Table 1. Areas for future research in polymyalgia rheumatica and giant cell arteritis: pathogenic mechanisms with matching clinical phenotypes, imaging modalities, possible biomarkers and possible therapies Pathogenetic Matching clinical Possible Imaging findings Possible treatment targets* mechanism symptoms Biomarkers* anti-infection therapies; immunisation; phase Trigger/activation of blockade of DC activation (anti-IL1 symptoms, No known imaging response, ‘flu-like’ innate immunity, DCs, inhibition with canakinumab/ fever, night sweats technique T-cells, B-cells 78 gevokizumab/ leflunomide); possibly IL-6 costimulatory blockade (abatacept); IL-6 blockade (tocilizumab, sirukumab) Headache, scalp pain, Characteristic inflammatory costimulatory blockade (abatacept); thickened arteries, imaging findings such as phase Arterial Inflammatory JAK inhibitors (tofacitinib, Baricitinib); painful arteries, sign (GCA) with response, ‘Halo’ infiltrate88,104,142,143 cytokine blockade (IL-6, IFN, TNF, constitutional sonography, neutrophilia IL-17, IL-23) symptoms MRA and/or PET Imaging signs of Jaw claudication, inflammation and damage: anti-VEGF; Vascular smooth muscle necrosis, sign, occlusion, anti-IFN; ‘Halo’ cell and intimal visual and other stenosis; Vascular biomarkers anti-IL-17 (secukinumab) proliferation 90 ischemic OCT-A changes of retinal inihibitors of neurotrophins manifestations and choroidal vessels, as inihibitors of endothelin well as nerve head Neo-angiogenesis, Increased axillary and Angiogenesis anti-VEGF; Jaw claudication, inhibitors of proteases (MMPs, possible haemorrhage of carotid thickness of media, markers such as ischemic damage such cathepsins, elastase) media 90,114 occlusion, stenosis and elevated VEGF
Table 1. Areas for future research in polymyalgia rheumatica and giant cell arteritis: pathogenic mechanisms with matching clinical phenotypes, imaging modalities, possible biomarkers and possible therapies Pathogenetic mechanism Matching clinical symptoms Imaging findings Possible Biomarkers* Possible treatment targets* Trigger/activation of innate immunity, DCs, T-cells, B-cells 78 ‘flu-like’ symptoms, fever, night sweats No known imaging technique phase response, possibly IL-6 anti-infection therapies; immunisation; blockade of DC activation (anti-IL1 inhibition with canakinumab/ gevokizumab/ leflunomide); costimulatory blockade (abatacept); IL-6 blockade (tocilizumab, sirukumab) Arterial Inflammatory infiltrate88,104,142,143 Headache, scalp pain, thickened arteries, painful arteries, constitutional symptoms Characteristic inflammatory imaging findings such as ‘Halo’ sign (GCA) with sonography, MRA and/or PET phase response, neutrophilia costimulatory blockade (abatacept); JAK inhibitors (tofacitinib, Baricitinib); cytokine blockade (IL-6, IFN, TNF, IL-17, IL-23) Vascular smooth muscle cell and intimal proliferation 90 Jaw claudication, necrosis, visual and other ischemic manifestations Imaging signs of inflammation and damage: ‘Halo’ sign, occlusion, stenosis; OCT-A changes of retinal and choroidal vessels, as well as nerve head Vascular biomarkers anti-VEGF; anti-IFN; anti-IL-17 (secukinumab) inihibitors of neurotrophins inihibitors of endothelin Neo-angiogenesis, possible haemorrhage of media 90,114 Jaw claudication, ischemic damage such Increased axillary and carotid thickness of media, occlusion, stenosis and Angiogenesis markers such as elevated VEGF anti-VEGF; inhibitors of proteases (MMPs, cathepsins, elastase)
170706%20Dasgupta_accepted.docx