AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

Systemic sclerosis (SSc) is a connective tissue disease of unknown etiology. Fibrotic changes of the skin, subcutaneous tissue, and viscera; abnormalities of the microvasculature; and immune dysfunction characterize this disorder. In one of the first references to SSc in the medical literature, Addison referred to the skin changes as "keloid" in nature.

Pathophysiology

SSc may affect any organ of the body, including the skin, GI tract, lungs, heart, kidneys, and musculoskeletal system. Altered connective tissue metabolism has been observed in SSc. Increased deposition of extracellular matrix components such as collagen, fibronectin, and glycosaminoglycans characterize this observation. Dermal fibroblasts caused by SSc synthesize collagen at an increased rate when compared with controls. Lymphokines such as interleukin (IL)–2, IL-4, and IL-6 were found in the sera of patients with scleroderma but not in healthy control subjects. Activated T cells, complement, or both likely stimulate the release of endothelial cytokines with subsequent endothelial damage, which facilitates adhesion and transvascular migration of CD4⁺CD8^- T cells and monocytes.

Integrins and cell adhesion molecules appear to contribute to the pathogenesis of SSc. The nearly universal presence of one or more antinuclear antibodies (ANAs) suggests that the humoral immune system is also likely involved.

Frequency

United States

In early national surveys (1960s), the incidence of SSc was reported to be 12 cases per 1 million population annually. More recent studies in the general population in South Carolina reported the prevalence of SSc as 19-75 per 100,000 population.

Mortality/Morbidity

Morbidity and mortality rates vary considerably, depending on the extent of the disease. In its most devastating form, usually referred to as progressive systemic sclerosis (PSS), the disease may inexorably progress to death, usually after several years or even decades of severe and debilitating morbidity. Progressive pulmonary fibrosis leading to respiratory failure has replaced malignant hypertension, renal failure, and acute GI bleeding as the cause of death in patients with SSc. As SSc is an adult disease, the overall mortality rate is much higher in adults than in children. In the case of morphea, which is a small localized patch of cutaneous fibrosis, no mortality occurs, and the involved area is little more than a nuisance.

• PSS is fatal in virtually 100% of both pediatric and adult patients after 10-20 years of progressive debilitating disease.
• Morphea, localized scleroderma, and linear scleroderma do not limit life expectancy. These conditions begin in early childhood (age 2-6 y) and account for at least 90% of all cases of pediatric scleroderma.

Race

Although reported worldwide, in the United States, adult SSc is more common in blacks than in whites, with a ratio of 2:1.

Sex

Females are affected more commonly than males, with an overall female-to-male ratio of approximately 2-3:1. The female-to-male ratio varies with the patient's age. During childbearing years, females predominate, with a female-to-male ratio of 15:1.

Age

SSc is rare in children. Fewer than 5% of all cases are diagnosed in children. When SSc does occur in children, onset is usually in mid childhood. The diagnosis is often missed for months to several years. Conversely, limited forms of scleroderma are common in children, and at least 90% of pediatric cases are of such limited extent. Scleroderma was recently recognized in infants.

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

History

Skin changes are the usual common presenting symptom in most pediatric cases of SSc. Such changes are often subtle and may take months to years to evolve. Swelling and puffiness of the hands and fingers; polyarthralgia or polyarthritis of the hands, fingers, feet, and toes; and Raynaud phenomenon often bring the patient to the physician's attention. Cold exposure or stress may induce vasoconstriction with the attendant episodic pallor or cyanosis, followed by vasodilation with suffusion and erythema.

Episodes may be severe and may lead to digital necrosis with subsequent development of digital pitting or frank gangrene. Malaise, fatigue, weakness, weight loss, low-grade fever, and other constitutional symptoms are common in the early phases of the disease. In rare cases, esophageal, small bowel, pulmonary, or muscle involvement may be the first abnormality recognized.

Physical

• CREST Syndrome, once thought to have prognostic and therapeutic implications, likely is nothing more than an incomplete form of SSc. The acronym CREST stands for calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasias.
• Peripheral vascular
  • In 1862, Maurice Raynaud described the constellation of episodic pallor, cyanosis, and erythema. The terms Raynaud phenomenon, Raynaud syndrome, and Raynaud disease are potentially confusing. Raynaud phenomenon describes pallor, cyanosis, suffusion, and tingling of the fingers, which occur abruptly and episodically. When the phenomenon is associated with a known cause (eg, scleroderma), it is Raynaud syndrome. When the phenomenon has been present for years without an apparent associated condition, the term Raynaud disease is appropriate.
  • Although Raynaud phenomenon is observed in approximately 50% of adults with SSc, it is distinctly unusual in children. Raynaud phenomenon rarely accompanies other pediatric systemic rheumatic diseases. In children with systemic lupus erythematosus (SLE), systemic vasculitis, and dermatomyositis, Raynaud phenomena is occasionally observed, usually after months to years of progressive disease. Furthermore, Raynaud phenomenon, without an underlying connective tissue disease and in an otherwise normally healthy child, is often benign and self-limited.
• Skin
• • Skin involvement is observed in virtually 100% of patients with scleroderma, as the skin is the most common target organ in scleroderma.
  • Initially, diffuse puffiness of the hands and feet develops. Puffiness is followed by the insidious development of tautness of the skin and underlying tissues, which evolves to hidebound skin adherent to underlying structures.
  • Hyperpigmentation or hypopigmentation is often seen and commonly misdiagnosed as vitiligo.
  • Telangiectasias may be a prominent component of the cutaneous lesions. Involvement of the hands is termed sclerodactyly.
  • With facial involvement, the lips become pursed, facial folds and features are flattened and lost, and the patient has difficulty opening the mouth and chewing.
  • In the en coup de sabre variant of scleroderma, hemifacial skin tightness and atrophy evolve, and a cleft develops along the midline, often including the calvaria, forehead, nose, palate, tongue, and chin.
• GI: Dysmotility of the esophagus is common in SSc. Newer diagnostic techniques reveal that almost 90% of patients have esophageal involvement. Clinically, symptomatic dysphagia is much less common. Esophageal manometry is the current diagnostic study of choice. Hypomotility of the small bowel (duodenal-jejunal junction) may lead to malabsorption in a small percentage of patients. Weight loss and inanition in a patient with SSc should raise a concern of GI involvement. Wide mouth sacculations of the colon are distinctive lesions in SSc.
• Lungs
• • Pulmonary involvement in SSc consists of pleuritis, pleural effusion, pulmonary hypertension, diffuse interstitial pneumonitis, and cor pulmonale, either alone or in combination.
  • Fibrosing alveolitis leading to interstitial pulmonary fibrosis is currently recognized as a major complication and cause of death in PSS. Until quite recently, SSc renal crisis was almost uniformly fatal. The introduction of angiotensin-converting enzyme (ACE) inhibitors has rendered this deadly complication treatable.
  • Currently, more than 50% of scleroderma-related deaths are secondary to pulmonary arterial hypertension (PAH), an almost invariable consequence of pulmonary fibrosis. Predictors of PAH include the extent of cutaneous involvement, decreasing carbon monoxide (CO) diffusion capacity, late disease onset, and male sex. Echocardiography tends to overestimate the prevalence of PAH (40-50%) compared to catheterization of the right side of the heart (20-25%).
  • PAH in PSS is further confounded by left ventricular dysfunction, which becomes evident only upon exertion. The pathophysiology of scleroderma lung disease has been well studied. Lymphocytes, polymorphonuclear leukocytes, and eosinophils are attracted to pulmonary tissues, produce inflammatory cytokines, and release reactive oxygen species and degradative enzymes. Thus begins a vicious cycle. As lung involvement progresses, it becomes detectable with high-resolution computed tomography (HRCT) of the chest.
  • PAH is idiopathic and develops primarily in association with systemic connective tissue disease (PSS, SLE) or following surgical repair of congenital systemic-to-pulmonary shunts.
• Heart: Inflammatory and fibrotic disease of the heart in SSc includes pericarditis, myocardial fibrosis, and contraction band necrosis of coronary vessels.
• Musculoskeletal: Myositis is not uncommon in SSc and must be distinguished from other connective tissue diseases. A more chronic myopathy, characterized by mild weakness and minimal muscle enzyme elevations, is more common than acute myositis. Although uncommon early in the disease progress, digital tuft resorption observed on radiographs is a classic finding in SSc. Long-bone growth arrest and fibrotic bands involving the joint capsule have been observed in long-standing cases of scleroderma. Contractures of the fingers and toes are quite common in long-standing disease. Subcutaneous calcinosis, which is common in pediatric dermatomyositis and adult SSc, is rare in childhood SSc. When it does occur, it usually involves extensor surfaces of both upper and lower extremities.
• Renal: The kidney is not commonly involved in SSc, but renal involvement is highly associated with mortality. Patients who develop proteinuria or hypertension are at increased risk for severe renal scleroderma. The renal lesion is a slowly progressive vasculitis; intimal proliferation, medial thinning, and adventitial fibrosis, with decreased blood flow and glomerular function, characterize this disorder. Acute renal failure follows a major stress (eg, trauma, hemorrhage, surgery).
• Nervous system: Entrapment neuropathy, caused by fibrosis impinging on the nerve, is the most common neurologic complication of SSc. Trigeminal neuropathy is the most common example in this disease, and it develops in patients with facial skin involvement. Peripheral nerve entrapment is observed in some children with linear scleroderma.

Causes

Idiopathic SSc is without known cause. However, a number of intriguing disease conditions are associated with cutaneous features that resemble scleroderma, including the following:

• Eosinophilic fasciitis
• Toxic oil syndrome (adulterated rapeseed oil)
• Eosinophilia myalgia syndrome (contaminated L-tryptophan)
• Silica- and silicon-associated scleroderma
• Chemical-associated fibrosis (bleomycin, vinyl chloride, pentazocine, other amines)
• Epoxy resin vapor
• Organic solvents (eg, benzene, xylene, toluene, methylene chloride, trichloroethylene, trichloroethane)
• Metabolic conditions have been associated with features of scleroderma.
• • Digital fibrosis in diabetes mellitus
  • Scleromyxedema
  • Carcinoid syndrome
  • Phenylketonuria
  • Porphyria cutanea tarda
  • Acromegaly
• Several rare conditions may have features similar to those of SSc, as follows:
• • Werner syndrome (premature aging with sclerodermatous skin changes and subcutaneous calcifications)
  • Hutchinson-Gilford syndrome (progeria)
  • Rothmund syndrome, also termed Rothmund-Thompson syndrome or poikiloderma congenitale (atrophic, hyperpigmented, telangiectatic cutaneous plaques)
  • Amyloidosis
• Two conditions bear special mention in pediatrics.
• • Lichen sclerosis et atrophicus is occasionally confused with sexual abuse in young females. Although the precise nature of the condition is not understood, an immune association clearly exists.
  • Graft-versus-host disease (GVHD) also has a complex immune etiopathogenesis and is of special interest when attempting to understand idiopathic SSc. Chronic GVHD is a disabling condition that complicates allogeneic bone marrow transplantation. Dermal sclerosis and atrophy, hyperpigmentation and/or hypopigmentation, Sicca syndrome, and immunodeficiency characterize GVHD. Its pathogenesis is not well understood. However, various cytokines including gamma interferon (IFN-g), tumor necrosis factor–alpha (TNF-a), and interleukins (IL-1, IL-6) have been implicated in the sclerodermatous changes that characterize chronic GVHD.

DIFFERENTIALS

Section 4 of 11  

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• Follow-up
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• Multimedia
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Other Problems to be Considered

Many of the pediatric systemic rheumatic diseases, including dermatomyositis, SLE, systemic vasculitis, and juvenile rheumatoid arthritis (JRA), have clinical and laboratory features that cause some confusion. On occasion, even experienced rheumatologists may have some difficulty in making a definitive diagnosis. Overlap syndromes are well described and mentioned in this topic because SSc, dermatomyositis, SLE, systemic vasculitis, and systemic JRA (ie, Still disease) have been observed by this author in various combinations or in evolution in various children with rheumatic disease.

Establishing a specific diagnosis is important for prognosis and treatment. In some patients, a specific diagnosis may take months to years to establish. In this author's experience, scleroderma and dermatomyositis overlap, and SLE and JRA overlap. Systemic vasculitis may mimic almost any of the other systemic rheumatic diseases.

WORKUP

Section 5 of 11  

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• Follow-up
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Lab Studies

• As with all systemic rheumatic diseases, perform routine CBC count, urinalysis, chemistry survey, erythrocyte sediment rate (ESR), and antinuclear antibody (ANA) tests.
• • These tests help to establish baseline values before the introduction of potentially toxic medications.
  • Early in the course of the disease, few, if any, laboratory abnormalities may be present. Later, mild anemia with slight thrombocytosis may be evident.
  • Peripheral eosinophilia should alert the clinician to one of the variants of scleroderma.
  • Hematuria, proteinuria, and cellular casts are an ominous sign in patients with SSc and may represent impending renal insufficiency.
  • Survey chemistries are useful in monitoring disease activity and drug-associated toxicities. The ESR is often normal or only mildly elevated.
• Rheumatoid factor (RF) is rarely positive in children with SSc but may be present in as many as 25% of adults with SSc.
• Immunologic tests may be helpful in patients with SSc. Children with SSc often have a positive ANA with nucleolar staining. Almost 100% of children with SSc have a positive speckled ANA. Antinucleolar staining (one cause of a speckled pattern) is observed almost exclusively in adult and pediatric SSc. Some of the many other autoantibodies that have been described in the sera of patients with SSc include the following:
• • Antitopoisomerase
  • Anti–RNA polymerase
  • Antiribonucleoprotein
  • Anticentromere
  • Anti-ku
  • Anti-Th
  • Anti-PM-Scl
• Quantitative immunoglobulin levels often reflect a modest immunoglobulin G (IgG) hyperglobulinemia. This nonspecific polyclonal gammopathy is detectable in many chronic inflammatory and systemic rheumatic diseases. Complement levels are normal in most cases. Test results for circulating immunocomplexes are usually negative.

Imaging Studies

• Barium swallow with small bowel follow-through, although once commonly obtained in patients with SSc, has been replaced by esophageal manometry.
• High-resolution thin-cut CT (HRCT) of the lungs has been helpful in making the diagnosis and following the progress of diffuse interstitial pneumonitis in patients with SSc. This author recommends HRCT as the study of choice in children with SSc.

Other Tests

• Although skin biopsies have been useful in assessing patients with SSc for years, the results are not specific and must always be correlated with clinical features. In immunofluorescence microscopy, this author has observed dermal and/or epidermal staining with IgM-specific antibody. The classic lupus band test observed in SLE is typically IgG antibody. Tests for collagen synthesis have not been consistently helpful, and their performance and interpretation requires the expertise of a research laboratory.

Procedures

• Esophageal manometry is currently the study of choice for diagnosis of this disorder. Esophageal involvement is present in almost 90% of patients, as revealed by newer diagnostic techniques.

Histologic Findings

Early in the course of SSc, an inflammatory reaction with subintimal vascular proliferation and an infiltration of round cells often goes unrecognized. After a varying length of time, fibrosis follows this reaction. Fibrosis characterizes the final common pathway in SSc. In the skin, thinning of the epidermis occurs, with loss of rete pegs as collagens and other matrix proteins accumulate in the dermis. Early studies made use of this feature to quantitate dermal thickness in skin biopsies and relate the degree of fibrosis with disease severity. Arteriolar and capillary endothelial proliferation precedes fibrosis in the visceral organs. Prognosis in the individual patient is related to the intensity and rapidity of fibrosis in the lungs, heart, GI tract, and kidney. Finally, atrophy ensues, and vital function is compromised.

Humoral and cellular immunity both contribute to the pathology of SSc, but the intimate details remain to be elucidated. The complex relationships among immune, vascular, and fibrotic perturbations may help explain the difficulties encountered in the treatment of patients with SSc.

TREATMENT

Section 6 of 11  

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Medical Care

General health measures, including nutrition, rest, school attendance, and exercise are emphasized when caring for a child with a chronic disease. Treating a child with SSc 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 SSc. However, therapeutic strategies have been developed that are directed toward the organ systems involved.

• Vascular therapy is multifaceted and 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. Calcium channel blockers (eg, nifedipine, nicardipine) are suggested. Local management of digital ulcers is indicated.
• The arthritis of SSc may respond to nonsteroidal anti-inflammatory drugs (NSAIDs), but to a lesser extent than the arthritis associated with other connective tissue diseases.
• Follow the typical recommendations for the relief of reflux associated with esophageal dysmotility.
• Interstitial lung disease associated with SSc is a major therapeutic challenge.
• • High-dose corticosteroids and cyclophosphamide have had a variable response in individual patients.
  • Patients who have developed PAH deserve special consideration. Because pulmonary vasoconstriction, endothelial and smooth muscle cell proliferation, and in situ thrombosis all contribute to the development of PAH, treatment with vasodilators, antiproliferative agents, and anticoagulants is recommended.
  • Major advancements in the treatment of PAH have been made.
    • Epoprostenol, a continuous IV infusion of prostacyclin, was shown to be effective in the treatment of severe PAH. Treprostinil (a continuous subcutaneous prostacyclin infusion), bosentan (an oral endothelin antagonist), and iloprost (an inhaled prostacyclin analog) have been shown to improve the 6-minute walk distances in patients with PAH when compared to placebo. Nitric oxide, a potent vasodilator, has been used to treat persistent pulmonary hypertension (PPH) in newborns and in patients after cardiac surgery for more than a decade.
• Previously, hypertensive renal crisis was the most dreaded complication of SSc. The development of ACE inhibitors (eg, captopril, enalapril) has remarkably improved the prognosis for such patients.
• Immunomodulatory therapy has been tried with variable success. Physicians have used many agents, including cyclosporin A, antilymphocyte globulin, intravenous immune serum globulin (IVIG), plasma exchange, methotrexate, and cyclophosphamide.
• Antifibrotic therapy deserves special mention. The fact that penicillamine interferes with collagen cross-linking in vitro is the oft-quoted basis for its use in SSc. Retrospective studies using historic controls suggested its beneficial effect. The difficulty in carrying out blinded controlled studies is obvious in a disease such as SSc, with its protean manifestations and infinite permeations of involvement in the individual patient.

Surgical Care

Because of the vagaries of SSc, 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 a patient with a ruptured viscus may be required. Amputation should be considered only in extreme cases. Sympathectomy as a treatment of the peripheral vascular disease has been abandoned.

Consultations

A team approach is required, and the rheumatologist team leader must be a specialist experienced in the care of patients with SSc. The team should include a nurse educator, occupational therapist, physical therapist, nutritionist, and social worker. School attendance, independence, and compliance with medication and exercise programs are encouraged and reinforced. Telemedicine may play a role in long-distance consultation and treatment of patients with SSc who reside far from full-service institutions. Recent experimental therapies to include system cell, renal, and lung transplantation are beyond the scope of this discussion.

MEDICATION

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Drug Category: Calcium channel blocking agents

These agents are helpful in treating patients who develop tissue ischemia of digital tip ulcers. Dihydropyridine calcium channel blockers (eg, nifedipine, nicardipine) have more pronounced peripheral vasodilatory effect.

Drug Category: ACE inhibitors

Previously, hypertensive renal crisis was the most dreaded complication of SSc. However, with the development of the ACE inhibitors (eg, captopril, enalapril), the prognosis of such patients has improved remarkably.

Drug Category: Nonsteroidal anti-inflammatory agents

These agents are used to treat the arthritis of SSc. They have analgesic, antiinflammatory, and antipyretic activities. Their mechanism of action is not known, but may inhibit cyclooxygenase activity and prostaglandin synthesis. Other mechanisms may also exist (eg, inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, various cell-membrane functions).

Drug Category: Immunosuppressive agents

Interstitial lung disease associated with SSc is a major therapeutic challenge. Treatment with high-dose corticosteroids, methotrexate, and cyclophosphamide has shown variable response among different patients. Slower-acting antirheumatic drug or disease-modifying antirheumatic drugs (eg, penicillamine) have been used for their anti-inflammatory and anticollagen effects.

Drug Category: Immune globulin

This agent is purified preparation of gamma globulin. It is derived from large pools of human plasma and comprises 4 subclasses of antibodies, approximating the distribution of human serum. Used for immune modulation.

Drug Category: Prostacyclin analogues

Prostacyclins, specifically epoprostenol, are indicated for the long-term treatment of pulmonary hypertension associated with scleroderma disease. May also reduce pain and the occurrence of digital ulcerations. Additionally, prostacyclins may improve lesion scores and ischemic lesion scores. Other prostacyclin analogues being investigated for use in SSc include an orally administered prostacyclin (beraprost), iloprost (Ventavis), and SC-administered treprostinil (Remodulin). Iloprost and treprostinil are currently FDA-approved for PAH. Iloprost is available as an aerosolized inhaled agent, but an IV form is currently under investigation.

FOLLOW-UP

Section 8 of 11  

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Further Inpatient Care

• Patients are admitted to the hospital on a limited basis, and then only to treat critical care emergencies, often in an ICU (eg, renal crisis, impending respiratory failure, surgical emergencies). Other treatments are often accomplished in ambulatory care units or at home.

Further Outpatient Care

• Outpatient care needs to be individualized. Stress independent activities of daily living, good nutrition, and a healthy and positive attitude. Monitor medication and admit patients to the hospital only for definitive medical or surgical treatment. The team (see Medical Care) is integral to the outpatient care of a child with SSc. The importance of continued schooling and independent living cannot be overemphasized.

In/Out Patient Meds

• Adolescents and young adults may have poor compliance, which can be a problem. Individual responsibility is encouraged and emphasized by the team, particularly the nurse educator and social worker.

Transfer

• The expertise of an experienced pediatric rheumatologist is required.

Deterrence/Prevention

• Idiopathic disease is not preventable. Conditions that resemble SSc secondary to toxins or metabolic perturbations may be quite amenable to preventive principles.

Complications

• Complications include subcutaneous calcinosis, esophageal dysfunction to the point of malnutrition, and wasting. Serious hypertension is an indication of advancing renal disease, and hypertensive crises occasionally occur. For more information about the potential lethal effects of PAH, see Pulmonary Hypertension, Eisenmenger Syndrome; Pulmonary Hypertension, Persistent Newborn; and Pulmonary Hypertension, Idiopathic.

Prognosis

• The mortality rate associated with PSS is high, with a large percentage of patients succumbing after a varying period of significant morbidity. Patients with limited forms of scleroderma are not at increased risk of death compared to the general population. This is true for all age groups with limited forms of scleroderma. Prognosis for individuals with secondary forms of the disease depends on the toxicity of the offending agent.

Patient Education

• As with all chronic disease, SSc requires continual reinforcement of education concerning adequate nutrition, independent mobility, and control of potential adverse effects of medication.

MISCELLANEOUS

Section 9 of 11  

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• Medication
• Follow-up
• Miscellaneous
• Multimedia
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Medical/Legal Pitfalls

• Issues of missed diagnosis (commonly another rheumatic disease) and obtaining informed consent for sometimes heroic therapies (leading to wrongful death litigation) constitute the major legal pitfalls. For this reason, experienced specialists are essential in the diagnosis and treatment of patients with SSc. These patients require a treatment team with a pediatric rheumatologist as team leader and case manager.

MULTIMEDIA

Section 10 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  An 8-year-old girl with overlap syndrome with evolution to progressive systemic sclerosis (PSS).
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Media type:  Photo

Media file 2:  Photo of hands showing sclerodactyly. This demonstrates the progression of disease over the past 7 years.
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Media type:  Photo

Media file 3:  Chest radiograph shows diffuse, coarse interstitial marking with bilateral lower lobe bronchiectasis.
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Media type:  X-RAY

Media file 4:  Axial CT scan of the chest of a 15-year-old female adolescent with PSS.
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Media type:  CT

Media file 5:  Esophagram demonstrating dysmotility.
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Media type:  X-RAY

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

• Black CM, Denton CP. Therapy of Systemic Sclerosis. In: Van de Putte LBA, Furst DE, Williams HJ, van Riel PLCM, eds. Therapy of Systemic Rheumatic Disorders. 1998:495-545.
• Bottoni CR, Reinker KA, Gardner RD. Scleroderma in childhood: a 35-year history of cases and review of the literature. J Pediatr Orthop. Jul-Aug 2000;20(4):442-9. [Medline].
• Hoeper MM. Pulmonary hypertension in collagen vascular disease. Eur Respir J. 2002;19: 571 - 576.
• Kaal SE, van Den Hoogen FH, de Jong EM. Systemic sclerosis: new insights in autoimmunity. Proc Soc Exp Biol Med. Oct 1999;222(1):1-8. [Medline].
• LeRoy EC. Pathogenesis of Systemic Sclerosis (scleroderma). In: Koopman WJ, ed. Arthritis and Allied Conditions. 1997:1481-1490.
• Levy BD. Eicosanoids in scleroderma: Lung disease hangs in the ballance. Arthritis Rheum. 2005;Dec:52(12): 3693-3697.
• Medsger TA Jr. Systemic Sclerosis (scleroderma): Clinical Aspects. In: Koopman WJ, ed. Arthritis and Allied Conditions. 1997;1433-1464.
• Medsger TA Jr, Steen V. Systemic Sclerosis and Related Syndromes. In: Schumacher HR Jr, Klippel VH, Koopman WJ, eds. Primer on the Rheumatic Diseases. 1993;118-127.
• Nagaya N. Drug therapy of primary pulmonary hypertension. AM J Cardiovasc Drugs. 2004;4(2): 75 - 85.
• Peterson LS, Nelson AM, Su WP. Classification of morphea (localized scleroderma). Mayo Clin Proc. Nov 1995;70(11):1068-76. [Medline].
• Poormoghim H, Lucas M, Fertig N. Systemic sclerosis sine scleroderma: demographic, clinical, and serologic features and survival in forty-eight patients. Arthritis Rheum. Feb 2000;43(2):444-51. [Medline].
• Silver RM. Variant Forms of Scleroderma. In: Koopman WJ, ed. Arthritis and Allied Conditions. 1997:1465-1480.
• Steen V. Advancements in diagnosis of pulmonary arterial hypertension in scleroderma. Arthritis Rheum. 2005;Dec:52(12): 3698-3700.
• Vancheeswaran R, Black CM, David J, et al. Childhood-onset scleroderma: is it different from adult-onset disease. Arthritis Rheum. Jun 1996;39(6):1041-9. [Medline].

Article Last Updated: Jul 14, 2006