Juvenile Systemic Sclerosis Research Articles

Heart transplantation in juvenile-onset systemic sclerosis with primary cardiac involvement: report of two cases and comprehensive literature review.

Juvenile onset systemic sclerosis is a rare chronic multisystem connective tissue disease characterized by skin induration, microangiopathy, autoimmune disturbances and widespread fibrosis of internal organs. Primary cardiac involvement in systemic sclerosis (SSc) is associated with a variable phenotype, including heart failure and arrhythmias, which lead to poor short-term prognosis. Isolated heart transplantation is a rare approach for the treatment of advanced heart failure in patients with systemic sclerosis. We report on two juvenile SSc patients receiving cardiac transplantation due to heart failure with malignant arrhythmias. One patient presented with severe dilated cardiomyopathy with recurrent ventricular tachycardia. Following the appearance of Raynaud phenomenon, he was subsequently diagnosed a rare form of systemic sclerosis sine scleroderma, without cutaneous manifestations or other organs involved. His cardiac condition was unresponsive to antiarrhythmic therapy and immunosuppression used to treat SSc, therefore he underwent successful heart transplantation. The second patient presented diffuse scleroderma with mild pulmonary, esophageal and renal involvement. While extracardiac manifestations were effectively kept under control with immunosuppressive therapy, cardiac involvement rapidly progressed with detection of fibrosis at cardiac magnetic resonance imaging and appearance of severe ventricular arrhythmia. Herein, an extensive multidisciplinary evaluation was pivotal in defining the entity and clinical stability of extracardiac involvement, and thus the patient could profit from heart transplantation. Our experience highlights the importance of considering heart transplantation in carefully selected SSc patients with primary cardiac involvement as a lifesaving procedure.

Juvenile Systemic Scleroderma: A comprehensive Review and Clinical Case Report from a Tertiary Care Hospital in India

Juvenile systemic sclerosis (JSSc) is a highly uncommon, chronic connective tissue disorder that affects multiple systems, marked by progressive deposition of collagen under the dermis, and various deep organs. Delay in diagnosis can cause irreversible vital organ damage, leading to severe morbidities and seriously affecting quality of life. We report a clinical case of a 9-year-old boy with extensive and diffuse skin manifestations with vascular, pulmonary, and gastrointestinal involvement. The sero-immunological test revealed positive ANA results and high titers of anti-topoisomerase (Scl-70) antibodies, indicative of severe manifestation of the disease. He was managed with systemic immunosuppression and other pharmacological and rehabilitative measures to prevent ongoing organ damage and alleviate the patient’s symptoms.

Challenging diagnostic of juvenile systemic sclerosis in limited sources: a case report

Challenging diagnostic of juvenile systemic sclerosis in limited sources: a case report

Interferons dominate damage and activity in juvenile scleroderma.

Juvenile scleroderma is a heterogeneous group of diseases associated with sclerotic skin lesions, grouped as juvenile systemic sclerosis and juvenile localized scleroderma. This study aims to measure the cytokine and chemokine levels involved in interferon (IFN) signalling in patients with juvenile scleroderma and determine their correlation with disease severity. Twenty-nine juvenile localized scleroderma, five juvenile systemic sclerosis, and nine healthy controls were included in the study. Cytokines and chemokines involved in IFN gene signalling (IL-1, IL-6, IL-8, IP-10, MCP1, TNF-α, CXCL-11, IFN-α, IFN-β, IFN-γ) and IFN-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 IFN signalling may be impaired in patients with juvenile scleroderma. Significant changes were observed in cytokines and genes related to IFN signalling, 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.

Clinical characteristics of juvenile systemic sclerosis in Korea: 31-year single-center study.

To evaluate the clinical and laboratory characteristics, therapeutic drugs, and prognosis of juvenile systemic sclerosis (JSSc) at a single center in Korea. This study was a retrospective analysis of patients with JSSc aged <16 years at disease onset and who were treated at our hospital between January 1992 and April 2023. All patients met the Pediatric Rheumatology European Society/American College of Rheumatology/European League against Rheumatism provisional classification criteria for JSSc, and those with localized scleroderma (morphea) were excluded. Among the 13 patients, proximal skin sclerosis (100%), Raynaud's phenomenon (RP) (84.6%), and sclerodactyly (69.2%) were present at the time of diagnosis. The most common symptom before diagnosis was RP, which was present in 10 patients (76.9%), whereas proximal skin sclerosis was observed in only five patients (38.5%). Thirteen patients had positive anti-nuclear antibody (ANA). At the time of diagnosis, five individuals had findings suggestive of interstitial lung disease (ILD) on a pulmonary function test (PFT) or chest computed tomography (CT), two of whom were asymptomatic. During follow-up, three patients developed ILD, one developed renal dysfunction, one developed heart disease, and none died. This study was the first descriptive analysis of clinical features of JSSc in South Korea. Clinical suspicion is essential for diagnosing JSSc in patients with RP, especially if ANA is positive; however, proximal skin sclerosis, which is crucial for diagnosing JSSc, was unrecognized in the early phase of the disease. PFT should be considered even if a patient is asymptomatic or has normal chest CT.

Juvenile Systemic Sclerosis Complicated by Interstitial Lung Disease and Myositis: A Case Report

Systemic sclerosis (SSc) is a rare connective tissue disorder characterized by fibrosis, vascular alterations, and organ dysfunction. Juvenile systemic sclerosis (jSSc), an infrequent form of the disease, primarily affects children, with an incidence of 0.27 to 1 per million. This report details the case of a 10-year-old male patient diagnosed with jSSc complicated by interstitial lung disease (ILD) and myositis. The patient initially presented with characteristic signs of skin thickening and Raynaud's phenomenon, which later advanced to the emergence of ILD and myositis. The case emphasizes the importance of vigilant screening for ILD in jSSc patients, given the severity and associated increased mortality of the complication, and improves our understanding of the underlying clinical features of this disease. It also calls attention to the challenges of managing the disease effectively and necessitates further research to improve treatment outcomes for such patients.

Proposed Response Parameters for Twelve-Month Drug Trial in Juvenile Systemic Sclerosis: Results of the Hamburg International Consensus Meetings.

Juvenile systemic sclerosis (SSc) is an orphan disease, associated with high morbidity and mortality. New treatment strategies are much needed, but clearly defining appropriate outcomes is necessary if successful therapies are to be developed. Our objective here was to propose such outcomes. This proposal is the result of 4 face-to-face consensus meetings with a 27-member multidisciplinary team of pediatric rheumatologists, adult rheumatologists, dermatologists, pediatric cardiologists, pulmonologists, gastroenterologists, a statistician, and patients. Throughout the process, we reviewed the existing adult data in this field, the more limited pediatric literature for juvenile SSc outcomes, and data from 2 juvenile SSc patient cohorts to assist in making informed, data-driven decisions. The use of items for each domain as an outcome measure in an open label 12-month clinical trial of juvenile SSc was voted and agreed upon using a nominal group technique. After voting, the domains agreed on were global disease activity, skin, Raynaud's phenomenon, digital ulcers, musculoskeletal, cardiac, pulmonary, renal, and gastrointestinal involvement, and quality of life. Fourteen outcome measures had 100% agreement, 1 item had 91% agreement, and 1 item had 86% agreement. The domains of biomarkers and growth/development were moved to the research agenda. We reached consensus on multiple domains and items that should be assessed in an open label, 12-month clinical juvenile SSc trial as well as a research agenda for future development.

E31 Diffuse juvenile systemic sclerosis patients show distinct organ involvement, antibody pattern and have significantly more severe disease in the largest jSSc cohort of the world. Results from the juvenile scleroderma inception cohort

Abstract Introduction Juvenile systemic sclerosis (jSSc) is an orphan disease with a prevalence of 3 in 1 000 000 children. In adult patients there are significant differences between the clinical presentation of diffuse and limited subtypes. We reviewed clinical differences in presentation of subtypes in patients in the juvenile systemic scleroderma inception cohort (jSSc). Objectives To study the clinical presentation of jSSc patients with diffuse (djSSc) and limited (ljSSc) subtypes. Methods We reviewed the baseline clinical characteristics of the patients, who were recruited to the jSScC till December 2022. jSScC is a prospective cohort of jSSc patients, who developed the first non-Raynaud’s symptom before the age of 16 years and are under the age of 18 years at the time of inclusion. Results The JSScC included 232 patients, 68% (n = 159) had diffuse subtype. The median age at onset of Raynaud phenomenon was 10.4 years (7.3–12.9) and the median age at the first non-Raynaud symptom was 10.9 years (7.3–13.0). Median disease duration was 2.5 years (1.0–4.6). The female/male ratio was significantly lower in the djSSc subtype (3:1 vs 5:1, P &amp;lt; 0.001). Antibody profile was similar, with the exception of a significantly higher number of anticentromere positive patients in the ljSSc (10% vs 2%, P = 0.02). Decreased FVC &amp;lt; 80% was found in ∼30% and decreased DLCO &amp;lt; 80% was found in around 40% in both subtypes. Abnormal HRCT findings were found in 44% of patients. Pulmonary hypertension assessed by ultrasound was identified in ∼5% in both groups. Gastrointestinal involvement occurred in 43% of djSSc and 36% in ljSSc (P = 0.303). Patients with diffuse subtype had significantly higher modified Rodnan Skin Score (16 vs 4, P = 0.001), more frequently sclerodactyly (85% vs 55%, P &amp;lt; 0.001), a history of digital ulceration (62% vs 30%, P &amp;lt; 0.001), active ulceration (21% vs 8%, P = 0.021), telangiectasia (44% vs 22%, P = 0.002), a decreased Body Mass Index z scores ≤ -2 (20% vs 6%, P = 0.008) and decreased joint range of motion (64% vs 48%, P = 0.022). Patients with ljSSc had significantly higher rate of cardiac involvement (11% vs 3%, P = 0.007). Regarding patient related outcomes djSSc patients had more severe disease with respect to patient reported global disease activity by VAS 0–100 (40 vs 30, P = 0.024), patient reported global disease damage by VAS 0–100 (40 vs 25, P = 0.001), patient reported assessment of ulceration activity by VAS 0–100 (10 vs 0, P = 0.001) and patient reported Raynaud activity by VAS 0–100 (30 vs 15, P = 0.001). Regarding physician related outcomes the physician reported global disease activity by VAS 0–100 (30 vs 20, P = 0.001), physician reported global disease damage by VAS 0–100 (30 vs 20, P = 0.004), and physician assessed ulceration activity by VAS 0–100 (5 vs 0, P = 0.018) were significantly higher in djSSc. Conclusion In the largest jSSc cohort in the world, djSSc patients have a significantly more severe disease. Patients and physician related outcomes were significantly more severe in djSSc group. Interestingly, we found no differences regarding interstitial lung disease, pulmonary hypertension or gastrointestinal involvement, although the number of patients with decreased BMI &amp;lt; -2 z scores was significantly higher in the djSSc patients. Ethics Our work is approved by the IRB of the Ärztekammer Hamburg

Pulmonary Nodules in Juvenile Systemic Sclerosis: A Case-Series from the National Registry for Childhood Onset Scleroderma (NRCOS).

Juvenile systemic sclerosis (jSSc) is a systemic inflammatory and fibrotic autoimmune disease. Adult guidelines recommend obtaining a screening high-resolution computed tomography scan (CT) at diagnosis. As these recommendations are adopted as standard of care for jSSc, increased screening with CT may lead to increased detection of nodules. The implications of nodules identified in jSSc are unclear and unreported. A retrospective chart review was performed on the prospectively enrolled National Registry for Childhood-Onset Scleroderma (NRCOS) cohort over an enrollment period of 20 years. Clinical associations with presence of nodules and nodule characteristics were investigated. In this jSSc cohort, the prevalence of pulmonary nodules was 31% (n = 17 of 54). Nodule characteristics were heterogeneous, and most displayed stability over time. More participants with nodules had structural esophageal abnormalities, restriction, and reduced diffusing capacity on lung function tests, and follow-up imaging. Most participants had multiple nodules, and although most nodules were <5 mm, most participants had at least one nodule >5 mm. Pulmonary nodules are seen in children with jSSc and may be related to more severe disease and/or esophageal dysfunction. More work is needed to provide guidance on radiologic follow-up and clinical management of pulmonary nodules in jSSc.

Childhood rheumatic diseases: bites not only the joint, but also the heart.

Cardiovascular involvement in juvenile rheumatic diseases is the primary manifestation in paediatric vasculitis and a major organ manifestation in paediatric connective tissue diseases. Though coronary vasculitis is the prototypical manifestation of Kawasaki disease, it can also be seen in patients with polyarteritis nodosa. Pericarditis is the most common manifestation seen in juvenile rheumatic diseases like systemic onset JIA, and lupus. Cardiac tamponade, valvular insufficiency, aortic root dilatation and arrhythmias are seen rarely. Cardiac involvement is often recognized late in children. The development of cardiac disease in juvenile systemic sclerosis is associated with a poor outcome. In long term, childhood onset of rheumatic diseases predisposes to diastolic dysfunction and premature atherosclerosis during adulthood. Key Points • Pericarditis is the most common cardiac manifestation in SLE and can lead to tamponade. • Conduction defects are common in juvenile mixed connective tissue disease and systemic sclerosis. • Pulmonary hypertension is a significant contributor to mortality in juvenile systemic sclerosis. • In Kawasaki disease, early treatment can reduce risk of coronary artery aneurysms.

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.

Application and performance of disease activity indices proposed for patients with systemic sclerosis in an international cohort of patients with juvenile systemic sclerosis.

Juvenile systemic sclerosis is a rare childhood disease. Three disease activity indices have been published for adult patients with systemic sclerosis: the European Scleroderma Study Group Index, a modified version of the European Scleroderma Study Group Index and the revised European Scleroderma Trials and Research index. The objective of this study was to determine the feasibility and performance of the three disease activity indices in a prospectively followed cohort of patients with juvenile systemic sclerosis. The analysis cohort was selected from the prospective international inception cohort enrolling juvenile systemic sclerosis patients. The correlation of the disease activity indices with the physicians' and the patients' global assessment of disease activity was determined. The disease activity indices were compared between patients with active and inactive disease. Sensitivity to change between 6- and 12-month follow-up was investigated by mixed models. Eighty percent of the 70 patients had a diffuse cutaneous subtype. The revised European Scleroderma Trials and Research index was highly correlated with the physician-reported global disease activity/parents-reported global disease activity (r = 0.74/0.64), followed by the European Scleroderma Study Group activity index (r = 0.61/0.55) and the modified version of the European Scleroderma Study Group activity index (r = 0.51/0.43). The disease activity indices significantly differed between active and inactive patients. The disease activity indices showed sensitivity to change between 6- and 12-month follow-up among patients who improved or worsened according to the physician-reported global disease activity and the parents-reported global disease activity. Overall, no disease activity score is superior to the other, and all three scores have limitations in the application in juvenile systemic sclerosis patients. Furthermore, research on the concept of disease activity and suitable scores to measure disease activity in patients with juvenile systemic sclerosis is necessary in future.

Scrotal Calcinosis in Juvenile Systemic Sclerosis.

Calcinosis cutis is the deposition of insoluble calcium in the skin and subcutaneous tissues, frequently associated with autoimmune connective tissue diseases, including systemic sclerosis (SSc).1 Calcinosis in SSc presents as subcutaneous nodules of variable size and shape, most frequently on the fingers, but can also affect other locations.2.

Juvenile Dermatomyositis and Diffuse Cutaneous Systemic Sclerosis Overlap

AbstractThe overlapping nature of autoimmune diseases makes diagnosing and stratifying prognosis extremely difficult. Scleromyositis, the most common overlap syndrome, is typically seen in adults and is rarely seen in children. An overlap syndrome like scleromyositis would have clinical features of at least two connective tissue diseases (juvenile dermatomyositis and systemic sclerosis). Furthermore, the presence of anti-PM/Scl antibodies is critical. We describe a patient who presented with widespread skin tightening, hoarseness of voice, dysphagia, and muscle weakness that had been present for 6 months. The patient was diagnosed with overlap juvenile scleromyositis (scleroderma-dermatomyositis overlap). In practice, distinguishing this syndrome from dermatomyositis and scleroderma is critical.

Sarcopenia and rheumatic diseases: is there any connection?

Sarcopenia is characterized by a loss of skeletal muscle mass, a decrease in muscle strength and/or physical performance, and is one of the main causes for limiting daily activities in the elderly. This is associated with an increased incidence of many adverse events such as dysfunction, falls, frailty, hospitalization, disability, and mortality. Primary (considered as a part of the aging process) and secondary sarcopenia (due to malabsorption, immobility/bed rest, starvation, hypothyroidism, osteoporosis, immune-mediated rheumatic diseases) are united by a chronic inflammatory process of different degrees. Sarcopenia supports one of the most widely accepted theories that low-grade chronic inflammation is important in the pathogenesis of many diseases. For a long time, sarcopenia was considered an age-related disease, but recently it has been reported to be more common in young subjects with autoimmune diseases. In particular, the relationship between sarcopenia and rheumatic diseases such as rheumatoid arthritis has been studied in detail. Although the pathogenesis of sarcopenia in autoimmune diseases is not fully understood, it is believed that a chronic inflammatory process contributes to the development of loss of muscle mass and strength, and is different depending on the underlying disease. The definition of sarcopenia varies between studies, which complicates and limits direct comparisons. Therefore, in this review, we demonstrate various diagnostic criteria for sarcopenia, focusing on its prevalence in patients with rheumatic diseases, including rheumatoid arthritis, juvenile idiopathic arthritis, axial spondylitis, psoriatic arthritis, and systemic sclerosis. We developed a structured search strategy for English language publications in PubMed using the term “sarcopenia” in combination with the following keywords: “inflammation”, “diagnosis”, “criteria”, “muscle mass”, “strength”, “outcomes”, “disability”, “mortality”, “pathophysiology”, “rheumatoid arthritis”, “juvenile arthritis”, “axial spondylitis”, “psoriatic arthritis”, “systemic sclerosis”. We focused on clinical trials, meta-analyses and review articles. Articles published only after 2000 year were included, however, we did not include major contributions published before. The search was completed on October 8, 2022.

Gender differences in juvenile systemic sclerosis patients: Results from the international juvenile scleroderma inception cohort.

To compare organ involvement and disease severity between male and female patients with juvenile onset systemic sclerosis. Demographics, organ involvement, laboratory evaluation, patient-reported outcomes and physician assessment variables were compared between male and female juvenile onset systemic sclerosis patients enrolled in the prospective international juvenile systemic sclerosis cohort at their baseline visit and after 12 months. One hundred and seventy-five juvenile onset systemic sclerosis patients were evaluated, 142 females and 33 males. Race, age of onset, disease duration, and disease subtypes (70% diffuse cutaneous) were similar between males and females. Active digital ulceration, very low body mass index, and tendon friction rubs were significantly more frequent in males. Physician global assessment of disease severity and digital ulcer activity was significantly higher in males. Composite pulmonary involvement was also more frequent in males, though not statistically significantly. After 12 months, they are the pattern of differences changed female patients had significantly more frequent pulmonary involvement. In this cohort, juvenile onset systemic sclerosis had a more severe course in males at baseline and but the pattern changed after 12 months. Some differences from adult findings persisted, there is no increased signal of pulmonary arterial hypertension or heart failure in male pediatric patients. While monitoring protocols of organ involvement in juvenile onset systemic sclerosis need to be identical for males and females.

The impact of COVID-19 on clinical course and treatment among patients with juvenile systemic sclerosis.

This study aimed to explore the influence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic among patients with juvenile systemic sclerosis (JSS). Twenty-seven patients (22 females, 5 males; mean age: 20 years; range, 17 to 22 years) diagnosed with JSS and followed up at the department of pediatric rheumatology were included in the cross-sectional study. A web-based survey was performed by focusing on patients' complaints, accessibility to health care, and compliance with routine treatment from January 1, 2021, to January 10, 2021. Five (18.5%) patients had deterioration of the disease, while six (22.2%) patients reported irregular usage of their routine scleroderma treatment during the last six months. Nine (33.3%) patients had missed their routine clinic control since the proclamation of the SARS-CoV-2 pandemic. Seven (25.9%) patients had household contact with coronavirus disease 2019 (COVID-19). Four (14.8%) patients were diagnosed with COVID-19, and only one (3.7%) was hospitalized. Nine patients were under biological treatment (tocilizumab); however, only one of them was diagnosed with COVID-19. The COVID-19 pandemic has not significantly disrupted the medical care of JSS patients. Telemedicine could be an acceptable option for JSS patients disenabled to come to the hospital.

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.

P11 An unusual case of Systemic Sclerosis/JDM overlap in a child with PAX8-related congenital hypothyroidism

Introduction/BackgroundJuvenile dermatomyositis is a rare inflammatory disease with a reported incidence of 0.8–4.1 per million children per year. It presents with a constellation of symptoms and signs of inflammation of skin and muscle, and is associated with significant morbidity if untreated. Juvenile systemic sclerosis (JSSc) is an even rarer rheumatological condition of childhood with significant risk of internal organ involvement, especially cardiopulmonary disease. We herewith present the case of a 7-year-old boy with history of hypothyroidism associated with a PAX8 gene variant who presented with clinical features of an overlap of Systemic Sclerosis with JDM with supportive autoantibody profile.Description/MethodA 7-year-old boy presented with a history of restricted range of movements in his hands – noted due to difficulties with pen grip – and calcinosis. He reported symptoms of fatigue, intolerance to cold with colour changes to hands and feet, stiffness of movements particularly in the morning, and infrequent episodes of choking. His past medical history was significant for hypothyroidism secondary to a paternally inherited PAX8 missense mutation, and there is a family history of Raynaud’s and hypothyroidism. A detailed examination identified diffusely swollen hands with sclerodactyly, calcinosis of his elbows and fingertips, and limited flexion of his fingers and wrists. He also had telangiectasia of his upper eyelids, Gottron’s papules over his knees and elbows, and sluggish circulation in his hands and feet. He had evidence of mild proximal muscle weakness.His investigations revealed mild elevation of muscle enzymes with normal inflammatory markers. His autoantibody profile showed a moderately positive ANA titre of 1600 with a nucleolar pattern, and was positive for anti-NXP2 and anti-SCL-100 antibodies MRI scan of the pelvis showed no evidence of myositis, echocardiogram was normal and a high-resolution CT scan of chest was normal with no features of interstitial lung disease.The overall picture was one of Systemic Sclerosis/JDM overlap with CREST syndrome. He was commenced on induction therapy with IV Methylprednisolone and Cyclophosphamide in view of the calcinosis. After three cycles of Cyclophosphamide and weaning course of oral corticosteroids, his energy levels are significantly improved and he has better overall mobility with no significant proximal muscle weakness (Childhood Myositis Assessment Scale score 49/53). However, flexion of his fingers remains limited albeit better; he has ongoing fingertip calcinosis but fewer lesions over his elbows. He has been commenced on weekly subcutaneous Methotrexate as he completes Cyclophosphamide.Discussion/ResultsThis patient had an unusual medical history of early onset thyroid dysfunction, the genetic testing for which revealed a missense PAX8 gene variant [c.49G>Ap.(Gly17Arg)] (also present in his father, who is euthyroid). This was classified as being of uncertain significance, although felt to clinically be the most likely cause for his hypothyroidism. There was no evidence to suggest that PAX8 gene mutations increased the risk of autoimmune conditions. There is evidence that PAX8 gene mutations, when expressed on malignant cells, may confer resistance to chemotherapy, which made us rethink the plan to commence him on Cyclophosphamide. However, we were reassured that in constitutional variants, there is no increased risk of cancer, and no known history of resistance to Cyclophosphamide.This patient also demonstrated an interesting antibody pattern, as he was positive for anti-NXP2 antibodies (indicating high risk for calcinosis) and anti-SCL-100 antibodies, which are associated with a clinical subset of patients with overlap of Systemic Sclerosis and JDM and associated with extensive extra-muscular features. He had two distinct clinical phenotypes of calcinosis, which is probably explained by the presence of two autoantibodies that increase the risk of calcinosis.Key learning points/ConclusionAlthough JDM has bimodal age group for presentation in childhood, only 3% of systemic sclerosis are seen in childhood, which makes this an extremely unusual presentation, given the age, gender and the overlap features (clinical and immunological).We explored whether this rare presentation could be linked to the underlying PAX8 gene mutations, but we could not find any association.With the clinical diagnosis of systemic sclerosis, it was important to rule out cardiopulmonary complications.The other consideration was regarding the choice of therapeutic agent - whether the germline PAX8 gene variants could increase the risk of malignancies or cause resistance to chemotherapeutic agents like Cyclophosphamide, for neither of which we could find any evidence.Extensive calcinosis cutis in this patient could be explained by the presence of two risk factors (CREST syndrome and JDM with NXP2 antibodies).

Juvenile diabetes and systemic sclerosis: just a coincidence?

BackgroundLimited joint mobility (LJM), previously known as cheiroarthropathy, refers to the presence of reduced extension at the finger joints in people with diabetes and may be associated with scleroderma-like syndromes such as diabetic sclerodactyly.While scleroderma-like syndromes and LJM have been observed in patients with long-term diabetes and associated complications, the coexistence of diabetes with Juvenile systemic sclerosis (jSSc) is rarely described.Case presentationWe describe the case of a 14-year-old boy with long-lasting type 1 diabetes (T1D) and suspected LJM associated with Raynaud phenomenon, sclerodactyly and tapering of the fingertips. A comprehensive work-up showed positive autoantibodies (ANA, anti-Ro-52, anti-Mi-2b), abnormal nailfold capillaroscopy with a scleroderma pattern, interstitial lung disease and cardiac involvement. The overall clinical picture was consistent with the diagnosis of jSSc.ConclusionsLJM can be the initial sign of underlying systemic sclerosis. Nailfold capillaroscopy may help differentiate jSSc from classical LJM in pediatric patients with T1D and finger contractures or skin induration of no clear origin.This case report provides a starting point for a novel hypothesis regarding the pathogenesis of jSSc. The association between T1D and jSSc may be more than a coincidence and could suggest a relationship between glucose metabolism, fibrosis and microangiopathy.