Page 724 - Clinical Immunology_ Principles and Practice ( PDFDrive )

CHaPtEr 51 Systemic Lupus Erythematosus 697

well as for determining the extent of active inflammatory disease
Chronic Diffuse Interstitial Lung Disease and fibrosis. Symptoms and signs of myocarditis include unex-
Chronic diffuse interstitial lung disease is a relatively uncommon plained tachycardia, an abnormal electrocardiogram (with ST- and
manifestation of SLE and is occasionally associated with anti-Ro T-wave abnormalities), cardiomegaly, and heart failure. Echo-
antibodies. It usually has a progressive course with a chronic cardiography may show systolic and diastolic ventricular dysfunc-
nonproductive cough, dyspnea, and pleuritic chest pains. Physical tion. Myocardial involvement without overt clinical signs occurs
examination is frequently remarkable for basilar rales with commonly and may be documented using Doppler echocar-
diminished diaphragmatic movement. Pulmonary function tests diography. A noninflammatory cardiomyopathy may be seen in
demonstrate a restrictive pattern with decreased diffusion capacity; association with high-dose cyclophosphamide and, although
oxygen saturation is decreased. Imaging often shows interstitial rarely, with hydroxychloroquine.
fibrosis that is more prominent at the lung bases. High-resolution
CT (HRCT) may also help determine the extent of treatable Valvular Heart Disease
disease, i.e., fibrosis (honeycombing) versus inflammation (ground Valvular abnormalities, with thickening, regurgitation, or ver-
glass). However, the most reliable method to assess the extent rucous vegetations, occur commonly in SLE (50–60%) and
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of pulmonary inflammation in comparison to fibrotic damage are documented by transesophageal echocardiography. The
is histological examination. Evaluation of bronchial alveolar characteristic Libman–Sacks lesion, nonbacterial verrucous
lavage fluid helps to exclude infection. vegetations, is observed at autopsy in 15–60% of patients. Mitral,
aortic, and tricuspid valves are most frequently involved. Clinically
Pulmonary Hypertension these lesions are usually asymptomatic, and hemodynamic
Pulmonary hypertension unrelated to chronic pulmonary emboli compromise, rupture of the chordae tendineae, or infection are
or interstitial lung disease occurs in SLE. Severe cases are rare; rare events. On histological examination, mononuclear cells,
the recent recognition of milder cases may be partially attributed hematoxylin bodies, fibrin and platelet thrombi, and immune
to increased awareness and findings of elevated pulmonary artery complexes are present. Antiphospholipid antibodies can be
pressures on echocardiograms obtained for evaluation of shortness associated with the development of valvular heart disease,
of breath. Patients typically present with progressive dyspnea although their pathogenic role remains unproven.
occurring in the absence of infiltrates on chest radiographs or
significant hypoxemia. Chest pain and a chronic nonproductive Pericarditis
cough are also frequently present. Pulmonary function testing Pericardial inflammation in SLE is frequent. Although asymp-
reveals a reduced DL CO . Elevated pulmonary artery pressure is tomatic pericarditis occurs in more than 50% of patients, clinically
confirmed with cardiac angiogram. Biopsy or autopsy specimens apparent pericarditis occurs in only 25%, and cardiac tamponade
of the lung reveal “plexiform” lesions that resemble those seen and constrictive pericarditis are infrequent. Pericardial fluid and
in primary pulmonary hypertension. thickening are easily detected by echocardiography; cardiac
silhouette enlargement on plain films is seen in the presence of
Shrinking-Lung Syndrome large effusions. There are no unique signs and symptoms
The shrinking-lung syndrome refers to the rare findings of of pericarditis in lupus patients. The histological findings of
shortness of breath occurring in the absence of pleuritis or acute pericarditis in lupus are inflammation with a mononuclear
interstitial lung disease plus a chest X-ray showing elevated cell infiltrate accompanied by immunoglobulin and complement
hemidiaphragms. Pulmonary function testing shows a restrictive deposition. Results of pericardial fluid analysis are neither sensitive
pattern with loss of lung volume. It had been generally accepted nor specific; the fluid is usually an exudate with elevated protein
that this syndrome results from diaphragmatic weakness (from concentrations, normal or low glucose levels, and an elevated
a myopathic process) or chest wall restriction; however, more WBC count that is primarily neutrophilic. Complement levels
recent studies suggest that pleuritis may play a causative role. in the fluid are low, and autoantibodies (ANA, dsDNA) and LE
There is no definitive therapy, although immunosuppressive cells have been reported.
therapy with cytotoxic agents usually results in an improvement
of lung function and respiratory symptoms. Coronary Artery Disease
Myocardial infarction, angina, and sudden death resulting from
Cardiac Involvement CAD are well described in SLE. Estimates of the prevalence of
There are a number of ways in which lupus affects the cardio- CAD vary widely depending on the methodology used for
vascular system; targets include the myocardium, valves, peri- ascertainment; however, the risk of myocardial infarction has
cardium, and vessels. been estimated to be 50-fold greater in young women with lupus
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than in normal age-matched controls. Cardiac events occur
Myocardium both late in the course of SLE as well as early, and may even
Myocardial dysfunction in SLE is likely to be secondary to factors predate the SLE diagnosis. Coronary artery vasculitis is a potential
other than lupus, such as hypertension, medications, or coronary cause of CAD but is exceedingly rare, and bland atherosclerotic
artery disease (CAD). However, a cardiomyopathy resulting plaque is typically described in surgical and postmortem speci-
from immune-mediated myocardial inflammation does occur, mens. Traditional risk factors for CAD, such as hypertension,
either in isolation or concomitant with myositis or other mani- diabetes, and hyperlipidemia, are enriched in lupus patients, and
festations of systemic disease. Inflammatory myocarditis is often an increased prevalence of the metabolic syndrome likely con-
associated with anti-RNP antibodies. Histopathology typically tributes additional risk. Lupus-related risk factors include duration
shows a mononuclear, inflammatory cell infiltrate. Perivascular of SLE, duration of corticosteroid use, renal disease, and absence
or myocardial wall deposits of immune complexes and comple- of use of hydroxychloroquine. The potential contributing influence
ment also occur. Myocardial biopsy is critical for diagnosis as of antibodies to phospholipids or disease activity continues to