The 2015 World Congress of Dermatology was held in Vancouver in June and appropriately as the meeting was being held in British Columbia, the British Association of Dermatologists was invited to organise a half day meeting called the Best of British. Amazingly 19 Professors of Dermatology from the UK presented at this meeting.
Professor Rustin presented the collaborative research that has been ongoing with Professor Arne Akbar at University College Hospital showing that the skin in an ageing person (>60) has an impaired immune response to a number of antigens injected into the skin compared to a younger group of healthy people. Surprisingly stimulation of cells collected from suction blisters overlying the site of antigen injection and then incubated with the same antigen results in a normal response. This would suggest that the local environment within the skin is having an inhibitory effect and it is now believed that this is due to increased numbers of regulatory T cells in elderly skin which down regulates the accumulation and proliferation of memory T lymphocytes. Furthermore they also found that the lymphocytes resident in the skin of the elderly have on their surface an increased expression of PD-1 which is a molecule that also inhibits the function of lymphocytes. These findings are particularly relevant since skin tumours arising in the skin such as basal cell carcinomas, squamous cell carcinomas and melanomas usually have lymphocytes within and around the tumours but they do not appear to be cytotoxic or killing the tumour cells. There is therefore a potential to correct this abnormality with antibodies against PD-1 and this strategy has already been converted into therapeutic success in the treatment of melanoma and more recently with lung, gastric, head and neck cancers using pembrolizumab or novilumab. On the background of this research Prof Akbar was recently awarded a £3 million pound grant from the MRC.
The treatment of psoriasis has been revolutionised with biologicals but unfortunately many patients fail with these drugs either due to lack of efficacy or because of side effects. Professor Griffiths from Manchester and other dermatology colleagues were awarded a £5million grant from the MRC and £2 million from industry sponsors to run a consortium entitled PSORT(psoriasis stratification to optimise relevant therapy) in order to determine which drug would be the most appropriate for that particular patient and to try and predict which patient would develop side effects. The study will involve collection of sophisticated pharmacological, genetic, transcriptomic and complex immune data from blood and skin samples and should deliver novel personalised medicine approaches to patients with psoriasis.
Professor Sean Whittaker from Guy's and St Thomas' Hospital described his involvement in the 100,000 Genomes Project with the recruitment of patients suffering from skin lymphomas, psoriasis and eczema. The aim will be to accurately phenotype patients (the pattern and extent of their skin disease) with these disorders and then to combine genome sequence data in order to better understand the pathogenesis of these diseases, develop prenatal testing, therapeutic stratification and to better understand mechanisms that control the reason why a patient develops a mild or severe form of the disease.
There were several talks about the cause of skin cancers particularly the more serious squamous cell carcinoma which has the unpredictable ability to metastasise and for which at the moment there is no successful treatment. Professors Harwood and Sterling from the Royal London and Addenbrookes Hospitals respectively talked about the role of the human papilloma viruses in the development of these cancers. There is still an ongoing debate as to whether these viruses are coincidentally present in these tumours or whether they are actively involved in the promotion of neoplasia by interfering with cellular repair and tumour suppressor gene function. Professor Leigh from Dundee also spoke about the role of mutations found in sun exposed skin and the high rate of inactivating mutations of the tumour suppressor genes NOTCH and CDKN2 and mutations in TGFBR1/2 which may cause the cancers. Clearly accurate identification of such mutations may open the way to develop targeted therapy in a similar way that we have vismodegib which acts as an inhibitor of the smoothened receptor following mutations in the patch gene causing basal cell carcinomas.
There was a talk about the cause of lichen sclerosus (LS) which is a scarring condition affecting genital and non-genital skin. Despite extensive investigations to exclude an infectious cause for this disease current opinion would suggest that penile and probably vulval LS is caused by an irritant reaction to urine secondary to micro-incontinence produced by anatomical abnormalities in the distal urethra. Another talk focussed on the cause of hair thinning in women which has been classified as androgenetic alopecia. Data was presented showing that androgens may well not be involved in the cause of this condition and that it should now be called female pattern hair loss.
Altogether this was an exhilarating series of lectures showcasing the exciting research that is ongoing in British Dermatology, Professor Rustin was proud to be part of this and contribute to the meeting and to know that British Dermatology is a major player in the field of world Dermatology.