Abstract

BackgroundOutcome measures which can differentiate activity (inflammation) from damage (fibrosis/atrophy) would facilitate development of new treatment strategies in juvenile localized scleroderma (JLS) to target the inflammatory phase of the disease.ObjectivesTo evaluate whether in JLS, non-invasive imaging modalities (high frequency ultrasounds (HFUS), multispectral imaging (MSI), laser doppler imaging (LDI) & infra-red thermography (IRT)) can detect differences between affected & non-affected skin, as a next step in developing these as outcome measures. Our hypothesis was that blood flow (and therefore temperature & oxygenation) would be increased in lesional skin.MethodsParticipants aged 4-17 were recruited from 3 paediatric rheumatology centres in the UK. For each participant, a single lesion was selected. HFUS (30MHz), MSI (bespoke camera and tuneable liquid crystal filter, coupled to custom analysis software, 500nm/710nm wavelengths), LDI and IRT imaging were performed at four sites relating to each lesion: two of affected skin (centre & inner edge of lesion) and two of non-affected skin (one cm from edge of lesion (‘outer’) & contralateral unaffected side). Imaging was performed at 4 visits at 3 monthly intervals. Mean values were compared between the four sites using data from all visits by mixed-effects linear regression to account for individual-level clustering.Results24 participants completed all 4 visits and 1 attended 3. 20 participants were female (80%) & 5 male (20%). Mean age at diagnosis was 7.6 years & disease duration 4.9 years. Subtype of disease was linear head in 5/25 (20%), linear limb 12/25 (48%), generalised morphea 1/25 (4%), mixed 5/25 (20%) and superficial plaque in 2/25 (8%).Table 1 shows a subset of data. All 4 imaging techniques could detect differences between healthy (outer/contralateral) & affected skin (centre/inner edge). For HFUS, there was strong evidence of a difference between affected & unaffected skin (p<0.001) indicating affected skin is thinner than unaffected. Higher mean values of oxygenation, perfusion & temperature were observed in affected compared to non-affected skin in MSI, LDI and IRT respectively. There was no statistical difference seen between inner edge and centre of the lesion in any of the methods.Table 1.Mean differences between different locations for each imaging techniqueImaging techniqueLocationOverall mean difference (95% CI)p-valueHFUS (mm)Centre - Contralateral-0.34 (-0.46, -0.22)<0.001Inner edge - Contralateral-0.30 (-0.40, -0.20)<0.001Centre - Outer-0.35 (-0.46, -0.24)<0.001Inner edge - Outer-0.31 (-0.40, -0.21)<0.001Centre - Inner edge-0.04 (-0.10, 0.02)0.168MSI (rel units)Centre - Contralateral0.06 (0.03, 0.10)<0.001Inner edge - Contralateral0.06 (0.03, 0.09)<0.001Centre - Outer0.04 (0.01, 0.07)0.012Inner edge - Outer0.03 (0.00, 0.06)0.028Centre - Inner edge0.01 (0.00, 0.02)0.251LDI Relative perfusion unitsCentre - Contralateral44.8 (24.4, 65.2)<0.001Inner edge - Contralateral47.9 (21.0, 74.8)<0.001Centre - Outer19.1 (1.0, 37.1)0.039Inner edge - Outer24.8 (6.7, 42.9)0.007Centre - Inner edge-3.5 (-20.3, 13.2)0.679IRT oCCentre - Contralateral0.58 (0.24, 0.91)0.001Inner edge - Contralateral0.44 (0.13, 0.75)0.005Centre - Outer0.44 (0.22, 0.66)<0.001Inner edge - Outer0.30 (0.09, 0.52)0.006Centre - Inner edge0.14 (-0.05, 0.32)0.153The overall mean difference is the measurement of the first location minus the measurement from the second location (e.g. centre minus contralateral), averaged across the four visits.ConclusionOur results suggest non-invasive imaging can detect differences between healthy & unaffected skin in JLS. Whether each technique is only measuring activity & not damage requires further evaluation. The leading edge of lesions has historically been considered as most active compared to the centre. However, no difference was seen between centre & inner edge measurements suggesting that in future studies, imaging protocols can be simplified.AcknowledgementsThis study was funded by Scleroderma & Raynaud’s UK.Disclosure of InterestsNone declared

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