Page 1013 - Clinical Immunology_ Principles and Practice ( PDFDrive )

CHaPter 72 Immunological Lung Diseases 977

of patients at presentation. Therefore the absence of hemoptysis is the most common presentation. Most of the patients with
does not exclude the diagnosis, particularly in the setting of a SLE who have pulmonary hypertension are female, with 3- and
falling hematocrit, diffuse pulmonary infiltrates, and blood-stained 5-year survival rates of 45% and 17%, respectively, representing a
BAL fluid. DAH in SLE most often results from pulmonary worse prognosis compared with that for patients with idiopathic
capillaritis, but it can also be caused by diffuse alveolar damage. pulmonary hypertension. The vascular changes of SLE-associated
Immunofluorescence studies show granular deposits of immu- pulmonary hypertension are similar to those seen in idiopathic
noglobulin G (IgG) and C3 along alveolar walls, interstitium, pulmonary hypertension with intimal hyperplasia, smooth
and capillary endothelial cells. muscle hypertrophy, and medial thickening. Several pathological
There are no controlled trials for the treatment of alveolar mechanisms have been proposed for the development of pul-
hemorrhage in SLE. Glucocorticoids, cytotoxic drugs, and monary hypertension, including vasoconstriction, in addition to
plasmapheresis have been used in various combinations. The vasculitis and thrombosis associated with antiphospholipid and
mortality rate associated with DAH is approximately 50%. Poor anticardiolipin antibodies. Serum endothelin levels are elevated
prognostic factors include the need for mechanical ventilation, in patients with SLE-associated pulmonary hypertension and
presence of infection, and prior treatment with cyclophosphamide. correlate with pulmonary arterial pressures.
As the pulmonary hypertension advances, the central pul-
Lupus Pleuritis monary arteries enlarge. Pulmonary function testing shows an
The pleura are the most common site of respiratory involvement isolated decrease in the diffusing capacity for carbon monoxide.
in SLE, with pleurisy and pleural effusions occurring in 50–80% Patients with SLE-associated pulmonary hypertension may
of patients. Lupus pleuritis can be the presenting manifestation respond to immunosuppressive therapy. In a small study, five
of disease, but more commonly, it develops in patients with of 12 patients with SLE responded to monthly intravenous
established SLE. It is often recurrent. The clinical manifestations bolus doses of cyclophosphamide in addition to systemic
include chest pain, fever, and dyspnea, and chest radiography glucocorticoids. A positive response was indicated by sustained
typically shows bilateral pleural effusions. The pleural fluid is hemodynamic improvement after at least 1 year of treatment
serous or serosanguineous and exudative in nature. Compared without the need for additional pulmonary hypertension–specific
with effusions in RA, the glucose is higher, and the lactate therapies. Patients who responded to immunosuppression could
dehydrogenase level is lower. The most helpful measurement is be maintained on azathioprine or mycophenolate mofetil to avoid
a pleural fluid ANA titer greater than 1 : 160. Examination of potential adverse effects of cyclophosphamide. Patients with SLE
the pleura reveals infiltration with plasma cells and lymphocytes, who were treated with bosentan did not have clinical worsen-
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accompanied by pleural thickening and fibrosis. Treatment with ing and showed an improvement in 6-minute walk distance.
nonsteroidal antiinflammatory drugs (NSAIDs) and/or gluco- Overall, the long-term survival of patients with SLE-associated
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corticoids is usually effective for relief of pleural discomfort. pulmonary hypertension is poor, and the optimal treatment
regimen for SLE-associated pulmonary hypertension remains
Interstitial Lung Disease unknown.
The presence of ILD in SLE is uncommon, especially compared
with SSc or RA. However, minor interstitial abnormalities can Respiratory Muscle Dysfunction
be found on HRCT in approximately one-third of patients with The shrinking lung syndrome is caused by diaphragmatic weakness
SLE who have normal results of chest radiography and physiologi- as well as weakness of other respiratory muscles. This entity
cal testing. The significance and natural history of these subclinical accounts for the findings of dyspnea without evidence of inter-
findings are uncertain. The presence of anti-SSA (Ro) has been stitial infiltrates or pulmonary vascular disease. It occurs in 25%
noted in approximately 80% of patients who have lupus with of patients with SLE. Chest radiography typically shows elevated
interstitial changes. In addition, the prevalence of ILD is increased diaphragms and basilar atelectasis. The pathogenesis of respiratory
in a subset of patients with SLE who have sclerodermatous skin muscle weakness is unknown, but it is not associated with general-
changes. ized muscle weakness. Glucocorticoids are frequently ineffective
The diagnosis of SLE is usually well established in patients in the treatment of this syndrome. Improvement has been noted
who develop the insidious form of ILD. The disease course is with inhaled β-agonist and theophylline therapy. Despite a variable
characterized by progressive dyspnea and cough; chest radiography response to therapy, it is unusual for this manifestation of SLE
shows reduced lung volumes and reticular interstitial infiltrates. to be progressive.
A restrictive lung function pattern with reduced diffusing capacity
and exercise-induced hypoxemia are typical. The histopathology Rheumatoid Arthritis
of chronic interstitial disease in SLE resembles NSIP, although RA is an autoimmune disease associated with autoantibodies
cases of BOOP, LIP, and UIP have been described. Response to directed against citrullinated antigens and characterized by the
therapy depends on the underlying histopathology, with the presence of a symmetrical, inflammatory polyarthritis (Chapter
UIP-like form being least responsive. 52). It occurs more frequently in women, with a female-to-male
ratio of 2 : 1. Disease onset is most commonly in the fourth to
Pulmonary Vascular Disease fifth decades of life. The pleuropulmonary complications of RA
Although previously thought to be unusual, the development of occur more commonly in individuals with subcutaneous nodules,
pulmonary hypertension has been increasingly noted in SLE, with high titers of rheumatoid factor, and more severe chronic articular
an incidence ranging from 0.5–14%. Pulmonary hypertension in involvement. Although RA itself is more common in women,
SLE has been associated with the presence of Raynaud syndrome, the pleuropulmonary manifestations have a higher incidence in
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serositis, digital vasculitis, and antiphospholipid antibodies. men. The pleuropulmonary complications of RA are numerous,
Dyspnea and fatigue, despite normal results on chest radiography, but the treatment-related lung toxicity and pulmonary infections