BJD
British Journal of Dermatology
M E E TI N G RE P O R T
Review of the 94th Annual Meeting of the British Association of Dermatologists, Glasgow 2014 R.M. Porter1 and S.M.C. George2 1 2
Academic Dermatology, Aneurin Bevan Health Board, St Woolos Hospital, Stow Hill, Newport NP20 4SZ, U.K. Department of Dermatology, Eastbourne District General Hospital, Kings Drive, Eastbourne BN21 2UD, U.K.
Summary Correspondence Susannah M. C. George. E-mail: [email protected]
Accepted for publication 25 January 2015
Funding sources None.
This is a review of the 94th Annual Meeting of the British Association of Dermatologists, held in Glasgow from 1 to 3 July 2014. The conference covered some of the latest developments in the treatment of atopic dermatitis, psoriasis and cancer, a follow-up on the methylisothiazolinone contact allergy epidemic, advances in genetically inherited disorders and somatic mutations underlying birth marks. In addition, there was an international perspective on vitiligo, leprosy and HIV, and a session discussing the regulatory process behind pharmaceutical development.
Conflicts of interest None declared. DOI 10.1111/bjd.13762
The 94th Annual Meeting of the British Association of Dermatologists (BAD) was held in Glasgow from 1 to 3 July 2014. Commencing with preconference sessions for trainees, staff and associate specialists, and Dermschool for undergraduates and juniors, the programme seemed more packed than ever, with sponsored breakfast and lunchtime symposia, and informal coffee break discussions on ‘hot topics’, including urticaria, onychomycosis, drug rashes and outcome measures for clinical trials in dermatology. While not attempting to provide a comprehensive summary of the entire meeting, we have selected some of the highlights of the invited talks and original research presentations. Posters were also submitted by Dermschool delegates, with prizes awarded for the best entries, to encourage and inspire dermatologists of the future.
Cutaneous allergy Dr Margarida Goncßalo (Coimbra) delivered the Prosser White Oration on patch testing in nonimmediate drug reactions. This is performed as for contact allergy,1 using potential culprit drugs and related chemicals, is most useful 6–12 months following the reaction, and permits study of cross-reactions and mechanisms involved. Subsequent presentations featured case reports of reactions to individual allergens, including that of a nurse with hand eczema caused by blue nitrile gloves, presented by Dr Adil Sheraz (Kent).2 This was not an isolated case, and the occupational health department had received many similar referrals. 1262
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Glove extract testing revealed phthalocyanine blue, a copperderived blue dye, as the culprit. Change to white nitrile gloves resulted in improvement in the nurse’s symptoms. Dr David Orton (London) updated delegates on the methylisothiazolinone (MI) contact allergy epidemic, which, despite media interest following last year’s annual meeting, is still present in dozens of supermarket products, including Niveaâ lotion and Huggiesâ wet wipes. Sensitization rates are increasing massively on a global scale, with a reported prevalence of positive patch test reactions of up to 15%.3 Subsequent presentations reinforced the magnitude of the MI problems. Dr Rachel Urwin and colleagues (Leeds) studied occupational exposure to MI by interrogating the EPIDERM database – a registry of occupational skin surveillance data.4 MI in polyvinylacetate glues caused occupational exposure and contact allergy in two furniture company workers.5 Severe skin and respiratory symptoms occurred in a 52-year-old woman 2 days after painting her lounge with B&Q (Value) Matt Emulsion paint.6
Atopic dermatitis Dr Michael Ardern-Jones (Southampton) presented recent developments in atopic dermatitis (AD). Loss-of-function mutations in FLG occur in 50% of patients with severe AD,7 but a reduced number of filaggrin repeats in FLG also increases risk.8 Genetic factors are not the whole story; the concordance rates for monozygotic and dizygotic twins are 72% and 23%, © 2015 British Association of Dermatologists
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respectively. Therefore, 30% of AD risk derives from other factors.9 Not all patients with AD are the same, and it is important to determine which patients respond to which treatments. In clinical trials, it is important to stratify by immunophenotype, genetics and biomarkers in order to facilitate the move towards personalized therapy.10 Many patients with AD have increased IgE levels, but trials of omalizumab have failed to show a significant improvement.11,12 However, blocking interleukin (IL)-4 and IL-13 with dupilumab (anti-IL-4 receptor-a), a fully humanized monoclonal antibody, produced a 50% reduction in Eczema Area and Severity Index (EASI) score in 85% of patients.13 Immunophenotype varies with disease phases, with T helper 2 cell predominance in acute disease and T helper 1 cell predominance in chronic disease; a number of trials have examined the effects of drugs that affect various components of the immune system. Other potential therapeutic strategies include restoration of barrier function by delivery of recombinant filaggrin monomers to the skin;14 coal tar, which increases filaggrin expression via the aryl hydrocarbon receptor;15 and prevention of AD in babies from high-risk families by regular emollient use from birth to the age of 6 months.16
Genetic disorders of the skin The inaugural BAD and Genetic Medicine (BADGEM) group meeting coincided with genetic characterization of several disorders, some of which had previously been challenging. This has resulted from technological advances, particularly in DNA sequencing, as summarized by Professor David Kelsell (London).17 Next-generation sequencing (NGS) involves fragmentation of the entire genome and can, after enrichment of the exons, be used to analyse the entire exome simultaneously. Professor John McGrath (London) presented several new subtypes of epidermolysis bullosa and changes to the classification, which now includes 18 different genes.18 Professor Vinzenz Oji (M€ unster) covered the latest developments in ichthyosis, including the recently characterized severe dermatitis, multiple allergies and metabolic wasting syndrome, caused by a loss-of-function mutation in DSG1,19 a gene coding a major desmosomal protein. Dr Kayria Muttardi (Watford) presented a novel mutation in CSTA, which codes for cystatin A, a protein involved in desmosome adhesion.20 These patients also had atopic eczema and asthma, conditions associated with poor barrier function. Professor Edel O’Toole (London) highlighted several genes causing aquagenic keratodermas. In this condition, contact with water causes palmoplantar skin to become white and spongy.21,22 Aquaporin 5 is involved in water transport and is potentially left in the open state by the underlying gene mutations.21 NGS is also useful for the diagnosis of known genetic disorders when the gene responsible is large or the disorder is caused by multiple genes. Xeroderma pigmentosum results from mutations in one of seven DNA repair genes or POLH, © 2015 British Association of Dermatologists
and can be associated with neurological problems, depending on subtype. Professor Alan Lehmann (Brighton) and Dr Mieran Sethi (London) highlighted some novel mutations associated with unusual clinical presentations, illustrating the role of genetic testing in obtaining prognostic information.23 Dr Robert Sarkany (London) and patient support group leader, Sandra Webb (Hemel Hempstead), have been instrumental in setting up a clinic, established in 2010, where patients can see all specialists (dermatologist, ophthalmologist, neurologist and geneticist) on the same day. There were parallels with Ehlers–Danlos syndrome (EDS), a group of inherited connective tissue disorders characterized by skin fragility, hyperextensibility and joint hypermobility, which also requires a multidisciplinary approach. Dr Nigel Burrows (Cambridge) described the clinical features of classical, hypermobility and vascular EDS, and outlined a framework for investigations, monitoring and management. Suspected cases can be referred to the EDS National Service at Northwick Park or Sheffield. Dr Glenda Sobey (Sheffield) outlined the importance of early genetic testing for appropriate management of a potentially life-threatening disorder. Gene therapy is not the only potential management strategy for inherited disorders.24 Options for recessive dystrophic epidermolysis bullosa include protein replacement with collagen VII and cell therapy with allogenic fibroblasts to aid wound healing. The latter is mediated via a paracrine effect, rather than production of normal protein by the fibroblasts. Another option is allogeneic bone marrow transplantation, which results in migration of donor cells to sites of injury with increased collagen VII deposition.25 In autosomal recessive congenital ichthyosis there is deficiency of an enzyme that cross-links proteins and lipids in the cornified envelope. Liposomal delivery of this enzyme is a possible future treatment strategy.26 Natural gene therapy, observed as patches of unaffected skin in patients with several genetic disorders is also being investigated as a potential source of patient-derived cells for wound treatment.27
Paediatrics Port wine stains can present with Sturge–Weber syndrome and neuro-ocular involvement. In patients with facial port wine stains, glaucoma screening is imperative, yet an audit by Dr Renuga Raghavendran and colleagues (West Midlands) found that only 79% were screened.28 Phakomatosis pigmentovascularis type II presents with both vascular and pigmentary birthmarks. Dr Regula Waelchli and colleagues (London) found the same GNA11 mutation in both lesions but not in blood, suggesting somatic mosaicism caused by a mutation in the same progenitor cell during development.29 Somatic mutations of codon 61 of NRAS often occur in congenital melanocytic naevus;30,31 however, different missense activating mutations in NRAS were found in three children with naevus spilus by Dr Veronica Kinsler and colleagues (London).32 British Journal of Dermatology (2015) 172, pp1262–1268
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Psoriasis Professor Jonathan Barker (London) reviewed new molecules in development that target the IL-17 pathway for the treatment of psoriasis. Recent advances include a new biological agent, secukinumab (anti-IL-17A),33 but biologics are only relevant in a small proportion of patients. Small molecules with the potential to be developed as topical agents are urgently required; Janus kinase inhibitors that block IL-17 release have shown promise in a preliminary study.34 A multicentre study from India concluded that itolizumab, a novel anti-CD6 monoclonal antibody that inhibits T-cell proliferation and proinflammatory cytokine production, was an effective and safe oral treatment for moderate-to-severe plaque psoriasis.35 Foundation year one Dr Elinor Farrell (Newport, Wales) presented her team’s work on development of an option grid to promote shared decision making for systemic treatment of plaque psoriasis.36 Mathematician Helen Jones (Cardiff) modelled phototherapy provision in Wales, where current facilities are restricted to the north and south, requiring patients to travel long distances or use biologics instead.37 Home phototherapy kits would eliminate lengthy journeys and potentially save National Health Service funds. Other talks considered a psychological perspective. A study from 13 European countries evaluated the psychological burden of skin disease in 3635 patients and 1359 controls. There were increased odds of depression, anxiety and impaired quality of life in a range of dermatological conditions, including psoriasis.38 Dr Sandy McBride and clinical psychologist Dr Alexandra Mizara (London) provided a comprehensive overview of psychological aspects of psoriasis: the negative schemas held by patients and the negative impact on employment, salary, risk of divorce and self-confidence, and resultant social anxiety and depression. Psychological distress is poorly recognized by clinicians, yet failure to address this affects treatment adherence and satisfaction. Dr McBride outlined a model for a new style consultation, addressing both physical and psychosocial aspects.
Understanding pharma ‘Understanding pharma’ aimed to clarify the regulatory process behind pharmaceutical development. Dr Kim Kjoeller, Senior Vice President of Global Development, LEO Pharma, suggested that the main reason for lack of creativity and innovation was an absence of coordination between research and development and commercial teams. Commercial companies often fail to understand requirements, and input from leading academics and patients is needed at all stages. Dr William McCulloch, President, Alba Biopharm Advisors, Inc., described the frustrations of the regulatory process in the context of cutaneous T-cell lymphoma (CTCL). Numerous therapies for CTCL exist, but none work well enough. Problems include a lack of standardized endpoints and response British Journal of Dermatology (2015) 172, pp1262–1268
criteria. Randomized controlled trials (RCTs) are problematic as there is currently no consensus on the best treatments for CTCL to use as a control arm. In an orphan disease where a RCT is not possible, it is essential to accept less rigorous evidence for drug approval. Dr Ian Hudson, Chief Executive, Medicines and Healthcare Products Regulatory Agency, gave the regulators’ side of the story. While regulation is perceived to cause delays, the Early Access to Medicine Scheme allows flexibility, where rapid access to unlicensed drugs is required for life-threatening diseases. Professor Sir Ian Kennedy (London) advocated regulation as an opportunity for management of risk for the benefit of patient and the professional, rather than a form of ‘police’. To achieve this, it is important to establish standards of care and expected norms of behaviour, and then monitor compliance.
Photodermatology Dr Tsui Ling (Salford) presented the updated BAD/British Photodermatology Group guidelines for psoralen and ultraviolet A treatment (PUVA).39 A comparison of the relative efficacy and safety of narrow band ultraviolet B (UVB), conventional oral treatments and biologics found that the best treatment varies between diseases. However, many centres have disposed of their PUVA equipment because of the potential for carcinogenicity. Narrowband UVB is more efficacious than PUVA for vitiligo, but recent evidence suggests that a xenon monochloride monochromatic excimer lamp that generates a monochromatic wavelength of 308 nm may be even more effective.40 In an Indian study of 400 patients, 195% had an excellent response (> 75% repigmentation after 1–10 sessions) and 380% had a good response (> 75% repigmentation in 10–20 sessions).41 Professor Hans Christian Wulf (Copenhagen) gave a ‘hopeless’ lecture on the difficulties in changing people’s behaviour and promoting responsible sun exposure. Most poignantly, while patients with malignant melanoma had less ultraviolet (UV) exposure the summer following diagnosis,42 after 1 year their exposure matched controls and after 3 years, exceeded it.43 Polymorphic light eruption (PLE) is believed to be due to reduced UV-induced immunosuppression. It is more common in women possibly because 17b-oestradiol causes an additional reduction of UV-induced immunosuppression.44 Dr Hari Reddy and colleagues (Middlesbrough) tested for a difference in severity pre- and postmenopause, finding strong evidence that postmenopausal women should be withdrawn from PLE therapy trials.45,46 Professor Vinod Sharma (New Delhi) discussed the specific problems of photodermatoses in dark skin. In a study from New Delhi, the most common photodermatoses among patients with skin types IV and V were polymorphic light eruption (599%) and chronic actinic dermatitis (CAD; 138%). Although rare in the U.K., in India CAD occurs most commonly in patients sensitized to Parthenium hysterophorus, a © 2015 British Association of Dermatologists
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flower of the compositae family. In 1956, U.S. shipments of wheat inadvertently led to the introduction of Parthenium to India.47 Parthenium flourished in the favourable climatic conditions and is now responsible for 40% of all contact dermatitis in India, named ‘Parthenium dermatitis’. As CAD seems to be associated with a history of eczema, Dr Catriona Harkins and colleagues (Dundee) investigated whether filaggrin mutations are linked to progression to CAD.48 A strong link between FLG mutations and AD was observed, but there was no link with CAD.
Cancer Maxillofacial surgeons Mr Roger Currie (Ayrshire) and Miss Carrie Newlands (Guildford) described the many surgical dilemmas in managing high-risk squamous cell carcinomas (SCCs). The aim of surgery is complete excision in all directions; high-risk lesions require a 6-mm margin and lower-risk ones a 4-mm margin, with a depth of 4 mm. No guidelines exist that define a clear or ‘close’ margin. Overall, the risk of metastasis is low (5%). Factors influencing metastatic potential include thickness and size, and perineural involvement and site, with cancers on the ear more likely to metastasize.49 Incomplete excision is an independent risk factor for regional metastases;50 recurrence may be unpredictable. Mohs surgery may be problematic because of the potential to miss skip lesions. Miss Newlands continued with a discussion of regional lymph node metastases, the use of imaging and the controversial role of sentinel node biopsy. Spread to regional lymphatics is associated with a 50% mortality. Skin lymphatics are unpredictable. The site of nodal disease depends on the site of the primary tumour. Most guidelines suggest no imaging in patients with high-risk SCCs. To be visible on ultrasound scanning, a deposit needs to be at least 4 mm in size. Sentinel node biopsy is not routinely performed in the U.K., but may be beneficial. Basal cell carcinoma (BCC) is most commonly caused by mutations affecting the Sonic Hedgehog pathway. Vismodegib is the first Hedgehog pathway inhibitor approved in the U.S.A. for advanced BCC not easily amenable to surgery. Dr John Lear (Manchester) presented the third interim analysis results of STEVIE, an open-label, multicentre trial to evaluate safety of vismodegib.51 Side-effects include muscle spasms, alopecia, dysgeusia, weight loss, appetite loss and nausea, consistent with previous studies. There was also preliminary efficacy data, with complete response in 175% (n = 300) and partial response in 398% of patients. Facial lentigo maligna may also be difficult to treat surgically. Dr Navara Anjum (London) described the use of reflectance confocal microscopy for monitoring topical imiquimod therapy.52 This can also be used to reduce the number of Mohs’ stages.53 When used with a fluorescent marker for nuclei, acridine orange, confocal microscopy may also facilitate accurate and more rapid Mohs’ surgery of high-risk BCC.54 © 2015 British Association of Dermatologists
The potent contact sensitizer diphencyprone (DCP) has shown promise in patients with malignant melanoma unresponsive to conventional therapy.55,56 Following initial sensitization with 2% DCP under occlusion, it is applied to the lesion to produce a tolerable contact reaction. Dr Fiona Worsnop and colleagues (London) treated 12 patients with metastatic melanoma, two with multiple SCCs and one with eccrine porocarcinomas with DCP. Two patients with metastatic melanoma had a complete response and five had a partial response, as did the patients with SCC. The patient with eccrine porocarcinomas had a complete response.57 The link between Breslow thickness and metastatic potential is well known. Chemotaxis has been implicated in cancer invasion,58 and Dr Andrew Muinonen-Martin and colleagues (Glasgow) have successfully identified lysophosphatidic acid (LPA) as a key stimulant of melanoma cell migration.59 Furthermore, tumour-generated LPA gradients are thought to be responsible for metastasis. This is only possible in tumours of sufficient size, hence the increased risk associated with Breslow thickness. A highlight of the meeting was the Arthur Rook Oration entitled ‘The magic and mayhem of human skin resident T cells’ by Dr Rachael Clark (Boston, MA). Memory T cells represent an immunological history that is the secret to how the body overcomes infection. It is now known that the resident T cells in epithelial barrier tissues of the skin, lung and gut differ from central memory T cells. There are an incredible 20 billion T cells in the skin alone, double that of the circulation.60 These resident memory T cells have skin-homing addresses in the form of cell surface markers that target them to the skin; they do not circulate to the lymph nodes of other organs like central memory T cells.61 This has increased understanding of the differences between mycosis fungoides and Sezary syndrome. In the former, the T cells have a skin-resident T-cell phenotype; in the latter, the T cells have the phenotype of central memory T cells.62
International perspective In 1937, Dr Hulusi Behҫet described the triple syndrome complex of aphthous ulceration, genital ulceration and hypopyon iritis. While cases of Behҫet syndrome most commonly span countries from Turkey and the Mediterranean to Japan, where it is one of the leading causes of blindness, the ‘Silk Route disease’ is very rare in the U.K. Professor Robert Moots (Liverpool) described the management options using an algorithm, which is available online.63 It can affect any part of the body; the vasculitis can affect any type of blood vessel. Diagnosis is by recognition of a constellation of clinical features and exclusion of other causes.64 The aetiology is unclear, although theories include genetic and environmental factors. A 2010 U.K. survey revealed that most waited > 12 years from initial symptoms to diagnosis and had seen more than six consultants in different hospitals. Many had lost jobs and received benefits. Like EDS and xeroderma pigmentosum, this also British Journal of Dermatology (2015) 172, pp1262–1268
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benefits from a multidisciplinary approach. In 2012, three national centres (one each in Liverpool, London and Birmingham) were commissioned. Patients are now managed in a ‘one-stop shop’ by specialists from numerous different disciplines, including rheumatology, oral medicine, gynaecology, ophthalmology and neurology, as well as by clinical psychologists, social workers and nurse specialists. A national database has been established, and there is central biologics funding and coordinated entry to clinical trials. Professor Amrinder Kanwar (Greater Noida) discussed the aetiology, clinical presentation, management and consequences of vitiligo from an Indian perspective. India has one of the highest prevalence rates for vitiligo, and it is a significant cosmetic problem and cause of psychological distress in those with dark skin types. Social and psychological consequences include impaired quality of life, low self-esteem, depression, and implications for employment and marriage. The aetiology is unclear and most likely polygenic or multifactorial. Pathogenesis is unknown, but numerous theories exist. Vitiligo koebnerizes and has a predilection for sites of friction or trauma. One suggestion is that friction causes melanocyte detachment and loss of pigmentation. Smoking is more common in those with lip involvement. Professor Kanwar reviewed the evidence for different treatments, including topical and oral steroids, oral minocycline, topical calcineurin inhibitors, phototherapy and surgery.65–67 Three other presentations on the surgical treatment of vitiligo focused on potential improvement of noncultured epidermal suspension transplantation by the use of suspensions prepared from hair follicle outer root sheaths.68–70 Although rare in the U.K., leprosy remains an important health problem in India. Dr Sunil Dogra and colleagues (Chandigarh) undertook a retrospective case note review of 59 children with leprosy diagnosed over an 11-year period.71 There was a high complication rate, particularly nerve involvement, due to delays in seeking treatment. Effective management requires early diagnosis with histological confirmation. Dr Felicia Srisaravanapavananthan and colleagues (Jaffna) sought to determine the optimum biopsy site in those with tuberculoid leprosy.72 They found that the highest diagnostic yield was from the active edge of the lesions rather than the centre. Dr David Paige (London) delivered a lecture on HIV in the post-highly active anti-retroviral therapy (HAART) era. Worldwide, > 75 million people have been infected with HIV. Thirty-eight million have died and 37 million are living with the disease, including one in 20 in sub-Saharan Africa. There are approximately 100 000 cases in the U.K., and the rate is still increasing. Many of the new diagnoses are in the those aged > 50 years, and 25% are unaware of their diagnosis. The introduction of HAART from 1995 to 1996 onwards has substantially decreased morbidity and mortality. Skin conditions commonly seen in patients include an itchy folliculitis, severe seborrhoeic dermatitis, atypical presentations of common infections and cutaneous reactions to drugs. British Journal of Dermatology (2015) 172, pp1262–1268
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94th Annual Meeting of the BAD, R.M. Porter and S.M.C. George 1267 21 Blaydon DC, Lind LK, Plagnol V et al. Mutations in AQP5, encoding a water-channel protein, cause autosomal-dominant diffuse nonepidermolytic palmoplantar keratoderma. Am J Hum Genet 2013; 93:330–5. 22 Kubo A, Shiohama A, Sasaki T et al. Mutations in SERPINB7, encoding a member of the serine protease inhibitor superfamily, cause Nagashima-type palmoplantar keratosis. Am J Hum Genet 2013; 93:945–56. 23 Sethi M, Haque S, Lehmann A et al. Clinical and molecular analysis of 13 XP-A patients from the UK: genotype–phenotpye correlation with prognostic importance. Br J Dermatol 2014; 171(Suppl. 1):59–60. 24 Hsu CK, Wang SP, Lee JY et al. Treatment of hereditary epidermolysis bullosa: updates and future prospects. Am J Clin Dermatol 2014; 15:1–6. 25 Wagner JE, Ishida-Yamamoto A, McGrath JA et al. Bone marrow transplantation for recessive dystrophic epidermolysis bullosa. N Engl J Med 2010; 363:629–39. 26 Aufenvenne K, Larcher F, Hausser I et al. Topical enzyme-replacement therapy restores transglutaminase 1 activity and corrects architecture of transglutaminase-1-deficient skin grafts. Am J Hum Genet 2013; 93:620–30. 27 Tolar J, McGrath JA, Xia L et al. Patient-specific naturally genereverted induced pluripotent stem cells in recessive dystrophic epidermolysis bullosa. J Invest Dermatol 2014; 134:1246–54. 28 Raghavendran R, Abdullah A, Ogboli M. Facial port wine stain and glaucoma: an audit in two tertiary laser units. Br J Dermatol 2014; 171(Suppl. 1):116–17. 29 Waelchli R, Thomas A, Kinsler V. The genetic basis of phakomatosis pigmentovascularis type II. Br J Dermatol 2014; 171(Suppl. 1):115. 30 Bauer J, Curtin JA, Pinkel D et al. Congenital melanocytic nevi frequently harbor NRAS mutations but no BRAF mutations. J Invest Dermatol 2007; 127:179–82. 31 Carr J, Mackie RM. Point mutations in the N-ras oncogene in malignant melanoma and congenital naevi. Br J Dermatol 1994; 131:72–7. 32 Kinsler V, Krengel S, Waelchli R. Naevus spilus congenital melanocytic naevi: a distinct genotype for a distinct phenotype. Br J Dermatol 2014; 171(Suppl. 1):117. 33 Langley RG, Elewski BE, Lebwohl M et al. Secukinumab in plaque psoriasis – results of two phase 3 trials. N Engl J Med 2014; 371:326–38. 34 Punwani N, Scherle P, Flores R et al. Preliminary clinical activity of a topical JAK1/2 inhibitor in the treatment of psoriasis. J Am Acad Dermatol 2012; 67:658–64. 35 Krupashankar DS, Dogra S, Kura M et al. Efficacy and safety of itolizumab, a novel anti-CD6 monoclonal antibody, in patients with moderate to severe chronic plaque psoriasis: results of a doubleblind, randomized, placebo-controlled, phase-III study. J Am Acad Dermatol 2014; 71:484–92. 36 Farrell E, Whistance R, Lloyd A et al. Shared decision-making in plaque psoriasis: development of an Option Grid to assist in decisions to commence oral therapy. Br J Dermatol 2014; 171(Suppl. 1):7. 37 Jones H, Shipley D, Smith L et al. Population-based mathematical modelling by location analysis and optimization predicts that investment in phototherapy will widen access and yield financial savings. Br J Dermatol 2014; 171(Suppl. 1):2. 38 Dalgard F, Kupfer J, Gieler U. The psychological burden of common skin diseases in 13 European countries. Br J Dermatol 2014; 171(Suppl. 1):3. 39 Ling TC, Clayton TH, Crawley J et al. British Association of Dermatologists and British Photodermatology Group guidelines for the safe and effective use of psoralen combined with ultraviolet A therapy 2014. Br J Dermatol 2014; 171(Suppl. 1):59.
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40 Park KK, Liao W, Murase JE. A review of monochromatic excimer light in vitiligo. Br J Dermatol 2012; 167:468–78. 41 Shah A, Shah B. Indian experience of a 308 nm monochromatic excimer lamp in 400 cases of vitiligo. Br J Dermatol 2014; 171(Suppl. 1):62. 42 Idorn LW, Datta P, Heydenreich J et al. Sun behaviour after cutaneous malignant melanoma: a study based on ultraviolet radiation measurements and sun diary data. Br J Dermatol 2013; 168:367–73. 43 Idorn LW, Datta P, Heydenreich J et al. A 3-year follow-up of sun behavior in patients with cutaneous malignant melanoma. JAMA Dermatol 2014; 150:163–8. 44 Aubin F. Why is polymorphous light eruption so common in young women? Arch Dermatol Res 2004; 296:240–1. 45 Reddy H, Wahie S, Carmichael AJ. Severity of polymorphic light eruption in pre- and post-menopausal women: a comparitive study. Br J Dermatol 2014; 171(Suppl. 1):9. 46 Reddy H, Carmichael AJ, Wahie S. Severity of polymorphic light eruption in pre- and post-menopausal women: a comparative study. J Eur Acad Dermatol Venereol 2015; 29:97–101. 47 Jeyatheswaran J, Yesudian P. Parthenium dermatitis: the scourge of India. Br J Dermatol 2014; 171(Suppl. 1):140. 48 Harkins CP, Waters A, Kerr A et al. Is there a role for filaggrin mutations in the pathogenesis of chronic actinic dermatitis? Br J Dermatol 2014; 171(Suppl. 1):61–2. 49 Brantsch KD, Meisner C, Schonfisch B et al. Analysis of risk factors determining prognosis of cutaneous squamous-cell carcinoma: a prospective study. Lancet Oncol 2008; 9:713–20. 50 Mourouzis C, Boynton A, Grant J et al. Cutaneous head and neck SCCs and risk of nodal metastasis – UK experience. J Craniomaxillofac Surg 2009; 37:443–7. 51 Lear J, Fife K, Gore M et al. Interim analysis of STEVIE, a singlearm, open-label, multicentre study to evaluate the safety of Hedgehog pathway inhibitor vismodegib in patients with advanced basal cell carcinoma. Br J Dermatol 2014; 171(Suppl. 1):3. 52 Anjum N, Pavel M, Coleman A et al. Reflectance confocal microscopy in the management of patients treated with topical 5% imiquimod for facial lentigo maligna. Br J Dermatol 2014; 171(Suppl. 1):4. 53 Daly ML, Anjum N, Patel M et al. In vivo reflectance confocal microscopy prior to paraffin-fixed ‘slow’ Mohs micrographic surgery can reduce the number of stages required to clear lentigo maligna. Br J Dermatol 2014; 171(Suppl. 1):66. 54 Craythorne E, Pavel M, Mallipeddi R et al. Fluorescence confocal microscopy during Mohs micrographic surgery: will this change everything? Br J Dermatol 2014; 171(Suppl. 1):66. 55 Damian DL, Thompson JF. Treatment of extensive cutaneous metastatic melanoma with topical diphencyprone. J Am Acad Dermatol 2007; 56:869–71. 56 Harland CC, Saihan EM. Regression of cutaneous metastatic malignant melanoma with topical diphencyprone and oral cimetidine. Lancet 1989; 2:445. 57 Worsnop F, Kutty A, Harper F et al. Topical diphencyprone immunotherapy as a treatment for cutaneous metatastic malignant melanoma, squamous cell carcinoma and eccrine porocarcinoma: a report of 15 cases. Br J Dermatol 2014; 171(Suppl. 1):4–5. 58 Roussos ET, Condeelis JS, Patsialou A. Chemotaxis in cancer. Nat Rev Cancer 2011; 11:573–87. 59 Muinonen-Martin A, Faller W, Susanto O et al. Self-generated lysophosphatidic acid gradients are a key driver of melanoma cell dispersal and invasion. Br J Dermatol 2014; 171(Suppl. 1):11. 60 Clark RA, Chong BF, Mirchandani N et al. A novel method for the isolation of skin resident T cells from normal and diseased human skin. J Invest Dermatol 2006; 126:1059–70. 61 Clark RA. Skin-resident T cells: the ups and downs of on site immunity. J Invest Dermatol 2010; 130:362–70.
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1268 94th Annual Meeting of the BAD, R.M. Porter and S.M.C. George 62 Campbell JJ, Clark RA, Watanabe R et al. Sezary syndrome and mycosis fungoides arise from distinct T-cell subsets: a biologic rationale for their distinct clinical behaviors. Blood 2010; 116:767–71. 63 National Health Service. Behcßet’s disease: Drug pathway. Available at: http://www.behcets.nhs.uk/images/downloads/Bechets%20drug% 20pathway%20v20-%20July%2025%202013.pdf (last accessed 4 April 2015). 64 Anon. Criteria for diagnosis of Behcßet’s disease. International Study Group for Behcßet’s Disease. Lancet 1990; 335:1078–80. 65 Gauthier Y, Surleve-Bazeille JE. Autologous grafting with noncultured melanocytes: a simplified method for treatment of depigmented lesions. J Am Acad Dermatol 1992; 26:191–4. 66 Holla AP, Sahni K, Kumar R et al. Acral vitiligo and lesions over joints treated with non-cultured epidermal cell suspension transplantation. Clin Exp Dermatol 2013; 38:332–7. 67 Olsson MJ, Juhlin L. Long-term follow-up of leucoderma patients treated with transplants of autologous cultured melanocytes, ultrathin epidermal sheets and basal cell layer suspension. Br J Dermatol 2002; 147:893–904.
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68 Vinay K, Dogra S, Parsad D et al. Clinical and treatment characteristics determining therapeutic outcome in patients undergoing autologous noncultured outer root sheath hair follicle cell suspension for treatment of stable vitiligo. Br J Dermatol 2014; 171(Suppl. 1):68–9. 69 Holla AP. Combined cell suspension transplantation in stable vitiligo. Br J Dermatol 2014; 171(Suppl. 1):69. 70 Parsad D. Modification of cellular grafting in vitiligo: a new era of surgical management of vitiligo. Br J Dermatol 2014; 171(Suppl. 1):68–9. 71 Dogra S, Narang T, Khullar R et al. Childhood leprosy in the postleprosy elimination era: a retrospective analysis of epidemiological and clinical characteristics of disease over 11 years from a tertiary care hospital in North India. Br J Dermatol 2014; 171(Suppl. 1):151. 72 Srisaravanapavananthan F, Satgurunathan K, Fernando J. Do the active edge, centre or adjacent normal skin have better histological yield in the diagnosis of tuberculoid leprosy? Br J Dermatol 2014; 171(Suppl. 1):151–2.
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British Journal of Dermatology
M E E TI N G RE P O R T
Review of the 94th Annual Meeting of the British Association of Dermatologists, Glasgow 2014 R.M. Porter1 and S.M.C. George2 1 2
Academic Dermatology, Aneurin Bevan Health Board, St Woolos Hospital, Stow Hill, Newport NP20 4SZ, U.K. Department of Dermatology, Eastbourne District General Hospital, Kings Drive, Eastbourne BN21 2UD, U.K.
Summary Correspondence Susannah M. C. George. E-mail: [email protected]
Accepted for publication 25 January 2015
Funding sources None.
This is a review of the 94th Annual Meeting of the British Association of Dermatologists, held in Glasgow from 1 to 3 July 2014. The conference covered some of the latest developments in the treatment of atopic dermatitis, psoriasis and cancer, a follow-up on the methylisothiazolinone contact allergy epidemic, advances in genetically inherited disorders and somatic mutations underlying birth marks. In addition, there was an international perspective on vitiligo, leprosy and HIV, and a session discussing the regulatory process behind pharmaceutical development.
Conflicts of interest None declared. DOI 10.1111/bjd.13762
The 94th Annual Meeting of the British Association of Dermatologists (BAD) was held in Glasgow from 1 to 3 July 2014. Commencing with preconference sessions for trainees, staff and associate specialists, and Dermschool for undergraduates and juniors, the programme seemed more packed than ever, with sponsored breakfast and lunchtime symposia, and informal coffee break discussions on ‘hot topics’, including urticaria, onychomycosis, drug rashes and outcome measures for clinical trials in dermatology. While not attempting to provide a comprehensive summary of the entire meeting, we have selected some of the highlights of the invited talks and original research presentations. Posters were also submitted by Dermschool delegates, with prizes awarded for the best entries, to encourage and inspire dermatologists of the future.
Cutaneous allergy Dr Margarida Goncßalo (Coimbra) delivered the Prosser White Oration on patch testing in nonimmediate drug reactions. This is performed as for contact allergy,1 using potential culprit drugs and related chemicals, is most useful 6–12 months following the reaction, and permits study of cross-reactions and mechanisms involved. Subsequent presentations featured case reports of reactions to individual allergens, including that of a nurse with hand eczema caused by blue nitrile gloves, presented by Dr Adil Sheraz (Kent).2 This was not an isolated case, and the occupational health department had received many similar referrals. 1262
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Glove extract testing revealed phthalocyanine blue, a copperderived blue dye, as the culprit. Change to white nitrile gloves resulted in improvement in the nurse’s symptoms. Dr David Orton (London) updated delegates on the methylisothiazolinone (MI) contact allergy epidemic, which, despite media interest following last year’s annual meeting, is still present in dozens of supermarket products, including Niveaâ lotion and Huggiesâ wet wipes. Sensitization rates are increasing massively on a global scale, with a reported prevalence of positive patch test reactions of up to 15%.3 Subsequent presentations reinforced the magnitude of the MI problems. Dr Rachel Urwin and colleagues (Leeds) studied occupational exposure to MI by interrogating the EPIDERM database – a registry of occupational skin surveillance data.4 MI in polyvinylacetate glues caused occupational exposure and contact allergy in two furniture company workers.5 Severe skin and respiratory symptoms occurred in a 52-year-old woman 2 days after painting her lounge with B&Q (Value) Matt Emulsion paint.6
Atopic dermatitis Dr Michael Ardern-Jones (Southampton) presented recent developments in atopic dermatitis (AD). Loss-of-function mutations in FLG occur in 50% of patients with severe AD,7 but a reduced number of filaggrin repeats in FLG also increases risk.8 Genetic factors are not the whole story; the concordance rates for monozygotic and dizygotic twins are 72% and 23%, © 2015 British Association of Dermatologists
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respectively. Therefore, 30% of AD risk derives from other factors.9 Not all patients with AD are the same, and it is important to determine which patients respond to which treatments. In clinical trials, it is important to stratify by immunophenotype, genetics and biomarkers in order to facilitate the move towards personalized therapy.10 Many patients with AD have increased IgE levels, but trials of omalizumab have failed to show a significant improvement.11,12 However, blocking interleukin (IL)-4 and IL-13 with dupilumab (anti-IL-4 receptor-a), a fully humanized monoclonal antibody, produced a 50% reduction in Eczema Area and Severity Index (EASI) score in 85% of patients.13 Immunophenotype varies with disease phases, with T helper 2 cell predominance in acute disease and T helper 1 cell predominance in chronic disease; a number of trials have examined the effects of drugs that affect various components of the immune system. Other potential therapeutic strategies include restoration of barrier function by delivery of recombinant filaggrin monomers to the skin;14 coal tar, which increases filaggrin expression via the aryl hydrocarbon receptor;15 and prevention of AD in babies from high-risk families by regular emollient use from birth to the age of 6 months.16
Genetic disorders of the skin The inaugural BAD and Genetic Medicine (BADGEM) group meeting coincided with genetic characterization of several disorders, some of which had previously been challenging. This has resulted from technological advances, particularly in DNA sequencing, as summarized by Professor David Kelsell (London).17 Next-generation sequencing (NGS) involves fragmentation of the entire genome and can, after enrichment of the exons, be used to analyse the entire exome simultaneously. Professor John McGrath (London) presented several new subtypes of epidermolysis bullosa and changes to the classification, which now includes 18 different genes.18 Professor Vinzenz Oji (M€ unster) covered the latest developments in ichthyosis, including the recently characterized severe dermatitis, multiple allergies and metabolic wasting syndrome, caused by a loss-of-function mutation in DSG1,19 a gene coding a major desmosomal protein. Dr Kayria Muttardi (Watford) presented a novel mutation in CSTA, which codes for cystatin A, a protein involved in desmosome adhesion.20 These patients also had atopic eczema and asthma, conditions associated with poor barrier function. Professor Edel O’Toole (London) highlighted several genes causing aquagenic keratodermas. In this condition, contact with water causes palmoplantar skin to become white and spongy.21,22 Aquaporin 5 is involved in water transport and is potentially left in the open state by the underlying gene mutations.21 NGS is also useful for the diagnosis of known genetic disorders when the gene responsible is large or the disorder is caused by multiple genes. Xeroderma pigmentosum results from mutations in one of seven DNA repair genes or POLH, © 2015 British Association of Dermatologists
and can be associated with neurological problems, depending on subtype. Professor Alan Lehmann (Brighton) and Dr Mieran Sethi (London) highlighted some novel mutations associated with unusual clinical presentations, illustrating the role of genetic testing in obtaining prognostic information.23 Dr Robert Sarkany (London) and patient support group leader, Sandra Webb (Hemel Hempstead), have been instrumental in setting up a clinic, established in 2010, where patients can see all specialists (dermatologist, ophthalmologist, neurologist and geneticist) on the same day. There were parallels with Ehlers–Danlos syndrome (EDS), a group of inherited connective tissue disorders characterized by skin fragility, hyperextensibility and joint hypermobility, which also requires a multidisciplinary approach. Dr Nigel Burrows (Cambridge) described the clinical features of classical, hypermobility and vascular EDS, and outlined a framework for investigations, monitoring and management. Suspected cases can be referred to the EDS National Service at Northwick Park or Sheffield. Dr Glenda Sobey (Sheffield) outlined the importance of early genetic testing for appropriate management of a potentially life-threatening disorder. Gene therapy is not the only potential management strategy for inherited disorders.24 Options for recessive dystrophic epidermolysis bullosa include protein replacement with collagen VII and cell therapy with allogenic fibroblasts to aid wound healing. The latter is mediated via a paracrine effect, rather than production of normal protein by the fibroblasts. Another option is allogeneic bone marrow transplantation, which results in migration of donor cells to sites of injury with increased collagen VII deposition.25 In autosomal recessive congenital ichthyosis there is deficiency of an enzyme that cross-links proteins and lipids in the cornified envelope. Liposomal delivery of this enzyme is a possible future treatment strategy.26 Natural gene therapy, observed as patches of unaffected skin in patients with several genetic disorders is also being investigated as a potential source of patient-derived cells for wound treatment.27
Paediatrics Port wine stains can present with Sturge–Weber syndrome and neuro-ocular involvement. In patients with facial port wine stains, glaucoma screening is imperative, yet an audit by Dr Renuga Raghavendran and colleagues (West Midlands) found that only 79% were screened.28 Phakomatosis pigmentovascularis type II presents with both vascular and pigmentary birthmarks. Dr Regula Waelchli and colleagues (London) found the same GNA11 mutation in both lesions but not in blood, suggesting somatic mosaicism caused by a mutation in the same progenitor cell during development.29 Somatic mutations of codon 61 of NRAS often occur in congenital melanocytic naevus;30,31 however, different missense activating mutations in NRAS were found in three children with naevus spilus by Dr Veronica Kinsler and colleagues (London).32 British Journal of Dermatology (2015) 172, pp1262–1268
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Psoriasis Professor Jonathan Barker (London) reviewed new molecules in development that target the IL-17 pathway for the treatment of psoriasis. Recent advances include a new biological agent, secukinumab (anti-IL-17A),33 but biologics are only relevant in a small proportion of patients. Small molecules with the potential to be developed as topical agents are urgently required; Janus kinase inhibitors that block IL-17 release have shown promise in a preliminary study.34 A multicentre study from India concluded that itolizumab, a novel anti-CD6 monoclonal antibody that inhibits T-cell proliferation and proinflammatory cytokine production, was an effective and safe oral treatment for moderate-to-severe plaque psoriasis.35 Foundation year one Dr Elinor Farrell (Newport, Wales) presented her team’s work on development of an option grid to promote shared decision making for systemic treatment of plaque psoriasis.36 Mathematician Helen Jones (Cardiff) modelled phototherapy provision in Wales, where current facilities are restricted to the north and south, requiring patients to travel long distances or use biologics instead.37 Home phototherapy kits would eliminate lengthy journeys and potentially save National Health Service funds. Other talks considered a psychological perspective. A study from 13 European countries evaluated the psychological burden of skin disease in 3635 patients and 1359 controls. There were increased odds of depression, anxiety and impaired quality of life in a range of dermatological conditions, including psoriasis.38 Dr Sandy McBride and clinical psychologist Dr Alexandra Mizara (London) provided a comprehensive overview of psychological aspects of psoriasis: the negative schemas held by patients and the negative impact on employment, salary, risk of divorce and self-confidence, and resultant social anxiety and depression. Psychological distress is poorly recognized by clinicians, yet failure to address this affects treatment adherence and satisfaction. Dr McBride outlined a model for a new style consultation, addressing both physical and psychosocial aspects.
Understanding pharma ‘Understanding pharma’ aimed to clarify the regulatory process behind pharmaceutical development. Dr Kim Kjoeller, Senior Vice President of Global Development, LEO Pharma, suggested that the main reason for lack of creativity and innovation was an absence of coordination between research and development and commercial teams. Commercial companies often fail to understand requirements, and input from leading academics and patients is needed at all stages. Dr William McCulloch, President, Alba Biopharm Advisors, Inc., described the frustrations of the regulatory process in the context of cutaneous T-cell lymphoma (CTCL). Numerous therapies for CTCL exist, but none work well enough. Problems include a lack of standardized endpoints and response British Journal of Dermatology (2015) 172, pp1262–1268
criteria. Randomized controlled trials (RCTs) are problematic as there is currently no consensus on the best treatments for CTCL to use as a control arm. In an orphan disease where a RCT is not possible, it is essential to accept less rigorous evidence for drug approval. Dr Ian Hudson, Chief Executive, Medicines and Healthcare Products Regulatory Agency, gave the regulators’ side of the story. While regulation is perceived to cause delays, the Early Access to Medicine Scheme allows flexibility, where rapid access to unlicensed drugs is required for life-threatening diseases. Professor Sir Ian Kennedy (London) advocated regulation as an opportunity for management of risk for the benefit of patient and the professional, rather than a form of ‘police’. To achieve this, it is important to establish standards of care and expected norms of behaviour, and then monitor compliance.
Photodermatology Dr Tsui Ling (Salford) presented the updated BAD/British Photodermatology Group guidelines for psoralen and ultraviolet A treatment (PUVA).39 A comparison of the relative efficacy and safety of narrow band ultraviolet B (UVB), conventional oral treatments and biologics found that the best treatment varies between diseases. However, many centres have disposed of their PUVA equipment because of the potential for carcinogenicity. Narrowband UVB is more efficacious than PUVA for vitiligo, but recent evidence suggests that a xenon monochloride monochromatic excimer lamp that generates a monochromatic wavelength of 308 nm may be even more effective.40 In an Indian study of 400 patients, 195% had an excellent response (> 75% repigmentation after 1–10 sessions) and 380% had a good response (> 75% repigmentation in 10–20 sessions).41 Professor Hans Christian Wulf (Copenhagen) gave a ‘hopeless’ lecture on the difficulties in changing people’s behaviour and promoting responsible sun exposure. Most poignantly, while patients with malignant melanoma had less ultraviolet (UV) exposure the summer following diagnosis,42 after 1 year their exposure matched controls and after 3 years, exceeded it.43 Polymorphic light eruption (PLE) is believed to be due to reduced UV-induced immunosuppression. It is more common in women possibly because 17b-oestradiol causes an additional reduction of UV-induced immunosuppression.44 Dr Hari Reddy and colleagues (Middlesbrough) tested for a difference in severity pre- and postmenopause, finding strong evidence that postmenopausal women should be withdrawn from PLE therapy trials.45,46 Professor Vinod Sharma (New Delhi) discussed the specific problems of photodermatoses in dark skin. In a study from New Delhi, the most common photodermatoses among patients with skin types IV and V were polymorphic light eruption (599%) and chronic actinic dermatitis (CAD; 138%). Although rare in the U.K., in India CAD occurs most commonly in patients sensitized to Parthenium hysterophorus, a © 2015 British Association of Dermatologists
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flower of the compositae family. In 1956, U.S. shipments of wheat inadvertently led to the introduction of Parthenium to India.47 Parthenium flourished in the favourable climatic conditions and is now responsible for 40% of all contact dermatitis in India, named ‘Parthenium dermatitis’. As CAD seems to be associated with a history of eczema, Dr Catriona Harkins and colleagues (Dundee) investigated whether filaggrin mutations are linked to progression to CAD.48 A strong link between FLG mutations and AD was observed, but there was no link with CAD.
Cancer Maxillofacial surgeons Mr Roger Currie (Ayrshire) and Miss Carrie Newlands (Guildford) described the many surgical dilemmas in managing high-risk squamous cell carcinomas (SCCs). The aim of surgery is complete excision in all directions; high-risk lesions require a 6-mm margin and lower-risk ones a 4-mm margin, with a depth of 4 mm. No guidelines exist that define a clear or ‘close’ margin. Overall, the risk of metastasis is low (5%). Factors influencing metastatic potential include thickness and size, and perineural involvement and site, with cancers on the ear more likely to metastasize.49 Incomplete excision is an independent risk factor for regional metastases;50 recurrence may be unpredictable. Mohs surgery may be problematic because of the potential to miss skip lesions. Miss Newlands continued with a discussion of regional lymph node metastases, the use of imaging and the controversial role of sentinel node biopsy. Spread to regional lymphatics is associated with a 50% mortality. Skin lymphatics are unpredictable. The site of nodal disease depends on the site of the primary tumour. Most guidelines suggest no imaging in patients with high-risk SCCs. To be visible on ultrasound scanning, a deposit needs to be at least 4 mm in size. Sentinel node biopsy is not routinely performed in the U.K., but may be beneficial. Basal cell carcinoma (BCC) is most commonly caused by mutations affecting the Sonic Hedgehog pathway. Vismodegib is the first Hedgehog pathway inhibitor approved in the U.S.A. for advanced BCC not easily amenable to surgery. Dr John Lear (Manchester) presented the third interim analysis results of STEVIE, an open-label, multicentre trial to evaluate safety of vismodegib.51 Side-effects include muscle spasms, alopecia, dysgeusia, weight loss, appetite loss and nausea, consistent with previous studies. There was also preliminary efficacy data, with complete response in 175% (n = 300) and partial response in 398% of patients. Facial lentigo maligna may also be difficult to treat surgically. Dr Navara Anjum (London) described the use of reflectance confocal microscopy for monitoring topical imiquimod therapy.52 This can also be used to reduce the number of Mohs’ stages.53 When used with a fluorescent marker for nuclei, acridine orange, confocal microscopy may also facilitate accurate and more rapid Mohs’ surgery of high-risk BCC.54 © 2015 British Association of Dermatologists
The potent contact sensitizer diphencyprone (DCP) has shown promise in patients with malignant melanoma unresponsive to conventional therapy.55,56 Following initial sensitization with 2% DCP under occlusion, it is applied to the lesion to produce a tolerable contact reaction. Dr Fiona Worsnop and colleagues (London) treated 12 patients with metastatic melanoma, two with multiple SCCs and one with eccrine porocarcinomas with DCP. Two patients with metastatic melanoma had a complete response and five had a partial response, as did the patients with SCC. The patient with eccrine porocarcinomas had a complete response.57 The link between Breslow thickness and metastatic potential is well known. Chemotaxis has been implicated in cancer invasion,58 and Dr Andrew Muinonen-Martin and colleagues (Glasgow) have successfully identified lysophosphatidic acid (LPA) as a key stimulant of melanoma cell migration.59 Furthermore, tumour-generated LPA gradients are thought to be responsible for metastasis. This is only possible in tumours of sufficient size, hence the increased risk associated with Breslow thickness. A highlight of the meeting was the Arthur Rook Oration entitled ‘The magic and mayhem of human skin resident T cells’ by Dr Rachael Clark (Boston, MA). Memory T cells represent an immunological history that is the secret to how the body overcomes infection. It is now known that the resident T cells in epithelial barrier tissues of the skin, lung and gut differ from central memory T cells. There are an incredible 20 billion T cells in the skin alone, double that of the circulation.60 These resident memory T cells have skin-homing addresses in the form of cell surface markers that target them to the skin; they do not circulate to the lymph nodes of other organs like central memory T cells.61 This has increased understanding of the differences between mycosis fungoides and Sezary syndrome. In the former, the T cells have a skin-resident T-cell phenotype; in the latter, the T cells have the phenotype of central memory T cells.62
International perspective In 1937, Dr Hulusi Behҫet described the triple syndrome complex of aphthous ulceration, genital ulceration and hypopyon iritis. While cases of Behҫet syndrome most commonly span countries from Turkey and the Mediterranean to Japan, where it is one of the leading causes of blindness, the ‘Silk Route disease’ is very rare in the U.K. Professor Robert Moots (Liverpool) described the management options using an algorithm, which is available online.63 It can affect any part of the body; the vasculitis can affect any type of blood vessel. Diagnosis is by recognition of a constellation of clinical features and exclusion of other causes.64 The aetiology is unclear, although theories include genetic and environmental factors. A 2010 U.K. survey revealed that most waited > 12 years from initial symptoms to diagnosis and had seen more than six consultants in different hospitals. Many had lost jobs and received benefits. Like EDS and xeroderma pigmentosum, this also British Journal of Dermatology (2015) 172, pp1262–1268
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benefits from a multidisciplinary approach. In 2012, three national centres (one each in Liverpool, London and Birmingham) were commissioned. Patients are now managed in a ‘one-stop shop’ by specialists from numerous different disciplines, including rheumatology, oral medicine, gynaecology, ophthalmology and neurology, as well as by clinical psychologists, social workers and nurse specialists. A national database has been established, and there is central biologics funding and coordinated entry to clinical trials. Professor Amrinder Kanwar (Greater Noida) discussed the aetiology, clinical presentation, management and consequences of vitiligo from an Indian perspective. India has one of the highest prevalence rates for vitiligo, and it is a significant cosmetic problem and cause of psychological distress in those with dark skin types. Social and psychological consequences include impaired quality of life, low self-esteem, depression, and implications for employment and marriage. The aetiology is unclear and most likely polygenic or multifactorial. Pathogenesis is unknown, but numerous theories exist. Vitiligo koebnerizes and has a predilection for sites of friction or trauma. One suggestion is that friction causes melanocyte detachment and loss of pigmentation. Smoking is more common in those with lip involvement. Professor Kanwar reviewed the evidence for different treatments, including topical and oral steroids, oral minocycline, topical calcineurin inhibitors, phototherapy and surgery.65–67 Three other presentations on the surgical treatment of vitiligo focused on potential improvement of noncultured epidermal suspension transplantation by the use of suspensions prepared from hair follicle outer root sheaths.68–70 Although rare in the U.K., leprosy remains an important health problem in India. Dr Sunil Dogra and colleagues (Chandigarh) undertook a retrospective case note review of 59 children with leprosy diagnosed over an 11-year period.71 There was a high complication rate, particularly nerve involvement, due to delays in seeking treatment. Effective management requires early diagnosis with histological confirmation. Dr Felicia Srisaravanapavananthan and colleagues (Jaffna) sought to determine the optimum biopsy site in those with tuberculoid leprosy.72 They found that the highest diagnostic yield was from the active edge of the lesions rather than the centre. Dr David Paige (London) delivered a lecture on HIV in the post-highly active anti-retroviral therapy (HAART) era. Worldwide, > 75 million people have been infected with HIV. Thirty-eight million have died and 37 million are living with the disease, including one in 20 in sub-Saharan Africa. There are approximately 100 000 cases in the U.K., and the rate is still increasing. Many of the new diagnoses are in the those aged > 50 years, and 25% are unaware of their diagnosis. The introduction of HAART from 1995 to 1996 onwards has substantially decreased morbidity and mortality. Skin conditions commonly seen in patients include an itchy folliculitis, severe seborrhoeic dermatitis, atypical presentations of common infections and cutaneous reactions to drugs. British Journal of Dermatology (2015) 172, pp1262–1268
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