Juvenile Localized Scleroderma Research Articles

Initial evaluation of an ultrasound measure for assessing the activity of skin lesions in juvenile localized scleroderma

To evaluate the construct validity of 2 proposed measures (the Ultrasound Disease Activity [U-DA] and the Tissue Thickness Score [TTS]) for evaluating sonographic differences in juvenile localized scleroderma skin lesions. We conducted a retrospective review of juvenile localized scleroderma patients who had ultrasound scans of their skin lesions between October 2005 and February 2009. Imaged lesions were classified as active or inactive based upon clinical assessment. Lesions had to have been imaged within 1 month of a clinic visit or have the same clinical assessment during both the visit before and the visit after the scan. Two physicians scored the scans using the U-DA, which scores for differences in lesion echogenicity and vascularity compared with normal tissue. Tissue thickness differences were evaluated by percent differences and by using the TTS. Wilcoxon's rank sum test was performed to assess differences. We studied 52 scans from 21 patients, 32 scans of active skin lesions and 20 scans of inactive skin lesions. Features reported by clinicians as indicative of active disease included erythema, warmth, violaceous color, new lesion, expansion of lesion, and induration. The U-DA was significantly different between active and inactive skin lesions (P = 0.0010) with significant differences found for the parameters of total echogenicity, hypodermis echogenicity, and deep tissue layer vascularity (P = 0.0014, P = 0.0023, and P = 0.0374, respectively). No significant differences were found for tissue layer thickness or TTS. The U-DA may be a useful tool in the identification of localized scleroderma activity. Further study is needed to prospectively evaluate the validity, reliability, and sensitivity of this potential monitoring tool.

Use of cryopreserved autologous cells for extracorporeal photochemotherapy: clinical applications

Using autologous cryopreserved mononuclear cells (MNCs) for extracorporeal photochemotherapy (ECP) offers several advantages, such as treating patients from geographically distant care centers or maintaining ECP schedule while dramatically reducing number of apheresis sessions. We previously reported that cryopreserved cells retain their immunomodulatory properties when exposed to UVA and psoralen. To date, there are no clinical data on the use of cryopreserved MNCs for ECP ("cryo-ECP"). Three patients were treated by cryo-ECP for refractory dermatomyositis, juvenile localized scleroderma, and acute graft-versus-host disease. For the first two patients, cryo-ECP aimed to reduce the number of apheresis sessions. Each cell product was split into three equal fractions: one was infused, and the other two were frozen for later infusion. The third patient was referred to our center from a hospital 700 km away. Fifteen apheresis procedures were performed during his stay: 12 were immediately treated and infused while three were cryopreserved. After discharge, the three cryopreserved bags were thawed, ECP-treated, and then sent back to the patient. In all three patients, cryo-ECP was safe and feasible. These cases illustrate promising clinical applications of the technique, opening perspectives for making ECP much more acceptable to patients while extending its indications.

Localized Severe Scleroderma: A Retrospective Study of 26 Pediatric Patients

Juvenile localized scleroderma includes different conditions characterized by skin hardening with increased collagen deposition. Although juvenile localized scleroderma is considered a relatively benign disease, lesions may extend through the dermis, subcutaneous tissue, muscles, and the underlying bone, leading to significant functional and cosmetic deformities. Furthermore, extracutaneous manifestations are described. We retrospectively analyzed a cohort of 26 patients with severe Juvenile localized scleroderma with particular attention to clinical features, therapy, and long-term outcome. A subgroup of three patients has been further evaluated with infrared thermography. Our findings were consistent with the current literature for demographic, laboratory, and clinical characteristics at disease onset, but, with our patients, the prevalence of extracutaneous manifestations was higher, thus confirming the potential for severe juvenile localized scleroderma to affect organs other than the skin, without increased risk of development toward systemic sclerosis. Correlation between various treatments and clinical endpoint showed that systemic therapy lead to a better outcome: in particular, methotrexate appeared the most effective drug, capable in halting the progression of the disease and sometimes inducing its regression.

Mycophenolate mofetil for localized scleroderma

Evaluation of: Martini G, Ramanan AV, Falcini F et al.: Successful treatment of severe or methotrexate-resistant juvenile localized scleroderma with mycophenolate mofetil. Rheumatology (Oxford) 48, 1410–1413 (2009). This retrospective study reports the outcome of mycophenolate mofetil (MMF) treatment in ten juvenile patients with severe or methotrexate-resistant localized scleroderma (two with pansclerotic morphea, five with linear scleroderma and three with generalized morphea). The clinical efficacy of MMF was assessed by clinical examination and thermography. The authors demonstrated efficacy of MMF in reducing the signs of inflammation, softening or lightening of skin lesions, which allowed reduction in dosage or withdrawal of corticosteroids and methotrexate in all patients. MMF was well tolerated and the investigators concluded that MMF is a valid alternative to methotrexate in arresting disease progression in juvenile localized scleroderma.

Juvenile localized scleroderma with autoimmune thyroid disorder

Juvenile localized scleroderma with autoimmune thyroid disorder

Scleroderma in children: Emerging management issues

Scleroderma is a set of rare connective tissue diseases of unknown etiology. It is characterized by thickening and hardening of the skin. Scleroderma is divided into two main subgroups: systemic and localized. The systemic form, also known as systemic sclerosis, involves diffuse skin involvement associated with fibrotic changes in internal organs. Juvenile localized scleroderma is a more common entity and is usually confined to a specific region of the body with no internal organ involvement. Therapeutics are divided into three main subgroups for juvenile systemic sclerosis: antifibrotics, anti-inflammatories, and vasodilators. For localized disease, anti-inflammatories, vitamin D analogues, and UV irradiation have been investigated. The rarity of scleroderma in children and the self-limiting nature of the disease together make randomized controlled trials very difficult. Therefore, most data on therapeutic modalities for this condition have to be extrapolated from studies conducted on adults. International cooperation, following a standardized operation protocol, is needed to validate these and future interventions such as autologous stem cell transplant and cytokine-directed therapies.

Juvenile linear scleroderma with unique forms of renal involvement

Linear scleroderma is the most common type of juvenile localized scleroderma, which usually involves the limbs. The linear lesions may extend through the dermis, subcutaneous tissue, muscles, and the underlying bone, leading to significant functional and cosmetic deformities. Renal involvement in juvenile localized scleroderma is a rare manifestation. Here we report two cases with juvenile linear scleroderma and unique renal manifestations, including unilateral renal arterial stenosis and immunoglobulin M nephropathy.

AWMF‐Leitlinie Nr. 013/066 Diagnostik und Therapie der zirkumskripten Sklerodermie

SummaryLocalized scleroderma is a rare autoimmune disease with primary affection of the skin, and occasional involvement of the fat tissue, muscle, fascia, and bone. Depending on the clinical subtype, the spectrum of skin lesions ranges from singular plaque lesions to severe generalized or linear subtypes which may lead to movement restrictions and permanent disability. This German S1‐guideline proposes a classification of localized scleroderma that, considering the extent and depth of fibrosis, distinguishes limited, generalized, linear, and deep forms of localized scleroderma, together with its associated subtypes. The guideline includes a description of the pathogenesis, of differential diagnoses, and particular aspects of juvenile localized scleroderma, as well as recommendations for histopathologic, serologic, and biometric diagnostic procedures. Based on studies of topical and systemic treatments as well as phototherapy for localized scleroderma published in international literature, a treatment algorithm was developed which takes account of the different subtypes and the extent of disease.

Successful treatment of severe or methotrexate-resistant juvenile localized scleroderma with mycophenolate mofetil

To evaluate the efficacy of mycophenolate mofetil (MMF) in the treatment of severe refractory juvenile localized scleroderma (JLS). A retrospective chart review was performed in patients with JLS who had been treated with MMF after the failure of a combination of MTX and corticosteroids for at least 4 months, or whose JLS had concomitant severe extracutaneous manifestations. Outcome was assessed through clinical examination and thermography. Adverse events were recorded. Ten patients (six females and four males) were enrolled in the study. JLS clinical subtypes were deep morphoea (two patients with disabling pansclerotic morphoea), generalized morphoea (three patients), linear scleroderma (five patients) affecting the limbs in two and face in three patients (en coup de sabre). The age at onset of disease was 8 (range 2-16) years, and the disease duration at the time of treatment with MMF was 18 (range 8-62) months. All MMF-treated patients experienced clinical improvement that allowed withdrawal or reduction of doses of corticosteroids and MTX. Over a follow-up of 27 (range 6-36) months, mild abdominal discomfort was reported in only one patient. MMF appears to be effective in arresting disease progression in severe or MTX-refractory JLS and is generally well tolerated. Further controlled studies are needed to confirm these data.

Diagnosis and Therapy of Localized Scleroderma

Localized scleroderma is a rare autoimmune disease with primary affection of the skin, and occasional involvement of the fat tissue, muscle, fascia, and bone. Depending on the clinical subtype, the spectrum of skin lesions ranges from singular plaque lesions to severe generalized or linear subtypes which may lead to movement restrictions and permanent disability. This German S1-guideline proposes a classification of localized scleroderma that, considering the extent and depth of fibrosis, distinguishes limited, generalized, linear, and deep forms of localized scleroderma, together with its associated subtypes. The guideline includes a description of the pathogenesis, of differential diagnoses, and particular aspects of juvenile localized scleroderma, as well as recommendations for histopathologic, serologic, and biometric diagnostic procedures. Based on studies of topical and systemic treatments as well as phototherapy for localized scleroderma published in international literature, a treatment algorithm was developed which takes account of the different subtypes and the extent of disease.

Health-related quality of life in children and adolescents with juvenile localized scleroderma

To examine the health-related quality of life (HRQOL) of children with juvenile localized scleroderma (JLS) and to compare them with patients with atopic dermatitis (AD) and healthy controls. The cohorts were identified through a diagnostic index and were seen between January 1996 and December 2006. We identified 81 JLS patients to whom we age- and sex-matched 75 AD patients and 75 healthy controls. All patients were mailed a survey containing the English-language version of the German Revised Children's Quality of Life Questionnaire (KINDL) and the Children's Dermatology Life Quality Index (CDLQI). Linear regression models, adjusted for age and sex, examined differences in the KINDL and CDLQI scores. Survey completion rates in the JLS, AD and healthy control groups were 40, 28 and 44%, respectively. There was no difference in KINDL scores between JLS vs AD (73 vs 74, P = 0.3) and JLS vs healthy controls (73 vs 74, P = 0.8). However, CDLQI scores showed some impairment in HRQOL in JLS patients as compared with a healthy reference population, but not to the degree seen in AD (2 vs 4, P = 0.05). An exploratory analysis showed that HRQOL did not differ among the types of JLS with either measure. JLS patients have some impairment in skin disease-specific HRQOL when compared with a healthy reference population, but not as severe as that seen in AD patients. Overall HRQOL in this JLS cohort was as good as healthy controls, a reassuring finding for patients, families and healthcare providers.

Juvenile localised scleroderma: a retrospective review of response to systemic treatment

Juvenile localised scleroderma (JLS) is a rare connective tissue disorder in childhood. Most lesions are benign and self-limiting, but some progress to cause functional disabilities and cosmetic disfigurement. These lesions require systemic treatment, the mainstay of which is corticosteroids and methotrexate. To report the experience of the use of systemic treatment in children with JLS in our department. We performed a retrospective chart review looking at the patients who received systemic treatment over 14 years and recorded their outcomes. Ten children with aggressive JLS were treated with systemic immunosuppressive therapy. There was an 80% response to treatment. Three of the responders relapsed off treatment, but responded to a further course of therapy. Mean disease duration at diagnosis was 8 months. Treatment was generally well tolerated with few side effects. Early recognition of aggressive localised scleroderma and appropriate referral is imperative for a good outcome.

Mycophenolate Mofetil in severe or methotrexate refractory localized scleroderma

Juvenile Localized Scleroderma (JLS), is characterised by presence of areas of skin thickening, which is relatively benign, but if deeper tissues such as muscle and bone are involved severe deformities may develop. Mycophenolate Mofetil (MMF) is increasingly utilised both for treatment of systemic sclerosis and immune-mediated skin diseases such as psoriasis, graft-versus-host and lichen planus. Our aim was to evaluate efficacy and safety of MMF in the treatment of JLS. Seven patients entered the study (3 M, 4 F). The JLS clinical subtypes were Pansclerotic morphea (2 pts), Generalized Morphea (1), En coup de Sabre (ECDS) (1), Mixed (ECDS/Linear) (3), The age at onset of the disease was 7.5 yrs (range 3 – 16.9) and the disease duration at diagnosis was 1.9 years (range 3 months – 4 years). Previous treatments before starting MMF were oral steroids in 6 pts, IV steroids in 5, MTX in 5, while the patient with ECDS received no treatment. MMF was started because of steroids side effects in one patient and MTX resistance in 5. In ECDS MMF was chosen because of concomitant cerebral vasculitis. All treated patients presented clinical improvement which allowed withdrawal of steroids. Over the follow-up of 27 months (range 6–36 months) only mild abdominal discomfort in one patient was reported. In conclusion MMF seems to be effective in severe or MTX-refractory JLS and is generally well tolerated. Further controlled studies are necessary to confirm these data.

Efficacy and safety of methotrexate treatment of juvenile localized scleroderma

Our goal is to study the efficacy and safety of MTX in juvenile localized scleroderma (JLS). Retrospective study of 59 chlidren with JLS from 3 to 17 y (M = 10.3) treated with MTX was performed. Group 1 (n = 18) – received prednisone 0.5 mg\kg for 6 weeks, taped to 0.1 mg\kg for 12 months + MTX 10 mg\body sq. weekly for 13.7 mo. Group 2 (n = 41) -MTX the same doses and duration. The efficacy was measured in 6 & 12 months using skin score, activity and sclerosis indexes (IA, IS) (1 – 3 points) of skin damage, the safety by clinical & laboratory methods. Group 1 patients had spread linear skin involvement (hemitype), with skin score significantly higher (p < 0.01) than in group 2, where children had mostly local linear skin damage. Previously 9 pts from Group 1, 31 pts from Group 2 received penicillamine (PA) with no effect. MTX therapy was effective in 73% of children unsuccessfully treated with PA & in 98% of patients received MTX as the first medication. Effect of therapy was significantly better in pts with disease duration less than 6 mo. In Group 1 significant improvement (p < 0.01) in skin score, IA, IS had been already achieved in 6 months of treatment, in Group 2 only in 12 mo. MTX was effective in children with linear skin, periarticular contractures. Nausea was the main adverse effect, in 17% of pts, with no correlation with genetic polymorfisms of methylenetetrahydrofolate reductase. MTX is effective and safe in linear JLS.

An update on selected connective tissue diseases in adolescents

This review highlights recent advances in our current understanding of several autoimmune disorders that affect adolescents. Systemic lupus erythematosus, juvenile dermatomyositis, and juvenile localized scleroderma stand out among the connective tissue diseases for their multiorgan involvement, significant potential morbidity, and the challenges of chronic treatment. A better understanding of the pathogenesis of these diseases and new insights into the relationship between the immune dysregulation and clinical features has allowed for the development of novel therapies that are more efficacious and targeted than traditional therapies. This article provides an update of the recent literature, highlighting advances that the general pediatrician should know in the care of adolescents with these diseases.

Localized scleroderma and systemic sclerosis: Is there a connection?

Excess fibrosis of the skin is a clinical hallmark of both localized scleroderma and systemic sclerosis. Localized scleroderma is generally thought to be a skin-limited disease whereas systemic sclerosis can have a wide range of internal organ involvement. Recent data suggest that a subset of patients with juvenile localized scleroderma can go on to develop systemic involvement of their disease. This raises the question of what the connection is, if any, between localized scleroderma and systemic sclerosis.

Ocular involvement in children with localised scleroderma: a multi-centre study

Background:Most of the available documentation in the literature on ocular involvement in localised scleroderma (LS) are descriptions of single cases in adult patients. This article reports the frequency and specific...

Localized scleroderma

Localized scleroderma, also known as morphoea, has a variety of clinical manifestations that can include systemic involvement. Early recognition, diagnosis and treatment may improve the long-term outcome. A large multicentre study coordinated by the Pediatric Rheumatology European Society has yielded important information on the epidemiology and clinical manifestations of juvenile localized scleroderma, especially as it pertains to systemic manifestations. Previous results using methotrexate and corticosteroids have been confirmed. Studies on phototherapy have also demonstrated efficacy. A new immunomodulator, imiquimod, has shown promise in an initial case series. Studies over the past year highlight the wide range of extracutaneous manifestations and different forms of localized scleroderma and suggest that treatment may be beneficial.

Congenital localized scleroderma

Juvenile localized scleroderma (JLS) usually has its onset during later childhood. This report describes the clinical and serologic features of six children with congenital localized scleroderma (CLS). A large, multinational study was conducted among pediatric rheumatology and dermatology centers by collecting information on demographics, family history, triggering environmental factors, clinical features, laboratory reports, and treatment of patients with JLS. Patients with onset at birth were carefully examined. Among 750 patients with JLS, 6 patients (0.8%) had scleroderma-related lesions at birth. Female-to-male ratio was 2:1. All patients had linear scleroderma, in four involving the face with en coup de sabre appearance. Two patients were misdiagnosed as having skin infection, one nevus, one salmon patch, and two undefined skin lesions. The mean diagnostic delay was 3.9 years. In comparison with the group of 733 patients with late-onset JLS, CLS presented a significantly more prolonged disease duration at diagnosis and a higher frequency of en coup de sabre subtypes. Congenital localized scleroderma is a rare and probably underestimated condition in neonates. The linear subtype was the exclusive manifestation of the disease. CLS should be included in the differential diagnosis of infants with cutaneous erythematous fibrotic lesions to avoid functional and aesthetic sequelae and to allow prompt therapy.

Juvenile localized scleroderma: clinical and epidemiological features in 750 children. An international study

Juvenile localized scleroderma (JLS) includes a number of conditions often grouped together. With the long-term goal of developing uniform classification criteria, we studied the epidemiological, clinical and immunological features of children with JLS followed by paediatric rheumatology and dermatology centres. A large, multicentre, multinational study was conducted by collecting information on the demographics, family history, triggering environmental factors, clinical and laboratory features, and treatment of patients with JLS. Seven hundred and fifty patients with JLS from 70 centres were enrolled into the study. The disease duration at diagnosis was 18 months. Linear scleroderma (LS) was the most frequent subtype (65%), followed by plaque morphea (PM) (26%), generalized morphea (GM) (7%) and deep morphea (DM) (2%). As many as 15% of patients had a mixed subtype. Ninety-one patients (12%) had a positive family history for rheumatic or autoimmune diseases; 100 (13.3%) reported environmental events as possible trigger. ANA was positive in 42.3% of the patients, with a higher prevalence in the LS-DM subtype than in the PM-GM subtype. Scl70 was detected in the sera of 3% of the patients, anticentromere antibody in 2%, anti-double-stranded DNA in 4%, anti-cardiolipin antibody in 13% and rheumatoid factor in 16%. Methotrexate was the drug most frequently used, especially during the last 5 yr. This study represents the largest collection of patients with JLS ever reported. The insidious onset of the disease, the delay in diagnosis, the recognition of mixed subtype and the better definition of the other subtypes should influence our efforts in educating trainees and practitioners and help in developing a comprehensive classification system for this syndrome.