Thirty Years of Progress in Vasculitis Diagnostics and Treatment
Eric L. Matteson, M.D., M.P.H.
Divisions of Rheumatology and Epidemiology
The occasion of the 30th anniversary of the Vasculitis Foundation marks a good point to look back on how far we have come with our understanding and treatment of vasculitis, and how far we still have to go. Prior to the 1960s, what we today know as ANCA associated vasculitis like granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), and polyarteritis nodosa (PAN) were fatal in over 80% of patients.
The outlook for patients suffering from these diseases started to improve somewhat with the introduction of cortisone in 1950 and its first use in treatment of giant cell arteritis and polyarteritis nodosa almost immediately thereafter. In 1971, a report of use of cyclophosphamide in ANCA vasculitis appeared, which triggered larger studies that demonstrated a dramatic improvement in survival, although with many patients had cyclophosphamide related side effects including bladder and bone marrow cancers and infertility and also suffered from glucocorticoid (steroid) related side effects.
By 1986, when the Vasculitis Foundation was founded, it was well appreciated that although patients were improving and living longer, they continued to suffer from not only treatment related side effects but also were living with the consequences of damage to their organs, including blindness, stroke, kidney failure, disfiguring facial disease, and need for organ transplantation, among the many disease related complications of vasculitis.
Since then, a number of things have happened that have improved our ability to study the diseases and advance the treatment of vasculitis. In my opinion, some of the most important of these are:
The advent of randomized trials:
Formal, large scale trials done by many institutions and centers across the US and internationally working together has been a major reason for improvement in vasculitis care.
Development of investigator cooperatives:
The development of investigator networks such as the Vasculitis Clinical Research Consortium and others has greatly enhanced the ability to pursue investigation and treatment studies.
New and better treatments:
An important result of the more systematic and collaborative efforts in developing therapies by the various work groups has been information about how long to use cyclophosphamide, how and when to use methotrexate, azathioprine and more recently mycophenolate mofetil and other drugs, how better to use steroids and plasmapheresis, and the groundbreaking work with rituximab. These approaches have resulted in improved outcomes and lower drug toxicity rates.
Among the blood tests, the ANCA (anti-neurophil cytoplasmic autoantibodies) came into routine use. ANCA are sensitive and specific markers for GPA and MPA. Other new tests developed in the last 30 years are able to better image involved blood vessels and organs. These include new magnetic resonance imaging (MRI) angiography, computed tomogram angiography (CT), positron emission tomography (PET scan), and use of vascular ultrasound.
Identification of causes of vasculitis:
We describe the systemic vasculitis diseases as “idiopathic”, meaning that we don’t know their cause. However, it has been discovered that at least some cases of PAN are due to infections with hepatitis B and hepatitis C. As well, a number of genes have been identified in ANCA associated diseases and giant cell arteritis which contribute to disease risk and in part determine how the diseases affect patients. None of the genes actually “cause” vasculitis, and there is considerable variation from person to person of the effects of the genes, but identification of these genes is an important start to understanding their role.
Classification of vasculitis diseases:
Better classification of vasculitis has helped clinicians and investigators separate the different diseases and study them in more detail. Some of the diseases have been renamed to appropriately reflect their actual biology (for example IgA vasculitis instead of Henoch Schönlein purpura; granulomatosis with polyangiitis [GPA] rather than Wegener’s granulomatosis); eosinophilic GPA instead of Churg-Strauss disease).
Patient partnerships and networks:
A particularly important and effective advance in the last 30 years has been the development of patient networks and support groups for vasculitis, most effectively the Vasculitis Foundation. This work has not only enhanced the education of patients and families, and physicians and other healthcare providers about vasculitis, but has brought the patient’s voice to the forefront of vasculitis care. Uniquely, the Vasculitis Foundation has also contributed to the understanding of the diseases by providing over $2,000,000 in funding for vasculitis research which has supported investigation, and training of vasculitis specialists.
This involvement of patients in understanding what kind of research and treatments are needed and what education is needed has greatly improved the quality and the meaningfulness of studies in vasculitis and improved care of patients with vasculitis.
Today, survival for some forms of vasculitis like giant cell arteritis is basically identical to that of people who do not have vasculitis. Survival for ANCA vasculitis has also marked improved, and today patients with GPA and MPA have survival between 80% and 97% at one year after diagnosis, and between 75% and 88% after 10 years following diagnosis.
The science of vasculitis and the outlook for patients with vasculitis has improved markedly in the 30 years since the Vasculitis Foundation predecessor was created. There is great momentum, energy and knowledge about vasculitis now, but also much to done in the next 30 years to find the causes, better treatments, and even cures for chronic forms of vasculitis.