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Juvenile Systemic Sclerosis

  • Author: Donald A Person, MD, FAAP, FACR; Chief Editor: Harumi Jyonouchi, MD  more...
 
Updated: Sep 12, 2014
 

Background

Juvenile systemic sclerosis (JSSc) is a rare connective tissue disease of unknown etiology. Characteristic features include fibrosis of the skin, subcutaneous tissues, and internal organs as well as abnormalities of the vascular and immune systems occurring in children 16 and younger. This disease is one of the most severe rheumatologic conditions diagnosed in children.

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Pathophysiology

One of the earliest processes thought to occur in JSSc is vascular injury. This results in upregulation of endothelial cell adhesion molecules, which facilitates local platelet aggregation and infiltration of inflammatory cells. This endothelial injury is manifested clinically as Raynaud phenomenon, pulmonary hypertension, and renovascular hypertension.

These inflammatory cells release cytokines, including transforming growth factor beta (TGF-β) and interleukin-1 (IL-1). Among its many effects, IL-1 is known to stimulate the release of platelet-derived growth factor, which stimulates fibroblasts to increase production and deposition of extracellular matrix components such as collagen, fibronectin, and glycosaminoglycans. This fibrosis may affect any organ of the body, most commonly the skin, GI tract, lungs, heart, kidneys, and musculoskeletal system.

Little is known about the role of the various autoantibodies, such as ANA, seen in almost all cases of juvenile systemic sclerosis, but their presence is suggestive of an autoimmune process underlying the aforementioned vascular injury and fibrosis. Resistance of lymphocytes to apoptosis seen in these patients is a potential mechanism for the persistence of autoreactive T cells in juvenile systemic sclerosis.

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Epidemiology

Frequency

United States

JSSc is a rare childhood disorder, an orphan disease whose incidence is said to be approximately 0.05 per 100,000 children.[1] In addition, 5-10% of adult cases of systemic sclerosis arise before age 16 years, thus meeting the age criterion for JSSc. New criteria aimed at more uniformly defining JSSc will hopefully aid in better estimation of incidence and prevalence of the condition.

Mortality/Morbidity

Mortality rates in JSSc are reportedly lower than in adult systemic sclerosis. Five and 20-year survival rates for JSSc are 89% and 69%, respectively.

The greatest morbidity and mortality is seen in those children who develop pulmonary, cardiac, and renal manifestations of the disease. A recently published report reveals that the most significant predictors of mortality at the time of diagnosis are pericarditis, elevated creatinine levels, and fibrosis on chest radiography.[2] The most common cause of early death in patients with juvenile systemic sclerosis is heart failure due to dilated cardiomyopathy, likely related to pulmonary hypertension and myocardial fibrosis.

In a review of 153 patients, those who died had a significantly shorter time to diagnosis from onset of symptoms compared with patients that were still alive at follow-up 8.8 vs 23 months.[3] This demonstrates that those patients who eventually die due to complications of JSSc likely have a more aggressive form that is more quickly recognized due to the severity of symptoms. This is consistent with mortality rates of most studies that show most deaths from JSSc occur within the first 5 years after diagnosis.

Morbidity from the disease is seen in most patients in the form of fibrosis of the skin, which may lead to contractures and loss of mobility, and Raynaud phenomenon with associated pain and paresthesias, as well as digital ulcers. Arthralgias, arthritis, and muscle weakness may occur in as many as a quarter of patients, and a small number may experience dyspnea, weight loss and dysphagia as well.

Race

In the United States, adult systemic sclerosis is more common in blacks than in whites, with a ratio of 2:1. No specific demographic data are available for JSSc.

Sex

Females are affected more often than males, with an overall female-to-male ratio of approximately 3.6:1, much lower than the 15:1 female-to-male predominance seen in adults.

Age

A child must be younger than 17 years at the time of disease onset to the meet the criteria for JSSc. The youngest patient documented with JSSc was only a few months old at disease onset. The average age of onset is 8.1-8.8 years in the two largest published case series. Due to the rarity of this condition and the subtle nature by which it can first appear, the average time from symptom onset to diagnosis is 1.9 years, taking as long as 12 years in some cases. Of note, children who died in these studies were diagnosed almost 2 years later than the average child with juvenile systemic sclerosis.

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Contributor Information and Disclosures
Author

Donald A Person, MD, FAAP, FACR Medical Director (Emeritus), Pacific Island Healthcare Project; Expert Consultant in Pediatrics, Pediatric Rheumatology, Telemedicine, and Scientific Review, Tripler Army Medical Center; Professor of Pediatrics, F Edward Herbert School of Medicine, Uniformed Services University of the Health Sciences; Clinical Professor of Pediatrics and Public Health (Retired), University of Hawaii, John A Burns School of Medicine

Donald A Person, MD, FAAP, FACR is a member of the following medical societies: Society for Experimental Biology and Medicine, American Academy of Pediatrics, American College of Rheumatology, American Medical Association, American Pediatric Society, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Association of Military Surgeons of the US, Clinical Immunology Society, Federation of American Societies for Experimental Biology, Pediatric Infectious Diseases Society, Society for Pediatric Research

Disclosure: Nothing to disclose.

Coauthor(s)

Cecilia P Mikita, MD, MPH Associate Program Director, Allergy-Immunology Fellowship, Associate Professor of Pediatrics and Medicine, Uniformed Services University of the Health Sciences; Staff Allergist/Immunologist, Walter Reed National Military Medical Center

Cecilia P Mikita, MD, MPH is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Allergy, Asthma and Immunology

Disclosure: Nothing to disclose.

Luke M Webb, MD Staff Physician, Department of Allergy and Immunology, Evans Army Community Hospital

Luke M Webb, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Allergy, Asthma and Immunology

Disclosure: Nothing to disclose.

David J Schwartz, MD Staff Physician, Department of Allergy and Immunology, Eisenhower Army Medical Center

David J Schwartz, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Allergy, Asthma and Immunology

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

David J Valacer, MD 

David J Valacer, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association for the Advancement of Science, American Thoracic Society, New York Academy of Sciences

Disclosure: Nothing to disclose.

Chief Editor

Harumi Jyonouchi, MD Faculty, Division of Allergy/Immunology and Infectious Diseases, Department of Pediatrics, Saint Peter's University Hospital

Harumi Jyonouchi, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association of Immunologists, American Medical Association, Clinical Immunology Society, New York Academy of Sciences, Society for Experimental Biology and Medicine, Society for Pediatric Research, Society for Mucosal Immunology

Disclosure: Nothing to disclose.

References
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An 8-year-old girl with overlap syndrome with evolution to progressive systemic sclerosis (PSS).
Photo of hands revealing sclerodactyly. This demonstrates the progression of disease over 7 years.
Chest radiograph revealing diffuse, coarse interstitial marking with bilateral lower lobe bronchiectasis.
Axial CT scan of the chest of a 15-year-old female adolescent with progressive systemic sclerosis (PSS).
Esophagram revealing dysmotility.
 
 
 
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