Etiology and pathogenesis
The exact cause of the disease has not been established. It is known that a genetic predisposition exists (familial cases, association with HLA antigens), while viral infections and environmental factors act as triggers. The peak manifestation occurs in preschool and early school age, with girls being affected 3.6 times more often than boys.
Pathogenesis is based on three sequential stages:
- Endothelial injury. The triggering mechanism arising from ischemia, infections, or the production of anti-endothelial antibodies.
- Endothelial dysfunction. Vascular remodeling occurs: the synthesis of the vasoconstrictor endothelin-1 increases sharply, while vasodilators (nitric oxide and prostacyclin) decrease. This leads to tissue ischemia. The intima and media of blood vessels become thickened.
- Cellular infiltration and fibrosis. Immune cells secrete profibrotic cytokines (specifically TGF-β and IL-1). The latter stimulates the release of platelet-derived growth factor (PDGF). Activated fibroblasts begin to excessively synthesize collagen and other components of the extracellular matrix.
Clinical presentation: skin and vessels
Skin syndrome is a specific marker of the disease. It sequentially passes through the stage of erythematous firm edema, then progresses to the induration stage (the skin becomes dense and cannot be gathered into a fold), and ends with atrophy accompanied by pigmentary changes, hair loss, and severe dryness (xerosis).
A “scleroderma mask” forms on the face: it becomes expressionless, the nose becomes sharp (“bird” beak appearance), lips thin out, and radial folds appear around the mouth (“purse-string” mouth sign). In later stages, stellate telangiectasias appear on the face and trunk.
One of the earliest signs is Raynaud's phenomenon — paroxysmal spasm of the arteries in the distal extremities. It has three phases: ischemia (pallor and numbness), cyanosis (bluish discoloration), and reactive hyperemia (redness with a sensation of warmth and pain).
Visceral lesions and musculoskeletal system
Internal organs are involved in the process with varying frequency and severity:
- Gastrointestinal tract: The most frequent visceral target. Esophageal hypomotility, dysphagia, and gastroesophageal reflux develop.
- Lungs: Diffuse or interstitial fibrosis forms. Pulmonary hypertension develops in 7% of children, accompanied by progressive respiratory failure.
- Heart: The myocardium is primarily affected (fibrosis), leading to decreased contractility and arrhythmias.
- Kidneys: Vascular bed involvement can lead to a life-threatening scleroderma renal crisis — malignant arterial hypertension with acute renal failure due to ischemic necrosis.
- Musculoskeletal system: Flexion contractures ("claw-hand" appearance), osteolysis of the nail phalanges, and arthralgias develop. In the active phase, a polymyositis-like picture with elevated creatine phosphokinase (CPK) levels is possible.
Diagnostic criteria for jSSc
Diagnosis is based on the PRES/ACR/EULAR (2004) criteria. Verification requires the presence of one major and two or more minor criteria.
- Major criterion: Scleroderma or skin induration proximal to the metacarpophalangeal/metatarsophalangeal joints.
- Minor criteria:
- Sclerodactyly (induration of the skin of the fingers).
- Raynaud's phenomenon, digital ulcers, or nailfold capillary abnormalities.
- Dysphagia or reflux.
- Renal crisis or arterial hypertension.
- Arrhythmias or heart failure.
- Pulmonary fibrosis, pulmonary hypertension.
- Contractures, arthritis, myositis.
- Tunnel neuropathies.
- Specific autoantibodies (ANA, anti-Scl-70, antifibrillarin, PM-Scl, or RNA polymerase antibodies).
Principles of treatment
Therapy aims to suppress fibrosis and prevent vascular catastrophes.
The mainstay of baseline therapy is glucocorticoids (0.5–1.0 mg/kg/day initially, followed by tapering) combined with cytostatics (methotrexate). For severe pulmonary involvement and rapidly progressive forms, cyclophosphamide or mycophenolate mofetil becomes the drug of choice.
Symptomatic therapy includes calcium channel blockers (nifedipine) and antiplatelet agents (dipyridamole) to improve microcirculation. ACE inhibitors (captopril) are prescribed for kidney involvement, and proton pump inhibitors are used for GI protection. Topical applications with dimethyl sulfoxide, topical steroids, and calcineurin inhibitors are used locally.
The disease variant can be remembered by the CREST syndrome acronym: C — calcinosis, R — Raynaud's phenomenon, E — esophageal dysmotility, S — sclerodactyly, T — telangiectasias.
Class and exam questions
How frequently do anticentromere antibodies (ACA) occur in the juvenile form?
Unlike adult patients, centromere antibodies (ACA) are rarely detected in children—in only 7–8% of cases.
What are the features of the diffuse form of the disease?
It is characterized by rapid progression of skin lesions with visceral involvement. The process spreads centrifugally: from distal to proximal parts and onto the trunk.
What is the prognosis in juvenile systemic sclerosis?
In childhood, the prognosis is more favorable than in adults. Five-year survival reaches 89%, although the outcome heavily depends on timely therapy and the presence of pulmonary hypertension.
What else to study on this topic
- Pathogenesis of scleroderma renal crisis
- Differential diagnosis with limited scleroderma and scleredema of Buschke
- Features of diffuse and limited forms of the disease
- Interpretation of capillaroscopy results
- Differences between juvenile scleroderma and juvenile dermatomyositis
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