290. Vasculitis of the young: Treat to target when precision medicine is not possible
Creators: name: Gallagher1, Kathy
Publisher: name: Zenodo
Year: 2022
Subjects: Vasculitis
ANCA
Abstracts
Giant Cell Arthritis
MPA
GPA
EGPA
Takayasu
IgA vasculitis

description: <strong>Background:</strong> Precision medicine refers to the concept of treating the right patient, with the right drug, at the right time. This is an aspiration for children with vasculitis but is not always possible, even with modern diagnostic molecular approaches. The differential diagnosis of paediatric vasculitis is increasingly broad encompassing chronic infection, malignancy, autoimmunity, an ever-expanding number of monogenetic autoinflammatory diseases, and a plethora of non-inflammatory genetic vasculopathies. Next-generation genetic sequencing has disrupted conventional diagnostic approaches but does not always deliver a precise diagnosis. A pragmatic treat-to-target approach is required to facilitate empiric therapeutic decisions (Box) which improves patient quality of life. We present 2 challenging cases illustrating this approach. <strong>Methods/Results:</strong> Patient A: a 19-month-old girl was born in good condition following uneventful pregnancy and delivery. At 4 hours old, she developed a widespread purpuric rash. Thrombocytopenia was noted transiently 70 x10<sup>9</sup>/L. Clotting, cell counts, bone marrow aspirate, and inflammatory markers were normal. ANCA was negative. Congenital infection and immune deficiency were excluded. Skin biopsy revealed florid leucocytoclastic vasculitis (LCV). Workup for interferonopathy (CT head and peripheral blood interferon gene signature) were normal. Whole exome sequencing did not reveal any genetic diagnosis. Cutaneous vasculitis without other organ involvement persisted throughout infancy, despite unsuccessful therapeutic trials of GC, topical tacrolimus, and oral janus kinase 1/2 inhibitor (baricitinib). Empiric treatment with anakinra to treat chronic cutaneous LCV is currently underway. All other targets in Box have been met, providing reassurance to parents (and doctors), in the face of no precise diagnosis. Patient B: a previously well 9-year-old boy presented to his GP with a painless lump on the volar aspect of his forerarm. A second lump appeared soon after. There were no fevers although ESR and CRP were both grossly elevated. USS revealed two saccular aneurysms of the brachial artery distal branches. Emergency treatment with high dose intravenous GC was instituted for presumed large vessel vasculitis (LVV). Non-invasive angiography was not suggestive of LVV, however, revealing multiple saccular, thin-walled, non-enhancing aneurysms of his whole aorta, intrarenal arteries, common iliacs, femorals, and brain. Acute back pain developed, necessitating emergency surgical repair of a large aorto-right iliac artery aneurysm and bilateral nephrectomy. Histology of the arterial wall revealed minimal inflammation, no granuloma, and fibrosis with dystrophic calcification. Immunofluorescence was negative. Histology did not resolve the diagnostic equipoise around LVV versus non-inflammatory genetic vasculopathy. Immunosuppression was paused in the immediate post-operative phase; dialysis was commenced; and ongoing investigations focusing on whole exome sequencing to explore a non-inflammatory vasculopathy are awaited. <strong>Conclusions:</strong> These two cases highlight the diagnostic and therapeutic challenges encountered in paediatric vasculitides and illustrate that a treat-to-target approach can still be utilised for children with imprecise diagnoses. The case for empiric immunomodulation in case A is clear, although this child did not have any organ or life-threatening features, and the treatment target is to resolve cutaneous LCV. In contrast, the case for empiric immunosuppression in case B is less clear-cut, even though life-threatening vasculopathic features are present since non-inflammatory vasculopathy may be a more likely cause than LVV. <strong>Disclosures:</strong> None <strong>Table 1</strong> Therapeutic targets for vasculitis without a precise diagnosis Prevent organ injury or death Normalise markers of systemic inflammation Minimise glucocorticoid (GC) toxicity Minimise burden of immunosuppression: <em>is this disease really inflammatory</em>? Maximise growth Minimise disruption to education: use oral medicines given at home