Pioneers in Dermatology and Venereology: An interview with Professor Dedee F. Murrell

I have always enjoyed looking at photographs, art, maps and diagrams. I grew up in Yorkshire, England and spent a gap year on an English-Speaking Union Scholarship at Loomis Chaffee School in Windsor, CT, prior to starting medical sciences at Cambridge University. In my third ‘long vacation’ at Cambridge, in 1984, I was fortunate to be offered an elective in dermatopathology at the Brigham and Women's Hospital, Harvard Medical School, with Ramzi Cotran, Marty Mihm and George Murphy—an opportunity made possible through the late Dr. Bob Rosson, who mentored me at the University of Connecticut the previous summer. This elective introduced me peripherally to dermatology. When I was a clinical medical student at Oxford University, I really enjoyed my dermatology attachment, seeing the diseases firsthand. I was able to be driven to clinics at High Wycombe with Fenella Wojnarowska, who was very inspiring, and be taught by Sue Burge, an excellent teacher who went on to become the first female Dean of Oxford Clinical School. After that, I entered the Renwick Vickers essay competition prize (certain topics were offered) and wrote about the Pathogenesis of Psoriasis, which won the prize. These factors inspired me to pursue dermatology. After meeting an Australian Rhodes Scholar at New College, Oxford, who had been offered orthopaedic training at Duke University following his D.Phil., and marrying in 1987, I focused on entering training in dermatology in the USA. This began in 1990 at the University of North Carolina at Chapel Hill, following a research fellowship in clinical trials at Duke University, assisted by Fenella and Sue. In terms of teaching dermatology, I would say during my residency at UNC Chapel Hill, the main clinical teachers were Dr. Al Briggaman (the chair) and Dr. Clayton Wheeler (the chair emeritus) who ran a weekly ‘kodachrome’ session of unknown cases from 7 to 9 am once a week. We were in clinics with them three times a week, in addition to 8–9 clinics weekly with many teaching conferences at UNC and every 2 weeks, with Duke. It was a fantastic learning experience and I did not want it to end. For clinical acumen—from Al Briggaman and Clayton Wheeler; for clinical trials—Elise Olsen, Jim Krueger, Carle Paul, Charles Ellis and Pascal Joly; for outcome measures and evidence-based medicine—Hywel Williams, Vicky Werth and Tamar Nijsten; for basic research—Ray Gammon and his lab team; Jim Krueger, Jouni Uitto; Eli Sprecher; volunteering abroad—Luitgard Wiest and Wingfield Rehmus. For career advice, Dr. Wilma Bergfeld, founder of the Women's Dermatologic Society and first woman president of the AAD, and other leading members of the WDS, including Lyn Drake, Joy Rico, Amy Paller and Jean Bolognia—about how to balance an academic career with having a family—‘delegate and don't try to be perfect’. At UNC, Al Briggaman, Luis Diaz and Lowell Goldsmith—‘pick an area you are interested in and focus on that’—help along the way with opportunities. When I navigated the move to dermatology in Australia, Ross Barnetson, John Doyle, Steven Kossard, Ian McCrossin, Cathy Reid and Rod Sinclair offered encouragement to keep pursuing academia. I have selected these papers based on the long-term benefit they have provided to both our specialty and to the careers of the mentees who worked on them, even if these are not my most highly cited papers, which are mostly consensus guidelines, reviews and clinical trials in common skin diseases. For pemphigus (PDAI): Rosenbach M, Murrell DF, Bystryn J-C, Delay S, Dick S, Fakharzadeh S, Hall R, Korman NJ, Lin J, Okawa J, Pandya AG, Payne AS, Rose M, Rubenstein D, Woodley D, Vittoria C, Werth BB, Williams EA, Taylor L, Troxel A, Werth VP: Reliability and validity of the two outcome instruments for pemphigus. J Invest Dermatol. 109:2404–2410, 2009. https://doi.org/10.1038/jid.2009.72 For bullous pemphigoid (BPDAI): Murrell DF, Daniel BS, Joly P, Borradori L, Amagai M, Hashimoto T, Caux F, Marinovic B, Sinha A, Hertl M, Bernard P, Sirois D, Cianchini G, Fairley JA, Jonkman MF, Pandya AG, Rubenstein D, Zillikens D, Payne AS, Woodley D, Zambruno G, Aoki V, Pincelli C, Diaz L, Hall RP, Meurer M, Mascaro JM Jr, Schmidt E, Shimizu H, Zone J, Swerlick R, Culton D, Lipozencic J, Bince B, Mimouni D, Grando S, Bystryn JC, Werth VP. Definitions and outcome measures for bullous pemphigoid: recommendations by an international panel of experts. J Am Acad Dermatol. 66(3):479–85, 2012. https://doi.org/10.1016/j.jaad.2011.06.032 Outcome measure design (QOLEB for EB): Frew JW, Martin LK, Nijsten T, Murrell DF. Quality of life evaluation in epidermolysis bullosa (EB) through the development of the QOLEB questionnaire: an EB-specific quality of life instrument. Br J Dermatol. 161(6):1323–30, 2009. https://doi.org/10.1111/j.1365-2133.2009.09347.x For clinical trials: Venugopal SS, Yan W, Frew JW, Cohn HI, Rhodes LM, Tran K, Melbourne W, Nelson JA, Sturm M, Fogarty J, Marinkovich MP, Igawa S, Ishida-Yamamoto A, Murrell DF. A phase II randomized vehicle-controlled trial of intradermal allogeneic fibroblast therapy for recessive dystrophic epidermolysis bullosa. J Am Acad Dermatol. 2013;69(6):898–908.e7. https://doi.org/10.1016/j.jaad.2013.08.014. Loh CH, Kim J, Su JC, Daniel BS, Venugopal SS, Rhodes LM, Intong LRA, Law MG and Murrell DF. Development, reliability and validity of a novel Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI). J Am Acad Dermatol. 2014;70(1):89–97.e13. https://doi.org/10.1016/j.jaad.2013.09.041. Yes, I was elected President of the Australasian Society of Dermatological Research, from August 2019 to 2021, after serving 2 years as the Secretary, being on the board since 2010, and running their first congress with external funding. Unfortunately, most of my presidency coincided with the pandemic, and both our annual ASDR meetings became virtual due to restrictions on interstate and even local travel. I was also in the executive team of the International Society of Dermatology between 2011 and 2017—serving as Executive Vice President and Chair of Communications (2013–2017) and President of the ICD2021 Congress in Melbourne (which turned into the world's first 24-h-a-day virtual ‘dermathon’). I was elected the first International Board Member of the EADV (2018–2022) and have since been re-elected for a second 4-year term. In the interim, I was elected Chair of the Communications Committee of the EADV. In the Women's Dermatologic Society, I have served as a Board Member, Chair of the International Committee and co-founding editor of the International Journal of Women's Dermatology. In the AAD, I was chair of the World Congress Task Force for 3 years and runner-up for the International Observer to the Board of the AAD after serving on the International Affairs Committee. I would say that my greatest achievement was bringing the international experts in autoimmune blistering diseases together—across several continents—to develop and validate outcome measures and definitions for pemphigus (PDAI), bullous pemphigoid (BPDAI) and mucous membrane pemphigoid (MMPDAI). In Sydney, we also developed quality of life (QOL) and EBDASI instruments for EB and for blistering diseases—ABQOL and TABQOL—which were revalidated internationally and are now in use in the clinical trials that have supported FDA and EMA registration of new treatments for these conditions. All of this work was done before the online meetings that are possible today. The Phase 3 RCT of the first BTK inhibitor—rilzabrutib—tested for an autoimmune condition missed its primary endpoint. I had designed the trial with my pemphigus expert colleagues and immunologists at Principia Bio. Unfortunately, the endpoint had been changed following FDA discussions with the new sponsor, a change unknown to the investigators until it was too late. Had the original endpoint been kept, and had patients not been excluded by FDA due to remote visits (despite having photos) during the pandemic, the drug would be registered by now. That was a decade of work for me. If you mean having fun then so far it would be co-hosting the inaugural EADV Games with my long-term and funny colleague, Prof. Frederic Caux, from Paris. He has been the host of this competition at the Journées Dermatologiques de Paris for several years and brought the concept to the EADV in Amsterdam last year. Eighteen different national teams competed in this knockout, which included a lot of jokes and music as well as the questions. We have hosted it again at the EADV Congress in Paris. Apart from that, sharing a pre-Mexican congress trip (with a focus on EB) in the Yucatán, Mexico, with John McGrath and Julio Salas Alanis was a laugh a minute—John should have been a stand-up comedian. I like attending and presenting at smaller and focused international congresses, ideally in places that need education or where experts from different fields can see patients. This is where I can brainstorm with very smart people and join them to see patients. I also feel inspired by them to go home and work on something new together, hopefully with my juniors, and to bring something useful to my patients. I have had these experiences in countries such as India, Iran, Kuwait, Mexico and Vietnam. These would include, in alphabetical order by surname, Robert Alan Briggaman, David Martin Carter, Robin Eady, Stefania Jablonska, Naomi Kanof, Rona MacKie, Hiroshi Shimizu, Jouni Uitto, Clayton Wheeler and Detlef Zillikens. Wilma Bergfeld, Chris Griffiths, William D. (Bill) James, Steven Kossard, John McGrath, Amy Paller, Eli Sprecher, Antonella Tosti, Victoria Werth and David Woodley. I enjoy learning about world history and culture by travelling, meeting people, reading and watching foreign films on these topics. I have many favourites in these categories. I like writers who can describe people who move between cultures and continents, or who overcome adversity—these include Elif Shafak and Jeffrey Archer. As a composer, I prefer Chopin for classical music and Josef Scott for modern Indie music. In painting, I love the Impressionists, particularly Monet. The most recent discovery, which was novel, was inspired by trying to understand why two young men with epidermolysis bullosa died unexpectedly in their teens. One, aged 15, with EB simplex, died at a party. It turned out that he had a novel mutation in the KLHL24 gene, which is expressed in both the cardiac muscle and the skin. This mutation can result in minimal skin disease but fatal cardiomyopathy. It took several years to work out with the help of my pre-dermatology fellow, Tim Cowan, in collaboration with the team in the Netherlands led by Marieke Bolling. The other case involved two brothers with intermediate junctional EB, who had the same homozygous frameshift mutations in LAMC2. The elder brother developed much more severe disease and died from respiratory failure. I saw a poster of a mouse model of JEB with lung involvement, which suggested a clue. It turned out that this was because the two brothers had different normal variants (polymorphisms) of the COL17A1 gene, which explained the disparity in disease severity. This was subsequently verified with a genetically engineered mouse at Jackson Laboratories. Hopefully as whole exome sequencing becomes more readily available, we will have many more answers to these types of mysteries. A perfect workday would start at 6 am with my outdoor exercise group—a mixed class of professionals who meet with a trainer next to Sydney Harbour—followed by an 8 am research meeting in the morning in the hospital when the mind is fresh. I love hearing my students and fellows present the projects they have been working on, especially if a novel outcome measure they have been validating with my international colleagues turns out to be useful. It is also exciting if a company with which we have been doing a clinical trial, either on an advisory board or as chief investigator, announces that the trial meets its primary and secondary endpoints. In the afternoon, I would be in clinic with my fellows and students and see some very happy patients whose psoriasis, atopic dermatitis, HS or pemphigus is invisible or under very good control thanks to novel biologics that I have had a hand in the trials and registration process. In the evening, I would meet my French tutor, Karima Mezoughem, at the Union and Schools Club in Sydney, for dinner and French conversation for 2 h. If it were on holiday, my perfect day would be in Kalkan, Türkiye. My husband and I, perhaps with one of our sons or daughter, or with one member of our family or friends who have come to stay, would walk down the Lycian way to exercise and swim in the Mediterranean Sea. We would enjoy Turkish coffee and baklava at a local café, go to visit our favourite ancient ruin, Tlos, a Lycian league city where games were held in the mountains and afterwards enjoy lunch under the trees at a trout farm with cold mountain water running through. We would then drive back to the villa for a swim in the pool and rest, followed by a sunset dinner overlooking the sea at one of the many rooftop restaurants. I am very concerned about the loss of the clinician investigators—the protected time that is needed to make the breakthroughs in clinical dermatology, as demonstrated by people like Emma Guttman, Alain Hovnanian, Alan Irvine, Jim Krueger, John McGrath, Amy Paller and Eli Sprecher. With health systems only rewarding the numbers of patients seen and restricting research time, young dermatologists grow bored and fed up with administrative tasks and may prefer to become their own bosses in private practice. This marginalizes dermatology even more from mainstream medicine. There are so many new fantastic treatments for our patients; thanks to the hard work of uncovering the pathogenic pathways in these complex diseases. They may not get funded in many countries as our specialty and diseases are trivialized, despite the stigma our patients suffer. I think that AI will take over many mundane tasks that slow down consultations. Hopefully, this will save time in clinics by condensing notes and letters and provide results from disparate labs more easily. Machine learning will help detect malignant pigmented lesions before they are clinically evident and possibly even allow mutation testing via non-invasive sticker analysis. Personalized medicine by biomarker/cytokine profiling could tailor treatments to individual patients. Artificial and gene-corrected skin grafts/equivalents and the use of spray on skin for wound healing also hold tremendous promise. Dermatology is a field with so many different aspects that you will never get bored if you find the areas you most enjoy, are curious about what is causing the problem, and are determined to find the best solution for your patients. Keep seeing patients even if you focus on lab work or clinical trials with a company. Mentor the next generation, as it is very fulfilling. The best things do not come from what is paid. *Note: The Pioneers in Dermatology and Venereology interview was conceived and conducted by Johannes Ring. None declared.