The session was opened by IPPF patient liaison and Director of Patient Services & Education, Janet Segall, speaking from her personal experience as a patient, about how much a patient support organization, 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 Michigan State University, 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, Brazylia, 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 foliaceous, known as fogo selvagem, in the rainforests of Brazil. 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 foliaceous, 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 1055% 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 Brazil 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. 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 randomized to potent topical steroids instead. Studies in the USA reported one year survival rates of 89% i 77%. Further studies are clearly needed to determine the causes of these different survival rates. The use of potent topical corticosteroids appears to be effective, especially in countries where the application of topical steroids can be provided and longer stays in hospital are possible. More studies are clearly needed to determine the optimal treatment of patients with bullous pemphigoid, and new trials will be starting soon in the UK which will help to , 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, Francja, 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 i Dedee Murrell, available online at
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 part of clinical trials 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. Jednakże, 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 Pennsylvania, 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. This is coming out in the Journal of Investigative Dermatology soon. While 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.
While 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. Thus, the changing pharmaceutical marketplace for ultraorphan illnesses present a unique challenge and opportunity for partnerships between Patient Advocacy Groups like the IPPF, insurance companies, and specialty pharmacies to develop novel and favorable models for expanding the orphan drug research pipeline and accelerating clinical trials that can lead to improved therapy and treatment outcomes. 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.