You are in: eMedicine Specialties > Radiology > CHEST Scleroderma, ThoracicArticle Last Updated: Aug 16, 2007AUTHOR AND EDITOR INFORMATIONSection 1 of 8
  Author: Tracy Elliot, MD, Assistant Professor, Department of Radiology, University of Alberta Health Sciences Center Tracy Elliot is a member of the following medical societies: Alberta Medical Association, American Roentgen Ray Society, Canadian Association of Radiologists, Radiological Society of North America, Royal College of Physicians and Surgeons of Canada, and Society of Thoracic Radiology Editors: Judith K Amorosa, MD, FACR, Clinical Professor and Program Director, Department of Radiology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School; Consulting Staff, Department of Radiology, Robert Wood Johnson University Hospital; Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand; John D Newell, Jr, MD, FACR, FCCP, FASER, Co-Director of Thoracic Imaging, UCDHSC; Director of Lung Imaging Center, Professor of Radiology and Professor of Medicine, Department of Radiology, University of Colorado Health Sciences Center, National Jewish Medical and Research Center; Univ. Colorado Hospital; Robert M Krasny, MD, Consulting Staff, Department of Radiology, The Angeles Clinic and Research Institute; Barry H Gross, MD, Professor, Department of Radiology, University of Michigan Medical School; Professor, University of Michigan Cancer Center Author and Editor Disclosure Synonyms and related keywords: progressive systemic sclerosis, PSS, scleroderma, SSc INTRODUCTIONSection 2 of 8
  BackgroundSystemic sclerosis is a multisystem disease of connective tissue that is accompanied by vasculopathy. Scleroderma, its original name, means hard skin. Clinically, progressive systemic sclerosis (PSS) is classified as diffuse or limited depending on the distribution of skin disease. PSS is considered limited when involvement is restricted to the distal extremities and face. The limited form is associated with a lower risk of visceral involvement, although pulmonary hypertension is more common. Diffuse cutaneous systemic sclerosis (dcSSc) and limited cutaneous systemic sclerosis (lcSSc) scleroderma overlap the following syndromes:
PathophysiologyImmunopathogenesis Recurrent ischemia with reperfusion in PSS generates reactive oxygen species that participate in intranuclear metal-ion catalyzed oxidation. These reactions are believed to alter the configuration of the autoantigenic components of intranuclear proteins, creating cryptic epitopes that stimulate self-reactive T cells. Autoantibodies in PSS A number of autoantibodies that recognize extracellular proteins have been identified, and evidence is increasing that these may be involved in disease pathogenesis. Two research groups have shown that one such protein, antiendothelial cell antibody, induces endothelial cell apoptosis. Immunogenetics The work of Fanning and colleagues supports the theory that the 3 main subtypes of PSS (ie, dcSSc, lcSSc, CREST syndrome) probably encompass 3 separate diseases, each having different pathogenic origins that influence autoantibody and disease expression.1 The proportion of PSS subtypes within a population varies among racial groups. This may be related to differences in genes that are not susceptible to human leukocyte antigen (HLA), as hypothesized by Tan et al,2 or alternatively, this may reflect environmental influences in different geographic locations, as hypothesized by Haustein and Anderegg.3 The relative frequency of autoantibody expression and relative frequencies of specific HLA class I and class II alleles associated with PSS also vary among racial groups within a disease subtype. These trends may reflect racial differences in immunogenetic background, as hypothesized by Harvey et al.4 FrequencyUnited StatesAnnual incidence is 14 cases per million. InternationalEstimated incidence is 20 cases per million, and the estimated prevalence is 500 cases per million. Mortality/MorbidityVisceral organ involvement is the primary cause of morbidity, while pulmonary disease is the most common cause of mortality.
RaceThe proportion of PSS subtypes differs among racial groups. In black women, diffuse scleroderma is diagnosed at an earlier age and carries a poorer prognosis, as reported by Laing et al.7 SexMale-to-female ratio is 1:3. AgeSymptoms manifest in the fourth to sixth decades, although a juvenile form exists. Clinical DetailsClinical diagnosis of PSS Serologic markers: A well-defined antinuclear antibody profile is available for scleroderma. Three main mutually exclusive serologic subgroups are recognized as follows, as reported by Harvey and McHugh4:
These autoantibodies may not be involved directly in disease pathogenesis; however, they are reliable markers of disease-specific pathology. For example, anti-RNAP III antibodies are associated with a higher risk of diffuse PSS, a greater likelihood of renal involvement, and the shortest cumulative survival times. Anti-Topo I positive patients have the greatest risk of interstitial lung fibrosis, with intermediate cumulative survival times and risk of renal disease. Anticentromere antibody is present in a high proportion of patients with the limited form of PSS. This serum profile has the longest cumulative survival times and is associated with the lowest risk of pulmonary fibrosis and renal disease. Skin biopsy: A skin biopsy is performed to confirm clinical suspicion. Biopsy does not provide a reliable distinction of localized scleroderma (morphea) from systemic scleroderma. Intravital capillaroscopy: Almost all patients with dcSSc or lcSSC present with Raynaud phenomenon. This can be distinguished from the Raynaud syndrome of idiopathic vasospasm by demonstrating the presence of cutaneous microangiopathy. Microscopic evaluation of epilluminated capillaries in the nail bed of patients with PSS reveals a chaotic distribution of focally aneurysmally enlarged capillaries. The combination of this pattern and leaky capillaries has a diagnostic sensitivity of greater than 80%. Clinical diagnosis of pulmonary disease in PSS Physiology: Diffusing capacity for carbon monoxide (DLCO) is sensitive for pulmonary disease, since findings are abnormal in 90% of symptomatic patients. Marked reductions in the mean DLCO are suggestive of the predominant vascular disease observed in overlap syndromes. In the absence of pulmonary hypertension, reductions in the DLCO correlate highly with the extent of fibrosing alveolitis, as seen on CT. Exercise pulmonary function tests (PFTs) are more sensitive to early disease than static PFTs. The dominant ventilatory defect is restrictive. Bronchoalveolar lavage: Bronchoalveolar lavage (BAL) fluid cell counts are used to assess the degree of inflammatory activity and to guide treatment. Abnormalities may be present early in the disease and precede radiographic changes (subclinical alveolitis). Echocardiography: Echocardiographic measurements of systolic pulmonary arterial pressure correlate well with right heart catheterization values. Lung biopsy: Transbronchial biopsy is nondiagnostic. Open lung biopsy may be performed to confirm active alveolitis when considering aggressive immunosuppressive therapy. Preferred ExaminationChest radiograph is insensitive, since findings are abnormal in only two thirds of patients with pulmonary disease. High-resolution CT (HRCT) is the best imaging test for assessing the extent and severity of pulmonary disease. Reported detection of fibrosis with HRCT is 60-90% compared to 60-100% at autopsy. Limitations of TechniquesHRCT findings are abnormal in most patients with functional impairment. False-negative HRCT imaging study findings have occurred in the setting of alveolitis, as documented by Remy-Jardin et al using BAL in patients with normal PFTs.8 DIFFERENTIALSSection 3 of 8
Asbestosis Idiopathic Pulmonary Fibrosis Other Problems to Be ConsideredOther diagnostic considerations with the usual interstitial pneumonitis (UIP) pattern of basal predominant fibrosis include other collagen vascular diseases, particularly rheumatoid arthritis and chronic hypersensitivity pneumonitis (can mimic idiopathic pulmonary fibrosis [IPF]). RADIOGRAPHSection 4 of 8
FindingsEarly findings - Subpleural reticular or reticulonodular opacity in a basal predominant distribution Late findings
Ancillary findings - Diffuse esophageal dilation with resultant "air esophagram sign" (useful when present to differentiate PSS from IPF, asbestosis, and rheumatoid arthritis) Degree of ConfidenceChest radiography is relatively insensitive in early disease, and findings may be minimal even in advanced disease; however, chest radiographic findings are observed in as many as two thirds of symptomatic patients, with findings suggestive of fibrosis demonstrated in 25-45% of patients. False Positives/NegativesInterstitial lung disease with a predominant lower lobe distribution on chest radiography may have numerous etiologies, including PSS. Clinical history and esophageal dilation on radiographs suggests PSS. Any phase of IPF, asbestosis, interstitial pulmonary edema, lymphangitic metastases, pulmonary hemorrhage, and other diffuse lung diseases may mimic PSS on chest radiographs. On the posteroanterior (PA) view, the breast shadows can mimic increased markings over the lower lung zones. Lateral view is critical so as to obtain a less obscured view of the lower lobes. CT SCANSection 5 of 8
FindingsPatients with suggested or known diagnosis of PSS should undergo the following: Standard resolution CT (SRCT) to exclude a lung neoplasm (which is slightly more common than in the general population) and to evaluate pleuropericardial, esophageal, cardiac, and pulmonary arterial abnormalities HRCT to evaluate lung parenchymal involvement
Degree of ConfidenceStudies have shown that HRCT is diagnostically accurate in specific subsets of patients with diffuse lung disease. In a study of 85 patients with diffuse lung disease by Swensen et al,9 radiologists more frequently had a high level of confidence in diagnosing UIP than any other pattern and listed it as the number one diagnosis in 89% of patients with that histologic finding. Imaging diagnoses were most accurate (90% correct) when a high level of confidence was present. Remy-Jardin and colleagues correlated HRCT findings with functional parameters and BAL results in patients with PSS.8 BAL findings were abnormal in 7 of 21 patients with normal imaging and PFTs, suggesting it is more sensitive than HRCT in detecting subclinical alveolitis. The extent of parenchymal destruction, which correlated with functional abnormality, was better depicted by HRCT. Diot and colleagues assigned point values for each abnormal finding present on HRCT of 52 patients with PSS.10 Total scores were inversely proportional to total lung capacity and DLCO. Receiver operator curve analysis demonstrated that an HRCT score of 7 or greater minimized false negatives (sensitivity of 0.60) while achieving a specificity of 0.83. The positive predictive value of HRCT in this study was 0.82. False Positives/NegativesFalse negatives have been documented by Remy-Jardin et al in patients with subclinical alveolitis.8 INTERVENTIONSection 6 of 8
A collaborative approach between pulmonologists and thoracic radiologists is important in the diagnosis and management of interstitial lung disease. Analysis of HRCT images of the chest can guide video-assisted thoracoscopic lung biopsy. An increased incidence of lung cancer is seen in patients with scleroderma, and the radiologist is involved in detection and diagnosis through CT-guided percutaneous lung biopsy. Perform percutaneous drainage of complicated parapneumonic effusions and empyemas with CT or US guidance. Special Concerns
MULTIMEDIASection 7 of 8
REFERENCESSection 8 of 8
Article Last Updated: Aug 16, 2007 | ||||||||||||||||||||||||||||||||||||||||||
