The largest meeting of dermatologists in the world is held annually by the American Academy of Dermatology
The largest meeting of dermatologists in the world is held annually by the American Academy of Dermatology (AAD) each year with about 14,000 dermatologists in attendance. The IPPF holds its annual medical advisory board meeting during the AAD as most of the international and national members attend. Last year, the IPPF decided to apply to the AAD to run a 3 hour symposium on autoimmune bullous diseases, and Professor Dedee Murrell volunteered to prepare and submit the application, which was approved in July last year. 11 speakers were chosen during the 3 hours with the program below;
Chair Dedee F Murrell, MD, on behalf of the International Pemphigus & Pemphigoid Foundation (winner of AAD 2008 Golden Triangle Award)
Description: This session will highlight advances in the diagnosis, characterization of and ttherapeutic arena related to pemphigus and pemphigoid. The recent international consensus on disease definitions for pemphigus and two disease severity measurement tools that are being studied will be presented. Attendees will learn about the genetic and environmental factors that predispose patients to develop pemphigus and pemphigoid. Experienced clinicians will give a critical review of the evidence for traditional and novel therapies. The key role played by the patient support group, IPPF, to advance the diagnosis and management of these ‘orphan’ diseases will be explained.
2.00-2.05 Importance of patient support groups for autoimmune bullous disease
Janet Segall, USA.
2.05-2.25 Practical diagnosis of pemphigus and pemphigoid
Jean Claude Bystryn, MD (USA)
2.25-2.45 Genetic predisposition towards pemphigus & pemphigoid
Animesh Sinha, MD, PhD (USA)
2.45-3.05 Environmental triggers of pemphigus & pemphigoid
Valeria Aoki, MD, PhD (Brasil)
3.05 -3.25 Prognosis and avoiding complications of treatment
Amit Pandya, MD(USA)-
3.25-3.45 Evidence-based management of pemphigoid
Russell P Hall,MD (USA)-
3.45-4.05 Evidence-based management of pemphigus
Pascal Joly ,MD, PhD(France)
4.05-4.25 Outcome measures and Consensus Statement on Definitions of Disease Endpoints, and Therapeutic Response in Pemphigus
Dedee F Murrell MD(Australia)
4.25-4.45 Measuring extent and activity of disease in pemphigus
Victoria P Werth, MD (USA)
4.45-5.00 Better diagnosis & management of pemphigus as an orphan disease
and future collaborations
David Sirois, MD (USA)
A large hall was allocated for the session, which was open to any registrant without an additional fee, and was full for most of the session, with about 300 dermatologists in the room. The session was opened by IPPF patient liaison officer, Janet Segall, speaking from her personal experience as a patient, about how much a patient support organisation, such as the IPPF she established, could make a difference to the lives of patients with these rare AIBD.
Dr Jean-Claude Bystryn, from New York University, went over very clearly the clinical and pathological features needed to diagnose pemphigus and pemphigoid, and how to distinguish their subtypes and tell them from other forms of bullous diseases. His presentation included very clear photographs of the diseases and diagrams designed to make this complex area of dermatology easy to understand.
Dr Animesh Sinha, from Wayne State Univ in Michigan, gave an enlightening presentation about the genetic risk factors that can predispose patients to developing pemphigus, including his own research. He explained that there is an increased risk of other autoimmune diseases in patients with AIBD, the most common of which is thyroid disease, in about 20% of cases. Almost half of pemphigus vulgaris patients reported having relatives with autoimmune diseases. There are no twin studies of AIBD, so if you are a twin with pemphigus or pemphigoid, please get in touch with Janet so she can link you with Dr Sinha, as twins with/without diseases can provide information about causes and triggers of the disease. Dr Sinha explained in detail about the tissue types that increase the risk of developing pemphigus, particularly one called DRB1-0402. His lab and others are actively researching genetic markers of pemphigus.
Dr Valeria Aoki, of the University of Sao Paulo, Brasil, was nominated to speak in lieu of Dr Luis Diaz, from the University of North Carolina at Chapel Hill, as he is on the board of the AAD, whose meeting clashed with ours. They have collaborated in very important research on what environmental triggers cause endemic pemphigus foliceus, known as fogo selvagem, in the rainforests of Brasil. People living in these indigenous reservations, as well as people moving into the reservation, develop high antibody levels to the protein that is targeted in the skin in pemphigus foliaceus, called Desmoglein 1. There is a particular species of black fly in these reservations which is thought to be somehow related to the triggering process. Up to 10% of healthy people in the reservations also made antibodies to Dsg1 but, crucially, not the disease-causing subtype of antibody, which is an IgG4 antibody, rather than IgG1, against a structurally crucial part of Dsg1. Dr Aoki also spoke about an endemic form of pemphigus vulgaris that has recently been found in Brasil as well. By studying this, more information could be gleaned about factors that trigger PV.
Next, we switched gears back to the practical clinical aspects of managing the many complications of treating AIBD, which was reviewed very well by Dr Amit Pandya, of the University of Texas, Southwestern, in Dallas. You could hear a pin drop in the audience as everyone’s eyes were glued to the screen. He spoke about the mortality of pemphigus having improved over the years, but the morbidity is what we need to improve on now. Mortality is lower due to early recognition of these diseases, earlier commencement of treatment and more appropriate use of prednisone or alternatives. Supportive treatments including sometimes overlooked basic aspects, such as nutrition, hygiene, moderate exercise to reduce muscle wasting and osteoporosis, avoiding tape; pain control, when antibiotics might be needed. He uses a very useful ‘dear doctor’ letter to the patients’ local physician, detailing all the complications that need to be watched for whilst they are on corticosteroids, including the importance of not suddenly stopping the steroids.
Extremely popular were the next two clinical talks, as well. Dr Russell Hall, chair of dermatology at Duke University, delivered a very succinct overview of the evidence for treatments in use for bullous pemphigoid. He explained that older studies had not always excluded other AIBD that attack the basement membrane, particularly epidermolysis bullosa acquisita, which is more resistant to therapy than BP. Survival rates reported for BP differed between different countries and centres, for example in France a 59% 1 year survival was reported in BP patients receiving oral steroids, but was much improved in those randomised to potent topical steroids instead. Studies in the USA reported one year survival rates of 89% and 77%. In countries where the application of topical steroids can be provided and longer stays in hospital, the use of TCS instead of oral steroids may well improve survival. He pointed out some new trials which will be starting soon in the UK to address these questions further.
New international member of the IPPF, Prof Pascal Joly, from the University of Rouen, France, carefully reviewed, in perfect English, the evidence for treatments in use for pemphigus. Much of this has recently been published as a detailed Cochrane Review by Linda Martin, Vicky Werth and Dedee Murrell, available from the weblink http://www.cochrane.org/reviews/en/ab006263.html. In addition, Dr Joly spoke in detail about the studies of rituximab for pemphigus vulgaris, which he has recently published in the New England Journal of Medicine, as leader of one of the most active group of dermatologists in the world doing clinical studies in pemphigus and pemphigoid.
The next two presentations were about the work of the International Pemphigus Definitions group, in order to develop a consensus about how pemphigus is staged clinically and how it should be graded. Prof Dedee Murrell, Chair of Dermatology at the University of New South Wales, St George Hospital, in Sydney, Australia, explained how she and Vicky Werth had coordinated meetings between disparate groups of dermatologists from all parts of the world who are experts in pemphigus, to hold face-to-face meetings alongside international congresses, to debate the very important topic of defining disease stages in pemphigus – in other words, what constitutes when the disease is under control, a remission on/off therapy, what minimal therapy for pemphigus is, what is a flare, what treatments and doses should be trialled before the patient is said to be ‘resistant’ to treatment. As a prelude to this, she and her fellow, Linda Martin, had reviewed all studies of pemphigus published with more than 5 patients and had found that more different definitions of outcome measures were used (116!) than there were studies (96). In order to compare treatments in an orphan disease, a statistical method, called meta-analysis, is used, which can be a very powerful tool for rare diseases for which very large randomized trials are impossible. However, to do meta-analysis, you need uniform outcome measures to be used in each study. Since the Definitions consensus for pemphigus was published in the JAAD last year, new trials are including these.
Dr Victoria Werth, Professor of Dermatology at the University of Pennsylavania, gave the second presentation on the advances being made in developing grading systems for pemphigus and other AIBD. She explained that there were certain standard steps that needed to be completed in order to develop and validate proposed disease extent and activity measures. She has successfully done this before for another autoimmune skin disease, lupus. There are two proposed disease extent and activity measures, one developed by IPPF MAB member Prof Michael Hertl, in Germany, called the ABSIS, and one developed by the Pemphigus Definitions group, including the experts from around the world, as well as Prof Hertl, and other German dermatologists, as a group, called the PDAI and PSS. Dr Werth reviewed the results of a validation study done on patients with pemphigus at Penn, with several expert dermatologists, mainly from the IPPF group, performing these gradings on the same patients on the same day. Whilst both the ABSIS and PDAI were sensitive, the PDAI was more sensitive at lower degrees of involvement and had a higher intra-rater reliability coefficient. She spoke about another study using photographs of these same patients, and other more severely involved patients, being assessed similarly but via a secure IPPF weblink, so that international experts could participate as well.
Finally, the session closed with a unique presentation by IPPF President, Dr David Sirois, Professor of Dentistry and Oral Medicine at New York University. He spoke about the opportunities for the pharmaceutical industry to support patients with orphan diseases, including AIBD, by using the fast tracking of applications for approval by the FDA, using the Orphan Drugs Act, 1983. Of 1700 new drug applications, over 300 have been approved, or about 11 new drugs for orphan diseases per year. Whilst orphan diseases may be rare, because patients usually require these expensive new treatments for many years, it is worth pursuing by these pharmaceutical companies as if they are given an approved listing for that indication, insurance companies are then obliged to fund them, and those drugs which have been approved for orphan diseases have averaged an expenditure of $500M/year. On the other hand, insurance companies, he said, were not going to spend time looking into projected costs for rare orphan diseases.
Judging by the high attendance, applause and questions, there was much enthusiasm for the session. At the AAD, the audience is asked to grade each presenter and only sessions with good gradings are invited back the next year. We anticipate excellent ratings based on the attendance and hope to return with this session at the AAD next year with more new information for the dermatologists across the globe.
Legends for photograph.
Speakers at the AAD Symposium on Management of Autoimmune Bullous Diseases. Left to right: Drs Amit Pandya, Animesh Sinha, Pascal Joly, Dedee Murrell, Jean-Claude Bystryn, Ms Janet Segall, Drs David Sirois, Victoria Werth, Russell Hall and Valeria Aoki.
Respectfully submitted, Dedee F Murrell, MD