observed. In this session we learned that the mouse telogen hair follicle has an easily identified collection of stem cells located in a bulge on the lateral wall which gives rise to the new anagen follicle. We also learned that cyclosporin delays cultured anagen hair follicles from entering catagen, which is consistent with the observed 177
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clinical benefit of cyclosporin in androgenetic alopecia. On the subject of androgen-dependent alopecia, it was stated that minoxidil induces hair re-growth in females only in the presence of optimal iron stores. Optimal iron stores were redefined as a serum ferritin greater than 40 micrograms/L. On the nail front keratin studies showed that the nail matrix and the hair matrix share in common the production of K2 keratin filaments, which are not produced by nonappendigeal skin. Furthermore the nail bed, whilst contributing up to one third of the nail plate thickness, only produces Kl and KIO filaments suggesting it does not contribute to the functional integrity of nail plate. The highlight of the next session was the disclosure that smoking is a risk factor for the subsequent development of psoriasis, but confers protection against the development of severe acne. Other papers suggested that H3 receptors are not found in the skin; that the rate of take of grafted cultured keratinocytes on full thickness wounds can be increased by initially grafting the wound with cultured autologous dermis seven days prior to the epidermal graft; and that new retinol esters are less irritating and are also effective in reversing extrinsic ageing and in treating solar keratoses. The fifth session related to immunobullous disease. The first paper showed that cimetidine can reduce dapsone-induced haematological toxicity by inhibiting the hydroxylation but not the acetylation of dapsone in the liver. Methaemoglobinaemia was reduced and higher trough levels of dapsone were achieved. Further studies are needed to evaluate the effect of
178
cimetidine on dapsone induced haemolysis. In another paper the heterogeneity of the linear igA target antigen was demonstrated. Two distinct antigens have now been identified: one is a 385 kDa epidermal antigen, and the second is a dermal antigen that is co-distributed with, but distinct from type VII collagen. The final session of the meeting was devoted to cytokines, and in particular their molecular genetics, intracellular signalling and "crosstalking" between cytokines. Cross-talking describes the phenomenon where opposing signals interact at multiple levels. These interactions occur firstly at the receptor and subsequently at the six or so protein kinases that act as second messengers for a larger number of hormones and cytokines, as well as at the sites of intracellular phosphorolation. Finally interaction occurs at the level of the biological response. By investigating cross-talk it is possible that we will develop a dynamic understanding of the role of cytokines in the skin. The highlight of the Annual Dinner was the talk given by Professor Sam Shuster to mark his retirement. Professor Suster vented some spleen on those in the audience whom he believed were involved in the demise of Dermatology through the generation of fatuous research merely to augment their curriculum vitae. His finale included tearing the most recent British Journal of Dermatology Supplement in half and throwing it twenty feet into the air to land on a table of seven blushing British dermatology Professors. Rodney Sinclair
REPORT OF MEETING A Review of the 1992 Annual Meeting of the British Society for Investigative Dermatology In the last week of September the annual scientific meeting of BSID was held in Sheffield. Forty-six papers were presented. Four guest lectures were given, and forty posters were on display. The first session was devoted to the p53 tumour suppressor gene and its role in psoriasis and nonmelanotic skin cancer. The session was dominated by four papers from the team of the new 34 year old professor Dermatology at Newcastle, J.L. Rees. The p53 gene product is a nuclear phosphoprotrein which is thought to have a central role in the negative regulation (inhibition) of cell growth and division, acting at the Gl phase of the cell cycle. Mutations in the p53 gene, which can be detected by a mutant p53 monoclonal antibody, are the commonest genetic event yet identified in human neoplasia. Mutant p53 is present in up to 50% of SCC and BCC and 20-30% of Bowen's Disease and actinic keratosis. Furthermore as p53 mutation is equally prevalent in skin cancers of renal transplant recipients it was suggested that virus (eg. HPV) may not be an important cause of skin cancer in these patients. The second session related to psoralen phototherapy (not PUVA). The take home messages were: P-UVB is more effective in psoriasis than UVB alone. The dose of 8-MOP better correlates with serum levels when calculated on the basis of surface area at 25mg/m' (linear correlation), than when calculated on weight at 0.6mg/kg (low serum levels in patients less than 50kg). The dose response curve for topical 8-MOP and oral 8-MOP are parallel. Thus the lower UVA dose required for bath PUVA represents the higher cutaneous concentration of psoralen and not a qualitative difference between the two procedures. Narrow-band phototherapy (311-313nm) is more effective than broad-band phototherapy (280-340nm) in the treatment of psoriasis, but it is also more tumorogenic in hairless mouse skin. Neither the level of endogenous pigmentation nor the amount of acquired pigmentation
interferes with the perception of minimal erythema dose (MED) in Caucasians. In Negroes however, the MED overestimates by a factor of two the erythemal sensitivity when correlated against cutaneous vasodilatation and cellular damage. The guest lecture at the end of this session was given by Dr J.J. Nordlund from Cincinatti on the pathogenesis of vitiligo, and his experience of 25 years of research in this condition. His main points were: That vitiligo may affect any pigment cell in the body, including the retina and the leptomeninges. That the skin is functionally aberrant in vitiligo, as evidenced by diminished contact sensitivity. That association with other autoimmune diseases is fortuitous and no greater than the national average in the USA. That the aetiological defect is in the translocation of tyrosinase in the melanocyte which leads to cell death and the secondary development of autoantobodies. Hence the immune system is not involved in the pathogenesis. The inheritance of vitiligo involves at least three genes and does not follow a simple Mendelian trait. That acrofacial vitiligo is merely an early manifestation of generalised disease and not a variant. That generalised spontaneous repigmentation is a rare event. Finally, the PUVA given for prolonged periods is an effective treatment. The third session was devoted to cutaneous appendages and the introductory lecture was given by Dr A.G. Messenger in the place of the late Professor F.J.G. Ebling, for whom a minutes silence was observed. In this session we learned that the mouse telogen hair follicle has an easily identified collection of stem cells located in a bulge on the lateral wall which gives rise to the new anagen follicle. We also learned that cyclosporin delays cultured anagen hair follicles from entering catagen, which is consistent with the observed 177
REPORT OF
MEETiNG
clinical benefit of cyclosporin in androgenetic alopecia. On the subject of androgen-dependent alopecia, it was stated that minoxidil induces hair re-growth in females only in the presence of optimal iron stores. Optimal iron stores were redefined as a serum ferritin greater than 40 micrograms/L. On the nail front keratin studies showed that the nail matrix and the hair matrix share in common the production of K2 keratin filaments, which are not produced by nonappendigeal skin. Furthermore the nail bed, whilst contributing up to one third of the nail plate thickness, only produces Kl and KIO filaments suggesting it does not contribute to the functional integrity of nail plate. The highlight of the next session was the disclosure that smoking is a risk factor for the subsequent development of psoriasis, but confers protection against the development of severe acne. Other papers suggested that H3 receptors are not found in the skin; that the rate of take of grafted cultured keratinocytes on full thickness wounds can be increased by initially grafting the wound with cultured autologous dermis seven days prior to the epidermal graft; and that new retinol esters are less irritating and are also effective in reversing extrinsic ageing and in treating solar keratoses. The fifth session related to immunobullous disease. The first paper showed that cimetidine can reduce dapsone-induced haematological toxicity by inhibiting the hydroxylation but not the acetylation of dapsone in the liver. Methaemoglobinaemia was reduced and higher trough levels of dapsone were achieved. Further studies are needed to evaluate the effect of
178
cimetidine on dapsone induced haemolysis. In another paper the heterogeneity of the linear igA target antigen was demonstrated. Two distinct antigens have now been identified: one is a 385 kDa epidermal antigen, and the second is a dermal antigen that is co-distributed with, but distinct from type VII collagen. The final session of the meeting was devoted to cytokines, and in particular their molecular genetics, intracellular signalling and "crosstalking" between cytokines. Cross-talking describes the phenomenon where opposing signals interact at multiple levels. These interactions occur firstly at the receptor and subsequently at the six or so protein kinases that act as second messengers for a larger number of hormones and cytokines, as well as at the sites of intracellular phosphorolation. Finally interaction occurs at the level of the biological response. By investigating cross-talk it is possible that we will develop a dynamic understanding of the role of cytokines in the skin. The highlight of the Annual Dinner was the talk given by Professor Sam Shuster to mark his retirement. Professor Suster vented some spleen on those in the audience whom he believed were involved in the demise of Dermatology through the generation of fatuous research merely to augment their curriculum vitae. His finale included tearing the most recent British Journal of Dermatology Supplement in half and throwing it twenty feet into the air to land on a table of seven blushing British dermatology Professors. Rodney Sinclair
