Systemic Sclerosis

Pediatric patients make up only 3% of all cases of systemic sclerosis (95). Disease expression is influenced by genetic, ethnic, and environmental factors (97,104). In adults, females out number males, with a ratio of 3-14:1, although sex distribution ratio varies with age (97,104). The disease is more common in African-Americans, with a younger mean age-of-onset and increased risk of diffuse disease (105).

Systemic sclerosis includes diffuse disease (formally known as progressive systemic sclerosis), limited disease (formally known as CREST syndrome) and overlap syndromes with scleroderma (97).

Diffuse disease can evolve rapidly over the first few months and is associated with the presence of anti-Scl 70 antibodies. It tends to involve the proximal extremities and trunk, with rapidly progressive skin involvement and vital organ disease. Risk of malignant phase hypertension, as well as severe cardiac or gastrointestinal involvement, is higher with diffuse disease (97).

Limited systemic sclerosis is associated with the presence of anti-centromere antibody and is confined to the face and extremities, distal to the elbows and knees (97). It tends to progress more slowly and may be stable for several years before the development of pulmonary hypertension. The presence of renal, cardiac or pulmonary disease within the first 5 years is associated with poor outcome.

Investigations

Inflammatory markers such as ESR do not tend to be raised in scleroderma. Anemia may be found due to esophageal blood loss, malabsorption, poor nutrition, and chronic disease. ANA is positive in 80% of adult patients with systemic sclerosis (95). Anti-Scl 70 antibody correlates with diffuse disease and a poor outcome. Anti-centromere antibodies correlate with limited disease and a better outcome (95). Studies in childhood scleroderma report a positive ANA in 22% to 100% of patients, and a positive anti-Scl in 40% of those that are ANA positive. Anti-centromere antibodies are uncommon, reflecting the rarity of limited disease in children (95). The significance of anti-cardiolipin antibodies, found in one-third of patients, is uncertain. Investigations should be done to look for specific organ involvement (Table 5).

Treatment

The management of systemic sclerosis depends on careful monitoring of organ specific manifestations and prompt treatment to avoid irreversible fibrotic tissue damage. In addition to organ-based treatments (Table 5), generalized systemic therapies are directed at the underlying process implicated in the disease. Immune suppression has been tried with various treatments including antithymocyte globulin, mycophenolate mofetil, methotrexate, ciclosporin, and cyclophosphamide (95,106). The association of corticosteroids with hypertensive renal crisis should also be carefully considered. Plasma exchange have also been used (107). The endothelin receptor agonist bosentan, has been tried with some success for digital ulcers and pulmonary hypertension (108,109). Autologous stem cell transplantation has been tried but has an associated mortality (95).

Prognosis

Data for prognosis in children and adolescents with systemic sclerosis are sparse. There is an opinion that the disease progresses towards organ failure and death in the same way as in adults. However, a 95% 5-year survival rate has been reported from a study looking at 135 patients with systemic sclerosis, much better than that reported in adult literature (110). It is not clear whether all patients in this cohort had true systemic sclerosis or scleroderma, and it has been our experience that more aggressive disease may be associated with earlier age of onset.

The fertility rate in patients with scleroderma seems to be similar to that of healthy controls, but there is a higher rate of premature and low birth weight infants. Pregnancy may be dangerous for patients with severe renal, cardiac, or pulmonary disease, and patients may be best advised to avoid pregnancy until the disease stabilizes. Potentially teratogenic medications should be avoided.

Table 5

Clinical Manifestations of Systemic Sclerosis

Organ

Manifestation

Investigations

Treatments

Skin

Peripheral edema, dryness, and pruritis

Serial photographs may be

Lubricants, topical corticosteroids

Skin thickening and tightening

useful.

Treatment for Raynaud's: Keep

Eventual softening

Capillaroscopy,

warm; vasodilators or calcium

Pinched nose and loss of facial creases

thermography

channel blockers

Loss of skin appendages in extremities

Vitamin C and E, fish oils

Hyperpigmentation and hypopigmentation

Prostaglandin El or prostacylin for

Cutaneous telangiectasis and subcutaneous

peripheral vascular changes

calcinosis (particularly limited form)

Diltiazem for calcinosis

Flexor tendon nodules

Cosmetic issues

Pitting scars on fingertips and loss of finger pulp

Raynaud's phenomenon (90%)

Dilatation and dropout of the nailfold capillaries

Joints

Joint stiffness, loss of range-of-movement, and

USS or MRI to detect

NSAID; physio- and occupational

contractures secondary to skin tightening and

subclinical synovitis

therapy

fibrosis of the joint capsule

DEXA scan

Podiatry

Synovial inflammation less common

Intraarticular steroid injections for

Erosions rare

synovitis

Osteoporosis

Advice re: physical exercise

Gut

Xerostomia (salivary gland fibrosis or overlap

Dental reviews

Artificial tears and oral sprays

with Sjogren's)

pH studies

Prokinetic agents

Dental loosening and tongue atrophy

Proton pump inhibitors

Table 5 Clinical Manifestations of Systemic Sclerosis (Continued)

Organ

Manifestation

Investigations

Treatments

Pulmonary disease

Restricted mouth opening from progressive skin tightening

Abnormalities of the lower esophageal sphincter and fibrosis of the lower two-thirds of the esophagus, resulting in poor propulsion and "lower dysphagia" Stricture formation; Barrett's esophagus Esophageal carcinoma Severe gastroesophageal reflux Delayed gastric emptying +/- severe atony Pseudo-obstruction from reduced motility of small intestine with bloating and cramping Diarrhea and malabsorption from bacterial overgrowth Constipation from large bowel involvement Present in the vast majority of patients Pulmonary hypertension and interstitial fibrosis Onset usually insidious, with shortness of breath, dry cough, fatigue, and reduced energy Clubbing is rare

Asymptomatic pleural effusions common Aspiration from severe gastroesophageal reflux

Plain abdominal X-ray, USS, barium follow-through or video capsule studies

Loss of colonic haustra and pseudo-diverticular can be seen radiologically Fecal fats Endoscopy may be indicated

Pulmonary function tests with TLCO High-resolution CT scan and high-resolution X-rays BAL or DTPA scanning

Intermittent antibiotics Stool softeners and enemas Total parenteral nutrition Surgery or laser therapy for vascular bleeds

Corticosteroids, cyclophosphamide, azathioprine, calcium channel blockers, vasodilators, D-penicillamine Ambulatory prostacyclin or bosentan Warfarin

Advice re: smoking

Heart Progressive fibrosis with small vessel obliterative disease, ischemia and re-perfusion, restrictive cardiomyopathy and congestive cardiac failure Pulmonary hypertension and cor pulmonale secondary to lung disease Myocarditis (rare) associated with polymyositis Kidneys Mild proteinuria, progresses with a decrease in creatinine clearance Can be associated with hypertension Malignant hypertension, often accompanied by microangiopathic hemolytic anemia, occurs in up to 20% CNS Central nervous system involvement rare, but neuropathies can occur

Endocrine Glandular fibrosis can occur resulting in hypothyroidism

ECG and ECHO Thallium scanning Right heart catheterization for pulmonary hypertension

Urine dipstick and urine albumin creatinine ratio GFR

Imaging

Nerve conduction studies Biopsy

Thyroid function tests

Calcium channel blockers, antiarrhythmic agents, corticosteroids Transplantation Advice re: smoking

Maintain good perfusion ACE inhibitors Anti-hypertensives Avoid steroids Dialysis where needed

Corticosteroids

Physiotherapy and occupational therapy Thyroxine as needed

Abbreviations: ACE, angiotensin converting enzyme; BAL, bronchoalevolar; DEXA, dual-energy X-ray absorptiometry; ECG, electrocardiogram; ECHO, echocardiogram; GFR, glomerular filtration rate; NSAID, nonsteroidal anti-inflammatory drug; USS, ultrasound scan.

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