Immunoglobulin A (
IgA) vasculitis (IgAV, also known as
Henoch-Schoenlein purpura, HSP) is the most common
vasculitis of childhood. It usually presents with a simple, self-limiting disease course; however, a small subset of patients may develop kidney involvement (IgAV-N) which occurs 4-12 weeks after disease onset and is the biggest contributor to long-term morbidity. Treatment currently targets patients with established kidney involvement; however; there is a desire to work towards early prevention of
inflammation during the window of opportunity between disease presentation and onset of significant
nephritis. There are no clinical trials evaluating drugs which may prevent or halt the progression of
nephritis in children with IgAV apart from the early use of
corticosteroids which have no benefit. This article summarises the latest scientific evidence and clinical trials that support potential therapeutic targets for IgAV-N that are currently being developed based on the evolving understanding of the pathophysiology of IgAV-N. These span the mucosal immunity, B-cell and T-cell modulation, RAAS inhibition, and regulation of
complement pathways, amongst others. Novel drugs that may be considered for use in early
nephritis include TRF-
budesonide; B-cell inhibiting agents including
belimumab,
telitacicept,
blisibimod, VIS649, and
BION-1301; B-cell depleting agents such as
rituximab,
ofatumumab, and
bortezomib;
sparsentan;
angiotensin converting enzyme inhibitors (ACE-Is); and
complement pathway inhibitors including
avacopan, iptacopan, and
narsoplimab. Further clinical trials, as well as pre-clinical scientific studies, are needed to identify mechanistic pathways as there may be an opportunity to prevent
nephritis in this condition. Key Points • Kidney involvement is the main cause of long-term morbidity and mortality in
IgA vasculitis despite the current treatment recommendations. • The evolving understanding of the pathophysiology of
IgA vasculitis is allowing exploration of novel treatment options which target underlying immune pathways. • Novel treatments currently being trialled in
IgA nephropathy may have benefit in
IgA vasculitis due to the similarities in the underlying pathophysiology, such as TRF-
budesonide, B-cell modulators, and
complement inhibitors. • Further studies, including clinical trials of novel drugs, are urgently needed to improve the long-term outcomes for children with
IgA vasculitis nephritis.