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Keeping the body warm is the cornerstone of initial therapy Wearing warms shirts, coats, and hats will help prevent the
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pulmonary vascular disease are reflected in restrictive lung physiology and low diffusing capacities Cardiac abnormalities include pericarditis, heart block, myocardial fibrosis, and right heart failure secondary to pulmonary hypertension Scleroderma renal crisis, resulting from obstruction of smaller renal blood vessels, is a marker for a poor outcome even though many cases can now be treated effectively with angiotensinconverting enzyme inhibitors
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Raynaud s phenomenon and antinuclear antibodies are present in virtually all patients Systemic features of dysphagia, hypomotility of gastrointestinal tract, pulmonary fibrosis, and cardiac and renal involvement
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Systemic sclerosis is a chronic disorder characterized by diffuse fibrosis of the skin and internal organs The causes of systemic sclerosis are not known, but autoimmunity, fibroblast dysregulation, graft-versus-host disease from fetal lymphocytes retained in the maternal circulation, and occupational exposure to silica have been implicated The interplay of these mechanisms may also be important: scleroderma patients have autoantibodies that stimulate platelet derived growth factor receptor (PDGFR), which in turn could cause fibroblast dysregulation Symptoms usually appear in the third to fifth decades, and women are affected two to three times as frequently as men Two forms of systemic sclerosis are generally recognized: limited (80% of patients) and diffuse (20%) Two bedside clues help distinguish the two subsets First, in the CREST syndrome (representing calcinosis cutis, Raynaud s phenomenon, esophageal motility disorder, sclerodactyly, and telangiectasia), hardening of the skin (scleroderma) is limited to the face and hands In contrast, in diffuse scleroderma, the skin changes also involve the trunk and proximal extremities Second, tendon friction rubs, especially frequent over the wrists, ankles, and knees, occur uniquely (but not universally) in diffuse scleroderma In general, patients with CREST syndrome have better outcomes than those with diffuse disease, largely because renal failure or interstitial lung disease rarely develops in patients with limited disease Cardiac disease is also more characteristic of diffuse systemic sclerosis Curiously, however, patients with limited disease are more susceptible to digital ischemia, leading to finger loss and to life-threatening pulmonary hypertension Gastrointestinal involvement (gut hypomotility) may occur in both forms of systemic sclerosis, leading to such potentially serious complications as pseudoobstruction
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Mild anemia is often present Among patients with severe renal disease, the peripheral blood smear can show findings consistent with a microangiopathic hemolytic anemia (because of mechanical damage to red cells from diseased small vessels) Elevation of the ESR is unusual Proteinuria and cylindruria appear in association with renal involvement Antinuclear antibody tests are nearly always positive, frequently in high titers (Tables 20 10 and 19 2) The scleroderma antibody (SCL-70) directed against topoisomerase III is found in one-third of patients with diffuse systemic sclerosis and in 20% of those with CREST syndrome; an anticentromere antibody is seen in 50% of those with CREST syndrome and in 1% of individuals with diffuse systemic sclerosis (Tables 20 10 and 19 2) Although present in only a small number of patients with diffuse systemic sclerosis, anti-Scl-70 antibodies may portend a poor prognosis, with a high likelihood of serious internal organ involvement (eg, interstitial lung disease) Anticentromere antibodies are highly specific for limited systemic sclerosis, but they also occur occasionally in overlap syndromes Other scleroderma autoantibodies are those directed against RNA polymerases (anti-RNAP I, II, III), B23, and PDGFR Anti-RNAP antibodies are associated with diffuse skin changes, cardiac and renal involvement, and increased mortality Antibodies to B23 are associated with pulmonary hypertension
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Differential Diagnosis
Several diseases with principally cutaneous manifestations may mimic systemic sclerosis in their skin findings These disorders include morphea and limited systemic sclerosis, two diseases often categorized as forms of localized scleroderma These disorders are generally limited to circumscribed areas of the skin and usually have excellent outcomes Morphea is associated with lavender plaques, typically located over the trunk Linear scleroderma may be associated with atrophy of underlying muscle and bone and may cause deformities that are both cosmetically and functionally disabling Eosinophilic fasciitis is a rare disorder presenting with skin changes that resemble diffuse systemic sclerosis The inflammatory abnormalities, however, are limited to the fascia rather than the dermis and epidermis Moreover, patients with eosinophilic fasciitis are distinguished from those with systemic scleroderma by the presence of peripheral blood eosinophilia, the absence of Raynaud s phenomenon, the good response to prednisone, and an association (in some cases) with paraproteinemias The eosinophilia-myalgia syndrome was first noted in patients who ingested L-tryptophan, an essential amino
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