INTRODUCTION — Scleroderma is a group of diseases that vary in severity and that can occur at any stage of life, although the clinical patterns of scleroderma in children differ from those in adulthood [1]. The predominant form of scleroderma in childhood is localized scleroderma. The juvenile systemic sclerosis (JSSc) form of scleroderma is uncommon but generally has more serious, potentially life-threatening morbidity than other sclerotic disorders.

Treatment is based upon disease severity, activity, and progression. However, laboratory assessment of these is difficult. Thus, regular follow-up and clinical review are the cornerstones of monitoring.

This topic reviews monitoring and management of JSSc. The classification, clinical presentation, and diagnosis JSSc are discussed in detail separately. Localized scleroderma in children and the pathogenesis of SSc are also discussed in detail elsewhere. (See "Juvenile systemic sclerosis (scleroderma): Classification, clinical manifestations, and diagnosis" and "Juvenile localized scleroderma" and "Pathogenesis of systemic sclerosis (scleroderma)".)

SSc in adults is also discussed in detail separately. (See "Clinical manifestations and diagnosis of systemic sclerosis (scleroderma) in adults" and "Overview of the treatment and prognosis of systemic sclerosis (scleroderma) in adults".)

ORGAN SYSTEM MONITORING — Many serologic markers of activity, such as intercellular adhesion molecule 1 (ICAM-1), collagen propeptides, products of type I collagen breakdown, immunologic markers (soluble interleukin 2 [sIL-2] receptor, neopterin), and vascular activation markers (E-selectin, thrombomodulin, von Willebrand factor), have been proposed throughout the years, but none have shown significant correlation with the clinical status of the patient. Thus, patients are monitored clinically rather than through laboratory markers of disease activity.

Organ systems are monitored for involvement, usually every three to four months as follows:

●Cardiovascular – Although uncommon, cardiac involvement is the leading cause of death in JSSc. Cardiac monitoring includes a standard electrocardiogram (ECG), echocardiogram, and 24-hour cardiac monitoring for arrhythmias.

ECG abnormalities include first-degree heart block, right and left bundle branch block, premature atrial and ventricular contractions, and nonspecific T-wave changes. The most frequent cardiac arrhythmias in children with JSSc are supraventricular, whereas ventricular arrhythmias are uncommon [2].

Echocardiographic abnormalities include pericardial effusions, thickening of the left ventricular wall, and decreased left ventricular compliance. The two-dimensional echocardiogram is important in confirming early pulmonary hypertension by documentation of a dilated right ventricle with thickening of the ventricular wall and straightening of the septum.

Right heart catheterization provides definitive confirmation but is indicated only in selected cases; for example, when echocardiographic data suggest a pulmonary artery hypertension.

Additional noninvasive and sensitive assessment tools for the early detection of cardiac involvement include cardiac magnetic resonance imaging (MRI) and speckle tracking strain rate (S-SR) echocardiography (STE). STE, if available, is indicated at every follow-up visit, especially in patients with a severe course of disease. Cardiac MRI is indicated when standard echocardiography or STE suggest myocardial abnormalities. As an example, myocardial fibrosis was detected using late-enhancement images (LGEs) on MRI in 15 to 66 percent of asymptomatic adult patients [3-5].

●Respiratory – Pulmonary function testing is routinely used to detect early signs of respiratory involvement. Characteristic findings of the respiratory tract involvement include a decrease in timed vital capacity (FVC), forced expiratory flow (FEV), and diffusing capacity of the lungs for carbon monoxide (DLCO) consistent with a restrictive pattern [6]. In case of abnormality, high-resolution computed tomography (HRCT) of the chest may confirm the presence of pulmonary disease in patients with abnormal pulmonary function. The most frequent findings on HRCT are ground-glass opacification, subpleural micronodules, linear opacities, and, later in the disease process, honeycombing [7,8]. A six-minute walk test is another potential tool for monitoring pulmonary function [9].

●Gastrointestinal – Gastrointestinal involvement is often asymptomatic initially. Thus, imaging is necessary for diagnosis. Scintigraphy or cine-esophagram can document decreased peristalsis in the lower part of the esophagus with distal dilation, strictures, and shortening. Esophageal manometry and 24-hour pH probe monitoring represent more sensitive indicators of diminished lower sphincter tone and presence of reflux [10]. These two studies are both performed if scintigraphy or esophagram is abnormal and the patient is able to tolerate and cooperate with the procedures.

●Skin – Skin induration is measured using the Modified Rodnan Skin Score (mRSS) (figure 1 and figure 2), corrected for body mass index (BMI) and the Tanner stage [11]. (See "Pretreatment evaluation of adults with systemic sclerosis (scleroderma)", section on 'Cutaneous'.)

●Microvascular – Capillary abnormalities can be detected by nailfold capillaroscopy and categorized into early, active, and late stages (figure 3 and picture 1) [12]. The early SSc pattern is characterized by a few enlarged/ectatic capillaries and hemorrhages but normal density of capillaries. In the active stage, multiple giant and enlarged/ectatic capillaries with hemorrhages and disordered capillaries due to capillary loss are seen. The late pattern is distinguished by completely disturbed architecture with loss of multiple capillaries and bushy capillaries (neovascularization), with giant capillaries and hemorrhages only occasionally visible.

In adults, the response to treatment for Raynaud phenomenon (RP) is assessed by patient/clinician RP activity assessment, RP frequency (number of attacks per week), and RP duration (mean duration of RP attacks per week) [13]. The same approach is taken in children, although it has not been validated in any studies. Digital ulcers as a complication of RP or vasculitis can be evaluated by both digital ulcer count and degree of pain by visual analog scale (VAS). An innovative technique for RP assessment is based on the use of infrared thermography after cold challenge. This gives an indirect measure of the microvascular flow (damage) and is useful in differentiating RP secondary to SSc from primary RP and acrocyanosis if the diagnosis is in question [14].

●Musculoskeletal –Osteoarticular involvement is assessed by evaluating for the presence of arthritis, limited range of motion in the joints, and tendon friction rubs. Imaging can be used to assess for tenosynovitis, arthritis, fasciitis, myositis, and bony changes associated with arthropathy. The childhood Myositis Activity Score (c-MAS) is used to assess muscle strength (table 1) [15].

●Renal – Renal function is monitored by standard urine analyses and creatinine clearance with calculation of the glomerular filtration rate. Patients on glucocorticoids should have their blood pressure and renal function carefully monitored (eg, every one to two months if the patient is on >0.5 mg/kg/day of prednisone) because of a potential increased risk of scleroderma renal crisis, particularly in patients with diffuse SSc and high or rapidly progressing skin score.

SCORING TOOLS — There is significant variability in disease severity in children. Thus, a multidimensional severity score, named "J4S," an acronym that stands for Juvenile Systemic Sclerosis Severity Score, including growth parameters, skin, and internal organ involvement, was designed to follow JSSc patients over time (table 2) [16]. The J4S includes a general category and eight organ system categories: vascular, cutaneous, osteoarticular, muscular, gastrointestinal, respiratory, cardiac, and renal. Each category is scored from 0 to 4 and then weighted based upon the clinical importance of the organ system involved. The parameters that are more sensitive to change are Raynaud phenomenon (RP), number of digital scars, and number of ulcers/gangrene for vascular involvement and the body mass index (BMI) for general assessment. J4S may have several applications for the pediatric age group since it can be used to guide decision making in daily clinical practice, compare study populations, and identify potentially reversible aspects of the disease.

Two tools that measure patient function and quality of life have been validated for children with juvenile idiopathic arthritis and juvenile dermatomyositis: the Childhood Health Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ-PF50). Although these two instruments also appear to be excellent tools to measure clinical outcomes in children with SSc, especially in clinical trials, validation of these measures is required.

MANAGEMENT OVERVIEW — A carefully designed treatment program is based upon disease severity and progression. This multi-team approach includes [17]:

●Skin care

●Vascular protection by avoidance of cold and sudden temperature changes

●Exercise program to maintain functional ability

●Psychologic and social support

●Disease-modifying and organ-targeted pharmacologic therapy including discussions with the patient and caregiver(s) of available options

●Surgical procedures, if needed

●Education of the patient and caregiver(s) to help understand the complexity of management decisions, guide decision making, and facilitate adherence with an often difficult and time-consuming treatment plan

The pharmacologic management of patients with JSSc is challenging because the etiology and pathogenesis are poorly understood and the disease is heterogenous with variable progression [18]. The treatment of JSSc focuses on controlling symptoms and minimizing progression of internal organ involvement. No drug has been shown to be of unequivocal benefit in either children or adults with SSc, and there are no randomized trials or observational studies of these therapies in children with JSSc. In addition, many of these drugs have significant side effects. As a result, careful consideration must be made as to whether or not to initiate treatment, including balancing the known toxicities of the medications against the unknown possible therapeutic gain.

Options for therapeutic approaches include:

●Immunomodulatory therapy, which is directed at controlling the underlying disease process

●Organ-targeted therapy, which is directed toward complications of specifically involved organs

●Experimental therapy

GENERAL MEASURES — Nonpharmacologic measures include the following [17]:

●General skin care includes avoiding irritating or drying substances and the daily application of lanolin or water-soluble cream as an emollient.

●Patients and caregivers should be told to avoid cold, trauma, heat, and sun exposure. Cold and trauma can exacerbate symptoms. Especially in cold climates, the caregiver should keep the child warm by maintaining a satisfactory household temperature and by use of appropriate clothing, including well-insulated mittens (not gloves), boots, and a hat. These children are also susceptible to hyperpigmentation from sunlight and have difficulty in dissipating heat through sclerotic skin.

●The child should be encouraged to be as physically active as possible. Physiotherapy will help maintain functional ability, muscle strength, and joint movement while preventing flexion contractures.

●The use of corrective splints may be necessary to treat or prevent contractures.

●In patients with gastrointestinal involvement, small, frequent meals; avoiding eating before bedtime; and raising the head of the bed are advised.

IMMUNOMODULATION — An activated immune system may be an important stimulus to both fibrotic and vascular lesions in SSc. The maximum damaging effect is most likely in the early stages of the disease. Initial immune activation may create autocrine loops through the production of cytokines and growth factors, for example, which require no further stimulus to perpetuate fibrotic and vascular lesions.

Many immunotherapies are used in adults with SSc with varying degrees of efficacy. These therapies are selected case by case and usually are reserved for patients with severe, refractory diffuse cutaneous SSc (dcSSc) or overlap syndromes. The following have the most reliable efficacy and may be used in children:

●Mycophenolate – Several observational studies have reported promising results with mycophenolate mofetil (MMF) for skin and pulmonary fibrosis [19-21]. One large observational study, including 326 patients from European centers, found that MMF was well tolerated and associated with improvement in skin disease over 12 months [22]. Another study comparing oral cyclophosphamide with MMF showed benefit for lung fibrosis and skin in both treatment arms [23].

●Glucocorticoids – High-dose systemic glucocorticoids are potentially toxic and have been implicated in precipitating renal crisis [24]. Glucocorticoids should be restricted to patients with myositis, active fibrosing alveolitis, symptomatic serositis, the early edematous phase of the skin disease, active arthritis, and/or tenosynovitis. The lowest possible effective dose should be used in these settings, preferably below 0.3 mg/kg/day of prednisone.

●Cyclophosphamide – The role of cyclophosphamide in SSc remains uncertain. Its efficacy as a single agent is variable but, in combination with glucocorticoids or plasma exchange, is possibly efficacious in patients with fibrosing alveolitis who do not yet have advanced fibrosis [25].

ORGAN-TARGETED THERAPY — The European League Against Rheumatism (EULAR) Scleroderma Trials and Research (EUSTAR) group has established evidence-based recommendations for treatment of specific organ involvement in SSc [26]. These recommendations are based upon observational studies and randomized trials in adults. However, there are no validated recommendations for JSSc. As such, a European project called Single Hub and Access Point for Pediatric Rheumatology in Europe (SHARE) was carried out to optimize and disseminate diagnostic and management regimens in Europe for children and young adults with rheumatic diseases [27]. As part of this effort, an international committee of experts in JSSc was created for the development of specific consensus-based recommendations.

Surgical procedures are variable and may include orthopedic procedures for tendon release, gastrointestinal surgical treatments for severe gastroesophageal reflux disease (GERD), and calcium removal in case of tumoral calcinosis.

In the following section, we present organ-targeted treatment strategies for JSSc based upon preliminary reports of SHARE experts in International Congresses and meetings and adult patient guidelines [26]. Pediatric-specific literature is reviewed here. A more complete discussion on organ-based treatment for SSc is found elsewhere in multiple organ-specific topics and an overview. (See "Overview of the treatment and prognosis of systemic sclerosis (scleroderma) in adults".)

Vascular involvement — Vasodilator agents are often used in patients with vascular involvement, mainly manifesting as Raynaud phenomenon (RP) and digital ulcerations or lung vascular disease (pulmonary hypertension). Specific treatment of RP is used in patients who do not respond to avoidance of precipitating circumstances such as cold or emotional stress. (See "Treatment of Raynaud phenomenon: Initial management", section on 'General measures' and "Juvenile systemic sclerosis (scleroderma): Classification, clinical manifestations, and diagnosis", section on 'Raynaud phenomenon'.)

The use of vasodilator agents in patients with JSSc is rather common, especially for vasospastic phenomenon of the extremities, despite the limited published evidence. The most widely used vasodilators are the calcium channel blockers (CCBs). Of these, nifedipine is the drug most commonly used. An alternative to CCBs is a phosphodiesterase type 5 inhibitor (PDE-5i) such as sildenafil. In view of costs and feasibility, CCBs or PDE-5i are used as first-line drugs when pharmacotherapy is needed in the treatment of RP in children with JSSc. Intravenous prostanoids such as the prostaglandin, iloprost, are used if other therapy fails [26]. Data from a study on a small group of pediatric patients treated with iloprost infusions for ischemic digits and digital ulcerations suggest that these agents are effective and have a good safety profile [13]. Use of these drugs for RP is off label. Treatment of RP is discussed in greater detail separately. (See "Treatment of Raynaud phenomenon: Initial management" and "Treatment of Raynaud phenomenon: Refractory or progressive ischemia".)

Digital ulcers are another severe and disabling complication of JSSc. In view of overall risk-to-benefit considerations, CCBs and PDE-5i are typically used as first-line therapy in SSc-related digital ulcers [28]. Prostanoids are used as first-choice treatment in rapidly progressive digital ulcers or in case of CCB resistance, with the same modalities as in severe RP. Endothelin 1, a potent vasoconstrictor and smooth muscle mitogen, is a possible target in patients with digital ulcers. Bosentan, a dual endothelin receptor antagonist, is recommended in the adult SSc population both for preventing digital ulcerations and for pulmonary hypertension [26]. Little evidence is available in children regarding use of bosentan for digital ulcerations [29]. However, the SHARE experts committee agree that bosentan is an option in patients with JSSc who have digital ulcerations refractory to other therapies and/or pulmonary hypertension. (See "Overview of the treatment and prognosis of systemic sclerosis (scleroderma) in adults", section on 'Raynaud phenomenon' and "Treatment of Raynaud phenomenon: Refractory or progressive ischemia".)

Interstitial lung disease — Pulmonary alveolitis is predominant early in the course of interstitial lung disease (ILD) and later progresses to fibrosis. EULAR guidelines suggest cyclophosphamide for adult patients with SSc-related ILD [26] based upon two randomized trials [23,30]. There are no published studies on cyclophosphamide in children with JSSc. Despite its known toxicity, cyclophosphamide is used in European pediatric scleroderma centers, and clinical practice experience suggests that cyclophosphamide (oral regimen of 1 to 2 mg/kg/ day for one year or 500 to 750 mg/m² once a month, maximum 1 g, intravenous pulse) is effective for JSSc pulmonary and cardiac involvement. An alternative is mycophenolate mofetil (MMF; 500 to 750 mg/m²/day). In an adult study, the use of both regimens resulted in significant improvements in prespecified measures of lung function, dyspnea, lung imaging, and skin disease [23]. As expected, MMF was better tolerated and associated with less toxicity than cyclophosphamide. (See "Treatment and prognosis of interstitial lung disease in systemic sclerosis (scleroderma)" and "Overview of pulmonary complications of systemic sclerosis (scleroderma)" and "Approach to the infant and child with diffuse lung disease (interstitial lung disease)" and "Juvenile systemic sclerosis (scleroderma): Classification, clinical manifestations, and diagnosis", section on 'Organ involvement'.)

Cardiac complications — Cardiac complications of JSSc are either primary (myocardial damage, fibrosis of the conduction system, and pericardial effusion) or secondary to pulmonary arterial hypertension [31]. Although rare, cardiac involvement is a significant cause of morbidity among children with JSSc, and cardiorespiratory complications are the leading cause of death. Thus, cardiac involvement requires prompt and aggressive immunosuppressive therapy. Some patients may also need a pacemaker for arrhythmia. The treatment of the cardiac complications is the same as for ILD. (See 'Interstitial lung disease' above and "Juvenile systemic sclerosis (scleroderma): Classification, clinical manifestations, and diagnosis", section on 'Organ involvement'.)

Skin involvement — Despite the lack of published data in children, there is a general consensus on the use of low-dose systemic glucocorticoids (eg, prednisone [0.3 to 0.5 mg/kg/day] for two to three months) in the active inflammatory phase of the disease, usually in combination with methotrexate (15 mg/m² as a single oral or subcutaneous dose per week) or an alternative disease-modifying antirheumatic drug (DMARD). The combination of systemic glucocorticoids and methotrexate is widely used in JSSc, especially in skin, subcutaneous, and articular involvement, and appears to have a good safety profile. After the first three months of treatment, prednisone is tapered down until stopping while methotrexate or the alternative DMARD is continued. In adults with SSc, results in randomized trials were inconclusive for methotrexate [32,33]. Nevertheless, the EULAR recommendations for treatment of SSc still support the use of methotrexate for skin disease [26]. (See "Juvenile systemic sclerosis (scleroderma): Classification, clinical manifestations, and diagnosis", section on 'Skin changes' and "Overview of the treatment and prognosis of systemic sclerosis (scleroderma) in adults", section on 'Skin'.)

The addition of mycophenolate mofetil (MMF) is an option in patients who do not tolerate the prednisone taper and are not controlled on methotrexate alone (methotrexate-refractory disease). Studies in adults have reported positive effects, mainly on cutaneous and pulmonary involvement, with good drug tolerance [19,30,34]. Cyclophosphamide is not indicated for isolated skin involvement. (See "Overview of the treatment and prognosis of systemic sclerosis (scleroderma) in adults", section on 'Skin' and "Immunomodulatory and antifibrotic approaches to the treatment of systemic sclerosis (scleroderma)".)

Renal disease — The prognosis for renal crisis was uniformly dismal until the introduction of angiotensin-converting enzyme (ACE) inhibitors (eg, captopril or enalapril) brought about a remarkable improvement in the outlook for prevention of vascular damage, effective long-term control of blood pressure, and stabilization of renal function. Conversely, published evidence does not support the preventive use of ACE inhibitors to decrease the risk of development of renal crisis [26]. Management of renal disease in SSc, including renal crisis, is discussed in detail separately. (See "Overview of the treatment and prognosis of systemic sclerosis (scleroderma) in adults", section on 'Renal' and "Kidney disease in systemic sclerosis (scleroderma), including scleroderma renal crisis" and "Juvenile systemic sclerosis (scleroderma): Classification, clinical manifestations, and diagnosis", section on 'Organ involvement'.)

Hemodialysis with or without bilateral nephrectomy and transplantation was an option in cases of irreversible renal failure or uncontrollable hypertension. However, the advent of ACE inhibitors makes this of primarily historic interest.

Musculoskeletal involvement — The treatment of musculoskeletal involvement (myositis, arthritis, and tenosynovitis) includes the use systemic glucocorticoids (eg, prednisone/prednisolone 0.3 to 0.5 mg/kg/day for two to three months followed by tapering down until stopping or to the minimal dose that is able to control inflammation) in combination with methotrexate. The use of potential nephrotoxins such as nonsteroidal antiinflammatory drugs (NSAIDs) should be avoided. Management of neuromuscular complications of SSc is discussed in detail separately. (See "Overview of the treatment and prognosis of systemic sclerosis (scleroderma) in adults", section on 'Musculoskeletal' and "Neuromuscular manifestations of systemic sclerosis (scleroderma)" and "Juvenile systemic sclerosis (scleroderma): Classification, clinical manifestations, and diagnosis", section on 'Musculoskeletal features' and "Proton pump inhibitors: Overview of use and adverse effects in the treatment of acid related disorders".)

Gastrointestinal disease — Few studies in children with JSSc address the most effective management for gastrointestinal disease, which includes GERD, erosive esophagitis, and malabsorption due to bacterial overgrowth. Proton pump inhibitors (PPIs) are still the drugs of choice, even in the early phase of disease, for prevention of SSc-related GERD and esophageal ulcers. JSSc patients on PPIs are at increased risk of hypochlorhydria, gastric bacterial colonization, and enteric infection, in particular, Clostridium difficile, as well as hypomagnesemia and vitamin B12 malabsorption and acute interstitial nephritis; therefore, their use should be closely monitored [35,36]. The management of GERD in children is reviewed in greater detail separately. (See "Management of gastroesophageal reflux disease in children and adolescents" and "Juvenile systemic sclerosis (scleroderma): Classification, clinical manifestations, and diagnosis", section on 'Organ involvement'.)

Several studies in adults suggest that prokinetic drugs such as domperidone may improve gastrointestinal signs and symptoms (dysphagia, early satiety, bloating, pseudo-obstruction) in SSc patients [37]. There are no published data on efficacy in children, but these drugs are sometimes used when other measures have failed.

Malabsorption is difficult to manage. Diarrhea and bloating are most often caused by bacterial overgrowth and are treated by rotating antibiotics because continuous therapy with one agent may result in the emergence of resistant organisms. Treatment is based upon adult SSc data. The choice of antibiotic is usually empirical and includes amoxicillin-clavulanate or oral cephalosporins. In refractory cases, metronidazole can be added for five to seven days to treat anaerobic flora [38]. Hyperalimentation may be necessary but is not an effective long-term choice [37]. (See "Treatment of gastrointestinal disease in systemic sclerosis (scleroderma)".)

EXPERIMENTAL THERAPY — Several drugs are under evaluation to treat different aspects of SSc in adults, including imatinib, rituximab, tocilizumab, and abatacept for skin and lung fibrosis and tocilizumab, riociguat, and selexipag for pulmonary arterial hypertension and other possible antifibrotic effects [39,40]. Nintedanib was approved by the US Food and Drug Administration (FDA) for the treatment of SSc-associated interstitial lung disease (ILD) in adults [41]. Unfortunately, no experience with these biologic agents have been reported in JSSc, except for rituximab. Investigational agents for SSc are discussed in greater detail separately. (See "Immunomodulatory and antifibrotic approaches to the treatment of systemic sclerosis (scleroderma)", section on 'Investigational approaches'.)

Two small case series have reported on the efficacy of rituximab in patients with JSSc [42,43]. In the first series of six patients with JSSc, treatment with rituximab in combination with cyclophosphamide resulted in subjective improvement in skin tightness and sense of well-being, but no changes in diffusing capacity of the lungs for carbon monoxide (DLCO) were observed [42]. In the second series of four patients treated with rituximab in addition to low-dose oral prednisone and mycophenolate mofetil (MMF) for one year, all patients showed a significant decrease in the number and duration of Raynaud phenomenon (RP) attacks and degree of cutaneous involvement [43]. Two patients showed a global cardiac improvement and decreased Juvenile Systemic Sclerosis Severity Score (J4S). The other two patients had improved respiratory function, and one of these two also had improved muscle strength and resolution of an arrhythmia.

One of the most aggressive approaches to therapy is immunoablation followed by reconstitution with autologous hemopoietic cell transplantation (HCT). The rationale for this therapy is the ablation of self-reactive lymphocytic clones that are potentially responsible for the disease process. Studies regarding autologous HCT have demonstrated efficacy in preventing disease progression in adult patients with SSc. However, the high incidence of treatment-related side effects, including a relatively high mortality rate, has limited its use in pediatric patients. The three main complications associated with HCT for SSc include treatment-related mortality (TRM), malignancies, and infections. The particular challenge is that the presence of cardiopulmonary or renal involvement at treatment start may make chemotherapy and fluid load associated with mobilization and conditioning hazardous, increasing the risk for early TRM.

Based upon emerging trial data, HCT may be most beneficial in selected patients with early, severe diffuse SSc. These patients may have moderate internal organ involvement and progressive disease despite an initial trial of immunosuppression. The lack of comorbidities, the more defined screening guidelines for JSSc patient selection, and the earlier referral of patients to specialized pediatric centers with expertise in both JSSc and transplantation are reasons for reconsidering HCT as a potential therapeutic strategy for children, particularly those who are early in the disease course (three years or less from the first non-Raynaud sign or symptom) before irreversible damage (eg, fibrosis) has resulted [44]. HCT for SSc is discussed in detail separately. (See "Immunomodulatory and antifibrotic approaches to the treatment of systemic sclerosis (scleroderma)", section on 'Autologous stem cell transplantation'.)

PROGNOSIS — In general, the prognosis of SSc in children appears better than in adults. Survival rates for childhood-onset SSc at 5, 10, 15, and 20 years after diagnosis are 89, 80 to 87, 74 to 87, and 69 to 82 percent, respectively [45-47]. (See "Overview of the treatment and prognosis of systemic sclerosis (scleroderma) in adults", section on 'Mortality'.)

Children with SSc have two possible courses. The vast majority manifest a slow disease course with lower mortality. In these patients, JSSc is usually most active during the first three to five years following onset of disease. Typical findings include fatigue, weight loss, rapidly advancing skin induration, arthritis, myositis, and tendonitis. Visceral involvement also commonly occurs during this period. After the first five years of disease, constitutional symptoms often abate, skin abnormalities may stabilize or occasionally improve, but visceral involvement may progress.

However, approximately 5 percent of children with JSSc have rapid development of internal organ involvement leading to severe disability and eventually to death. These patients typically present with rapidly progressive disease, for which there are now promising treatments [47,48].

The most common causes of death in children are related to the involvement of the cardiac, renal, and pulmonary systems. Cardiomyopathy is a leading cause of early death, especially in children [47,49]. This complication is rare and usually associated with diffuse cutaneous disease and features of polymyositis. Aggressive immunosuppressive treatment is effective on muscle, skin, and lung involvement but may not prevent progression of myocardial dysfunction [49].

SUMMARY AND RECOMMENDATIONS

●Treatment is based upon disease severity, activity, and progression. However, laboratory assessment of these is difficult. Thus, regular follow-up and clinical review are used. Sequential skin scores should be recorded, and objective assessment is necessary for organ-based complications, such as pulmonary fibrosis, pulmonary hypertension, or renal involvement. A multidimensional severity score, the Juvenile Systemic Sclerosis Severity Score (J4S), provides a more global index of severity (table 2). (See 'Organ system monitoring' above and 'Scoring tools' above.)

●The modified Rodnan skin score (mRSS) is a widely accepted tool for evaluating the extent of skin fibrosis (figure 1 and figure 2). Capillary abnormalities can be detected by nailfold capillaroscopy. Gastrointestinal involvement is often asymptomatic. Thus, imaging such as esophageal technetium scintigraphy is necessary for diagnosis. The assessment of cardiac involvement is traditionally based on periodic monitoring with electrocardiography (ECG) and conventional echocardiography. The diagnosis of interstitial lung disease (ILD) in juvenile systemic sclerosis (JSSc) is based on pulmonary function tests and imaging. (See 'Organ system monitoring' above.)

●Treatment is divided into nonpharmacologic measures and pharmacologic therapy, which includes general immunomodulation and organ-targeted therapy. (See 'Management overview' above.)

●Nonpharmacologic measures include skin care, an exercise program, and the use of corrective splints. (See 'General measures' above.)

●The pharmacologic management of patients with JSSc is challenging because the etiology and pathogenesis are poorly understood and the disease is heterogenous with variable progression. The treatment of JSSc is mainly symptomatic and is tailored to the individual needs of the patient based upon their specific clinical manifestations of the disease and organ involvement. No drug has been shown to be of unequivocal benefit in either children or adults with SSc, and there are no randomized trials of these therapies in children with JSSc. (See 'Immunomodulation' above and 'Organ-targeted therapy' above and 'Experimental therapy' above.)

●Patients with JSSc have a significant risk of severe morbidity and can have a poor prognosis. JSSc is usually most active during the first three to five years following onset of disease. After the first five years of disease, constitutional symptoms often abate and skin abnormalities stabilize or occasionally improve, but visceral involvement may progress. The overall outcome in JSSc is better than in those with adult-onset SSc, with higher survival rates seen in children. The most common causes of death in children are related to the involvement of cardiac, renal, and pulmonary systems. (See 'Prognosis' above.)