The Hidradenitis Suppurativa Priority Setting Partnership.

BACKGROUND: Hidradenitis suppurativa (HS) has been neglected by medical researchers and society in general, despite being a relatively common, painful, chronic skin disease. OBJECTIVES: To generate a top 10 list of HS research priorities, from the perspectives of patients with HS, carers and clinicians, to take to funding bodies. METHODS: A priority setting partnership was established between patients with HS, carers and clinicians, following the James Lind Alliance process. Survey 1 requested submission of HS uncertainties, which were grouped into 'indicative uncertainties' for prioritization in survey 2. The 30 highest-ranked indicative uncertainties were reduced to a 'top 10' list using nominal group technique at a prioritization workshop attended by all relevant HS stakeholders. RESULTS: In total 1495 potential uncertainties were submitted in survey 1, including 57% from patients with HS and carers, and grouped into 55 indicative uncertainties. Ranking in survey 2 was completed by 371 participants, 50% of whom were patients and carers. The final workshop was attended by 22 HS stakeholders and four facilitators and produced a top 10 list, the three highest priorities in descending order being (i) What is the most effective and safe group of oral treatments in treating HS? (ii) What is the best management of an acute flare? (iii)What is the impact of HS and its treatment on people with HS? CONCLUSIONS: The top 10 HS research priorities have been directly disseminated to funders to raise awareness of HS. The next step is to generate research questions that will provide the evidence needed to improve care for patients with HS.

Psoriasis: an evidence-based update. Report of the 9th evidenced based update meeting, 12 May 2011, Loughborough, UK.

The Centre of Evidence Based Dermatology, University of Nottingham, U.K. holds an annual Evidence Based Update (EBU) Meeting focused on important dermatological topics, which have in the past included eczema, urticaria, blistering disorders, skin infections, skin cancer and hair disorders. These one-day meetings aim to summarize the most recent evidence in the form of systematic reviews and recently completed clinical trials. This year, the 9th EBU meeting took place in Loughborough, U.K. on 12 May 2011 and was devoted to psoriasis. The latest updates on topical treatments, nail psoriasis, genetics and clinical implications, rational use of biologics, new and unpublished studies on combination of phototherapy and biologics for psoriasis, and on treatments of palmoplantar pustular psoriasis were discussed by a panel of renowned international speakers.

Updates from the British Association of Dermatologists 91st annual meeting, 5-7 July 2011, London, U.K.

This is a synopsis of the significant research and clinical papers presented at the British Association of Dermatologists (BAD) meeting held on the 5-7 July 2011 in London, U.K. The conference and satellite symposia highlighted the recent biological, epidemiological and therapeutic advances in dermatology. This report is not meant as a substitute for reading the conference proceedings and related references quoted in this article.

Everyday clinical experience of alitretinoin in the treatment of severe chronic hand eczema: seven case studies.

Chronic hand eczema (CHE) is a debilitating and distressing disease for patients, the physical symptoms of which are compounded by psychosocial problems. Alitretinoin is an endogenously occurring physiological vitamin A derivative (retinoid) that possesses strong anti-inflammatory and immunomodulatory activity. It is currently the only licensed product for severe CHE unresponsive to treatment with potent topical corticosteroids, and has been proven to be highly effective in clinical trials with two-thirds of patients who responded to treatment remaining in remission at 6 months. For those that did relapse, a second study showed they could be successfully retreated with a further 3-6 month course of alitretinoin. Seven case studies of alitretinoin have been provided by consultant dermatologists showing its use in normal UK clinical practice. The cases chosen demonstrate the efficacy of alitretinoin across several different subtypes of CHE, and the positive effects the treatment brought to patients' quality of life.

Urticaria: an evidence-based update. Conference report.

Summary Evidence-based update meetings are held annually by the Centre of Evidence Based Dermatology, University of Nottingham. Topics are chosen by delegates at the previous year's conference and in the past have included blistering disorders, psoriasis, hair disorders and skin cancers. Once the topic is identified, a trials database search is undertaken with the aim of including speakers who are actively involved in trials that address the subject in question. This year, the eighth Evidence Based Update meeting focused on urticaria and took place in Loughborough University on 14 May 2009. The latest data on the diagnosis and management of acute and chronic urticaria, including cold and solar urticaria, and the impact of food intolerance on chronic urticaria, were presented by an international panel of renowned speakers, who sometimes expressed different viewpoints. The highlights of the meeting included an informal atmosphere, an international perspective, and a practical question and answer session. Over 70% of the delegates stated that they would be changing their clinical practice following on from the meeting. The evidence-based update meeting in 2010 will be devoted to eczema.

Updates from the British Association of Dermatologists 89th Annual Meeting, 7-10 July 2009, Glasgow, U.K.

This is a synopsis of the significant research and clinical papers presented at the British Association of Dermatologists meeting held during 7-10 July 2009 in Glasgow, U.K. The conference and satellite symposia highlighted the recent biological, epidemiological and therapeutic advances in dermatology. This report is not meant as a substitute for reading the conference proceedings and related references quoted in this article.

Report from the 67th annual meeting of the American Academy of Dermatology.

The 67th Annual Meeting of the American Academy of Dermatology took place in San Francisco on 6-10 March 2009. The flavour of this busy but well-organized convention was a mixture of practical, hands-on teaching sessions, led and delivered by experts, with breakthrough cutting-edge scientific sessions. Aesthetic dermatology comprised a significant part of the meeting. It is impossible to encompass all the important presentations made at the meeting and satellite symposiums, but we highlight here a few medical pearls on dermoscopy, melanoma and oncology, inflammatory dermatoses and community-acquired methicillin-resistant Staphylococcus aureus. Our report is not intended as a substitute for reading the conference proceedings, educational session handouts, online updates and related references quoted in this article.

Footprints of the EADV: a meeting report from the 17th Congress of the European Academy of Dermatology and Venereology.

The 17th Congress of the European Academy of Dermatology and Venereology took place in Paris on 17-20 September 2008 and brought together nearly 11,000 participants. Various plenary lectures, subspecialty meetings, 'free communications', 'top ten', 'test yourself' and 'junior' sessions, 19 courses and 14 'lunches with the expert', six forums, 27 symposia and 45 workshops were pressed into the 4 days of the meeting. Over 1700 posters were presented and exhibited. The themes of a number of symposiums, workshops and sessions overlapped, offering additional educational opportunities despite a very busy schedule. The meeting was well organized. Aesthetic dermatology comprised a significant part of the meeting. It is impossible to encompass all important presentations and we highlight a few medical pearls presented at the meeting; however, our report is not intended as a substitute for reading the conference proceedings and related references quoted in this article.

Blistering skin disorders: an evidence-based update. Conference report.

Evidence-based update meetings are held annually by the Centre of Evidence Based Dermatology, University of Nottingham. Past topics have included important themes such as eczema, psoriasis, hair disorders and skin cancers. This year, the seventh Evidence Based Update meeting focused on blistering disorders and took place in Loughborough University on 5 June 2008. The latest data on incidence and mortality, therapeutic trials and management of bullous pemphigoid, pemphigus and epidermolysis bullosa (EB) were presented by an international panel of renowned speakers. The highlights of the meeting included an informal atmosphere, an international perspective, a practical question and answer session and hearing first-hand a patient and carer's perspective of living with EB.

More than skin deep: atherosclerosis as a systemic manifestation of psoriasis.

There is now growing evidence that psoriasis, like other inflammatory diseases such as rheumatoid arthritis and systemic lupus erythematosus, is a systemic disorder that is associated with enhanced atherosclerosis and risk of coronary artery disease. Here we summarize the available epidemiological evidence for this association and analyse pathogenic features that are common to psoriasis and atherosclerosis. Further prospective studies are urgently needed to extend knowledge of the risk of cardiovascular morbidity and mortality in patients with psoriasis and to confirm the degree to which treatment of psoriasis reduces this risk. Nevertheless, existing data are sufficient to indicate that severe psoriasis should be more widely recognized as a potential risk factor for cardiovascular disease and should be considered with the established factors when formulating strategies for the management of cardiovascular risk.

Medical management of contact dermatitis.

Allergic and irritant contact dermatitis are important dermatological problems. Although the frequencies of positive reactions to a number of allergens have decreased during last 30 years because of better avoidance (and at least in part due to improved legislation), contact allergy to other agents is rising. The medical treatment starts from a correct identification of triggers of contact dermatitis which could allow patients to reduce or avoid exposure to these agents in future. A good clinical history, examination and immunological tests including patch testing are of crucial importance at this stage. Further management includes emollients, topical and oral corticosteroids, topical calcineurin inhibitors, azathioprine and ciclosporin. Methotrexate and alitretinoin are recent additions to the armamentarium of dermatologists who manage contact dermatitis.

Whither... the future for contact dermatitis? A report from the 2007 International Review of Current Problems in Contact Dermatitis.

In our report we summarize presentations made at the International Review of Current Problems in Contact Dermatitis meeting which took place at the St John's Institute of Dermatology, London, on 1 June 2007, and which brought together over 100 dermatologists from the U.K., continental Europe and the U.S.A. During this small and informal meeting, the state-of-the art lectures on various aspects of contact dermatitis were followed by energetic discussions.

Role for CD40-CD40 ligand interactions in the immune response to solid tumours.

CD40-mediated interactions play an important role in the response to infections, transplantation, and cancer by affecting the development, activation, proliferation and differentiation of a variety of immune cells. In the current study we examined the role of CD40-mediated interactions in immune responses to bladder, pancreatic and breast carcinomas as well as melanoma cell lines using soluble human CD40L (rhCD40L) or anti-CD40 mAb in vitro. CD40 expression was readily detected in a large proportion of the cell lines and was augmented but not induced de novo by treatment with IFNgamma. Treatment of CD40-positive cell lines with rhCD40L or anti-CD40mAb enhanced cell surface expression of ICAM-1 and FAS and stimulated the production of IL-6, IL-8, GROalpha, GM-CSF and TNFalpha but not IL-4, IL-10, TGFbeta, MCP-1, RANTES, MIP-1beta, or IP-10. In addition, incubation of CD40+ tumour cell lines with immobilised rhCD40L or anti-CD40 mAb in vitro resulted in significant inhibition of proliferation and a corresponding decrease in viability. This CD40-mediated inhibition of cell growth was due, at least in part, to alterations in cell cycle and the induction of apoptosis. Transfection of CD40-negative tumour cell lines with the cDNA for CD40 conferred responsiveness to rhCD40L and anti-CD40 antibody. Finally, the presence of CD40 on the surface of carcinoma lines was found to be an important factor in the generation of tumour-specific T cell responses.

Cytokine modulation of epidermal growth factor receptor expression on bladder cancer cells is not a major contributor to the antitumour activity of cytokines.

Epidermal growth factor is a potential mitogen for many different human tumours. Its effect is mediated via a bispecific receptor (EGFR), the expression of which correlates well with invasive disease. We investigated the modulation of EGFR by cytokines produced following bacillus Calmette Guerin (BCG)-immunotherapy. Our data demonstrate the IFN gamma, TNF alpha and IL-1 alpha can decrease the expression of EGFR on some bladder tumour cell lines. IFN gamma reduced EGFR expression on two of eight cell lines (RT4, SD). However, IL-1 and TNF did not share this activity. When cells were treated with a combination of all three cytokines, EGFR was decreased on three cell lines (RT4, RT112, SD) and furthermore, the change in the receptor expression was even more marked. Treatment with phorbol ester (thereby activating protein kinase C) resulted in rapid disappearance of the receptor from the cell surface. Interestingly, the decrease of EGFR expression did not require protein synthesis. Although the cytokines studied could down modulate EGFR, this only occurred on three out of eight cell lines; therefore, it is unlikely that the suppression of proliferative activity caused by cytokine-induced decrease of EGFR expression is central to the antitumour action of BCG therapy, but in a proportion of tumours this mechanism may be involved.

Autocrine regulation of ICAM-1 expression on bladder cancer cell lines: evidence for the role of IL-1 alpha.

We have studied the autocrine regulation of essential expression of the intercellular adhesion molecule-1 (ICAM-1) on 8 transitional cell carcinoma (TCC) cell lines (histopathological grades 1-3). The constitutive expression of ICAM-1 was regulated by soluble factors in an autocrine fashion. These factors were produced by all cell lines, with the exception of the MGH-U1 cell line. The effects observed could be largely attributed to IL-1 alpha. However, the residual ICAM-1 inducing activity (up to 30% of ICAM-1 induction) could not be associated with any known ICAM-1 inducers (IFN gamma, TNF alpha, TNF beta, IL-1 alpha, IL-1 beta, IL-4, retinoic acid, LPS). In contrast to recombinant derived cytokines, the IL-1 alpha present in tissue culture supernatant was only able to induce ICAM-1 on high-grade tumours and not low-grade cells. This discriminative effect is similar to that noted following in vitro culture of tumour cells with bacillus Calmette-Guerin organisms. Whether the production of soluble factors (e.g., IL-1 alpha) by TCC cell lines plays an essential autocrine role for bladder tumours and/or affects the interaction with cells of the immune system needs to be investigated further.

Induction of ICAM 1 expression on bladder tumours by BCG immunotherapy.

AIMS: To determine the expression of intercellular adhesion molecule 1 and 2 (ICAM 1 and 2) in transitional cell carcinoma cells before and after immunotherapy with Calmette-Guérin bacillus (BCG). METHODS: Frozen sections from 22 untreated bladder carcinomas were immunohistochemically examined with monoclonal antibodies to ICAM 1 and 2. Urinary cytospin slides were made for six patients for each of the six clinical instillations which constitute a therapeutic course. These slides were also stained for ICAM 1 and for leucocyte function associated antigen 1 (LFA 1). RESULTS: Bladder cancer cells did not essentially express either ICAM 1 or 2, but cells in the stromal areas surrounding tumour expressed both these antigens. After repeated instillations of BCG organisms ICAM 1 positive normal and neoplastic epithelial cells were observed in the urine. Cells obtained from the first three instillations expressed lower densities of ICAM 1 than those from the later instillations. Many neutrophils expressing LFA-1 and some lymphocytes were also noted in the cytospin slides and some of these were conjugated to tumour cells expressing ICAM 1. Six months after treatment a single maintenance dose of BCG induced ICAM 1 expression. CONCLUSION: Untreated superficial bladder carcinoma cells do not express ICAM 1 or 2, but these important immunological molecules were expressed in the stromal areas of tissue. Importantly, neoplastic cells in the urine expressed ICAM 1 after immunotherapy. This molecule can render bladder tumour cells vulnerable to non-antigen specific cytotoxicity mediated by activated lymphocytes.