Some Highlights from the 2006 Vasculitis Foundation Symposium

The biennial Vasculitis Foundation Symposium was held in Baltimore, MD from July 7th through July 9th. This year, the Vasculitis Foundation partnered with the Johns Hopkins University Vasculitis Center to provide a forum for medical and scientific discussion of advances in the field of vasculitis. The VF, formerly known as the Wegener’s Granulomatosis Association, lived up to its new name and mission by actively encouraging the participation of patients from all the vasculitides. CSS was well represented with over 26 patients and family members present at the event! Attendees were given the opportunity to learn about the latest information about vasculitis, its treatments, and side effects. They were inspired by reports on research trials and encouraged and hopeful about further advances in understanding the disease. The conference was a wealth of information, and a wonderful opportunity for those with CSS and other vasculitic diseases to meet each other. New friendships flourished effortlessly as CSSers shared common stories and experiences.

The presenting physicians, who are world renown experts in their fields, selflessly donated their time to this Symposium. They have our heartfelt gratitude for their commitment and genuine concern for all vasculitis patients. These wonderful doctors, deserving special recognition and thanks, are listed below:

Dr Nabih Abdou, Dr. Robin Chernoff, Dr. Megan Clowse, Dr. Kirsten de Groot, Dr. Ronald Falk, Dr. Paul Flint, Dr. Howard Francis, Dr. James Garrity, Dr. Duvuru Geetha, Dr. Philp Hashkes, Dr. David Hellman, Dr. Gary Hoffman, Dr. Eric Hoy, Dr. Sanjay Kedhar, Dr. Paul Krakovitz, Dr. Stacey LaBahn, Dr. Carol Langford, Dr Robert Lebovics, Dr. Augustine Lee, Dr. Robert Lorenz, Dr. Eric Matteson, Dr. Thomas McDonald, Dr. Peter Merkel, Dr. Alicia Neu, Dr. Richard O’Brien, Dr. Niels Rasmussen, Dr. Anthony Rosen, Dr. Philip Seo, Dr. Ulrich Specks, Dr. John Stone, Dr. Sangeeta Sule, Dr. Michael Wechsler, and Dr. Mark Wylam

The Symposium consisted of both breakout sessions and podium presentations. Dr. John Stone, the Director of the Johns Hopkins University Vasculitis Center and a member of the CSSA Medical Advisory Board, gave a podium presentation on Saturday entitled What’s New in Treatment. Dr. Stone spoke about Rituximab, one of the newest and most promising treatments being studied right now. Currently there are eight centers participating in the RAVE (Rituximab for ANCA-associated vasculitis) trial. Although the trial is only open to those with Wegener's or Microscopic Poyangiitis at this time, CSS patients may be included in the not too distant future. So far in these trials they have seen an 83% complete remission rate in the first months the drug is given, with a 32% relapse rate within 9-21 months. There were no significant side effects reported in the trials. Some researchers are hopeful that this may be the first drug that could actually replace Cytoxan, which is advantageous since it is much less toxic.

Dr. Stone spoke about how Rituximab depletes B cells, thus disrupting communication between B cells and T cells. It also interrupts cytokine production, and leads to a reduction of ANCA, all of which play a role in the autoimmune process that leads to disease. Researchers found that for 6-12 months after treatment with Rituximab, patients had no B cells. B cells are an important part of the immune system. In autoimmune diseases the B cells may be behaving incorrectly leading to vasculitis, but B cells also have a very important role in fighting bacteria and viruses.

Later on several doctors spoke informally about a possible adverse effect Rituximab may have on the immune system. Even though Rituximab be a wonderful treatment for vasculitis, tampering with the immune system could potentially bring on an immune deficiency state that could be temporary just while using the drug, or it could permanently alter the immune system leading to a severe immune deficiency. Many times these treatments are a balancing act. This is especially true in autoimmune diseases, because you can't just destroy the misbehaving cells as you would bacteria, you have to balance the treatment to control the abnormal behavior of the cells, while you preserve the good function that the cell provides.

During his podium presentation, Dr. Stone also discussed Churg Strauss specifically. He said researchers have lowered expectations that patients with CSS will be able to get completely off steroids. The asthma in CSS is not the “average” asthma suffered by even severe asthmatics. The asthma of CSS is generally steroid dependent. Even in remission, CSS patients typically require some form of steroids throughout their lives to control their asthma. Roughly 85% of CSS patients require ongoing low dose prednisone just for asthma control. The remission rate for CSS with treatment is 92%, with a relapse rate of 26%. One reason for the relatively low rate of relapse in CSS patients may be that patients often continue on low dose steroids to control their asthma. This low dose may also serve to keep them in remission for their CSS.

Dr. Stone also mentioned that studies with the new biological drug anti-IL-5 are promising for CSS. Researchers are hopeful that it may in time prove to be a viable treatment for eosinophilic diseases. So far the studies with anti-IL-5 for Hypereosinophilic Syndrome have been promising, with most patients showing significant improvement. However, anti-IL-5 used in the treatment of asthma showed that while the drug reduced eosinophils, it had little effect on disease activity. The drug is still in clinical trials, and is expected to get FDA approval in the next few years.

Dr. Michael Wechsler, who also serves on the Medical Advisory Board for the CSSA, led a well attended breakout session on Churg Strauss on Saturday afternoon. Dr. Wechsler said that he is optimistic for the future of those with CSS. He is finding that Methotrexate is more useful than once believed for the treatment of CSS, and he also reiterated the importance of steroid sparing drugs. Although the vast majority patients with CSS remain steroid dependent, optimizing asthma management may allow for the lowest possible dose of oral steroid. Dr. Wechsler also discussed the Singulair issue, and whether it had a potential role in causing CSS. He feels that studies have shown that the use of Singulair for asthma has not been proven to create a risk factor for CSS. The asthma associated with CSS often warrants treatment with many different kinds of drugs. Severe asthmatics have the greatest risk of developing CSS anyway, and the numerous drugs used in an attempt to control asthma all came into the market in the late 90's at the same time. It would be hard to distinguish one as more causative than another. Dr Wechsler feels that the occurrence of Churg Strauss syndrome in asthmatic patients receiving Singulair appears to be related to an unmasking of an underlying vasculitic syndrome that is initially clinically recognized as moderate to severe asthma and treated with corticosteroids. Supporting the theory that Singulair does not play a role in the development of CSS is the fact that cases of pediatric CSS are extremely rare with no rise in incidence even though this population is the largest consumer of Singulair.

Dr. Rich O’Brien of the Johns Hopkins Department of Neurology led a discussion on peripheral neuropathy, which affects from 60 to 80% of CSS patients. Dr. O'Brien stated that the presentation of vasculitic neuropathy is usually rapidly progressive (within 6 months), it is asymmetric in the limbs, and it causes severe weakness. There can be exceptions to these signs, such as the fact that 20-40% of vasculitic neuropathies can present with a symmetric pattern similar to the general neuropathy seen in the elderly population. The peroneal nerve is the most commonly involved nerve, which can cause foot drop. This nerve is the most frequently biopsied for evidence of vasculitic neuropathy. In 30% of cases the biopsy is normal, even though there is active disease. A combined muscle/nerve biopsy has a significantly higher (10-20%), likelihood of showing disease than nerve biopsy alone. The percentage of neuropathy in each vasculitic disease varies. Active neuropathy is always treated with prednisone, with Cytoxan added if there is multi organ involvement. IVIG is showing promise as treatment in the neuropathic features of these diseases. Pain management for neuropathy is an important issue. For acute pain oxycodone or Tramadol can be used. For chronic pain, most of the medications used cause a 50% reduction in symptoms. Elavil, Nortriptyline, Neurontin, and newer drugs such as Lyrica, Duloxetine, and Venlafaxine are used for chronic pain. Also, the treatment for neuropathy is usually the treatment for the primary disease. The prognosis for most neuropathies is usually a complete but slow healing, with some residual numbness. It is less likely to heal if the damage is long standing, and in an older patient.

On Sunday morning each disease group had a casual question and answer period with an expert in their disease. The CSS group was extremely fortunate that Dr. Gary Hoffman of the Center for Vasculitis Care and Research at The Cleveland Clinic met with them for a round table discussion over breakfast. Even though this session was held at 7:00 AM, attendance was so great that CSSers overflowed the room! Many topics were covered and Dr. Hoffman was tireless in answering questions. One of the most important discussions centered around the need for steroid sparing drugs in the treatment of CSS. He stated it is best to get the steroid dose as low as possible with the aid of an additional drug such as Imuran or Methotrexate, rather than to stay on a dose of steroids above 10 mg/daily. Dr. Hoffman also told us that the need for biopsy proven vasculitis is not necessary if all the other signs of disease are there such as: high blood eosinophils, severe asthma and sinus issues, lung infiltrates on CT, and new numbness or joint pains. He also reiterated the importance of being seen at leading Vasculitis Centers, because many times disparate symptoms are not connected in a timely matter, and diagnosis is delayed, leading to organ damage. The four centers across the country, Boston University School of Medicine, the Cleveland Clinic Foundation, Johns Hopkins University School of Medicine, and the Mayo Clinic, are so much more familiar with the disease and recognize the signs quickly. Also, treatment varies tremendously, so even among teaching hospitals, patients are sometimes times treated with high doses of steroids for too long a period of time without the aid of steroid sparing drugs, leading to a great deal of harsh steroid side effects. Going to the experts to begin with often saves time, damage, and money in the long run.

Later, Sunday afternoon Dr. Hoffman wrapped up the conference with the podium presentation Treatments, Medications, Living with Vasculitis in the FUTURE. Dr Hoffman said that researchers are having success in replacing the more toxic medication Cytoxan with Methotrexate, especially in less severe cases of vasculitic disease, resulting in fewer side effects from medication. Also recently doctors have begun to change their recommendations for length of Cytoxan use. Cytoxan used to be given for 1-2 years following diagnosis, but now is being used for shorter periods of time with relatively the same success. It is now more commonly used for 3-6 months, with a more rapid cross over to Imuran or Methotrexate. Also, Dr. Hoffman said that sometimes there may no initial response to Methotrexate. Many times this treatment is then considered a failure and patients are switched to another medication. However, if Metrotrexate is continued, but at higher doses, it often becomes successful in treatment of the disease.Doctors sometimes give up on it too early and move on to more toxic medications.

After listening to all the medical experts and learning about new research, we feel that we are at a good place in time as new information and discoveries are coming in all the time. CSS was once almost always a fatal disease and now the vast majority of patients are able to achieve medically maintained remissions! Even the medical community seems amazed at what the last 20 years of research has brought about in the understanding and treatment of vasculitic diseases.There is only more hope on the horizon for the development of less toxic treatment and possibly even a cure. Patients can help in these efforts by helping to fund research, enrolling in studies, and raising awareness both in the general public and among young doctors and researchers.

These were just a few of the topics presented at the Symposium that were relevant to CSS patients. For a complete listing visit the VF web site. CSSers were pleased to be able to participate in this Symposium and are already making plans to attend the next VF Symposium, which is being planned in conjunction with the Mayo Clinic and scheduled for the Summer of 2008.

The CSSA would like to extend sincere thanks to Vasculitis Foundation, including its' members and its' Board of Directors for opening the Symposium to all vasculitis patients, and to all the volunteers who helped make the Symposium possible, including the Kullman family, and especially to the medical professionals who gave so generously of their time. In addition, the CSSA is very grateful for the interest and participation of so many CSS patients and their families. We look forward meeting old friends and making new ones at the 2008 VF Symposium at the Mayo Clinic in Rochester, Minnesota.

Happy CSS Participants at the Symposium