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).
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.