Laboratory Studies
The following findings may be found with laboratory studies:
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Increased erythrocyte sedimentation rate
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Thrombocytopenia
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Hypergammaglobulinemia
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Microangiopathic hemolytic anemia
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Increased creatine phosphokinase levels in patients with muscle involvement
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Increased urea and creatinine levels in patients with kidney involvement
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C-reactive protein: The nonspecific inflammatory marker C-reactive protein was found elevated in about one quarter of patients with systemic sclerosis, especially early disease, in whom it correlated with disease activity, severity, poor pulmonary function, and shorter survival. [34]
Imaging Studies
Chest radiographs may show normal findings in 5-10% of the patients, even when the patients have respiratory tract symptoms. In approximately 30-60% of patients, fibrosis of the basal parts of the lungs is observed. Occasionally, pictures of diffuse ground-glass and honeycomb lung patterns are observed. In patients with honeycomb lung patterns, changes are irreversible. These changes can be an important feature of patient's response to treatment.
Bone radiography reveals generalized osteopenia, which most commonly affects the hands. Intra-articular calcifications often are observed.
High-resolution computed tomography (HRCT) and scintigraphy reveal thickening of the alveolar walls and intestinal tissue and honeycomb-appearing lungs.
Gastrointestinal tract changes may be depicted. Scintigraphy of the esophagus may reveal a disturbance of the esophageal passage. [35] Manometric esophageal changes may be observed during invasive examination. Upper gastrointestinal tract evaluation should be performed only in systemic sclerosis, but not in morphea. [36]
Cardiac and pulmonary vascular involvement in systemic sclerosis should be evaluated. Cardiac abnormalities may be assessed by Doppler echocardiography. [37] Left- and right-sided heart diseases were found to be common in persons with systemic sclerosis. A few patients had a restrictive mitral flow pattern, possibly due to primary cardiac involvement of systemic sclerosis. Diastolic dysfunction is the most common cardiac finding. [38] Early detection of cardiac and renal involvement in patients even without symptoms is recommended to avoid further complications. [39]
Because cardiac involvement is one of the major problems in systemic sclerosis, evaluation of ventricular function using echocardiographic strain imaging should be considered, because it appears to be useful to detect subclinical cardiac involvement in systemic sclerosis patients with normal standard echocardiographic and tissue Doppler velocity findings. [40]
Since the initial changes in systemic sclerosis are believed to involve microcirculation, its evaluation using laser Doppler flowmetry in the distal portion of the upper extremity has been advocated. [41]
High-resolution ultrasound imaging of skin involvement in these patients can be used to quantitatively evaluate dermal thickness in systemic sclerosis. [42]
Other Tests
With bronchoalveolar lavage (BAL), abnormal numbers of granulocytes, particularly neutrophils and eosinophils are present in BAL fluid. In addition, the concentration of vascular endothelial growth factor may be low. [43]
Lung function tests reveal ventilation-perfusion changes, including the following:
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Reduced carbon monoxide diffusion capacity
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A reduced partial pressure of oxygen, with a normal or low partial pressure of carbon dioxide
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Restrictive ventilatory defect, with reductions in pulmonary compliance, vital capacity, and total lung capacity
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Decreased diffusion capacity of carbon monoxide transfer factor (DLCO) levels, which is a measure of diffusion capacity
The gas transfer measurement (KCO), adjusted for alveolar volume, is also reduced.
Heart changes, including myocardial disease, pericardial problems, conduction system disease, and arrhythmias, can be observed with the following tests:
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Electrocardiography (ECG)
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Holter 24-hour monitoring
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Doppler ultrasonography (US)
Exophthalmos, macroglossia, and/or gigantism may be present, with increased polyphasic potentials of normal or decreased amplitude.
Antihistone antibodies can be observed in the course of systemic sclerosis, but they are not characteristic. The following antinuclear antibodies (ANAs) are characteristic of scleroderma:
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Antibodies against topoisomerase I DNA (Scl 70) are detected in the serum of patients with systemic sclerosis. The antibodies are detected in two thirds of patients with dSSc and interstitial lung fibrosis.
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Anticentromere antibodies (ACAs) are most commonly detected in patients with lSSc; in these patients, changes in the heart, kidneys, and lungs (without fibrosis) are observed less frequently than in other patients.
ANAs can be detected in the course of systemic sclerosis. ANAs include antibodies against fibrillarin, a 34-kd protein of ribonucleoprotein U3 RNP; antibodies against the ribonucleoprotein nucleolar 7-2 RNA protein particle Th RNP; and antibodies to 20-110-kd proteins related to preribosomes (PM-Scl). Anti-PM/Scl antibodies are seen in roughly 24% of patients with polymyositis/systemic sclerosis overlap syndrome. They are also found in 3-10% of systemic sclerosis patients. [44, 45] The spectrum of systemic sclerosis-associated ANA differs in patients with and without cutaneous involvement. [46] ANA serum levels in patients with systemic sclerosis are not correlated with disease activity.
Elevated high-sensitivity C-reactive protein appears related to the occurrence of antimitochondrial antibody in these patients. [47]
With capillary microscopy, enlarged capillaries are observed in all three portions of the capillary nail fold—arterial, apical, and venous—and especially at the edge of the nail fold. Adjacent areas are avascular. Nailfold videocapillaroscopy may be value in assessing these patients. [48]
Spirometry demonstrates functional lung disturbances. In approximately 70% of patients, the DLCO is decreased.
Histologic Findings
In the active indurative phase, a loss of rete ridges occurs, epidermal skin appendages atrophy, and collagen fibers in the reticular dermis appear broad and hyalinized. A loss of space between collagen bundles is noted. Mononuclear cells, mostly T cells, form a variable perivascular infiltrate in the deep dermis and subcutis. Later, sclerotic changes predominate. The number of adnexal structures is reduced, and a loss of periadnexal fat is noted.
In one study, progressive systemic sclerosis histologic changes were systematically scored in skin biopsy specimens of dorsal forearm and upper inner arm in 53 consecutive patients and controls. The amount of hyalinized collagen, myofibroblasts, mean epidermal thickness, the mononuclear cellular infiltration, and the frequency of focal exocytosis varied significantly between those with and those without local clinical skin involvement. [49]
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Face of 65-year old woman with systemic sclerosis and skin thickening of 20 years' duration: Note the pinched nose, taut skin with numerous telangiectasias, and retraction of the lips.
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Telangiectasias affecting the face: They are pronounced and numerous, especially in the atrophic phase of the disease. Radical furrowing around the mouth is also characteristic in the later stage of the disease.
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Raynaud phenomenon of the hands: Symmetrical acral vasospasm is present, with characteristic pallor, cyanosis, suffusion, and a sense of fullness and tautness.
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Puffy appearance of the woman's hand in the edematous phase of early scleroderma.
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In systemic sclerosis, ulceration at the tip of the finger is regarded to be secondary to ischemia.
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Hand of a woman with scleroderma of several years' duration: The thickened, tight, thin skin over the fingers is the result of self-amputation of the distal phalanx due to ischemia. Moderately severe flexion contractures of the fingers are present.
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In systemic sclerosis, skin hyperpigmentation of the lower legs is surrounded by areas of hypopigmentation. The result is a salt-and-pepper appearance.
