SYSTEMIC LUPUS ERYTHEMATOSUS
Systemic lupus erythematosus (SLE) is a systemic autoinflammatory disorder that most commonly affects women of childbearing age. Hispanics and African Americans present earlier and with more active and aggressive disease than whites. When SLE is diagnosed after age 50 years, there is a lower female : male ratio; a higher incidence of neurologic, serosal, and pulmonary involvement; greater accumulated organ damage; and higher mortality.
The frequency and characteristics of pulmonary
involvement depend on the clinical phenotype studied and the sensitivity of the
investigative methods used. Infectious pneumonia remains the primary concern,
particularly in those treated with corticosteroids or other immunomodulatory
therapy, and infection should generally be the first consideration in patients
presenting with new or worsening respiratory symptoms or abnormal chest
imaging. Drug reactions are also important to consider because pulmonary
toxicity has been noted with a number of medications commonly used to treat
patients with SLE patients, including azathioprine, mycophenolate,
cyclophosphamide, methotrexate, and nonsteroidal antiinflammatory drugs
(NSAIDs).
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Pulmonary physiologic abnormalities are common. A low
diffusing capacity with or without a concomitant restrictive ventilatory defect
is the most common finding. One-third or more will have isolated diffusion
impairment. Airflow limitation, usually subclinical, is identified in the
minority of patients. Chest imaging results are commonly abnormal.
High-resolution computed tomography (HRCT) scan features of interstitial lung
disease (ILD) are present in at least one-third of asymptomatic subjects with
airway abnormalities seen in one-fifth. The most common abnormalities are a
combination of ground-glass and reticular opacities in the middle and lower
lung zones, with interlobular and intralobular lines, parenchymal bands,
centrilobular nodularity, and focal consolidation less commonly observed.
One-fifth of patients have otherwise unexplained mediastinal lymphadenopathy.
Pleural disease is believed to be the most common
clinically relevant pulmonary manifestation. Up to one- third of patients
present with pleuritis (symptoms of pleurisy with or without pleural effusion).
The effusions are usually bilateral and small to moderate in size, although
extremely large effusions may occur.
A variety of patterns of ILD have been described. The
most common patterns observed include cellular, fibrotic, or mixed nonspecific
interstitial pneumonia, although organizing pneumonia, and more rarely, diffuse
amyloidosis, have been reported. Patterns of usual interstitial pneumonia and
lymphoid interstitial pneumonia, particularly when secondary Sjögren syndrome
is present, are also seen.
One of the more clinically severe pulmonary
manifestations is diffuse alveolar hemorrhage (DAH). Respiratory failure may
develop, and when it occurs, mechanical ventilation is frequently necessary.
Rarely, DAH may be the presenting manifestation of SLE. Pathologic findings
include intraalveolar hemorrhage and hemosiderin-laden alveolar macrophages
with or without capillaritis (i.e., bland hemorrhage). A pathologic pattern of
diffuse alveolar damage, with its hyaline membranes (and varying degrees of
cellular interstitial infiltrates), is occasionally observed. The prognosis is
variable; approximately half of patients die during their hospitalization. Survival depends on
the degree of hypoxemia, the presence and severity of coincident extrapulmonary
SLE manifestations, and the presence of infection. DAH can recur. Acute lupus
pneumonitis is characterized by the abrupt onset of nonspecific symptoms,
including dyspnea, cough, fever, pleuritic chest pain, and occasionally
hemoptysis. Radiographic abnormalities are usually extensive and include
diffuse ground-glass opacities and areas of consolidation. When surgical lung
biopsy is performed, the histologic pattern has been described as DAD with or
without alveolar hemorrhage and capillaritis.
The prevalence of pulmonary arterial hypertension in
patients with SLE is unknown but is lower than that seen in scleroderma. In
shrinking lung syndrome, patients present with dyspnea and elevated diaphragms
on chest imaging. Measurement of transdiaphragmatic pressure suggests weakness
as the cause. Progression is uncommon. With treatment, diaphragmatic motion may
not normalize, and if it happens, it occurs only after several weeks of
therapy.
Antiphospholipid antibodies (aPLs) are a family of
acquired autoantibodies that bind serum proteins such as prothrombin, various
protein-phospholipid complexes, and β-2 glycoprotein
I. They can be found in up to two-thirds of SLE patients and are associated
with vascular thrombosis; pregnancy morbidity; and several nonthrombotic
intrathoracic complications, including PAH, DAH, adult respiratory distress
syndrome, and cardiac valvular lesions. The two most well known and clinically important are
the lupus anticoagulant (LA) and anticardiolipin antibodies (aCLs).
Antiphospholipid syndrome (APS) refers to the combination of clinically
important vascular events and the presence of the LA or aCL. Clinically
significant small vessel occlusion in three or more organs may occur, a scenario
referred to as catastrophic APS (CAPS). CAPS is often associated with
physiologic stressors such as infection, neoplasm, and surgery. Respiratory
failure is common, and mortality rates approach 50%. Lifelong anticoagulation
is required, but recurrent thrombosis is common.
