A 4-year-old boy presented with a one-year history of skin redness and tightening over the right upper extremity. His mother had initially noticed the lesion after applying a temporary tattoo. He complained of occasional itching and pain over the area. His mother was concerned that his arm appeared to be “shrinking.” He had no prior medical problems or preceding infections and his immunizations were up-to-date. He had difficulty grasping a crayon due to involvement of his fingers. On exam, he had a large area of skin tightening extending from the right scapular region and upper arm down to the forearm, index finger and thumb (Figure 178-1). He was referred to a dermatologist who performed a punch biopsy confirming a diagnosis of morphea (localized scleroderma). He was treated with topical fluticasone without benefit and referred to a pediatric rheumatologist for systemic therapy with methotrexate. Serologic testing showed a negative ANA and scleroderma antibody and he has had no features of systemic scleroderma.

Scleroderma (from the Greek scleros, to harden) is a term that describes the presence of thickened, hardened skin. It may affect only limited areas of the skin (morphea), most or all of the skin (scleroderma), or also involve internal organs (systemic sclerosis).

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  Scleroderma is a spectrum of disorders that can be occur at any stage of life, but the clinical patterns seen in childhood differ somewhat from that seen in adults.

  
  
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  The prevalence rates of diseases that share scleroderma as a clinical feature are reported ranging from 4 to 253 cases per 1 million individuals of all ages.¹

  
  
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  The most common form of childhood scleroderma is morphea (localized scleroderma or LSc) which principally involves the skin, subcutaneous fascia, muscle, and bone. It is 10 times more common than systemic sclerosis and may include circumscribed or generalized morphea, bullous morphea, deep morphea, and linear morphea (including the en coup de sabre subtype, characterized by a vertical scar on the forehead resembling a stroke from a sword). ²

  
  
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  In a retrospective multicenter review of 750 children with LSc, the most common subtype was linear morphea (65%), followed by circumscribed morphea (26%), mixed subtype (15%), generalized morphea (7%), and deep morphea (2%). Overall, the mean age of presentation was 7.3 years (range 0 to 16 years, median age 6.1 years).³

  
  
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  In the US, the incidence of morphea has been estimated at 25 cases per 1 million individuals (of any age) per year.¹ Although data are scarce, it is estimated that childhood LSc occurs only in 1 per 1 million.² LSc infrequently progresses into a systemic form and can sometimes merge or overlap with eosinophilic fasciitis.⁴

  
  
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  Juvenile systemic sclerosis (JSSc) is a chronic multisystem connective tissue disorder characterized by sclerodermic skin changes and abnormalities of the visceral organs. Systemic sclerosis has an annual incidence of 1 to 2 per 100,000 adults and children in the US.¹ Onset of JSSc in childhood is very uncommon and accounts for only 3 percent of all cases of systemic sclerosis.⁶

  
  
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  The risk of JSSc is similar in both sexes in younger children, but it occurs three times more often in girls than in boys aged eight years or more.⁷

  
  
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  The incidence of JSSc in the United Kingdom and Ireland was estimated to be 0.27 cases per million children/year in a 2005 to 2007 survey.⁸ The incidence of JSSc in other populations is unknown.

  
  
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  Worldwide, there are higher rates of scleroderma in the US and Australia than in Japan or Europe.⁹

  
  
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  Pulmonary, cardiac, and renal disease are the leading causes of death as a consequence of these diseases.¹⁰

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  The etiology and pathogenesis of scleroderma remains uncertain. Two theorized contributing pathogenic processes include vasculopathy, abnormal fibroblast function, and autoimmune dysfunction.

  
  
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  Scleroderma disorders can be subdivided into three groups: localized scleroderma (morphea; Figures 178-1 to 178-3), systemic sclerosis (Figures 178-4 to 178-7), and other scleroderma-like disorders that are marked by the presence of thickened, sclerotic skin lesions.

  
  
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  A multicenter European study of 750 children with LSc defined the prevalence and the clinical features of extracutaneous findings in patients with LSc.¹¹ There was one or more extracutaneous manifestations in 22 percent of children. In 92 percent of the cases, the skin lesion was the presenting sign of disease. The overall distribution of extracutaneous manifestations included:

  
  
  
  
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    Arthritis—19 percent.

    
    
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    Neurologic findings—4 percent.

    
    
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    Raynaud’s phenomenon—3 percent.

    
    
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    Vascular findings (vasculitic rash and deep vein thrombosis)—2 percent.

    
    
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    Ocular findings—3 percent.

    
    
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    Gastrointestinal symptoms (GERD)—2 percent.

    
    
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    Restrictive lung disease—1 percent.

    
    
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    Two patients had cardiac findings (pericarditis and arrhythmia) and one patient had nephritis.

  
  
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  Systemic sclerosis is used to describe a systemic disease characterized by skin induration and thickening accompanied by variable tissue fibrosis and inflammatory infiltration in numerous visceral organs. Systemic sclerosis can be diffuse (DcSSc) or limited to the skin and adjacent tissues (limited cutaneous systemic sclerosis [LcSSc]).

  
  
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  The majority of children with JSSc present with Raynaud phenomenon and/or skin changes (tightening, thinning, and atrophy) of the hands and face. In a multicenter retrospective study of 153 children with JSSc, the median age of onset was 8.1 years and the mean duration of symptoms prior to diagnosis was 1.9 years.⁷ Eleven percent had a family history of autoimmune disease. Findings at diagnosis included:

  
  
  
  
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    Raynaud phenomenon—70 percent.

    
    
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    Skin induration proximal to the MCP and MTP joints—63 percent.

    
    
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    Musculoskeletal symptoms (arthralgia, muscle weakness, and arthritis)—33 percent.

    
    
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    Weight loss—18 percent.

    
    
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    Dyspnea—10 percent.

    
    
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    Dysphagia—10 percent.

  
  
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  The most common vascular dysfunction associated with scleroderma is Raynaud phenomenon (Figure 178-7). Raynaud phenomenon is produced by arterial constriction in the digits. The characteristic color changes progress from white (pallor), to blue (acrocyanosis), to finally red (reperfusion hyperemia). Raynaud phenomenon generally precedes other disease manifestations, sometimes by years. Many patients develop progressive structural changes in their small blood vessels, which permanently impair blood flow, and can result in digital ulceration or infarction. Other forms of vascular injury include pulmonary artery hypertension, renal crisis, and gastric antral vascular ectasia.

  
  
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  Patients with limited cutaneous scleroderma (LcSSc) usually have skin sclerosis restricted to the hands and, to a lesser extent, the face and neck. With time, some patients develop scleroderma of the distal forearm. They often eventually display the CREST syndrome, which presents with Raynaud phenomenon (Figure 178-7), esophageal dysmotility, sclerodactyly (Figures 178-4 and 178-5), telangiectasias (Figure 178-6), and calcinosis cutis (Figure 178-8). This variant is rare in children.

  
  
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  Patients with diffuse cutaneous scleroderma (DcSSc) often present with sclerotic skin on the chest, abdomen, or upper arms and shoulders. The skin may take on a “salt-and-pepper” look (Figure 178-9). They are more likely to develop internal organ damage caused by ischemic injury and fibrosis than those with LcSSc or morphea.

  
  
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  Arthralgias are the presenting symptom in about 15 percent of children and are usually mild and transient. Joint contractures are most common at the proximal intraphalangeal joints and elbows. Arthritis and myositis may occur in up to 30 percent of children, and may precede the diagnosis of JSSc.⁷ Myositis leads to muscle weakness and myalgia, and is associated with elevated levels of creatinine kinase (CPK).

  
  
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  GI involvement is seen in 30 to 74 percent of children with systemic sclerosis,^7,12 although half of these patients may be asymptomatic. Any part of the GI tract may be involved. Potential signs and symptoms include dysphagia, choking, heartburn, cough after swallowing, bloating, constipation, and/or diarrhea, pseudoobstruction, malabsorption, and fecal incontinency. Chronic gastroesophageal reflux is more common in children and recurrent episodes of aspiration may contribute to the development of interstitial lung disease. Vascular ectasia in the stomach (often referred to as “water-melon stomach” on endoscopy) is a common late finding, and may lead to GI bleeding and anemia.

  
  
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  Pulmonary involvement is seen in more than 70 percent of patients, usually presenting as dyspnea on exertion and a nonproductive cough. Fine “Velcro” rales may be heard at the lung bases with lung auscultation. Pulmonary vascular disease occurs in 10 to 40 percent of patients with systemic sclerosis, and is more common in patients with limited cutaneous disease. The risk of lung cancer is increased approximately 5-fold in patients with scleroderma.

  
  
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  Autopsy data suggest that 60 to 80 percent of patients with DcSSc have evidence of kidney damage.¹³ Some degree of proteinuria, a mild elevation in the plasma creatinine concentration, and/or hypertension are observed in as many as 50 percent of patients.¹⁴ Severe renal disease develops in 10 to 15 percent of patients, most commonly in patients with DcSSc.

  
  
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  Symptomatic pericarditis occurs in 7 to 20 percent of patients, which has a 5-year mortality rate of 75 percent.¹⁵ Primary cardiac involvement includes pericarditis, pericardial effusion, myocardial fibrosis, heart failure, myocarditis associated with myositis, conduction disturbances, and arrhythmias.¹⁶ Patchy myocardial fibrosis is characteristic of systemic sclerosis, and is thought to result from recurrent vasospasm of small vessels. Arrhythmias are common and are most caused by fibrosis of the conduction system.

  
  
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  Pulmonary vascular disease occurs in 10 to 40 percent of patients with scleroderma, and is more common in patients with limited cutaneous disease. It may occur in the absence of significant interstitial lung disease, generally a late complication in adults, and is usually progressive. Severe pulmonary arterial hypertension, sometimes with pulmonale and right-sided heart failure or thrombosis of the pulmonary vessels may develop.

  
  
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  Contractures may develop, with contractures of the fingers being most common. Neuropathies and central nervous system involvement, including headache, seizures, stroke, vascular disease, radiculopathy, and myelopathy, occur.