Juvenile Systemic Sclerosis Treatment & Management

General recommendations on the pharmacologic management of juvenile systemic sclerosis (JSSc) is difficult; no drug has been shown to have unequivocal benefit in the pediatric or adult form of the disease. The treatment of children with chronic disease is multifaceted and also requires attention to general health measures including; nutrition, rest, maximizing school attendance, and exercise. Treating a child with systemic sclerosis requires a team approach, ideally including a nurse educator, physical therapist, occupational therapist, nutritionist, and social worker. No treatment or combination of medical or surgical treatments has proven unequivocally efficacious in juvenile systemic sclerosis. However, therapeutic strategies have been developed that are directed toward the individual patient and the organ systems involved in that patient.

Given the lack of consensus that existed regarding the pharmaceutical management of juvenile systemic sclerosis, an European League Against Rheumatism (EULAR) task force, which included pediatric rheumatologists and representatives of patients who had juvenile systemic sclerosis, was developed. In 2007, this group attempted to establish some treatment recommendations for the treatment of juvenile systemic sclerosis. The group established a final set of 14 recommendations. Among experts in the field, a consensus of greater than 85% was reached on 9 of these 14 recommendations.^[4]

• Meta-analysis on dihydropyridine-type antagonist and prostanoids indicated that nifedipine and intravenous iloprost reduce both the severity and frequency of Raynaud phenomenon attacks in patients with juvenile systemic sclerosis. Dihydropyridine-type antagonist (eg, nifedipine) should be considered first-line therapy for juvenile systemic sclerosis–associated Raynaud phenomenon. Intravenous (IV) prostanoids (eg, iloprost) should be used to treat severe Raynaud phenomenon.
• Two randomized clinical trials have demonstrated that intravenous prostanoid (particularly iloprost) are effective in healing digital ulcers.
• Despite some conflicting data and its known toxicity, cyclophosphamide should be considered for the treatment of juvenile systemic sclerosis–related interstitial lung disease. As with the use of cyclophosphamide in other conditions (juvenile systemic lupus erythematosus [SLE]), in order to prevent hemorrhagic cystitis, adequate hydration and frequent voiding must be emphasized.
• Glucocorticoids (most commonly prednisone), have few indications in treating juvenile systemic sclerosis. The use of glucocorticoids in treating juvenile systemic sclerosis–associated myositis, arthritis, and tenosynovitis, may be indicated. However, several studies have demonstrated a higher incidence of renal crisis in patients with juvenile systemic sclerosis treated with glucocorticoids emphasizes; thus, careful monitoring of blood pressure and renal function is needed in these patients.
• ACE inhibitors and angiotensin receptor blockers (ARBs) are considered to be the most effective and safest treatment option for long term management of hypertension, renal insufficiency, and renal crisis in patients with juvenile systemic sclerosis.
• Methotrexate has been shown to improve a clinical monitoring scale known as the skin score in early diffuse systemic sclerosis in adults. Although studies in children are not currently available, expert opinion suggests that methotrexate would be the treatment of choice for skin manifestations of juvenile systemic sclerosis, particularly in the earlier phases of the disease.
• Recommendations for treatment of GI manifestations of juvenile systemic sclerosis include proton pump inhibitors (PPIs), including omeprazole for preventing or treating gastroesophageal reflux symptoms. Prokinetic agents for treating symptoms related to motility disturbances. Finally, rotating antibiotics to include doxycycline and ciprofloxacin to decreased bacterial overgrowth which can lead to malabsorption.
• Interstitial lung disease associated with juvenile systemic sclerosis is a major therapeutic challenge. Treatment recommendations made by the EULAR group also included recommendations for treatment of pulmonary artery hypertension associated with juvenile systemic sclerosis. Randomized clinical trials have demonstrated improved exercise tolerance in patients with pulmonary artery hypertension with the use of several medications, including bosentan, sitaxsentan (clinical trials stopped worldwide because of liver injury), and sildenafil. Despite the emerging evidence that these medications may benefit these patients, many experts in the field have called for further pediatric trials before making general recommendations regarding these medications in pulmonary artery hypertension secondary to juvenile systemic sclerosis.
• On December 10, 2010, Pfizer announced that sitaxsentan (also known as sitaxentan; brand name of Thelin) is being withdrawn in regions where it is approved (the European Union, Canada, Australia). Additionally, clinical trials for sitaxsentan are being discontinued worldwide. This decision was based on a review of safety information from clinical trials and postmarketing reports of life-threatening idiosyncratic risk for liver injury.
• Additional treatment considerations are as follows:

  • Vascular therapy may take on several forms and is not necessarily pharmacologic. Early on, Raynaud phenomenon may respond to avoidance of tobacco, cold exposure, and vasoconstricting medications.
  • Biofeedback has been helpful in some patients with the development of tissue ischemia of digital tip ulcers. Local management of digital ulcers is indicated.
  • The arthritis of systemic sclerosis may respond to nonsteroidal anti-inflammatory drugs (NSAIDs) but to a lesser extent than the arthritis associated with other connective tissue diseases.

Because involvement in patients with juvenile systemic sclerosis widely varies, surgical management must be individualized.

• Surgery to release contractures is occasionally indicated, and a few patients benefit from the surgical release of entrapped nerves.
• Emergency life-saving surgery in patients with juvenile systemic sclerosis who have a ruptured viscus may be required.
• Amputation should be considered only in extreme cases and if no other therapeutic options have proven effective.
• Sympathectomy as a treatment of the peripheral vascular disease has been abandoned.

The treatment of severe, chronic and debilitating pediatric diseases such as juvenile systemic sclerosis requires a team approach.

• The pediatric rheumatologist team leader must be a specialist experienced in the care of patients with juvenile systemic sclerosis.
• The team should also include a pediatric gastroenterologist, pediatric nephrologist, and pediatric pulmonologist.
• The team should also include a nurse educator, occupational therapist, physical therapist, nutritionist, and social worker.
• Telemedicine may play a role in long-distance consultation and treatment of patients with juvenile systemic sclerosis who reside far from full-service institutions.
• Recent experimental therapies that necessitate other consultations, such as stem cell, renal, and lung transplantation, are beyond the scope of this discussion.