Juvenile Localized Scleroderma Research Articles

Superb microvascular imaging for evaluating the activity of juvenile localised scleroderma: a preliminary study.

To investigate microvascular changes in juvenile localised scleroderma (JLS) lesions using superb microvascular imaging (SMI) and assess SMI's utility in evaluating disease activity. This prospective study enroled 16 children (7 males) with pathologically diagnosed JLS between January 2021 and June 2023. Lesions were assessed using Localised Scleroderma Cutaneous Assessment Tools, including the localised scleroderma skin activity index (LoSAI) and localised scleroderma skin damage index (LoSDI). Lesions with LoSAI scores > 0 were classified as active. The thickness and blood flow of the lesions and healthy skin layers of the contralateral site were evaluated using ultrasound. SMI was used to detect microvascular blood flow in the lesions and healthy skin, and the vascular index (VI) was calculated. The difference in VI between active lesions and healthy skin was correlated with LoSAI and total scores. Of 46 lesions, 23 were active and 23 inactive. The skin thickness of the lesion was 0.094 ± 0.024 cm, and that of the healthy site was 0.108 ± 0.026 cm (p < 0.001). The VI of the active lesions and healthy skin were 7.60 (3.60, 12.80)% and 1.10 (0.50, 2.10)%, respectively (p < 0.001). The VI of the inactive lesions and the healthy skin were 0.85 (0.00, 2.20)% and 1.60 (1.00, 3.10)%, respectively (p = 0.011). VI differences between active lesions and healthy skin positively correlated with the LoSAI clinical score (r = 0.625, p = 0.001) and total score (r = 0.842, p < 0.001). SMI can quantitatively detect microvascular blood flow changes in JLS skin, indicating lesion activity and severity. SMI is a convenient, non-invasive, technique for detecting active JLS lesions and can provide valuable information to guide treatment options. Current grading systems of juvenile localised scleroderma rely on subjective clinical information. Superb Microvascular Imaging identified that vascular indexes between active lesions and healthy skin positively correlated with clinical scores. Superb Microvascular Imaging effectively assesses microvascular blood flow, aiding juvenile localised scleroderma lesion activity evaluation.

Evaluation of autologous fat grafting in the treatment of juvenile localized scleroderma with facial involvement

Objectives: The objective of this study was to evaluate the effect of autologous fat grafting in patients with juvenile localized scleroderma with facial involvement. Methods: We retrospectively studied patients with juvenile localized scleroderma who were followed at the Hamburg Center for Pediatric and Adolescent Rheumatology at least 6 months post-operative follow-up and received at least one autologous fat transplantation for a facial lesion. Autologous fat grafting was conducted independent of disease-modifying treatment and/or disease activity. The effectiveness of the intervention was evaluated by assessing the immediate volume enhancement after injection of fat tissue compared with volume retained after 6 months. The volume enhancement was calculated from three-dimensional photo images analyzed in Mirror Medical Imaging Software, Canfield Scientific (New Jersey, USA). Results: Data of 22 juvenile patients were assessed from March 2006 to September 2021. In six patients, the photos could not be evaluated for the study. The median age of the remaining 16 patients at the beginning of the first fat graft was 8 years (range = 2.5–22 years). Patients underwent mean three interventions (range = 1–9). Evaluation of three-dimensional images showed that the volume retention at 6 months post autologous fat grafting is approximately 50%. The Modified Localized Scleroderma Skin Severity Index value did not correlate to volume changes at 6 months. In 4 of 16 patients, a decrease of the Localized Scleroderma Damage Index occurred. In all seven patients with cheek involvement, mean tragus-nose distance difference decreased (mean decrease 1.09 cm). We did not observe any significant clinical side effects. Conclusion: In this first bigger pediatric case series, the mean facial lesion volume increased around 50% after a mean of three interventions at 25 months of follow-up. No flares of the underlying disease were noted. Autologous fat grafting is a promising method to improve the cosmetic appearance of those patients.

Interferons Dominate Damage and Activity in Juvenile Scleroderma.

Twenty-nine juvenile localized scleroderma five juvenile systemic sclerosis, and nine healthy controls were included in the study. Patients with juvenile localized scleroderma were scored according to the LoSAI (LoSCAT activity index), LoSDI (LoSCAT damage index), and PGA-A (physician global assessment-activity) indices. Cytokines and chemokines involved in interferon gene signaling (IL-1, IL-6, IL-8, IP-10, MCP1, TNF-α, CXCL-11, IFN-α, IFN-β, IFN-γ) and interferon-stimulated genes (ISGs) including IFI27, IFI44, ISIG15, IFIT1, OAS1, RSAD2 were measured by ELISA and RT-PCR method respectively. A significant increase in IFN-α, IFN-β, IFN-γ, TNF-α, IL -1, IL -6 IL -8, IP-10, and MCP1 levels was observed in patients with juvenile systemic sclerosis compared with the healthy control group. Furthermore, IFN- α and IP-10 were elevated in both juvenile localized scleroderma and juvenile systemic sclerosis compared to the healthy control group. IFN-γ and IFN-α positively correlated with LoSAI and LoSDI levels, respectively. According to PGA-A analysis, IFN-β, IFN-γ, TNF-α, IL -8, IP10, MCP1, and CXCL11 were significantly higher in active disease than in the inactive state in both groups. The results suggest that interferon signaling may be impaired in patients with juvenile scleroderma. Significant changes were observed in cytokines and genes related to IFN signaling, which may have a crucial role in monitoring disease activity. In addition, we have gained important insights into the possibility of using IFN-α and IFN-γ as biomarkers for monitoring juvenile scleroderma activity and damage.

Antibody status against measles and rubella in juvenile localized scleroderma patients on sDMARDs: a prospective case-control study.

Antibody status against measles and rubella in juvenile localized scleroderma patients on sDMARDs: a prospective case-control study.

Juvenile localized scleroderma

Juvenile scleroderma, often referred to as juvenile localized scleroderma or "morphea", is arare inflammatory disease of the skin and skin-related structures, accompanied by local sclerosis and tissue fibrosis. Depending on the clinical manifestation, four different subtypes can be defined: limited, generalized, linear, and mixed. To prevent possible sequelae of the disease, the diagnosis should be made as early as possible and therapy should be initiated at specialized centers in multiprofessional pediatric and dermatologic collaboration. In this review, we present the main clinical, laboratory, and therapeutic characteristics of juvenile localized scleroderma and summarize recommendations.

Connective tissue nevus misdiagnosed as juvenile localized scleroderma

BackgroundConnective tissue nevi (CTN) are congenital hamartomas caused by excessive proliferation of dermis components. In children, CTN can mimic juvenile localized scleroderma (JLS), an immune mediated skin disorder that requires aggressive immunosuppression. Objectives: Aim of our study was to describe a series of pediatric patients with CTN misdiagnosed as JLS and the discerning characteristics between the two conditions.MethodsRetrospective analysis of children referred to our Center during the last two decades for JLS who received a final diagnosis of CTN. Clinical, laboratory, histopathological and instrumental data (MRI and thermography) were collected and compared with those with JLS.ResultsSeventeen patients with mean age at onset 4.6 years entered the study. All came to our Center with a certain diagnosis of JLS (n = 15) or suspected JLS (n = 2). The indurated skin lesions were flat and resembled either circumscribed morphea or pansclerotic morphea. In 14 patients (82.4%) they were mainly localized at the lower limbs and in three (17.6%) at the upper limbs. No patient had laboratory inflammatory changes or positive autoantibodies. Skin biopsies confirmed the diagnosis of CTN: non-familial collagenoma in eleven (64.7%), mixed CTN in four (23.5%) and familial CTN in two (11.8%). Mean age at final diagnosis was 9.5 years, with a mean diagnostic delay of 4.8 years (range 1–15 years). Sixteen patients underwent musculoskeletal MRI that was normal in all except two who showed muscle perifascial enhancement. Thermography was normal in all patients. At our first evaluation, eleven patients (64.7%) were on systemic treatment (methotrexate 11, corticosteroids 7, biologics 2), three (17.6%) on topical corticosteroids and three untreated.ConclusionsCTN can be misdiagnosed as JLS and therefore aggressively treated with prolonged and inappropriate immunosuppression. The absence of inflammatory appearance of the skin lesions, normal instrumental and laboratory findings and the accurate evaluation of skin biopsy are crucial to address the right diagnosis.

42086 Disease Course and Risk of Relapse in Juvenile Localized Scleroderma

42086 Disease Course and Risk of Relapse in Juvenile Localized Scleroderma

Non-invasive imaging and clinical skin scores in juvenile localized scleroderma.

To evaluate whether in juvenile localized scleroderma (JLS), non-invasive imaging can differentiate affected from non-affected skin and whether imaging correlates with a validated skin score [Localised Scleroderma Cutaneous Assessment Tool (LoSCAT)]. A total of 25 children with JLS were recruited into a prospective study and a single 'target' lesion was selected. High-frequency ultrasound (HFUS, measuring skin thickness), infrared thermography (IRT, skin temperature), laser Doppler imaging (LDI, skin blood flow) and multispectral imaging (MSI, oxygenation) were performed at four sites: two of affected skin (centre and inner edge of lesion) and two of non-affected skin (1 cm from the edge of the lesion 'outer' and contralateral non-affected side) at four visits at 3 month intervals. Differences between affected and non-affected skin were detected with all four techniques. Compared with non-affected skin, affected skin was thinner (P < 0.001), with higher temperature (P < 0.001-0.006), perfusion (P < 0.001-0.039) and oxygenation (P < 0.001-0.028). Lesion skin activity (LoSCAT) was positively correlated with centre HFUS [r = 0.32 (95% CI 0.02, 0.61), P = 0.036] and negatively correlated with centre LDI [r = -0.26 (95% CI -0.49, -0.04), P = 0.022]. Lesion skin damage was positively correlated with centre and inner IRT [r = 0.43 (95% CI 0.19, 0.67), P < 0.001 and r = 0.36 (95% CI 0.12, 0.59), P = 0.003, respectively] and with centre and inner LDI [r = 0.37 (95% CI 0.05, 0.69), P = 0.024 and r = 0.41 (95% CI 0.08, 0.74), P = 0.015, respectively]. Non-invasive imaging can detect differences between affected and non-affected skin in JLS and may help to differentiate between activity (thicker, less well-perfused skin) and damage (thinner, highly perfused skin).

Barriers to care in juvenile localized and systemic scleroderma: an exploratory survey study of caregivers’ perspectives

BackgroundJuvenile localized scleroderma (LS) and systemic sclerosis (SSc) are rare pediatric conditions often associated with severe morbidities. Delays in diagnosis are common, increasing the risk for permanent damage and worse outcomes. This study explored caregiver perspectives on barriers they encountered while navigating diagnosis and care for their child’s scleroderma.MethodsIn this cross-sectional study, caregivers of juvenile LS or SSc patients were recruited from a virtual family scleroderma educational conference and a juvenile scleroderma online interest group. The survey queried respondents about their child’s condition and factors affecting diagnosis and treatment.ResultsThe response rate was 61% (73/120), with 38 parents of LS patients and 31 parents of SSc patients. Most patients were female (80%) and over half were non-Hispanic white (55%). Most families had at least one person with a college education or higher (87%), traveled ≤ 2 h to see their rheumatologist (83%), and had private insurance (75%). Almost half had an annual household income ≥ $100,000 (46%). Families identified the following factors as barriers to care: lack of knowledge about scleroderma in the medical community, finding reliable information about pediatric scleroderma, long wait times/distances for a rheumatology/specialist appointment, balance of school/work and child’s healthcare needs, medication side effects, and identifying effective medications. The barrier most identified as a major problem was the lack of knowledge about juvenile scleroderma in the medical community. Public insurance, household income less than $100,000, and Hispanic ethnicity were associated with specific barriers to care. Lower socioeconomic status was associated with longer travel times to see the rheumatologist/specialist. Diagnosis and systemic treatment initiation occurred at greater than one year from initial presentation for approximately 28% and 36% of patients, respectively. Families of LS patients were commonly given erroneous information about the disease, including on the need and importance of treating active disease with systemic immunosuppressants in patients with deep tissue or rapidly progressive disease.ConclusionCaregivers of children with LS or SSc reported numerous common barriers to the diagnosis, treatment, and ongoing care of juvenile scleroderma. The major problem highlighted was the lack of knowledge of scleroderma within the general medical community. Given that most of the caregiver respondents to the survey had relatively high socioeconomic status, additional studies are needed to reach a broader audience, including caregivers with limited English proficiency, geographical limitations, and financial constraints, to determine if the identified problems are generalizable. Identifying key care barriers will help direct efforts to address needs, reduce disparities in care, and improve patient outcomes.

Juvenile localized scleroderma: A disease with significant morbidity.

Juvenile localized scleroderma: A disease with significant morbidity.

Application of integrated traditional Chinese and Western medicine in the treatment of juvenile localized scleroderma with skin ulcer: a case report

Application of integrated traditional Chinese and Western medicine in the treatment of juvenile localized scleroderma with skin ulcer: a case report

Juvenile localized scleroderma: A single-centre experience from India.

Juvenile localized scleroderma (JLS) or morphoea, a rare chronic autoimmune disease predominantly affects skin, subcutaneous tissue and occasionally the adjacent muscle, fascia and bone. We report the largest single-centre cohort of patients with JLS from India. Patients who were diagnosed to have JLS were enrolled from the Paediatric Dermatology Clinic and the Paediatric Rheumatology Clinic of a tertiary care referral hospital in India. Collected data included details of the clinical profile, laboratory investigations and management. We analysed 84 patients with Juvenile localized scleroderma. Median age of disease onset was 5 years, and median age at diagnosis was 8 years. Commonest subtype was linear scleroderma (57 patients, 67.7%) followed by plaque morphoea and generalized morphoea. Fourteen patients (16.6%) were noted to have extracutaneous manifestations (ECMs). These included arthritis in eight (33.3%), brain parenchymal abnormalities in four (4.7%) and pulmonary involvement in two (8.3%) patients. Antinuclear antibody (ANA) was positive in eight/25 patients (32%; diffuse and speckled pattern in four patients each). One amongst these also had elevated anti-dsDNA titres. Positive ANA was found to have no association with ECMs (p 1.000). Patients were treated using methotrexate (61 patients; 72.6%), dexamethasone oral mini-pulse (OMP; 35 patients; 41.6%), calcipotriol (39 patients; 46.4%), topical corticosteroids (32 patients; 38%) and topical tacrolimus (three patients; 3.7%). Using linear regression analysis, administration of dexamethasone OMP and calcipotriol was found to be a predictor of good treatment response (p 0.034 and 0.019, respectively). Early use of systemic corticosteroids along with methotrexate may be more beneficial than methotrexate therapy alone.

80 Case series of juvenile scleroderma at Aga Khan University Hospital, Nairobi

BackgroundJuvenile scleroderma includes a range of conditions presenting with skin fibrosis. It’s classified into two major categories, localized and systemic. Juvenile localized scleroderma (morphea) is limited to the skin and forms majority of pediatric presentations (>95%). Though rare, juvenile systemic sclerosis involves the skin and other internal organs and is associated with a poorer prognosis.ObjectiveTo characterize the clinical profile of two cases of scleroderma at Aga Khan university hospital, Nairobi.MethodsRetrospective review of medical records of two patients with Juvenile scleroderma managed at Aga Khan university hospital, Nairobi.ResultsThe first patient was a 7-year-old boy presenting with joint pains for 2 months, restricted activities and limping. He also had a non-itchy lesion on the right thigh for about 6 years. On examination, there was an 8 by 18 cm, flat, shiny skin lesion with ill-defined margins and skin thickening around it. There were 2 punched out scars from previous skin biopsy sites with latest biopsy showing atrophic epidermis, dermal collagen homogenization with thick sclerosed fibers in keeping with morphea. Pulmonary function tests revealed mild restrictive lung disease. There were no other systems involved on further evaluation. He was started on weekly methotrexate, daily prednisone, daily folic acid and omeprazole to be followed up in clinic.The second case is a 5-year-old girl who presented with 3-year history of inability to walk. Physical examination revealed areas of skin hypopigmentation and hyperpigmentation on the neck and back with active lesions on the left flank and posterior right leg. She had left lower limb atrophy and extreme wasting of thigh and calf muscles, a contracture of the left knee, ankle and limb length discrepancy. Her investigations revealed positive rheumatoid factor, positive antinuclear antibody (ANA), microcytic hypochromic anaemia and skin biopsy with features of morphea. She received six courses of high dose methyl prednisone over six months, weekly methotrexate, daily folic acid, daily prednisone that was tapered off gradually, calcium supplementation and iron supplementation. In addition, she received isoniazid for tuberculosis prophylaxis with pyridoxine. Her management was multidisciplinary involving orthopedics, physiotherapy, occupational therapy, and dieticians. She developed a new skin lesion on the left forearm about five months after initiation of treatment but no worsening of symptoms or other new lesions thereafter.ConclusionJuvenile scleroderma though rare has a high risk of misdiagnosis with delay in initiation of treatment. It is associated with significant morbidity and early diagnosis, treatment and follow up is imperative for good outcomes.

High-dose immunoglobulin therapy for steroid-resistant myositis in juvenile localized scleroderma.

Juvenile localized scleroderma (jLS) is an autoimmune disease characterized by a mixture of inflammation and fibrosis on the skin and other underlying tissues.1 It often involves the muscles and joints, thus leading to serious problems in growth and motor dysfunctions during childhood. Recently, novel targeted drugs have been introduced for the treatment of jLS; however, these therapeutic options, apart from methotrexate (MTX) and corticosteroids (CS), have limited evidence supporting their long-term safety and efficacy against refractory jLS.

Treatment of juvenile localized scleroderma: current recommendations, response factors, and potential alternative treatments.

Juvenile localized scleroderma (jLS) is a chronic autoimmune and fibrosing disease associated with a high risk for functional impairment. Antifibrotic options are limited, so current treatment strategies are focused on disease activity control. Pediatric rheumatologists are in consensus on the need to treat with systemic immunosuppressants, in particular, methotrexate. However, more than 30% of patients fail initial methotrexate treatment. This review provides an update on current management and reviews reports on potential alternative treatments. An overview of current treatment recommendations and its efficacy are discussed. Recent studies have identified several factors associated with likelihood of treatment response. These include time to initiation of treatment, certain subtypes, and extracutaneous involvement. Findings from recent reports of alternative systemic immunomodulators, including biologic medications, will be summarized. Methotrexate treatment has greatly improved outcome for most jLS patients but a substantial portion have refractory cutaneous and/or extracutaneous disease. Treatment response factors are being identified, which could lead to improved management strategies. Recent studies provide further support on mycophenolate mofetil as an alternative treatment. Data on biologic therapies is encouraging, with data suggesting efficacy for many extracutaneous manifestations but more studies are needed to evaluate these and other options for jLS.

Особливості перебігу та діагностики ювенільної локалізованої склеродермії: аналіз клінічних випадків

Juvenile localized scleroderma is characterized by foci of atrophic skin and lying beneath tissues, but damage of deep soft tissues, bones and joints can be observed, which, in addition to cosmetic changes, can lead to functional disorders and pain. A comparison of literature data and personal observations about the features of the onset, the development of clinical symptoms, the course, results of laboratory and instrumental examinations in children with localized scleroderma was carried out. Purpose - analyze your own data on the diagnosis and course of the pathological process in patients with localized form of juvenile scleroderma and based on the latest data from literary sources, we compare the own data with those from modern literature in the diagnosis of this rare disease. Materials and methods. We observed 48 patients with juvenile scleroderma for the period 2010-2020. The ultrasound examination of blood vessels, ultrasound examination of the abdominal cavity organs, heart and joints, X-ray examination of the lungs and joints, electrocardiographic examination, MRI examination and the indices of autoimmune activity were determined. Results. The features of the course and diagnosis of juvenile localized scleroderma have been analyzed, namely, local skin lesions in the form of multiple foci with later development of sclerosis and atrophy are observed, so as Raynaud’s syndrome, articular syndrome in the form of arthralgias. When conducting laboratory studies, indicators of general inflammatory activity in localized scleroderma are informative. Ultrasound examination of the skin and muscles versus traditional traumatic biopsy is an informative method for diagnosing changes in the dermis, subcutaneous tissue, soft tissues and blood vessels, which is a sign of active scleroderma. Conclusions. Juvenile localized scleroderma has definite features of the clinical course, it is important to bear in mind when establishing the diagnosis: local skin lesion in the form of multiple foci with later development of sclerosis and atrophy, Raynaud’s syndrome, articular syndrome in the form of arthralgias, uninformative laboratory data, visceral damages are frequently manifested by functional disorders, unevenness pathological process in vessels with changes primarily in the intima-media complex, informative ultrasound examination of the skin and muscles. The research was carried out in accordance with the principles of the Helsinki declaration. The study protocol was approved by the Local ethics committee of all participating institutions. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors. Key words: juvenile localized scleroderma, clinical manifestations, diagnosis.

POS0168 NON-INVASIVE IMAGING IN JUVENILE LOCALISED SCLERODERMA: HIGH-FREQUENCY ULTRASOUND, THERMOGRAPHY, LASER DOPPLER &amp; MULTISPECTRAL IMAGING

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) &amp; infra-red thermography (IRT)) can detect differences between affected &amp; non-affected skin, as a next step in developing these as outcome measures. Our hypothesis was that blood flow (and therefore temperature &amp; 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 &amp; inner edge of lesion) and two of non-affected skin (one cm from edge of lesion (‘outer’) &amp; 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%) &amp; 5 male (20%). Mean age at diagnosis was 7.6 years &amp; 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) &amp; affected skin (centre/inner edge). For HFUS, there was strong evidence of a difference between affected &amp; unaffected skin (p&lt;0.001) indicating affected skin is thinner than unaffected. Higher mean values of oxygenation, perfusion &amp; 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)&lt;0.001Inner edge - Contralateral-0.30 (-0.40, -0.20)&lt;0.001Centre - Outer-0.35 (-0.46, -0.24)&lt;0.001Inner edge - Outer-0.31 (-0.40, -0.21)&lt;0.001Centre - Inner edge-0.04 (-0.10, 0.02)0.168MSI (rel units)Centre - Contralateral0.06 (0.03, 0.10)&lt;0.001Inner edge - Contralateral0.06 (0.03, 0.09)&lt;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)&lt;0.001Inner edge - Contralateral47.9 (21.0, 74.8)&lt;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)&lt;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 &amp; unaffected skin in JLS. Whether each technique is only measuring activity &amp; 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 &amp; inner edge measurements suggesting that in future studies, imaging protocols can be simplified.AcknowledgementsThis study was funded by Scleroderma &amp; Raynaud’s UK.Disclosure of InterestsNone declared

Research Progress on Pathogenesis and Treatment of Juvenile Localized Scleroderma

Research Progress on Pathogenesis and Treatment of Juvenile Localized Scleroderma

Juvenile localized scleroderma: clinical picture, diagnosis, therapeutic update (literature review and own observations)

Among rheumatic diseases in children, a special place belongs to juvenile localized scleroderma, which is highlighted as a separate form in the structure of scleroderma diseases and is characterized by: the onset of the disease up to 16 years, skin lesions, often focal or linear (hemiforma), a tendency to form contractures and the development of limbs abnormalities. This form of the disease is characterized by damage to the skin mainly involving the surrounding muscles. The cause of juvenile localized scleroderma is unclear. Three main components underlie the development of the disease: damage to the vascular bed, activation of the immune system with a violation of its regulation and release of cytokines, as well as altered collagen synthesis with proliferation of fibroblasts and the subsequent development of fibrosis. Several forms of juvenile localized scleroderma have been identified, differing in clinical manifestations and depth of lesion of subjacent tissues, and among the skin manifestations, five subtypes are distinguished: plaque, generalized, linear, pansclerotic, and mixed. Diagnosis is based on an analysis of the history and typical clinical picture of the disease. Specific laboratory tests to confirm the disease has not been developed. Modern treatment principles for juvenile localized scleroderma involve the use of different groups of drugs, including methotrexate, corticosteroids, tacrolimus, cyclosporine, imatinibum, mycophenolate mofetil, retinoids, PUVA therapy (Psoralen + UltraViolet A), use of slow calcium channel antagonists (nifedipinum group), bosentan. The studies currently being conducted in the world on the standardization of basic therapy of juvenile localized scleroderma are likely to reveal the optimal variant and duration of treatment for each form of the disease and improve the prognosis of the disease. The article also presents the results of own clinical observations.

Prior elicitation of the efficacy and tolerability of Methotrexate and Mycophenolate Mofetil in Juvenile Localised Scleroderma.

Evidence is lacking for safe and effective treatments for juvenile localised scleroderma (JLS). Methotrexate (MTX) is commonly used first line and mycophenolate mofetil (MMF) second line, despite a limited evidence base. A head to head trial of these two medications would provide data on relative efficacy and tolerability. However, a frequentist approach is difficult to deliver in JLS, because of the numbers needed to sufficiently power a trial. A Bayesian approach could be considered. An international consensus meeting was convened including an elicitation exercise where opinion was sought on the relative efficacy and tolerability of MTX compared to MMF to produce prior distributions for a future Bayesian trial. Secondary aims were to achieve consensus agreement on critical aspects of a future trial. An international group of 12 clinical experts participated. Opinion suggested superior efficacy and tolerability of MMF compared to MTX; where most likely value of efficacy of MMF was 0.70 (95% confidence interval (CI) 0.34-0.90) and of MTX was 0.68 (95% CI 0.41-0.8). The most likely value of tolerability of MMF was 0.77 (95% CI 0.3-0.94) and of MTX was 0.62 (95% CI 0.32-0.84). The wider CI for MMF highlights that experts were less sure about relative efficacy and tolerability of MMF compared to MTX. Despite using a Bayesian approach, power calculations still produced a total sample size of 240 participants, reflecting the uncertainty amongst experts about the performance of MMF. Key factors have been defined regarding the design of a future Bayesian approach clinical trial including elicitation of prior opinion of the efficacy and tolerability of MTX and MMF in JLS. Combining further efficacy data on MTX and MMF with prior opinion could potentially reduce the pre-trial uncertainty so that, when combined with smaller trial sample sizes a compelling evidence base is available.