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less speci c markers, as they are positive in other autoimmune­ diseases [19]. Lupus-type circulating anticoagulants, anticardiolipin antibodies, and anti-B2GP1 antibodies are associated with antiphospholipid syndrome.

Pulmonary Manifestations

Pleural Disease

Pleural disease is the most common lung manifestation observed approximately in 60% of patients (50–83% in autopsy series) (Table 14.1) [20, 21].

Treatment choice for pleural disease depends on the severity of symptoms and the amount of liquid. Small asymptomatic effusions may not require speci c treatment, while non-steroidal anti-infammatory drugs and corticosteroids (prednisone dose 0.5 mg/kg) are mostly used when treatment is required [22]. In refractory cases, immunosuppressive and corticosteroid-sparing agents, such as azathioprine, mycophenolate mofetil, or methotrexate should be discussed. Chest tube drainage or pleurodesis are only rarely required for symptomatic relief of resistant disease.

Acute Lupus Pneumonitis and Di use Alveolar Hemorrhage

The most life-threatening lung manifestations are acute lupus pneumonitis and diffuse alveolar hemorrhage, which are observed only in a minority of patients (2–4%) [21]. A recent meta-analysis described potent risk factors correlated with increased risk of hemorrhage in SLE patients, such as neuropsychiatric involvement, nephritis, higher Systemic Lupus Erythematosus Disease Activity Index 2000 score, and low levels of C3 and C4 complement fractions, platelets, and hemoglobin [23].

Clinical data about treatment for acute immune-mediated lung injury associated with SLE are limited (no prospective controlled studies), and treatment strategies are based on other autoimmune conditions associated with pulmonary hemorrhage and acute pneumonitis. Corticosteroids are widely accepted as the rst line of therapy, and intravenous pulses of corticosteroids are usually given (methylprednisolone 500 mg–1000 mg/day). Cyclophosphamide, rituximab, plasmapheresis, and intravenous immunoglobulins have been also used in critically ill patients [24].

Shrinking Lung Syndrome

The shrinking lung syndrome caused by diaphragmatic dysfunction, although well recognized, is a very rare manifestation [25].

There is no evidence for the optimal management of the shrinking lung syndrome. Corticosteroids and immunosuppressive agents, including azathioprine, mycophenolate mofetil, and rituximab, have been mainly used [26].

Individual cases have been improved with inhaled β-agonists [27], and theophylline [28].

Thrombotic Manifestations

Antiphospholipid syndrome is associated with SLE with a prevalence of 30% [29] and can be associated with thrombotic events, with or without pulmonary embolism in 35–42%, compared to 9% in patients with SLE alone [30]. Pulmonary embolism is an important entity to be considered in patients with SLE, and in that case, the initial management does not differ from the established guidelines. Thrombotic manifestations are mostly observed in patients who have secondary antiphospholipid syndrome [31]. Anticoagulant therapy, mainly with warfarin, is strongly recommended in antiphospholipid syndrome, due to the lack of evidence on novel oral anticoagulants. Pregnant women suffering from antiphospholipid syndrome require treatment with both aspirin and low molecular weight heparin throughout the pregnancy period.

Interstitial Lung Disease

Interstitial lung involvement has been found in about 15% of patients (Table 14.1). Non-speci c interstitial pneumonia (NSIP), organizing pneumonia (OP), lymphocytic interstitial pneumonia (LIP), and less commonly, usual interstitial pneumonia (UIP) have been described [32]. Treatment of SLE-­ ILD is based on limited data and is mostly extrapolated from studies about other CTD-ILDs. The rst-line treatment usually relies on corticosteroids, while mycophenolate mofetil or azathioprine are used as maintenance therapy. Rituximab and cyclophosphamide can be used in more severe cases [33].

Other Pulmonary Manifestations

Airways can be concerned in approximately 16% of the patients, mostly asymptomatic. Infection is the most common parenchymal disease observed in SLE, and it should always be excluded in patients with respiratory symptoms, particularly in patients under immunosuppressive therapy [34, 35]. Clinically signi cant pulmonary hypertension (PH) is a rare but severe complication of SLE, typically associated with scleroderma clinical features and anti-RNP antibodies [36–38].

Prognosis

SLE presents with a highly variable clinical course, while pulmonary infections and thrombotic events govern morbidity and mortality). PH also affects survival with two-year mortality just above 50%, but the most frequent causes of death are thromboses and infections [34, 38]. More rare causes associated with poor prognosis are acute lupus pneumonitis and diffuse alveolar hemorrhage, with mortality ranging from 50% to 90% despite treatment [39] (Table 14.3).