I38. From Bark to B Cells

Abstract

William Heberden in his commentaries on the history and cure of diseases described two children aged 4 and 5 with an unusual illness characterized by purpura and arthralgias. The first child was treated with purging and the second decoction of cinchona bark. These case descriptions are now generally recognized to be the first descriptions of IgA vasculitis. Heberden clearly recognized that these cases were different and worth recording from amongst the vast bulk of young patients with infectious disease. The classification of vasculitis has developed considerably over the last two hundred years, IgA vasculitis illustrates the changes which have occurred. During the mid-19th century Henoch and Schonlein described the condition characterized by purpura, arthralgia, nephritis and gastrointestinal disturbance which was then eponymously named after them. During the 1970s it was first recognized that IgA deposition in skin and renal biopsies was a key pathological feature of Henoch-Schonlein purpura (HSP), to the extent that the Chapel Hill Consensus Conference in 2012 felt able to recommend that HSP should be renamed IgA vasculitis. IgA vasculitis predominately occurs in children (and adolescents) as observed by Heberden and it is one of the commonest causes of systemic vasculitis. Overall vasculitis occurs either in childhood or in the elderly. The classification and diagnosis of vasculitis remains a challenge in the absence of validated diagnostic criteria, although the DCVAS study aims to address this. The differential diagnosis of vasculitis is broad and includes infection, malignancy, occlusive vasculopathy and angiographic mimics. Recognition of vasculitis has undoubtedly improved over the past two decades. This is especially true following the introduction of routine testing for the presence of ANCA, a development which has led to the recognition of AAV as a subset of the systemic vasculitides. The treatment of all forms of vasculitis has progressed since the days of bark, bleeding and purging, with the introduction of B cell depletion it is now based on scientific rationale rather than empiricism. The introduction of glucocorticoids resulted in significant improvement with reduction in visual loss in GCA and improving mortality in the AAV. Cytotoxic agents especially cyclophosphamide in combination with glucocorticoids resulted in further improvement in mortality in the AAV to the extent that they have been converted from disease with a very high mortality to chronic diseases requiring long term therapy. The modern treatment paradigm of remission induction, consolidation and maintenance therapy has been underpinned by a suite of multinational European clinical trials which have provided a solid evidence base for therapy. Many patients now remain on therapy for many years and they and their carers require appropriate medical, education and social support.