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Juvenile systemic sclerosis (JSSc) is a chronic multisystem connective
tissue disease characterized by the symmetrical thickening and hardening
of the skin, associated with fibrous changes in such internal organs
as the esophagus, intestinal tract, heart, lungs and kidneys, plus
arthritis and myositis. A Committee on Classification Criteria for JSSc,
including pediatricians, rheumatologists, and dermatologists, recently
proposed new classification criteria (Table 206-1).1
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Systemic sclerosis is a rare condition in any age group, with
an estimated annual incidence ranging from 0.45 to 1.9 in 100,000,
and a prevalence of approximately 15 to 24 in 100,000.2
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Onset in childhood is particularly uncommon: children under age
16 account for less than 5% of all cases,3 and
fewer than 10% develop systemic sclerosis before age 20.4,5 Juvenile
systemic sclerosis develops at a mean age of 8.1 years, with a peak
incidence between ages 10 and 16.3 The disease
is almost 4-fold more prevalent in females, but there is no recognized
racial predilection.6
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Clinical Manifestations
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Children developing scleroderma typically present with Raynaud
phenomenon and skin changes (eFig. 206.1).
Raynaud phenomenon is the first sign of the disease in 70% of
patients and in 10% it is complicated by digital infarcts (eFig. 206.2). It is more common in the fingers
but can be observed in other acral regions including the toes, ears,
lips, tongue, and tip of the nose.
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Proximal skin induration usually develops somewhat later and
is the second most common complaint, present in 41% of
patients at disease onset.6 Cutaneous changes characteristically evolve
in a sequence beginning with edema, followed by induration, and
eventually resulting in marked skin tightening and joint contractures.
The skin becomes waxy in texture, tight, hard, and bound to subcutaneous
structures. This is particularly noticeable in skin of the digits
and face where the characteristic expressionless appearance of the
skin may be the first clue to the diagnosis (Fig.
206-1).
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Other presenting complaints include arthralgia, arthritis, and,
although less frequently, muscle weakness, dyspnea, and calcinosis. Unlike
adult disease, telangiectasis is rarely present in children with
JSSc. Examination of the periungual nail folds with an ophthalmoscope
may demonstrate capillary dropout, tortuous dilated loops, and occasionally
distorted capillary architecture. As with other manifestations of
the disease, nail bed capillary changes tend to evolve over time.
Nail fold capillaries changes are reported in 10% of patients
at the onset of the disease, and in 25% at diagnosis and
in 40% overall at some time during the course of the disease.6
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In children with juvenile systemic sclerosis, visceral organ
involvement may be widespread; when it occurs, it is associated
with significant morbidity. The gastrointestinal and cardiopulmonary
systems are most commonly involved, but effects on the kidneys,
peripheral nerves, and musculoskeletal system also can lead to significant
discomfort and disability. Cardiorespiratory complications are the
leading cause of death in children with juvenile systemic sclerosis.3,7,8
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Gastrointestinal involvement occurs in 30% to 70% of
children with juvenile systemic sclerosis. Most affected patients
have esophageal dysfunction, resulting in gastroesophageal reflux
and dysphagia. Manometry, esophageal scintigraphy, and intraesophageal 24-hour
pH monitoring provide more sensitive indicators of diminished lower
esophageal sphincter tone and gastroesophageal reflux.9 Large
bowel involvement is less frequent and presents as alternating complaints of
constipation and diarrhea, bloating or abdominal discomfort. Lactulose
breath test to evaluate bacterial overgrowth, endoscopy or colon
scintigraphy are useful tools to evaluate this portion of the intestinal
tract.
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Pulmonary involvement, although frequently asymptomatic, also
may present as a dry, hacking cough or as dyspnea on exertion. Other abnormalities
associated with juvenile systemic sclerosis may include pleuritis,
abnormal diffusion capacity for carbon monoxide (DLCO) (which may
be the earliest manifestation of interstitial fibrosis) or pulmonary
arterial hypertension.3,6 Unlike adult scleroderma,
juvenile systemic sclerosis is infrequently complicated by pulmonary
interstitial fibrosis. The classic radiographic features of interstitial
lung disease consist of symmetric, reticulonodular shadowing, most
pronounced at the lung bases. High-resolution computed tomography (HRCT)
may reveal pulmonary disease even in the presence of a normal chest
radiograph. In children, HRCT findings include ground glass opacification,
subpleural micronodules, linear opacities, and honeycombing.10 Pulmonary
hypertension occurs rarely in pediatric scleroderma. When it develops
it may be a result of either angiopathy of the pulmonary vascular bed
or secondary to pulmonary fibrosis. Thus, regular screening with
echocardiography is an important tool for detecting early pulmonary hypertension,
while regular pulmonary function tests including DLCO and spirometry
are sensitive means of detecting early involvement of the respiratory
tract.
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Cardiac involvement is present in around one fifth of pediatric
scleroderma patients and represents a primary cause of morbidity among
children with juvenile systemic sclerosis.3,10,11 Pericardial
effusions are not common and when present are usually of no hemodynamic
significance. Pulmonary hypertension caused by pulmonary vascular
disease can lead to myocardial damage and right-heart failure.
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There are limited data on the prevalence of renal involvement
in children with juvenile systemic sclerosis. In a case series of
children with systemic sclerosis, about 10% had some kind
of renal involvement including either increased urinary protein
excretion or an elevated serum creatinine level.6 Although
renal involvement in children appears to be less severe or frequent
than in adults, the abrupt onset of accelerated hypertension with
acute renal failure (scleroderma renal crisis) remains one of the
most severe and dangerous complications of juvenile systemic sclerosis.
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About one fourth of juvenile systemic sclerosis patients have
anemia of chronic disease, or less commonly, macrocytic anemia due
to malabsorption of vitamin B12 or folate. Leukocytosis is not prominent
but correlates with the degree of visceral or muscle disease. Patients
with myositis have elevated levels of a variety of muscle enzymes,
including aldolase, lactose dehydrogenase (LDH), and creatine kinase.3,6
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High titers of antinuclear antibodies (ANA) are found in up to
80% of children with juvenile systemic sclerosis. The prevalence
of both antitoposomerase I (Scl-70) and anticentromere antibodies
(ACA), quite specific for this condition, is lower in children as
compared to adults. Thus, 34% of children with juvenile
systemic sclerosis test positive for anti-Scl-70, and 7% for
ACA, compared to up to 70% and 55% of adult patients,
respectively.6
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No controlled trials, and very few reports of any sort, are available
to help guide the treatment of juvenile systemic sclerosis.
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Nonpharmacologic measures for alleviating symptoms in juvenile
systemic sclerosis begin with avoiding cold and trauma, which can
exacerbate vasospasm and tissue damage. In addition, physiotherapy
can help maintain functional ability, muscle strength, and joint movement
while preventing flexion contractures. Corrective splints, especially
while patients sleep, are also useful for treating or preventing
joint and muscle contractures.
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Pharmacologic management of patients with juvenile systemic sclerosis
is particularly challenging: No medication has been shown to be
of unequivocal benefit in either children or adults with systemic
sclerosis. Calcium channel blockers, usually oral nifedipine or
nicardipine, are used as first-line therapy for Raynaud phenomenon.
Iloprost or other available parenteral prostanoids are used to treat
more severe systemic sclerosis–related peripheral vascospasm
and digital ulcers.8,12 In all cases, these medications must
be used with caution in systemic sclerosis because pulmonary or
cardiac vessels are not dilated as effectively as peripheral vessels
by these agents, and therefore a “steal syndrome” with decreased
central blood flow may result. Steroids may be used with care for
treating myositis or arthritis, but these may precipitate scleroderma
renal crisis.13,14 Pulmonary involvement accompanied
by inflammation may be treated with cyclophosphamide, although when
interstitial lung disease is purely fibrotic, no therapies are known
to be effective.15,16
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Low-dose methotrexate has been shown to benefit sclerodermatous
skin changes in adults, and therefore are the treatment of choice
for skin manifestations in children, especially during the early
phase of the disease.17
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Angiotensin-converting enzyme (ACE) inhibitors (eg, captopril,
losartan) are effective for the long term control of blood
pressure and are life saving in cases of scleroderma renal crisis.18 It
is notclear whether or not they have a role in
preventing this condition.
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Proton pump inhibitors (PPI) such as omeprazole and lansoprazole
are indicated for the prevention of gastroesophageal reflux disease (GERD)
and esophageal ulcers. Prokinetic drugs such as domperidone may
be beneficial in the management of symptomatic motility disturbances.
Rotating antibiotics, such as metronidazole and doxycycline, are
indicated to treat malabsorption owing to bacterial overgrowth.
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New drugs for the treatment of pulmonary arterial hypertension,
such as bosentan, sitaxentan, and sildenafil, recently have been
introduced in adult patients with systemic sclerosis. There is limited
experience at present to estimate their risks and benefits in children,
but so far the few case reports of their use in juvenile systemic
sclerosis suggest that these agents likely have a role in children.
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Generally, the prognosis of juvenile systemic sclerosis is poor.
Skin tightness and joint contractures inevitably lead to severe
disability,19 despite the fact that the skin may
eventually soften years after onset of the disease. The most common
causes of death in children are related to involvement of the cardiac,
renal, and pulmonary systems. Cardiomyopathy, although rare, can
be one of the causes of early death, especially in children.20 Interstitial
lung disease and renal failure or acute hypertensive encephalopathy
supervene as a potentially fatal outcome in few children and seem
more likely to occur early in the disease course.7,11
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Survivorship has not been determined in any large series of children
because of the rarity of this disease and the availability of very
few retrospective data. The overall mortality rate at 5 years is
around 6% to 15% and is better than that for adults.
The causes of death in juvenile systemic sclerosis include cardiac
failure (67%), end-stage renal failure (13%),
respiratory failure (10%), infections (7%), and
hypertensive encephalopathy (3%).7,11